"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                653 \n\n\n\nABSTRACT \nIntroduction: Healthcare drivers, including ambulance \ndrivers, were less concerned about health and safety during \nthe COVID-19 pandemic, with not only the risk of COVID-19 \ninfection but also a higher risk of prolonged states of \nalertness, stress, burnout, fatigue and road traffic accident. \nThis study aimed to determine the prevalence of stress and \nits associated factors among healthcare drivers, especially \nduring the COVID-19 pandemic.  \n \nMaterials and Methods: This study employs a cross-\nsectional study design and utilises self-reported data \nobtained from locally validated personal stress inventory \nquestionnaires. The data collection period spanned from \nAugust 1 to 31, 2020. The study sample consisted of 163 \nhealthcare drivers affiliated with the Negeri Sembilan State \nHealth Department. The Chi-square test and Fisher\u2019s exact \ntest were the first used to determine the association \nbetween variables prior to conducting multiple logistic \nregression to predict the relationship between dependent \nand independent variables.  \n \nResults: In COVID-19's first year, 7.4% (n = 12) of healthcare \ndrivers reported perceived stress with ambulance drivers \nreporting more stress (10.6%; n = 5) than non-ambulance \ndrivers (6.0%; n = 7). Simple statistical analysis identified \nperceived stress significantly associated with household \nincome, smoking status and performing on-call. Further \nanalysis by multiple logistic regression found that perceived \nstress was significantly related to smoking (aOR 19.9, 95% \nCI: 1.86-213.90), and performing on-call (aOR 8.69, 95% CI \n1.21-62.28). Nevertheless, no association was found \nbetween perceived stress and age, ethnicity, marital status, \neducation, household income, co-morbidities, driving \nassignment, employment duration, needing a part-time job \nor motor vehicle accident history.  \n \nConclusion: The study found that the perceived stress \namongst Malaysian healthcare drivers during the COVID-19 \npandemic was relatively low. This could be due to fewer life-\nthreatening tasks, emergencies, assigned tasks and \nincrease income due to overtime during the COVD-19 \n\n\n\npandemic. The OSH team's efforts to provide consistent \nsafety and health training, including stress management, \nmay have contributed to the healthcare driver\u2019s ability to \neffectively manage the stressful circumstances encountered \nduring the pandemic. In order to enhance salary \ncompetitiveness, employers should provide financial \nmanagement education alongside subsidised housing and \nchildcare provisions. Healthcare drivers who smoke should \nbe taught different stress reduction techniques so that they \ncan handle their stress in a healthy way.  \n \nKEYWORDS:  \nHealthcare; health drivers; ambulance drivers; EMS drivers; stress; \nperceived stress; COVID-19; pandemic; prevalence \n \n \nINTRODUCTION \nThe Global populations have been devastated by the COVID-\n19 epidemic. The impact has existed for almost 2 years since \nthe World Health Organization (WHO) announced the Public \nHealth Emergency of International Concern (PHEIC).1 Every \npart of human life was affected by the COVID-19 epidemic, \nbut economic and social devastation stood out.2,3 \nNevertheless, there are over 8 million confirmed COVID-19 \ninfections worldwide, with two million deaths in 2020, and it \nis increasing day by day.4 Low-income and poor countries \nwere badly affected and had difficulty surviving during the \nCOVID-19 pandemic, as warned by the WHO and the World \nBank Organisation.5,6   \n \nThis pandemic has given a strike to the healthcare system \ncapacity. The occupancy of COVID-19 patients is more than \nthe capacity of healthcare facilities and hospitals worldwide. \nCertain countries (South Africa, the United Kingdom, \nGermany, China and Malaysia) built field hospitals to cope \nwith the pandemic situation.7\u20139 The impacts of the COVID-19 \npandemic are completely different in countries such as Italy, \nSpain and Malaysia, which experienced a surge of cases but \nrelied on the inadequacy of hospital beds and healthcare \nprofessionals.7,10 But, more importantly, during the COVID-19 \npandemic, overwhelmed, short-staffed healthcare facilities \nlead to stress and burnout among healthcare workers, \n\n\n\nStress perceived by drivers in public healthcare facilities \nin Negeri Sembilan during the first year of the COVID-19 \npandemic  \n \nAbdul Aziz Harith, MPH1,2, Zuraida Mohamed, MPH (OH)3, Azyyati Mohammad, MPH3, Lim Kuang Kuay, MSc2, \nNaiemy Reffin, MPH4, Malindawati Mohd Fadzil, MSc4, Shahida Ismail, MPH4, Nofi Yuliani Dahlan, MPH4, \nMuhammad Zulfakhar Zubir, MSc4, Mohd Ihsanuddin Abas, MPH5 \n\n\n\n     \n1Occupational and Aviation Medicine, Department of Medicine, University of Otago Wellington, Wellington New Zealand, New \nZealand, 2Occupational Health Research Centre, Institute for Public Health, National Institutes of Health, Shah Alam, Selangor \nMalaysia, Malaysia, 3Occupational and Environmental Health Unit, Public Health Division, Negeri Sembilan State Health \nDepartment, Negeri Sembilan, Malaysia, 4Department of Community Health, Faculty of Medicine, Universiti Kebangsaan \nMalaysia, Malaysia, 5Community Medicine Unit, Faculty of Medicine, Universiti Sultan Zainal Abidin, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 30 August 2023                                                                                                                                                                         \nCorresponding Author: Abdul Aziz bin Harith                                                                                                                                                                     \nEmail: drazizkpaskkm@gmail.com; abdulaziz.harith@postgrad.otago.ac.nz\n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 653\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n654                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nespecially on the front lines. The WHO has alerted worldwide \nhealthcare organisations and governments to identify and \ntackle the unprecedented issues related to healthcare workers \nduring the COVID-19 pandemic.11  \n \nTiredness, mental stress and burnout are some of the major \nissues among healthcare workers during the COVID-19 \npandemic.12 The well-being of healthcare workers, on the \nother hand, is much more important in maintaining a high \nstandard of quality care for patients because it is directly \nrelated to healthcare worker productivity.13\u201315 Healthcare \nworkers are expected to work intensely because of the high \nburden of COVID-19 patients and a lack of staff (because of \nbeing infected or affected more by the pandemic). The 11th \nRevision of the International Classification of Diseases (ICD-\n11) defined burnout as a syndrome conceptualised as \nresulting from chronic workplace stress that has not been \nsuccessfully managed.16 But tackling stress issues among \nhealthcare workers is crucial and more beneficial to reducing \nburnout among frontline healthcare workers and \nmaintaining the productivity of healthcare services. \n \nFrontline healthcare workers comprise medical physicians, \nnurses, medical doctor assistants, healthcare assistants, \nreceptionists, cleaners and ambulance drivers.17 Ambulance \ndrivers are less concerned with health and safety compared to \ndoctors and nurses during the COVID-19 pandemic. Some \nreports suggest that ambulance workers may be particularly \nvulnerable to first-responder mental health issues.18 \nAmbulance drivers are not only at a higher risk of COVID-19 \ninfection, but they are also at a higher risk of road accidents \ndue to high driving speeds under emergency conditions and \nencountering unpleasant aspects of life.19 They often work \nunder time pressure and at irregular hours, which leads to \nprolonged states of alertness and fatigue.20,21 Afshari et al. \nidentified six main stressors for emergency medical service \n(EMS) drivers: complexity of patients' clinical conditions, \ninterruption of EMS provision, health hazards, interpersonal \nissues, inter-professional interactions and legal conflicts.22 \n \nHealthcare and ambulance drivers are comparable to full-\ntime professional drivers, who are exposed to a variety of \nstressors, such as the behaviour of other drivers, congested \nroads, ergonomic considerations, noise, climate conditions \nand job scheduling, resulting in deteriorating well-being and \nperformance.23,24 John and Linda's 2006 study also revealed \nthat older driver, women and those with a history of reported \naccidents in conditions of limited visibility, adverse weather \nand while performing common driving tasks are more prone \nto experience stress.25 Despite that, according to Maga\u00f1a et \nal.26, the level of stress experienced while driving can be \ninfluenced by four factors: the well-being (physical and \nmental condition) of the driver, the road and traffic \nconditions, the condition of the vehicle and external \ndisturbances.  \n \nThe Institute for Health System Research (IHSR) reported that \n129 ambulance accidents occur in Malaysia on average each \nyear.27 This situation is problematic for the organisation as a \nresult of increased turnover, absenteeism and exposure to \nsubstantial claims for compensation. The majority of \nambulance accidents (70.4%) occurred during the day, and \n55.7% occurred on weekdays. Accidents occurred on straight \nroads in 49.7% of cases and on 35.4% of federal roads. \n\n\n\nAccording to Syazmin et al., health drivers or ambulance \ndrivers were ranked second among Malaysian healthcare \nworkers involved in road traffic accidents, with a 53.7 per \n10,000 worker accident rates.28 The mental health of a driver \nis critical because it directly influences their driving \nbehaviour. Assessment of the stress status of frontline \nhealthcare drivers is critical before it progresses to burnout \nwith increasing mental distance from one's job and feelings \nof isolation especially during the COVID-19 pandemic. Thus, \nthis study aimed to determine the prevalence of stress and its \nassociated factors among healthcare drivers, especially \nduring the COVID-19 pandemic. \n \n \nMATERIALS AND METHODS \nThe Study Design \nThe stress among drivers in public healthcare facilities survey \nwas a cross-sectional study conducted from 1st August until \n31st August 2020. It covers seven district health offices, seven \ndistrict dental offices and seven hospitals under the Negeri \nSembilan State Health Department (SHD). The \nresponsibilities of healthcare drivers within the department \n(ambulance driver or non-ambulance driver) are \ninterchangeable depending on where the driver is posted \n(hospital, district health or dental office or primary care \nclinics). However, all drivers were deployed as front-liners in \nmanaging COVID-19 in the hospital and community. Simple \nrandom sampling was used to select drivers based on the 397 \ndrivers in the list provided by the Negeri Sembilan SHD.  \n \nThe total sample size required was 149 based on the 95% \nconfidence interval (CI), marginal error of 5% and the \nnearest expected stress prevalence among drivers based on \nthe emergency care personnel met posttraumatic stress \ndisorder; 18.6%.29 The sample was increased by 10% to \naccount for the non-response rate, which resulted in 164 but \nrounded into 170 respondents.  \n \nThe inclusion criteria comprise working at the present \nworkplace for at least 6 months, having Malaysian \nnationality, working during the COVID-19 pandemic for at \nleast the last 2 weeks, and being a registered driver under the \nNegeri Sembilan SHD. The selection of a 6-month service \nduration was based on the understanding that individuals \ntypically require a period of 3\u20136 months to adapt to a new \nworkplace environment. Drivers diagnosed with mental \nhealth illnesses and those on long-term sick leave were \nexcluded from this study. \n \nSurvey Instrument \nA validated Malay version of the Personal Stress Inventory \n(PSI) survey was distributed to healthcare drivers. The \ninventory comprised 51 items with 11 subscales using a four-\npoint Likert scale from \u2018never\u2019 (0), \u2018once or twice\u2019 (1), \u2018every \nweek\u2019 (2) and \u2018nearly every day\u2019 (3). The healthcare drivers' \nreplies to each of the 51 items, with scores ranging from 0 to \n153, were added together to create a final score. Rokiah \nvalidated this inventory in Malaysia with a sensitivity of \n95.1%, specificity of 77% and a total score of over 36, \nsignifying respondents were experiencing stress.30 The \nCronbach alpha of this instrument is 0.968. One answered \nthe questionnaires anonymously to maintain the driver's \nprivacy.  \n \n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 654\n\n\n\n\n\n\n\n\nStress perceived by drivers in public healthcare facilities in Negeri Sembilan during the first year of the COVID-19 pandemic\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                655 \n\n\n\nData Variables \nThe questionnaires encompass various categories of data, \nincluding demographic data (age, gender, ethnicity, marital \nstatus, level of education, healthcare facilities), co-\nmorbidities (height, weight, tobacco use, drug use, \nhypertension status, diabetes status) and occupational \ndemography (employment duration in MOH, employment \nyears at unit, number of drivers at working unit, working \nhours, main driving assignment driver, work schedule, on-\ncall status, satisfaction on work schedule, part-time job and \nhad a part-time job).  \n\n\n\nDuring a minimum duration of 1 month amid the COVID-19 \npandemic, the management allocated the principal \nresponsibility, which entailed determining the primary \ndriving assignment. This involved either performing duties as \nan ambulance operator or operating the management \nvehicle to facilitate the transportation of healthcare \npersonnel or the delivery of parcels. The work schedule was \nestablished by considering the driver's availability during \nregular office hours (8 a.m. to 5 p.m.) as well as the three \navailable shift hours (7 a.m. to 3 p.m., 3 p.m. to 11 p.m. and \n11 p.m. to 7 a.m.).  \n\n\n\nVariables                                               n                               %                                                           Frequency (n) \n                                                                                                                                         Stress (%)                         None stress (%) \nHealthcare drivers                             163                           100                                        12 (7.4)                                 141 (92.6) \nAmbulance drivers                               47                            28.8                                        5 (10.6)                                  42 (89.4) \nNon-ambulance drivers                      116                           71.2                                         7 (6.0)                                   109 (94) \n                                                               \n\n\n\nTable I: Prevalence of perceived stress among healthcare drivers (n=163)\n\n\n\nVariables                                                                              n                                        Percentage (%)                               p-value \nDemographic characteristics                                                                                                                                                       \nAge groups                                                                                                                                                                               0.710 \n <30                                                                                    5                                                   3.1                                                 \n 30\u201339                                                                               81                                                 49.7                                                \n 40\u201349                                                                               52                                                 31.9                                                \n >50                                                                                   25                                                 15.3                                                \nHousehold income                                                                                                                                                                  0.044a \n MYR <2000                                                                      76                                                 46.6                                                \n MYR 2000\u20133000                                                              43                                                 26.4                                                \n MYR >3000                                                                      44                                                 27.0                                                \nEthnic                                                                                                                                                                                        0.649 \n Malay                                                                            154                                                95.7                                                \n Chinese                                                                           1                                                   0.6                                                 \n Indian                                                                             6                                                   3.7                                                 \nMarital status                                                                                                                                                                            0.519 \n Single                                                                             12                                                  7.4                                                 \n Married                                                                        145                                                90.1                                                \n Divorced/Widow                                                            4                                                   2.5                                                 \nLevel of education                                                                                                                                                                   0.385 \n High School Certificate                                               145                                                90.1                                                \n Certificate                                                                     12                                                  7.5                                                 \n Diploma                                                                         4                                                   2.5                                                 \nHealth status \nBody mass index (BMI)                                                                                                                                                           0.241 \n Underweight                                                                  3                                                   1.9                                                 \n Normal                                                                          45                                                 28.0                                                \n Overweight                                                                   63                                                 39.1                                                \n Obese                                                                            50                                                 31.1                                                \nNon-communicable diseases                                                                                                                                                       \n Diabetes mellitus                                                          22                                                 13.7                                          0.498 \n Hypertension                                                                14                                                  8.7                                           0.725 \n Hypercholesterolaemia                                                 1                                                   0.6                                           0.926 \n Heart diseases                                                                1                                                   0.6                                           0.926 \nComorbidities                                                                                                                                                                           0.811 \n Single                                                                             28                                                 17.2                                                \n Double                                                                            5                                                   3.1                                                 \n No comorbid                                                                130                                                79.8                                                \nSmoking status                                                                                                                                                                        0.009a \n Smoker                                                                          89                                                 55.3                                                \n None smoker                                                                72                                                 44.7                                                \nAlcoholic status                                                                                                                                                                       0.579 \n Drinker                                                                           2                                                   1.2                                                 \n\n\n\nNone drinker                                                               159                                                98.8                                                \n \naChi-square test. \n\n\n\nTable II: Demographic characteristics of health drivers and association with perceived stress (n=163)\n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 655\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n656                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nVariables                                                                              n                                            Mean (SD)                                   p-value \nEmployment years at Ministry of Health                         163                                           10.6 (7.4)                                      0.120 \nEmployment years at Unit                                                163                                            8.0 (6.8)                                       0.168 \nNum. of driver at working unit                                        163                                            7.9 (7.8)                                       0.073 \nWorking hours (hours/week)                                            163                                          54.7 (20.0)                                     0.313 \nVariables                                                                              n                                        Percentage (%)                                      \nMain driving assignment                                                                                                                                                         0.330 \n\n\n\nAmbulance driver                                                         47                                                 28.8                                                \nNon-ambulance driver                                                116                                                71.2                                                \n\n\n\nWork schedule                                                                                                                                                                         0.435 \nOffice hour                                                                  135                                                82.8                                                \nShift hour                                                                      28                                                 17.2                                                \n\n\n\nOn-call status                                                                                                                                                                           0.032a \nYes                                                                                 83                                                 50.9                                                \nNo                                                                                  80                                                 49.1                                                \n\n\n\nSatisfaction on work schedule                                                                                                                                               0.373 \nYes                                                                                157                                                96.3                                                \nNo                                                                                   6                                                   3.7                                                 \n\n\n\nPart-time job                                                                                                                                                                            0.464 \nRequire                                                                         128                                                78.5                                                \nNot require                                                                   35                                                 21.5                                                \n\n\n\nHad a part-time job                                                                                                                                                                  0.866 \nYes                                                                                 58                                                 35.6                                                \nNo                                                                                 105                                                64.4                                                \n\n\n\nMotor vehicle accident (MVA)                                                                                                                                                      \nMVA with department vehicle                                                                                                                                                 0.446 \n\n\n\nYes                                                                                  7                                                   4.3                                                 \nNo                                                                                 156                                                95.7                                                \n\n\n\nNum. of accidents last 6 months                                                                                                                                           0.446 \nNone                                                                            156                                                95.7                                                \nAt least once                                                                  7                                                   4.3 \n \n\n\n\naFisher\u2019s exact test. \n \n\n\n\nTable III: Occupational characteristic of healthcare drivers (n=163)\n\n\n\nVariables                                                               Simple logistic regression                                         Multiple logistic regression \n                                                              cOR                   95% CI                     p                           aOR                 95% CI                    p \nAge                                                            1.049                 0.97\u20131.12                0.194                        1.06               0.94\u20131.19              0.316 \nMarital status                                                                                                                                                                                                \n\n\n\nSingle/widow/divorce                    1425419.79            0.00\u20130.00                 1.00                     11177.57           0.00\u20130.00              0.998 \nMarried                                                                                                           Reference                                                                    Reference \n\n\n\nBMI                                                       0.96                  0.85\u20131.08                0.490                        0.91               0.78\u20131.05              0.198 \nSmoking status                                                                                                                                                                                             \n\n\n\nYes                                                        9.76                 1.23\u201377.51               0.030                       19.99            1.86\u2013213.90           0.013* \nNo                                                                                                             Reference                                                                    Reference \nComorbidities                                       0.77                  0.16\u20133.71                0.749                        0.71               0.10\u20134.52              0.712 \n\n\n\nEducation level                                                                                                   0.447                                                                            0.665 \nHigh school cert                                   1.24                 0.14\u201310.64               0.841                        1.11              0.07\u201317.21             0.940 \nDiploma                                                4.56                 0.43\u201348.00               0.206                        8.40             0.08\u2013851.18            0.366 \nDegree                                                                                                      Reference                                                                    Reference \n\n\n\nHousehold income                                                                                                                                                                                       \n<MYR 2000                                           0.61                  0.06\u20136.14                0.677                        0.60              0.03\u201311.22             0.737 \nMYR 2000\u20133000                                   2.41                  061\u20139.53                0.209                        3.60              0.48\u201326.73             0.210 \n>MYR 3000                                                                                               Reference                                                                    Reference \n\n\n\nDriving assignment                                                                                                                                                                                      \nAmbulance driver                                1.85                  0.55\u20136.16                0.314                        0.40               0.06\u20132.41              0.317 \nNon-ambulance driver                                                                             Reference                                                                    Reference \nEmployment at unit                            1.07                  1.00\u20131.16                0.044                        1.09               0.98\u20131.21              0.110 \nWorking hours                                    0.595                 0.15\u20132.35                0.460                        1.10               0.16\u20137.14              0.921 \n\n\n\nOn-call status                                             5.342                1.13\u201325.20               0.034                        8.69              1.21\u201362.28            0.031* \nSchedule satisfaction                                                                                                                                                                                    \n\n\n\nYes                                                       0.377                 0.04\u20133.51                0.391                        1.63             0.01\u2013148.54            0.831 \nNo                                                                                                             Reference                                                                    Reference \n\n\n\nHad a part-time job                                                                                                                                                                                     \nYes                                                       0.952                 0.27\u20133.31                0.938                        1.27               0.30\u20135.33              0.741 \nNo                                                                                                             Reference                                                                    Reference \n\n\n\n \n*Significant result. \nCOR = crude odds ratio. \naOR = adjusted odds ratio \n\n\n\nTable IV: Logistic Regressions of perceived stress risk factors among healthcare drivers during the COVID-19 pandemic\n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 656\n\n\n\n\n\n\n\n\nStress perceived by drivers in public healthcare facilities in Negeri Sembilan during the first year of the COVID-19 pandemic\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                657 \n\n\n\nMeanwhile, the designation of on-call status was established \nin response to the need for individuals in a shift-based work \nsystem to be available for post-office hours or double shifts. A \nmotor vehicle accident was operationally defined as an \nincident involving a driver operating a healthcare vehicle \nwho was involved in a collision while carrying out their \nprofessional responsibilities. The health status of the \nhealthcare drivers was determined based on the yearly health \nassessment, either by the Occupational and Environmental \nHealth Unit in district health offices or the Occupational \nSafety and Health Unit in hospitals. \n \nData Collection \nThe questionnaires were distributed and collected by the \nOccupational and Environmental Health Officer in each \ndistrict and hospital. The chosen drivers were approached at \nwork and given a study explanation as well as a participant \ninformation sheet. They were given a week to decide whether \nor not to participate in this study, and informed consent \nforms were given to them after they agreed to participate and \nwere then provided with a series of questionnaires. They had \n3 days to finish the questionnaires. The completed \nquestionnaires were submitted to the Occupational and \nEnvironmental Health Officer in each district and hospital \nupon completion. \n \nData Analysis \nThe Statistical Package for the Social Sciences (SPSS) version \n22 was used to analyse the data. The distribution of the data \nwas not normal. Thus, the association between demographic \ncharacteristics, health status, occupational characteristics \nand stress status was determined using the Chi-square test, \nFisher Exact test, Mann\u2013Whitney test and Kruskal\u2013Wallis test \ndepending on the data variables. Moreover, the collected \ndata underwent multiple logistic regression analysis in order \nto validate the significant risk factors associated with \nperceived stress among healthcare drivers in Negeri Sembilan \nduring the first year of the COVID-19 pandemic. \n \nEthical Consideration \nThis study was registered in the National Medical Research \nRegistry (NMRR-20-2187-56430 (IIR)). The study was \nconducted in accordance with the Declaration of Helsinki \nand was approved by the Medical Research Ethics Committee \n(MREC), Ministry of Health Malaysia (KKM/NIHSEC/ P20-\n2576 (4)), on 25 January 2021. \n \n \nRESULTS \nThe total number of participants in this study was 163, \nresulting in a response rate of 95.8%. In general, non-\nambulance drivers make up 71.2% (n = 116) of the \nhealthcare drivers working for the Negeri Sembilan SHD, \nwhile ambulance drivers make up 28.8% (n = 47) of the \nworkforce. At the end of the first year of the COVID-19 \npandemic, 7.4% of healthcare drivers reported experiencing \nsome degree of perceived stress. Moreover, from the findings \npresented in Table I, ambulance drivers at the Negeri \nSembilan SHD had perceived higher levels of stress (10.6%) \ncompared to non-ambulance drivers (6.0%). \n \n \n\n\n\nAs shown in Table II, the majority of respondents were aged \n30\u201339 (49.7%), had a monthly household income of less than \nMYR 2,000 (46.6%), were Malay (95.7%), were married \n(90.1%) and had their highest education of a high school \ncertificate (90.1%). In addition, 70% of healthcare drivers are \noverweight or obese; 55.2% are smokers and 98.8% do not \nconsume alcohol. The majority of drivers in the SHD are in \ngood health (79.8%), whereas 20.8% have at least one \ncomorbid disease; 13.7% have diabetes, 8.7% have \nhypertension, 0.6% have hypercholesterolaemia and 0.6% \nhave heart disease. A majority of them are smokers (55.3%), \nwhilst only 1.2% consume alcohol. In addition, a correlation \nexists between household income (p = 0.044), smoking status \n(p = 0.009) and perceived stress. However, there is no \nsignificant relationship between other demo-graphic \nparameters (such as age, race, marital status and education \nlevel) and experienced stress, or between perceived stress and \nother health concerns (like BMI, diabetes mellitus, \nhypertension, hypercholesterolaemia, heart diseases, \ncomorbidities and alcoholism). \n \nMore than 7 out of 10 healthcare drivers working with the \nNegeri Sembilan SHD are assigned as non-ambulance drivers \nor department transport service drivers. They have been \nworking with the ministry of health on average for 10.6 \u00b1 7.4 \nyears, and the majority of them work during office hours \n(82.2%). On average, the healthcare drivers in the \ndepartment have been with the ministry of health in the \ncurrent hospital or district health office unit for 8 \u00b1 6.8 years. \nOn average, they worked around 52.6 \u00b1 20 hours per week \nduring the COVID-19 pandemic. More than half of them did \nwork on an on-call basis (50.9%) after office hours and were \nsatisfied with their working schedule (96.3%). Nevertheless, \nperceived stress among healthcare drivers was associated \nwith on-call status (p = 0.032). Having said that, most of \nthem still feel that they need a part-time job (78.5%) on top \nof their full-time job, but only 35.6% of them have a part-\ntime job. On the category of motor vehicle accidents \ninvolving department vehicles, seven healthcare drivers had \na history of motor vehicle accidents involving department \nvehicles during their employment, with 4.3% reported \naccidents during the COVID-19 pandemic. However, there is \nno association found between perceived stress and duration \nof employment, working hour duration, work schedule, \nhaving part-time job and motor vehicle accident.   \n \nA logistic regression analysis was conducted to examine the \nassociation between perceived stress and several variables \namong healthcare drivers during the COVID-19 pandemic. \nThe result indicated that three variables were found to be \nstatistically significant (p<0.05) predictors of perceived stress. \nThese variables included smoking (OR 9.76, 95% CI 1.23\u2013\n77.51), duration of employment at the current unit (OR 1.07, \n95% CI 1.00\u20131.16) and on-call status (OR 5.34, 95% CI 1.13\u2013\n25.20). Meanwhile, the multiple logistic regression revealed \nthat healthcare drivers who are smokers had a significantly \nhigher odds ratio of 19.99 (95% CI 1.86\u2013213.90) compared to \nnon-smokers. In addition, these individuals were found to \nhave 8.69 times the odds (95% CI 1.21\u201362.28) of engaging in \non-call duties compared to healthcare drivers not doing an \non-call. \n \n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 657\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n658                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nDISCUSSION \nDrivers in the healthcare industry play an important role \nbecause their jobs include moving people's lives. Stress level \nof healthcare drivers or ambulance drivers is very dynamic \ndepending on the stressors at the workplace. The level of \nstress among healthcare drivers at the SHD of Negeri \nSembilan remained under control at the end of the first year \nof the COVID-19 pandemic, in contrast to the pool \nprevalence of stress among first responders including \nambulance drivers for medical emergencies, which reported \n17% stress prevalence during the first year of the COVID-19 \npandemic.31 Despite that, the level of perceived stress in \nalmost similar prevalence with the study conducted by \nNordin et al. on healthcare workers in northwest Malaysia, \nwho reported a 6.4%32 with almost a similar study timeframe. \nHowever, with regards to an Asia-Pacific study among \nhealthcare workers in 2020, which involved India, Singapore, \nMalaysia, Vietnam and Indonesia, Malaysia was found to be \nthe second highest (5.7%) after Indonesia, which was 6.8%.33 \nHowever, the prevalence of stress would vary depending on \nthe healthcare facilities and respondents, even though the \nstudies were conducted in a nearly identical timeframe, such \nas a study in the Sarawak Hospital, Malaysia that recorded \n57.1%34 and a study in the primary health clinics of Selangor, \nMalaysia which reported it to be at 2.8%.35 Based on this \nstudy, ambulance drivers experienced higher prevalence \ncompared to non-ambulance drivers, which differ in job \nassignments. \n \nFurthermore, this study also noted that low household \nincome (less than MYR 2,000), performing on-call and \nsmoking were associated with perceived stress among \nhealthcare drivers. Household income of less than 2,000 \nMalaysian Ringgit (MYR) is the lowest of the four categories \nof household income below the B40 threshold in Malaysia.36 \nHowever, further analysis using multiple logistic regression \nrevealed no significant association between stress and \nhousehold income. Nonetheless, employers should prioritise \nhealthcare drivers when allocating resources like \ngovernment-subsidized housing and child care in order to \nmanage their salary competitiveness. Financial management \neducation may be useful for this occupation category as well. \nThe stress of being on call has been established by other \nstudies,37 but prospective healthcare drivers should still be \nreminded of their responsibilities. However, this may also be \nthe result of working excessive hours without taking \nadequate breaks or poorly managing a roaster.38 According to \na study conducted in the USA, medium to high levels of inter-\nshift recovery were highest for shifts over 12 h in length \n(61.6%), lowest for shifts under 12 h in length (47.7%) and \nhighest for shifts of 12 h (40.2%).39 Nevertheless, the \nOccupational Safety and Health (OSH) team must conduct \nlocality assessments of workers to determine safe maximum \nworkweeks and break times, as varying working conditions \nmay have a cumulative effect on employee productivity.40 \n \nDrivers in the healthcare industry play a crucial role, so it is \nimperative that they are in good physical and mental health. \nBased on this study, more than half of the healthcare workers \nin the Negeri Sembilan SHD are smokers. This puts them at \nrisk for cardiovascular diseases and cancers such as \nhypertension, heart disease, peripheral arterial disease and \n\n\n\nlung cancer, despite the fact that the vast majority of them (8 \nout of 10) are healthy and have no other health issues. \nContrarily, a study of Swedish ambulance workers revealed \nthat they had a higher prevalence of heart problems \n(paroxysmal tachycardia, atrial fibrillation, flutter, and other \ncardiac arrhythmias), high blood pressure and dorsopathies \nthan individuals in other occupations.41 As cardiovascular \ndiseases can result in motor vehicle accidents,42 a yearly \nphysical examination and fitness certificate must include a \nheart evaluation, such as an electrocardiogram (ECG). \nFurthermore, continuous awareness and participation in \ninterventional activities at the workplace need to be \nemphasised by the Occupational Safety and Health team. \n \nAdditionally, this study did not find significant associations \nbetween stress among ambulance drivers and other factors \nsuch as gender, age, household income, type of shift work, \nrisk of getting COVID-19 infection, adequacy of personal \nprotective equipment, history of accidents within 1 year and \npressure from family members and patients compared to the \nother studies.43,44 According to the study conducted by Amro et \nal. found that younger female drivers displayed higher levels \nof stress compared to both male and older ambulance \ndrivers.43 In contract to gender, the observation that driving is \npredominantly associated with males in Malaysia is \nexpected, as there is a notable lack of female applicants for \nsuch positions. In contrast to the present study, Pinnalin et al. \nconducted a study that revealed supplementary variables \nlinked to stress levels among ambulance drivers amidst the \nCOVID-19 pandemic. These variables encompassed monthly \nhousehold income, the nature of shift work, the ambulance \ndriver\u2019s accident record within the previous year, as well as \nthe influence exerted by family members and patients.44     \n \nDespite the fact that the perceived stress levels of healthcare \ndrivers appear to be under control, the OSH team must \ncontinue to exert effort to maintain the situation. Because \nstress management training continuously increases drivers\u2019 \nawareness, train them to control, reduce and tolerate the \ninternal and external demands of a certain situation in \nwhich their individual resources are exceeded. Even though, \naccording to a study conducted in Switzerland, paramedics \nrequire less psychological support than other professions due \nto their high level of experience and long-standing training \nin stress management over the course of their careers, they \nare often used to address stressful situations as they are part \nof a coordinated and ordered emergency response and have \nto constantly handle very high levels of stress. According to \nresearch by Lawn et al., the needs of ambulance workers in \nterms of mental health can be classified into four main \ncategories: organisational support, informal support, the use \nof humour and individual ways of coping, such as \ndetachment and external support.18 In a general way, \nstopping unpleasant emotions and thoughts is the most \neffective coping strategy for the reduction of stress levels and \nan increase in positive mental states.                                       \n \nA limitation of this study is that it was unable to identify the \nfactors associated with each driver, as the sample size may \nnot have been adequate given that the study was conducted \nin a single stratum and addressed the study objective, as the \nstress associated with ambulance drivers may differ from that \n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 658\n\n\n\n\n\n\n\n\nStress perceived by drivers in public healthcare facilities in Negeri Sembilan during the first year of the COVID-19 pandemic\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                659 \n\n\n\nof other drivers. In addition, this is a cross-sectional study \nthat only reflects the assessment conducted during the study. \nFollowing up from this study, the OSH team could initiate \nanother research on the adaptability of healthcare drivers in \nMalaysia to varying working hours in terms of \nenvironmental adaptation, which would help policymakers, \nset the working hours limit for healthcare drivers, especially \nin relation to adequate breaks for on-call drivers. In addition, \nan interventional study based on the healthcare driver's \nbehaviour therapy could enhance the overall performance of \ndrivers in terms of occupational safety and health as it \nincreases the driver\u2019s insight. \n \n \nCONCLUSION \nThe study found that perceived stress among Malaysian \nhealthcare drivers during the OVID-19 pandemic was \nrelatively low. The implementation of movement control \norders during the COVID-19 pandemic in Malaysia resulted \nin a reduction in the frequency of life-threatening tasks, \nemergencies and assigned tasks. The consistent provision of \nsafety and health training by the OSH team, which includes \nstress management and a smoking cessation programme, \npotentially contributed to the healthcare driver\u2019s ability to \nmanage the stressful situation. In order to enhance salary \ncompetitiveness, employers ought to offer financial \nmanagement education alongside subsidised housing and \nchildcare provisions. \n \n \nACKNOWLEDGMENTS \nThe authors would also like to offer their appreciation to the \nDirector General of Health Malaysia for permitting this paper \nto be published. This study has been presented at the 28th \nInternational Symposium on Epidemiology in Occupational \nHealth (EPICOH) on October 25\u201328, 2021 through virtual \nplatform. \n \n \nDECLARATION OF INTEREST \nThe authors would like to disclose that they have no conflict \nof interests to declare and have no competing interests in this \nstudy. This research was self-funded and received no external \nfunding. \n \n \nREFERENCES \n1. World Health Organization. COVID 19, Public Health Emergency \n\n\n\nof International Concern (PHEIC) WHO Web page: World Health \nOrganization; 2020. Available from: \nhttps://www.who.int/publications/m/item/covid-19-public-\nhealth-emergency-of-international-concern-(pheic)-global-\nresearch-and-innovation-forum. \n\n\n\n2. 2. Scapaticci S, Neri CR, Marseglia GL, Staiano A, Chiarelli F, \nVerduci E. The impact of the COVID-19 pandemic on lifestyle \nbehaviors in children and adolescents: an international \noverview. 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Prevalens tekanan dan penyebab tekanan kerja di \nkalangan jururawat terlatih hospital Kuala Lumpur [prevalence \nand causes of occupational stress among staff nurses in HKL] \n(Kuala Lumpur, Malaysia: National University of Malaysia; \n1994. \n\n\n\n31. Huang G, Chu H, Chen R, Liu D, Banda KJ, O'Brien AP, et al. \nPrevalence of depression, anxiety, and stress among first \nresponders for medical emergencies during COVID-19 pandemic: \na meta-analysis. J Glob Health. 2022; 12: 05028. \n\n\n\n32. Nordin S, Yaacob NA, Kelak J, Ilyas AH, Daud A. The Mental \nHealth of Malaysia's Northwest healthcare workers during the \nrelaxation of COVID-19 restrictions and its associated Factors. Int \nJ Environ Res Public Health. 2022; 19(13): 7794. \n\n\n\n33. Chew NWS, Ngiam JN, Tan BY-Q, Tham S-M, Tan CY-S, Jing M, \net al. Asian-Pacific perspective on the psychological well-being of \nhealthcare workers during the evolution of the COVID-19 \npandemic. BJPsych Open. 2020; 6(6): e116. \n\n\n\n34. Sim SK, Lau BL, Zaila SR, Hazira N, Aniqah NM, Panicker J, et al. \nPsychological symptoms among healthcare workers handling \nCOVID-19 patients. Med J Malaysia. 2021; 76(2): 138-44. \n\n\n\n35. Salaton NF, Bulgiba A. depression, anxiety, and stress among \nfrontline primary health care workers during the COVID-19 \npandemic. Asia Pacif J Public Health. 2022; 34(4): 416-9. \n\n\n\n36. Department of Statistics M. Household income and basic \namenities survey report 2019 Putrajaya; 2020. \n\n\n\n37. Nicol AM, Botterill JS. On-call work and health: a review. Environ \nHealth. 2004; 3(1): 15. \n\n\n\n38. Willis E, Lawn S, Roberts L, Couzner L, Mohammadi LM, Goble E. \nThe impact of emergency call taking on the mental health and \nwellbeing of ambulance call-takers: a systematic thematic \nnarrative of qualitative research. Austral J Paramed. 2020; 17: 1-\n11. \n\n\n\n39. Patterson PD, Buysse DJ, Weaver MD, Callaway CW, Yealy DM. \nRecovery between work shifts among emergency medical services \nclinicians. Prehosp Emerg Care. 2015; 19(3): 365-75. \n\n\n\n40. Thielmann B, Schnell J, B\u00f6ckelmann I, Schumann H. Analysis of \nwork related factors, behavior, well-being outcome, and job \nsatisfaction of workers of emergency medical service: a \nsystematic review. Int J Environ Res Public Health. 2022; 19(11): \n6660. \n\n\n\n41. Karlsson K, Nasic S, Lundberg L, M\u00e5rtensson J, Jonsson A. Health \nproblems among Swedish ambulance personnel: long-term risks \ncompared to other professions in Sweden - a longitudinal register \nstudy. Int J Occup Saf Ergon. 2022; 28(2): 1130\u201335.  \n\n\n\n42. Ronna BB, Thiese MS, Ott U, Effiong A, Murtaugh M, Kapellusch \nJ, Garg A, Hegmann K. The association between cardiovascular \ndisease risk factors and motor vehicle crashes among \nprofessional truck drivers. J Occup Environ Med. 2016; 58(8): \n828\u201332.  \n\n\n\n43. Amro TM, Arcos Gonz\u00e1lez P, Montero Vi\u00f1uales E, Castro Delgado \nR. Impact of COVID-19 pandemic on stress and burnout levels \namongst emergency medical technicians: a cross-sectional study \nin Spain. Ann Med. 2022; 54(1): 3007\u20133016.  \n\n\n\n44. Pinalin P, Chaiyanun T, Sara A, Suchinda Jarupat M, Jutatip S. \nThe stress level and stress related factors among ambulance \ndrivers. Nurs J CMU 2021; 48(4): 2021.  \n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 660\n\n\n\n\n\n\n\n\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                635 \n\n\n\nABSTRACT \nIntroduction: Epilepsy is a neurological disease with high \nglobal prevalence. Almost one-third of epilepsy patients \ncontinue having seizures despite adequate treatment. \nPerampanel has been widely used in the Western countries \nas an adjunctive therapy for both generalized and focal \nseizures. Owing to its high cost, the use of perampanel is \nlimited in our country.  \n \nMaterials and Methods: We conducted a descriptive, \nretrospective study among epilepsy patients treated with \nperampanel. We aimed to assess the efficacy and safety of \nperampanel as an adjunctive in our hospital.  \n \nResults and Conclusions: From our cohort of 25 patients, \nmost of the patients were either on one or three anti-seizure \nmedications (ASMs) prior to initiation of perampanel. \nPerampanel was added in 88% of them due to persistent \nseizures. Twenty-two (88%) patients experienced reduction \nin seizure frequency. 12% experienced mild side effects, \nwhich were leg cramps, hyponatremia and drowsiness. Only \n1 patient stopped perampanel due to its side effects.  \n \nConclusion: Perampanel is a well-tolerated ASM that should \nbe widely used as an adjunctive. More studies with regards \nto its efficacy and safety involving more centres are \nencouraged in Malaysia. \n \nKEYWORDS:  \nEpilepsy, refractory, anti-seizure medication, perampanel, \ndizziness \n \n \nINTRODUCTION \nEpilepsy is a chronic brain disorder, characterised by two or \nmore unprovoked seizures occurring more than 24 hours \napart, due to the abnormal excessive or synchronous \nneuronal activity in the brain. The prevalence of epilepsy \ndiffers in different countries, ethnics, and socioeconomic \nstatuses, with an overall lifetime population prevalence, \nworldwide, of 7.60 per 1,000.1 The overall lifetime prevalence \nof epilepsy in Asian countries correlates with the worldwide \ndata, varying from 1.5 to 14.0 per 1000 population, and it is \nreported as 7.8 per 1000 population in Malaysia.2 \n \nTreatment for epilepsy includes anti-seizure medications \n(ASMs), which are expected to achieve seizure freedom in \n70% of patients. The remaining 30% of patients might need \n\n\n\na substitution or an addition of a second ASM.3 All ASMs can \nbe categorised into broad- and narrow-spectra. Broad-\nspectrum ASMs such as valproic acid are commonly initiated \nin generalized or uncertain type of epilepsy; whereas narrow-\nspectrum ASMs such as carbamazepine and phenytoin are \nused in the treatment of focal seizures.4 Recent years, many \nnew ASMs with a wide variety of mechanisms of action were \nintroduced with high hopes for a better seizure control. \nHowever, prospective audits on new ASMs such topiramate, \nlevetiracetam, zonisamide, pregabalin, and lacosamide as an \nadjunctive therapy were disappointing with a low seizure \nfreedom rate of less than 25%.5 \n \nPerampanel is one of the new ASMs introduced as an \nadjunctive therapy for epilepsy. It is a selective, non-\ncompetitive antagonist of \u03b1-amino-3-hydroxy-5-methyl-4-\nisoxazolepropionic acid (AMPA)-type glutamate receptors on \npost-synaptic neurons.6 Many promising data were reported \nin the Western countries for the use of perampanel as an \nadjunctive therapy in refractory focal-onset seizures as well as \ngeneralized tonic-clonic seizures.7-9 The commonly reported \nside effects of perampanel are dizziness, convulsion, and \nsomnolence, which are statistically insignificant at low \ndoses.10 The utilisation of perampanel in the Asian \npopulation, especially in South East Asia is relatively low as \ncompared to the Western countries, with limited information \non its clinical performance and safety profile. More clinical \nstudies are warranted for better cognizance of perampanel as \nan adjunctive treatment in the Asian population. \n \nThe aim of this study was to determine the change in seizure \nfrequency and responder rate upon initiation of perampanel \nas an adjuntive ASM. We also studied the adverse events \nrelated to perampanel and the reasons for its \ndiscontinuation. \n \n \nMATERIALS AND METHODS \nThis was a single-centre, descriptive, retrospective study done \nat the Hospital Canselor Tuanku Muhriz after obtaining \napproval of the Research Ethics Committee (Project Code: FF-\n2021-422). All patients with epilepsy treated with \nperampanel were included in this study. Those with missing \ndata were excluded.  \n \nTwenty-five epilepsy patients treated with perampanel as an \nadjunctive therapy from January 2015 till December 2020 \n\n\n\nEfficacy and safety of adjunctive treatment with perampanel \nin epilepsy patients \n \nKuan Yee Lim, Dr Int Med1, Ching Soong Khoo, FRCP1,2, Rathika Rajah, Dr Int Med1, Hui Jan Tan, FRCP1,2, Farah \nWaheeda Tajurudin, MPharm3 \n\n\n\n     \n1Department of Medicine, Hospital Canselor Tuanku Muhriz, 2Department of Medicine, Faculty of Medicine, Universiti \nKebangsaan Malaysia, 3Department of Pharmacy, Hospital Canselor Tuanku Muhriz \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 13 August 2023                                                                                                                                                                         \nCorresponding Author: Ching Soong Khoo                                                                                                                                                                          \nEmail: chingsoongkhoo@gmail.com \n\n\n\n13-Efficacy00110.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 635\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n636                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nwere recruited from the Neurology Clinic of our hospital. The \npatients\u2019 demographics and characteristics of their seizures \nwere collated in a data collection sheet. \n \nThe statistical analysis was performed using IBM Statistical \nProduct and Service Solutions (SPSS) version 26.0. Descriptive \nstatistics were used to present the variables recorded. We \ntabulated the descriptive statistics to summarize our data. \nNormally distributed data were expressed using mean \u00b1 \nstandard deviation; whereas data that was not normally \ndistributed were reported using median (inter-quartile range). \n \nIn this study, the efficacy of perampanel (seizure reduction) \nwas taken as at least 50% reduction in seizure frequency \ncompared to the baseline; whereas the safety of perampanel \nwas measured as presence of any side effects among patients \nwho were on perampanel.   \n \n\n\n\nRESULTS \nA total of 25 patients had perampanel as an adjunctive ASM. \nTwelve (48.0%) were Chinese, 11 (44.0%) Malay and 1 (4.0%) \neach, were Indian and other races. The mean age (\u00b1 standard \ndeviation [SD]) of our patients was 37.5 years (\u00b1 13.4 years), \nwith predominantly males (17, 68.0%). Eleven (44.0%) \npatients had other medical illnesses, which included \nmetabolic diseases (3, 12.0%), brain related diseases (3, \n12.0%), genetic diseases (3, 12.0%), malignancy (1, 4.0%) \nand autoimmune diseases (1, 4.0%) (Table I). \n \nThe mean duration of epilepsy in our cohort was 1.6 years (\u00b1 \n0.9 years). Regarding the types of epilepsy, they were almost \nequally distributed between generalised (13, 52.1%) and focal \n(12, 47.9%) epilepsy. The aetiology of epilepsy in most of our \npatients was unknown (12, 48.0%), while a small number \nwere contributed by structural (5, 20.0%) and infectious (5, \n20.0%) causes (Table II). \n\n\n\nCharacteristics                                                                                                   n (%) \nEthnicity                                                                                                                    \n\n\n\nMalay                                                                                                          11 (44.0) \nChinese                                                                                                       12 (48.0) \nIndian                                                                                                           1 (4.0) \nOthers                                                                                                           1 (4.0) \n\n\n\nAge (year)                                                                                                                 \n0-20                                                                                                              3 (12.0) \n21-40                                                                                                           11 (44.0) \n41-60                                                                                                            9 (36.0) \n61-80                                                                                                             2 (8.0) \n\n\n\nGender                                                                                                                      \nMale                                                                                                            17 (68.0) \nFemale                                                                                                         8 (32.0) \n\n\n\nMedical diseases                                                                                                       \nMetabolic                                                                                                    3 (12.0) \nBrain related                                                                                               3 (12.0) \nMalignancy                                                                                                   1 (4.0) \nGenetic                                                                                                        3 (12.0) \nAutoimmune                                                                                                1 (4.0) \nNone                                                                                                           14 (56.0) \n\n\n\n\n\n\n\nTable I: Patients\u2019 demographic characteristics (n = 25)\n\n\n\nCharacteristics                                                                                                   n (%) \nType of epilepsy                                                                                                       \n\n\n\nGeneralised onset                                                                                      13 (52.0) \nFocal onset                                                                                                 12 (48.0) \nUnknown onset                                                                                           0 (0.0) \n\n\n\nDuration of disease (year)                                                                                       \nLess than one                                                                                               2 (8.0) \n1-10                                                                                                             10 (40.0) \n11-20                                                                                                            8 (32.0) \n21 and above                                                                                              5 (20.0) \n\n\n\nAetiology \nStructural                                                                                                     5 (20.0) \nGenetic                                                                                                         2 (8.0) \nInfectious                                                                                                     5 (20.0) \nMetabolic                                                                                                     1 (4.0) \nUnknown                                                                                                   12 (48.0) \n\n\n\nEEG                                                                                                                            \nNormal                                                                                                         3 (12.0) \nAbnormal spikes                                                                                        22 (88.0)                                                            \n\n\n\nMRI                                                                                                                            \nNormal                                                                                                        14 (56.0) \nAbnormal                                                                                                   11 (44.0) \n\n\n\n\n\n\n\nTable II:\u2008Epilepsy characteristics (n = 25)\n\n\n\n13-Efficacy00110.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 636\n\n\n\n\n\n\n\n\nEfficacy and safety of adjunctive treatment with perampanel in epilepsy patients\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                637 \n\n\n\nMost of our patients were on at least one (7, 28.0%) or three \n(7, 28.0%) ASMs (mean \u00b1 SD = 2.4 \u00b1 1.1) prior to the addition \nof perampanel. More than three-quarter (22, 88.0%) had \nperampanel added due to persistent seizures with previous \nASMs. Three (12.0%) patients had both persistent seizures \nand side effects from the previous ASM, which led to the \naddition of perampanel. After adding perampanel, 22 \n(88.0%) experienced at least 50% reduction in seizure \nfrequency from their baseline, and only three (12.0%) had no \nchange in seizure frequency. \n \nThe mean (\u00b1 SD) duration of perampanel use among our \npatients was 1.5 years (\u00b1 1.1 years). Only 3 (12.0%) \ncomplained of side effects, which were leg cramps, \nhyponatremia and drowsiness. Thirteen (52.0%) patients are \nstill on perampanel; 1 (4.0%) on the other hand stopped \ntreatment due to drowsiness. The remaining 11 (44.0%) \npatients were not on perampanel as they defaulted follow up \nor died (Table III). \n \n \nDISCUSSION \nMost of our patients with epilepsy are of Malay (11, 44.0%) \nand Chinese (12, 48.0%) ethnicity. This is representative of \nthe national population whereby Malay and Chinese form \nthe two largest ethnic groups in Malaysia. In the West, whites \nare more prone to having primary generalized epilepsy, \nwhereas no racial differences were seen in temporal or frontal \nlobe epilepsy.11 However in Malaysia, there are no recent \n\n\n\nstudies to suggest ethnic preponderance towards types of \nepilepsy. Our epilepsy patients are predominantly male (17, \n68.0%). This can be explained by the fact that they are more \nvulnerable to head injuries, stroke and CNS infections \nleading to seizures.12 \n \nKeezer et al., mentioned in their paper that almost half of the \nadults with epilepsy have at least one medical comorbidity. \nDiseases such as depression, dementia, anxiety, heart related \ndiseases and peptic ulcer diseases are strongly related to \nepilepsy due it its bidirectional relations.13 In our current \ncohort, they did not have any psychiatric or heart related \nissues. \n \nWhen treating epilepsy, the gold standard is to use \nmonotherapy at its most tolerated dose. Most of the time, a \nsecond or third agent is needed, thus achieving seizure \nfreedom in more than half patients.14 The average ASMs used \nby our patients were two ASMs, prior to addition of \nperampanel. Almost all of them had perampanel added due \nto persistent seizures and/or adverse effects from other ASMs. \nThe recent PERaMpanel pooled analysIs of effecTiveness and \ntolerability (PERMIT) study showed that perampanel can be \nused as mono, or an adjunctive therapy to treat epilepsy, \nowing to its broad-spectrum properties.15,16 The use of \nperampanel contributes to a significant reduction in seizure \nfrequency, similar to our study in which up to 88.0% of the \npatients had seizure reduction. \n \n\n\n\nCharacteristics                                                                                                   n (%) \nNumber of ASMs prior to perampanel                                                                   \n\n\n\n1                                                                                                                   7 (28.0) \n2                                                                                                                   6 (24.0) \n3                                                                                                                   7 (28.0) \n4 and more                                                                                                  5 (20.0) \n\n\n\nIndications for adding perampanel                                                                        \nPersistent seizures with previous ASM                                                     22 (88.0) \nSide effects from previous ASM                                                                 0 (0.0) \nBoth                                                                                                             3 (12.0) \n\n\n\nChanges in seizure frequency                                                                                 \nNo change in seizure frequency                                                               3 (12.0) \nSeizure reduction$                                                                                      22 (88.0) \nIncrease in seizure frequency                                                                     0 (0.0)                                                              \n\n\n\nDuration on perampanel (year)*                                                                            \nLess than 1                                                                                                  5 (23.8) \n1-2                                                                                                                5 (23.8) \n2-3                                                                                                                6 (28.6) \nMore than 3                                                                                                5 (23.8) \n\n\n\nSide effects from perampanel                                                                                 \nYes\u2020                                                                                                              3 (12.0) \nNo                                                                                                               22 (88.0) \n\n\n\nContinuation of perampanel                                                                                  \nYes                                                                                                              13 (52.0) \nNo                                                                                                               12 (48.0) \n\n\n\nReasons discontinuing perampanel (n = 12)                                                          \nDue to side effects                                                                                       1 (8.3) \nOthers#                                                                                                        11 (91.7) \n\n\n\n \n*4 missing data as patients died/defaulted follow up / transferred care to another hospital \n\u2020Side effects reported include leg cramps, hyponatremia, drowsiness. \n#Other causes such as patients died or defaulted follow up. \n$Seizure reduction refers to at least 50% reduction in seizure frequency from baseline (efficacy of perampanel). \nASM = Anti-seizure medication \n\n\n\nTable III: Perampanel and epilepsy (n = 25)\n\n\n\n13-Efficacy00110.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 637\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n638                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nPatients on perampanel commonly reported experiencing \nside effects, namely dizziness, fatigue, somnolence and \nirritability.10 This was seen among those on perampanel 12 \nmg per day and the discontinuation rate among this group \nwas as high as 5% due to its side effects. The incidence of \ndizziness among this group was as high as 20%.17 One of our \npatients had to discontinue perampanel owing to dizziness \naffecting the daily activities. \n \nAlthough the incidence is low, one of the most concerning \nside effects of perampanel is worsening of depression and \naggression when not used in caution in patients with pre-\nexisting psychiatric illness.10 None of our patients suffered \nfrom any neuropsychiatric illnesses. We noted that one \npatient had hyponatremia secondary to perampanel. \nHyponatremia caused by perampanel was rarely reported \nand the incidence is only less than 1% of general \npopulation.18 \n \nOur study has several limitations. The sample size was too \nsmall due to the high cost of perampanel, which most \npatients could not afford.  This is a single-centre and \nretrospective study, the findings of which might not be \ngeneralizable. Many patients also lost to follow up while on \nperampanel. \n \n \nCONCLUSIONS \nPerampanel is a well-tolerated ASM that could be considered \nas an adjunctive treatment among epilepsy patients in \nMalaysia. More studies on the efficacy, retention rate and \nside effects of perampanel involving a larger population are \nencouraged. \n \n \nACKNOWLEDGEMENT \nThe authors would like to thank the staff of the Neurology \nUnit and Department of Pharmacy, Hospital Canselor \nTuanku Muhriz for their help in completing the study.   \n \n \nCONFLICT OF INTEREST \nThe authors declared no potential conflicts of interest with \nrespect to the research, authorship, and/or publication of this \narticle. The authors received no financial support for the \nresearch, authorship, and/or publication for this article.  \n \n \n \n \n\n\n\nREFERENCES \n1. Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020; \n\n\n\n54(2): 185-91. \n2. Fong SL, Lim KS, Tan L, Zainuddin NH, Ho JH, Chia ZJ, Choo WY, \n\n\n\nPuvanarajah SD, Chinnasami S, Tee SK, Raymond AA. \nPrevalence study of epilepsy in Malaysia. Epilepsy Res 2021; 170: \n106551. \n\n\n\n3. Sander JW. The use of antiepileptic drugs\u2014principles and \npractice. Epilepsia 2004; 45: 28-34. \n\n\n\n4. Subbarao BS, Silverman A, Eapen BC. Seizure Medications. \nStatPearls [Internet]. 2023 Jan. \n\n\n\n5. Brodie MJ, Kelly K, Stephen LJ. Prospective audits with newer \nantiepileptic drugs in focal epilepsy: insights into population \nresponses? Epilepsy Behav 2014; 31: 73-6. \n\n\n\n6. Plosker GL. Perampanel: as adjunctive therapy in patients with \npartial-onset seizures. CNS Drugs 2012; 26: 1085-96. \n\n\n\n7. Franco V, Crema F, Iudice A, Zaccara G, Grillo E. Novel treatment \noptions for epilepsy: focus on perampanel. Pharmacol Res 2013; \n70(1): 35-40. \n\n\n\n8. French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza \nA, Kumar D, Rogawski MA. Adjunctive perampanel for refractory \npartial-onset seizures: randomized phase III study 304. Neurol \n2012; 79(6): 589-96. \n\n\n\n9. French JA, Krauss GL, Wechsler RT, Wang XF, DiVentura B, \nBrandt C, Trinka E, O'Brien TJ, Laurenza A, Patten A, Bibbiani F. \nPerampanel for tonic-clonic seizures in idiopathic generalized \nepilepsy: a randomized trial. Neurol 2015; 85(11): 950-7. \n\n\n\n10. Rugg\u2010Gunn F. Adverse effects and safety profile of perampanel: a \nreview of pooled data. Epilepsia. 2014; 55: 13-5. \n\n\n\n11. Santiago M, Niedermeyer E. Racial factors and epileptic seizure \ndisorders. J Epilepsy 1988; 1(1): 31-3. \n\n\n\n12. McHugh JC, Delanty N. Epidemiology and classification of \nepilepsy: gender comparisons. Int Rev Neurobiol 2008; 83: 11-26. \n\n\n\n13. Keezer MR, Sisodiya SM, Sander JW. Comorbidities of epilepsy: \ncurrent concepts and future perspectives. Lancet Neurol 2016; \n15(1): 106-15. \n\n\n\n14. Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution \nor add-on?. Seizure. 2000; 9(7): 464-8. \n\n\n\n15. Akamatsu N, Kanemoto K, Maehara T. Optimal use of \nperampanel in the treatment of patients with epilepsy based on \nthe clinical evidence and characteristics. Brain and Nerve Shinkei \nKenkyu no Shinpo 2022; 74(7): 927-37. \n\n\n\n16. Villanueva V, D'Souza W, Goji H, Kim DW, Liguori C, McMurray \nR, Najm I, Santamarina E, Steinhoff BJ, Vlasov P, Wu T. PERMIT \nstudy: a global pooled analysis study of the effectiveness and \ntolerability of perampanel in routine clinical practice. J Neurol \n2022; 269(4): 1957-77. \n\n\n\n17. Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for \nfocal epilepsy: insights from early clinical experience. Acta \nNeurologica Scandinavica 2016; 133(3): 160-72. \n\n\n\n18. Morimoto M, Suzaki I, Shimakawa S, Hashimoto T, Nakatsu T, \nHamada S, Kyotani S. Three cases in which drug-induced \nhyponatremia was improved by replacing carbamazepine with \nlacosamide. Clin Case Rep 2020; 8(7): 1166-70. \n\n\n\n\n\n\n\n13-Efficacy00110.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 638\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                583 \n\n\n\nABSTRACT \nIntroduction: Fragrance allergy remains an important cause \nof contact dermatitis. We aim to describe the characteristics \nof patients with contact sensitisation to fragrances who \nunderwent patch testing in the Department of Dermatology \nHospital Kuala Lumpur. \n \nMaterials and Methods: This is a 5-year retrospective study \nof patients who developed positive reactions to fragrance \nallergens at the Department of Dermatology, Hospital Kuala \nLumpur, Malaysia between January 2017 and December \n2021. Patch tests were performed with European Baseline \nSeries and relevant extended series. Patch test readings \nwere recorded according to the International Contact \nDermatitis Research Group recommendation. \n \nResults: A total of 854 patients underwent patch test during \nthe study period with 133 (15.6%) patients developing at \nleast one positive reaction to fragrance allergens. The \nmedian age of patients at presentation was 40 years (range \n16-79) old with 78.2% females. The most common initial \npresentation was hand eczema (55.6%). Other commonly \ninvolved sites include face (38.3%), leg (35.3%) and trunk \n(22.6%). The most frequent sensitising fragrance allergens \nwere Fragrance Mix I (10.5%), Balsam of Peru (7.1%) and \nFragrance Mix II (4.9%). Sixty patients (45%) developed \npositive reaction to more than one fragrance allergens. \nTwelve patients (9%) developed positive patch test reactions \nto their own products such as skincare, hair dye and hand \nwash. Current relevance was recorded in 96 patients (72.2 \n%). \n \nConclusion: Contact sensitisation to fragrance allergens \nwas detected in about 15% of our patients who underwent \npatch test. The most common sensitising allergens were \nFragrance Mix I and II and Balsam of Peru.  \n \nKEYWORDS:  \nFragrances, allergic contact dermatitis, contact sensitisation to \nfragrances, patch test, Balsam of Peru \n \n \nINTRODUCTION \nContact dermatitis is defined as inflammation of the dermis \nand epidermis resulting from direct contact between a \nsubstance and the surface of the skin. It is the result of a type \n\n\n\nIV hypersensitivity reaction involving the T lymphocytes of \nimmune system. It can arise from exposure to various \nallergens which include metals, preservatives, woods and \nplants, plastic, rubber, medicines, medical devices, cosmetics \nand fragrances.1 \n \nAccording to International Fragrance Association (IFRA), \nfragrance ingredient is \u201cany basic substance used for its \nodour properties or malodour coverage.\u201d2 Fragrances are \nfrequently present in a variety of products for instance \ncosmetics (fine fragrances and aftershaves, lip balms, \nlipsticks, deodorants), household products (detergents), \ntoiletries (shampoos, soaps, lotions, creams, sunscreens), wet \nwipes, baby products, paper products, fabric and clothes, \ntopical pharmaceuticals, essential oils, industrial products \n(paints, rubber, plastic, insecticides, herbicides), and even \nflavouring agents in oral hygiene products, foods or drinks.3,4 \nPatch testing remains pivotal in diagnosing fragrance \nallergy. \n \nThis study aims to describe the characteristics of patients who \nhave contact allergy to fragrances in Hospital Kuala Lumpur, \nMalaysia. \n \n \nMATERIALS AND METHODS \nThis is a 5-year retrospective study of patients who developed \npositive reactions to fragrance allergens upon patch testing \nat the Department of Dermatology, Hospital Kuala Lumpur, \nMalaysia between January 2017 and December 2021. \n \nPatch tests were performed with European Standard Series \nand relevant extended series from Chemotechnique \nDiagnostics using IQ chambersTM. Extended series used \ninclude cosmetic series, metal series, rubber series, dental \nseries, medicament series, textile series, shoe series, plastic \nand glue series and hairdressing series. Fragrance allergens \nthat were tested in the study included Fragrance Mix I, \nFragrance Mix II, Balsam of Peru, and hydroxyisohexyl 3-\ncyclohexene carboxaldehyde (HICC) (Lyral) in the European \nbaseline series, as well as tea tree oil (oxidised), peppermint \noil, benzyl alcohol, musk mix and benzyl salicylate in the \ncosmetic series. Patients were also tested with their own \nproducts, including hair dye, hair shampoo, cosmetics, skin \ncare products, soap and toothpaste. Toothpaste and leave-on \ncosmetics such as lipstick, facial powder, facial foundation \n\n\n\nContact sensitisation to fragrance allergen: A 5-year \nretrospective study of patients in the Department of \nDermatology, Hospital Kuala Lumpur \n \nVivian Tai, MD1, Sharifah Rosniza Syed Nong Chek, AdvMDerm2, Min Moon Tang, AdvMDerm2 \n\n\n\n     \n1Department of Medicine, Hospital Kuala Lumpur, Ministry of Health, Malaysia, 2Department of Dermatology, Hospital Kuala \nLumpur, Ministry of Health, Malaysia  \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 03 July 2023                                                                                                                                                                              \nCorresponding Author: Tai Vivian                                                                                                                                                                                       \nEmail: viviantai.91@gmail.com \n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 583\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n584                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nCharacteristics                                                                                                                                        n = 133 (%) \nMedian age in years (range)                                                                                                                  40 (16 \u2013 79) \nMale:female ratio                                                                                                                                         1:3.6 \nEthnicity, n (%)                                                     Malay                                                                           75 (56.4) \n                                                                              Chinese                                                                        41 (30.8) \n                                                                              Indian                                                                            13 (9.8) \n                                                                              Others                                                                            4 (3.0) \nOccupations, n (%)                                               White collar workers                                                   32 (24.1) \n                                                                              Healthcare workers                                                     30 (22.5) \n                                                                              Blue Collar workers                                                     15 (11.3) \n                                                                              Pink collar workers                                                       11 (8.3) \n                                                                              Housewife                                                                    22 (16.5) \n                                                                              Unemployed                                                                23 (17.3) \nPatch test series used, n (%)                                European baseline                                                      133 (100) \n                                                                              Cosmetic                                                                       45 (33.8) \n                                                                              Rubber                                                                         34 (25.6) \n                                                                              Dental                                                                          18 (13.5) \n                                                                              Metal                                                                            18 (13.5) \n                                                                              Shoes                                                                            14 (10.5) \n                                                                              Hairdressing                                                                   9 (6.8) \n                                                                              Textile                                                                              8 (6) \n                                                                              Medicaments                                                                   8 (6) \n                                                                              Plastic and glue                                                               4 (3) \n                                                                              Own products                                                              65 (48.9) \n\n\n\nTable I: Characteristics of patients who developed positive reaction to fragrance allergens in patch testing\n\n\n\nSites                                                                                                                                   n (%) \nHand                                                                                                                                74 (55.6) \nFace                                                                                                                                  51 (38.3) \n                                                    Not otherwise specified                                             33 (24.8) \n                                                    Lips                                                                              17 (12.8) \n                                                    Ears                                                                               11 (8.3) \n                                                    Eyelids                                                                           8 (6.0) \n                                                    Nose                                                                               3 (2.3) \nLeg                                                                                                                                   47 (35.3) \nTrunk                                                                                                                               30 (22.6) \nArm                                                                                                                                  17 (12.8) \nNeck                                                                                                                                  12 (9.0) \nAnal/genital                                                                                                                      11 (8.3) \nScalp                                                                                                                                  8 (6.0) \nScattered generalised                                                                                                       8 (6.0) \n \n\n\n\nTable II: Sites of lesions in 133 patients who were sensitized to fragrance allergens\n\n\n\nAllergens                                                                                                        Number of patient positive to allergen (Sensitisation rate %) \nEuropean baseline series            Fragrance mix I                                                                                      90 (10.5) \nn =854                                         Balsam of Peru                                                                                        61 (7.1) \n                                                    Fragrance mix II                                                                                      42 (4.9) \nCosmetic series                            Tea tree oil oxidised                                                                                7 (2.9) \nn=242                                           Peppermint oil                                                                                         5 (2.4) \n                                                    Lyral                                                                                                         10 (1.2) \n                                                    Musk mix                                                                                                  1 (0.5) \n                                                    Benzyl alcohol                                                                                          1 (0.4) \n                                                    Benzyl salicylate                                                                                        0 (0) \n\n\n\nTable III:The sensitisation pattern of current cohort\n\n\n\nCompound 1                               Compound 2                                                                                            CR, % \nFragrance Mix I                           Colophony                                                                                                  12.2 \n                                                    Propolis                                                                                                       3.3 \n                                                    Sesquiterpene lactone mix                                                                        2.2 \nFragrance Mix II                          Colophony                                                                                                   9.5 \n                                                    Propolis                                                                                                         0 \n                                                    Sesquiterpene lactone mix                                                                          0 \nBalsam of Peru                            Colophony                                                                                                  13.1 \n                                                    Propolis                                                                                                       4.9 \n                                                    Sesquiterpene lactone mix                                                                        1.6 \n\n\n\nTable IV: Combined cross-reactivity (CR) rates\n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 584\n\n\n\n\n\n\n\n\nContact sensitisation to fragrance allergen\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                585 \n\n\n\nand deodorants were tested \u201cas is\u201d. Cleaning products such as \nfacial wash, shampoo and shower gel were diluted with water \nto 10% (w/w). \n \nPatches were applied to the patients and removed after 48 \nhours. Initial reading was recorded at 48 hours and final \nreading was noted at 96 hours after patch application. The \nparameters studied include positive patch test reactions and \nthe source of allergens. Readings were recorded according to \nthe International Contact Dermatitis Research Group \nrecommendation.5,6 A positive patch test reaction is defined \nas a reaction that fulfils at least a 1+ reaction (i.e., +, ++ or \n+++). Other reactions that can be found during patch tests are \nirritant reaction (IR), doubtful reaction (+?) and angry back \nreaction, but these are not considered as a positive patch test \nreaction. \n \n \nRESULTS \nThere was a total of 854 patients who underwent patch test \nbetween January 2017 and December 2021 at Department of \nDermatology, Hospital Kuala Lumpur. Out of these, 133 \n(15.6%) patients developed at least one positive reaction to \nfragrance allergens. The demographic data was shown in \nTable I. The median age of patients was 40 years (range 17 to \n79) and 78.2% of patients were female. The initial \npresentations include allergic contact dermatitis (18.8%), \nhand eczema (14.3%), contact dermatitis (12%), discoid \neczema (10.5%), atopic eczema (7.5%), cheilitis (7.5%), hand \nand feet eczema (6.8%) and lichen planus/lichenoid reaction \nof oral mucosa (6.8%). Other less frequent presentations \ninclude face eczema, oral ulcer, papular eczema, stasis \neczema, allergic contact gingivitis, chronic urticaria, contact \nurticaria, papular urticaria, feet eczema, insect bite \ndermatitis, irritant contact dermatitis, metal allergy, \npalmoplantar eczema, photoaggravated dermatitis, \nseborrheic dermatitis and ashy dermatoses.  \n \nThe most common sites of involvement were hands (55.6%), \nface (38.3%), legs (35.3%) and trunk (22.6%) as shown in \nTable II. As shown in Table III, the most frequent sensitising \nallergens were Fragrance Mix I (10.5%), balsam of Peru \n(7.1%) and Fragrance Mix II (4.9%). Other sensitising \nallergens included tea tree oil oxidised (2.9%), peppermint oil \n(2.4%), Lyra (1.2%), musk mix (0.5%) and benzyl alcohol \n(0.4%). None of our patients were sensitised to benzyl \nsalicylate. There were 60 (45%) patients who developed \npositive reaction to more than one fragrance allergen. For our \npatients who were sensitised to fragrance mix I, cross-\nreactivity (CR) rate to colophony was 12.2% (Table IV). In \n\n\n\npatients who were allergic to balsam of Peru, CR rate to \ncolophony was 13.1%. Around 9% of patients who were \nsensitised to Fragrance Mix II also cross-sensitised with \ncolophony. None of the patients who were sensitized to \nFragrance Mix II cross-reacted with propolis and \nsesquiterpene lactones (SQL) mix.  \n \nThere were 12 patients (9%) who developed positive patch \ntest reactions to their own products such as skin care products \n(n = 4), hair dye (n = 3), hand wash (n = 3), hair shampoo (n \n= 1) and cosmetic (n = 1). Relevance of positive patch test \nreaction was assessed in all and 96 patients (72.2%) were \nfound to have current relevance, mostly to their own toiletries \n(46.6%), followed by their household products (15.5%), \ncosmetics (9.5%), gloves (9.5%), footwear (6.9%), hair dye \n(3.4%) and food or flavouring (2.6%). \n \n \nDISCUSSION \nFragrances represent the second most common cause of \nallergic contact dermatitis (ACD) after nickel.7,8 It is known to \nbe the most common cause of allergies to cosmetics.9 The \nprevalence of contact sensitisation to fragrances differs \nworldwide and the most common contributing allergens were \nFragrance mix I, Balsam of Peru and Fragrance mix II (Table \nV).11,13,15,16 The prevalence of fragrance contact allergy in the \ngeneral population is 0.7\u20132.6%.10 A study across 12 European \ncountries from 2009 to 2012 showed that 12.7% out of more \nthan 50,000 patients patch tested revealed positive reactions \nto Fragrance Mix I, Fragrance Mix II, Lyral, balsam of Peru, \noil of turpentine, or a combination of these.11 In Spain, \npositive patch test reactions towards fragrance allergens were \nfound in 1.7 to 15.1% of study population.12-14 A smaller study \nin Thailand showed that 22.1% of 312 patients reacted to \nFragrance Mix I, Fragrance Mix II, Balsam of Peru, or \ncombinations.15 Our study which showed a prevalence of \n15.6% of fragrance allergy was similar to other studies to \ndate.10,16  \n \nIn a study of 3119 patients patch-tested in 2008 to 2011 \nacross five European countries, women were found to be \naffected twice as often as men.16,17 Our study presented similar \ncharacteristics. Typically, women in their mid-40s, \ncommonly present with facial or hand eczema due to \nfragrance allergy,10,16,18-20 likely due to increased use of \nfragranced products among women. Sensitisation is more \ncommon at an older age likely due to age-related poor skin \nbarrier function from asteatotic eczema,20 and increased use \nof, as well as cumulative exposure with age to, products with \nfragrance.21 Face is commonly affected likely due to the direct \n\n\n\nAuthor country                            Study period               n             Common age group             Positive patch            Top two allergens \n                                                                                                                    (years)                       test reaction (%) \nFrosch et al., Germany11               2009 to 2012           56813                       >40                                     NA                      1) Fragrance mix I \n                                                                                                                                                                                               2) Balsam of Peru \nCuesta et al., Spain13                    2004 to 2008            1253                        >40                                      9.3                       1) Balsam of Peru \n                                                                                                                                                                                              2) Fragrance mix I \nVejanurug et al., Thailand15        2013 to 2014             312                         >40                                   26.9%                    1) Fragrance mix I \n                                                                                                                                                                                              2) Fragrance mix II \nHafner et al., Brazil16                    2000 to 2015            1870                         40                                    13.8%                    1) Fragrance mix I \n                                                                                                                                                                                                  2) Colophony \n\n\n\nTable V: Worldwide studies on contact sensitisation to fragrances\n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 585\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n586                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\napplication of cosmetics, indirect transfer from contaminated \nhands, or airborne contact (mists, sprays, and aerosols).10 \nEyelids are the most susceptible area to fragrance allergy as it \nhas the thinnest epidermis.22 The other commonly involved \narea is the lips, especially the unkeratinised epithelium.23 \n\n\n\nWhen it comes to lips involvement, food flavourings are \nfrequently the contributor. Hands are commonly involved \nowing to the use of fragrance containing household products, \ncosmetics and topical medications.21 It is apparent that from \nour study there is a significant number of our patients who \nhad dermatitis at the groin, pruritus ani or pruritis vulva \n(8.3%). This could be due to the fact that topical \nmedicaments used in these areas also contained fragrances. \nThese areas may also develop ectopic contact dermatitis from \nthe transfer of fragrance allergens from the hands to these \nsensitive areas.  \n \nCheng et al. reported a common presentation of \npapular/vesicular lesions or patchy dermatitis with \neczematous papules among patients presented with \nfragrance allergy. Chronic lichenified pruritic plaques may \nalso be seen.3 Our study showed similar findings where the \ninitial presentations of fragrance allergy include eczematous \nlesions, papular lesions or lichen planus or lichenoid reaction \nof oral mucosa. \n \nOur study revealed that Fragrance Mix I is the most common \nsensitising allergen (10.5%), which is similar to other \nstudies.3,10,18,24 Fragrance Mix I consisted of 8 fragrance \nchemicals including cinnamyl alcohol, cinnamal, \nhydroxycitronellal, amyl cinnamal, geraniol, eugenol, \nisoeugenol and oak moss absolute. Oak moss absolute is the \nmost common individual allergen contributing to fragrance \nallergy while amyl cinnamal is the least frequent contributor \nof fragrance allergy.9 Oak moss absolute is an extract derived \nfrom lichen growing on oak trees in the Mediterranean area, \nand it has a complex composition and has been used in \nmany fragrance products, including perfumes, colognes and \naftershaves.8 Geraniol is a commonly used fragrance terpene \n(appreciated for its fresh, flowery odour), occurring naturally \nin many flowers and plants, and is present in high \nconcentrations in essential oils of rose and geranium.8 \n\n\n\nHydroxycitronellal and geraniol are the fragrances most \nwidely found in perfumes.25 Cinnamal, hydroxycitronellal \nand isoeugenol are commonly present in deodorants. \nIsoeugenol can also be found in lip products, \nhydroalcoholics, aftershaves, women\u2019s facial and hand \ncreams, intimate wipes, and make-up removers.  \n \nThe rate of sensitisation of Balsam of Peru was comparable to \nprevious studies.3,10 Balsam of Peru, also known as Myroxylon \npereirae, is a natural complex resin derived from a Central \nAmerican tree (or Myroxylon pereirae tree).9,26 It is frequently \npresent in a wide variety of products ranging from drugs, \nperfumes, aroma compounds, cleaning products, dental \ncement and liquids, cosmetic products to foods. Balsam of \nPeru is used in topical medicaments to treat wounds as it has \nantibacterial properties. Its most important allergen is \nformed by the polymerisation of an ester of benzoic acid or \ncinnamic acid and coniferyl alcohol.27 Its crude use in \nperfumes has been banned by International Fragrance \nAssociation (IFRA) since 1982 but its extracts and distillates \ncan still be used in manufacturing of perfumes.26  \n\n\n\nThe third most frequent sensitising allergen is Fragrance Mix \nII (4.9%), similar to previous studies.24 Fragrance Mix II \nconsists of hexyl cinnamic aldehyde, hydroxyisohexyl 3-\ncyclohexene carboxaldehyde, farnesol, coumarin, citral and \ncitronellol. The most frequent sensitising individual allergen \nis hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC), \nalso known as Lyral; the least frequent one is citronellol. \nSince the addition of Fragrance Mix II as standard test for \nfragrance allergy, there has been an increase in the \nsensitivity for detection of fragrance sensitisation with respect \nto traditional markers for fragrances (Fragrance Mix I and \nBalsam of Peru).9 Citronellol is most widely found in hygiene \nproducts and daily moisturizers.25 Lyral contributes to 1.2% of \npositive patch test result in our cohort, similar to other \nstudy.10 Lyral is more commonly found in deodorants.28 It is \ninteresting to note that not all our patients who were positive \nto Lyral were also positive to Fragrance Mix II. This could be \ndue to the higher concentration of Lyral when tested as an \nindividual allergen compared to its concentration in the \nFragrance Mix II. Of note, Lyral has been banned from \ncosmetics products in EU since August 2021 hence it will be \ninteresting to observe if the trend of Lyral sensitivity decreases \nsubsequently. \n \nA total of 45% of our patients developed positive reaction to \nmore than one fragrance allergens in our study, likened to \nanother study.24 There are more than 2500 existing fragrance \ningredients and at least 100 ingredients are known contact \nallergens.12 Hence, it is crucial to supplement standard patch \ntesting with patients\u2019 own products. Hair care products \ncommonly contain a great amount of fragrances. For \ninstance, only 2.8% of 324 styling products were free of \nfragrances.10 Studies have shown significant cross \nsensitization between colophony, propolis and fragrance. In \nsubjects who are allergic to colophony; fragrance and \npropolis may be significant cross-reactors. Similarly, in \nsubjects who are allergic to propolis; fragrance and \ncolophony are considered to be significant cross-reactors.29 \nHowever, for patients allergic to fragrance, cross sensitisation \nto propolis or colophony is not significant in terms of cross-\nreactivity rate.29 A 10% CR rate was considered to be \nsignificant enough to recommend avoidance of a potential \ncross-reacting allergen based on the American Contact \nDermatitis Society\u2019s Contact Allergy Management Program \n(CAMP) recommendations.30 Nonetheless, our study showed \notherwise (Table V). For our patients who were sensitive to \nFragrance Mix I, colophony may be a significant cross-\nreactor with a CR rate of 10.5%, but not propolis and SQL \nmix. Patients allergic to Balsam of Peru also showed a \nsignificant cross sensitisation to colophony (13.1%) but not to \npropolis and SQL Mix. We therefore recommend our patients \nwho develop contact sensitisation to Fragrance Mix I and \nBalsam of Peru to also avoid colophony, in view of the CR \nrate of more than 10%. \n \nClinical relevance is crucial to translating research results \ninto clinical use. The rate of currently relevant sensitisations \nreflect the extent of current exposure and the consequent \ndisease state. This may rise or decline with time, hence \nshowing the direct effect of a fragrance contact allergy to the \nindividual.26 It is believed that a strong positive reaction is \nmore likely to have clinical relevance than a weak positive \nreaction. The recorded relevance in our study was high \n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 586\n\n\n\n\n\n\n\n\nContact sensitisation to fragrance allergen\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                587 \n\n\n\n(72.2%), similar to another study.31 This is likely due to \nfragrance sensitisation acting as a provoking factor for a \nspectrum of dermatoses. Unless fragrance-containing \nproducts are avoided, previous dermatoses will not improve \ndespite appropriate treatment and protective measures.13   \n \nContact allergy to fragrance is mostly not related to \noccupation32, but more commonly originates from personal \nuse of scented cosmetics. However, secondary occupational \nexposure to fragrance ingredients may happen at workplace. \nPrevious literature showed a high prevalence of allergy to \nFragrance Mix I among healthcare workers due to irritant \nhand contact dermatitis from repeated washing disrupting \nthe skin barrier, allowing better allergen penetration, hence \nsubsequent application of products containing fragrances \nintroduces a source for allergen exposure.3 Sensitivity to \nBalsam of Peru has been found to be more common among \nhealthcare workers especially dentists.33 Dentists also have a \nhigher risk for allergy to eugenol (one of the components of \nFragrance Mix I) due to exposure from mouthwashes, \ndressings, impression materials, and periodontal packings.19 \nAbout a fifth of our cohort were healthcare workers. Out of \nthese, eight out of 30 healthcare workers (26.7%) had \nfragrance allergy related to work. Food handlers may be \nfrequently exposed to components of Fragrance Mix I \n(cinnamal and cinnamic alcohol) and Balsam of Peru due to \nhandling of spices and essential oils.3 Hairdressers, \nbeauticians and aromatherapists are also particularly at risk \nfor fragrance allergy.10 Overall, our study has shown a fairly \nequal distribution of fragrance allergy across different \noccupations. \n \nAs fragrances are widely used in daily products, it is \nextremely difficult for sensitized patients to avoid them \ncompletely without limiting their daily activities. Some \nproducts may also omit labelling fragrance in their \ningredient if it was used for masking odour instead of \nimparting pleasant odour. Regulations have been imposed to \nsafeguard consumer\u2019s health and safety including \nmandatory labelling of fragrance ingredients on products\u2019 \ningredient label if products sold contained any of the 26 \nfragrances governed by EU regulations.12,31 Unfortunately, \nneither Balsam of Peru nor the extracts and distillates are \nincluded in the mandatory labelling as yet. Hence, there \nshould be continuous efforts in identifying common \nfragrance allergens and they should be regulated \ncontinuously by authority bodies. Tighter regulations should \nbe enforced to ensure that fragrance ingredients are labelled \naccordingly and correctly.10  \n \nEssential oils are sources of fragrance allergens and expanded \npatch testing involving essential oils may be considered in \npatients suspected to have fragrance allergy. So far, our study \nincluded few individual ingredients of essential oils which are \npresent in the cosmetic series, namely the tea tree oxidized \nextract and peppermint oil. From our study, there were 2.9% \nand 2.4% of our patients who were sensitized to tea tree oil \noxidized and peppermint oil respectively, hence it is essential \nto monitor these fragrance allergens in our populations. \nSince fragrance series was not available in our setting at \npresent, we may include cosmetic series if we are \ninvestigating patients for fragrance allergy, as it contains a \n\n\n\nfew essential oils. Cosmetic series also contains sorbitan \nsesquioleate, which is the dispersing agent used in Fragrance \nmix I hence testing for this will help to differentiate between \ntrue Fragrance mix I allergy and sorbitan sequioleate allergy. \n \nManagement of patients with fragrance allergic contact \ndermatitis includes avoidance of products with labelled \nknown sensitising fragrances. Clinicians may advise patients \nto fully avoid the use of fragrance-containing products such \nas perfumes and toiletries. If patients need to use such \nproducts, they should be advised to avoid applying these \nproducts at areas of skin that are potentially traumatized \n(beard region, hands, and shaved areas) or occluded (axilla), \nas well as areas of high absorption (eyelids, genitals, and \naxilla) and areas of chronic dermatitis (e.g., stasis \ndermatitis). Exposure to air and oxidation of products should \nbe prevented by replacing lid between uses. Household \nproducts such as dishwashing liquid, clothes detergent, toilet \ncleaners or floor cleaners also contain fragrance and patients \nshould avoid skin contact with these products by using gloves \nor boots as protection as these household products usually \nhave no fragrance-free alternatives. We should also educate \nour patients to avoid using products out of its shelf life \n(commonly 1 year) as certain fragrance ingredients \nautoxidise into allergenic products.34 Patients with \nsensitisation to Balsam of Peru may benefit from a balsam-\nrestricted diet, as Balsam of Peru has been associated with \nsystemic contact dermatitis if ingested.35 Examples of foods \nand drinks rich in Balsam of Peru include citrus fruit, spices \nsuch as vanilla and cinnamon, chocolate, cola, and \ntomatoes.36 In general, avoiding exposure in infants and \nyoung children is ideal as sensitisation to an allergen is \nlifelong once acquired. \n \nThere is limitation to this study. Individual ingredients of \nfragrance mix I and fragrance mix II were not tested in all \nsubjects showing positive reaction to the mixes. We should \nconsider to purchase the fragrance allergy series which \ncontains more fragrance allergens in order to detect more \ncases of fragrance allergy. Our findings may not be \nrepresentative of the whole Malaysian population as this is \nonly a single centre study.  \n \n \nCONCLUSION \nContact sensitisation to fragrance allergens was detected in \nabout 15% of our patients who underwent patch test. It is \nmore prevalent in women and commonly involves hands \nand face. The most common sensitising allergens were \nFragrance Mix I, Fragrance Mix II and Balsam of Peru. \nCurrent relevance of positive patch test reaction was found in \nalmost three quarter of our patients and these were mostly \ntowards their own toiletries, household products and \ncosmetics. It is crucial to test patients\u2019 own products during \nworkup for allergen sensitisation to ensure that these relevant \nreactions are not missed. \n \n \nCONFLICT OF INTEREST DECLARATION \nThe authors have no conflict of interest to declare. \n \n \n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 587\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n588                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nACKNOWLEDGEMENT \nThe authors would like to thank the Director General of \nHealth, Malaysia for permission to publish this paper. \n \n \nREFERENCES \n1. Ufer W, Werfel T, Lepoittevin JP, White IR. Contact allergy \u2013 \n\n\n\nemerging allergens and public health impact. Int J Environ Res \nPublic Health 2020; 17(7): 2404. \n\n\n\n2. IFRA. IFRA code of practice: Definitions [cited July 2022]. \nAvailable from: https://ifrafragrance.org/about-ifra/ifra-code-of-\npractice/definitions.  \n\n\n\n3. Cheng J, Zug KA. Fragrance allergic contact dermatitis. \nDermatitis 2014; 25(5): 232-45. \n\n\n\n4. van Amerongen CCA, Ofenloch RF, Cazzaniaga S, Elsner P, \nGoncalo M, Naldi L, et al. Skin exposure to scented products used \nin daily life and fragrance contact allergy in the European \ngeneral population \u2013 The EDEN Fragrance Study. Contact Derm \n2021; 84(6): 385-94. \n\n\n\n5. Johansen JD, Aalto-Korte K, Agner T, Andersen KE, Bircher A, \nBruze M, et al. European Society of Contact Dermatitis guideline \nfor diagnostic patch testing \u2013 recommendations on best practice. \nContact Derm 2015; 73(4): 195-221. \n\n\n\n6. Spiewak R. Patch testing for contact allergy and allergic contact \ndermatitis. The Open Allergy J 2008; 1: 42-51. \n\n\n\n7. Schnuch A, Uter W, Geier J, Gefeller O. Epidemiology of contact \nallergy: an estimation of morbidity employing the clinical \nepidemiology and drug-utilization research (CE-DUR) approach. \nContact Derm 2002; 47(1): 32-9. \n\n\n\n8. Hagvall L, Karlberg AT, Christensson JB. Finding the optimal \npatch test material and test concentration to detect contact \nallergy to geraniol. Contact Derm 2013; 68(4): 224-31. \n\n\n\n9. Gonzalez-Munoz P, Conde-Salazar L, Vano-Galvan S. Allergic \ncontact dermatitis caused by cosmetic products. Actas \nDermosifiliogr 2014; 105(9): 822-32. \n\n\n\n10. Reeder ML. Allergic contact dermatitis to fragrances. Dermatol \nClin 2020; 38(3): 371-77. \n\n\n\n11. Frosch PJ, Johansen JD, Schuttelaar MA, Silvestre JF, Sanchez-\nPerez J, Weisshaar E, et al. Patch test results with fragrance \nmarkers of the baseline series\u2014analysis of the European \nSurveillance System on Contact Allergies (ESSCA) network 2009-\n2012. Contact Derm 2015; 73(3): 163-71. \n\n\n\n12. Heisterberg MV, Menn\u00e9 T, Johansen JD. Contact allergy to the 26 \nspecific fragrance ingredients to be declared on cosmetics \nproducts in accordance with the EU cosmetics directive. Contact \nDerm 2011; 65(5): 266-75. \n\n\n\n13. Cuesta L, Silvestre JF, Toledo F, Lucas A, P\u00e9rez-Crespo M, Ballester \nI. Fragrance contact allergy: A 4-year retrospective study. Contact \nDerm 2010; 63(2): 77-84. \n\n\n\n14. Uter W, Geier J, Frosch P, Schnuch A. Contact allergy to \nfragrances: Current patch test results (2005-2008) from the \nInformation Network of Departments of Dermatology. Contact \nDerm 2010; 63(5): 254-61. \n\n\n\n15. Vejanurug P, Tresukosol P, Sajjachareonpong P, Puangpet P. \nFragrance allergy could be missed without patch testing with 26 \nindividual fragrance allergens. Contact Derm 2016; 74(4): 230-\n35. \n\n\n\n16. Hafner MFS, Munhoz SDG, Jeldes AG, Lazzarini R. Positive results \nof patch tests with fragrance markers: Analysis of a 15-year \nperiod at a Brazilian dermatology center. An Bras Dermatol \n2018; 93(6): 910-12. \n\n\n\n17. Diepgen TL, Ofenloch R, Bruze M, Cazzaniga S, Coenraads PJ, \nElsner P, et al. Prevalence of fragrance contact allergy in the \ngeneral population of five European countries: a cross-sectional \nstudy. Br J Dermatol 2015; 173(6): 1411-9. \n\n\n\n18. Johansen JD. Fragrance contact allergy: a clinical review. Am J \nClin Dermatol 2003; 4(11): 789-98. \n\n\n\n19. Katz AS, Sherertz EF. Facial dermatitis: patch test results and final \ndiagnoses. Dermatitis 1999; 10(3): 153-6. \n\n\n\n20. Buckley DA, Rycroft RJG, White IR, McFadden JP. Contact allergy \nto individual fragrance mix constituents in relation to primary \nsite of dermatitis. Contact Derm 2000; 43(5): 304-5. \n\n\n\n21. Green CM, Holden CR, Gawkrodger DJ. Contact allergy to topical \nmedicaments becomes more common with advancing age: an \nage-stratified study. Contact Derm 2007; 56(4): 229-31. \n\n\n\n22. Park ME, Zippin JH. Allergic contact dermatitis to cosmetics. \nDermatol Clin 2014; 32(1): 1-11. \n\n\n\n23. Zug KA, Kornik R, Belsito DV, DeLeo VA, Fowler Jr JF, Maibach \nHI, et al. Patch-testing North American lip dermatitis patients: \ndata from the North American Contact Dermatitis Group, 2001 \nto 2004. Dermatitis 2008; 19(4): 202-8. \n\n\n\n24. Nardelli A, Carbonez A, Drieghe J, Goossens A. Results of patch \ntesting with fragrance mix 1, fragrance mix 2, and their \ningredients, and Myroxylon pereirae and colophonium, over a \n21-year period. Contact Derm 2013; 68(5): 307-13. \n\n\n\n25. Arribas MP, Soro P, Silvestre JF. Allergic contact dermatitis to \nfragrances. Part I. Actas Dermo 2012; 103(10): 874-9. \n\n\n\n26. Uter W, Johansen JD, Borje A, Karlberg AT, Liden C, Rastogi S, et \nal. Categorization of fragrance contact allergens for \nprioritization of preventive measures: clinical and experimental \ndata and consideration of structure-activity relationships. \nContact Derm 2013; 69(4): 196-230. \n\n\n\n27. Nardelli A, Carbonez A, Ottoy W, Drieghe J, Goossens A. \nFrequency of and trends in fragrance allergy over a 15-year \nperiod. Contact Derm 2008; 58(3): 134-41. \n\n\n\n28. Watkins S, Zippin J. Allergic contact dermatitis and cosmetics. \nCutis. 2012; 90(4): 201-4 \n\n\n\n29. Shi Y, Nedorost S, Scheman L, Scheman A. Propolis, colophony, \nand fragrance cross-reactivity and allergic contact dermatitis. \nDermatitis 2016; 27(3): 123-6. \n\n\n\n30. Andrew S, Ricky H, David S, Nineveh BSY. Contact allergy cross-\nreactions: Retrospective clinical data and review of the literature. \nDermatitis 2017; 28(2): 128-40. \n\n\n\n31. Van Oosten EJ, Schuttelaar ML, Coenraads PJ. Clinical relevance \nof positive patch test reactions to the 26 EU-labelled fragrances. \nContact Derm 2009; 61(4): 217-23. \n\n\n\n32. Uter W, Schnuch A, Geier J, Pfahlberg A, Gefeller O. Association \nbetween occupation and contact allergy to the fragrance mix: a \nmultifactorial analysis of national surveillance data. Occup \nEnviron Med 2001; 58(6): 392-8. \n\n\n\n33. Warshaw EM, Schram SE, Maibach HI, Belsito DV, Marks Jr JG, \nFowler Jr JF, et al. Occupation-related contact dermatitis in North \nAmerican health care workers referred for patch testing: cross-\nsectional data, 1998 to 2004. Dermatitis 2008; 19(5): 261-74. \n\n\n\n34. Buckley DA. Fragrance ingredient labelling in products on sale in \nthe U.K. Br J Dermatol 2007; 157(2): 295-300. \n\n\n\n35. Salam TN, Fowler JFJr. Balsam-related systemic contact \ndermatitis. J Am Acad Dermtol 2001; 45(3): 377-81. \n\n\n\n36. de Groot AC. Myroxylon pereirae resin (Balsam of Peru) \u2013 A \ncritical review of the literature and assessment of the significance \nof positive patch test reactions and the usefulness of restrictive \ndiets. Contact Derm 2019; 80: 335-53. \n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 588\n\n\n\n\n\n\n\n\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                675 \n\n\n\nABSTRACT \nIntroduction: Postpartum depression (PPD) is a mental and \nemotional condition that can affect women during their first \npostnatal year and concern globally. This study aimed to \ndetermine the overall prevalence and determinants of \npostpartum depression (PPD) in Association of Southeast \nAsian Nations (ASEAN) countries. \n \nMaterials and Methods: A systematic search of \nobservational studies conducted in ASEAN countries \nbetween 1 January 2010 and 31 December 2020 was \nperformed in the Medline, PubMed and Google Scholar \ndatabases. The quality of studies was evaluated based on \nThe Joanna Briggs Institute Checklist. The analysis was \nperformed with Review Manager software version 5.4. Meta-\nanalysis of the estimates from primary studies was \nconducted by adjusting for possible publication bias and \nheterogeneity.  \n \nResults: Twenty-five studies including 19924 postnatal \nmothers were included in this review. The pooled prevalence \nof PPD is 22.32% (95% CI: 18.48, 26.17). Thailand has the \nhighest prevalence of PPD with a pooled prevalence of \n74.1% (95% CI: 64.79, 83.41). The prevalence of PPD was \nhighest when the assessment for PPD was conducted up to \n6 weeks postpartum with a pooled prevalence of 25.24% \n(95% CI: 14.08, 36.41). The identified determinants of PPD \nwere unplanned pregnancy, term pregnancy, lack of family \nsupport and physical violence. There were limited studies \ndone and high heterogeneity in terms of quality, \nmethodology, culture, screening method and time of PPD \nmeasurement. \n \nConclusions: Approximately one in five postpartum women \nin ASEAN countries had PPD. The risk factor that lowers the \nrisk of PPD is unplanned and term pregnancies, while \nwomen with a lack of family support and experienced \nphysical violence increase the risk of PPD. Robust \nprevalence studies are needed to assess the magnitude of \nthis problem in ASEAN countries.     \n \nKEYWORDS:  \nPostnatal depression, postpartum depression, ASEAN countries, \nrisk of postpartum depression \n \n\n\n\nINTRODUCTION \nPostpartum depression (PPD) is a mental and emotional \ncondition that can affect women during their first postnatal \nyear and is a concern globally.1 It involves the woman herself \nand the family institution and, subsequently, the economy of \nthe family itself.2 PPD is often overlooked and causes \nmorbidity to new mothers and their families. PPD is defined \nas a major depressive episode \u2018with peripartum onset if the \nonset of mood symptoms occurs during pregnancy or within \nfour weeks following deliveries\u2019 based on the Diagnostic and \nStatistical Manual of Mental Disorders, fifth edition (DSM-5). \nMultiple studies and clinical practices define PPD as \noccurring within 4 weeks after childbirth, 3 months, 6 months \nor up to 12 months after delivery. \n \nA recent systematic review and meta-analysis by Abel et al.3 \non 58 studies conducted between 2007 and 2017 reported \nthat the PPD prevalence ranged between 18.2% and 25.6%. \nThey also highlighted that the prevalence was higher in low-\nincome countries, with a pooled prevalence of 25.8%, \ncompared to middle-income countries, which was 20.7%. \nWang et al.4 conducted a systematic review and meta-\nanalysis among 565 studies involving 1,236 365 women from \ninception and July 2021 found that the global prevalence of \nPPD is 17.22% (95% CI: 16.00, 18.51). They reported that \nSouth Africa has the highest prevalence, which is 39.96%.  \n \nThe literature on PPD revealed several risk factors that can \ncontribute to women\u2019s PPD. The risk factors are different \namong the developed and developing countries. It can be \ndivided into socio-demographic categories, marital and \npregnancy factors and psychosocial factors. The examples of \nsocio-demographic factors are unintended or birth5\u20137, \noccupation and marital status8 and low socio-economic and \neducation status.6,9,10 For marital and pregnancy factors such \nas intimate partner violence,11 domestic violence5,12,13 \n\n\n\npsychosocial factors identified were partner conflict, \nperfectionism, lack of family and parental support, reduced \nsocial support,6,10,14 and depression during pregnancy or \nhistory of depression before pregnancy.5,10 \n \nASEAN countries comprise an intergovernmental \norganisation of 10 Southeast Asian countries: Brunei, \nCambodia, Indonesia, Laos, Malaysia, Myanmar, the \nPhilippines, Singapore, Thailand and Vietnam. The most \n\n\n\nA 10-year systematic review and meta-analysis of \ndeterminants of postpartum depression in the Association \nof Southeast Asian Nations countries \n \nSiti Syafiqah Sainuddin, MMed, Norhayati Mohd Noor, PhD, Azidah Abdul Kadir, PhD, Rosnani Zakaria, \nFRACGP \n\n\n\n     \nDepartment of Family Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia\n\n\n\nSYSTEMATIC / NARRATIVE REVIEW ARTICLE\n\n\n\n This article was accepted: 17 August 2023                                                                                                                                                                         \nCorresponding Author: Prof Azidah Abdul Kadir                                                                                                                                                                 \nEmail: azidahkb@usm.my \n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 675\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n676                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nstriking characteristic of ASEAN countries is that it has a wide \ndiversity of socio-cultural, hence different socio-economic \nstatuses. We find many studies related to PPD in developed \nand other developing countries but very limited studies \nrelated to ASEAN countries. This can be due to a lack of \nexposure and intervention about PPD in women.  \n \nTherefore, in this systematic review and meta-analyses, we \naimed to estimate the overall prevalence of PPD and its \ndeterminants in ASEAN countries. Findings from this study \nwill be used to identify the need for early screening and \ndetection, encourage the development of an intervention to \nreduce its occurrence and support women with PPD. \n\n\n\n \n \nMATERIALS AND METHODS \nA systematic review and meta-analysis of studies were \nconducted according to the Preferred Reporting Items for \nSystematic Reviews and Meta-Analyses (PRISMA) \nguidelines.15 The protocol for this systematic review and \nmeta-analysis has been registered in the PROSPERO (Protocol \nNo. CRD42021234127), and the protocol includes only the \ndeterminants of PPD in ASEAN countries. The inclusion \ncriteria are studies conducted in ASEAN countries that report \nthe prevalence and determinants of PPD over 10 years from \n1st January 2010 to 31st December 2020. Studies with cross-\nsectional, case\u2013control and cohort designs published in \nEnglish were included. Case series/reports, conference papers, \nproceedings, articles available only in abstract form, editorial \nreviews, letters of communication, commentaries and \nqualitative studies were excluded. \n \nA systematic search was performed in the Medline (PubMed) \nand Google Scholar databases for articles between 1st \nJanuary 2010 and 31st December 2020. The investigation \nwas done using the Medical Subject Headings (MeSH) search \nterms: \u2018determinants,\u2019 \u2018risk factors,\u2019 \u2018postnatal depression,\u2019 \n\u2018perinatal depression,\u2019 \u2018maternal depression\u2019 and \u2018maternal \nblues\u2019. Reference lists of included citations were cross-checked \nto find additional potentially eligible studies. \n \nAll records identified by our search strategy were exported to \nEndNote X8 software. Duplicate articles were removed. Two \nindependent reviewers screened the titles and abstracts of the \nidentified themes. The full texts of eligible studies were \nobtained and read thoroughly to assess their suitability. In a \nconflict between the two reviewers, a consensus discussion \nwas held, and a third reviewer was consulted.  \n \nThe data were extracted into Microsoft Excel. This included \nfirst author, year of publication, study location, study design, \nsetting, study population, sample size, PPD definition, risk \nfactors and data for the calculation of effect estimates. Data \nfor risk factors included physical and biological, \npsychological, obstetric, paediatrics, socio-demographic and \ncultural factors. \n \nA critical appraisal was done to assess the data quality using \nthe Joanna Briggs Institute Meta-Analysis for cross-sectional, \ncase\u2013control and cohort studies (Aromataris and Munn, \n2020). The risk of bias was considered low when more than \n70% of the answers were \u2018yes,\u2019 moderate when 50\u201369% of the \nresponses were \u2018yes\u2019 and high when up to 0%\u201349% of the \n\n\n\nanswers were \u2018yes.\u2019 The risk factors were reported as an odds \nratio with a 95% confidence interval. The analysis was \nperformed with Review Manager software version 5.4 (Nordic \nCochrane Centre). We used a random-effects model to pool \ndata. The I2 statistic was used to assess heterogeneity and use \nthe guide as outlined: 0%\u201340% might not be necessary; 30%\u2013\n60% may represent moderate heterogeneity; 50%\u201390% may \nrepresent substantial heterogeneity and 75%\u2013100% would be \nconsiderable heterogeneity; 50%\u201390% may represent \nsignificant heterogeneity 17Subgroup analysis was \nperformed based on ASEAN countries and the time of \nassessment of the study design. Funnel plots were used to \nassess the publication bias. \n \n \nRESULTS \nCharacteristics of the Included Studies \nA total of 7609 articles were retrieved through an electronic \nsearch, of which 7559 were eligible for assessment after \nremoving ten duplicate records. Of the 7559 articles screened \nfor eligibility, 7250 were excluded. A total of 349 articles \nunderwent full-text evaluation for eligibility, of which 312 \nwere excluded because articleswere not from ASEAN \ncountries (n = 293) but only prenatal depression (n = 19). In \nthis review, 37 articles underwent quality assessment, of \nwhich 25 articles with low risk of bias were included in the \nfinal analysis, as shown in Fig 1, whereas four studies with a \nmoderate risk of bias and six studies with a high risk of bias \nwere excluded. \n \nTable I shows 25 studies included in this review: Malaysia (n \n= 4),11,16\u201318 Singapore (n = 3),19\u201321 Thailand (n = 5),14,22\u201325  \nIndonesia (n = 6),26\u201331, Vietnam (n = 5),32\u201336, Philippines \n(n = 1)8 and Laos (n = 1)37. Fifteen studies were cross-\nsectional,8,11,14,16,22,23,26,28\u201332,34,36,37 two were case\u2013control,19,24 and \neight were cohort studies.17,18,20,21,25,27,33,35 According to the data, \nthe smallest sample size was 31 women, and the largest was \n6636 women. The majority of the included studies used \nEdinburgh Postnatal Depression Scale (EPDS), which is 21 \nstudies out of 25.8,11,14,17,18,20,21,23\u201331,33\u201337 From this, nine studies \nusing cut-off points \u226512,11,14,17,18,23,28,30,34,36 seven studies using cut-\noff points \u226510,8,21,25,26,29,35,37 two studies using cut-off point \n\u226513,20,27 one study using cut-off point \u2265433 and \u22651124, \nrespectively, and one study not explicitly mentioned the cut-\noff point.31 Other than that, four studies using different types \nof measures of PPD, which are Mini International \nNeuropsychiatric Interview (MINI),16 The Diagnostic and \nStatistical Manual of Mental Disorders, fourth edition (DSM-\nIV),19 Center for Epidemiological Studies Depression Scale \n(CES-D)22 and Case-Finding Instruments for Depression.32  \n \nPrevalence of PPD in ASEAN Countries \nA total of 25 studies were included, with a total of 19,924 \nsamples size. The pooled prevalence of PPD was 22.32% (95% \nCI: 18.48, 26.17). Figures 2 and 3 show a funnel plot. A \nsubgroup analysis based on countries was performed in \nFigure 4. Thailand showed the highest pooled prevalence of \nwomen with PPD, which is 74.10% (95% CI: 64.79, 83.41). \nThis is because the study22 was done among a particular \ngroup population of women with human immunodeficiency \nvirus and a small sample size of 85 mothers. Apart from that, \na limited number of studies are available, such as Laos37 and \nThe Philippines.8 \n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 676\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                677 \n\n\n\nN\no.\n\n\n\n   \nA\n\n\n\nut\nho\n\n\n\nr \n   \n\n\n\n\n\n\n\n\n\n\n\n   \nSt\n\n\n\nud\ny \n\n\n\nar\nea\n\n\n\n\n\n\n\n\n\n\n\n   \n S\n\n\n\ntu\ndy\n\n\n\n\n\n\n\n\n\n\n\n  S\nam\n\n\n\npl\ne \n\n\n\n   \n  M\n\n\n\nea\nsu\n\n\n\nre\ns \n\n\n\n\n\n\n\n P\nre\n\n\n\nva\nle\n\n\n\nnc\ne \n\n\n\n\n\n\n\n   \n T\n\n\n\nim\ne \n\n\n\nof\n a\n\n\n\nss\nes\n\n\n\nsm\nen\n\n\n\nt  \n   \n\n\n\n\n\n\n\n\n\n\n\nFa\nct\n\n\n\nor\ns \n\n\n\nas\nso\n\n\n\nci\nat\n\n\n\ned\n w\n\n\n\nith\n P\n\n\n\nPD\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(R\neg\n\n\n\nio\nn)\n\n\n\n\n\n\n\n\n\n\n\n   \n d\n\n\n\nes\nig\n\n\n\nn\n   \n\n\n\n\n\n\n\n\n\n\n\nSi\nze\n\n\n\n\n\n\n\n\n\n\n\nof\n P\n\n\n\nPD\n   \n\n\n\n\n\n\n\n o\nf P\n\n\n\nPD\n (%\n\n\n\n) \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n1\n   \n\n\n\n   \nZa\n\n\n\nin\nal\n\n\n\n e\nt \n\n\n\nal\n.16\n\n\n\n\n\n\n\n   \n  M\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\n\n\n\n\n\n\n\n\nC\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 4\n\n\n\n11\n   \n\n\n\n\n\n\n\n   \n M\n\n\n\nIN\nI \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n6.\n8\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n6\u2013\n\n\n\n8 \nw\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n H\no\n\n\n\nu\nse\n\n\n\nw\nif\n\n\n\ne \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nC\n\n\n\nae\nsa\n\n\n\nri\nan\n\n\n\n s\nec\n\n\n\nti\no\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPr\nev\n\n\n\nio\nu\n\n\n\ns \nh\n\n\n\nis\nto\n\n\n\nry\n o\n\n\n\nf \nd\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nN\no\n\n\n\nn\n-e\n\n\n\nxc\nlu\n\n\n\nsi\nve\n\n\n\n b\nre\n\n\n\nas\ntf\n\n\n\nee\nd\n\n\n\nin\ng\n\n\n\n \n2\n\n\n\n\n\n\n\nY\nu\n\n\n\nsu\nff\n\n\n\n e\nt \n\n\n\nal\n.17\n\n\n\n\n\n\n\n   \n M\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\n\n\n\n\n\n\n\n\nC\no\n\n\n\nh\no\n\n\n\nrt\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  2\n\n\n\n07\n2\n\n\n\n\n\n\n\n   \n  E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n14\n.3\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 1\n, 3\n\n\n\n a\nn\n\n\n\nd\n 6\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n W\no\n\n\n\nm\nen\n\n\n\n d\nep\n\n\n\nre\nss\n\n\n\ned\n d\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n W\n\n\n\no\nm\n\n\n\nen\n w\n\n\n\nit\nh\n\n\n\n c\no\n\n\n\nn\nsi\n\n\n\nst\nen\n\n\n\nt \nw\n\n\n\no\nrr\n\n\n\nie\ns \n\n\n\no\nf \n\n\n\nn\new\n\n\n\nb\no\n\n\n\nrn\n \n\n\n\n3\n   \n\n\n\n   \nN\n\n\n\no\nrh\n\n\n\nay\nat\n\n\n\ni \n   \n\n\n\n\n\n\n\n\n\n\n\nM\nal\n\n\n\nay\nsi\n\n\n\na\n   \n\n\n\n\n\n\n\n   \nC\n\n\n\no\nh\n\n\n\no\nrt\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  7\n42\n\n\n\n\n\n\n\n\n\n\n\n E\nPD\n\n\n\nS\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n4.\n\n\n\n8\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n1 \nan\n\n\n\nd\n 6\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n   \n -\n\n\n\n M\no\n\n\n\nth\ner\n\n\n\n w\nit\n\n\n\nh\n S\n\n\n\nM\nM\n\n\n\n\n\n\n\n   \n  e\n\n\n\nt \nal\n\n\n\n.18\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  2\n\n\n\n.1\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n1 \nan\n\n\n\nd\n 6\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n   \n -\n\n\n\n M\no\n\n\n\nth\ner\n\n\n\n w\nit\n\n\n\nh\no\n\n\n\nu\nt \n\n\n\nSM\nM\n\n\n\n \n4\n\n\n\n\n\n\n\nA\nh\n\n\n\nm\nad\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \nM\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\n\n\n\n\n\n\n\n\nC\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 6\n\n\n\n63\n9\n\n\n\n\n\n\n\n   \n  E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n4\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n6\u2013\n\n\n\n16\n w\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n  -\n E\n\n\n\nxp\no\n\n\n\nse\nd\n\n\n\n t\no\n\n\n\n in\nti\n\n\n\nm\nat\n\n\n\ne \np\n\n\n\nar\ntn\n\n\n\ner\n v\n\n\n\nio\nle\n\n\n\nn\nce\n\n\n\n\n\n\n\n   \n  e\n\n\n\nt \nal\n\n\n\n.11\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n E\nm\n\n\n\no\nti\n\n\n\no\nn\n\n\n\nal\n v\n\n\n\nio\nle\n\n\n\nn\nce\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nU\n\n\n\nn\np\n\n\n\nla\nn\n\n\n\nn\ned\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLa\n\n\n\nck\n o\n\n\n\nf \nfa\n\n\n\nm\nily\n\n\n\n s\nu\n\n\n\np\np\n\n\n\no\nrt\n\n\n\n d\nu\n\n\n\nri\nn\n\n\n\ng\n c\n\n\n\no\nn\n\n\n\nfi\nn\n\n\n\nem\nen\n\n\n\nt \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPa\n\n\n\nrt\nn\n\n\n\ner\n\u2019s\n\n\n\n u\nse\n\n\n\n o\nf \n\n\n\nal\nco\n\n\n\nh\no\n\n\n\nl \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nB\n\n\n\nei\nn\n\n\n\ng\n f\n\n\n\nro\nm\n\n\n\n h\no\n\n\n\nu\nse\n\n\n\nh\no\n\n\n\nld\n w\n\n\n\nit\nh\n\n\n\n a\n lo\n\n\n\nw\n in\n\n\n\nco\nm\n\n\n\ne \n5\n\n\n\n\n\n\n\nSu\nh\n\n\n\nit\nh\n\n\n\nar\nan\n\n\n\n\n\n\n\n\n\n\n\n   \nSi\n\n\n\nn\ng\n\n\n\nap\no\n\n\n\nre\n   \n\n\n\n\n\n\n\n C\nas\n\n\n\ne\u2013\nco\n\n\n\nn\ntr\n\n\n\no\nl \n\n\n\n\n\n\n\n   \n74\n\n\n\n4\n   \n\n\n\n\n\n\n\n   \n D\n\n\n\nSM\n-I\n\n\n\nV\n   \n\n\n\n\n\n\n\n   \n  1\n\n\n\n2.\n9\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 4\n\u20138\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n -\n A\n\n\n\nb\nse\n\n\n\nn\nce\n\n\n\n o\nf \n\n\n\nla\nb\n\n\n\no\nu\n\n\n\nr \nep\n\n\n\nid\nu\n\n\n\nra\nl a\n\n\n\nn\nal\n\n\n\ng\nes\n\n\n\nia\n \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n.19\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n In\n\n\n\ncr\nea\n\n\n\nsi\nn\n\n\n\ng\n a\n\n\n\ng\ne \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nFa\nm\n\n\n\nily\n h\n\n\n\nis\nto\n\n\n\nry\n o\n\n\n\nf \nd\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nH\nis\n\n\n\nto\nry\n\n\n\n o\nf \n\n\n\nd\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPr\n\n\n\nev\nio\n\n\n\nu\ns \n\n\n\nh\nis\n\n\n\nto\nry\n\n\n\n o\nf \n\n\n\nPP\nD\n\n\n\n \n6\n\n\n\n\n\n\n\nTh\nam\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nSi\nn\n\n\n\ng\nap\n\n\n\no\nre\n\n\n\n\n\n\n\n   \n C\n\n\n\no\nh\n\n\n\no\nrt\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  1\n24\n\n\n\n7\n   \n\n\n\n\n\n\n\n  E\nPD\n\n\n\nS\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n20\n\n\n\n.1\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 3\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nB\no\n\n\n\nrd\ner\n\n\n\nlin\ne \n\n\n\nh\nig\n\n\n\nh\n d\n\n\n\nep\nre\n\n\n\nss\niv\n\n\n\ne/\n a\n\n\n\nn\nxi\n\n\n\net\ny \n\n\n\nsy\nm\n\n\n\np\nto\n\n\n\nm\ns \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n.24\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n P\n\n\n\no\no\n\n\n\nr \nsu\n\n\n\nb\nje\n\n\n\nct\niv\n\n\n\ne \nsl\n\n\n\nee\np\n\n\n\n q\nu\n\n\n\nal\nit\n\n\n\ny \nd\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n \n7\n\n\n\n\n\n\n\nTe\no\n\n\n\n e\nt \n\n\n\nal\n.20\n\n\n\n\n\n\n\n\n\n\n\n   \nSi\n\n\n\nn\ng\n\n\n\nap\no\n\n\n\nre\n   \n\n\n\n\n\n\n\n C\no\n\n\n\nh\no\n\n\n\nrt\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  1\n\n\n\n24\n9\n\n\n\n\n\n\n\n   \n  E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n9.\n8\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n1 \n\n\n\nm\no\n\n\n\nn\nth\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n -\n T\n\n\n\nra\nd\n\n\n\nit\nio\n\n\n\nn\nal\n\n\n\n-I\nn\n\n\n\nd\nia\n\n\n\nn\n-C\n\n\n\no\nn\n\n\n\nfi\nn\n\n\n\nem\nen\n\n\n\nt \nd\n\n\n\nie\nt \n\n\n\nas\nso\n\n\n\nci\nat\n\n\n\ned\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \nw\n\n\n\nit\nh\n\n\n\n le\nss\n\n\n\n P\nPD\n\n\n\n s\nym\n\n\n\np\nto\n\n\n\nm\ns \n\n\n\n8\n   \n\n\n\n   \nR\n\n\n\no\nss\n\n\n\n e\nt \n\n\n\nal\n.22\n\n\n\n\n\n\n\n\n\n\n\n  T\nh\n\n\n\nai\nla\n\n\n\nn\nd\n\n\n\n\n\n\n\n\n\n\n\nC\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 8\n\n\n\n5\n   \n\n\n\n\n\n\n\n\n\n\n\nC\nES\n\n\n\n-D\n   \n\n\n\n\n\n\n\n\n\n\n\n  7\n4.\n\n\n\n1\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 6\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n L\no\n\n\n\nw\n s\n\n\n\nel\nf-\n\n\n\nes\nte\n\n\n\nem\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nIn\nfa\n\n\n\nn\nt \n\n\n\nh\nea\n\n\n\nlt\nh\n\n\n\n s\nta\n\n\n\ntu\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLo\nw\n\n\n\n e\nd\n\n\n\nu\nca\n\n\n\nti\no\n\n\n\nn\n le\n\n\n\nve\nl \n\n\n\n9\n   \n\n\n\n   \nPa\n\n\n\nn\nya\n\n\n\nyo\nn\n\n\n\ng\n  \n\n\n\n\n\n\n\n\n\n\n\nTh\nai\n\n\n\nla\nn\n\n\n\nd\n   \n\n\n\n\n\n\n\n   \nC\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 1\n73\n\n\n\n1\n   \n\n\n\n\n\n\n\n  E\nPD\n\n\n\nS\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n8.\n\n\n\n4\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n12\n m\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n M\nat\n\n\n\ner\nn\n\n\n\nal\n h\n\n\n\nea\nlt\n\n\n\nh\n \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n.23\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n M\n\n\n\nar\nit\n\n\n\nal\n c\n\n\n\no\nn\n\n\n\nfl\nic\n\n\n\nt \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nEc\n\n\n\no\nn\n\n\n\no\nm\n\n\n\nic\n b\n\n\n\nu\nrd\n\n\n\nen\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nSt\nre\n\n\n\nss\nfu\n\n\n\nl l\nif\n\n\n\ne \nev\n\n\n\nen\nts\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPr\n\n\n\nev\nio\n\n\n\nu\ns \n\n\n\nd\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n \n10\n\n\n\n   \n R\n\n\n\no\no\n\n\n\nm\nru\n\n\n\nan\ng\n\n\n\nw\no\n\n\n\nn\ng\n\n\n\n   \nTh\n\n\n\nai\nla\n\n\n\nn\nd\n\n\n\n\n\n\n\n\n\n\n\nC\nas\n\n\n\ne\u2013\nco\n\n\n\nn\ntr\n\n\n\no\nl \n\n\n\n\n\n\n\n   \n31\n\n\n\n3\n   \n\n\n\n\n\n\n\n   \n E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n16\n.9\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 4\n\u20136\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n -\n H\n\n\n\nis\nto\n\n\n\nry\n o\n\n\n\nf \nlif\n\n\n\net\nim\n\n\n\ne \nm\n\n\n\naj\no\n\n\n\nr \nd\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n &\n\n\n\n P\nPD\n\n\n\n\n\n\n\n   \n  e\n\n\n\nt \nal\n\n\n\n.24\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n H\nis\n\n\n\nto\nry\n\n\n\n o\nf \n\n\n\nd\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n d\nu\n\n\n\nri\nn\n\n\n\ng\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nM\nu\n\n\n\nlt\nip\n\n\n\nar\nit\n\n\n\ny \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nU\n\n\n\nn\nw\n\n\n\nan\nte\n\n\n\nd\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nC\nh\n\n\n\nild\nca\n\n\n\nre\n s\n\n\n\ntr\nes\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPr\n\n\n\nem\nen\n\n\n\nst\nru\n\n\n\nal\n s\n\n\n\nyn\nd\n\n\n\nro\nm\n\n\n\ne \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPa\n\n\n\nin\n s\n\n\n\nym\np\n\n\n\nto\nm\n\n\n\ns \nd\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n e\nar\n\n\n\nly\n p\n\n\n\nu\nrp\n\n\n\ner\niu\n\n\n\nm\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nU\nse\n\n\n\n o\nf \n\n\n\nca\nff\n\n\n\nei\nn\n\n\n\n d\nu\n\n\n\nri\nn\n\n\n\ng\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nB\nab\n\n\n\ny \nfe\n\n\n\ned\nin\n\n\n\ng\n p\n\n\n\nro\nb\n\n\n\nle\nm\n\n\n\n \n11\n\n\n\n   \n H\n\n\n\nas\nse\n\n\n\nrt\n e\n\n\n\nt \nal\n\n\n\n.14\n   \n\n\n\n\n\n\n\nTh\nai\n\n\n\nla\nn\n\n\n\nd\n   \n\n\n\n\n\n\n\n   \nC\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 2\n25\n\n\n\n\n\n\n\n\n\n\n\n E\nPD\n\n\n\nS\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n36\n\n\n\n.0\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n2 \nm\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n P\nar\n\n\n\ntn\ner\n\n\n\n c\no\n\n\n\nn\nfl\n\n\n\nic\nt \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPe\nrf\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nis\nm\n\n\n\n  \n12\n\n\n\n   \n P\n\n\n\nh\no\n\n\n\no\nsu\n\n\n\nw\nan\n\n\n\n\n\n\n\n\n\n\n\n  T\nh\n\n\n\nai\nla\n\n\n\nn\nd\n\n\n\n\n\n\n\n\n\n\n\nC\no\n\n\n\nh\no\n\n\n\nrt\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  4\n\n\n\n49\n   \n\n\n\n\n\n\n\n   \n E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n47\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 1\n a\n\n\n\nn\nd\n\n\n\n 3\n m\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n -\n L\n\n\n\no\nw\n\n\n\n in\nco\n\n\n\nm\ne \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n.25\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n L\n\n\n\nim\nit\n\n\n\ned\n s\n\n\n\no\nci\n\n\n\nal\n s\n\n\n\nu\np\n\n\n\np\no\n\n\n\nrt\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLo\nw\n\n\n\n p\nsy\n\n\n\nch\no\n\n\n\nlo\ng\n\n\n\nic\nal\n\n\n\n w\nel\n\n\n\nl b\nei\n\n\n\nn\ng\n\n\n\n\n\n\n\nTa\nbl\n\n\n\ne \nI: \n\n\n\nSu\nm\n\n\n\nm\nar\n\n\n\ny \nof\n\n\n\n re\nse\n\n\n\nar\nch\n\n\n\n a\nrti\n\n\n\ncl\nes\n\n\n\n in\ncl\n\n\n\nud\ned\n\n\n\n in\n s\n\n\n\nys\nte\n\n\n\nm\nat\n\n\n\nic\n re\n\n\n\nvi\new\n\n\n\n a\nnd\n\n\n\n m\net\n\n\n\na-\nan\n\n\n\nal\nys\n\n\n\nis\n fo\n\n\n\nr P\nPD\n\n\n\n in\n A\n\n\n\nSE\nAN\n\n\n\n c\nou\n\n\n\nnt\nrie\n\n\n\ns\n\n\n\nco\nn\n\n\n\nt.\n...\n\n\n\n. p\ng\n\n\n\n 6\n78\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 677\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n678                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nN\no.\n\n\n\n   \nA\n\n\n\nut\nho\n\n\n\nr \n   \n\n\n\n\n\n\n\n\n\n\n\n   \nSt\n\n\n\nud\ny \n\n\n\nar\nea\n\n\n\n\n\n\n\n\n\n\n\n   \n S\n\n\n\ntu\ndy\n\n\n\n\n\n\n\n\n\n\n\n  S\nam\n\n\n\npl\ne \n\n\n\n   \n  M\n\n\n\nea\nsu\n\n\n\nre\ns \n\n\n\n\n\n\n\n P\nre\n\n\n\nva\nle\n\n\n\nnc\ne \n\n\n\n\n\n\n\n   \n T\n\n\n\nim\ne \n\n\n\nof\n a\n\n\n\nss\nes\n\n\n\nsm\nen\n\n\n\nt  \n   \n\n\n\n\n\n\n\n\n\n\n\nFa\nct\n\n\n\nor\ns \n\n\n\nas\nso\n\n\n\nci\nat\n\n\n\ned\n w\n\n\n\nith\n P\n\n\n\nPD\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(R\neg\n\n\n\nio\nn)\n\n\n\n\n\n\n\n\n\n\n\n   \n d\n\n\n\nes\nig\n\n\n\nn\n   \n\n\n\n\n\n\n\n\n\n\n\nSi\nze\n\n\n\n\n\n\n\n\n\n\n\nof\n P\n\n\n\nPD\n   \n\n\n\n\n\n\n\n o\nf P\n\n\n\nPD\n (%\n\n\n\n) \n13\n\n\n\n   \n D\n\n\n\nir\na \n\n\n\net\n a\n\n\n\nl.26\n   \n\n\n\n\n\n\n\n   \n  I\n\n\n\nn\nd\n\n\n\no\nn\n\n\n\nes\nia\n\n\n\n\n\n\n\n   \n  C\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 4\n4 \n\n\n\n\n\n\n\n   \n E\n\n\n\nPD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 2\n\n\n\n0.\n5\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 2\n m\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n- \nLo\n\n\n\nw\n m\n\n\n\nat\ner\n\n\n\nn\nal\n\n\n\n e\nd\n\n\n\nu\nca\n\n\n\nti\no\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPr\nim\n\n\n\nip\nar\n\n\n\nit\ny \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nM\nat\n\n\n\ner\nn\n\n\n\nal\n a\n\n\n\ng\ne \n\n\n\n<\n23\n\n\n\n y\nea\n\n\n\nrs\n o\n\n\n\nld\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nH\nav\n\n\n\ne \na \n\n\n\nh\nis\n\n\n\nto\nry\n\n\n\n o\nf \n\n\n\nch\nild\n\n\n\nre\nn\n\n\n\n d\nea\n\n\n\nth\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nU\nn\n\n\n\nw\nan\n\n\n\nte\nd\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n  \n14\n\n\n\n   \n N\n\n\n\nu\nrb\n\n\n\nae\nti\n\n\n\n e\nt \n\n\n\nal\n.27\n\n\n\n\n\n\n\nIn\nd\n\n\n\no\nn\n\n\n\nes\nia\n\n\n\n\n\n\n\n   \n  C\n\n\n\no\nh\n\n\n\no\nrt\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  2\n83\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n8.\n37\n\n\n\n\n\n\n\n\n\n\n\n   \n  1\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n -\n C\n\n\n\nh\nild\n\n\n\nca\nre\n\n\n\n s\ntr\n\n\n\nes\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n15\n\n\n\n.1\n9\n\n\n\n\n\n\n\n\n\n\n\n   \n  2\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nM\nar\n\n\n\nit\nal\n\n\n\n s\nat\n\n\n\nis\nfa\n\n\n\nct\nio\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n26\n\n\n\n.1\n5\n\n\n\n\n\n\n\n\n\n\n\n   \n  3\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLi\nfe\n\n\n\n s\ntr\n\n\n\nes\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nN\no\n\n\n\nn\n a\n\n\n\ncc\nep\n\n\n\nta\nn\n\n\n\nce\n o\n\n\n\nf \nb\n\n\n\nab\ny \n\n\n\ng\nen\n\n\n\nd\ner\n\n\n\n \n15\n\n\n\n   \n P\n\n\n\nu\ntr\n\n\n\nia\nrs\n\n\n\nih\n e\n\n\n\nt \nal\n\n\n\n, \n   \n\n\n\n   \nIn\n\n\n\nd\no\n\n\n\nn\nes\n\n\n\nia\n   \n\n\n\n\n\n\n\n  C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 2\n\n\n\n00\n   \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 1\n8.\n\n\n\n5\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 2\n\n\n\n\u20136\n w\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n L\nab\n\n\n\no\nr \n\n\n\nco\nm\n\n\n\np\nlic\n\n\n\nat\nio\n\n\n\nn\n \n\n\n\n\n\n\n\n  2\n01\n\n\n\n8\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n -\n U\n\n\n\nn\nw\n\n\n\nan\nte\n\n\n\nd\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLo\nw\n\n\n\n f\nam\n\n\n\nily\n in\n\n\n\nco\nm\n\n\n\ne \n16\n\n\n\n   \n N\n\n\n\nu\nrb\n\n\n\nae\nti\n\n\n\n e\nt \n\n\n\nal\n.28\n\n\n\n\n\n\n\nIn\nd\n\n\n\no\nn\n\n\n\nes\nia\n\n\n\n\n\n\n\n   \n  C\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 1\n66\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n9.\n88\n\n\n\n\n\n\n\n\n\n\n\n   \n  6\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n S\ntr\n\n\n\nes\nsf\n\n\n\nu\nl l\n\n\n\nif\ne \n\n\n\nev\nen\n\n\n\nts\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nC\nh\n\n\n\nild\nca\n\n\n\nre\n s\n\n\n\ntr\nes\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nM\n\n\n\nar\nit\n\n\n\nal\n s\n\n\n\nat\nis\n\n\n\nfa\nct\n\n\n\nio\nn\n\n\n\n \n17\n\n\n\n   \n U\n\n\n\nsn\naw\n\n\n\nat\ni e\n\n\n\nt \nal\n\n\n\n.31\n   \n\n\n\n  I\nn\n\n\n\nd\no\n\n\n\nn\nes\n\n\n\nia\n   \n\n\n\n\n\n\n\n  C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 1\n\n\n\n00\n   \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 4\n9.\n\n\n\n0\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n2 \nm\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n S\nm\n\n\n\nal\nle\n\n\n\nr \np\n\n\n\nar\nit\n\n\n\ny \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nW\n\n\n\no\nrk\n\n\n\nin\ng\n\n\n\n m\no\n\n\n\nth\ner\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLo\n\n\n\nw\ner\n\n\n\n h\nu\n\n\n\nsb\nan\n\n\n\nd\n s\n\n\n\nu\np\n\n\n\np\no\n\n\n\nrt\n \n\n\n\n18\n   \n\n\n\n P\nu\n\n\n\ntr\na \n\n\n\net\n a\n\n\n\nl.30\n   \n\n\n\n\n\n\n\n   \nIn\n\n\n\nd\no\n\n\n\nn\nes\n\n\n\nia\n   \n\n\n\n\n\n\n\n  C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 3\n\n\n\n1 \n   \n\n\n\n\n\n\n\n E\nPD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 3\n2.\n\n\n\n3\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n2 \nm\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n M\nat\n\n\n\ner\nn\n\n\n\nal\n a\n\n\n\ng\ne \n\n\n\no\nf \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n \n\n\n\n19\n   \n\n\n\n S\nu\n\n\n\nzu\nki\n\n\n\n e\nt \n\n\n\nal\n.32\n\n\n\n\n\n\n\n   \n V\n\n\n\nie\ntn\n\n\n\nam\n   \n\n\n\n\n\n\n\n   \n C\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 3\n00\n\n\n\n\n\n\n\n   \nC\n\n\n\nas\ne-\n\n\n\nFi\nn\n\n\n\nd\nin\n\n\n\ng\n  \n\n\n\n\n\n\n\n  2\n3.\n\n\n\n1\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 3\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPa\nre\n\n\n\nn\nta\n\n\n\nl a\nn\n\n\n\nd\n f\n\n\n\nam\nili\n\n\n\nal\n c\n\n\n\no\nn\n\n\n\nfl\nic\n\n\n\nt \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  I\n\n\n\nn\nst\n\n\n\nru\nm\n\n\n\nen\nts\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nR\n\n\n\nec\nen\n\n\n\nt \nm\n\n\n\no\nvi\n\n\n\nn\ng\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  f\n\n\n\no\nr \n\n\n\nD\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n -\n L\n\n\n\nac\nk \n\n\n\no\nf \n\n\n\nco\nn\n\n\n\nfi\nd\n\n\n\nen\nce\n\n\n\n in\n c\n\n\n\nh\nild\n\n\n\nre\nar\n\n\n\nin\ng\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLe\n\n\n\nss\n r\n\n\n\nel\nax\n\n\n\ned\n f\n\n\n\nee\nin\n\n\n\ng\n t\n\n\n\no\nw\n\n\n\nar\nd\n\n\n\n t\nh\n\n\n\ne \nch\n\n\n\nild\n \n\n\n\n20\n   \n\n\n\n F\nis\n\n\n\nh\ner\n\n\n\n e\nt \n\n\n\nal\n.33\n\n\n\n\n\n\n\n   \n  V\n\n\n\nie\ntn\n\n\n\nam\n   \n\n\n\n\n\n\n\n   \n C\n\n\n\no\nh\n\n\n\no\nrt\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  4\n97\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 0\n\n\n\n.9\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n8 \nw\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n  -\n E\n\n\n\nxp\no\n\n\n\nsu\nre\n\n\n\n t\no\n\n\n\n e\nit\n\n\n\nh\ner\n\n\n\n li\nfe\n\n\n\nti\nm\n\n\n\ne \no\n\n\n\nr \np\n\n\n\ner\nin\n\n\n\nat\nal\n\n\n\n IP\nV\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n4\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n6 \n\n\n\nm\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n(e\n\n\n\nm\no\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n a\nb\n\n\n\nu\nse\n\n\n\n, p\nh\n\n\n\nys\nic\n\n\n\nal\n a\n\n\n\nn\nd\n\n\n\n s\nex\n\n\n\nu\nal\n\n\n\n v\nio\n\n\n\nle\nn\n\n\n\nce\n  \n\n\n\n21\n   \n\n\n\n M\nu\n\n\n\nrr\nay\n\n\n\n e\nt \n\n\n\nal\n.34\n\n\n\n\n\n\n\n   \nV\n\n\n\nie\ntn\n\n\n\nam\n   \n\n\n\n\n\n\n\n   \n C\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 4\n31\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n8.\n1\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 6\n m\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n- \nPo\n\n\n\nve\nrt\n\n\n\ny \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nFo\n\n\n\no\nd\n\n\n\n in\nse\n\n\n\ncu\nri\n\n\n\nty\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nB\nei\n\n\n\nn\ng\n\n\n\n f\nri\n\n\n\ng\nh\n\n\n\nte\nn\n\n\n\ned\n o\n\n\n\nf \nfa\n\n\n\nm\nily\n\n\n\n m\nem\n\n\n\nb\ner\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nIn\n\n\n\nti\nm\n\n\n\nat\ne \n\n\n\np\nar\n\n\n\ntn\ner\n\n\n\n v\nio\n\n\n\nle\nn\n\n\n\nce\n \n\n\n\n22\n   \n\n\n\n T\nh\n\n\n\no\n T\n\n\n\nra\nn\n\n\n\n e\nt \n\n\n\nal\n.35\n\n\n\n\n\n\n\nV\nie\n\n\n\ntn\nam\n\n\n\n\n\n\n\n\n\n\n\n C\no\n\n\n\nh\no\n\n\n\nrt\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  1\n\n\n\n27\n4 \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 8\n.2\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n12\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nW\no\n\n\n\nm\nen\n\n\n\n e\nxp\n\n\n\no\nse\n\n\n\nd\n t\n\n\n\no\n e\n\n\n\nm\no\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n v\nio\n\n\n\nle\nn\n\n\n\nce\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nTy\np\n\n\n\ne \no\n\n\n\nf \nem\n\n\n\np\nlo\n\n\n\nym\nen\n\n\n\nt \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLa\n\n\n\nck\n o\n\n\n\nf \nfa\n\n\n\nm\nily\n\n\n\n s\nu\n\n\n\np\np\n\n\n\no\nrt\n\n\n\n a\nft\n\n\n\ner\n d\n\n\n\nel\niv\n\n\n\ner\ny \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLo\nw\n\n\n\ner\n le\n\n\n\nve\nl o\n\n\n\nf \ned\n\n\n\nu\nca\n\n\n\nti\no\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nH\nu\n\n\n\nsb\nan\n\n\n\nd\n p\n\n\n\nre\nfe\n\n\n\nre\nn\n\n\n\nce\n f\n\n\n\no\nr \n\n\n\na \nsp\n\n\n\nec\nif\n\n\n\nic\n s\n\n\n\nex\n o\n\n\n\nf \nch\n\n\n\nild\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPr\nes\n\n\n\nen\nce\n\n\n\n o\nf \n\n\n\nm\nen\n\n\n\nta\nl d\n\n\n\nis\no\n\n\n\nrd\ner\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nD\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n d\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n \n23\n\n\n\n   \n D\n\n\n\no\n e\n\n\n\nt \nal\n\n\n\n, 2\n01\n\n\n\n8\n   \n\n\n\n\n\n\n\nV\nie\n\n\n\ntn\nam\n\n\n\n\n\n\n\n\n\n\n\n C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 1\n\n\n\n16\n   \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 2\n7.\n\n\n\n6\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n <\n\n\n\n 1\n y\n\n\n\nea\nr \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n  -\n L\n\n\n\no\nw\n\n\n\n le\nve\n\n\n\nl o\nf \n\n\n\ned\nu\n\n\n\nca\nti\n\n\n\no\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nB\n\n\n\nei\nn\n\n\n\ng\n t\n\n\n\nh\ne \n\n\n\nfi\nrs\n\n\n\nt-\nti\n\n\n\nm\ne \n\n\n\nm\no\n\n\n\nth\ner\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nD\n\n\n\nis\nsa\n\n\n\nti\nsf\n\n\n\nac\nti\n\n\n\no\nn\n\n\n\n a\nb\n\n\n\no\nu\n\n\n\nt \nfa\n\n\n\nm\nily\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLi\n\n\n\nm\nit\n\n\n\ned\n c\n\n\n\no\nm\n\n\n\nm\nu\n\n\n\nn\nic\n\n\n\nat\nio\n\n\n\nn\n a\n\n\n\nn\nd\n\n\n\n in\nte\n\n\n\nra\nct\n\n\n\nio\nn\n\n\n\n w\nit\n\n\n\nh\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \no\n\n\n\nth\ner\n\n\n\ns \n24\n\n\n\n   \n L\n\n\n\nab\nra\n\n\n\ng\nu\n\n\n\ne \net\n\n\n\n a\nl.8\n\n\n\n\n\n\n\nPh\nili\n\n\n\np\np\n\n\n\nin\nes\n\n\n\n\n\n\n\n   \nC\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 1\n65\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n6.\n4\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 6\n w\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n  -\n O\n\n\n\ncc\nu\n\n\n\np\nat\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nM\n\n\n\nar\nit\n\n\n\nal\n s\n\n\n\nta\ntu\n\n\n\ns \n25\n\n\n\n   \n S\n\n\n\no\nu\n\n\n\np\nh\n\n\n\nal\nak\n\n\n\n\n\n\n\n\n\n\n\n   \n L\n\n\n\nao\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 4\n\n\n\n28\n   \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 3\n1.\n\n\n\n8\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 6\n\n\n\n-8\n w\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n  -\n\n\n\n U\nn\n\n\n\nin\nte\n\n\n\nn\nd\n\n\n\ned\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n, 2\n\n\n\n02\n0\n\n\n\n\n\n\n\n\n\n\n\n   \nLa\n\n\n\no\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n -\n L\n\n\n\no\nw\n\n\n\n b\nir\n\n\n\nth\n s\n\n\n\nat\nis\n\n\n\nfa\nct\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nD\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n d\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n \n N\n\n\n\no\nte\n\n\n\n: P\nPD\n\n\n\n =\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n d\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n, M\nIN\n\n\n\nI: \nM\n\n\n\nin\ni I\n\n\n\nn\nte\n\n\n\nrn\nat\n\n\n\nio\nn\n\n\n\nal\n N\n\n\n\neu\nro\n\n\n\np\nsy\n\n\n\nch\nia\n\n\n\ntr\nic\n\n\n\n In\nte\n\n\n\nrv\nie\n\n\n\nw\n, E\n\n\n\nPD\nS:\n\n\n\n E\nd\n\n\n\nin\nb\n\n\n\nu\nrg\n\n\n\n P\no\n\n\n\nst\nn\n\n\n\nat\nal\n\n\n\n D\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n S\nca\n\n\n\nle\n, D\n\n\n\nSM\n-I\n\n\n\nV\n: D\n\n\n\nia\ng\n\n\n\nn\no\n\n\n\nst\nic\n\n\n\n a\nn\n\n\n\nd\n S\n\n\n\nta\nti\n\n\n\nst\nic\n\n\n\nal\n M\n\n\n\nan\nu\n\n\n\nal\n o\n\n\n\nf \nM\n\n\n\nen\nta\n\n\n\nl D\nis\n\n\n\no\nrd\n\n\n\ner\ns,\n\n\n\n f\no\n\n\n\nu\nrt\n\n\n\nh\n e\n\n\n\nd\nit\n\n\n\nio\nn\n\n\n\n, C\nES\n\n\n\n-D\n: C\n\n\n\nen\nte\n\n\n\nr \nfo\n\n\n\nr \nEp\n\n\n\nid\nem\n\n\n\nio\nlo\n\n\n\ng\nic\n\n\n\nal\n S\n\n\n\ntu\nd\n\n\n\nie\ns \n\n\n\nD\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n S\nca\n\n\n\nle\n, I\n\n\n\nPV\n: I\n\n\n\nn\nti\n\n\n\nm\nat\n\n\n\ne \np\n\n\n\nar\ntn\n\n\n\ner\n v\n\n\n\nio\nle\n\n\n\nn\nce\n\n\n\n\n\n\n\nTa\nbl\n\n\n\ne \nI: \n\n\n\nSu\nm\n\n\n\nm\nar\n\n\n\ny \nof\n\n\n\n re\nse\n\n\n\nar\nch\n\n\n\n a\nrti\n\n\n\ncl\nes\n\n\n\n in\ncl\n\n\n\nud\ned\n\n\n\n in\n s\n\n\n\nys\nte\n\n\n\nm\nat\n\n\n\nic\n re\n\n\n\nvi\new\n\n\n\n a\nnd\n\n\n\n m\net\n\n\n\na-\nan\n\n\n\nal\nys\n\n\n\nis\n fo\n\n\n\nr P\nPD\n\n\n\n in\n A\n\n\n\nSE\nAN\n\n\n\n c\nou\n\n\n\nnt\nrie\n\n\n\ns\nco\n\n\n\nn\nt \n\n\n\nfr\no\n\n\n\nm\n...\n\n\n\n.. \np\n\n\n\ng\n 6\n\n\n\n77\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 678\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                679 \n\n\n\nFactors Affecting PPD \nA total of 25 studies reported risk factors for PPD. Similar \nfactors were searched for in each study. The selected studies \nidentified 23 risk factors, which were then divided into five \ngroups as shown in Table II: (1) Physical and biological \nfactors which include gestational diabetes in pregnancy,19,36 \nhypertension in pregnancy,19,36 health of the mothers;19,23,32 (2) \nPsychological factor such as history of family death,8,36 lack of \nfamily support,17,23,24,35 little family attachment,8,23,36 spouse \nassistance for child rearing,8,17,23,31 physical violence;23,35 (3) \nObstetric and paediatric factor which were unplanned \npregnancy,8,16,17,19,23,24,37 term pregnancy,8,23,35,37 low birth \nweight,8,32,37 types of delivery,8,16,17,19,37 labour difficulty,8,19,37 \nparity8,16,31,36,37 and breastfeeding;8,16,23,36 (4) Socio-demographic \nfactor which were mother age,8,16,17,23,26,30,31,35\u201337 mother \neducation level,8,17,19,26,30\u201332,35\u201337 marital status,8,19,23,37 \noccupational status of the mother,817,19,30\u201332,35,37 economic \nburden,23,32,37 type of family,8,36 urban area36,37 and (5) cultural \nfactor which include gender preferences.8,17,37  \n \nIn the meta-analyses, four factors were significantly \nassociated with PPD, as shown in Figures 6\u20139. There was an \nunplanned pregnancy, term pregnancy, poor family support \nand physical violence. Seven studies8,16,1719,23,24,37 with 5864 \nwomen were included to analyse the relationship between \nunplanned pregnancy and PPD. The pooled result showed \nthat women with unplanned pregnancies had a lower risk of \nPPD with an odd of 0.69 compared to women with planned \npregnancies (OR: 0.69, 95% CI: 0.53, 0.91). In comparison, \nfour studies8,23,35,37 with a total of 3598 women were included \nin this analysis for the association of term pregnancy with \nPPD. The pooled analysis showed that women with term \n\n\n\npregnancy had a lower risk of PPD with an odds of 0.55 \ncompared to women with preterm pregnancy (OR: 0.55, 95% \nCI: 0.40, 0.74). For the association of family support and PPD, \nfour studies17,23,24,35 were included for analysis, with a total of \n5390 women involved. The pooled result showed that women \nlacking family support had a higher risk of PPD with odds of \n5.10 compared to women with good family support (OR: \n5.10, 95% CI: 1.95, 13.38). Meanwhile, two studies23,35 were \nincluded with a total of 3005 women to assess the association \nbetween physical violence and PPD, which showed that \nwomen who experienced physical violence had a higher risk \nof PPD with the odds of 2.16 compared to women without \n(OR: 2.16, 95% CI:1.56, 2.99). \n \n \nDISCUSSION \nIn this study, we found that the pooled prevalence of PPD in \nASEAN countries was 22.32%, comparable with middle-\nincome countries, which were 20.8%;3 but lower than Middle \nEast countries, which were 27%.6 The prevalence of PPD in \nASEAN countries was higher than the recently reported \nglobal prevalence estimates of 17.22%.4 This estimated \nprevalence could be related to the limited number of research \navailable in ASEAN countries and the fact that most ASEAN \ncountries are from middle- and low-income countries.  \n \nBesides that, the pooled prevalence based on the subgroup \nanalysis of the time of assessment showed a higher \nprevalence in the first 6 weeks of postpartum, which was \n25.24%. This is slightly similar to the study3 whereby the \nprevalence of PPD was higher in the first ten weeks of \npostpartum. This is possibly due to women\u2019s attempts to \n\n\n\nVariables                                                                                                                      Number of studies \nPhysical and biological factors \n Gestational diabetes in pregnancy                                                                                    2 \n Hypertension in pregnancy                                                                                                2 \n Health of the mothers                                                                                                        3 \nPsychological factor \n History of family death                                                                                                       2 \n Lack of family support                                                                                                        4 \n Little family attachment                                                                                                     3 \n Spouse assistance for child-rearing                                                                                    4 \n Physical violence                                                                                                                  2 \nObstetric and paediatric factor \n Unplanned pregnancy                                                                                                         7 \n Term pregnancy                                                                                                                   4 \n Low birth weight                                                                                                                 3 \n Types of delivery                                                                                                                 5 \n Labour difficulty                                                                                                                  3 \n Parity                                                                                                                                    5 \n Breastfeeding                                                                                                                      4 \nSocio-demographic factor \n Mother age                                                                                                                         10 \n Mother education level                                                                                                      10 \n Marital status                                                                                                                       4 \n Occupation of the mothers                                                                                                8 \n Economic burden                                                                                                                 3 \n Type of family                                                                                                                      2 \n Urban area                                                                                                                           2 \nCultural factor \n Gender preferences                                                                                                             3 \n\n\n\nTable II: Summary of risk factors included in systematic review and meta-analysis for PPD in ASEAN countries\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 679\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n680                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nFig. 1: PRISMA flow diagram.\n\n\n\nadjust for babysitting and transition into motherhood. Other \nthan that, the possibility of hormone dysregulation following \nchildbirth also contributes to the depression.3 \n \nFrom our study, we found four significant risk factors \nassociated with PPD. There were unplanned pregnancy, term \npregnancy, poor family support and physical violence. \nAccording to current study findings, women experiencing \nphysical violence and lack or poor family support were at \nincreased risk of PPD. In this situation, usually after delivery, \nthe mother will go through a new phase and transition \nwhereby the mother needs support from the family to help, \nteach and manage the newborn. Hence, if they had a lack of \nsupport from family members or experienced physical \nviolence, it could aggravate women\u2019s condition and \ncontribute to PPD. These findings were similar to various \nsystematic reviews/meta-analysis as described below.3,38\u201340 \n\n\n\n\n\n\n\n\n\n\n\nAccording to a systematic review and meta-analysis on PPD \nand its association with adverse infant health outcomes in \nlow- and middle-income countries,3 a mother's stress and \ndepression symptoms could be worsened by a lack of social \nsupport because it affects the mother's self-confidence. Sawyer \net al.38 highlighted in a systematic review of postnatal \npsychological well-being in Africa that women who have \npoor support and marital/family conflict were associated \nwith depression. Domestic violence has been associated with \nperinatal mental disorders, including antenatal and PPD.39 A \nsystematic review and meta-analysis on domestic violence \nand perinatal mental disorders39 highlighted that women \nwith PPD reported a high prevalence and risk for intimate \npartner violence during the lifetime (OR 2.9, 95% CI 1.8\u20134.8), \nduring the past year (OR 2.8, 95% CI 1.7\u20134.6) and during \npregnancy (OR 4.4, 95% CI 2.9\u20136.5). These findings are \nconsistent with our results that demonstrated poor family \nsupport and intimate physical violence was associated with \nPPD.  \n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 680\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                681 \n\n\n\nFig. 2: Forest plot of the prevalence of PPD in ASEAN countries.\n\n\n\nFig. 3: Funnel plot for assessing publication bias.\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 681\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n682                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nFig. 4: Forest plot of a subgroup based on the countries for PPD.\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 682\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                683 \n\n\n\nFig. 5: Forest plot of the subgroup analysis based at different assessment time points for PPD.\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 683\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n684                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nFig. 6: Forest plot for association between unplanned pregnancy and PPD. \n\n\n\nFig. 7: Forest plot for association between term pregnancy and PPD.\n\n\n\nFig. 8: Forest plot for association between poor family support and PPD.\n\n\n\nFig. 9: Forest plot for association between physical violence and PPD.\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 684\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                685 \n\n\n\nFor unplanned and preterm pregnancies, our study showed a \nlower risk of PPD and was in contrast with other studies,3,4,40 \nwhereby these risk factors favour PPD. This is probably due to \nthe minimal study from ASEAN countries, different tools in \nPPD assessment method, a wide range of PPD assessment \ntime, greater variety of sample size and cultural and \nbackground factors.  \n \nBased on the measurement tools used for diagnosis of PPD, \nabout 84% of included studies used EPDS, whereas 16% used \ndifferent diagnostic tools: MINI, DSM-IV, CES-D and Case-\nFinding Instruments for Depression. Out of 84%, eight \nstudies11,17,18,24,25,33,35,36 used validated EPDS, five studies14,27,28,34,37 \nused back-to-back translation and another eight \nstudies8,20,21,23,26,29\u201331 not mentioned about validation of EPDS. \nAll this has a significant impact on the result because of the \nconsiderable disparities, and the result is difficult to interpret. \nFurthermore, different cut-off points for EPDS also \nsignificantly impacted the result. According to Levis et al.40 a \ncut-off value of 11 or higher showed maximised sensitivity \nand specificity, and 12 of the included \nstudies11,14,17,18,20,23,24,27,28,30,34,36 using cut-off point \u226511. \n \nMore research on PPD would be beneficial in identifying \npostnatal depression in mothers as soon as possible after \ngiving birth and acting immediately to prevent morbidity, \ndeath, disabilities and negative impacts on the child's future \ndevelopment. This is especially crucial for the development of \nmaternal health care in ASEAN countries. Aside from that, \nthis research is limited to papers published in English and \nlimited studies about PPD in ASEAN countries. \n \n \nCONCLUSION \nThe prevalence of PPD in ASEAN countries was 22.32%. \nUnplanned and term pregnancies lower the risk of PPD, while \npoor family support and women who have experienced \nphysical violence increase the risk of PPD. This review also \nfound a very limited study among ASEAN countries and a \nscarcity of high-quality studies in ASEAN that can be used to \ngenerate generalisability evidence. More studies are needed \nto assess this problem\u2019s magnitude and plan a proper \nintervention program. Apart from that, the findings can be \nused to identify the need for early detection, encourage the \ndevelopment of an intervention to reduce its occurrence and \nsupport mothers with PPD. \n \n \nREFERENCES \n1. Almond P. Postnatal depression: a global public health \n\n\n\nperspective. Perspect Public Health. 2009; 129(5): 221\u20137. \n2. Klainin P, Arthur DG. Postpartum depression in Asian cultures: a \n\n\n\nliterature review. Int J Nurs Stud. 2009; 46(10): 1355\u201373. \n3. Dadi AF, Miller ER, Mwanri L. 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Sexual Reprod Healthcare. \n2016; 10: 25\u201331. \n\n\n\n25. Phoosuwan N, Manwong M, Eriksson L, Lundberg PC. Perinatal \ndepressive symptoms among Thai women: a hospital-based \nlongitudinal study. Nursing Health Sci. 2020; 22(2): 309\u201317. \n\n\n\n\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 685\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n686                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n26. Dira AIKP, Wahyuni AAS. Prevalence and risk factors of \npostpartum depression in the city of Denpasar using Edinburg \nPostnatal Depression Scale Jurnal Midwifery Update (MU) 2020; \n2(2):100-109.  \n\n\n\n27. Nurbaeti I, Deoisres W, Hengudomsub P. Postpartum depression \nin Indonesian mothers: its changes and predicting factors. Pacific \nRim Int J Nurs Res. 2018; 22(2): 93-105. \n\n\n\n28. 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Intimate \npartner violence and perinatal common mental disorders among \nwomen in rural Vietnam. Int Health. 2013; 5(1): 29\u201337. \n\n\n\n34. Murray L, Dunne MP, Van Vo T, Anh PNT, Khawaja NG, Cao TN. \nPostnatal depressive symptoms amongst women in Central \nVietnam: a cross-sectional study investigating prevalence and \nassociations with social, cultural and infant factors. BMC \nPregnancy Childbirth. 2015; 15(1): 234. \n\n\n\n35. Tho Tran N, Nguyen HTT, Nguyen HD, Ngo TV, Gammeltoft T, \nRasch V, et al. Emotional violence exerted by intimate partners \nand postnatal depressive symptoms among women in Vietnam: \na prospective cohort study. PLoS One. 2018; 13(11): e0207108-e. \n\n\n\n36. Do TKL, Nguyen TTH, Pham TTH. Postpartum depression and \nrisk factors among Vietnamese women. Biomed Res Int. 2018; \n2018: 4028913. \n\n\n\n37. Inthaphatha S, Yamamoto E, Louangpradith V, Takahashi Y, \nPhengsavanh A, Kariya T, et al. Factors associated with \npostpartum depression among women in Vientiane Capital, Lao \nPeople\u2019s Democratic Republic: a cross-sectional study. PLoS One. \n2020; 15(12): e0243463. \n\n\n\n38. Sawyer A, Ayers S, Smith H. Pre- and postnatal psychological \nwellbeing in Africa: a systematic review. J Affective Disord. 2010; \n123(1-3): 17\u201329. \n\n\n\n39. Howard LM, Oram S, Galley H, Trevillion K, Feder G. Domestic \nviolence and perinatal mental disorders: A systematic review and \nmeta-analysis. PLoS Med. 2013; 10(5): e1001452. \n\n\n\n40. Levis B, Negeri Z, Sun Y, Benedetti A, Thombs BD. Accuracy of \nthe Edinburgh Postnatal Depression Scale (EPDS) for screening to \ndetect major depression among pregnant and postpartum \nwomen: systematic review and meta-analysis of individual \nparticipant data. BMJ. 2020; 371: m4022. \n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 686\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nT\nH\n\n\n\nE M\nED\n\n\n\nIC\nA\n\n\n\nL JO\nU\n\n\n\nR\nN\n\n\n\nA\nL O\n\n\n\nF M\nA\n\n\n\nLA\nYSIA\n\n\n\n V\nO\n\n\n\nL. 7\n8\n\n\n\n ISSU\nE N\n\n\n\nO\n 5\n\n\n\n SEPT\nEM\n\n\n\nB\nER\n\n\n\n 2\n0\n\n\n\n2\n3\n\n\n\nVolume: 78\n\n\n\nIssue No: 5\n\n\n\nSeptember 2023\n\n\n\n\n\n\n\n\n Printed by: Digital Perspective Sdn. Bhd. \n42-1, Level 1, Plaza Sinar, Taman Sri Sinar, 51200 Kuala Lumpur.  Tel: 03-6272 3767\n\n\n\nEmail: dpsbkl@gmail.com\n\n\n\nMJM\nOfficial Journal of the \nMalaysian Medical Association\n\n\n\nVolume  78    Number 5   September 2023\n\n\n\nPP 2121/01/2013 (031329) MCI (P) 124/1/91 ISSN 0300-5283\n\n\n\nEDITORIAL BOARD\n\n\n\nThe Medical Journal of  Malaysia is published six times a year.  \nMJM is published bimonthly ie.  January, March, May, July, September and November. \n\n\n\nAll articles which are published, including editorials, letters and book reviews \nrepresent the opinion of the authors and are not necessarily those of the \n\n\n\nMalaysian Medical Association unless otherwise expressed. \n\n\n\nCopyright reserved \u00a9 2023 \nMalaysian Medical Association \n\n\n\nAdvertisement Rates: \nEnquiries to be directed to the Secretariat. \n\n\n\nSubscription Rates: \nPrice per copy is RM100.00 or RM360.00 per annum, for all subscribers. \n\n\n\nSecretariat Address: \nMalaysian Medical Association \n\n\n\n4th Floor, MMA House, 124, Jalan Pahang, 53000 Kuala Lumpur. \nTel: (03) 4042 0617, 4041 8972, 4041 1375   Fax: (03) 4041 8187 \n\n\n\nE-mail: info@mma.org.my / mjm@mma.org.my\nWebsite: www.mma.org.my\n\n\n\n  Editor In Chief \nProf Datuk Dr Lekhraj Rampal \n\n\n\nInternational Advisory Board \nLaureate Professor Dr Nicholas Talley \n\n\n\nProf Dr Mahesh Choolani \n\n\n\nEditor \nProf Dr Shatriah Ismail \n\n\n\nEditorial Manager \nMs Mahaletchumy Alagappan\n\n\n\nAssoc Prof Dr Subapriya Suppiah \n\n\n\nProf Dato\u2019 Dr NKS Tharmaseelan \n\n\n\nProf Dr Baharudin Abdullah \n\n\n\nEditors\nDr Liew Boon Seng \n\n\n\nProf Dr Philip Rajan Devesahayam \n\n\n\nProf Dr Verasingam Kumarasamy  \n\n\n\n Dr Terence Ong Ing Wei \n\n\n\n Dr Navin Kumar Devaraj \n\n\n\n Dr Ravindran Vashu  \n\n\n\nA-INSIDE MJM(Sept23).qxp_INSIDE MJM(NEW)  25/09/2023  4:20 PM  Page i\n\n\n\n\n\n\n\n\n ii                                                                                                                                                   Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n The Medical Journal of Malaysia \n\n\n\nThe Medical Journal of Malaysia (MJM) welcomes articles of interest on all aspects of \nmedicine in the form of original papers, review articles, short communications, \ncontinuing medical education, case reports, commentaries and letter to Editor. Articles are \naccepted for publication on condition that they are contributed solely to The Medical \nJournal of Malaysia. \n \nNOTE: MJM is published bimonthly ie.  January, March, May, July, September and \nNovember. \n \nREQUIREMENTS FOR ALL MANUSCRIPTS \nPlease ensure that your submission to MJM conforms to the International Committee of \nMedical Journal Editors Recommendations for the Conduct, Reporting, Editing, and \nPublication of Scholarly Work in Medical Journals. \n \nNeither the Editorial Board nor the Publishers accept responsibility for the views and \nstatements of authors expressed in their contributions. \n \nThe Editorial Board further reserves the right to reject papers read before a society. To \navoid delays in publication, authors are advised to adhere closely to the instructions given \nbelow. \n \nMANUSCRIPTS \nManuscripts should be submitted in English (British English). Manuscripts should be \nsubmitted online through MJM Editorial Manager, http://www.editorialmanager.com/mjm. \n \nInstructions for registration and submission are found on the website. Authors will be able \nto monitor the progress of their manuscript at all times via the MJM Editorial Manager. For \nauthors and reviewers encountering problems with the system, an online Users\u2019 Guide and \nFAQs can be accessed via the \u201cHelp\u201d option on the taskbar of the login screen. \n \nMJM charges a one-time, non-refundable Article Processing Charge (APC) upon \nsubmission. Waiver of the APC applies only to members of the editorial board, and authors \nwhose articles are invited by the editor. In addition, recipients of the MJM Reviewer \nRecognition Award from the previous year may enjoy a waiver of the APC for the next \ncalendar year (e.g. recipients of MJM Reviewer Recognition Award 2022 will enjoy waiver \nof APC for articles submitted between January and December 2023). \n  \nMJM \nMember: RM500 \nNon Member: RM800 \nOverseas: USD200 \n \nMJM Case Report \nMember: RM400 \nNon Member: RM500 \n \nPreparing your manuscript \n  \nThe MJM Article Processing Charge is a non-refundable administrative fee. Payment of the \nAPC does not guarantee acceptance of the manuscript. Submitted articles will only be sent \nfor reviews once the MJM APC has been successful completed. \n \nAll submissions must be accompanied by a completed Copyright Assignment Form, \nCopyright Transfer Form and Conflict of Interest Form duly signed by all authors. Forms \ncan be download from MJM website at https://www.e-mjm.org/ \n \nManuscript text should be submitted as Microsoft Word documents. Tables and flow-\ncharts should be submitted as Microsoft Word documents. Images should be submitted as \nseparate JPEG files (minimum resolution of 300 dpi). \n \nPEER REVIEW PROCESS \nAll submissions must include at least two (2) names of individuals who are especially \nqualified to review the work. All manuscripts submitted will be reviewed by the Editor in-\ncharge before they are send for peer review. Manuscripts that are submitted to MJM \nundergo a double-blinded peer review and are managed online. Proposed reviewers must \nnot be involved in the work presented, nor affiliated with the same institution(s) as any \nof the authors or have any potential conflicts of interests in reviewing the manuscript. The \nselection of reviewers is the prerogative of the Editors of MJM. \n \nELIGIBILITY AS AN AUTHOR \nMJM follows the recommendation of the International Committee of Medical Journal \nEditors (ICMJE) for eligibility to be consider as an author for submitted papers. The ICMJE \nrecommends that authorship be based on the following four (4) criteria: \n1 Substantial contributions to the conception or design of the work; or the acquisition, \n\n\n\nanalysis, or interpretation of data for the work; AND \n2 Drafting the work or revising it critically for important intellectual content; AND \n3 Final approval of the version to be published; AND \n4 Agreement to be accountable for all aspects of the work in ensuring that questions \n\n\n\nrelated to the accuracy or integrity of any part of the work are appropriately \ninvestigated and resolved. \n\n\n\n \nTYPES OF PAPERS \nOriginal Articles: \nOriginal Articles are reports on findings from original unpublished research. Preference \nfor publications will be given to high quality original research that make significant \n\n\n\ncontribution to medicine. Original articles shall consist of a structured Abstract and the \nMain Text. The word count for the structured abstract should not exceed 500 words. The \nmain text of the articles should not exceed 4000 words, tables/illustrations/figures/images \nup to five (5) and references up to 40. Manuscript describing original research should \nconform to the IMRAD format, more details are given below.  \n \nOriginal articles of cross-sectional and cohort design should follow the corresponding \nSTROBE check-lists; clinical trials should follow the CONSORT check-list. \n \nReview Articles: \nReview Articles are solicited articles or systematic reviews. MJM solicits review articles from \nMalaysian experts to provide a clear, up-to-date account of a topic of interest to medical \npractice in Malaysia or on topics related to their area of expertise. Unsolicited reviews will \nalso be considered, however, authors are encouraged to submit systematic reviews rather \nthan narrative reviews. Review articles shall consist of a structured Abstract and the Main \nText. The word count for the structured abstract should not exceed 500 words. Systematic \nReview are papers that presents exhaustive, critical assessments of the published literature \non relevant topics in medicine. Systematic reviews should be prepared in strict compliance \nwith MOOSE or PRISMA guidelines, or other relevant guidelines for systematic reviews. \n \nShort Communications: \nShorts communication are short research articles of important preliminary observations, \nfindings that extends previously published research, data that does not warrant \npublication as a full paper, small-scale clinical studies, and clinical audits. Short \ncommunications should not exceed 1,500 words and shall consist of a Summary and the \nMain Text. The summary should be limited to 100 words and provided immediately after \nthe title page. The number of tables/illustrations/figures/images should be limited to three \n(3) and the number of references to ten (10). \n \nContinuing Medical Education (CME) Articles: \nA CME article is a critical analysis of a topic of current medical interest. The article should \ninclude the clinical question or issue and its importance for general medical practice, \nspecialty practice, or public health. It shall consist of a Summary and the Main Text. The \nsummary should be limited to 500 words and provided immediately after the title page \nUpon acceptance of selected articles, the authors will be requested to provide five multiple-\nchoice questions, each with five true/false responses, based on the article. For guideline, \nplease refer to: Sivalingam N, Rampal L. Writing Articles on Continuing Medical \nEducation for Medical Journals. Med J Malaysia. 2021 Mar;76(2):119-124. \n \nCase Reports: \nPapers on case reports (one to five cases) must follow these rules: Case reports should not \nexceed 2,000 words; with a maximum of two (2) tables; three (3) photographs; and up to \nten (10) references. It shall consist of a Summary and the Main Text. The summary should \nbe limited to 250 words and provided immediately after the title page. Having a unique \nlesson in the diagnosis, pathology or management of the case is more valuable than mere \nfinding of a rare entity. Being able to report the outcome and length of survival of a rare \nproblem is more valuable than merely describing what treatment was rendered at the \ntime of diagnosis. There should be no more than seven (7) authors. \n \nPlease note that all Case Reports will be published in the new MJM Case Reports Journal \n(www.mjmcasereports.org). \n \nCommentaries: \nCommentaries will usually be invited articles that comment on articles published in the \nsame issue of the MJM. However, unsolicited commentaries on issues relevant to medicine \nin Malaysia are welcomed. They should not exceed 2,000 words. They maybe \nunstructured but should be concise. When presenting a point of view, it should be \nsupported with the relevant references where necessary. \n \nLetters to Editor: \nLetters to Editors are responses to items published in MJM or to communicate a very \nimportant message that is time sensitive and cannot wait for the full process of peer \nreview. Letters that include statements of statistics, facts, research, or theories should \ninclude only up to three (3) references. Letters that are personal attacks on an author will \nnot be considered for publication. Such correspondence must not exceed 1,500 words. \n \nEditorials: \nThese are articles written by the editor or editorial team concerning the MJM or about \nissues relevant to the journal. \n \nSTRUCTURE OF PAPERS \nTitle Page: \nThe title page should state the brief title of the paper, full name(s) of the author(s) (with \nthe surname or last name bolded), degrees (limited to one degree or diploma), \naffiliation(s), and corresponding author\u2019s address. All the authors\u2019 affiliations shall be \nprovided after the authors\u2019 names. Indicate the affiliations with a superscript number at \nthe end of the author\u2019s degrees and at the start of the name of the affiliation. If the author \nis affiliated to more than one (1) institution, a comma should be used to separate the \nnumber for the said affiliation. \n \nDo provide preferred abbreviated author names for indexing purpose, e.g. L Rampal (for \nLekhraj Rampal), BS Liew (for Liew Boon Seng), B Abdullah (for Baharudin Abdullah), \nHoe VC (for Victor Hoe Chee Wai). \nPlease indicate the corresponding author and provide the affiliation, full postal address \nand email. \n\n\n\nINSTRUCTION TO AUTHORS\nMJM\n\n\n\nA-INSIDE MJM(Sept23).qxp_INSIDE MJM(NEW)  25/09/2023  4:20 PM  Page ii\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                  iii \n\n\n\nArticles describing Original Research should consist of the following sections (IMRAD \nformat): Abstract, Introduction, Materials and Methods, Results, Discussion, \nAcknowledgment and References. Each section should begin on a fresh page. \nScientific names, foreign words and Greek symbols should be in italic. \n \nAbstract and Key Words: \nA structured abstract is required for Original and Review Articles. It should be limited to \n500 words and provided immediately after the title page. Below the abstract provide and \nidentify three (3) to 10 key words or short phrases that will assist indexers in cross-\nindexing your article. Use terms from the medical subject headings (MeSH) list from Index \nMedicus for the key words where possible. Key words are not required for Short \nCommunications, CME articles, Case Reports, Commentaries and Letter to Editors. \n \nIntroduction: \nClearly state the purpose of the article. Summarise the rationale for the study or \nobservation. Give only strictly pertinent references, and do not review the subject \nextensively. \n \nMaterials and Methods: \nDescribe your selection of the observational or experimental subjects (patients or \nexperimental animals, including controls) clearly, identify the methods, apparatus \n(manufacturer's name and address in parenthesis), and procedures in sufficient detail to \nallow other workers to reproduce the results. Give references to established methods, \nincluding statistical methods; provide references and brief descriptions of methods that \nhave been published but are not well-known; describe new or substantially modified \nmethods, give reasons for using them and evaluate their limitations. \n \nIdentify precisely all drugs and chemicals used, including generic name(s), dosage(s) and \nroute(s) of administration. Do not use patients' names, initials or hospital numbers. \nInclude numbers of observation and the statistical significance of the findings when \nappropriate. \n \nWhen appropriate, particularly in the case of clinical trials, state clearly that the \nexperimental design has received the approval of the relevant ethical committee. \n \nResults: \nPresent your results in logical sequence in the text, tables and illustrations. Do not repeat \nin the text all the data in the tables or illustrations, or both: emphasise or summarise only \nimportant observations in the text. \n \nDiscussion: \nEmphasise the new and important aspects of the study and conclusions that follow from \nthem. Do not repeat in detail data given in the Results section. Include in the Discussion \nthe implications of the findings and their limitations and relate the observations to other \nrelevant studies. \n \nConclusion: \nLink the conclusions with the goals of the study but avoid unqualified statements and \nconclusions not completely supported by your data. Avoid claiming priority and alluding \nto work that has not been completed. State new hypotheses when warranted, but clearly \nlabel them as such. Recommendations, when appropriate, may be included. \n \nAcknowledgements: \nAcknowledgements of general support, grants, technical assistance, etc., should be \nindicated. Authors are responsible for obtaining the consent of those being acknowledged.   \n \nReferencing guide: \nThe Medical Journal of Malaysia, follows the Vancouver numbered referencing style. \nCitations to someone else's work in the text, should be indicated by the use of a number.  \nIn citing more than one article in the same sentence, you will need to include the citation \nnumber for each article. A hyphen should be used to link numbers which are inclusive, \nand a comma used where numbers are not consecutive. The following is an example \nwhere works 1.3,4,5.have been cited in the same place in the text.  \n \nSeveral effective drugs are available at fairly low cost for treating patients with \nhypertension and reducing the risk of its sequelae.1,3-5   \n \nThe list of all of the references that are cited in the article should be presented in a list \nlabelled as \u2018References\u2019. This reference list appears at the end of the paper. Authors are \nresponsible for the accuracy of cited references and these should be verified by the \nauthor(s) against the original documents before the manuscript is submitted. It is \nimportant that the author should never place in the list of references a document that he \nor she has not seen. The Journals names should be abbreviated according to the style used \nin the Index Medicus. All authors when six or less should be listed; when seven or more \nlist only the first six and add et al.   \n \nIf you are citingthe author\u2019s name in your text, you must insert the citation number as \nwell. Jewell BL (8) underlined that as focus in the SARS-CoV-2 pandemic shifts to the \nemergence of new variants of concern (VOC), characterising the differences between new \nvariants and non-VOC lineages will become increasingly important for surveillance and \nmaintaining the effectiveness of both public health and vaccination programme.  If you \nare citing more than one author\u2019s name in your text and you want to cite author names \nin your text, use \u2018et al.\u2019 after the first author. Example: Rampal et al. (9) highlighted that \nthe. disregard of the manuscript guidelines and instruction to authors of the journal you \nsubmit, is one of the common reasons for \u2018Rejection\u2019 of the article.  \n \nExample references Journals: \nStandard Journal Article \nRampal L and Liew BS. Coronavirus disease (COVID-19) pandemic. Med J Malaysia 2020; \n75(2): 95-7. \nRampal L, Liew BS, Choolani M, Ganasegeran K, Pramanick A, Vallibhakara SA, et al. \nBattling COVID-19 pandemic waves in six South-East Asian countries: A real-time \nconsensus review. Med J Malaysia 2020; 75(6): 613-25. \n \n\n\n\nNCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence \nand progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 \npopulation-representative studies with 104 million participants. Lancet 2021; 11; \n398(10304): 957-80. \n \nBooks and Other Monographs: \nPersonal Author(s) \nGoodman NW, Edwards MB. 2014. Medical Writing: A Prescription for Clarity. 4 th \nEdition. Cambridge University Press. \n \nChapter in Book \nMcFarland D, Holland JC. Distress, adjustments, and anxiety disorders. In: Watson M, \nKissane D, Editors. Management of clinical depression and anxiety. Oxford University \nPress; 2017: 1-22. \n \nCorporate Author \nWorld Health Organization, Geneva. 2019. WHO Study Group on Tobacco Product \nRegulation. Report on the scientific basis of tobacco product regulation: seventh report of \na WHO study group. WHO Technical Report Series, No. 1015. \n \nNCD Risk Factor Collaboration (NCD-RisC). Rising rural body-mass index is the main \ndriver of the global obesity epidemic in adults. Nature 2019; 569: 260\u201364. \n \nWorld Health Organization. Novel Coronavirus (2019-nCoV) Situation  Report 85, April \n14, 2020. [cited April 2020] Accessed from: https://www.who.int/docs/defaultsource/ \ncoronaviruse/situationreports/20200414-sitrep-85-covid-19. \n \nOnline articles \nWebpage: Webpage are referenced with their URL and access date, and as much other \ninformation as is available. Cited date is important as webpage can be updated and URLs \nchange. The \"cited\" should contain the month and year accessed. \n \nMinistry of Health Malaysia. Press Release: Status of preparedness and response by the \nministry of health in and event of outbreak of Ebola in Malaysia 2014 [cited Dec 2014]. \nAvailable from: http://www.moh.gov.my/english.php/database_stores/store_ \nview_page/21/437. \n \nOther Articles: \nNewspaper Article \nPanirchellvum V. 'No outdoor activities if weather too hot'. the Sun. 2016; March 18: 9(col. \n1-3). \n \nMagazine Article  \nRampal L.World No Tobacco Day 2021 -Tobacco Control in Malaysia. Berita MMA. 2021; \nMay: 21-22.   \n \nTables: \nAll tables and figures should have a concise title and should not occupy more than one \nprinted page. The title should concisely and clearly explain the content of the table or \nfigure. They should be numbered consecutively with Roman numerals (e.g Table I) and \nfigures with Arabic numerals (e.g. Figure 1), and placed after the sections of the \nmanuscript which they reflect, particularly the results which they describe on separate \npages. Cite tables in the text in consecutive order. Indicate table footnotes with lower-case \nletters in superscript font. Place the information for the footnote beneath the body of the \ntable. If a table will be submitted as a separate document, the filename should contain \nthe surname of the first author and match its label in the manuscript (e.g., SMITH Table \nI).Vertical lines should not be used when constructing the tables. All tables and figures \nshould also be sent in electronic format on submission of the manuscript as \nsupplementary files through the journal management platform. Clinical Photographs \nshould conceal the subject's identity. Tables and flow-charts should be submitted as \nMicrosoft Word documents. Images should be submitted as separate JPEG files (minimum \nresolution of 300 dpi).   \n \nPhotographs of Patients: \nProof of permission and/or consent from the patient or legal guardian must be submitted \nwith the manuscript. A statement on this must be included as a footnote to the relevant \nphotograph. \n \nColour reproduction: \nIllustrations and diagrams are normally reproduced in black and white only. Colour \nreproductions can be included if so required and upon request by the authors. However, \na nominal charge must be paid by the authors for this additional service; the charges to \nbe determined as and when on a per article basis. \n \nAbbreviations: \nUse only standard abbreviations. The full-term for which an abbreviation stands should \nprecede its first use in the abstract, article text, tables, and figures, unless it is a standard \nunit of measurement. Abbreviations shall not be used in the Title. Abbreviations should \nbe kept to a minimum. \n \nFormatting of text: \nNumbers one to ten in the text are written out in words unless they are used as a unit of \nmeasurement, except in tables and figures. Use single hard-returns to separate \nparagraphs. Do not use tabs or indents to start a paragraph. Do not use the automated \nformatting of your software, such as hyphenation, endnotes, headers, or footers \n(especially for references). Submit the Manuscript in plain text only, removed all \u2018field \ncodes\u2019 before submission. Do not include line numbers. Include only page number. \n \nBEST PAPER AWARD \nAll original papers which are accepted for publication by the MJM, will be considered for \nthe \u2018Best Paper Award\u2019 for the year of publication. No award will be made for any \nparticular year if none of the submitted papers are judged to be of suitable quality.\n\n\n\n The Medical Journal of Malaysia \n\n\n\nA-INSIDE MJM(Sept23).qxp_INSIDE MJM(NEW)  25/09/2023  4:20 PM  Page iii\n\n\n\n\n\n\n\n\n iv                                                                                                                                                  Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nCONTENTS                                                                                                               Page \n\n\n\n\n\n\n\nEditorial \n\n\n\n\n\n\n\n\u2022 The evolution of the Medical Journal of Malaysia - beyond a century                                                            551  \nLiew Boon Seng, Lekhraj Rampal   \n\n\n\n\n\n\n\nOriginal Articles \n\n\n\n\n\n\n\n\u2022 Noise-induced hearing loss among manufacturing factory workers in Kuching, Sarawak:                           559 \nPrevalence and associated risk factors                                                                                                                       \nHalim Ismail, Azizul Idris, David Chan Chee Hoong, Hanis Ahmad, Hafiz Baharudin, Naiemy Reffin,  \n\n\n\nHibatul Hakimi Jamaludin, Nor Azila Aris, Huam Zhe Shen \n \n\n\n\n\u2022 Walking further. How surgery can help the cerebral palsy child                                                                   566\nSyed Azhariff, Rashidah Ismail, Manimalar Selvi Naicker, Abd Halim Rashid, Brenda Saria Yuliawiratman,  \nAmaramalar Selvi Naicker  \n\n\n\n\n\n\n\n\u2022 Non-intubated vs. intubated video-assisted thoracoscopic bullectomy \u2013 a retrospective cohort study         570 \nPalaniappa Meiyappan Palaniappan, Diong Nguk Chai, Benedict Dharmaraj, Amiruddin Nik Mohamed Kamil,  \n\n\n\nNarasimman Sathiamurthy \n \n\n\n\n\u2022 Evaluating the impact of a pre-recorded online video on doctor's knowledge and attitude towards          574 \nleprosy in Sabah and Labuan - a quasi experimental study                                                                                \nXin Yun Teoh, Sook Yee Michelle Voo, Nadirah Sulaiman \n\n\n\n\n\n\n\n\u2022 Contact sensitization to fragrance allergen: a 5-year review in the Department of Dermatology,             583 \nHospital Kuala Lumpur                                                                                                                                          \nVivian Tai, Sharifah Rosniza Syed Nong Chek, Min Moon Tang \n\n\n\n \n\u2022 Impedance changes in cochlear implant electrodes one year after switch on: A cohort study at a             589 \n\n\n\ntertiary referral hospital in Jakarta, Indonesia \nSemiramis Zizlavsky, Rangga Saleh, Harim Priyono \n\n\n\n\n\n\n\n\u2022 Intravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public        594 \nprimary stroke centres versus acute stroke ready hospitals: Comparison of real-world clinical outcomes        \nSchee Jie Ping, Ang Chai Liang, Crystal Teoh Sing Chiek, Tan Hui Jieh, Chew Sin Hong, Anderson Steven, Hii Ding Wei,  \nChin Yen Theng, Loh Ee Wen, Desmond Samuel, Pravind Narayanan, Mazlina Husin, Linda Then Yee Yen, Cheah Chun Fai,  \nCheah Wee Kooi, Zainura Che Isa, Aznita Ibrahim, Chia Yuen Kang, Khairul Azmi Ibrahim, Looi Irene, Law Wan Chung,  \nZariah Abdul Aziz \n\n\n\n\n\n\n\n\u2022 Effectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) in preventing hospitalisation and death among         602 \nCOVID-19 patients: a prospective cohort study                                                                                                      \nChew Lan Sim, Lim Xin Jie, Chang Chee Tao, Ros Sakinah Kamaludin, Leow Hon Lunn, Ong Su Yin, Norirmawath Saharuddin,  \n\n\n\nNor Aida Sanusi, Normi Kamaruzaman, Zaiton Kamarruddin, Philip Rajan \n \n\n\n\n\u2022 Serum interleukin 40: an innovative diagnostic biomarker for patients with systemic lupus                     609 \nerythematosus                                                                                                                                                          \n\n\n\nAmal Mahdi Al Rubaye, Inas K. Sharquie, Faiq I. Gorial \n \n\n\n\n\u2022 Clinicopathological study of gastric cancer in a Malaysian tertiary public health care centre                    616  \n\n\n\nHtet Htet, Thin Thin Win, Wong Siew Tung, Noor Hasni Bt Shamsudin, Kandasami Palayan \n \n\n\n\n\u2022 Parental affordability and willingness to pay for universal masking amongst government school            621 \nstudents in Kuching, Sarawak                                                                                                                                 \n\n\n\nAnselm Ting Su, Jew Win Kuan, Musdi Hj Shanat, Baderin Osman, Haalah Mahmud \n \n\n\n\nA-INSIDE MJM(Sept23).qxp_INSIDE MJM(NEW)  25/09/2023  4:20 PM  Page iv\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                    v \n\n\n\nCONTENTS                                                                                                               Page \n \n\u2022 A cross-sectional study on the sleep quality among type 2 diabetes mellitus patients and its associated     627 \n\n\n\nfactors                                                                                                                                                                          \nNorhazimah Saparwan, Noorlaili Mohd Tohit, Salmiah Md Sharif \n\n\n\n\n\n\n\n\u2022 Efficacy and safety of adjunctive treatment with perampanel in epilepsy patients                                        635  \nKuan Yee Lim, Ching Soong Khoo, Rathika Rajah, Hui Jan Tan, Farah Waheeda Tajurudin \n\n\n\n\n\n\n\n\u2022 Outcome of cardiopulmonary in the emergency department of a tertiary hospital in Malaysia                   639 \nMohamad Iqhbal Kunji Mohamad, Mohd Amin Mohd Mokhtar, Mohamad Rodi Bin Isa, Mohd Fazrul Mokhtar \n\n\n\n\n\n\n\n\u2022 Development of an online animated sexting prevention module based on the prototype willingness         646 \nmodel to reduce intention and willingness to sexting among diploma students                                                   \nNorain Mansor, Norliza Ahmad, Salmiah Md Said, Tan Kit Aun, Rosnah Sutan \n\n\n\n\n\n\n\n\u2022 Stress perceived by drivers in public healthcare facilities in Negeri Sembilan during the first year of          653 \nthe COVID-19 pandemic                                                                                                                                            \nAbdul Aziz Harith, Zuraida Mohamed, Azyyati Mohammad, Lim Kuang Kuay, Naiemy Reffin, Malindawati Mohd Fadzil,  \n\n\n\nShahida Ismail, Nofi Yuliani Dahlan, Muhammad Zulfakhar Zubir, Mohd Ihsanuddin Abas \n \n\n\n\n\u2022 Three-year epidemiology of hospitalised paediatric burn patients in a Malaysian Tertiary Hospital           661 \n2016 \u2013 2018                                                                                                                                                                 \nChuen Xian Low, Ying Quan Kok, Xuan Song Loo, Chin Fang Ngim, Raymond Zhun Ming Lim, Soong Yuen Quah \n\n\n\n\n\n\n\nSystematic / Narrative Review Article  \n \n\n\n\n\u2022 Current management of appendicular mas - a narrative review                                                                     669  \nKumar Hari Rajah, Somanathan Menon, Ganesh Ramachandran \n\n\n\n\n\n\n\n\u2022 A 10-year systematic review and meta-analysis of determinants of postpartum depression in the              675 \nAssociation of Southeast Asian Nations countries                                                                                                    \nSiti Syafiqah Sainuddin, Norhayati Mohd Noor, Azidah Abdul Kadir, Rosnani Zakaria \n\n\n\n\n\n\n\nLetter To Editor \n \n\n\n\n\u2022 Nanoparticles produced from propolis extract: Their applications in medicine, why not?                             687  \nLe Pham Tan Quoc \n\n\n\n\n\n\n\nAcknowledgement                                                                                                      688 \n\n\n\n\n\n\n\nA-INSIDE MJM(Sept23).qxp_INSIDE MJM(NEW)  25/09/2023  4:20 PM  Page v\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023 551 \n\n\n\nINTRODUCTION \nThe Medical Journal of Malaysia (MJM) is the oldest medical \njournal not only in Malaysia but also in the region, serving \nmore than 17,000 doctors, and the wider healthcare \ncommunity. The vision of the MJM is to be the foremost \nmedical journal that promotes the integration of medical \nresearch and scholarly publication across South East Asia \nnations in particular and the world at large. The mission of \nthe MJM is to improve all peoples\u2019 lives by assisting and \nstrengthening the capacities of members of the Malaysian \nMedical Associations (MMA) and Medical Associations of \nSouth East Asian Nations (MASEAN) by training and \npublishing sound scientific articles. MJM is a double-blind \npeer-reviewed scientific journal. It publishes multidisciplinary \nmanuscripts that seek to advance medical and health \nsciences research, including all aspects of clinical and \npreventive medicine; political, economic, environmental \nsocial and technological (PEEST) subjects related to medical \npractice. The journal follows the International Committee of \nMedical Journal Editors (ICMJE) and Committee on \nPublication Ethics (COPE) guidelines with regard to \nconcerning its editorial policies on publication ethics, \nscientific misconduct, consent and peer review criteria. The \naim of this editorial is to record the history of MJM. \n\n\n\nHistory of MJM \nIn this editorial, we trace the history of the MJM from its \ninception. The first medical journal ever published in \nSoutheast Asia was the Journal of Straits Medical Association \n(JStMA). It was the official journal of the Straits Medical \nAssociation (StMA) which was established in 1890 [Figure \n1(A)]1. The StMA was then led by Dr. D. J. Galloway as the \nPresident [Figure 2 (A)]2, with Dr. W. Gilmore Ellis being the \nVice President. The first edition of the journal was under the \neditorship of Dr. Max F, Simon who was then the principal \ncivil medical officer of the Straits Settlements.3 \n\n\n\nThe journal published the minutes of meetings, rules of the \nassociation, reports of the committee and the address by Dr \nGalloway. There were only three manuscripts in the March\u2013\nSeptember 1890 issue, on \u2018Puerperal Eclampsia\u2019, \u2018A case of \nSyphilitic Coma\u2019 and \u2018A type of Puerperal Fever\u2019 in the 48 \npages issue. Dr. Max F. Simon dated 21st November 1892 \nmentioned that nearly all the members of the medical \nprofession in the Straits Settlement which included the whole \nof the Malay Peninsular had joined as corresponding \nmembers of the StMA, which has been recognised as a branch \nof the British Medical Association (BMA). He stated that a \njournal may be established which shall contain contributions \nfrom all the practitioners in the Malay Peninsula. The \nheadquarters of the association was in Singapore. He hoped \n\n\n\nthat the journal would become a means of communication \nbetween all medical men in the whole Peninsular of Malaya, \nnotes of cases and improved methods of treatment which \nmay be forwarded and received for publication, besides as a \nrecord of the proceedings of the association.3 \n\n\n\nAccording to the research work by W.S. Tiew (1999) on \u2018Some \nScholarly English Periodicals In Pre-Independent Malaysia: \nAn Historical Overview\u2019, he found that the JStMA was one of \nthe earliest Pre-independent Malaysian Scholarly English \nPeriodicals, with the Journal of the Indian Archipelago and \nEastern Asia was the first published in 1847, followed by the \nJournal of Eastern Asia (1875), the Journal of the Straits \nBranch of the Royal Asiatic Society (1878) and the \nAgricultural Bulletin of the Malay Peninsula (1891).4 \n\n\n\nThe second issue of the JStMA (October 1890\u2013March 1891) \nwas edited by Dr. Max Frank Simon. There were papers on \n\u2018Parangi disease\u2019, \u2018Case of Myxoedema\u2019, \u2018Beri-beri to \naccompany microscopical specimens\u2019 with notes of \ndiscussion on Beri-beri, notes of cases and a memorandum on \nAncylostomiasis in the 36 pages issue. The third issue (April \n1891\u2013March 1892) was with a new editor, Dr. W. Gilmore \nEliis. There were eight papers including one on Leprosy. \nAccording to the editor (in his editorial), the third number of \nthe JStMA was bulkier than the previous issues with 60 pages. \nThe fourth issue of the JStMA (April 1892\u2013March 1893) was \nedited by Dr. T.S. Kerr. A few interesting papers were papers \non \u2018Disorders of sleep\u2019, \u2018Malarial diarrhea\u2019, \u2018Amok of the \nMalays\u2019, \u2018Treatments of sciatica\u2019 and \u2018Ulcerative tuberculous \nof the lobe of the ear\u2019 in a 75-page issue. \n\n\n\nThe fifth issue of the JStMA (April 1893\u2013December 1894) with \n17 scientific papers was the period of the transaction of the \nStMA until the end of 1894, which thereafter became a \nbranch of the BMA. Interesting papers include topics on \n\u2018Acromegaly\u2019 and \u2018Spinal concussion\u2019 and a paper on \nunqualified practice in Singapore were published in the 158-\npage issue. It was noted in the minutes of the regular \nmonthly meeting on 4th November 1893 that Dr. Middleton, \nthe secretary, reported that 15 out of the 23 circulars sent to \nmembers not residing in Singapore indicated their \nwillingness to join the BMA, with two expressing \nunwillingness. In the annual general meeting dated 16th \nDecember 1893, it was unanimously agreed that the \nsecretary should draw up the necessary requisition of joining \nthe BMA. The annual subscription of the journal was fixed at \n$9 with $3 as the annual subscription to the branch. All the \npapers in the issues were discussed in the monthly meeting \nprior to the publications.5 All the first five volumes were \nprinted by the Government Printing Office in Singapore. \n\n\n\nThe evolution of the Medical Journal of Malaysia - beyond a \ncentury \n\n\n\nLiew Boon Seng, MS (Neurosurgery), Lekhraj Rampal, DrPH\n\n\n\nEDITORIAL \n\n\n\n This article was accepted: 29 August 2023\nCorresponding Author: Prof Datuk Dr Lekhraj Rampal \nEmail: dr_rampal1@hotmail.com\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 551\n\n\n\n\n\n\n\n\nEditorial \n\n\n\n552                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nOn 1st January 1894, the StMA was admitted as a branch of \nBMA, known as the Malaya Branch of the British Medical \nAssociation (MBBMA).6 In their regular monthly meeting \nheld on 6th May 1894, a committee was formed to draft new \nrules and by-laws for the purpose of transmission to the \nbranch organisation committee of the BMA. The membership \nof the new entity was 38 members. The publication of the \nJStMA was discontinued following the formation of this new \nentity.6 \n \nBy 1910, half of 215 registered medical practitioners in British \nMalaya including Singapore joined the association.7 The \nrevival of the journal with a new name, the Journal of the \nMBBMA, occurred in 1904 [Figure 1B(i)]8. The news was \npublished in the Straits Times on 29th June 1904. Dr. J. Kirk, \nas the chairman of the editorial committee, along with the \nassistance of Dr. McDowell, who established the local branch \nof the BMA, ensured the journal's reappearance with greater \nregularity in its issues. Articles on topics such as dengue fever \nby Dr. More and malarial fever by Dr. Galloway were \nconsidered relevant at that time. The second volume was \npublished in 1905. These two volumes were printed by the \nPinang Gazette Press Ltd, located in Penang, Malaya. \n \nThe third volume (Session 1905\u20131906 and January 1907) of \nthe Journal of the MBBMA was published. The 118-page \nvolume contained the minutes of the Council of the Malay \nBranch 1904 and 1905, minutes of meetings of the Singapore \ndivision for 1905 and 1906, the report of the Medical \nRegistration Bill Committee and 14 other papers. [Figure \n1B(ii)]9. However, due to insufficient contributions and \neditorial issues, the journal could not sustain its publication \nin 1907. \n \nThe journal was revived in January 1911 as the Malaya \nMedical Journal (MMJ). It was considered as the IX volume \n(previously five volumes as the JStMA and three volumes as \nthe Journal of the MBBMA).  Dr. Gilbert E Brooke was the \neditor with his last issue in October 1912 [Figure 1C(i)10 and \n1C(ii)11]. The journal was the organ of the MBBMA and the \nMalaya Branch of the Far Eastern Association of Tropical \nMedicine. There were a total of two volumes, each consisting \nof four parts. The first volume, which was published in 1911, \nincludes a 74-page January issue, a 66-page April issue, a 97-\npage July issue and a 74-page October issue. The second \nvolume, which was published in 1912, includes a 68-page \nJanuary issue, a 58-page May issue, a 34-page August issue \nand a 48-page October issue. The two volumes were printed \nby the Methodist Publishing House in Singapore [Price $4.00 \nper annum ($2.00 to BMA members), Single copies $1.00]. \n \nHe was replaced by Dr. J.W. Scharff in 1922, and the journal \nwas given a new name, the Transactions of the MBBMA, with \n56 pages.7 Dr. J.W. Scharff served as the editor until 1923. For \nthe subsequent twelve volumes issued between January 1926 \nand March 1937, the journal was renamed as the Malayan \nMedical Journal, by the MBBMA. There were four editors, \nnamely Dr. T.S. Macaulay (1926), Dr. JR. Kayo-Mouat (1927), \nDr. G.H. Macalister (1928-1929) and Dr. G.V. Allen (1930-\n1937) for those issues [Figure 2(B)]12. \n \nOn 17th December 1926, the quarterly MMJ was officially \nadopted as the official organ of the MBBMA. There were six \n\n\n\noriginal articles in its first January\u2013December 1926 issue, \ncovering topics such as \u2018Epidemic Jaundice\u2019, \u2018Leptospirosis\u2019, \n\u2018A system of Intelligence as a Handmaiden of Hygiene\u2019, \n\u2018Occupational Cancer with Special Reference to the Industries \nof Malaya\u2019, \u2018Epithelioma adenoidescysticum\u2019 and \u2018An \nexperiment with Paris Green as an Anopheles \nludlowaelarvicide\u2019. A special obituary notice of the late Miss \nElizabeth Fletcher, Matron of the General Hospital, Singapore \nwas published too. The subscription rate was six dollars per \nannum. The managing headquarters was located in Kuala \nKrai, Kelantan.13 \n \nThe MMJ reverted to its previous name, the Journal of the \nMBBMA for its five volumes of quarterly publications \nbetween 1937 and 1941 [Figure 1D(i)14 and 1D(ii)15]. The \nAdvertising & Publicity Bureau Ltd, Singapore was the \nprinting company of the journal. A supplementary issue of \nthe Journal of the MBBMA was published in June 1941 which \nconsisted of the names of Asiatic members.16 A study done by \nTeng et al in 2019 showed that out of five medical journals \npublished in pre-independence British Malaya from 1890 to \n1941, the MMJ published 59.5% of the articles.17 \n \nThere was no publication during World War II. However, \nfollowing World War II with the return of the British to \nMalaya and Singapore, the journal reappeared as the \nMedical Journal of Malaya under the same association, the \nMBBMA, from 1946 to 1959. The journal was printed by the \nYoung Advertising & Marketing Ltd, Singapore. The first two \nvolumes published between 1946 and 1947 were under Dr. \nD.W.G. Faris as the editor, while Dr. D.E.C. Mekie was the \neditor for the subsequent seven volumes published between \n1948 and 1954. Dr. H.M. McGladdery was the next editor for \nthe 11th volume (September 1956) through the 15th volume \n(2nd issue in December 1960).  \n \nThe close relationship between MBBMA and BMA can be \nobserved in a correspondence published on 8th January 1949 \nin its parent journal, the British Medical Journal (BMJ). The \ncorrespondence was written by Dr. Webb Johnson, the \nPresident of the Royal Medical Benevolent Fund regarding \ngift parcels sent by MBBMA.18 However in 1958, the situation \nchanged. In November 1958, medical doctors in both the \nFederation of Malaya and Singapore decided to withdraw \nfrom the MBBMA and established a new entity, the Malayan \nMedical Association. On 5th November 1958, an article was \npublished in the Straits Times, stating that \u2018the 1,500 doctors \nin Singapore and Federation will be holding their inaugural \nmeeting of the Malayan Medical Association on 10th \nNovember 1958\u2019. A draft of the constitution with 13 items \nwas introduced.19 However, the drafted constitution of the \nMalayan Medical Association was rejected by the Malaya \nRegistrar of Societies (ROS) as reported in the Straits Times \ndated 7th March 1959. The rejection was on the grounds that \ndoctors from both the Federation of Malaya and Singapore \nwere considered separate political entities before the \nformation of Malaysia and a single association could not \nrepresent doctors in both territories.20 \n \nThe Malayan Medical Association appealed against the \ndecision, arguing that the association is a professional, non-\npolitical body and political objections should therefore not \nimpede the formation of a pan-Malayan organisation for \n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 552\n\n\n\n\n\n\n\n\nThe evolution of the Medical Journal of Malaysia - Beyond a Century\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                553 \n\n\n\nFig. 1: A:First edition of the Journal of Straits Medical Association March\u2013September 1890; B(i): The front page of the Journal of the \nMalaya Branch of the BMA session 1904\u20131905; B(ii): The contents of the Volume 3: Session 1905\u20131906 of the Journal of the \nMalaya Branch of the BMA; C (i): The front page of the Malaya Medical Journal, January 1911, Vol IX. Part 1; C (ii): The front \npage of the Malaya Medical Journal, January 1912, Vol X. Part 1; D (i): The content page of the Journal of the Malaya Branch of \nthe British Medical Association, Volume II, No. 4 (1st March 1939); D(ii): Front page of the Journal of the Malaya Branch of the \nBritish Medical Association, Volume 3, No. 3 (December 1939); E(i): Index page of the Medical Journal of Malaya, Volume 11, \nSeptember 1956\u2013June 1957; E(ii): Front page of the Medical Journal of Malaya, Volume 12, No. 2 December 1957; E(iii): Index \npage of the Medical Journal of Malaya, Volume 14, September 1959\u2013June 1960; E(iv): Front page of the Medical Journal of \nMalaya, Volume 15, No.2 December 1960; F(i) Front page of the Medical Journal of Malaysia, Volume 47, Issue 3 September 1992; \nF(ii) Front page of the Medical Journal of Malaysia, Volume 59, Issue 2 June 2004; F(iii) Front page of the Medical Journal of \nMalaysia, Volume 64, Issue 1 March 2009 \n\n\n\nA B (i) B (ii)\n\n\n\nD (i) D (ii)C (i) C (ii)\n\n\n\nE (iii) E (iV)E (i) E (ii)\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 553\n\n\n\n\n\n\n\n\nEditorial \n\n\n\n554                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nFig. 2: (A): Dr. David James Galloway; (B): Dr. George Vance Allen; (C): Dr. A. A. Sandosham; (D): Dr. Paul C.Y. Chen; (E): Dr. Victor K.E. \nLim; (F): Dr. John T. Arokiasamy; (G): Dr. Azhar M. Zain; (H): Dr. K.G. Lim; (I): Dr. Khoo Kah Lin; (J):Professor Datuk Dr. Lekhraj \nRampal\n\n\n\nA B C D\n\n\n\nE F G\n\n\n\nI J\n\n\n\nH\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 554\n\n\n\n\n\n\n\n\nThe evolution of the Medical Journal of Malaysia - Beyond a Century\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                555 \n\n\n\ndoctors. On 2nd July 1959, the Federation Government again \nturned down the request of 1500 doctors in the Federation \nand Singapore to register their newly formed Malayan \nMedical Association. The decision was made by Mr. J. G. \nAdams, the Registrar of Trade Union and Societies, based on \nthe Federation's interest in having a Federation body with \nFederation citizens as officials.21 \n\n\n\n\n\n\n\nThe Straits Times, dated 4th August 1959, reported that \u2018The \noldest medical organisation in Malaya, the MBBMA, which is \n\n\n\nmore than 50 years old, will be dissolved soon\u2019. The last \npresident of the association was Dr. A.W.S. Thevathasan.22 \nOn 31st August 1959, news regarding the formation of a new \nmedical association, the Singapore Medical Association \n(SMA) was reported. On 15th September 1959, the new \nassociation took over the functions of the present Alumni \nAssociation of the King Edward VII College of Medicine and \nthe Faculty of Medicine, University of Malaya, as well as the \nBritish Medical Centre. This news was announced by Dr. V. \nThambipillai, the President of the Alumni Association. He \n\n\n\nFig. 3: The Medical Journal of Malaysia Metrics 1999\u20132022.\n\n\n\n*Bar graphs using left vertical axis and line graphs using right vertical axis \nSource: Scimago Journal & Country Rank \n\n\n\nFig. 4: The Medical Journal of Malaysia: Number of articles according to the types of articles and number of supplements in 2013\u20132022 \n(including the new 2022 MJM Case Reports journal).\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 555\n\n\n\n\n\n\n\n\nEditorial \n\n\n\n556                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nalso mentioned the formation of a similar body, the Malayan \nMedical Association, in the Federation.23 \n \nTwo medical associations were formed to replace the \nMBBMA: the SMA on 15th September 1959, and the Malayan \nMedical Association on 24th October 1959. Both medical \nassociations were affiliated with the BMA, based in London. \nSince then, the Medical Journal of Malaya has been under \nthe Malayan Medical Association and has been handled by \nthe same editor, Dr. H.M. McGladdery, until 1965 [Figure \n1E(i), 1E(ii) and 1E(iii)]. \n \nThe SMA established its own medical journal, the Singapore \nMedical Journal (SMJ), in 1960.24 The SMJ published an article \nentitled \u2018Galloway Memorial Lecture\u2019 which was written by \nDr. J.W. Scharff in 1960. In that article, it was stated that \u2018Sir \nDr. David Galloway was the first president of the Straits \nMedical Association in 1890. Four years later, he became the \npresident of the newly formed MBBMA. He passed away on \n5th March 1943 at the age of 85 years old\u2019.25 \n \nDr. A.A. Sandosham was the first Malaysian to serve as the \neditor for the Medical Journal of Malaya, appointed by the \n\n\n\nMalayan Medical Association, from 1965 until [Figure 2(C)]26. \nA  total of three volumes, spanning from the 3rd issue of the \nvolume XXIV to the 4th issue of the volume XXVI, were under \nthe editorship of  Dr. A.A. Sandosham. The Straits Times Press \n(S) Sendirian Berhad, Thomson Road, Singapore was the \nprinting company of the journal. \n \nIn 1972, following the formation of Malaysia in 1963, the \njournal was renamed as the Medical Journal of Malaysia \n(MJM) in September 1972, following the renaming of the \nMalayan Medical Association to Malaysia Medical \nAssociation (MMA) (Table I). Dr. A.A. Sandosham continued \nas the honorary editor of the MJM. He was replaced by Dr. \nPaul C.Y. Chen, the honorary editor for the 4th issue of the \n31st volume, in June 1977 [Figure 2(D)]. \n \nIn the 1st issue of the 37th volume of the MJM, published in \nMarch 1982, the honorary editor, Dr. Paul C.Y. Chen wrote \nan editorial titled \u2018The medical journal of Malaysia: Past and \nFuture\u2019. In the editorial, which marks the journal's 92nd year, \nhe stated that \u2018the MJM is the leading medical journal in the \nregion. To maintain the highest level of editorial and medical \nwriting, the journal has acquired the part-time services of an \n\n\n\nName of the journal                                                 Labeled volume                 Published month,                    Editor/Honorary Editor/ \n                                                                              (cumulative volume)                         year                                 Editor-In-Chief [Issue] \nJournal of Straits Medical                                               1,2 (2)                        Mar,1890\u2013Mar,1891                          Dr. Max Simon \nAssociationa                                                                        3 (3)                          Apr,1891\u2013Mar,1892                      Dr. W. Gilmore Ellis \n                                                                                          4,5 (5)                         Apr,1892\u2013Dec,1894                            Dr. T. S. Kerr \nJournal of the Malaya Branch of                                    1-3 (8)                            1904\u2013Jan,1907                                   Dr. J. Kirk \nthe British Medical Associationb                                            \nMalaya Medical Journalb                                                9,10 (10)                       Jan,1911\u2013Oct,1912                       Dr. Gilbert E Brooke \nThe transaction of the Malaya                                         (11)                                  1922\u20131923                                 Dr. J.W. Scharff \nBranch of the British Medical Associationb                           \nMalayan Medical Journalb                                                  (12)                           Jun,1926\u2013Mar,1927                     Dr. J.W. Scharff [1,2];  \n                                                                                                                                                                                  Dr. T.S. Macaulay [3,4] \n                                                                                            (13)                           Jun,1927\u2013Mar,1928                       Dr. JR. Kayo-Mouat \n                                                                                          (14,15)                        Jun,1928\u2013Mar,1930                       Dr. G.H. Macalister \n                                                                                          (16-23)                        Jun,1930\u2013Mar,1937                           Dr. G.V . Allen \nThe Journal of the Malaya Branch of the                     (23-28)                        Jun,1937\u2013Mar,1942 \nBritish Medical Associationb                                                                                                 \nThe Medical Journal of Malayab                                  1,2 (29,30)                     Sep,1946\u2013Jun,1948                          Dr. D.W.G. Faris \n                                                                                     3\u201310 (31-38)                    Sep,1948\u2013Jun,1956                          Dr. D.E.C. Mekie \n                                                                                    11-13 (39-41)                   Sep,1956\u2013Jun,1959                      Dr. H.M. McGladdery \nThe Medical Journal of Malayac                                14-18 (42-46)                   Sep,1959\u2013Jun,1964                      Dr. H.M. McGladdery \n                                                                                          19 (46)                        Sep,1964\u2013Jun,1965                 Dr. H.M. McGladdery [1,2];  \n                                                                                                                                                                               Dr. A.A. Sandosham [3.4] \n                                                                                    20-26 (47-53)                   Sep,1965\u2013Jun,1972                       Dr. A.A. Sandosham \nThe Medical Journal of Malaysiad                              27-30 (48-57)                   Sep,1972\u2013Jun,1976                       Dr. A.A. Sandosham \n                                                                                          31 (58)                        Sep,1976\u2013Jun,1977                  Dr. A.A. Sandosham [1-3]; \n                                                                                                                                                                                  Dr. Paul C.Y. Chen [4] \n                                                                                    32-41 (59-68)                   Sep,1977\u2013Dec,1986                        Dr. Paul C.Y. Chen \n                                                                                    42-45 (69-72)                   Mar,1987\u2013Dec,1990                   Dr. N. Chandrasekharan \n                                                                                    46-53 (73-80)                   Mar,1991\u2013Dec,1998                       Dr. Victor K.E. Lim \n                                                                                    54-63 (81-90)                   Mar,1999\u2013Dec,2008                   Dr. John T. Arokiasamy \n                                                                                    64,65 (91, 92)                  Mar,2009\u2013Dec,2010                        Dr. Azhar M. Zain \n                                                                                     66,67 (93,94)                   Feb,2011\u2013Dec,2012                             Dr. K.G. Lim \n                                                                                          68 (95)                        Feb,2013\u2013Dec,2013                        Dr. K.G. Lim [1-3]; \n                                                                                                                                                                                  Dr. Khoo Kah Lin [4-6] \n                                                                                          69 (96)                        Feb,2014\u2013Dec,2014                         Dr. Khoo Kah Lin \n                                                                                   70-78*(97-105)                   Feb,2015\u2013present                        Dr. Lekhraj Rampal \n \nPublishers of journal: aStraits Medical Association; bBritish Medical Association Malaya Branch; cMalayan Medical Association; dMalaysian Medical Association; \n*Until the 2023 issue \n\n\n\nTable I: Information on Pre- and Current volumes of the Medical Journal of Malaysia, 1890\u2013 Present\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 556\n\n\n\n\n\n\n\n\nThe evolution of the Medical Journal of Malaysia - Beyond a Century\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                557 \n\n\n\nexecutive assistant, tasked with assisting in maintaining the \ndifficult and meticulous editorial policy of the Journal\u2019. \nDuring his tenure as the honorary editor, the journal faced \nfinancial problems as the cost of publication continued to \nrise.27 \n\n\n\n \nIn 1987, the first BMA Congress was held in Kuala Lumpur to \nrecognise the MMA as one of the former overseas branches of \nBMA. Despite the fact that MMA was an independent \nassociation in sovereign states, the BMA Congress helped to \nmaintain the old ties and create new ones.28 Dr. N. \nChandrasekharan was the honorary editor from 1987 until \n1990. He was replaced by Dr. Victor K.E. Lim in 1990 [Figure \n2(E)]. The second article on the history of the MJM was \npublished in 1995.29 Dr. John T. Arokiasamy [Figure 2(F)] \nserved as the next honorary editor from 1999 until 2008 and \nwas subsequently replaced by Dr. Azhar M. Zain. [Figure \n2(G)]. Dr. K.G. Lim [Figure 2(H)] took over the helm from Dr. \nAzhar M. Zain in 2011. \n \nIn 2011, the Honarary Editor at that time, Dr. Lim Kean Ghee \nwrote an editorial for the 66th volume of the MJM entitled \n\u2018The Medical Journal of Malaysia: Its History and Its \nMission\u2019.30 The first volume is considered to date back to the \npublication of the Medical Journal of Malaya in 1946. \nHowever, according to him, the Medical Journal of Malaysia \ncan claim 121 years of history based on the heritage of the \nforerunning medical associations such as the StMA, which \nwas established in 1890.30 The appearance of the MJM has \nbeen changing over years (Figure 1). \n \nDr. K.G. Lim\u2019s tenure as the Honorary Editor ended after the \n3rd issue of the 68th volume. Dr. Khoo Kah Lin [Figure 2(I)] \nreplaced him and served until the end of 2014 (Table I). His \nposition as the Honorary Editor was taken over by Dr. Lekhraj \nRampal in 2015. At the annual General Meeting of the \nMalaysian Medical Association in 2019, the post of Honorary \nEditor was changed to Editor in Chief. Dr. Lekhraj Rampal \nhas been serving as the EIC of the MJM from 2015 and \nremains the EIC at the present tenure. A summary of all the \nprevious and current versions of MJM and its editors, \nhonorary editors and EICs are shown in Table I. \n \nIn 2019, the EIC, Professor Datuk Dr. Lekhraj Rampal \ninformed the Editorial Board Members, that the time was now \nripe for moving to the next level. He stated that steps need to \nbe taken to improve the quality and quantity and its impact \nfactor on the health sector. MJM editorial board needs to \nidentify the bottlenecks and remove them. During the period \n2019/2021, bottlenecks were identified and removed to \nensure better quality and quantity. Articles that were \naccepted were published in the next issue. The staff was \nreplaced. Criteria were set for applicants to join the in as \neditors. Younger members were admitted as Editorial Board \nmembers. They had to apply and meet certain criteria. In \n2021, the Editorial Board decided to separate the MJM into \ntwo journals, namely, the Medical Journal of Malaysia and \nthe Medical Journal of Malaysia Case Reports (MJM Case \nReports). This policy change explained by Prof Rampal was \nthat the case reports were not well cited and the journal \ncitation index was being affected.  \n \n \n\n\n\nThe first volume of the MJM without case reports was volume \n77, issue no. 4, published in July 2022. However, the need for \na separate journal for case reports was felt for the training of \nyoung doctors. The policy to have a separate journal for case \nreports was approved in the Annual General Meeting of the \nMMA. The first issue of MJM Case Reports was published in \nAugust 2022 with a new International Standard Serial \nNumber (ISSN) 2948-3859. It contained 22 articles. It is being \npublished regularly, three issues per year.  Case reports \nrepresent a relevant form of advancing medical scientific \nknowledge, especially of rare diseases or conditions. They are \nimportant learning resources for doctors. They are usually the \nfirst encounter that trainees or residents will have in their \nearly careers. It serves also as a platform for them to write \nand learn the techniques of scientific writing.  \n \nMJM: The way forward \nCurrently, in 2023, with the 78th volume, we are also \ncelebrating 133rd years anniversary of the journal since the \npublication of its first version of the JStMA in 1890. Over one \ncentury, we have covered many milestones. The most noted \nis that of sustainability and an increased number of scientific \nmanuscripts published in each volume.  \n \nThe MJM continues to provide a scientific platform for \nmedical doctors and scientists to contribute new knowledge \nwhich leads to better healthcare for the population. The \nreviewing and editing of our medical journal have been \nconducted on a voluntary basis by the medical fraternity. The \nMJM follows the COPE Guidelines and a double-blind peer \nreview system. From initially being only the printed version, \nthe MJM has since 2010 been made available online with free \naccess. The MJM can be accessed at the uniform resource \nlocator http://www.e-mjm.org.31 The availability of archives \nof previous issues from 1980 was made available in 2013.32 In \n2020, under the leadership of the EIC, Professor Datuk Dr. \nLekhraj Rampal, he and his team have performed rigorous \nsearches for the availability of non-digitised issues of the \nMJM. Those issues from 1979 were first made available online \nin December 2020. Most of the past issues from 1960 were \nmade available online in February 2022. The MJM is \ncurrently indexed in MEDLINE, EMBASE, PubMed and \nScopus. The MJM is now moving forward to be indexed in the \nDirectory of Open Access Journals (DOAJ) and Science \nCitation Index Expanded (SCIE). \n \nMJM SCImago Journal Rank (SJR) h-index is 39 (Q3) in \n2023.33 The Medical Journal of Malaysia Metrics 1999\u20132022 \nin the SJR website shows a positive linear correlation \ncoefficient between year and number of citations per \ndocument. The same correlation was shown between the year \nand the total citations with almost zero linear correlation \ncoefficient between year and self-citation. These figures \nindicate that the increasing number of total citations was not \ndue to self-citation with the number of self-citations \nremaining low over the past 23 years in the MJM (Figure 3). \nAbrizah reported that MJM was one of the Malaysian \nmedical journals with the highest h-index score based on the \nMalaysian Medical Journals Indexed in MyCite in 2015 \nreport.34 There has been an increasing trend of original \narticles being submitted to the MJM. Despite the separation of \ncase reports and case series from the MJM, there have been \nencouraging numbers of publications in the MJM Case \n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 557\n\n\n\n\n\n\n\n\nEditorial \n\n\n\n558                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nReports. The number of proceedings from meetings held in \nMalaysia has been encouraging due to its high prestige \n(Figure 4). \n \n \nCONCLUSION \nThe MJM has evolved from its initial publications of variously \nnamed as the Journal of Straits Medical Association in 1890, \nJournal of the Malaya Branch of the BMA session in 1904, the \nMalaya Medical Journal in 1911, the Medical Journal of \nMalaya in 1946 and the current MJM since 1972. MJM has \nbeen served by 22 editors since its inception in 1890. \nCurrently, in 2023, with the 78th volume, we are also \ncelebrating 133 years anniversary of the journal since the \npublication of its first version of the JStMA in 1890. Over one \ncentury, we have covered many milestones. The most noted \nis that of sustainability, an increased number of scientific \nmanuscripts published, the number of issues each year and \nincreased citations. The MJM is now the journal of choice \namong clinical researchers in Malaysia to publish their \nresearch findings and is one of the most cited medical \njournals published in Malaysia. It has marched forward to \nensure the MJM remains as an open-access journal with its e-\nversion with limited copies of the printed form. The MJM \ncontinues to improve the lives of all people by assisting and \nstrengthening the capacities of clinicians, academicians, \npractitioners and scientists by publishing sound scientific \narticles. \n \n \nACKNOWLEDGEMENTS \nWe wish to express our sincere gratitude to Dr. Azhar M. Zain \nand Dr. K.G. Lim (former Editors of MJM), Professor Dr. Victor \nHoe and Professor Dr. Pakeer Oothuman for spending their \nprecious time reviewing this paper. We also wish to express \nour sincere appreciation to the MMA EXCO Members \n(2022/2023) led by Dr. Muruga Raj A/L Rajathurai for their \nfull support to the current editorial board of the MJM. \n \n \nREFERENCES \n1. The Journal of the Straits Medical Association. 1890. \n\n\n\nEresources.nlb.gov.sg. [cited August 2023]. Available from: \nhttps://eresources.nlb.gov.sg/  \n\n\n\n2. Singapore Government Agency. Our History of Healthcare. [cited \nAugust 2023]. Accessed from: \nhttps://www.roots.gov.sg/en/stories-landing/stories/history-of-\nhealthcare-sg \n\n\n\n3. Simon MF. Introductory Note. The Journal of the Straits Medical \nAssociation. 1890; 1:i-ii \n\n\n\n4. Tiew WS. Some scholarly English periodicals in pre-independent \nMalaysia: An historical overview. Malaysian Journal of Library \nand Information Science. 1999;4 (1):27-40 \n\n\n\n5. Kerr TS. Annual General Meeting. The Journal of the Straits \nMedical Association. 1894; 5:7-11 \n\n\n\n6. Khoo FY. X-rays in Singapore 1896-1975. Singapore University \nPress for the Radiological Society of Singapore. 1981 \n\n\n\n7. Chia JYJ. Straits Medical Association. Singapore Infopedia. \nEresources.nlb.gov.sg. [cited August 2023]. Accessed from: \nhttps://eresources.nlb.gov.sg/ \n\n\n\n8. The Journal of the Malaya Branch of the BMA. 1904-1905. \nEresources.nlb.gov.sg. [cited August 2023]. Accessed from:  \nhttps://eservice.nlb.gov.sg/  \n\n\n\n9. The Journal of the Malaya Branch of the BMA. 1904-1906; 3. \nEresources.nlb.gov.sg. [ cited August 2023]. Accessed from: \nhttps://eservice.nlb.gov.sg/  \n\n\n\n10. The Malaya Medical Journal. 1911; 9(Part 1). \nEresources.nlb.gov.sg. [cited August 2023]. Accessed from: \nhttps://eservice.nlb.gov.sg/ \n\n\n\n11. The Malaya Medical Journal. 1912;10 (Part 1). \nEresources.nlb.gov.sg. [cited August 2023]. Accessed from:  \nhttps://eservice.nlb.gov.sg/ \n\n\n\n12. Wikimedia Foundation. George Vance Allen. Wikipedia. August \n15, 2023. [cited August 2023]. Accessed from: \nhttps://en.wikipedia.org/wiki/George_Vance_Allen  \n\n\n\n13. Malayan Medical Journal: Adopted as Official Organ of B.M. \nAssociation. The Straits Times. 1926; Dec 17:9 \n\n\n\n14. The Journal of the Malaya Branch of the British Medical \nAssociation. 1939; II (4). Eresources.nlb.gov.sg. [cited August \n2023]. Accessed from: https://eservice.nlb.gov.sg/ \n\n\n\n15. The Journal of the Malaya Branch of the British Medical \nAssociation. 1939;3(3). Eresources.nlb.gov.sg. [cited August \n2023]. Accessed from: https://eservice.nlb.gov.sg/ \n\n\n\n16. Anderson RE. Medical Prisoners in Singapore. Br Med J. \n1945;2(4427):660-1. \n\n\n\n17. Teng CL, Lim KG, Ang CY, Chan SY, Sam EKS, Wee JCS, et al. Pre-\nindependence medical journals in British Malaya: A content \nanalysis. IeJSME 2019 13(2): 23-26 \n\n\n\n18. Webb J. Malaya Branch of B.M.A. and R.M.B.F. Br Med J, \n1949;1:70 \n\n\n\n19. Doctors unite on \u2018service before self\u2019 banner. The Straits Times. \n1958; Nov 5:8 \n\n\n\n20. New association for doctors rejected. The Straits Times. 1959; Mar \n7:8 \n\n\n\n21. A \u2018No\u2019 to A Malayan Medical Body: Federation refuses \nregistration. The Straits Times. 1959; Jul 2:7 \n\n\n\n22. Two local bodies to replace the British Medical Association. The \nStraits Times. 1959; Aug 4:16 \n\n\n\n23. Singapore doctors get all-in-one association. The Straits Times. \n1959; Aug 31:4 \n\n\n\n24. Wikimedia Foundation.  Singapore Medical Journal. Wikipedia. \n2023; May 5. [cited August 2023]. Accessed from: \nhttps://en.wikipedia.org/wiki/ Singapore_Medical_Journal \n\n\n\n25. Scharff JW. The life and times of Sir David Galloway Singapore \nMed J. 1960;1(3):84-6 \n\n\n\n26. Malaysian Society of Parasitology and Tropical Medicine. [cited \nAugust 2023]. Accessed from: https://msptm.org/about/ \n\n\n\n27. Chen CT. The Medical Journal of Malaysia: Past and Future. Med \nJ Malaysia. 1982;37(1):1-6 \n\n\n\n28. Beecham  L,  Smith  T.  Conference  Report:  Minarets  and \nmicrochips: the BMA in Kuala Lumpur. Br Med J (Clin Res Ed). \n1987 Oct 31;295(6606):1126\u20139. PMCID: PMC1248191. \n\n\n\n29. Lim VKE. A short history of the Medical Journal of Malaysia. Med \nJ Malaysia. 1995;50 Suppl A:S11-3. \n\n\n\n30. Lim KG. The Medical Journal of Malaysia: its history and its \nmission. Med J Malaysia. 2011;66(3):173-174. \n\n\n\n31. Lim KG. The e-mjm. Med J Malaysia. 2010 Jun;65(2):97. \n32. Lim KG. The e-mjm goes LIVE to PubMed. Med J Malaysia. 2013 \n\n\n\nJun;68(3):195-4. \n33. Medical Journal of Malaysia. Scimago Journal & Country Rank. \n\n\n\n[cited August 2023]. Accessed from: https://www.scimagojr.com/ \njournalsearch.php?q=17838&tip=sid \n\n\n\n34. Abrizah A. Performance of Malaysian Medical Journals. Malays \nJ Med Sci. 2016 Mar;23(2):1-5. \n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 558\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                559 \n\n\n\nABSTRACT \nIntroduction: Noise-induced hearing loss (NIHL) is a \ncommon problem worldwide. Increased globalisation, as \nwell as industrialisation, gives rise to an increase in the \nincidence of NIHL worldwide. Malaysia is not spared from \nthis problem, either. The objectives were to determine the \nprevalence of NIHL and its associated factors among \nmanufacturing factory workers. \n \nMaterial and Methods: A cross-sectional study was done in \nKuching, Sarawak, involving 173 randomly selected \nrespondents among manufacturing factory workers. Data \ncollected were respondents' workplace monitoring data and \ntheir audiometry records obtained from the factory record, \nand the otoscopy examinations performed. In addition, \nrespondents were required to fill up an interviewer-guided \nquestionnaire.  \n \nResults: The prevalence of NIHL was high (49.7%). The \nfactors which were found to have a significant association \nwith NIHL in bivariate analysis were age (p < 0.05, 95% CI), \nmale gender (p < 0.05; OR \u2013 7.60; CI 3.34 \u201318.38), duration of \nemployment (p <0.05), knowledge of noise level (p < 0.05; OR \n\u2013 4.11; CI 1.10 \u2013 15.28), working at polishing department (p < \n0.05; OR \u2013 4.23; CI  2.13 \u2013 8.43), and smoking (p < 0.05; OR \u2013 \n39.6; CI 16.5 \u2013 94.8). Pack\u2013years of smoking were also found \nto have a significant association with p < 0.05. However, only \nsmoking was statistically significant in multivariate analysis, \nwhere the risk of developing NIHL was 27.55 (p < 0.005; CI \n10.74 \u2013 70.64) among smokers. \n \nConclusion: The high prevalence of NIHL despite the \nexisting Hearing Conservation Program (HCP) may indicate \nthat there may be some elements in HCP that require close \nmonitoring by the factory management, and the importance \nof smoking cessation among the workers exposed to noise \nat the workplace should be highlighted. \n \nKEYWORDS:  \nNoise-induced hearing loss, manufacturing factory, audiometry, \nprevalence, Sarawak \n \n \nINTRODUCTION \nOccupational noise-induced hearing loss (NIHL) is a \nprevalent occupational disorder, and hearing loss caused by \n\n\n\nworkplace noise exposure is a significant health issue \nglobally.1 NIHL occurs due to long-term exposure to excessive \nnoise, usually over the years. Therefore, continuous or \nintermittent noise in the workplace that exceeds 85dB(A) \nduring an 8-hour shift, or impact noise that exceeds \n120dB(A) , is deemed dangerous.1,2 \n \nGlobally, NIHL is responsible for 16% of cases of debilitating \nhearing loss in adults, indicating that it does not directly \ncause early death but does result in significant disability.2,3 In \nMalaysia, occupational NIHL, which includes NIHL, hearing \nimpairment, and Permanent Standard Threshold Shift, was \nthe most frequently reported occupational disease in 2021, \naccounting for 3648 cases (68.9%).4 Although the data may \nnot reflect the entire Malaysian population, it is clear that \nNIHL is a significant concern impacting many employees in \nMalaysia.  \n \nNIHL is related to multiple factors, and the risk factors for \ndeveloping NIHL can be non-modifiable such as age and \ngender, or can be modifiable. In addition to occupational \nnoise, other causes (such as organic solvents, high \ntemperatures, lack of hearing protection devices, smoking, \nalcohol, heredity, comorbidities) may serve independently or \nsynergistic effects with noise to increase the risk of NIHL.5-6 \n\n\n\nTobacco smoking is a risk factor for various diseases, and \nseveral scientific literatures has shown that it may be related \nto NIHL.7-9 Some toxic and harmful substances like nicotine \nfrom tobacco burning may affect hearing.10 Smokers were \nalmost twice as likely as non-smokers to develop hearing loss. \nThis association persisted in studies that excluded those with \nnon-age-related hearing loss and those with no history of \noccupational noise exposure.10,11 Several meta-analysis \nstudies have found evidence of an association between \ncigarette smoke and hearing loss.10-12 \n \nThe intensity, frequency, duration of exposure, and type of \nnoise significantly impact the risk of health hazards, notably \noccupational hearing loss. Individuals with NIHL may \nendure severe morbidity due to hearing loss, concomitant \ntinnitus, and poor speech discrimination.13 Non-auditory \neffects may impacts workplace communication and safety. \nThe non-auditory reaction to noise may be affected by sound \nqualities such as the rate, loudness, consistency, complexity, \nduration (period of exposure) and noise meaning.14 Noise has \nbeen linked to increased stress, cardiovascular health \n\n\n\nNoise-induced hearing loss among manufacturing factory \nworkers in Kuching, Sarawak: Prevalence and associated \nrisk factors \n \nHalim Ismail, DrPH, Azizul Idris, MScCH, David Chan Chee Hoong, MPH, Hanis Ahmad, MPH, Hafiz Baharudin, \nMPH, Naiemy Reffin, MScCH, Hibatul Hakimi Jamaludin, MD, Nor Azila Aris, MD, Huam Zhe Shen, MD \n\n\n\n     \nDepartment of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 26 June 2023                                                                                                                                                                             \nCorresponding Author: David Chan Chee Hoong                                                                                                                                                                \nEmail: davidcch10@gmail.com\n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 559\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n560                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n(hypertension, changes in heart rate), irritation, poor sleep \nand mental health issues. Because of this broad spectrum of \nimpacts, experts believe noise can interact as a general, non-\nspecific stressor.14-15 Studies have proved that a sound pressure \nlevel of 95-90 dB(A) can induce hearing loss of more than 25 \ndB(A), whereas a sound pressure level of 85-90 dB(A) can \ncause hearing loss of less than 2dB(A).16 The risk of NIHL can \nbe minimised if noise is decreased to below 80 dB(A). \nRegulation six of the Occupational Safety and Health (Noise \nExposure) Regulations 2019 states that the NEL as the daily \nnoise exposure level should not exceed 85dB(A) or daily \npersonal dose (cumulative noise exposure of an employee \ncorrected for a typical working day of eight hours) a hundred \nper cent (100%). The criterion for maximum sound level \npressure (SPL) exceeding 115dB(A) at any time or the peak \nSPL exceeding 140dB(C) necessitates the implementation of \nactivities to reduce risk of NIHL. This dose limit uses a 3-dB \ntime-intensity trade-off as the exchange rate.2,18  \n \nA thorough medical history can assist in establishing whether \nany of these disorders may be contributing to an individual's \nhearing loss.2,17,18 Poor knowledge and awareness among \nemployees and a lack of enforcement by governing bodies \nwere cited as factors for the risk of NIHL. In addition, hearing \nprotection is not often adequately fitted, and even when it is, \nit wears out and fails to provide the specified laboratory \nvalues of attenuation in the field.17,18  \n \nResearch showed that occupational noise exposure is a \nsignificant concern and pervasive in the industrial industry.19 \nProcessing tasks are a significant aspect of the manufacturing \nindustry, and the complexity of process noise such as forging, \ngrinding, cutting, polishing, and welding is very noticeable.20 \nAlthough the reported NILH cases have dramatically \nincreased since 2010, there is a significant disparity between \nthe number of cases diagnosed and the number of workers \nexposed to hazardous noise. In addition, there is no \nestablished data on NIHL among manufacturing sector \nworkers in Sarawak. Therefore, this study aims to determine \nthe proportion of NIHL and its associated factors among \nmanufacturing factory workers.  \n \n \nMATERIALS AND METHODS \nStudy design \nThis retrospective cross-sectional study was conducted among \nmanufacturing factory workers in Sarawak to evaluate the \nmedical record, area monitoring, personal monitoring, and \nworkers' audiometry assessment from the factory records.  \n \nThis research has been approved by UKM ethical committee \n(UKM FPR.4/244/FF-2016-219) and the manufacturing \ncompany management board. \n \nStudy subject and methods \nThis study included all workers from the polishing and \nplating department of the manufacturing factory who went \nfor an annual audiometry assessment and were exposed to \nnoise at work above noise exposure limits (NEL) of 85 dB(A). \nHowever, workers who have underlying medical diseases that \nmay compromise blood flow to organs and increase viscosity, \nlike diabetes mellitus, hyperlipidaemia, and hypothyroidism, \n\n\n\nhistory of usage of the ototoxic drug, history of severe and \nfrequent ear infections with or without ear surgery were \nexcluded from the study. Additionally, workers with a history \nof exposure to non-occupational noise, such as involvement \nin the war, and loud explosion activities, such as hunting, \nwere excluded.  \n \nEligible workers were selected by a simple random sampling \nmethod, where each subject was chosen randomly and by \nchance.  \n \nSelected respondents then undergo an otoscopic examination \nand audiometric assessment. Those with abnormal otoscopic \nfindings such as ear wax, ear discharge, perforated tympanic \nmembrane, and ear infection were ruled out from the study. \nAn audiometry assessment was conducted for selected \nworkers after they were not exposed to noise for 14 hours \nbefore the test. Furthermore, all respondents were using \nhearing protective devices uniformly as they worked in an \narea requiring hearing protection before entry.  \n \nFactors such as age, gender, duration of working, working \ndepartment in the company, smoking habits (packed year), \nknowledge of noise level of the workplace unit, and usage of \nhearing protective devices were obtained through a \nsociodemographic questionnaire.   \n \nWritten and oral informed consent was obtained from all \nparticipants. They were assured anonymity as well as \nconfidentiality. \n \nDiagnosis of NIHL \n1. History taking and physical examination \nTo ensure that the NIHL was caused by the current \nemployment and not due to previous job exposure or other \nnon-occupational exposure, several histories such as \nmedical, non-occupational, previous employment, drugs, \nrecreational and social histories of exposure risk in the \nhistory taking were included in the sociodemographic \nquestionnaire. History of hearing loss, ear pain, ear \ndischarge, head injury, history of tinnitus, recent surgery on \near, nose, and throat, or head surgery was considered. \nHobbies that involve noise exposure, such as loud music, \nclubbing, hunting, and scuba diving as a hobby were \ndocumented.   \n \nRespondents underwent a thorough head, ear, neck and \ncranial nerve examination and an otoscopic examination.  \n \n2. Audiometric assessment \nThere must be a positive history of exposure to noise at the \nworkplace. Audiometric examination results were used to \ndetermine hearing loss among the respondents. The \naudiometric results should have a hearing threshold of more \nthan 25 dB(A) at 4 kHz with a characteristic dip followed by \nrecovery at higher frequencies to determine whether hearing \nloss was related to noise exposure. The dip depth in NIHL \nalone should not be more than 75 dB(A) in higher \nfrequencies and should not be more than 40 dB(A) in lower \nfrequencies. If those dips were not consistent with the \ncharacteristic of noise exposure, then the hearing loss could \nbe due to other factors such as presbycusis.  \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 560\n\n\n\n\n\n\n\n\nNoise-induced hearing loss among manufacturing factory workers in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                561 \n\n\n\n   Variables                                                         Frequency (n)                                      Percentage (%) \nAge group                                                                                                                                              \n\n\n\n20 \u2013 24.9                                                                        51                                                          29.5 \n25 \u2013 29.9                                                                        54                                                          31.2 \n30 \u2013 34.9                                                                        42                                                          24.3 \n35 \u2013 39.9                                                                        21                                                          12.1 \n40 \u2013 44.9                                                                         2                                                            1.2 \n\u2265 45                                                                                 3                                                            1.7 \n\n\n\nGender                                                                                                                                                   \nMale                                                                              131                                                         75.7 \nFemale                                                                           42                                                          24.3 \n\n\n\nDuration of employment \n1 \u2013 4.9                                                                           116                                                         67.1 \n5 \u2013 9.9                                                                            38                                                          22.0 \n10 \u2013 14.9                                                                        10                                                           5.8 \n15 \u2013 19.9                                                                         2                                                            1.2 \n\u2265 20                                                                                 7                                                            4.0 \n\n\n\nDepartment                                                                                                                                           \nPlating                                                                           58                                                          33.5 \nPolishing                                                                       115                                                         66.5 \n\n\n\nNoise level knowledge \nYes                                                                                 14                                                           8.1 \nNo                                                                                 159                                                         91.9 \n\n\n\nHPD usage \nYes                                                                                 36                                                          20.8 \nNo                                                                                 137                                                         79.2 \n\n\n\nSmoking history \nYes                                                                                 82                                                          47.4 \nNo                                                                                  91                                                          52.6 \n\n\n\nPack \u2013 years+ \n< 0.9                                                                              106                                                         61.3 \n1 \u2013 4.9                                                                            37                                                          21.4 \n5 \u2013 9.9                                                                            25                                                          14.5 \n10 \u2013 14.9                                                                         3                                                            1.7 \n\u2265 15                                                                                 2                                                            1.2 \n\n\n\n \nHPD = Hearing protective device \n+ smoking was quantified based on pack years which are calculated based on the number of cigarettes per day times the years of cigarette consumption. \n \n\n\n\nTable I: Sociodemographic characteristics of respondents (n = 173)\n\n\n\n                                                                         Frequency (n)                                                     Percent (%) \nYes                                                                              86                                                                      49.7 \nNo                                                                               87                                                                      50.3 \nTotal                                                                          173                                                                    100.0 \n \n\n\n\nTable II: Prevalence of NIHL\n\n\n\nVariables                                                                                                                 NIHL (%)                                 c2 value                p value \n                                                                                                                  Yes                                No \n\n\n\nGender                                                                   Male                     79 (60.3%)                   52 (39.7%)              24.22                 < 0.001* \n                                                                             Female                    7 (16.7%)                    35 (83.3%)                                                \nPrevious employment                                             Yes                       5 (45.5%)                     6 (54.5%)               0.085                     0.77 \n                                                                                 No                       81(50.0%)                     81(50.0%)                                                 \nDepartment                                                         Plating                   42 (72.4%)                   16 (27.6%)              17.99                < 0.0005* \n                                                                            Polishing                 44 (38.3%)                   71 (61.7%)                                                \nNoise level knowledge                                           Yes                      11 (78.6%)                    3 (21.4%)                5.08                    0.024* \n                                                                                 No                      75 (47.2%)                   84 (52.8%)                                                \nHearing protective device usage                           Yes                      20 (55.6%)                   16 (44.4%)               0.62                      0.43 \n                                                                                 No                      66 (48.2%)                   71 (51.8%)                                                \nSmoking                                                                  Yes                      72 (87.8%)                   10 (12.2%)              90.49                <0.0005* \n                                                                                 No                      14 (15.4%)                   77 (84.6%)                                                \n \n* Statistically significant p < 0.05\n\n\n\nTable III: Association between gender, previous employment, department, noise level knowledge, hearing protective device usage, \nsmoking, and NIHL\n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 561\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n562                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nVariables                                             NIHL                          N                    Mean \u00b1 Std. deviation               t-test, (t)                     p value \nAge                                                       Yes                          86                            30.69 \u00b1 7.19                          3.902                       <0.001* \n                                                              No                           87                            27.02 \u00b1 4.97                                                                  \nDuration of employment                    Yes                          86                             5.71 \u00b1 5.39                                                                   \n                                                              No                           87                             3.15 \u00b1 2.37                            4.05                       <0.0005* \nPack-years                                             Yes                          86                             3.44 \u00b1 3.36                            8.62                       <0.0005* \n                                                              No                           87                             0.22 \u00b1 0.86                                 \n                                                                  \n*Statistically significant p < 0.05 \n \n\n\n\nTable IV: Association between age, duration of employment, pack-years and NIHL\n\n\n\nVariables                                                     aOR                              p value                                                   95% C.I. for OR \n                                                                                                                                                        Lower                                Upper \nAge                                                              0.98                                 0.70                                      0.91                                   1.07 \nSmoking*                                                    27.55                                0.00                                     10.74                                 70.64 \nGender                                                         2.42                                 0.13                                     0.778                                  7.50 \nNoise level knowledge                               1.37                                 0.72                                     0.242                                  7.73 \nDepartment                                                 2.37                                 0.09                                     0.874                                  6.43 \n \n*Statistically significant p < 0.05 \n\n\n\nTable V:\u2008Multiple logistic regression between variables and NIHL\n\n\n\nStatistical analysis \nData analysis was done with Statistical Package for Social \nSciences (SPSS) version 22. The statistical test used was \nPearson's Chi-Square test, and if there were any cells with an \nexpected value less than 5, a Chi-square test with Yates \ncorrection was performed. For qualitative data with \nquantitative binominal data, student t-tests were done. Two-\ntailed p values were calculated, and the p value of <0.05 were \nconsidered to have a significant association. Multivariate \nanalysis using multiple logistic regression (MLR) with forward \nand backward stepwise analysis was used to determine the \nfinal model of this study.  \n \n \nRESULTS \nA total of 298 respondents participated in this study. Of these \n298 respondents, 125 were excluded from further analysis \nbecause they did not fulfil the inclusion criteria.  \n \nRegarding sociodemographic characteristics, as shown in \nTable I, most respondents were in the 25 to 30 age group \n(31.2%). The mean age of the respondents was 28.84 \u00b1 6.42 \nyears, where the youngest respondent was 21 years of age \nand the oldest was 54 years of age. Most were male workers \n(75.7%), the majority with a duration of employment \nbetween 1 to 5 years. Most respondents were from polishing \ndepartment (115, 65%), while the rest were from plating \ndepartment. These represent two of the significant activities \nin the manufacturing company.  \n \nRegarding duration of smoking, less than half of the \nrespondents were smokers, 82 respondents (47.4%), and their \nmean duration of smoking was 3.94 \u00b1 5.54 years. On the \nother hand, the mean pack \u2013 years calculated was 1.82 \u00b1 \n2.92, and the majority of the respondents (61.3%) had pack \u2013 \nyears of less than 0.99.  \n \nA high percentage of the workers (80.5%) have a normal \notoscopy finding, and only 2% have perforated ear drums. \n\n\n\nThe overall prevalence of hearing loss in this manufacturing \ncompany was 49.7%, as shown in Table II. \n \nThe bivariate analysis has shown that males workers \n(c2=24.22, p<0.001) in the plating department c2=17.99, \np<0.05) are more likely to develop NIHL (Table III). Smokers \nwere found to have a higher risk (unadjusted Odds Ratios, OR \n= 39.6; CI = 16.5 94.8) of developing NIHL than those who did \nnot smoke. The difference was statistically significant (p value \n< 0.05). In pack -years, those with the higher pack\u2013years of \nsmoking were likelier to develop NIHL than those with lower \npack \u2013 years (Table IV). \n \nIn the multiple logistic regression, only smoking was \nstatistically significant with an adjusted OR of 27.55 (95%CI \n10.74 \u2013 70.64). Despite other variables having statistically \nnon-significant results, males are two times more likely to \ndevelop NIHL than females. In addition, those who do not \nknow the noise level are one time more likely to develop \nNIHL than those who know the noise level, and those in \npolishing department are twice more likely to develop NIHL \ncompared to plating department after adjusting with others \nrisk factors (Table V). \n \n \nDISCUSSION \nThe study was done on a population of manufacturing \nfactory workers involving 298 workers. However, only 173 \nrespondents were eligible to be included after the exclusion. \nThis study found that the prevalence of NIHL in this \ncompany was as high as 49.7%. It was similar to other \nresearchers who found a high prevalence of NIHL in various \nindustries in Asia and Malaysia.23-25 \n \nAge is one of the vital factors found in other research and has \na statistical significance in this research, too. It proves that \nthe older the person, the more likely she or he is to develop \nNIHL. This is consistent with other research showing that \nolder people are more likely to develop NIHL. However, in \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 562\n\n\n\n\n\n\n\n\nNoise-induced hearing loss among manufacturing factory workers in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                563 \n\n\n\nNIHL, it differs from age-related hearing loss (AHL), which \nappears later, as in NIHL, it appears in younger age groups. \nIf other parameters are excluded, age can also be the most \nimportant single factor for NIHL.26 Young age group \ndistribution may be exposed enough to noise higher than PEL \nfor a considerable time, thus giving an early diagnosis of \nNIHL. \n \nFurthermore, the working group is primarily young and fit, \nlikely to get employed and stay employed (Hawthorne's \neffect). NIHL differs as it develops earlier in adults exposed to \nnoise than age-related hearing loss (presbycusis).27 A young \nperson exposed to noise shows a threshold shift compared to \nan older person who does not show any threshold shift, as \npostulated in some research. This explains the younger group \npopulation who developed NIHL in this study.28 \n \nGender is important in developing NIHL, as male workers are \nmore likely to be employed in manufacturing industries. \nHowever, few other studies also replicate that male \npredominance.29,30 Hearing sensitivity also declines in men \ntwice as fast as women of the same age and found \nlongitudinal declines in hearing sensitivity at 30 compared to \nwomen, which is seen at a later age.29 Furthermore, lifestyle \nhabit, such as smoking, is more common in males than in \nfemales.  \n \nDuration of employment indicates when the person is \nexposed to noise and predisposed to NIHL. The longer the \nperson is exposed to noise, the more likely they will develop \nNIHL. Duration of employment indicates dose\u2014response \nrelationship, thus corresponding with this research's \nfindings.28,31 The previous history of employment in a noisy \nenvironment was not statistically significant. This is probably \nbecause most workers employed at this manufacturing \ncompany are young, which is probably their first job. Plating \ndepartment was statistically significant in developing NIHL \ncompared to polishing department, although both \ndepartments are exposed to noise above NEL. That may be \npartly due to lacking control at the source as well. Workers \naware of the NEL are more likely to develop NIHL than those \nnot aware of the NEL. This is because those diagnosed have \nbeen told about their findings and made aware of the noise \nlevel. This contrasts with a study that indicates that those \nunaware of noise levels are more likely to develop NIHL.32 \n \nKnowledge is an essential aspect of the Hearing Conservation \nProgram (HCP). Although some research showed that the \nworkers\u2019 knowledge of hearing conservation was good,32 \nresearch in Malaysia shows that the knowledge, usage of \nHearing Protective Devices (HPD), and attitude towards NIHL \nprevention were low.25,33 Although 23.3% of the workers wore \nHPD at work, they may not have worn it correctly and thus \ndid not offer complete protection compared to properly fit \nHPD. Properly fit HPD may attenuate 15\u201320 dB (A).26 \nFurthermore, this was also proven during the walkthrough \nsurvey that most workers were non-compliant in wearing \nHPD due to a long time of usage and lack of social \ncommunication. However, using HPD on an average of 50% \nof the time also offers protection compared to those who did \nnot wear HPD.34 There could be a lack of knowledge regarding \nthe importance of hearing conservation among the workers, \nand some may not adhere to it entirely\u2014for example, proper \n\n\n\nusage of PPE and exchange of PPE once it is spoiled or \ndamaged.  \n \nThis study proves the hypothesis that there is a significant \nrelationship between smoking and NIHL and pack\u2013years of \ncigarette consumption. Smoking is a lifestyle habit that \npredisposes its users and those surrounding them to multiple \nhealth hazards. Cigarette smoke lacks an antioxidant effect, \nwhere reports that endogenous antioxidants significantly \ninfluences susceptibility to auditory damage.35 Therefore, it is \nprobable that the number of endogenous antioxidants in \nsmokers is reduced, thus predisposing them to cochlear \ndamage. Other researchers also found that smoking and \nhearing loss is statistically significant in those exposed to \noccupational noise with OR 1.85, 95% CI 1.33\u20132.57, and \npack-years of smoking remained significantly associated with \nhearing loss.36 The precise mechanism of smoking and NIHL \nis unknown. A simple additive effect of smoking and noise \nmight be compatible with NIHL potentiation caused by long-\nterm exposure to excessive noise and carbon monoxide \nexposure from smoking. Nicotine and other tobacco \ncompounds could be ototoxic.36,37 The fundamental \npathologic processes are the established vascular changes \n(cochlear hair cells damaged by raising carbon monoxide \nhaemoglobin, cochlear hypoxia, capillary vasoconstriction, \nor decreasing cochlear blood flow volume) associated with \nsmoking as well as long-term exposure to loud noise.36-41 \n\n\n\nEvidence suggests synergistic effects of smoking, noise, and \nage on hearing loss and a multiplicative effect of smoking \nand age on hearing loss. Some other studies also found that \nmedian age\u2013corrected hearing thresholds at 3 and 4 kHz in \nsmokers are significantly higher [7 dB (A)] than in those who \ndo not smoke.36,37  \n \nThis study has achieved its objectives and proved most of its \nhypotheses, as this manufacturing company reveals the \nprevalence of NIHL in almost half of the workforce. This \nstudy also manifests that the HCP, which this manufacturing \ncompany has implemented, may not be as effective as they \nare still weak areas of compliance. Although the seven \nelements of HCP have been adhered to, they may not be \nenough, especially on the worker's part. \n \nThe main limitation of our study was the small sample size. \nThe targeted sample size was not achieved as turnout was not \nas expected, as the study was done during regular working \nhours, and they followed shift and team systems. In addition, \nthe secondary data may influence the audiometric result as it \ncan be operator dependent. Furthermore, the instructions \ngiven to the respondents may not be accurate and thus may \nreflect misclassification bias. Hawthorne's effect, most of the \nemployees are young as the young and fit are most likely to \nbe employed and remain employed. Thus, the sample \npopulation is mainly of the young age group of less than 45 \nyears. \n \n \nCONCLUSION \nThe study found that occupational noise exposure is a severe \nhazard, mainly distributed in the manufacturing industry, \nwith the complexity of the process noise, such as forging, \ngrinding, cutting, and welding, particularly prominent. The \nrising trend in Malaysia over the past few years is probably \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 563\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n564                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\ndue to the increasing nature of investments and government \ninitiatives for small and medium-scale industries. Other than \nthe increasing nature of industries entering Malaysia, other \nfactors could contribute to increased cases, such as poor \ncompliance towards HCP. Smoking cessation programmes \nneed to be incorporated, and the benefits are of a broad \nrange as well. Reward or merit can be given to those who \nsuccessfully stopped smoking and helped reduce the \nincidence and prevalence of NIHL. \n \n \nACKNOWLEDGEMENTS \nWe thank the Department of Public Health Medicine,, \nFaculty of Medicine, National University of Malaysia, for the \ntechnical support. In addition, no external funding was \nreceived for this study. \n \n \nREFERENCES \n\n\n\n1. \u015aliwi\u0144ska-Kowalska M, Zaborowski K. WHO environmental noise \nguidelines for the European region: A systematic review on \nenvironmental noise and permanent hearing loss and tinnitus. \nInt J Environ Res Public Health 2017; 14(10): 1139. \n\n\n\n2. 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Inj Prev 2015; 21: e88-e92. \n\n\n\n21. Hu Shuangqiu, Hu Weijiang, Yang Shu, et al. Investigation on \nnoise exposure level and health status of workers in \ntransportation equipment manufacturing industry [J]. Chin Jo \nLabor Health Occup 2021; 39(7): 498-502.  \n\n\n\n22. Zhou J, Shi Z, Zhou L, et al Occupational noise-induced hearing \nloss in China: a systematic review and meta-analysis. BMJ Open \n2020; 10: e039576.  \n\n\n\n23. Fuente, A Hickson, L. Noise-induced hearing loss in Asia. Int J \nAudiol 2011; 50(sup1): S3-S10. \n\n\n\n24. Ahmad Kamarudin N, Fredie Robinson, Saupin S, Mohammad \nAH, Domingo O, Salan N hafizah H. Hearing loss among vector \ncontrol unit workers in Bornean Malaysia: a cross sectional risk \nfactors study. MJPHM 2022; 22(2): 61-7. \n\n\n\n25. Ismail, AF, Daud, A, Ismail, Z and Abdullah, B. Noise-induced \nhearing loss among quarry workers in a north-eastern state of \nMalaysia: a study on knowledge, attitude and practice. Oman \nMed J 2013; 28(5): 331. \n\n\n\n26. Toppila, E, Pyykk\u00f6, I, Starck, J. Age and noise-induced hearing \nloss. Scand Audiol 2001; 30(4): 236-44. \n\n\n\n27. Cruickshanks KJ, Klein R, Klein BEK, Wiley TL, Nondahl DM, \nTweed TS. Cigarette smoking and hearing loss: the epidemiology \nof hearing loss study. J Am Med Assoc 1998; 279(21): 1715-9. \n\n\n\n28. Rabonowitz PM, Galusha D, Dixon-Ernst C, Clougherty JE, \nNeitzel RL. The dose-response relationship between in-ear \noccupational noise exposure and hearing loss. Occupational and \nenvironmental medicine vol. 2013; 70(10): 716-21. \n\n\n\n29. Pearson, JD, Morrell, CH, Gordon\u2010Salant, S, Brant, LJ, Metter, EJ, \nKlein, LL and Fozard, JL. Gender differences in a longitudinal \nstudy of age\u2010associated hearing loss. J Acoust Soc Am 1995; \n97(2): 1196-1205. \n\n\n\n30. Xin Sun. Occupational noise exposure and worker's health in \nChina[J]. China CDC Weekly, 2021; 3(18): 375-7. \n\n\n\n31. Shakhatreh, FM, Abdul-Baqi, KJ, Turk, MM. Hearing loss in a \ntextile factory. Saudi Med J 2000; 21(1): 58-60. \n\n\n\n32. Ologe, FE, Akande, TM, Olajide, TG. Noise exposure, awareness, \nattitudes and use of hearing protection in a steel rolling mill in \nNigeria. Occup Medic 2005; 55(6): 487\u201389. \n\n\n\n33. Rus, RM, Daud, A, Musa, KI, Naing, L. Knowledge, attitude and \npractice of sawmill workers towards noise-induced hearing loss in \nkota bharu, kelantan. Malays J Med Sci 2008; 15(4): 28. \n\n\n\n34. Pyykk\u00f6, I, Toppila, E, Zou, J, Kentala, E. Individual susceptibility \nto noise-induced hearing loss. Audiol Medic 2007; 5(1): 41-53. \n\n\n\n35. Le Prell, CG, Yamashita, D, Minami, SB, Yamasoba, T, Miller, JM. \nMechanisms of noise-induced hearing loss indicate multiple \nmethods of prevention. Hea Res 2007; 226(1\u20132): 22-43. \n\n\n\n36. Wild DC, Brewster MJ, Banerjee AR. Noise\u2010induced hearing loss is \nexacerbated by long\u2010term smoking. Clinic Otolaryng 2005; 30(6): \n517-20. \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 564\n\n\n\n\n\n\n\n\nNoise-induced hearing loss among manufacturing factory workers in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                565 \n\n\n\n37. Prignot J. Quantification and chemical markers of tobacco-\nexposure. Eur Respir J 1987; 70(1): 1. \n\n\n\n38. Chen GD. Effect of hypoxia on noise-induced auditory \nimpairment. Hear Res 2002; 172(1 2), 186\u201395.  \n\n\n\n39. Starck J, Toppila E, Pyykko I. Smoking as a risk factor in sensory \nneural hearing loss among workers exposed to occupational \nnoise. Acta Otolaryngol 1999; 119(3), 302\u20135.  \n\n\n\n40. Fechter LD, Thorne PR, Nuttall AL. Effects of carbon monoxide on \ncochlear electrophysiology and blood flow. Hearing Res 1987; \n27(1): 37-45. \n\n\n\n41. Blanchet C, Erostegui C, Sugasawa M, Dulon D. Acetylcholine-\ninduced potassium current of guinea pig outer hair cells: its \ndependence on a calcium influx through nicotinic-like receptors. \nJ Neurosci 1996; 16(8): 2574-84. \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 565\n\n\n\n\n\n\n\n\n566                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: The prevalence of cerebral palsy (CP) in \nMalaysia is estimated at 2.6 per 1000 live births which is \ncomparable to that of Australian and European data with \nranges of 2.3- 4.21,2. Surgical intervention for the \nimprovement of gait function and mobility in CP is a \ncommon practice, however scarce literature of its outcomes \nis available in Southeast Asia. This paper aims to address \nand compare outcomes of surgical interventions in our \ncentre with other countries. \n \nMaterial and Methods: Patients with Spastic CP with Gross \nMotor Function Classification System (GMFCS) I-III that \nunderwent lower limb surgical intervention in our centre \nfrom 2008-2018 were retrospectively reviewed for The Spinal \nAlignment and Range of Motion Measure ROM subscale \n(SAROMM) scores and Functional Mobility Scale (FMS) 18 \nmonths after surgery. Changes in SAROMM, FMS scores and \nminimal clinically important difference (MCID) were \ndetermined.  \n \nResults: 19 patients were included in the study with mean \nage of 12.58. All patients underwent muscle tendon \nprocedures. Box plot analysis of SAROMM showed \nreduction of median scores at 6(26.3%) and 12(47.4%) \nmonths which plateaus at 18 months post-surgery. Repeated \nmeasure ANOVA analysis showed there was a statistically \nsignificant effect of time on SAROMM scores (p <0.001) with \nMCID of 13.4. Improvement of FMS scores was the most at \n50m with 13 children (p < 0.05), one at 5m and five at 500m. \nNone reported worsening of FMS scores at 18 months. There \nwere no changes of GMFCS levels by the end of 18 months. \n \nConclusion:\u2008Surgeries performed on GMFCS I-III patients \nwith the aim of gait improvement translates into improved \nmobility with results comparable to other countries. \n \nKEYWORDS:  \nCerebral palsy, SAROMM, Functional Mobility Scale, Contracture \nrelease \n \n \n\n\n\nINTRODUCTION \nCerebral palsy (CP) is an umbrella term to describe a group \nof disorders characterised my abnormalities of movement \nand posture, causing activity limitation due to a non-\nprogressive brain damage during early development. Even \nthough CP is a static encephalopathy, the musculoskeletal \npathology is progressive leading to secondary deformities of \nbones and joints with loss of function and deterioration of \ntheir walking pattern.  \n \nThere are currently no cure or treatment for the brain \ndamage suffered by CP patients which causes the complex \nmusculoskeletal dysfunctions. Physical therapy, medical and \nneurosurgical interventions serve to reduce and regulate the \nhypertonia while orthopaedic interventions aim to restore \nanatomical structures in an attempt to preserve the walking \nfunction as well as patients\u2019 activity level and therefore their \nquality of life.3 Appropriate holistic care of children with CP \nrequires myriad of disciplines to improve their long-term care \nconsidering their medical and social aspects as well as their \nrehabilitation, education, and assistance.4  \n \nSurgical intervention aims to improve gait, increase mobility \nand treat hip subluxation or dislocations. In a randomised \ncontrol trial of surgery vs conservative treatment of CP \npatients by Thomason et al in 2011, the authors discovered \nthat surgery improved the gait after one year of follow up \nwith good quality of life and functional mobility observed at \n2 years of follow up.5 These findings were further \nsubstantiated by Firth et al., Feger et al., and Chang et al., \nwith outcomes showing surgical intervention to be superior to \nconservative treatment of CP in the long run.6\u20138  \n\n\n\n \n \nMATERIALS AND METHODS \nThis study is a medical record review of 32 children with \nspastic CP that underwent orthopaedic surgical intervention \nbetween 2008-2018 at a tertiary referral university hospital \nfor sub-specialised orthopaedic care. Nineteen patients were \nincluded in the study based on our inclusion criteria which \nincluded a diagnosis of Spastic CP of GMFCS I-III and \ncompleted 18 months of follow up. Patients that are more \n\n\n\nWalking further. How surgery can help the cerebral palsy \nchild \n \nSyed Azhariff (Dr Ortho & Trauma)1, Rashidah Ismail (MRehabMed)2, Manimalar Selvi Naicker \n(MPath,MMedStat)3, Abd Halim Rashid (MS Ortho)4, Brenda Saria Yuliawiratman (MRehabMed)5,6, \nAmaramalar Selvi Naicker (MRehabMed)2 \n\n\n\n     \n1Department of Orthopaedics & Traumatology, Hospital Tuanku Ampuan Najihah, Kuala Pilah Negeri Sembilan, Malaysia, \n2Department of Orthopaedics & Traumatology, Rehabilitation Medicine Unit, Pusat Perubatan Universiti Kebangsaan Malaysia, \nKuala Lumpur Malaysia, 3Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur Malaysia, \n4Department of Orthopaedics & Traumatology, Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur Malaysia, \n5IHT Rehabilitation Centre, Persiaran SILC, Kawasan Perindustrian SILC, lskandar Puteri, Johor, Malaysia, 6VAMED Healthcare \nServices, Menara Tan & Tan, Kuala Lumpur, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 30 June 2023                                                                                                                                                                             \nCorresponding Author: Syed Azhariff                                                                                                                                                                                  \nEmail: syedazhariff@gmail.com\n\n\n\n2-Walking00217.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 566\n\n\n\n\n\n\n\n\nWalking further. How surgery can help the cerebral palsy child\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                567 \n\n\n\nthan 18 years old at time of surgery, history of dorsal \nrhizotomy or intrathecal baclofen surgery were excluded \nfrom the study.  \n \nSurgery was done by three surgeons throughout the 10 years \nwho are experienced in performing these surgeries with \nexperience of 5-20 years between them. The surgical \nindications included gait dysfunction, restricted knee \nextension and flexion, inability to achieve neutral ankle \nposition. 5\u20137,9  \n \nPatients were assessed preoperatively by a multidiscipline \nteam of neuropaediatrician, rehabilitation physician and \npaediatric orthopaedic surgeon prior to decision for surgery \nas well as determination of surgical level and method.  \n \nAdductor release of adductor longus and gracilis were done as \ndescribed by Shore et al.10 Hamstring release involves the \nfractional lengthening of the semitendinosus and \nsemimembranosus. If the increment of popliteal angle \nachieved is <20\u00b0 then biceps femoris is also released.11 \nSurgical correction of equinous deformity includes \ngastrocsoleus recession and triple hemisection of Achilles \ntendon. Both procedures involve the identification of the \nmuscle belly and Achilles tendon with subsequent \nlengthening as described by Firth et al and Takahashi et al.6,12 \nAll patients were kept on casts for two weeks after surgery \nwhich is then continued for 6 weeks total after wound \ninspection. They are then changed to orthoses throughout \ntheir rehabilitation period and follow up.  \n \nOutcome data collected were changes in Gross Motor \nFunction Classification System (GMFCS) levels13 ,  Functional \nMobility Scale (FMS)14 and Spinal Alignment and Range of \nMotion Measure Range of Motion subscale (SAROMM).15 \nStatistical analysis of data collected were analysed using SPSS \nversion 24. Repeated measure ANOVA test was used to \nevaluate the statistical significance of score changes at 18 \nmonths and pre surgical intervention scores.  \n \n \nRESULTS \nNineteen children were included in the study with age \nranging from 5-18 years old (mean=12.58). Nine male and 10 \nfemale children were enrolled. There were five GMFCS I, \nseven GMFCS II, and seven GMFCS III.  Fifteen patients \nunderwent single level surgery, while 4 patients underwent \nsurgery of at least 2 levels. In total 27 lower limbs underwent \nsurgical intervention. All patients underwent muscle tendon \nprocedures (Table I).  \n \nThere were no post-surgical intervention complications such \nas haemorrhage, surgical site infection. Box plot analysis of \nSAROMM showed reduction of median scores at 6 months \nand 12 months which then plateaus at 18 months (Figure 1). \nRepeated measure ANOVA analysis showed there was a \nstatistically significant effect of time on SAROMM scores with \nmean change of 13.4 (p < 0.001, Standard Deviation, SD = \n8.7) at 18 months after surgery.   \n \nThe FMS scores at 18 months post-surgery were compared \nwith their baseline for the distance of 5m, 50m, 500m. \n\n\n\nImprovement of FMS scores was the most at 50m with 13 \nchildren (p < 0.05), one at 5m and five at 500m (Table II). \nNone reported worsening of FMS scores at 18 months. There \nwere no changes of GMFCS levels by the end of 18 months. \n \n \nDISCUSSION \nThe purpose of this study was to assess the impact of \northopaedic surgical intervention on children with cerebral \npalsy. In addition to measuring the range of motion of their \njoints, we also evaluated changes in their mobility, aiming to \ndetermine whether surgical intervention and concurrent \nphysical therapy had a meaningful impact on the quality of \nlife on these children. \n \nThe role of surgical intervention for children with cerebral \npalsy is to improve function and decrease discomfort with the \nassumption that by gait improvement, the general function \nof the patient will improve.16 The SAROMM which has fair to \ngood construct validity was used to detect change in ROM \nfrom baseline and follow up.17 In addition, to determine if \nchange in score is clinically relevant, the minimal clinically \nimportant difference (MCID) is also determined. The results \ngarnered from our study shows that there is a mean change \nin score of 13.4 which is more than the MCID reported by \nChen et al., of 4.07.17 Thus, surgical intervention improves the \nROM of contracted joints within 12 months to be of clinical \nsignificance.  \n \nImprovement in SAROMM scores peaks by 12 months and is \nthe same at 18 months. indicating that after surgical \nintervention, the maximal improvement of ROM is seen by \n12 months and is preserved at 18 months. Apart from this, \nthere were no cases of recurrence detected within the 18 \nmonths period of follow up. However, recurrence of \ncontractures, maintenance of functional levels or functional \ndecline may not be apparent within the short period of follow \nup as it may require at least 5 years of follow up and up to \nearly adulthood to detect recurrence and fully evaluate the \nresults of contracture release.18 \n \nThe mobility and ROM gains observed among CP children \nare not due to surgery alone and is in synchrony with \nphysical therapy. Surgical intervention must be combined \nwith an intensive post-operative rehabilitation programme \nindividually catered and performed under the guidance of \nexperienced physical therapists to maximise functional \nimprovement.5 However, in our setting, the postsurgical \nintervention physical therapy was not strictly controlled and \nthe changes in physical therapy may have been confounded \nsimilar to Chang et al.8 Couple this with inadequacy of \nrecords of therapy sessions, the impact of physical therapy on \nambulatory gains are difficult to assess.  \n \nTo our knowledge, this is the first study in our region to look \nat outcomes of surgical intervention and rehabilitation \nobjectively among CP children. The results achieved are \nsimilar to other studies in improvements of ROM and \nfunctional mobility. The study is limited by its small sample \nsize despite a review of 10 years. This may be due to lack of \nawareness and how misunderstood CP is among Malaysians. \nWe also postulate that parents are reluctant to subject their \n\n\n\n2-Walking00217.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 567\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n568                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nAge                Gender                       GMFCS                   Limb involvement                    Level involvement                         Procedure \n\n\n\n5                     Female                            III                                Bilateral                                        Knee                                           HR \n5                       Male                               I                                     Left                                           Ankle                                          GR \n8                       Male                              II                                     Left                                           Ankle                                     PR + TAL \n9                     Female                            III                                Bilateral                                        Ankle                                          GR \n11                     Male                              III                                Bilateral                                        Knee                                           HR \n11                     Male                               I                                     Left                                           Ankle                                          GR \n12                   Female                            II                                     Left                                            Knee                                           HR \n13                   Female                            III                                Bilateral                                   Hip + Knee                                 HR + TAL \n13                   Female                            II                                     Left                                     Knee + Ankle                               HR + TAL \n14                   Female                            III                                Bilateral                                        Knee                                           HR \n14                   Female                            II                                   Right                                           Knee                                           HR \n14                     Male                              II                                   Right                                    Knee + Ankle                               HR + TAL \n14                   Female                            III                                Bilateral                                        Ankle                                          TAL \n15                     Male                               I                                     Left                                           Ankle                                          GR \n15                   Female                            II                                 Bilateral                                        Ankle                                          TAL \n15                     Male                               I                                    Right                                          Ankle                                          TAL \n16                     Male                               I                                    Right                                    Knee + Ankle                               HR + TAL \n17                     Male                              II                                   Right                                          Ankle                                          GR \n18                   Female                            III                                Bilateral                                        Knee                                           HR \n \n*HR = Hamstring release, GR = Gastrocsoleus recession, PR = Plantar release, TAL = Tendon Achilles lengthening, AR = Adductor release \n\n\n\nTable I: Summary of patients\n\n\n\n                                                          5M                                               50M                                                500M \n                                                     (p value)                                               \nN                                                         1                                                  13                                                     5 \n                                                       (0.351)                                          (0.027)                                             (0.351) \nGMFCS I                                              1                                                   3                                                      2 \nGMFCS II                                             0                                                   4                                                      3                                \nGMFCS III                                            0                                                   6                                                      0 \nMean                                                4.74                                              4.32                                                 3.89 \nSD                                                     1.66                                              1.73                                                 2.13 \n \nGMFCS = Gross Motor Function Classification System \nSD= standard deviation  \n\n\n\nTable II: FMS score improvement at 5m, 50m, 500m at 18 months compared to pre-surgery\n\n\n\nFig. 1: Boxplot analysis of SAROMM showing reduction of median scores at 6 & 12 months which then plateaus at 18 months.\n\n\n\n2-Walking00217.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 568\n\n\n\n\n\n\n\n\nWalking further. How surgery can help the cerebral palsy child\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                569 \n\n\n\nchildren to painful surgery for the sake of gait improvement. \nApart from that, this study is limited to one centre and results \nare not to be generalised to the whole country to reflect the \nlack of access to surgical and rehabilitative facilities \navailable for CP children.  \n \nFurthermore, the lack of a dedicated gait analysis facility at \nour centre hampers our ability of making accurate and \nconcise surgical planning retarding the growth and \ndevelopment of Single Event Multi-Level Surgery (SEMLS) \nwhich is commonly practised in other countries. We were also \nconcerned that the ambulatory function ratings were \nassigned retrospectively using the information available, \nwhich could have impacted their accuracy. \n \n \nCONCLUSION \nWith available data from this research, surgeries performed \non GMFCS I-III patients with the aim of gait improvement \ndoes translate into better mobility outcome which are \ncomparable to present available literature5,6,19. This research \nshould prove to be a steppingstone to expand the research by \nhaving longer follow up of patients thereby increasing the \nsample size thus the strength of the study. Longer follow up \nalso allows us look for recurrences and how surgery has \nimpacted the quality of life and functionality in the \ncommunity.  Furthermore, an addition of gait analysis \nfacilities may enhance the decision-making process and \nallow more accurate surgical prescription for contracture \nrelease among CP children.  \n \n \nREFERENCES \n1. Sellier E, McIntyre S, Smithers-Sheedy H, Platt MJ. European and \n\n\n\nAustralian cerebral palsy surveillance networks working together \nfor collaborative research. Neuropediatrics. 2020;51(02):105-112. \n\n\n\n2. Kamaralzaman S, Ying TC, Mohamed S, Toran H, Satari N, \nAbdullah N. The economic burden of families of children with \ncerebral palsy in Malaysia. Malaysian Journal of Public Health \nMedicine. 2018; 2018(Specialissue1). \n\n\n\n3. Novak I, McIntyre S, Morgan C, Campbell L, Dark L, Morton N, \net al. A systematic review of interventions for children with \ncerebral palsy: state of the evidence. Dev Med Child Neurol. \n2013; 55(10): 885-910. \n\n\n\n4. Bulekbayeva S, Daribayev Z, Ospanova S, Vento S. Cerebral \npalsy: a multidisciplinary, integrated approach is essential. \nLancet Glob Health. 2017; 5(4): e401.  \n\n\n\n5. Thomason P, Baker R, Dodd K, Taylor N, Selber P, Wolfe R, et al. \nSingle-Event Multilevel Surgery in Children with Spastic Diplegia. \nJ Bone Joint Surg. 2011; 93(5): 451-60.  \n\n\n\n6. Firth GB, Passmore E, Sangeux M, Thomason P, Rodda J, Donath \nS, et al. Multilevel surgery for equinus gait in children with \nspastic diplegic cerebral palsy medium-term follow-up with gait \nanalysis. Journal of Bone and Joint Surgery - Series A. 2013; \n95(10): 931-8.  \n\n\n\n7. Feger MA, Lunsford CD, Sauer LD, Novicoff W, Abel MF. \nComparative Effects of Multilevel Muscle Tendon Surgery, \nOsteotomies, and Dorsal Rhizotomy on Functional and Gait \nOutcome Measures for Children With Cerebral Palsy. PM and R. \n2015; 7(5): 485-93.  \n\n\n\n8. Chang CH, Chen YY, Yeh KK, Chen CL. Gross motor function \nchange after multilevel soft tissue release in children with \ncerebral palsy. Biomed J. 2017; 40(3): 163-8.  \n\n\n\n9. Kerr Graham H, Selber P. Musculoskeletal aspects of cerebral \npalsy. J Bone Joint Surg Br. 2003; 85(2): 157-166.  \n\n\n\n10. Shore BJ, Yu X, Desai S, Selber P, Wolfe R, Graham HK. Adductor \nsurgery to prevent hip displacement in children with cerebral \npalsy: the predictive role of the Gross Motor Function \nClassification System. J Bone Joint Surg Am. 2012; 94(4): 326-34.  \n\n\n\n11. Ahmed AAY, Rafalla AAA. Clinical outcome of hamstring \nlengthening to correct flexed knee gait in patients with spastic \ndiplegia. Egypt Orthop J. 2017: 352-8.  \n\n\n\n12. Takahashi S, Shrestha A. The vulpius procedure for correction of \nequinus deformity in patients with hemiplegia. J Bone Joint Surg \nBr. 2002; 84(7): 978-80.  \n\n\n\n13. Palisano R, Rosenbaum P, Bartlett D, Livingston M, Walter S, \nRussell D, et al. Gross Motor Function Classification System \nExpanded and Revised. Reference: Dev Med Child Neurol. 2007; \n39: 214-23.  \n\n\n\n14. Graham HK, Harvey A, Rodda J, Nattrass GR, Pirpiris M. The \nFunctional Mobility Scale (FMS). J Pediatr Orthop 2004; 24(5): \n514-20. \n\n\n\n15. Bartlett DJ. The use of the spinal alignment and range of motion \nmeasure with children and young people with cerebral palsy. \nDev Med Child Neurol. 2013; 55(8): 685-6.  \n\n\n\n16. Davids JR, Ounpuu S, DeLuca PA, Davis RB. Optimization of \nwalking ability of children with cerebral palsy. Instr Course Lect. \n2004; 53(11): 511-22.  \n\n\n\n17. Chen CL, Wu KPH, Liu WY, Cheng HYK, Shen IH, Lin KC. Validity \nand clinimetric properties of the spinal alignment and range of \nmotion measure in children with cerebral palsy. Dev Med Child \nNeurol. 2013; 55(8): 745-750.  \n\n\n\n18. Joo SY, Knowtharapu DN, Rogers KJ, Holmes L, Miller F. \nRecurrence after surgery for equinus foot deformity in children \nwith cerebral palsy: assessment of predisposing factors for \nrecurrence in a long-term follow-up study. J Child Orthop. 2011; \n5(4): 289-96.  \n\n\n\n19. Harvey A, Graham HK, Morris ME, Baker R, Wolfe R. The \nFunctional Mobility Scale: ability to detect change following \nsingle event multilevel surgery. Dev Med Child Neurol. 2007; \n49(8): 603-7.  \n\n\n\n2-Walking00217.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 569\n\n\n\n\n\n\n\n\n570                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Thoracic surgery procedures evolved \nenormously over time from open surgery to video assisted \nthoracoscopic surgery (VATS) and now non-intubated \nuniportal VATS. At our centre, the initial approach for \nbullectomy was by uniportal intubated VATS (iVATS) for \nmost cases. Only in mid-2020, in the midst of COVID-19 \npandemic, uniportal non-intubated VATS (NiVATS) took \nprecedence. We compared the outcome of bullectomy via \niVATS versus NiVATS for a period of 5 years. \n \nMaterials and Methods: We reviewed the medical records of \nall patients that underwent bullectomy from 1st June 2017 to \n31st May 2022. Mann Whitney U-test was completed for all \nvariables. Primary objective was to compare operating time \n(OT), global operating time (GOT), post-operative length of \nstay (LOS) and complication rate.  \n \nResults: A total of 90 bullectomies performed in which 36 \nwere approached via iVATS and 54 NiVATS. It was found that \nthe post-operative LOS, GOT, and OT were significantly \nshorter in the NiVATS as compared to iVATS. Complication \nrate between both groups showed no significant difference.  \n \nConclusion: NiVATS bullectomy demonstrated a safe and \nreliable alternative surgical approach with superior surgical \noutcome than iVATS bullectomy.  \n \nKEYWORDS:  \nThoracic surgery, bullectomy, NIVATS \n \n \nINTRODUCTION \nTraditionally thoracic cases are performed intubated with \neither double lumen or bronchial blocker to achieve single \nlung ventilation. The associated risk of intubation primarily \nled to transition to non-intubated approach.1,2 The likely \nreason of the slow transition to non-intubated is both the \nfamiliarity of surgeon with the cases and a supportive \nanaesthesia team. Challenges faced during the surgery led to \nmany cases being performed with intubated general \nanaesthesia. With the advancement of good regional \nblockade and intravenous anaesthesia, non-intubated \nthoracic surgery has become feasible and is an option for \nmost thoracic procedures in recent times.1-5 \n\n\n\nThere is no doubt that the COVID-19 pandemic brought \nmany changes to the way institutionalised medicine has \nbeen practiced.6 For the most part of the pandemic, it resulted \nin a generalised cessation of elective non-emergent \nprocedures across specialties worldwide, leading to a backlog \nof cases. Being an aerosol generating procedure (AGP), non-\nurgent thoracic surgery procedures were put on hold. The \nadvantage of non-intubated video assisted thoracoscopic \nsurgery (NiVATS) not requiring intubation and hence the \nreduction in augmentation of the airway reduced the AGP \nexposure risk of healthcare personnel, in specific our \nanaesthesia colleagues. This is especially during the \nextubation period when patients cough.7 Hence, selective \nthoracic surgery procedures were continued to be performed \nin our centre with the introduction of non-intubated \ntechnique. Bullectomy cases were regularly performed as we \nserve as the regional referral centre for thoracic cases.  \n \nThis retrospective cohort study aimed to examine the \ndifferences in outcome for those who underwent uniportal \nintubated video assisted thoracoscopic surgery (iVATS) versus \nNiVATS bullectomy in the aspects of post-operative length of \nstay (LOS), global operating time (GOT), operating time (OT) \nand complication rate. \n \n \nMATERIALS AND METHODS \nWe retrospectively reviewed the medical records of all \npatients that underwent iVATS and NiVATS bullectomy from \n1st June 2017 to 31st May 2022 in the Thoracic Unit of \nHospital Kuala Lumpur. All patients with spontaneous \npneumothorax within the age group of 12-80 years and with \npre-operative Contrast Enhanced Computed Tomography of \nThorax showing evidence of bullae or bleb were included in \nthe study. Exclusion criteria were if patients underwent more \nthan one procedure in the same sitting or if other pathology \nwere identified during the surgery. All patients were given \nregional anaesthetic block by anaesthetists prior to \ninduction. The surgical procedures were explained in detail to \nthe patient and a written consent obtained.  \n \nDemographic data and pertinent information were gathered \nfrom the medical records and analysed. The primary \noutcome of post-operative LOS in the hospital, OT, GOT and \ncomplications were analysed. Complications were \n\n\n\nNon-intubated vs. intubated video-assisted thoracoscopic \nbullectomy \u2013 a retrospective cohort study \n \nPalaniappa Meiyappan Palaniappan, MRCS1, Diong Nguk Chai, MMed(Surg)1, Benedict Dharmaraj, \nMMed(Surg)1, Amiruddin Nik Mohamed Kamil, MMed(Anaesthesiology)2, Narasimman Sathiamurthy, \nMMed(Surg)1 \n\n\n\n     \n1Thoracic Surgery Unit, Department of General Surgery, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia, \n2Department of Anaesthesia, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 03 July 2023                                                                                                                                                                              \nCorresponding Author: Narasimmman Sathiamurthy                                                                                                                                                         \nEmail: drnara@hotmail.com\n\n\n\n3-Non-intubated00111.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 570\n\n\n\n\n\n\n\n\nNon-intubated vs. intubated video-assisted thoracoscopic bullectomy \u2013 a retrospective cohort study\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                571 \n\n\n\nMeasure                                                         Number of patients (%)                                             U                                 p value \n                                                       iVATS                                      NiVATS \n                                                       (n=36)                                      (n=54) \n\n\n\nGender \n Male                                               31 (84)                                      48 (89)                                    -                                        - \n\n\n\nFemale                                            5 (16)                                        6 (11)                                     -                                        -  \nAge (Median, year)                               27.0                                          25.0                                 1148.5                               0.146 \nSmoking/vaping                                   21(58)                                      29 (53)                                927.0                                0.667 \n\n\n\nTable I: Demographic summary of iVATS versus NiVATS bullectomy. \n\n\n\nMeasure                                                                       Median                                                           U                                 p value \n                                                       iVATS                                      NiVATS \n\n\n\nLOS (days)                                               4.5                                            3.0                                   660.0                               0.008* \nGOT (minutes)                                      149.0                                         90.0                                  256.5                             < 0.001* \nOT (minutes)                                          91.0                                          60.0                                  274.5                             < 0.001* \nComplications, N                                      3                                               2                                    1017.0                                0.35 \n\n\n\nChest drain >5 days                           2                                               2 \n     Surgical site infection                        1                                               0 \n \nNote \n*Statistical significance p < .05 \nN: Number of participants \nLOS (days): Post-operative length of stay \nGOT (minutes): Global operating time \nOT (minutes): Operating time \n\n\n\nTable II: Outcome summary of iVATS versus NiVATS bullectomy \n\n\n\nProcedures                                                                                                NiTS cases, n = 94 (%) \nBullectomy                                                                                                              54 (57) \nDecortication                                                                                                             7 (7) \nLymph node biopsy                                                                                                  7 (7) \nEndoscopic thoracic sympathectomy                                                                       7 (7) \nWedge resection                                                                                                       6 (6) \nLobectomy                                                                                                                 3 (3) \nTracheal resection and reconstruction                                                                    3 (3) \nPleurodesis                                                                                                                3 (3) \nPleural                                                                                                                        3 (3) \nMediastinal biopsy                                                                                                    1 (1) \n\n\n\nTable III: Non-intubated thoracic surgery (NITS) cases performed\n\n\n\nFirst author (year)                    Type of study           Number of patients                                  Outcomes (p value) \n                                                                                                                                   LOS                    GOT         Complications        Recurrence \nAhmed et al. (2022) 12                Retrospective                         140                      <0.0001*           <0.0001*                0.79                     0.49 \nNoda et al. (2012)13                    Retrospective                          16                            0.7                   0.006*                 0.02*                     - \nPompeo et al. (2017)14                       RCT                                  43                       <0.0001*           <0.0001*                 -                             - \nIrons et al. (2016)15                     Retrospective                          62                        <0.001*            <0.0001*                 -                        N = 0 \nLiu, J et al. (2014)16                            RCT                                 194                      < 0.001*                     -                  0.004*                        - \nPalaniappa et al. (2022)            Retrospective                          90                         0.008*               <0.001*               0.35                     N = 0 \n \nNote. \n*Statistical significance p < .05 \nLOS (days): Post-operative length of stay \nGOT (minutes): Global operating time \n \n\n\n\nTable IV:\u2008Summary of Bullectomy Studies Performed Comparing NiVATS versus iVATS\n\n\n\ndocumented and classified as per Clavein-Dindo \nclassification. \n \nNiVATS in our study is defined as cases that are performed \nwith the patient having spontaneous breathing without \nmuscle relaxant, under deep sedation via intravenous \nanaesthesia and without an endotracheal tube (ETT) across \nthe glottis.8 iVATS is when a patient is on muscle relaxant \nand inhalational anaesthesia under mechanical ventilation \nwith an ETT across the glottis.8 \n\n\n\n\n\n\n\nLOS was defined as the post-operative  hospitalisation \nduration. OT was defined as the time taken for the surgical \nprocedure (skin-to-skin) whereas GOT involved operating \ntime and anaesthesia period from induction to the time \npatient reaches recovery bay post-operatively.9 All patients \nwere followed up for a period of 1 year, after which they were \ndischarged. Chest X-ray was performed during the first visit to \nthe clinic at two weeks after discharge. No chest X-rays were \nperformed in subsequent visits unless indicated. All data were \nstatistically analysed via SPSS statistics v27. Mann Whitney \nU-test was performed for all variables. \n\n\n\n3-Non-intubated00111.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 571\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n572                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nRESULTS \nThroughout the study duration, 90 patients underwent \nuniportal VATS bullectomy, out of which 36 cases via iVATS \nand 54 cases via NiVATS. Table I below summarises the \ndemographic data. \n \nAll the outcome variables of the study violated the normality \nassumption test of Kolmogorov-Smirnov test and hence the \nMann-Whitney U test was utilised. Demographically, age \nand incidence of smoking showed no statistical significance \n(Table I ). \n \nThe test revealed that the post-operative LOS was \nsignificantly shorter in the NiVATS group as compared to the \niVATSgroup (p = 0.008) with a small effect size. As for GOT \nand OT, it was found that patients in the NiVATS group had \na significantly shorter time compared to the iVATS group \nwith large effect size (p < 0.001) as shown in Table II below. \n \nOut of the 90 cases, Five patients (5.56%) were found to have \ncomplications. Two patients (3.7%) in the NiVATS group had \npoor lung expansion post-operatively, requiring prolonged \nchest drain of more than 5 days. This was also seen in the \niVATS group with an additional recorded case (8.3%) of \nsurgical site infection. No statistical significance was seen \ncomparing complications between patients in the NiVATS \nand iVATS group (p = 0.35). All the complications fall under \nthe category of Clavein-Dindo Classification Grade II. There \nwas no procedure related mortality. \n \n \nDISCUSSION \nSince the start of thoracic services in June 2017, thus far 1200 \nthoracic surgical procedures have been performed by a rather \nsmall unit (one thoracic consultant with two thoracic \nsurgeons). Only in June 2020 did the concept of non-\nintubated thoracic surgery (NITS) take precedence and till \ndate a total of 94 (8%) cases of various pathologies have been \nperformed as shown in Table III below. \n \nNiVATS bullectomy was the commonest NITS procedure \nperformed (57%), hence it was chosen to be used as a \ncomparison with iVATS bullectomy in this study.Criteria for \nNITS surgery are short procedure of <2 hours, simple surgery, \nEastern Cooperative Oncology Group (ECOG) score of <1, \nAmerican Society of Anesthesiologists (ASA) class one or two, \nwith a good airway, a body mass index less than 30, and no \nsignificant cardiopulmonary issues.10 However with progress \namong surgeons and anaesthetist and as the learning curve \nimproves; these criteria have expanded further to include \nmore complex surgeries as the indication arises. \n \nOur centre has been performing bullectomy surgery by \nuniportal iVATS from June 2017 to May 2020 and after which \ntill to date, NiVATS technique is used. Savitsky et al. reported \nthe incidence of spontaneous pneumothorax to be estimated \nat 17 to 24/100 000 in the male population and 1 to \n6/100 000 in the female population.11 This is in line with \nmale preponderance in our case series. Both the groups \ncomprise of smokers or vapers without significant difference, \nwhich could be the cause of the bullae or bleb formation. \nThere were no comorbid to report in this young cohort with \nthe median age between 25 to 27 years. \n\n\n\nFocusing on literature search comparing bullectomies \nperformed via NiVATS and iVATS, a few centres have \nembarked and published their findings. Summary of these \nstudies are shown in Table IV below. \n \nBased on Table IV, it is evident that NiVATS ensures a shorter \nLOS and reduced GOT. Recurrence and complications rates \nare similar. Noda et al. showed statistical in-significant result \ncomparing the length of stay and this could be due to the \nsmall population size of that study. Our study showed \nsignificant results for all three primary outcomes of LOS, GOT \nand OT. Complications showed no significant difference (p = \n0.35). This is in accordance to previous studies done. \n \nThe shorter LOS is highly attributable to the reduced \nanaesthesia effect post-surgery and faster recovery. All the \npatients received regional anaesthesia and this helps to \ncontrol immediate post-operative pain as well.16,17 GOT and \nOT are lower in the NiVATS group in line with the papers \npublished. Shorter GOT is due to the reduction of anaesthesia \nhours as patients are non-intubated and recovery is faster. OT \non the other hand comprises only the time of procedure \nperformed by a surgeon. The shorter time needed is likely due \nto the familiarity of surgeons rather than the type of \nanaesthesia. The steep learning curve of NiVATS requires one \nto adapt the skill and hence the initial cases performed may \ntake a longer operating time.16 18 The process of transition \nfrom iVATS to NiVATS has to be in a stepwise manner. It is \nencouraged for thoracic surgeons to have performed at least \n50 iVATS procedures including complex lobectomies and \nsuccessful handling of intraoperative bleeding prior to \nembarking on NiVATS.18 \n \nIt has to be highlighted that there was no conversion to \nintubated or open thoracotomy as far as NiVATS bullectomy \nis concerned and our pneumothorax recurrence rate at 1 year \nfollow-up is zero as well. This is likely due to surgeon \nfamiliarity with bullectomy under iVATS hence the transition \n(NiVATS) outcome was excellent. Similarly, a meta-analysis \nby Tacconi et al. comprising of 1,441 participants showed a \nlow conversion rate of 2.4%, majority being for adhesions \n(1.31%) followed by major bleeding (0.34%).19 This indicates \nNiVATS is a safe alternative option for bullectomy in a well \nselected population. \n \nIn handling complications intra-operatively, the surgical and \nanaesthetic team should be alert and prepared for an \nunfavourable situation that may need conversion to iVATS or \neven thoracotomy. Preparation of instruments for an open \nsurgery as well as preparedness for lateral intubation by \nanaesthetist has to be ensured prior to start of the case. \nLimitations during NiVATS must be clear with low threshold \nfor conversion to ensure patient safety. \n \nIn our study, the complications rate was found to be \ninsignificant, however there are reported papers with a lower \ncomplication rate in NiVATS compared to iVATS (Table IV). \nThe likelihood of our finding is due to small sample size in \nboth arms and short follow-up duration. \n \n \n \n \n\n\n\n3-Non-intubated00111.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 572\n\n\n\n\n\n\n\n\nNon-intubated vs. intubated video-assisted thoracoscopic bullectomy \u2013 a retrospective cohort study\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                573 \n\n\n\nCONCLUSION \nThoracic surgery has always been deemed as a surgery with \nhigh morbidity. NiVATS bullectomy in selected group of \npatients is a viable safe alternative with superior outcomes \ncompared to iVATS. Keeping the benefits in mind, the \nmanaging teams, both surgeons and anaesthetists, must also \nbe prepared to handle crisis situation intraoperatively. The \nlong-term efficacy of non-intubated VATS remains to be \ninvestigated via a well-designed, large-scale, multi-centred \nRCT. \n \n \nCONFLICT OF INTEREST  \nNone \n \n \nREFERENCES \n1. Sesma J, \u00c1lvarez M, G\u00e1lvez C, Bolufer S, Lirio F, Maf\u00e9 JJ, et al. \n\n\n\nNon-intubated vats for the management in primary \nspontaneous pneumothorax. Video-assist Thorac Surg 2019; 4: \n23. \n\n\n\n2. Starke H, Zinne N, Leffler A, Zardo P, Karsten J. Developing a \nminimally-invasive anaesthesiological approach to non-\nintubated uniportal video-assisted thoracoscopic surgery in \nminor and major thoracic surgery. J Thorac Dis 2020; 12(12): \n7202-17.  \n\n\n\n3. Chuang JH, Hung WT, Chen JS. Narrative review of non-\nintubated video-assisted thoracic surgery (NI-VATS) for lung \ncancer: A focus on lobectomy. Video-Assist Thorac Surg 2021; 6: \n25.  \n\n\n\n4. Fur\u00e1k J, Par\u00f3czai D, Buri\u00e1n K, Szab\u00f3 Z, Zombori T. Oncological \nadvantage of nonintubated thoracic surgery: Better Compliance \nof adjuvant treatment after lung lobectomy. Thorac Canc 2020; \n11(11): 3309-16.  \n\n\n\n5. Wang ML, How CH, Hung MH, Huang HH, Hsu HH, Cheng YJ, et \nal. Long-term outcomes after nonintubated versus intubated \nthoracoscopic lobectomy for clinical stage I non-small cell lung \ncancer: A propensity-matched analysis. J Formos Med Assoc \n2021; 120(11): 1949-56. \n\n\n\n6. Wang R, Zhong R, Liang H, Zhang T, Zhou X, Huo Z, et al. \nThoracic surgery and COVID-19: Changes and managements \nduring the pandemic. J Thorac Dis 2021; 13(3): 1507-16.  \n\n\n\n7. Brown J, Gregson F, Shrimpton A, Cook T, Bzdek B, Reid J, et al. \nA quantitative evaluation of aerosol generation during tracheal \nintubation and extubation. Anaesthesia 2020; 76(2): 174-81. \n\n\n\n8. Anile M, Vannucci J, Ferrante F, Bruno K, De Paolo D, Bassi M, et \nal. Non-intubated thoracic surgery: Standpoints and \nperspectives. Front Surg 2022; 9. \n\n\n\n9. Zhang K, Chen HG, Wu WB, Li XJ, Wu YH, Xu JN, et al. Non-\nintubated video-assisted Thoracoscopic Surgery vs. intubated \nvideo-assisted thoracoscopic surgery for thoracic disease: A \nsystematic review and meta-analysis of 1,684 cases. J Thorac Dis \n2019; 11(8): 3556-68. \n\n\n\n10. Gelzinis T. The anesthetic management of patients undergoing \nnon intubated video-assisted Thorac Surg Cur Anesthes Rep \n2021; 11(4): 437-45. \n\n\n\n11. Savitsky E, Oh SS, Lee JM. The evolving epidemiology and \nmanagement of spontaneous pneumothorax. J Am Med Assoc \n2018; 320(14): 1441.  \n\n\n\n12. Elkhouly AG, Karamustafaoglu YA, Galvez C, Rao M, Lerut P, \nGrimonprez A, et al. Nonintubated versus intubated \nthoracoscopic bullectomy for primary spontaneous \npneumothorax: A multicenter propensity-matched analysis. \nAsian Cardiovascular and Thoracic Annals 2022; 30(9): 1010\u20136. \n\n\n\n13. Noda M, Okada Y, Maeda S, Sado T, Sakurada A, Hoshikawa Y, \net al. Is there a benefit of awake thoracoscopic surgery in patients \nwith secondary spontaneous pneumothorax? J Thorac Cardio \nSurg 2012; 143(3): 613-6.  \n\n\n\n14. Pompeo E, Tacconi F, Mineo D, Mineo TC. The role of awake \nvideo-assisted thoracoscopic surgery in spontaneous \npneumothorax. J Thorac Cardio Surg 2007; 133(3): 786-90.  \n\n\n\n15. Irons JF, Miles LF, Joshi KR, Klein AA, Scarci M, Solli P, et al. \nIntubated versus nonintubated general anesthesia for video-\nassisted Thoracoscopic Surgery\u2014a case-control study. J \nCardiothorac Vasc Anesth 2017; 31(2): 411-7. \n\n\n\n16. Liu J, Cui F, Li S, Chen H, Shao W, Liang L, et al. Nonintubated \nvideo-assisted thoracoscopic surgery under epidural anesthesia \ncompared with conventional anesthetic option. Surg Innov 2014; \n22(2): 123-30. \n\n\n\n17. Navarro-Mart\u00ednez J, Galiana-Ivars M, Rivera-Cogollos MJ, \nG\u00e1lvez C, Nadal SB, Lamaign\u00e8re MO, et al. Management of intra \noperative crisis during non intubated thoracic surgery. Thorac \nSurg Clin 2020; 30(1): 101-10.  \n\n\n\n18. Grott M, Eichhorn M, Eichhorn F, Schmidt W, Kreuter M, Winter \nH. Thoracic surgery in the non-intubated spontaneously \nbreathing patient. Respir Res 2022; 23(1). \n\n\n\n19. Tacconi F, Pompeo E. Non-intubated video-assisted Thoracic \nSurgery: Where Does Evidence Stand? J Thorac Dis 2016; 8(S4). \n\n\n\n3-Non-intubated00111.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 573\n\n\n\n\n\n\n\n\n574                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction:\u2008Global actions have been implemented \nworldwide to eliminate leprosy. However, under-recognition \nand stigmatisation continue to be the challenges. In Sabah, \nthe grade two disability rate was 0.15/100,000 population in \n2019, implicating a significant delay in diagnosis. This study \naimed to assess the knowledge and attitude towards leprosy \nand the impact of lecture intervention among doctors in \nSabah and Labuan, Malaysia. \n \nMaterials and methods: This study consists of two parts. \nFirst, a cross-sectional study on the knowledge of and \nattitude towards leprosy using an online quesitonnaire was \nconducted among doctors working in the primary care \nclinics and hospitals in Sabah and Labuan. Subsequently, \nthe participants were asked to watched an online pre-\nrecorded video lecture on leprosy and to answered the same \nquestionnaire.   \n \nResults: Of the 310 participants, one fifth (20.6%) had good \nknowledge and 36.5% had positive attitude towards leprosy. \nBeing a specialist (adjusted odds ratio [aOR] 4.55, 95% \nconfidence interval [CI] 2.17\u20139.57, p < 0.001), managed \u2265 5 \nleprosy cases (aOR 3.37, 95% CI 1.52\u20137.47, p = 0.003), and \ninvolved in educational activities related to leprosy within \nlast year (aOR 4.7, 95% CI 1.69\u201313.04, p < 0.001) were the \nsignificant predictors of good knowledge. Working in \ntertiary care was significantly associated with good attitude \ntowards leprosy (OR 2.19, 95% CI 1.22\u20133.94, p = 0.025). There \nwas a significant improvement in participants\u2019 knowledge \npost-intervention (87.0% participants post-lecture vs 20.6% \nparticipants pre-lecture with good knowledge, p < 0.001). \n \nConclusion: The proportion of doctors in Sabah and Labuan \nwith good knowledge and attitude towards leprosy was low. \nKnowledge of leprosy improved significantly post-\nintervention. This highlights the need for educational and \ntraining programmes to improve doctors\u2019 knowledge of \nleprosy.  \n \nKEYWORDS:  \nLeprosy, Hansen\u2019s disease, knowledge, attitude, doctors \n \n \nINTRODUCTION \nLeprosy is an infectious disease caused by Mycobacterium \nleprae that primarily affects the skin and peripheral nerves. \n\n\n\nUntreated disease can lead to mutilating deformities and \nassociated with social stigma. Early diagnosis and treatment \nplay an important role in the prevention of disabilities.1  \n \nGlobally, there were 202,256 new cases detected in 118 \ncountries in 2019. The majority of the new cases (79%) were \nreported in India and Brazil. According to the WHO disability \ngrading, grade 2 disabilities were characterised by visible \ndeformity or visual damage.2 Of the new cases, 10,816 cases \nwere detected with grade 2 disabilities (G2D) with a rate at \n1.4 per million population and 370 (3.4%) cases were \nchildren under the age of 15.3  \n \nMalaysia achieved leprosy elimination in 1994.4 Although \nthe number of new cases has declined over the past years, \nthere were 198 new cases detected in 2019 in Malaysia.5 \nSabah has the highest number of cases in Malaysia with 75 \n(37.9%) new cases. Among which four (5.3%) cases were \nchildren and 6 (8%) cases had grade 2 disabilities with a G2D \nrate of 0.15/100,000.6 Sabah did not achieve the WHO target \nof G2D < 0.02 per 100,000 population and new child cases of \n< 3%. This is an indication of late diagnosis and lack of \ncommunity awareness. \n \nIn Malaysia, the public health sector comprises of three \nlevels: primary, secondary, and tertiary care with a wide \nnetwork of health clinics and hospitals. The primary care \nservice comprises of outpatient clinics at the first point of \nconsultation for patients at the local community. Patients \nmay then be referred to secondary and tertiary care services.7 \nBoth Sabah and Labuan are located on the Northern Borneo \nof Malaysia. In 2019, the incidence rate of leprosy in Sabah \nwas 1.9 per 100,000 population as compared to 0.61 in \nMalaysia.5 Thus, it is important for doctors to have adequate \nknowledge and training in leprosy to recognise and diagnose \nleprosy early. This study aimed to assess the knowledge and \nattitude towards leprosy among medical doctors in Sabah \nand Labuan. \n \n \nMATERIALS AND METHODS \nStudy design and population \nThis was a cross-sectional study with online questionnaire \nconducted among medical doctors working in the primary \ncare clinics, district hospitals (secondary care), emergency \ndepartment and medical department of specialist hospitals \n(tertiary care) in Sabah and Labuan from June 2021 till April \n\n\n\nEvaluating the impact of a pre-recorded online video on \nDoctor's knowledge and attitude towards leprosy in Sabah \nand Labuan - a quasi experimental study \n \nXin Yun Teoh, MRCP1,2, Sook Yee Michelle Voo, AdvMDerm1, Nadirah Sulaiman, BBiomedSc3 \n\n\n\n     \n1Department of Dermatology, Hospital Queen Elizabeth, Sabah, Malaysia, 2Department of Medicine, Dermatology Unit, \nUniversity Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia, 3Clinical Research Centre, Hospital Queen \nElizabeth, Sabah, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 03 July 2023                                                                                                                                                                              \nCorresponding Author: Teoh Xin Yun                                                                                                                                                                                 \nEmail: xinyunteoh@gmail.com\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 574\n\n\n\n\n\n\n\n\nEvaluating the impact of a pre-recorded online video on Doctor's knowledge and attitude towards leprosy\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                575 \n\n\n\n2022. Doctors working in the Dermatology department were \nexcluded.  \n \nThe target participants were recruited by convenience \nsampling. A link to the questionnaire in Google Form was \ndistributed via email to the relevant clinics and departments \nin hospitals. Participants answered an online self-\nadministered questionnaire on leprosy and provided their \nemail at the end of the questionnaire. After completion of the \nquestionnaire, participants later received a link to the pre-\nrecorded 5-minute video lecture and the same set of \nquestionnaire via email. Participants were given a 3-month \ntime frame to watch the video lecture and complete the post-\nvideo questionnaire. After completion of the questionnaire, \nparticipants received their scores and the answers on the \nknowledge section of the questionnaire.  \n \nThis study was approved by the Medical Research and Ethics \nCommittee, Ministry of Health, Malaysia, and was registered \nwith the National Medical Research Registry (NMRR-21-1443-\n60619). \n \nQuestionnaire development and content validation \nThe questionnaire was developed by the investigators of this \nstudy. The content validation of the questionnaire was \nconducted by five senior consultant dermatologists. The \nquestionnaire and the content validation form were sent via \nemail to the consultant dermatologists. The dermatologists \nrated each question on a four-point Likert scale (1- totally \nirrelevant content, 2- irrelevant content, 3- relevant content, \n4- extremely relevant content). The relevance rating for each \nitem was recoded as 1 (relevance scale of 3 or 4) or 0 \n(relevance scale of 1 or 2). Then, the sum of the relevance \nrating of each item was divided by the number of the expert, \ne.g., (1+1+1+1+1)/5 = 1. The average content validity index \n(CVI) across all items was 1, which met the satisfactory level. \nNext, pre-testing of the questionnaire was carried out to ten \npotential participants. The ten responses were included in \nthis study as there were no major changes from the pre-test. \n \nVideo lecture \nThe 5-minute video lecture was prepared and delivered by the \nprincipal investigator. The video lecture explained the cause \nof leprosy, mode of transmission, classifications, clinical \nfeatures, treatment and complications. The content of the \nvideo was approved by three senior consultant \ndermatologists. \n \nQuestionnaire \nInformed consent was obtained from all participants. \nDemographic data and professional characteristics of the \nparticipants were collected in the questionnaire. There was a \ntotal of 24 questions in the questionnaire: 20 questions on \nknowledge and 4 questions on attitude. The questions on \nknowledge comprised of cause of leprosy, mode of \ntransmission, clinical features, treatment and complications. \nEvery correct answer on the knowledge section will be \nawarded 1 mark; no mark will be awarded for wrong or \nunanswered questions. The total marks will be converted to \n100% for interpretation. Categorisation of the score was as \nfollowing:  \u2265 70% good knowledge, 40 - 69% average knowledge \nand < 40% poor knowledge.  \n\n\n\nFor the attitude section of the questionnaire, a five-point \nLikert scale was used. The score was calculated as the \nfollowing: 1- strongly disagree, 2- disagree, 3- neutral, 4- \nagree, 5- strongly agree. Lower total score indicates better \nattitude. Participants who answered disagree or strongly \ndisagree on all questions (with a score of \u2264 8) were regarded \nas having good attitude. A score > 8 was regarded as having \npoor attitude. Categorisation of the knowledge and attitude \nscore were decided by the investigators of this study after \ndiscussion with the three senior consultant dermatologists. \n \nStatistical analysis \nThe data were tabulated and analysed using IBM\u00ae Statistical \nPackage for the Social Sciences (SPSS) Statistics, version 22.0. \nDescriptive analyses were conducted for demographic and \nprofessional characteristics. Continuous variables were \nexpressed as means and standard deviations (SD) and \ncategorical variables as frequencies and percentages. Simple \nlogistic regression analysis was done to analyse factors \nassociated with good knowledge and good attitude. \nMultivariate logistic regression analysis was conducted for \nvariables associated with good knowledge. Forward and \nbackward stepwise variable selection procedures were \napplied. McNemar\u2019s test was done to analyse participants\u2019 \nknowledge and attitude pre and post-intervention. A p-value  \nof < 0.05 was considered statistically significant. \n \n \nRESULTS \nDemographic characteristics of the participants and \nexperience with leprosy patients \nA total of 310 participants were included in this study. The \nmean age of the participants was 31.5 \u00b1 2.91 years. Among \nthe participants working in tertiary hospitals, 129 (95.6%) \nwere from medical department and 6 (4.4%) from emergency \ndepartment.  \n \nThe majority of the participants had limited experience with \nleprosy. More than 80% of them had previously came across, \ndiagnosed, or managed less than five patients with leprosy. \nHigher proportion of primary care (22.5%) and tertiary care \ndoctors (20.7%) came across \u2265 5 leprosy patients compared to \nthe secondary care doctors (11.6%). Overall, more specialists \n(25%) managed \u2265 5 leprosy patients than medical officers \n(9.4%). The majority of the participants (84.8%) did not \nreceive undergraduate teaching on leprosy. Two-thirds \n(67.7%) of the participants last accessed leprosy materials \nmore than a year ago (Table I).  \n \nKnowledge of leprosy \nAs shown in Table I, participants who were specialists, \nworking in primary care or tertiary care, being in service for \n\u2265 5 years, experience with leprosy patients (came across or \ndiagnosed or managed \u2265 5 leprosy cases), previously received \nundergraduate teaching on leprosy and involved in \neducational activities related to leprosy within last year had \nbetter knowledge. \n \nTable II shows the responses to questionnaire pre and post-\nvideo lecture. The majority of the participants were familiar \nwith the causative microorganism (96.5%) and the \ninvestigations of suspected leprosy patients (83.5%). One-\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 575\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n576                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nCharacteristics                                                      Overall                                        Knowledge                                            Attitude \n                                                                           n (%)                   Good               Average               Poor               Good              Poor \n                                                                          n=310                 (\u226570%)              (40-69%)             (<40%)               (\u22648)                 (>8) \n                                                                                                      n = 64                n = 216               n = 30             n = 113           n = 197 \n\n\n\nAge - years, Mean (SD)                                       31.5 (2.91)          32.4 (3.45)          31.3 (2.72)         30.9 (2.58)       31.5 (2.85)      31.5 (2.94) \nGender \n\n\n\nMale                                                               140 (45.2)            28 (20.0)             99 (70.7)             13 (9.3)           57 (40.7)         83 (59.3) \nFemale                                                           170 (54.8)            36 (21.2)            117(68.8)            17(10.0)          56 (32.9)        114 (67.1) \n\n\n\nEthnicity \nBumiputera Sabah                                         59 (19.0)              9 (15.3)              44(74.6)              6 (10.2)           23 (39.0)         36 (61.0) \nMalay                                                              95 (30.6)             22 (23.2)             56 (58.9)            17 (17.9)          33 (34.7)         62 (65.3) \nChinese                                                          115 (37.1)            26 (22.6)             83 (72.2)              6 (5.2)            39 (33.9)         76 (66.1) \nIndian                                                              38 (12.3)              7 (18.4)              30 (78.9)              1 (2.6)            16 (42.1)         22 (57.9) \nOthers                                                               3 (0.9)                      0                     3 (100)                    0                 1 (50.0)           1 (50.0) \n\n\n\nPosition \nMedical officer                                              266 (85.8)            44 (16.5)            193 (72.6)           29 (10.9)          93 (35.0)        173 (65.0) \nSpecialist                                                         44 (14.2)             20 (45.5)             23 (52.3)              1 (2.3)            20 (45.5)         24 (54.5) \n\n\n\nWorkplace \nPrimary care                                                    89 (28.7)             26 (29.2)             55 (61.8)              8 (9.0)            30 (33.7)         59 (66.3) \nSecondary care                                               86 (27.7)               8 (9.3)               61(70.9)             17 (19.8)          23 (26.7)         63 (73.3) \nTertiary care                                                  135 (43.5)            30 (22.2)            100 (74.1)             5 (3.7)            60 (44.4)         75 (55.6) \n\n\n\nYears of service \n< 5                                                                  174 (56.1)            29 (16.7)            124 (71.3)           21 (12.1)          59 (33.9)        115 (66.1) \n\u2265 5                                                                  136 (43.9)            35 (25.7)             92 (67.6)              9 (6.6)            54 (39.7)         82 (60.3) \n\n\n\nNumber of leprosy patients came across  \n< 5                                                                  252 (81.3)            40 (15.9)            184 (73.0)           28 (11.1)          86 (34.1)        166 (65.9) \n\u2265 5                                                                   58 (18.7)             24 (41.4)             32 (55.2)              2 (3.4)            27 (46.6)         31 (53.4) \n\n\n\nNumber of leprosy patients diagnosed                      \n< 5                                                                    301 (97)              59 (19.6)            212 (70.4)           30 (10.0)         108 (35.9)       193 (64.1) \n\u2265 5                                                                       9 (3)                  5 (55.6)               4 (44.4)                    0                 5 (55.6)           4 (44.4) \n\n\n\nNumber of leprosy patients managed                        \n< 5                                                                  274 (88.4)            46 (16.8)            199 (72.6)           29 (10.6)          95 (34.7)        179 (65.3) \n\u2265 5                                                                   36 (11.6)             18 (50.0)             17 (47.2)              1 (2.8)            18 (50.0)         18 (50.0) \n\n\n\nReceived undergraduate teaching on  \nleprosy \n\n\n\nYes                                                                  263 (84.8)            58 (22.1)            178 (67.7)           27 (10.3)          99 (37.6)         33 (70.2) \nNo                                                                    47 (15.2)              6 (12.8)              38 (80.9)              3 (6.4)            14 (29.8)        164 (62.4) \n\n\n\nLast involved in educational  \nactivities related to leprosy \n\n\n\nNever                                                               61 (19.7)              8 (13.1)              43 (70.5)            10 (16.4)          17 (27.9)         44 (72.1) \nWithin last year                                              39 (12.6)             18 (46.2)             21 (53.8)                   0                17 (43.6)         22 (56.4) \nMore than 1 year                                          210 (67.7)            38 (18.1)            152 (72.4)            20 (9.5)           79 (37.6)         44 (72.1) \n\n\n\nEducational source on leprosy accessed \nWebsite                                                          170 (54.8)            36 (21.2)            119 (70.0)            15 (8.8)           67 (39.4)        103 (60.6) \nContinuing Medical Education                    104 (33.5)            27 (26.0)             69 (66.3)              8 (7.7)            48 (46.2)         56 (53.8) \nLeprosy Management Manual                      47 (15.2)             13 (27.7)             33 (70.2)              1 (2.1)            20 (42.6)         27 (57.4) \nTextbook                                                        118 (38.1)            25 (21.1)             82 (69.5)             11 (9.3)           40 (33.9)         78 (66.1) \nJournal articles                                               33 (10.6)              7 (21.2)              25 (75.8)              1 (3.0)            13 (39.4)         20 (66.7) \nCourses                                                              3 (1.0)                2 (66.7)               1 (33.3)                    0                 1 (33.3)           2 (66.7) \nNever access any leprosy related                   30 (9.7)               5 (16.7)              21 (70.0)             4 (13.3)            8 (26.7)          22 (73.3)  \nresources                                                                                                                                                                                                  \n\n\n\n\n\n\n\nTable I: Demographic characteristics of the participants, experience with leprosy patients, knowledge and attitude towards leprosy\n\n\n\nthird (33.5%) of the participants thought that leprosy was \ntransmitted by direct contact. Only 64 (20.6%) participants \nhad good knowledge (score \u2265 70%). Nearly two-thirds of the \nparticipants (69.7%) had average knowledge (score 40 - 69%) \nand the remaining 30 (9.7%) participants had poor \nknowledge (score < 40%).  \n \nTable III shows the univariate and multivariate logistic \nregression analysis of the potential predictors of better \nknowledge score. Position as a specialist (adjusted odds ratio \n[aOR] = 4.55, 95% confidence interval [CI] = 2.17\u20139.57, p < \n0.001), previously managed \u2265 5 leprosy cases (aOR = 3.37, \n95% CI = 1.52\u20137.47, p = 0.003), and last accessed educational \n\n\n\nmaterials related to leprosy within the last year (aOR = 4.7, \n95% CI = 1.69\u201313.04, p < 0.001) were significantly associated \nwith good knowledge.  \n \nAttitude towards leprosy \nMore than one-third (37.8%) of the participants thought \npatients with leprosy need to be isolated from the \ncommunity. Only 113 (36.5%) of the participants had good \nattitude towards leprosy (score \u2264 8). Participants who were \nspecialists, working in tertiary care, with working experience \n\u2265 5 years, experience with leprosy patients, previously \nreceived undergraduate teaching on leprosy and involved in \neducational activities related to leprosy within last year had \n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 576\n\n\n\n\n\n\n\n\nEvaluating the impact of a pre-recorded online video on Doctor's knowledge and attitude towards leprosy\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                577 \n\n\n\nKnowledge and attitude questions                                                     Pre-video lecture, n = 310               Post-video lecture, n = 270 \n                                                                                                                          n (%)                                                    n (%) \n\n\n\nLeprosy is caused by which microorganism? \nMycobacterium leprae*                                                                               299 (96.5)                                            267 (98.9) \nTreponema pallidum                                                                                      10 (3.2)                                                 3 (1.1) \nMadurella mycetomatis                                                                                  1 (0.3)                                                      0 \nMycobacterium ulcerans                                                                                     0                                                          0 \n\n\n\nLeprosy is also known as: \nHansen\u2019s disease*                                                                                         299 (96.5)                                            268 (99.2) \nHumphrey\u2019s disease                                                                                        11 (3.5)                                                 1 (0.4) \nHartmann\u2019s disease                                                                                              0                                                      1 (0.4) \nHarry\u2019s disease                                                                                                     0                                                          0 \n\n\n\nThe mode of transmission for leprosy is: \nDirect contact                                                                                               104 (33.5)                                              12 (4.4) \nDroplet*                                                                                                        180 (58.1)                                            257 (95.2)  \nFaecal oral route                                                                                             17 (5.5)                                                 1 (0.4) \nVector                                                                                                               9 (2.9)                                                      0 \n\n\n\nLeprosy primarily affects:  \nI. Bone, II. Nerve, III. Skin, IV. Eyes \n\n\n\nI, II                                                                                                                     2 (0.6)                                                  1 (0.4) \nII, III *                                                                                                             121 (39.0)                                             99 (36.7) \nII, III, IV                                                                                                          128 (41.3)                                            146 (54.1) \nAll of the above                                                                                             59 (19.0)                                               24 (8.9) \n\n\n\nWhat are the typical cutaneous features of leprosy?  \nI. Hypopigmented patch,  \nII. Loss of sensation,  \nIII. Loss of hair, IV. Loss of sweating \n\n\n\nI, II                                                                                                                  147 (47.4)                                             40 (14.8) \nII, III                                                                                                                   8 (2.6)                                                  1 (0.4) \nII, III, IV                                                                                                            12 (3.9)                                                 3 (1.1) \nAll of the above*                                                                                          143 (46.1)                                            226 (83.7) \n\n\n\nWhat are the cardinal signs of leprosy? \nI. Skin patch with loss of sensation \nII. Enlarged/thickened peripheral nerve with  \ncorresponding loss/impairment of function \nIII. Presence of acid-fast bacilli in slit skin smear \nIV. Loss of corneal reflex \n\n\n\nI, II                                                                                                                   78 (25.2)                                               12 (4.5) \nI, II, III*                                                                                                           125 (40.3)                                            235 (87.0) \nII, III                                                                                                                  14 (4.5)                                                 6 (2.2)  \nAll of the above                                                                                             93 (30.0)                                               17 (6.3) \n\n\n\nWhich nerve is the most frequently affected  \nnerve in leprosy? \n\n\n\nOptic                                                                                                               82 (26.4)                                                9 (3.3) \nPopliteal                                                                                                          21 (6.8)                                                 1 (0.4) \nSciatic                                                                                                               12 (3.9)                                                 1 (0.4) \nUlnar*                                                                                                            195 (62.9)                                            259 (95.9) \n\n\n\nWhich is the most severe form of leprosy? \nBorderline tuberculoid                                                                                    1 (0.3)                                                  1 (0.4) \nLepromatous*                                                                                               269 (86.8)                                            259 (95.9) \nMid borderline                                                                                                 1 (0.3)                                                      0 \nTuberculoid                                                                                                    39 (12.6)                                               10 (3.7) \n\n\n\nWhich of the following patient has leprosy? \n(patients\u2019 photos) \n\n\n\na                                                                                                                        6 (1.9)                                                  3 (1.1) \nb *                                                                                                                   42 (13.6)                                              35 (13.0) \nc                                                                                                                     257 (82.9)                                            229 (84.8) \nd                                                                                                                        5 (1.6)                                                  3 (1.1) \n\n\n\nWhat are the complications of leprosy? \nI. Claw hand, II. Lagophthalmos, III. Scleritis,  \nIV. Neuropathic ulcers \n\n\n\nI, II                                                                                                                   45 (14.5)                                               15 (5.6) \nII, III                                                                                                                   8 (2.6)                                                  6 (2.2) \nII, III, IV                                                                                                           53 (17.1)                                                4 (1.5) \nAll of the above *                                                                                         204 (65.8)                                            245 (90.7) \n\n\n\n\n\n\n\nTable II:\u2008Responses to knowledge and attitude questions\n\n\n\ncont..... pg 578\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 577\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n578                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nKnowledge item                                                                                    Pre-video lecture, n = 310               Post-video lecture, n = 270 \n                                                                                                                          n (%)                                                    n (%) \n\n\n\nWhat constitutes WHO grade 2 disabilities in leprosy?  \nI. Loss of sensation, II. Blindness, III. Resorption of digits,  \nIV. Loss of corneal reflex \n\n\n\nI, II                                                                                                                   95 (30.6)                                              42 (15.5) \nII, III *                                                                                                              69 (22.3)                                             126 (46.7) \nIII, IV                                                                                                               39 (12.6)                                               20 (7.4) \nAll of the above                                                                                            107 (34.5)                                             82 (30.4) \n\n\n\nWhat are the clinical manifestations of type 2 reaction?  \nI. Painful nodules, II. Fever, III. Lymphadenopathy,  \nIV. Arthralgia \n\n\n\nI, II                                                                                                                   37 (11.9)                                               10 (3.7) \nI, II, III                                                                                                              56 (18.1)                                              36 (13.3) \nII, III                                                                                                                 40 (12.9)                                                4 (1.5)  \nAll of the above*                                                                                          177 (57.1)                                            220 (81.5) \n\n\n\nInvestigations for patients suspected of leprosy include:  \nI. Skin biopsy, II. Slit skin smear, III. Peripheral blood smear,  \nIV. Blood culture \n\n\n\nI, II*                                                                                                                259 (83.5)                                            261 (96.7) \nI, II, IV                                                                                                             42 (13.6)                                                5 (1.8) \nI, IV                                                                                                                   5 (1.6)                                                      0 \nII, III                                                                                                                   4 (1.3)                                                  4 (1.5) \n\n\n\nLeprosy should be notified to the nearest district health  \noffice within: \n\n\n\n1 month                                                                                                            5 (1.6)                                                      0 \n1 week *                                                                                                        139 (44.8)                                            247 (91.5) \n2 weeks                                                                                                            7 (2.3)                                                  2 (0.7) \n24 hours                                                                                                        159 (51.3)                                              21 (7.8) \n\n\n\nThe following drugs are used in leprosy treatment except: \nClofazimine                                                                                                    52 (16.8)                                                1 (0.4) \nDapsone                                                                                                         36 (11.6)                                                1 (0.4) \nIsoniazid *                                                                                                     208 (67.1)                                            263 (97.4) \nRifampicin                                                                                                       14 (4.5)                                                 5 (1.9) \n\n\n\nWhat is the duration of treatment for paucibacillary leprosy? \n3 months                                                                                                         21 (6.8)                                                 3 (1.1) \n6 months*                                                                                                     191 (61.6)                                            259 (95.9)  \n9 months                                                                                                        37 (11.9)                                                5 (1.9) \n12 months                                                                                                      61 (19.7)                                                3 (1.1) \n\n\n\nWhat is the duration of treatment for multibacillary leprosy? \n6 months                                                                                                         23 (7.4)                                                 3 (1.1) \n9 months                                                                                                        31 (10.0)                                                4 (1.5) \n12 months*                                                                                                   179 (57.8)                                            257 (95.2) \n18 months                                                                                                      77 (24.8)                                                6 (2.2) \n\n\n\nWhich of the following drugs is known to cause generalized  \npigmentation of skin? \n\n\n\nRifampicin                                                                                                      35 (11.3)                                               12 (4.5) \nDapsone                                                                                                        125 (40.3)                                             34 (12.6) \nClofazimine*                                                                                                 139 (44.8)                                            222 (82.2) \nIsoniazid                                                                                                         11 (3.6)                                                 2 (0.7) \n\n\n\nCase study 1 \nA 50-year-old man diagnosed with borderline leprosy,  \ntreatment was started 1 month ago. The existing plaques and  \npatches on his trunk and arms became more erythematous  \nand indurated in the last 4 days. How will you manage the  \npatient before referring to a dermatologist? \n\n\n\nStop his leprosy treatment immediately                                                      37 (11.9)                                               20 (7.4) \nEnsure the patient continues his leprosy treatment*                                 88 (28.4)                                             175 (64.8) \nArrange for an urgent slit skin smear                                                          42 (13.6)                                               13 (4.8) \nPerform full blood count, renal profile and liver                                      143 (46.1)                                             62(23.0) \nfunction test                                                                                                                                                                      \n\n\n\n\n\n\n\nTable II:\u2008Responses to knowledge and attitude questions\n\n\n\ncont..... pg 579\n\n\n\ncont from..... pg 577\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 578\n\n\n\n\n\n\n\n\nEvaluating the impact of a pre-recorded online video on Doctor's knowledge and attitude towards leprosy\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                579 \n\n\n\nbetter attitude (Table I). Working in the tertiary care hospitals \nwas an independent predictor of good attitude (OR = 2.19, \n95% CI = 1.22\u20133.94, p = 0.025).  \n \nPre and post-intervention \nThere was a significant increase in proportion of participants \nwith good knowledge post-video lecture (87.0 vs 20.6, p < \n0.001) (Table IV). However, there was no significant change \nof attitude post-intervention.  \n \n \nDISCUSSION \nOnly one-fifth of our study participants had good knowledge \nof leprosy. This finding is consistent with previous studies.8-10 \nIn Ethiopia, 519 (86.3%) healthcare workers had poor \nknowledge of the signs and symptoms of leprosy, leprosy \nreactions and management.8 Similarly, a study in South \nAfrica revealed general lack of basic knowledge of leprosy \namong the primary care doctors.9 Furthermore, poor \nknowledge was reported among 50% of the doctors in \nworking in the dermatology field in China.11  \n \n\n\n\nOur study participants had limited experience with leprosy \npatients (came across, diagnosed or managed < 5 cases of \nleprosy). In Italy, only 11 (10.8%) of the doctors had \ninteraction with a leprosy case, and only 6.9% had diagnosed \nleprosy before and none had managed a leprosy patient.12 In \nSouthern Malawi, 13 (37%) healthcare workers had never \nseen a leprosy patient and 29 (83%) had never diagnosed \nleprosy before.13 Among doctors working in dermatology field \nin China, 20% of them had never seen a leprosy patient and \n41% had never diagnosed leprosy.11 Lack of experience of \ndoctors in leprosy could be due to the lack of exposure to \nleprosy cases in non-endemic areas.  \n \nDiagnosing leprosy is challenging as it can mimic any skin \ncondition.14 In Malaysia, a case series of 27 leprosy patients \nreported that there were missed diagnoses by primary care \ndoctors in 12 patients (44\u00b74%).15 Previous experience with \nleprosy patients was an important predictor of better \nknowledge in our study and previous studies.8,10 Abeje et al \nreported that good knowledge was associated with training \nand exposure to leprosy.8 In Italy, higher knowledge score \nwas reported among doctors who had diagnosed or interacted \n\n\n\nKnowledge item                                                                                    Pre-video lecture, n = 310               Post-video lecture, n = 270 \n                                                                                                                          n (%)                                                    n (%) \n\n\n\nCase study 2 \nA 35-year-old woman with lepromatous leprosy completed  \nher treatment 1 year ago. She complained of painful nodules  \nover arms and legs of 2 weeks duration. Examination showed  \nmultiple, scattered, tender, erythematous subcutaneous  \nnodules. What is your next step in management before  \nreferring to a dermatologist? \n\n\n\nRestart leprosy treatment                                                                              21 (6.8)                                                 6 (2.2) \nPerform a slit skin smear                                                                              139 (44.8)                                             51 (18.9) \nStart prednisolone                                                                                        81 (26.1)                                             104 (38.5) \nSymptomatic treatment *                                                                             69 (22.3)                                             109 (40.4) \n\n\n\nLeprosy patients need to be isolated from community during  \nthe treatment period. \n\n\n\nStrongly disagree                                                                                           41 (13.2)                                              45 (16.7) \nDisagree                                                                                                         88 (28.4)                                              76 (28.1) \nNeutral                                                                                                           64 (20.6)                                              45 (16.7) \nAgree                                                                                                              87 (28.1)                                              78 (28.9) \nStrongly agree                                                                                                30 (9.7)                                                26 (9.6) \n\n\n\nIf someone in your family has leprosy, you would never  \ndisclose it to anyone.  \n\n\n\nStrongly disagree                                                                                           58 (18.7)                                              66 (24.4) \nDisagree                                                                                                         87 (28.1)                                              81 (30.0) \nNeutral                                                                                                          109 (35.2)                                             78 (28.9) \nAgree                                                                                                              46 (14.8)                                              32 (11.9) \nStrongly agree                                                                                                10 (3.2)                                                13 (4.8) \n\n\n\nLeprosy patients should not take part in any social activities. \nStrongly disagree                                                                                           82 (26.4)                                              81 (30.0) \nDisagree                                                                                                        138 (44.5)                                            112 (41.5) \nNeutral                                                                                                           61 (19.7)                                              37 (13.7) \nAgree                                                                                                               25 (8.1)                                               29 (10.7) \nStrongly agree                                                                                                 4 (1.3)                                                 11 (4.1) \n\n\n\nYou will avoid working with a colleague with leprosy. \nStrongly disagree                                                                                           81 (26.1)                                              89 (33.0) \nDisagree                                                                                                        147 (47.4)                                             94 (34.8) \nNeutral                                                                                                           57 (18.4)                                              58 (21.5) \nAgree                                                                                                               19 (6.1)                                                20 (7.4) \nStrongly agree                                                                                                 6 (2.0)                                                  9 (3.3) \n\n\n\n \n*Correct answer(s)  \n\n\n\nTable II:\u2008Responses to knowledge and attitude questions\ncont from..... pg 578\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 579\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n580                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n                                                              Good knowledge (univariate)                                       Good knowledge (multivariate) \n                                                        Crude              95% confidence             p-value a      Adjusted       95% confidence      p-value a \n                                                          odds               interval of OR                                       odds            interval of OR                \n                                                          ratio            Lower            Upper                                   ratio           Lower     Upper  \n                                                          (OR)              value              value                                   (OR)            value       value \n\n\n\nAge group (years) \n< 30                                                    1.00               1.03                4.69               0.043                 \n\u2265 30                                                    2.20                                          \n\n\n\nLevel of care \nPrimary care                                       4.02               1.70                9.50               0.006 \nTertiary                                              2.79               1.21                6.41              0.001 b \nSecondary                                          1.00                                                           0.016 b                                                                         \n\n\n\nPosition                                                                                                                      <0.001                                                                  <0.001 \nMedical officer                                  1.00                                                                                 1.00 \nSpecialist                                            4.21               2.14                8.27                                    4.55              2.17          9.57                 \n\n\n\nYears in service                                                                                                           0.052 \n< 5                                                      1.00 \n\u2265 5                                                      1.73               1.00                3.12                    \n\n\n\nNumber of leprosy cases                                                                                          <0.001                \ncame across \n\n\n\n< 5                                                      1.00 \n\u2265 5                                                      3.74               2.01                6.97                    \n\n\n\nNumber of leprosy cases                                                                                           0.017 \ndiagnosed  \n\n\n\n< 5                                                      1.00 \n\u2265 5                                                      5.13               1.34               19.68 \n\n\n\nNumber of leprosy patients                                                                                     <0.001                                                                   0.003 \nmanaged \n\n\n\n< 5                                                      1.00                                                                                 1.00                                   \n\u2265 5                                                      4.96               2.40               10.25                                   3.37              1.52          7.47 \n\n\n\nReceived teaching on leprosy                                                                                   0.153 \nduring undergraduate \n\n\n\nNo                                                       1.00 \nYes                                                      1.93               0.78                4.78                                                                              \n\n\n\nLast time involved in any                                                                                         <0.001                                                                  <0.001 \neducational activities related  \nto leprosy \n\n\n\nNever                                                  1.00                                                                                 1.00 \nMore than a year                              1.46               0.64                3.33              0.364 b            1.02              0.43          2.42          0.963 b \nWithin last year                                 5.68               2.14               15.04            <0.001 b           4.70              1.69         13.04         0.003 b \n\n\n\n \na Likelihood Ratio (LR) test     b Wald test \nThe model has no interaction terms, no multicollinearity problem and no outliers. \nHosmer-Lemeshow goodness-of-fit test for both models was not significant. \nEighty one percent cases are predicted correctly whether they have good knowledge and AUC of ROC is 72.9% (acceptable discrimination).  \n* No factors associated with good attitude generated from multiple logistic regression \n \n\n\n\nTable III: Factors associated with good knowledge\n\n\n\nKnowledge and attitude                               Pre-intervention,                                   Post-intervention,                                p-value b \n                                                                               n = 310                                                    n = 270 a \n                                                                                 n (%)                                                        n (%)                                                    \nKnowledge                                                                                                                                                                                     <0.001 \n          Good                                                           64 (20.6)                                                  235 (87.0) \n          Average                                                     216 (69.7)                                                  35 (13.0) \n          Poor                                                             30 (9.7)                                                          0                                                       \nAttitude                                                                                                                                                                                           0.044 \n          Good                                                          113 (36.5)                                                 114 (42.2) \n          Poor                                                           197 (63.5)                                                 156 (57.8)                                                \n \na Response rate for post-intervention is 87.1% \nb McNemar\u2019s test (knowledge regroup to two groups - good knowledge vs average to poor) \n            \n\n\n\nTable IV: Pre and post-intervention knowledge and attitude\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 580\n\n\n\n\n\n\n\n\nEvaluating the impact of a pre-recorded online video on Doctor's knowledge and attitude towards leprosy\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                581 \n\n\n\nwith leprosy patients.12 Our participants who were specialists \nand with longer working experience had better knowledge. \nThis is likely due to specialists having more experience \nmanaging leprosy patients (managed \u2265 5 leprosy patients). \nPrimary care doctors with limited experience reported having \nless confidence in diagnosis and management of leprosy.4 \nOur cohort working in primary care clinic or tertiary hospital \nhad better knowledge compared to those working in \nsecondary care (district hospitals). This is likely due to the \nprimary care and tertiary care doctors having more exposure \nto leprosy patients (came across \u2265 5 leprosy patients). The \nmajority of our cohort working in tertiary hospital were from \nthe medical department. It is possible that they were well-\nread on leprosy as a subject in internal medicine.  \n \nThe majority of our cohort did not receive undergraduate \nteaching on leprosy. In India, only 40% of medical students \nwere aware of the cardinal signs of leprosy.16 Furthermore, \nour study found no association between undergraduate \nteaching in leprosy and good knowledge and positive \nattitude. Among medical students in Nigeria, despite having \nlectures on leprosy, only 24.7% of them had good knowledge \nof leprosy.10 A study in India revealed medical interns had \nbetter knowledge and attitude compared to final year \nmedical student.16 A 1-day training program among Indian \nmedical students significantly improved their knowledge and \nattitude towards leprosy.17 This emphasises that over and \nabove teaching medical students about leprosy, exposure to \nleprosy cases and training are imperative to improve \nknowledge and attitude. \n \nRecent access to educational source on leprosy was an \nindependent predictor of good knowledge of leposy. A study \nin Hyderabad revealed that the government doctors had \nbetter knowledge than private practice doctors possibly due to \ncontinuing medical education programmes.18 Private doctors \nin Mumbai were reported to have inadequate knowledge \nlikely due to lack of continuing education on leprosy.19 \n \nOnly 25.8% of healthcare workers in Ethiopia had positive \nattitude towards leprosy patients.8 Negative attitude was also \nreported among doctors working in dermatology field in \nChina.11 In a Sri Lankan study, 34.3% of healthcare providers \nwere scared of leprosy and 22.5% of healthcare providers \nthought that leprosy patients need to be isolated from \nothers.20 Similar to our findings, misconceptions were \nreported among the healthcare workers in Guyana, where \nhalf of them believed leprosy was transmitted through touch \nand half were afraid of this disease.21 Ekeke et al reported that \ngood knowledge of leprosy was associated with positive \nattitude.10 Likewise, a study in Nigeria found that good \nknowledge correlate with favourable attitude towards \nleprosy.22 \n \nThere was a significant improvement in participants' \nknowledge of leprosy post-video lecture intervention. \nConsistent with our findings, interns in Nigeria who attended \nclinical demonstration on leprosy had better knowledge.10 A \nstudy of healthcare providers in Bangladesh demonstrated an \nincrease in knowledge after leprosy training.23 Similarly, there \nwas improvement in knowledge and confidence level among \nfamily medicine physicians in Malaysia after a 3-day lecture \nand hands-on training course.4 Doctors working in \n\n\n\ndermatology field in China demonstrated improvement in \nknowledge and attitude after a lecture and training \nworkshop.11 On the contrary, our study found no significant \nimprovement in doctors\u2019 attitude post-video lecture \nintervention. This may be because attitude change takes \ntime. Annually, the Sabah health department organises a \none-day physical course with lectures on leprosy for the \ndoctors and medical assistants working in government clinics \nand hospitals. Despite that, only a small proportion of the \ndoctors in our study had good knowledge and attitude. This \nis probably because of the nature of physical course that only \nallows limited numbers of participants each time.  \n \nAs our study was conducted during the covid pandemic, \nonline video lecture on leprosy was done as an intervention \nto improve knowledge of leprosy. Post-test questionnaire was \ndone immediately post-video lecture and we were not able to \nassess long term improvement in knowledge and attitude. We \nrecommend regular video lecture training conducted by the \ndermatologists for the medical officers and specialists from all \nlevels of care for exposure and revision to improve knowledge \nof leprosy. Teledermatology consultation is cost effective, \ntime efficient, and will be helpful to increase knowledge \namong the doctors and thus optimise patients\u2019 care. Future \nstudies to assess the impact of hands-on training workshop \ninvolving leprosy patients on knowledge and attitude \ntowards leprosy will be valuable. \n \n \nCONCLUSION \nThe proportion of medical doctors in Sabah and Labuan with \ngood knowledge and good attitude towards leprosy was low. \nPosition as a specialist, experience with leprosy patients and \nrecent education in leprosy were associated with good \nknowledge and attitude. Knowledge of leprosy improved \nsignificantly post-intervention. This highlights the need for \neducational and training programmes to improve doctors\u2019 \nknowledge of leprosy. \n \n \nREFERENCES \n1. Fischer M. Leprosy - an overview of clinical features, diagnosis, \n\n\n\nand treatment. J Dtsch Dermatol Ges 2017; 15(8): 801-27.  \n2. Brandsma JW, Van Brakel WH. WHO disability grading: \n\n\n\noperational definitions. Lepr Rev 2003; 74(4): 366-73. \n3. World Health Organization. Towards Zero Leprosy. Global \n\n\n\nLeprosy (Hansen\u2019s disease) Strategy 2021\u20132030. Geneva: WHO; \n2021, September 14, 2022. [cited  Sept 2022]. Available from: \nhttps://www.who.int/publications/i/item/9789290228509 \n\n\n\n4. Yap FBB, Kiung ST. Knowledge and confidence in the diagnosis \nand management of leprosy among Family Medicine Specialists \nin Malaysia. J Dermatol Dermatol Surg 2016; 46\u201350.  \n\n\n\n5. Ministry of Health Malaysia. Health Indicators 2020. Putrajaya: \nMOH; 2021, September 14, 2022. [cited Sept 2022]. Available \nfrom: https://www.moh.gov.my/moh/resources/Penerbitan/ \nPenerbitan%20Utama/HEALTH%20INDICATOR/01_Petunjuk_K\nesihatan_2020.pdf \n\n\n\n6. Jabatan Negeri Kesihatan Sabah. Laporan Kusta (Januari-\nDisember 2019). Sabah: JKNS. 2020, September 14, 2022. [cited \nSept 2022].  \n\n\n\n7. Sarifah SSR. Public healthcare facility planning in Malaysia: \nusing location allocation models. Healthcare delivery system in \nMalaysia. Malaysia: University of Malaya; 2012. [cited 2022 Sept \n14]. p.37 44. Available from: https://pdfs.semanticscholar.org/ \n964a/1b464f8705306ec827571c23d5d4a1513ab4.pdf \n\n\n\n\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 581\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n582                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n8. Abeje T, Negera E, Kebede E, Hailu T, Hassen I, Lema T, et al. \nPerformance of general health workers in leprosy control \nactivities at public health facilities in Amhara and Oromia \nStates, Ethiopia. BMC Health Serv Res 2016; 16: 122.  \n\n\n\n9. Ukpe IS. A study of health workers\u2019 knowledge and practices \nregarding leprosy care and control at primary care clinics in the \nEerstehoek area of Gert Sibande district in Mpumalanga \nProvince, South Africa. SA Fam Pract 2006; 48(5): 16\u201323.  \n\n\n\n10. Ekeke N, Chukwu JN, Nwafor CC, Meka AO, Aguwa E, Uwakwe \nK, et al. Are there knowledge and attitude deficits on leprosy? A \nstudy among medical interns and final year students in \nsoutheast Nigeria. Lepr Rev 2020; 91: 108-18.  \n\n\n\n11. Chen SM, Zhang L, Liu DC, Liu HX. Assessment of knowledge \nand skills in early diagnosis of leprosy and attitudes towards \nleprosy amongst doctors working in dermatological services, \nShandong Province, People's Republic of China. Lepr Rev \n2004;75(4): 348-56.  \n\n\n\n12. Ricc\u00f2 M, Vezzosi L, Ranzieri S, Balzarini F, Mezzoiuso AG, \nVaccaro FG. Understanding leprosy in a nonendemic area: a \npilot study on knowledge, attitudes, beliefs of medical \nprofessionals from North-Western Italy. Acta Biomed 2020; \n91(4): e2020187.   \n\n\n\n13. Mponda K, Anafi G, Laja ET, Chidothe R, et al. Knowledge about \nleprosy among health care workers In Balaka District, Southern \nMalawi. Res Square 2020.  \n\n\n\n14. Kumar B. World Leprosy Day 2015: Renewing commitment for a \nleprosy free world! Indian J Med Res 2015; 141: 1-4.  \n\n\n\n15. Kwan Z, Pailoor J, Tan LL, Robinson S, Wong SM, Ismail R. \nLeprosy--an imported disease. Lepr Rev 2014; 85(3): 170-6.  \n\n\n\n16. Giri PA, Phalke DB, Aarif SM. A study of knowledge, attitude and \npractices regarding leprosy among undergraduates and interns \nof a medical college and hospital from rural India. Indian J Lepr \n2011; 83(2): 75-80.  \n\n\n\n17. Tiwari R, Srivastava DK, Bansal M, Adhikari P, Mishra S. An \nassessment of the impact of one day training programme on \nknowledge and attitude of undergraduate students on leprosy at \nG.R Medical College, Gwalior Madhya Pradesh. Natl J \nCommunity Med 2013; 4(2): 344\u20138.  \n\n\n\n18. Bajaj DR, Matlani BL, Soomro FR, Iqbal MP. Knowledge, attitude \nand practices regarding leprosy among general practitioners at \nHyderabad. J Coll Physicians Surg Pak 2009; 19(4): 215-8.  \n\n\n\n19. Uplekar MW. Private doctors and public health: The case of \nleprosy in Bombay, India. Natl Med J India 1990; 3(4): 162-6.  \n\n\n\n20. Wijeratne MP, \u00d8stbye T. Knowledge, Attitudes and Practices \nrelating to Leprosy among Public Health Care Providers in \nColombo, Sri Lanka. Lepr Rev 2017; 88(1): 75-84.  \n\n\n\n21. Briden A, Maguire E. An assessment of knowledge and attitudes \ntowards amongst leprosy/Hansen's disease workers in Guyana. \nLepr Rev 2003; 74(2): 154-62.  \n\n\n\n22. Ewhrudjakpor C. Health care providers knowledge as correlates \nof their attitudes towards leprosy sufferers in Nigeria. Ethno-Med \n2008; 24(2): 115-20.  \n\n\n\n23. Kabir H, Hossain S. Knowledge on leprosy and its management \namong primary healthcare providers in two districts of \nBangladesh. BMC Health Serv Res 2019; 19(1): 787.  \n\n\n\n\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 582\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                583 \n\n\n\nABSTRACT \nIntroduction: Fragrance allergy remains an important cause \nof contact dermatitis. We aim to describe the characteristics \nof patients with contact sensitisation to fragrances who \nunderwent patch testing in the Department of Dermatology \nHospital Kuala Lumpur. \n \nMaterials and Methods: This is a 5-year retrospective study \nof patients who developed positive reactions to fragrance \nallergens at the Department of Dermatology, Hospital Kuala \nLumpur, Malaysia between January 2017 and December \n2021. Patch tests were performed with European Baseline \nSeries and relevant extended series. Patch test readings \nwere recorded according to the International Contact \nDermatitis Research Group recommendation. \n \nResults: A total of 854 patients underwent patch test during \nthe study period with 133 (15.6%) patients developing at \nleast one positive reaction to fragrance allergens. The \nmedian age of patients at presentation was 40 years (range \n16-79) old with 78.2% females. The most common initial \npresentation was hand eczema (55.6%). Other commonly \ninvolved sites include face (38.3%), leg (35.3%) and trunk \n(22.6%). The most frequent sensitising fragrance allergens \nwere Fragrance Mix I (10.5%), Balsam of Peru (7.1%) and \nFragrance Mix II (4.9%). Sixty patients (45%) developed \npositive reaction to more than one fragrance allergens. \nTwelve patients (9%) developed positive patch test reactions \nto their own products such as skincare, hair dye and hand \nwash. Current relevance was recorded in 96 patients (72.2 \n%). \n \nConclusion: Contact sensitisation to fragrance allergens \nwas detected in about 15% of our patients who underwent \npatch test. The most common sensitising allergens were \nFragrance Mix I and II and Balsam of Peru.  \n \nKEYWORDS:  \nFragrances, allergic contact dermatitis, contact sensitisation to \nfragrances, patch test, Balsam of Peru \n \n \nINTRODUCTION \nContact dermatitis is defined as inflammation of the dermis \nand epidermis resulting from direct contact between a \nsubstance and the surface of the skin. It is the result of a type \n\n\n\nIV hypersensitivity reaction involving the T lymphocytes of \nimmune system. It can arise from exposure to various \nallergens which include metals, preservatives, woods and \nplants, plastic, rubber, medicines, medical devices, cosmetics \nand fragrances.1 \n \nAccording to International Fragrance Association (IFRA), \nfragrance ingredient is \u201cany basic substance used for its \nodour properties or malodour coverage.\u201d2 Fragrances are \nfrequently present in a variety of products for instance \ncosmetics (fine fragrances and aftershaves, lip balms, \nlipsticks, deodorants), household products (detergents), \ntoiletries (shampoos, soaps, lotions, creams, sunscreens), wet \nwipes, baby products, paper products, fabric and clothes, \ntopical pharmaceuticals, essential oils, industrial products \n(paints, rubber, plastic, insecticides, herbicides), and even \nflavouring agents in oral hygiene products, foods or drinks.3,4 \nPatch testing remains pivotal in diagnosing fragrance \nallergy. \n \nThis study aims to describe the characteristics of patients who \nhave contact allergy to fragrances in Hospital Kuala Lumpur, \nMalaysia. \n \n \nMATERIALS AND METHODS \nThis is a 5-year retrospective study of patients who developed \npositive reactions to fragrance allergens upon patch testing \nat the Department of Dermatology, Hospital Kuala Lumpur, \nMalaysia between January 2017 and December 2021. \n \nPatch tests were performed with European Standard Series \nand relevant extended series from Chemotechnique \nDiagnostics using IQ chambersTM. Extended series used \ninclude cosmetic series, metal series, rubber series, dental \nseries, medicament series, textile series, shoe series, plastic \nand glue series and hairdressing series. Fragrance allergens \nthat were tested in the study included Fragrance Mix I, \nFragrance Mix II, Balsam of Peru, and hydroxyisohexyl 3-\ncyclohexene carboxaldehyde (HICC) (Lyral) in the European \nbaseline series, as well as tea tree oil (oxidised), peppermint \noil, benzyl alcohol, musk mix and benzyl salicylate in the \ncosmetic series. Patients were also tested with their own \nproducts, including hair dye, hair shampoo, cosmetics, skin \ncare products, soap and toothpaste. Toothpaste and leave-on \ncosmetics such as lipstick, facial powder, facial foundation \n\n\n\nContact sensitisation to fragrance allergen: A 5-year \nretrospective study of patients in the Department of \nDermatology, Hospital Kuala Lumpur \n \nVivian Tai, MD1, Sharifah Rosniza Syed Nong Chek, AdvMDerm2, Min Moon Tang, AdvMDerm2 \n\n\n\n     \n1Department of Medicine, Hospital Kuala Lumpur, Ministry of Health, Malaysia, 2Department of Dermatology, Hospital Kuala \nLumpur, Ministry of Health, Malaysia  \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 03 July 2023                                                                                                                                                                              \nCorresponding Author: Tai Vivian                                                                                                                                                                                       \nEmail: viviantai.91@gmail.com \n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 583\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n584                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nCharacteristics                                                                                                                                        n = 133 (%) \nMedian age in years (range)                                                                                                                  40 (16 \u2013 79) \nMale:female ratio                                                                                                                                         1:3.6 \nEthnicity, n (%)                                                     Malay                                                                           75 (56.4) \n                                                                              Chinese                                                                        41 (30.8) \n                                                                              Indian                                                                            13 (9.8) \n                                                                              Others                                                                            4 (3.0) \nOccupations, n (%)                                               White collar workers                                                   32 (24.1) \n                                                                              Healthcare workers                                                     30 (22.5) \n                                                                              Blue Collar workers                                                     15 (11.3) \n                                                                              Pink collar workers                                                       11 (8.3) \n                                                                              Housewife                                                                    22 (16.5) \n                                                                              Unemployed                                                                23 (17.3) \nPatch test series used, n (%)                                European baseline                                                      133 (100) \n                                                                              Cosmetic                                                                       45 (33.8) \n                                                                              Rubber                                                                         34 (25.6) \n                                                                              Dental                                                                          18 (13.5) \n                                                                              Metal                                                                            18 (13.5) \n                                                                              Shoes                                                                            14 (10.5) \n                                                                              Hairdressing                                                                   9 (6.8) \n                                                                              Textile                                                                              8 (6) \n                                                                              Medicaments                                                                   8 (6) \n                                                                              Plastic and glue                                                               4 (3) \n                                                                              Own products                                                              65 (48.9) \n\n\n\nTable I: Characteristics of patients who developed positive reaction to fragrance allergens in patch testing\n\n\n\nSites                                                                                                                                   n (%) \nHand                                                                                                                                74 (55.6) \nFace                                                                                                                                  51 (38.3) \n                                                    Not otherwise specified                                             33 (24.8) \n                                                    Lips                                                                              17 (12.8) \n                                                    Ears                                                                               11 (8.3) \n                                                    Eyelids                                                                           8 (6.0) \n                                                    Nose                                                                               3 (2.3) \nLeg                                                                                                                                   47 (35.3) \nTrunk                                                                                                                               30 (22.6) \nArm                                                                                                                                  17 (12.8) \nNeck                                                                                                                                  12 (9.0) \nAnal/genital                                                                                                                      11 (8.3) \nScalp                                                                                                                                  8 (6.0) \nScattered generalised                                                                                                       8 (6.0) \n \n\n\n\nTable II: Sites of lesions in 133 patients who were sensitized to fragrance allergens\n\n\n\nAllergens                                                                                                        Number of patient positive to allergen (Sensitisation rate %) \nEuropean baseline series            Fragrance mix I                                                                                      90 (10.5) \nn =854                                         Balsam of Peru                                                                                        61 (7.1) \n                                                    Fragrance mix II                                                                                      42 (4.9) \nCosmetic series                            Tea tree oil oxidised                                                                                7 (2.9) \nn=242                                           Peppermint oil                                                                                         5 (2.4) \n                                                    Lyral                                                                                                         10 (1.2) \n                                                    Musk mix                                                                                                  1 (0.5) \n                                                    Benzyl alcohol                                                                                          1 (0.4) \n                                                    Benzyl salicylate                                                                                        0 (0) \n\n\n\nTable III:The sensitisation pattern of current cohort\n\n\n\nCompound 1                               Compound 2                                                                                            CR, % \nFragrance Mix I                           Colophony                                                                                                  12.2 \n                                                    Propolis                                                                                                       3.3 \n                                                    Sesquiterpene lactone mix                                                                        2.2 \nFragrance Mix II                          Colophony                                                                                                   9.5 \n                                                    Propolis                                                                                                         0 \n                                                    Sesquiterpene lactone mix                                                                          0 \nBalsam of Peru                            Colophony                                                                                                  13.1 \n                                                    Propolis                                                                                                       4.9 \n                                                    Sesquiterpene lactone mix                                                                        1.6 \n\n\n\nTable IV: Combined cross-reactivity (CR) rates\n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 584\n\n\n\n\n\n\n\n\nContact sensitisation to fragrance allergen\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                585 \n\n\n\nand deodorants were tested \u201cas is\u201d. Cleaning products such as \nfacial wash, shampoo and shower gel were diluted with water \nto 10% (w/w). \n \nPatches were applied to the patients and removed after 48 \nhours. Initial reading was recorded at 48 hours and final \nreading was noted at 96 hours after patch application. The \nparameters studied include positive patch test reactions and \nthe source of allergens. Readings were recorded according to \nthe International Contact Dermatitis Research Group \nrecommendation.5,6 A positive patch test reaction is defined \nas a reaction that fulfils at least a 1+ reaction (i.e., +, ++ or \n+++). Other reactions that can be found during patch tests are \nirritant reaction (IR), doubtful reaction (+?) and angry back \nreaction, but these are not considered as a positive patch test \nreaction. \n \n \nRESULTS \nThere was a total of 854 patients who underwent patch test \nbetween January 2017 and December 2021 at Department of \nDermatology, Hospital Kuala Lumpur. Out of these, 133 \n(15.6%) patients developed at least one positive reaction to \nfragrance allergens. The demographic data was shown in \nTable I. The median age of patients was 40 years (range 17 to \n79) and 78.2% of patients were female. The initial \npresentations include allergic contact dermatitis (18.8%), \nhand eczema (14.3%), contact dermatitis (12%), discoid \neczema (10.5%), atopic eczema (7.5%), cheilitis (7.5%), hand \nand feet eczema (6.8%) and lichen planus/lichenoid reaction \nof oral mucosa (6.8%). Other less frequent presentations \ninclude face eczema, oral ulcer, papular eczema, stasis \neczema, allergic contact gingivitis, chronic urticaria, contact \nurticaria, papular urticaria, feet eczema, insect bite \ndermatitis, irritant contact dermatitis, metal allergy, \npalmoplantar eczema, photoaggravated dermatitis, \nseborrheic dermatitis and ashy dermatoses.  \n \nThe most common sites of involvement were hands (55.6%), \nface (38.3%), legs (35.3%) and trunk (22.6%) as shown in \nTable II. As shown in Table III, the most frequent sensitising \nallergens were Fragrance Mix I (10.5%), balsam of Peru \n(7.1%) and Fragrance Mix II (4.9%). Other sensitising \nallergens included tea tree oil oxidised (2.9%), peppermint oil \n(2.4%), Lyra (1.2%), musk mix (0.5%) and benzyl alcohol \n(0.4%). None of our patients were sensitised to benzyl \nsalicylate. There were 60 (45%) patients who developed \npositive reaction to more than one fragrance allergen. For our \npatients who were sensitised to fragrance mix I, cross-\nreactivity (CR) rate to colophony was 12.2% (Table IV). In \n\n\n\npatients who were allergic to balsam of Peru, CR rate to \ncolophony was 13.1%. Around 9% of patients who were \nsensitised to Fragrance Mix II also cross-sensitised with \ncolophony. None of the patients who were sensitized to \nFragrance Mix II cross-reacted with propolis and \nsesquiterpene lactones (SQL) mix.  \n \nThere were 12 patients (9%) who developed positive patch \ntest reactions to their own products such as skin care products \n(n = 4), hair dye (n = 3), hand wash (n = 3), hair shampoo (n \n= 1) and cosmetic (n = 1). Relevance of positive patch test \nreaction was assessed in all and 96 patients (72.2%) were \nfound to have current relevance, mostly to their own toiletries \n(46.6%), followed by their household products (15.5%), \ncosmetics (9.5%), gloves (9.5%), footwear (6.9%), hair dye \n(3.4%) and food or flavouring (2.6%). \n \n \nDISCUSSION \nFragrances represent the second most common cause of \nallergic contact dermatitis (ACD) after nickel.7,8 It is known to \nbe the most common cause of allergies to cosmetics.9 The \nprevalence of contact sensitisation to fragrances differs \nworldwide and the most common contributing allergens were \nFragrance mix I, Balsam of Peru and Fragrance mix II (Table \nV).11,13,15,16 The prevalence of fragrance contact allergy in the \ngeneral population is 0.7\u20132.6%.10 A study across 12 European \ncountries from 2009 to 2012 showed that 12.7% out of more \nthan 50,000 patients patch tested revealed positive reactions \nto Fragrance Mix I, Fragrance Mix II, Lyral, balsam of Peru, \noil of turpentine, or a combination of these.11 In Spain, \npositive patch test reactions towards fragrance allergens were \nfound in 1.7 to 15.1% of study population.12-14 A smaller study \nin Thailand showed that 22.1% of 312 patients reacted to \nFragrance Mix I, Fragrance Mix II, Balsam of Peru, or \ncombinations.15 Our study which showed a prevalence of \n15.6% of fragrance allergy was similar to other studies to \ndate.10,16  \n \nIn a study of 3119 patients patch-tested in 2008 to 2011 \nacross five European countries, women were found to be \naffected twice as often as men.16,17 Our study presented similar \ncharacteristics. Typically, women in their mid-40s, \ncommonly present with facial or hand eczema due to \nfragrance allergy,10,16,18-20 likely due to increased use of \nfragranced products among women. Sensitisation is more \ncommon at an older age likely due to age-related poor skin \nbarrier function from asteatotic eczema,20 and increased use \nof, as well as cumulative exposure with age to, products with \nfragrance.21 Face is commonly affected likely due to the direct \n\n\n\nAuthor country                            Study period               n             Common age group             Positive patch            Top two allergens \n                                                                                                                    (years)                       test reaction (%) \nFrosch et al., Germany11               2009 to 2012           56813                       >40                                     NA                      1) Fragrance mix I \n                                                                                                                                                                                               2) Balsam of Peru \nCuesta et al., Spain13                    2004 to 2008            1253                        >40                                      9.3                       1) Balsam of Peru \n                                                                                                                                                                                              2) Fragrance mix I \nVejanurug et al., Thailand15        2013 to 2014             312                         >40                                   26.9%                    1) Fragrance mix I \n                                                                                                                                                                                              2) Fragrance mix II \nHafner et al., Brazil16                    2000 to 2015            1870                         40                                    13.8%                    1) Fragrance mix I \n                                                                                                                                                                                                  2) Colophony \n\n\n\nTable V: Worldwide studies on contact sensitisation to fragrances\n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 585\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n586                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\napplication of cosmetics, indirect transfer from contaminated \nhands, or airborne contact (mists, sprays, and aerosols).10 \nEyelids are the most susceptible area to fragrance allergy as it \nhas the thinnest epidermis.22 The other commonly involved \narea is the lips, especially the unkeratinised epithelium.23 \n\n\n\nWhen it comes to lips involvement, food flavourings are \nfrequently the contributor. Hands are commonly involved \nowing to the use of fragrance containing household products, \ncosmetics and topical medications.21 It is apparent that from \nour study there is a significant number of our patients who \nhad dermatitis at the groin, pruritus ani or pruritis vulva \n(8.3%). This could be due to the fact that topical \nmedicaments used in these areas also contained fragrances. \nThese areas may also develop ectopic contact dermatitis from \nthe transfer of fragrance allergens from the hands to these \nsensitive areas.  \n \nCheng et al. reported a common presentation of \npapular/vesicular lesions or patchy dermatitis with \neczematous papules among patients presented with \nfragrance allergy. Chronic lichenified pruritic plaques may \nalso be seen.3 Our study showed similar findings where the \ninitial presentations of fragrance allergy include eczematous \nlesions, papular lesions or lichen planus or lichenoid reaction \nof oral mucosa. \n \nOur study revealed that Fragrance Mix I is the most common \nsensitising allergen (10.5%), which is similar to other \nstudies.3,10,18,24 Fragrance Mix I consisted of 8 fragrance \nchemicals including cinnamyl alcohol, cinnamal, \nhydroxycitronellal, amyl cinnamal, geraniol, eugenol, \nisoeugenol and oak moss absolute. Oak moss absolute is the \nmost common individual allergen contributing to fragrance \nallergy while amyl cinnamal is the least frequent contributor \nof fragrance allergy.9 Oak moss absolute is an extract derived \nfrom lichen growing on oak trees in the Mediterranean area, \nand it has a complex composition and has been used in \nmany fragrance products, including perfumes, colognes and \naftershaves.8 Geraniol is a commonly used fragrance terpene \n(appreciated for its fresh, flowery odour), occurring naturally \nin many flowers and plants, and is present in high \nconcentrations in essential oils of rose and geranium.8 \n\n\n\nHydroxycitronellal and geraniol are the fragrances most \nwidely found in perfumes.25 Cinnamal, hydroxycitronellal \nand isoeugenol are commonly present in deodorants. \nIsoeugenol can also be found in lip products, \nhydroalcoholics, aftershaves, women\u2019s facial and hand \ncreams, intimate wipes, and make-up removers.  \n \nThe rate of sensitisation of Balsam of Peru was comparable to \nprevious studies.3,10 Balsam of Peru, also known as Myroxylon \npereirae, is a natural complex resin derived from a Central \nAmerican tree (or Myroxylon pereirae tree).9,26 It is frequently \npresent in a wide variety of products ranging from drugs, \nperfumes, aroma compounds, cleaning products, dental \ncement and liquids, cosmetic products to foods. Balsam of \nPeru is used in topical medicaments to treat wounds as it has \nantibacterial properties. Its most important allergen is \nformed by the polymerisation of an ester of benzoic acid or \ncinnamic acid and coniferyl alcohol.27 Its crude use in \nperfumes has been banned by International Fragrance \nAssociation (IFRA) since 1982 but its extracts and distillates \ncan still be used in manufacturing of perfumes.26  \n\n\n\nThe third most frequent sensitising allergen is Fragrance Mix \nII (4.9%), similar to previous studies.24 Fragrance Mix II \nconsists of hexyl cinnamic aldehyde, hydroxyisohexyl 3-\ncyclohexene carboxaldehyde, farnesol, coumarin, citral and \ncitronellol. The most frequent sensitising individual allergen \nis hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC), \nalso known as Lyral; the least frequent one is citronellol. \nSince the addition of Fragrance Mix II as standard test for \nfragrance allergy, there has been an increase in the \nsensitivity for detection of fragrance sensitisation with respect \nto traditional markers for fragrances (Fragrance Mix I and \nBalsam of Peru).9 Citronellol is most widely found in hygiene \nproducts and daily moisturizers.25 Lyral contributes to 1.2% of \npositive patch test result in our cohort, similar to other \nstudy.10 Lyral is more commonly found in deodorants.28 It is \ninteresting to note that not all our patients who were positive \nto Lyral were also positive to Fragrance Mix II. This could be \ndue to the higher concentration of Lyral when tested as an \nindividual allergen compared to its concentration in the \nFragrance Mix II. Of note, Lyral has been banned from \ncosmetics products in EU since August 2021 hence it will be \ninteresting to observe if the trend of Lyral sensitivity decreases \nsubsequently. \n \nA total of 45% of our patients developed positive reaction to \nmore than one fragrance allergens in our study, likened to \nanother study.24 There are more than 2500 existing fragrance \ningredients and at least 100 ingredients are known contact \nallergens.12 Hence, it is crucial to supplement standard patch \ntesting with patients\u2019 own products. Hair care products \ncommonly contain a great amount of fragrances. For \ninstance, only 2.8% of 324 styling products were free of \nfragrances.10 Studies have shown significant cross \nsensitization between colophony, propolis and fragrance. In \nsubjects who are allergic to colophony; fragrance and \npropolis may be significant cross-reactors. Similarly, in \nsubjects who are allergic to propolis; fragrance and \ncolophony are considered to be significant cross-reactors.29 \nHowever, for patients allergic to fragrance, cross sensitisation \nto propolis or colophony is not significant in terms of cross-\nreactivity rate.29 A 10% CR rate was considered to be \nsignificant enough to recommend avoidance of a potential \ncross-reacting allergen based on the American Contact \nDermatitis Society\u2019s Contact Allergy Management Program \n(CAMP) recommendations.30 Nonetheless, our study showed \notherwise (Table V). For our patients who were sensitive to \nFragrance Mix I, colophony may be a significant cross-\nreactor with a CR rate of 10.5%, but not propolis and SQL \nmix. Patients allergic to Balsam of Peru also showed a \nsignificant cross sensitisation to colophony (13.1%) but not to \npropolis and SQL Mix. We therefore recommend our patients \nwho develop contact sensitisation to Fragrance Mix I and \nBalsam of Peru to also avoid colophony, in view of the CR \nrate of more than 10%. \n \nClinical relevance is crucial to translating research results \ninto clinical use. The rate of currently relevant sensitisations \nreflect the extent of current exposure and the consequent \ndisease state. This may rise or decline with time, hence \nshowing the direct effect of a fragrance contact allergy to the \nindividual.26 It is believed that a strong positive reaction is \nmore likely to have clinical relevance than a weak positive \nreaction. The recorded relevance in our study was high \n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 586\n\n\n\n\n\n\n\n\nContact sensitisation to fragrance allergen\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                587 \n\n\n\n(72.2%), similar to another study.31 This is likely due to \nfragrance sensitisation acting as a provoking factor for a \nspectrum of dermatoses. Unless fragrance-containing \nproducts are avoided, previous dermatoses will not improve \ndespite appropriate treatment and protective measures.13   \n \nContact allergy to fragrance is mostly not related to \noccupation32, but more commonly originates from personal \nuse of scented cosmetics. However, secondary occupational \nexposure to fragrance ingredients may happen at workplace. \nPrevious literature showed a high prevalence of allergy to \nFragrance Mix I among healthcare workers due to irritant \nhand contact dermatitis from repeated washing disrupting \nthe skin barrier, allowing better allergen penetration, hence \nsubsequent application of products containing fragrances \nintroduces a source for allergen exposure.3 Sensitivity to \nBalsam of Peru has been found to be more common among \nhealthcare workers especially dentists.33 Dentists also have a \nhigher risk for allergy to eugenol (one of the components of \nFragrance Mix I) due to exposure from mouthwashes, \ndressings, impression materials, and periodontal packings.19 \nAbout a fifth of our cohort were healthcare workers. Out of \nthese, eight out of 30 healthcare workers (26.7%) had \nfragrance allergy related to work. Food handlers may be \nfrequently exposed to components of Fragrance Mix I \n(cinnamal and cinnamic alcohol) and Balsam of Peru due to \nhandling of spices and essential oils.3 Hairdressers, \nbeauticians and aromatherapists are also particularly at risk \nfor fragrance allergy.10 Overall, our study has shown a fairly \nequal distribution of fragrance allergy across different \noccupations. \n \nAs fragrances are widely used in daily products, it is \nextremely difficult for sensitized patients to avoid them \ncompletely without limiting their daily activities. Some \nproducts may also omit labelling fragrance in their \ningredient if it was used for masking odour instead of \nimparting pleasant odour. Regulations have been imposed to \nsafeguard consumer\u2019s health and safety including \nmandatory labelling of fragrance ingredients on products\u2019 \ningredient label if products sold contained any of the 26 \nfragrances governed by EU regulations.12,31 Unfortunately, \nneither Balsam of Peru nor the extracts and distillates are \nincluded in the mandatory labelling as yet. Hence, there \nshould be continuous efforts in identifying common \nfragrance allergens and they should be regulated \ncontinuously by authority bodies. Tighter regulations should \nbe enforced to ensure that fragrance ingredients are labelled \naccordingly and correctly.10  \n \nEssential oils are sources of fragrance allergens and expanded \npatch testing involving essential oils may be considered in \npatients suspected to have fragrance allergy. So far, our study \nincluded few individual ingredients of essential oils which are \npresent in the cosmetic series, namely the tea tree oxidized \nextract and peppermint oil. From our study, there were 2.9% \nand 2.4% of our patients who were sensitized to tea tree oil \noxidized and peppermint oil respectively, hence it is essential \nto monitor these fragrance allergens in our populations. \nSince fragrance series was not available in our setting at \npresent, we may include cosmetic series if we are \ninvestigating patients for fragrance allergy, as it contains a \n\n\n\nfew essential oils. Cosmetic series also contains sorbitan \nsesquioleate, which is the dispersing agent used in Fragrance \nmix I hence testing for this will help to differentiate between \ntrue Fragrance mix I allergy and sorbitan sequioleate allergy. \n \nManagement of patients with fragrance allergic contact \ndermatitis includes avoidance of products with labelled \nknown sensitising fragrances. Clinicians may advise patients \nto fully avoid the use of fragrance-containing products such \nas perfumes and toiletries. If patients need to use such \nproducts, they should be advised to avoid applying these \nproducts at areas of skin that are potentially traumatized \n(beard region, hands, and shaved areas) or occluded (axilla), \nas well as areas of high absorption (eyelids, genitals, and \naxilla) and areas of chronic dermatitis (e.g., stasis \ndermatitis). Exposure to air and oxidation of products should \nbe prevented by replacing lid between uses. Household \nproducts such as dishwashing liquid, clothes detergent, toilet \ncleaners or floor cleaners also contain fragrance and patients \nshould avoid skin contact with these products by using gloves \nor boots as protection as these household products usually \nhave no fragrance-free alternatives. We should also educate \nour patients to avoid using products out of its shelf life \n(commonly 1 year) as certain fragrance ingredients \nautoxidise into allergenic products.34 Patients with \nsensitisation to Balsam of Peru may benefit from a balsam-\nrestricted diet, as Balsam of Peru has been associated with \nsystemic contact dermatitis if ingested.35 Examples of foods \nand drinks rich in Balsam of Peru include citrus fruit, spices \nsuch as vanilla and cinnamon, chocolate, cola, and \ntomatoes.36 In general, avoiding exposure in infants and \nyoung children is ideal as sensitisation to an allergen is \nlifelong once acquired. \n \nThere is limitation to this study. Individual ingredients of \nfragrance mix I and fragrance mix II were not tested in all \nsubjects showing positive reaction to the mixes. We should \nconsider to purchase the fragrance allergy series which \ncontains more fragrance allergens in order to detect more \ncases of fragrance allergy. Our findings may not be \nrepresentative of the whole Malaysian population as this is \nonly a single centre study.  \n \n \nCONCLUSION \nContact sensitisation to fragrance allergens was detected in \nabout 15% of our patients who underwent patch test. It is \nmore prevalent in women and commonly involves hands \nand face. The most common sensitising allergens were \nFragrance Mix I, Fragrance Mix II and Balsam of Peru. \nCurrent relevance of positive patch test reaction was found in \nalmost three quarter of our patients and these were mostly \ntowards their own toiletries, household products and \ncosmetics. It is crucial to test patients\u2019 own products during \nworkup for allergen sensitisation to ensure that these relevant \nreactions are not missed. \n \n \nCONFLICT OF INTEREST DECLARATION \nThe authors have no conflict of interest to declare. \n \n \n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 587\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n588                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nACKNOWLEDGEMENT \nThe authors would like to thank the Director General of \nHealth, Malaysia for permission to publish this paper. \n \n \nREFERENCES \n1. Ufer W, Werfel T, Lepoittevin JP, White IR. Contact allergy \u2013 \n\n\n\nemerging allergens and public health impact. Int J Environ Res \nPublic Health 2020; 17(7): 2404. \n\n\n\n2. IFRA. 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Clinical relevance \nof positive patch test reactions to the 26 EU-labelled fragrances. \nContact Derm 2009; 61(4): 217-23. \n\n\n\n32. Uter W, Schnuch A, Geier J, Pfahlberg A, Gefeller O. Association \nbetween occupation and contact allergy to the fragrance mix: a \nmultifactorial analysis of national surveillance data. Occup \nEnviron Med 2001; 58(6): 392-8. \n\n\n\n33. Warshaw EM, Schram SE, Maibach HI, Belsito DV, Marks Jr JG, \nFowler Jr JF, et al. Occupation-related contact dermatitis in North \nAmerican health care workers referred for patch testing: cross-\nsectional data, 1998 to 2004. Dermatitis 2008; 19(5): 261-74. \n\n\n\n34. Buckley DA. Fragrance ingredient labelling in products on sale in \nthe U.K. Br J Dermatol 2007; 157(2): 295-300. \n\n\n\n35. Salam TN, Fowler JFJr. Balsam-related systemic contact \ndermatitis. J Am Acad Dermtol 2001; 45(3): 377-81. \n\n\n\n36. de Groot AC. Myroxylon pereirae resin (Balsam of Peru) \u2013 A \ncritical review of the literature and assessment of the significance \nof positive patch test reactions and the usefulness of restrictive \ndiets. Contact Derm 2019; 80: 335-53. \n\n\n\n5-Contact00053.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 588\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                589 \n\n\n\nABSTRACT \nIntroduction: Monitoring of impedance field telemetry is \ncrucial to maintaining optimal function of cochlear implants. \nThis study aims to investigate impedance changes in \ncochlear implant electrodes one year after switch on. \n \nMaterials and Methods: A retrospective repeated cross-\nsectional study was conducted by recruiting patients with \ncochlear implants presenting to the Dr. Cipto \nMangunkusumo National General Hospital, Jakarta, \nIndonesia between 2017 and 2021. Basal (b1, b2) and apical \n(a1, a2) electrodes, representing the outermost and \ninnermost parts of the cochlear implant electrodes, were \nmeasured at switch on and at 1 year post-implantation. \n \nResults: A total of 123 patients, with a total of 123 cochlear \nimplant samples, were included in the analysis. We found a \nsubstantial change in electrical impedance between switch \non and follow-up periods, where the impedance levels of \nbasal electrodes decreased (b1: mean difference (MD) \u22121.13 \n[95% confidence interval (CI): \u22121.71, \u22120.54], p<0.001; b2: MD \n\u22120.60 [95%CI: \u22121.17, \u22120.03], p=0.041) and those of apical \nelectrodes increased (a1: MD 0.48 [95%CI: \u22120.28, 0.99], \np=0.064; a2: MD 0.67 [95%CI: 0.12, 1.22], p=0.017). We also \nfound that the choice of surgical approaches for implant \ninsertion may affect the electrode impedance. \nCochleostomy approach resulted in a higher impedance \nthan round window in basal (b1) and apical (a2) electrodes \nboth at switch on and follow-up (b1 at switch on and at \nfollow-up: p=0.019 and p=0.004; a2 at follow-up: p=0.012). \nExtended round window approach also resulted in a higher \nimpedance than round window in basal (b1) and apical (a2) \nelectrodes at follow-up (p=0.013 and p=0.003, respectively). \n \nConclusion: Electrical impedance of cochlear implant \nelectrodes may change over time, highlighting the \nimportance of regular impedance assessments for cochlear \nimplant users to ensure optimal device function. The round \nwindow approach resulted in better initial and long-term \nimpedance levels compared to cochleostomy, and better \nlong-term impedance levels than extended round window. \nExtended round window approach also gives better \nimpedance level than cochleostomy. Further research \nshould investigate the potential interplay between surgical \napproach and other factors that may impact impedance \nlevels to confirm our findings. \n \n\n\n\nKEYWORDS:  \nCochlear implant, cross-sectional, electrical impedance, follow-up \nstudies, surgical approach \n \n \nINTRODUCTION \nCochlear implants are widely used for the habilitation and \nrehabilitation of patients with profound sensorineural \nhearing loss (SNHL). Such implants use a software connecting \nan external component, i.e., speech processor, to an internal \ncomponent consisting of an array of electrodes surgically \nimplanted into the cochlea. The electrodes play a crucial role \nin aural habilitation by stimulating the auditory nerve fibers \nin the cochlea, enabling the brain to receive auditory input \nand perceive sound, thereby improving hearing and speech \ndevelopment especially in children with congenital SNHL.  \n \nTo maintain an optimal function, it is essential to regularly \nexamine the electrode impedance in cochlear implants. \nElectrical impedance, a parameter measuring the resistance \nor opposition of electrodes to the flow of electrical current, is \nevaluated both intraoperatively and during mapping \nsessions to describe the integrity of the electrodes and the \nelectrical current between the electrodes and the surrounding \ncochlear tissues.1,2 Any changes in impedance levels may \nindicate issues with the electrodes and/or cochlear implants, \nsuch as short circuits, open circuits, or damaged devices.1,3 \n \nElectrical impedance of a cochlear implant may be affected \nby several factors including electrode placement, tissue \nchanges (e.g., inflammation or damage), electrode corrosion, \nand the duration of use. Long-term use of the device may \nlead to a reduction in its efficiency in delivering electrical \ncurrent to the surrounding cochlear tissues, resulting in an \nincrease in impedance and decreased implant effectiveness.2-4 \nTherefore, it is saliently important to perform follow-up \nexaminations post-implantation to investigate potential \nchanges in the electrical impedance of cochlear implants \nover time. This study aims to investigate changes in \nimpedance levels in patients with cochlear implants one year \nafter implantation at a tertiary referral hospital in Jakarta, \nIndonesia. \n \n \nMATERIALS AND METHODS \nA retrospective repeated cross-sectional study was conducted \nby including patients using cochlear implants presenting to \n\n\n\nImpedance changes in cochlear implant electrodes one year \nafter switch on: A cohort study at a tertiary referral hospital \nin Jakarta, Indonesia \n \nSemiramis Zizlavsky, MD PhD, Rangga Saleh, MD, Harim Priyono, MD PhD \n\n\n\n     \nDepartment of Otorhinolaryngology Head and Neck Surgery (ORL-HNS), Faculty of Medicine Universitas Indonesia/Dr. Cipto \nMangunkusumo Hospital, Jakarta, Indonesia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 04 July 2023                                                                                                                                                                              \nCorresponding Author: Semiramis Zizlavsky                                                                                                                                                                       \nEmail: semiramiszizlavsky@gmail.com\n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 589\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n590                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nthe Ear, Nose, and Throat (ENT) outpatient clinic of the \nDepartment of Otorhinolaryngology and Head and Neck \nSurgery, Dr. Cipto Mangunkusumo National General \nHospital, Jakarta, Indonesia between 2017 and 2021. All \npatients underwent complete electrode insertion using \nimplants manufactured by MED-EL (PULSAR, SONATA, OR \nSYNCHRONY models; Innsbruck, Austria), Cochlear\u00ae (Slim \nStraight\u00ae (CI622) or Contour Advance\u00ae (CI612) models; \nSydney, Australia), or Advanced BionicsTM implants \n(HiFocus\u2122 1J or HiFocus\u2122 Mid-Scala models; Bangalore, \nIndia), and patients with device failures were excluded from \nthis study. The parents or guardians of the children provided \nwritten informed consent for the children to participate in \nthis study. The study protocol has been approved by the \nResearch Ethics Committee, Faculty of Medicine Universitas \nIndonesia and Cipto Mangunkusumo National General \nHospital (ethical no. 22-02-0181). This study is reported \naccording to the Strengthening the Reporting of \nObservational Studies in Epidemiology (STROBE) guidelines.5 \n \nMeasurement of the impedance levels (k\u03a9) of the cochlear \nimplants was performed at switch on and at 1 year post-\nimplantation. The electrodes investigated in this study were \nbasal electrodes (b1, b2) and apical electrodes (a1, a2; Figure \n1). In addition, we also recorded data on cochlear implants \n(type of electrodes, hearing preservation technique, surgical \napproach for implant insertion) and comorbidities (inner ear \nmalformation and obliteration of scala tympani). The round \nwindow insertion was used as the hearing preservation \ngroup, whereas extended round window and cochleostomy \ninsertion were used as the non-hearing preservation group. \nThe cochlear implantation procedures in this study were \nperformed by two surgeons which can be consider as bias and \na limitation to this study. The collected data were then \ntabulated, described narratively and analysed using paired \nsample t tests to compare values from consecutive fitting \nsessions, and one-way analysis of variance (ANOVA) \nfollowed by Tukey\u2019s HSD post hoc tests to compare \nimpedance values between surgical approaches at each \nmapping session, whichever appropriate, to compare values \nfrom consecutive fitting sessions. Dichotomous data were \npresented in frequencies and proportions, while continuous \ndata in mean \u00b1 standard deviation (SD) or mean difference \n(MD) and 95% confidence intervals (95% CI). All statistical \nanalysis were performed using SPSS 24.0 (SPSS Inc., Chicago, \nIL), and a p value of \u22640.05 denotes statistical significance. \n \n \nRESULTS \nA total of 123 patients with ages ranging from 1 to 45 years \nold, cumulating a total of 123 samples of cochlear \nimplantation procedures, were included in the present study. \n50.4% (62/123) patients were female, and about 64.2% \n(79/123) received implantation on the right side. Most of the \nchildren underwent hearing preservation technique (106 \npatients, 86.2%) with lateral wall electrodes (114 patients, \n92.7%). 71.5% (88/123) of the children underwent round \nwindow insertion, followed by an extended round window \napproach (18 patients, 14.6%) and cochleostomy (17 \npatients, 13.8%). No children presented with inner ear \nmalformation (0/123 patients, 0.0%), and two patients \n(1.6%) had obliterated scala tympani (Table I). \n\n\n\nWe found a statistically significant changes in electrical \nimpedance between switch on and 1 year post-implantation \nperiods, where the impedance values of b1 and b2 electrodes \ndecreased at 1 year follow-up (b1: MD \u22121.13 [95%CI: \u22121.71, \n\u22120.54], p<0.001; b2: MD \u22120.60 [95%CI: \u22121.17, \u22120.03], \np=0.041), while those of a2 electrode slightly increased (MD \n0.67 [95%CI: \u22120.12, 1.22], p=0.017; Table II). We also \nobserved a slight increase in the impedance value of a1 \nelectrode, although not statistically significant (MD 0.48 \n[95%CI: 0.28, 0.99], p=0.064). \n \nWe also found that the choice of surgical approaches for \nimplant insertion contributed to the evolution of apical and \nbasal impedance at switch on and 1-year follow-up post-\nimplantation (Table III). In basal (b1) electrodes, \ncochleostomy approach resulted in a higher impedance both \nat switch on and follow-up compared to round window \napproach (p=0.019 and p=0.004, respectively), while the \nextended round window approach resulted in a significantly \nhigher impedance level than round window approach only \nat follow-up (p=0.013). Meanwhile, in apical (a2) electrodes, \nboth extended round window and cochleostomy approaches \nhad a substantially higher/lower impedance levels than the \nround window approach at follow-up (p=0.003 and p=0.012, \nrespectively), but not at switch on (p=0.428 and p>0.999, \nrespectively). \n \n \nDISCUSSION \nImpedance field telemetry is a widely used parameter to \nassess the integrity of a cochlear implant device during \nimplantation and mapping sessions. This enables clinicians \nto ensure the optimal function of cochlear implants in order \nto improve hearing and speech abilities of patients with \nsevere-to-profound SNHL. This study, assessing the \nimpedance levels of basal (b1 and b2) and apical (a1 and a2) \nelectrodes, which represent the outermost and innermost part \nof the cochlear implant electrodes, found that significant \nchanges in impedance levels occur over time, where the \nimpedance values were decreased in basal electrodes and \nincreased in apical electrodes at 1-year post-implantation. \n \nIt is known that impedance levels of a cochlear implant may \nchange over time due to various factors affecting the tissues \nsurrounding the device. Following implantation, fibrous \ntissues, protein exudates, and macrophages may surround \nthe electrodes, caused by inflammation or other tissue \nchanges, thereby potentially altering the electrical properties \nof the surrounding tissues and leading to changes in \nimpedance levels. Additionally, the metal components of the \nimplant may gradually corrode and thus induce further \nchanges in impedance levels of the electrodes.6 Previous \nstudies have shown that the impedance levels of a cochlear \nimplant electrode will increase substantially in the first week \nafter implantation and are expected to plateau within one to \ntwo months.7,8 In addition to wear and tear, other factors that \nmay also affect the impedance levels of a cochlear implant \ninclude tissue changes and electrode placement. As \npreviously stated, the environment surrounding the device \nmay contribute to the impedance levels of the electrodes. This \nindicates that any tissue changes (e.g., inflammation, \ninfection, fibrosis) and the location of the electrodes in the \n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 590\n\n\n\n\n\n\n\n\nImpedance changes in cochlear implant electrodes one year after switch on\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                591 \n\n\n\nSample characteristics                                                                                                      n (%) \nSex  \n\n\n\nMale                                                                                                                            61 (49.6) \nFemale                                                                                                                        62 (50.4) \n\n\n\nSide of implantation                                                                                                                \nRight                                                                                                                           79 (64.2) \nLeft                                                                                                                              44 (35.8) \n\n\n\nType of electrode                                                                                                                     \nLateral wall                                                                                                                114 (92.7) \nPerimodiolar                                                                                                                 9 (7.3) \n\n\n\nHearing preservation technique                                                                                              \nYes                                                                                                                              106 (86.2) \nNo                                                                                                                               17 (13.8) \n\n\n\nScala tympani approach                                                                                                           \nRound window                                                                                                           88 (71.5) \nExtended round window                                                                                          18 (14.6) \nCochleostomy                                                                                                             17 (13.8) \n\n\n\nInner ear malformation                                                                                                           \nYes                                                                                                                                 0 (0.0) \nNo                                                                                                                               123 (100) \n\n\n\nScala tympani obliteration                                                                                                       \nYes                                                                                                                                 2 (1.6) \nNo                                                                                                                              121 (98.4)\n\n\n\nTable I: Clinical characteristics of the study population (n = 123)\n\n\n\nElectrode                                           Switch on (k\u03a9)              Follow-up (k\u03a9)                                                Changes \n                                                                                                                                                 MD                      95% CI                 p value \nBasal electrodes              b1                  8.94 \u00b1 3.75                     7.81 \u00b1 3.05                       \u22121.13                \u22121.71, \u22120.54             <0.001 \n                                        b2                          \u00b1                                      \u00b1                               \u22120.60                \u22121.17, \u22120.03              0.041 \nApical electrodes            a1                          \u00b1                                      \u00b1                                0.48                    0.28, 0.99                 0.064 \n                                        a2                  6.41 \u00b1 2.80                     7.09 \u00b1 2.35                        0.67                    0.12, 1.22                 0.017 \n \nUnless otherwise stated, data are expressed as mean \u00b1 standard deviations. p value derived from paired t tests. CI, confidence interval; MD, mean difference. \n \n \n\n\n\nTable II: Impedance levels (k\u03a9) of the measured electrodes at switch on and at 1 year follow-up\n\n\n\nElectrodes                                                  Switch on                                                                                  Follow-up \n                           Approach to           RW                 ERW                   C              Approach to            RW                  ERW                     C \n                          scala tympani                                                                            scala tympani               \nb1 electrode              RW                                          1.74                 2.68                    RW                                             2.17                   2.49 \n                                                                               (p=0.203)         (p=0.019)                                                               (p=0.013)          (p=0.004) \n                                  ERW                 \u22121.74                                       \u22120.94                  ERW                  \u22122.17                                           0.32 \n                                                       (p=0.203)                                 (p>0.999)                                     (p=0.013)                                    (p>0.999) \n                                    C                    \u22122.68               0.94                                              C                    \u22122.49               \u22120.32 \n                                                       (p=0.019)        (p>0.999)                                                             (p=0.004)          (p>0.999)                   \na2 electrode              RW                                          2.17                 2.49                    RW                                            \u22121.95                 \u22121.73 \n                                                                               (p=0.428)         (p>0.999)                                                              (p=0.003)           (p=0.012) \n                                  ERW                 \u22122.17                                        0.32                   ERW                   1.95                                            0.22 \n                                                       (p=0.428)                                 (p=0.253)                                     (p=0.003)                                    (p>0.999) \n                                    C                    \u22122.49              \u22120.32                                             C                      1.73                 \u22120.22  \n                                                       (p>0.999)        (p=0.253)                                                             (p=0.012)          (p>0.999)                   \n \nData expressed as mean difference (p values). p values derived from Tukey\u2019s HSD post hoc ANOVA test. RW, round window; ERW, extended round window; \nC, cochleostomy \n\n\n\nTable III: Comparison of impedance levels of the b1 and a2 cochlear implant electrodes between surgical approaches  \nfor implant insertion\n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 591\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n592                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\ncochlea may affect the electrical current flow and \nsubsequently affect the impedance levels of the electrodes.2,4  \nWith regards to electrode placement, our findings suggest \nthat the surgical approach to implant insertion had an effect \non impedance levels of the electrodes. In this study, we \nrecorded three surgical approaches: round window, extended \nround window, and cochleostomy. In brief, the round window \napproach is a standard method of surgery, performed by \ncreating a small opening in the bone of the round window \nniche, while cochleostomy is a conventional method that \ninvolves drilling a hole in the cochlear bone to insert the \nelectrode array.9 On the other hand, the extended round \nwindow approach is a combination of both round window \nand cochleostomy approaches and is usually performed in \nsituations where the round window is not easily visible \nand/or accessible.10 To date, limited research has been \nconducted to compare the effect of different surgical \napproaches on the impedance levels of cochlear implant \nelectrodes. A previous systematic review by Avasarala et al.11 \n\n\n\nfound that two out of three studies reported that there were \nno substantial differences on impedance levels between \nsurgical approaches, while one study found that round \nwindow approach yielded a lower initial impedance value.11 \n\n\n\nThe study found that significant differences in switch on \nimpedance were observed in the basal-middle electrodes and \nnot in the apical region12, which is consistent with our \nfindings. This may be explained by the fact that traditional \ncochleostomy, which involves drilling a bigger hole in the \ncochlear bone, may induce more extensive tissue damage, \nresulting in higher impedance.13,14 Previous studies foind that \nimpedance level has a correlation to the clinical outcome of \ncochlear implantation. Impedance level might indirectly \nshow the biological changes in the cochlea due to electrode \ninsertion. Changes such as bone formation or the distance \nbetween the electrode and the modiolus will affect the \nimpedance level at mapping. Decreased word score is \ncorrelated with an increased impedance level.15 Nonetheless, \nit should be noted that the outcome of cochlear implantation \n\n\n\nsurgeries is also affected by several factors such as clinical \ncharacteristics of the patients (e.g., age at implantation, \ncomorbidities, duration of implantation, and severity of \nhearing loss) and surgeon's experience and available \nresources. This suggests that further studies are needed to \nconfirm our findings. \n \nThe present study is limited due to its cross-sectional design, \nsuggesting that causalities between variables were unknown. \nFurthermore, other potential confounding factors, such as \nage at intervention and characteristics of patients\u2019 hearing \nloss were not recorded in this study. The fact that there was \nno patient with inner ear anomalies and only two patients \nwith obliterated scala tympani also limited our analysis. \nThese suggest that future studies should also consider these \npotential confounding factors when assessing the impedance \nlevels of cochlear implants over time. \n \n \nCONCLUSION \nThis study adds to the body of evidence supporting the \npremise that the electrical impedance of cochlear implant \nelectrodes may change over time, thereby highlighting the \nimportance of regular impedance assessments for cochlear \nimplant users to ensure the optimal function of the devices. \nIn this cohort, the impedance level of basal electrodes \ndecreased at one year post-implantation, while those of \napical electrodes increased. The present study also suggests \nthat the choice of surgical approach for implant insertion \nmay play a role in the impedance levels of the electrode \narrays. Further research should investigate the potential \ninterplay between surgical approach and other factors that \nmay impact impedance levels to confirm our findings. \n \n \nACKNOWLEDGEMENT \nNot applicable. \n \n\n\n\nFig. 1: Location of the basal (b1, b2) and apical (a1, a2) cochlear implant electrodes in the scala tympani.\n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 592\n\n\n\n\n\n\n\n\nImpedance changes in cochlear implant electrodes one year after switch on\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                593 \n\n\n\nREFERENCES \n1. Leone CA, Mosca F, Grassia R. Variazioni nel tempo \n\n\n\ndell\u2019impedenza degli elettrodi nelle diverse partizioni cocleari in \nadulti con impianto cocleare. Acta Otorhinolaryngologica Italica \n2017; 37(4): 312-9.  \n\n\n\n2. Saoji AA, Adkins WJ, Olund AP, Graham M, Patel NS, Neff BA, et \nal. Increase in cochlear implant electrode impedances with the \nuse of electrical stimulation. Int J Audiol 2020; 59(11): 881\u20138.  \n\n\n\n3. Asal SI, Sobhy OA, Massad ND. Study of telemetry changes over \ntime in children with a cochlear implant. Egypt J Otolaryngol \n2018; 34(3): 198-202.  \n\n\n\n4. Thompson NJ, Dillon MT, Buss E, Park LR, Pillsbury HC, \nO\u2019Connell BP, et al. Electrode array type and its impact on \nimpedance fluctuations and loss of residual hearing in cochlear \nimplantation. Otol Neurotol 2020; 41(2): 186-91.  \n\n\n\n5. von Elm E, Altman DG, Egger M, Pocock SJ, G\u00f8tzsche PC, \nVandenbroucke JP. The Strengthening the Reporting of \nObservational Studies in Epidemiology (STROBE) statement: \nguidelines for reporting observational studies. Lancet 2007; \n370(9596): 1453-7.  \n\n\n\n6. Wissel K, Brandes G, P\u00fctz N, Angrisani GL, Thieleke J, Lenarz T, \net al. Platinum corrosion products from electrode contacts of \nhuman cochlear implants induce cell death in cell culture \nmodels. PLoS One 2018; 13(5): 1-20.  \n\n\n\n7. Hu HC, Chen JKC, Tsai CM, Chen HY, Tung TH, Li LPH. Evolution \nof impedance field telemetry after one day of activation in \ncochlear implant recipients. PLoS One 2017; 12(3): e0173367.  \n\n\n\n8. Wei JJF, Tung TH, Li LPH. Evolution of impedance values in \ncochlear implant patients after early switch-on. PLoS One 2021; \n16(2): e0246545 \n\n\n\n9. Jiam NT, Jiradejvong P, Pearl MS, Limb CJ. The effect of round \nwindow vs cochleostomy surgical approaches on cochlear \nimplant electrode position: a flat-panel computed tomography \nstudy. JAMA Otolaryngol Head Neck Surg 2016; 142(9): 873\u201380.  \n\n\n\n10. Friedland DR, Runge-Samuelson C. Soft cochlear implantation: \nrationale for the surgical approach. Trends Amplif 2009; 13(2): \n124.  \n\n\n\n11. Avasarala VS, Jinka SK, Jeyakumar A. Complications of \ncochleostomy versus round window surgical approaches: a \nsystematic review and meta-analysis. Cureus. 2022; 14(5): \ne25451. \n\n\n\n12. Liu X, Xie L, Wang Y, Yang B. Lower initial electrode impedances \nin minimally invasive cochlear implantation. Acta Otolaryngol \n2019; 139(5): 389-95.  \n\n\n\n13. Jia H, Venail F, Piron JP, Batrel C, Pelliccia P, Artier\u0300es F, et al. \nEffect of surgical technique on electrode impedance after \ncochlear implantation. Ann Otol Rhinol Laryngol 2011; 120(8): \n529-34.  \n\n\n\n14. Burghard A, Lenarz T, Kral A, Paasche G. Insertion site and \nsealing technique affect residual hearing and tissue formation \nafter cochlear implantation. Hear Res 2014; 312: 21-7.  \n\n\n\n15. Caswell-Midwinter B, Doney EM, Arjmandi MK, Jahn KN, \nHerrmann BS, Arenberg JG. The relationship between \nimpedance, programming and word recognition in a large \nclinical dataset of cochlear implant recipients. Trends Hear 2022; \n26: 23312165211060983.\n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 593\n\n\n\n\n\n\n\n\n594                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Intravenous thrombolysis (IVT) with \nrecombinant tissue plasminogen activator is beneficial in \nacute ischaemic stroke (AIS). We aim to compare the real-\nworld clinical outcomes and service efficiency of IVT in \nMalaysian primary stroke centres (PSCs) versus acute \nstroke ready hospitals (ASRHs). \n \nMaterials and Methods: We conducted a multi-centre cohort \nstudy involving 5 PSCs and 7 ASRHs in Malaysia. Through \nreview of medical records of AIS patients who received IVT \nfrom 01 January 2014 to 30 June 2021, real-world data was \nextracted for analysis. Univariate and multivariate \nregression models were employed to evaluate the role of \nPSCs versus ASRHs in post-IVT outcomes and \ncomplications. Statistical significance was set at p<0.05.  \n \nResults: A total of 313 multi-ethnic Asians, namely 231 from \nPSCs and 82 from ASRHs, were included. Both groups were \ncomparable in baseline demographic, clinical, and stroke \ncharacteristics. The efficiency of IVT delivery (door-to-\nneedle time), functional outcomes (mRS at 3 months post-\nIVT), and rates of adverse events (intracranial haemorrhages \nand mortality) following IVT were comparable between the 2 \ngroups. Notably, 46.8% and 48.8% of patients in PSCs and \nASRHs group respectively (p=0.752) achieved favourable \nfunctional outcome (mRS\u22641 at 3 months post-IVT). \nRegression analyses demonstrated that post-IVT functional \noutcomes and adverse events were independent of the role \nof PSCs or ASRHs. \n \nConclusion: Our study provides real-world evidence which \nsuggests that IVT can be equally safe, effective, and \nefficiently delivered in ASRHs. This may encourage the \nestablishment of more ASRHs to extend the benefits of IVT \nto a greater proportion of stroke populations and enhance \nthe regional stroke care. \n\n\n\nKEYWORDS:  \nAcute ischemic stroke, thrombolysis, stroke ready hospitals, \nfunctional outcomes, efficiency, safety \n \n \nINTRODUCTION \nIntravenous thrombolysis (IVT) with recombinant tissue \nplasminogen activator (rt-PA) has been a well-established \nemergency intervention in acute ischaemic stroke (AIS) since \n1995.1-9 However, such therapy may not be readily available \nin district/community hospitals, especially in countries with \nlower neurologist: population ratio. We hypothesise that as \n(i) the efficacy of IV rt-PA has been extensively proven,1-7 (ii) \ncoupled with the presence of objective, internationally \nstandardised indications and contraindications of IV rt-PA in \nAIS,1-2,9 (iii) in addition to the availability of local evidence-\nbased protocol and (iv) the growing use of telemedicine to \nguide decision-making, IVT can potentially be administered \nin these district/community hospitals without neurologist in \na timely, safe and effective manner. \n \nAccordingly, evidence has consistently shown the beneficial \neffects of IVT in AIS even when administered by non-\nneurologists in non-stroke centres.10-12 However, similar \ntargeted research involving multi-ethnic Asian populations \nin this region is scarce. We aim to appraise and compare the \nreal-world efficiency, effectiveness and safety of IVT among \nmulti-ethnic Asians in Malaysian public primary stroke \ncentres (PSCs) versus acute stroke-ready hospitals (ASRHs). \n \n \nMATERIALS AND METHODS \nWe conducted a multi-centre cohort study (combination of \nhistorical, retrospective and prospective cohort) involving \nanalyses of real-world data. This real-world study involved \nfive public PSCs and seven public ASRHs in Malaysia. \nQualifying criteria of PSCs and ASRHs were in accordance \n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute \nischaemia stroke in Malaysian public primary stroke centres \nversus acute stroke ready hospitals: Comparison of real-\nworld clinical outcomes \n \nSchee Jie Ping1,2, Ang Chai Liang1, Crystal Teoh Sing Chiek3, Tan Hui Jieh4, Chew Sin Hong5, Anderson Steven3, \nHii Ding Wei3, Chin Yen Theng6, Loh Ee Wen7, Desmond Samuel8, Pravind Narayanan9, Mazlina Husin6, Linda \nThen Yee Yen3, Cheah Chun Fai4, Cheah Wee Kooi10, Zainura Che Isa11, Aznita Ibrahim11, Chia Yuen Kang5, \nKhairul Azmi Ibrahim6, Looi Irene12, Law Wan Chung3, Zariah Abdul Aziz6 \n\n\n\n     \n1Department of Medicine, Tawau Hospital, Sabah, Malaysia, 2Division of Neurology, Department of Medicine, Faculty of \nMedicine, University of Malaya, Malaysia, 3Department of Medicine, Sarawak General Hospital, Sarawak, Malaysia, \n4Department of Medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia, 5Department of Medicine, Queen Elizabeth \nHospital, Sabah, Malaysia, 6Department of Medicine, Sultanah Nur Zahirah Hospital, Terengganu, Malaysia, 7Department of \nMedicine, Bintulu Hospital, Sarawak, Malaysia, 8Department of Medicine, Miri Hospital, Sarawak, Malaysia, 9Department of \nMedicine, Sarikei Hospital, Sarawak, Malaysia, 10Department of Medicine, Taiping Hospital, Perak, Malaysia, 11Department of \nMedicine, Sultan Abdul Halim Hospital, Kedah, Malaysia, 12Department of Medicine, Seberang Jaya Hospital, Penang, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 05 July 2023                                                                                                                                                                              \nCorresponding Author: Crystal Teoh Sing Chiek                                                                                                                                                                  \nEmail: crystalteoh13@gmail.com\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 594\n\n\n\n\n\n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                595 \n\n\n\nwith the American Stroke Association & The Joint \nCommission Stroke Certification criteria. The five PSCs were \nSarawak General Hospital, Queen Elizabeth Hospital, \nSultanah Nur Zahirah Hospital, Seberang Jaya Hospital and \nRaja Permaisuri Bainun Hospital. Meanwhile, the seven \nASRHs were Tawau Hospital, Taiping Hospital, Bintulu \nHospital, Miri Hospital, Sarikei Hospital, Sultan Abdul Halim \nHospital and Lahad Datu Hospital. Clinical data were \ncollected through a review of medical records and extracted \nfrom the local stroke registry. \n \nThe data collection period was from December 2019 to \nDecember 2021. All patients who received IVT from 1 January \n2016 to 31 December 2021 in these 12 study centres were \npotential subjects. These patients were being followed up for \nfunctional outcomes in Modified Rankin Scale (mRS) and \nmortality status. Assessments findings were documented \ncontemporaneously in their medical records and stroke \nregistries. This study was a combination of historical, \nretrospective and prospective cohort study as we included \npatients who (i) received IVT and had at least 3 months of \nfollow-up post-IVT at the beginning of data collection period \n(historical cohort); (ii) received IVT and were still under \nongoing follow-up at the beginning of data collection period \n(retrospective cohort); (iii) received IVT within the data \ncollection period, followed by the standard follow-up for at \nleast 3 months (prospective cohort). \n \nThe first author (S.J.P.), who is also the principal and \ncoordinating investigator of the study, had full access to the \ndata. The authors vouch for the accuracy and completeness \nof data, in addition to strict adherence to study protocol and \nstatistical analysis. \n \nStudy Populations/Patients \nOur inclusion criteria were patients (i) with clinical diagnosis \nof AIS according to WHO criteria13, (ii) age of \u226518 years at the \ntime of receiving IVT, (iii) received IVT within 4.5 hours from \nAIS onset, at a dose of 0.9 mg/kg and maximum 90 mg, (iv) \n\u22653 months of follow-up after IVT. Patients who died within 3 \nmonths post-IVT were included in the analyses on mortality \noutcome. Exclusion criteria were patients (i) aged <18 years \nat the time of receiving IVT, (ii) received IVT in an extended \nwindow, i.e., >4.5 hours after AIS onset, (iii) received other \nreperfusion therapies (e.g. intra-arterial thrombolysis,  \nmechanical/endovascular thrombectomy) within 90 days \npost-IVT, (iv) no data on door-to-needle time (DNT), \nintracranial haemorrhages following IVT, mRS at 3 months \npost-IVT and   mortality up to 3 months post-IVT.  \nAnonymized real-world data were collected through a review \nof medical records and local stroke registry. Informed consent \nwas obtained from all study subjects, approving the use of \ntheir anonymised data in analyses and publication of \nfindings. \n \nClinical Assessments and Outcome Measures \nSubtypes of AIS among study patients were grouped \naccording to the TOAST classification.14 These five subtypes \nwere (i) large artery atherosclerosis, (ii) small vessel occlusion, \n(iii) cardioembolism, (iv) other determined aetiologies and (v) \nundetermined aetiologies.  Stroke severity upon presentation, \nmeasured by National Institutes of Health Stroke Scale \n(NIHSS), was assessed by neurologists in PSCs and trained \n\n\n\nphysicians in ASRHs, respectively. The Alberta Stroke \nProgram Early CT Score (ASPECTS) were evaluated and \nreported by radiologists.15,16 \n \nThe onset-to-needle time (ONT) was defined as the duration \nfrom the onset of AIS symptoms to the time of IVT \nadministration. The DNT was defined as the duration from \nthe time of patient\u2019s arrival at emergency department to the \ntime of first bolus dose of thrombolytic. mRS was employed to \nmeasure the degree of disability. Intracranial haemorrhages \n(ICH) following IVT, namely   (i)   any ICH, (ii) symptomatic \nICH (sICH) as per ECASS III definition2 and (iii) fatal ICH were \nrecorded. Mortality following IVT, namely (i) inpatient \nmortality, i.e., mortality within the same/index hospital \nadmission and (ii) all-cause mortality within 3 months (90 \ndays) post-IVT, were recorded. \n \nAIS characteristics and severity upon presentation were \nevaluated by using TOAST subtypes, NIHSS and ASPECTS \nscore. The efficiency of IVT delivery was evaluated through \nDNT and proportion of patients with DNT <60 minutes. The \neffectiveness of IVT was assessed through mRS at 3 months \n(90 \u00b1 5 days), number of patients with favourable functional \noutcomes (mRS \u22641 at 3 months) and unfavourable functional \noutcomes (mRS \u2265 2 at 3 months). Meanwhile, safety of IVT \nwas assessed by rates of any ICH, sICH, fatal ICH, inpatient \nmortality and 90 days all-cause mortality. \n \nStatistical Analysis \nStatistical Package of Social Sciences (SPSS) for Windows \nversion 28.0 (IBM Corporation, Armonk, NY, USA) was \nemployed. Baseline demographic and clinical characteristics \nwere presented as absolute numbers and percentage for \ncategorical variables, mean and standard deviation (SD) for \nnormally distributed continuous variables, and median and \ninterquartile ranges for continuous variables with skewed \ndistribution or ordinal data. Shapiro\u2013Wilk test was used to \nassess the normality of data distribution. \n \nUpon comparing the variables between two groups (PSCs \nversus ASRHs), the independent sample t test and Mann\u2013\nWhitney U test were used for the analyses of continuous \nvariables, while Pearson\u2019s chi-square and Fisher\u2019s exact test \nwere used for the analyses of categorical variables.   A two-\nsided P value of <0.05 was considered statistically significant. \nUnivariable and multivariable logistic regression analyses \nwere conducted to investigate the association between \nvarious outcomes of interest and independent variables. All \nvariables with p value of <0.1 in the univariable analyses \nwere included in the final multivariable analyses. The results \nwere presented in the form of crude odds ratios (OR) and \nadjusted OR with the respective 95% confidence interval (CI). \nP value of <0.05 signifies statistical significance. \n \nStandard Protocol Approvals and Study Registrations \nThis study was registered with the Malaysian National \nMedical Research Register (study ID: NMRR-19-3731-52272). \nStudy protocol was approved and supported by the National \nInstitutes of Health Malaysia. Ethical approval was obtained \nfrom the Malaysian Medical Research and Ethics Committee. \nApproval for publication was granted by the Director-\nGeneral of Health Malaysia. \n \n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 595\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n596                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nThis study followed the Strengthening the Reporting of \nObservational Studies in Epidemiology (STROBE) reporting \nguideline. This study was conducted in strict compliance with \nethical principles outlined in the Declaration of Helsinki and \nMalaysian Good Clinical Practice Guideline. Strictly no minor \nnor vulnerable subjects were enrolled in the study. Only \nanonymised, non-identifying data were extracted/collected. \n \n \nRESULTS \nA total of 313 multi-ethnic Asian patients, namely 231 \n(73.8%) from PSCs and 82 (26.2%) from ASRHs were \nincluded. The baseline demographic (age, gender, ethnicity) \nand clinical characteristics (comorbidities/vascular risk \nfactors) of these two groups of patients were comparable, with \nthe exception of the proportions of active smokers. Rates of \nprior antiplatelet and/or anticoagulant use within 7 days \nprior to stroke onset were similar in both PSCs and ASRHs \ngroups (29.0% vs 29.3%) as well. Types of antiplatelets and \nanticoagulants used were listed in Table I. \n \nStroke Characteristics and Severity at Presentation \nThese two groups of patients demonstrated similar \nproportions in each TOAST subtype. Both groups recorded \ncomparable NIHSS upon presentation, namely a median \nNIHSS of 11 (IQR: 8\u201317) in PSCs and a median NIHSS of 12 \n(IQR: 9\u201316) in ASRHs (p = 0.833).  Both groups also have \ncomparable ASPECTS, with a median ASPECTS of 9 (IQR: 8\u2013\n10) in both PSCs and ASRHs (p = 0.879) groups (Table I). \n \nEfficiency of Delivery of IVT \nBoth groups recorded similar ONT. Notably, the DNT was \ncomparable between the two groups as well, namely a \nmedian of 85 (IQR: 56\u2013118) minutes in PSCs and a median of \n93 (IQR: 60\u2013125) minutes in ASRHs, p = 0.470. In addition, \nthe proportion of patients with DNT <60 minutes was similar, \nnamely 30.7% in PSCs and 30.5% in ASRHs, p = 0.967 (Table \nII). \n                                                                                                    \nClinical Outcomes Following IVT  \nmRS at 3 months was identical between the two groups, with \na median of 2 (IQR: 1\u20134) in PSCs and  2 (IQR: 1\u20133) in ASRHs, \np = 0.707. Percentage of patients with favourable functional \noutcomes, i.e., mRS \u2264 1 at 3 months post-IVT, was \ncomparative as well, namely 46.8% in PSCs and 48.8% in \nASRHs, p = 0.752 (Table II and Figure 1 mRS bar chart). \n \nHaemorrhages and Mortality following IVT \nBoth PSCs and ASRHs groups demonstrated similar rates of (i)   \nany ICH, 17.7% vs 18.3%, p = 0.912; (ii) symptomatic ICH, \n10.4% vs 7.3%, p = 0.417; (iii) fatal ICH, 3.9% vs 4.9%, p = \n0.749, (iv) inpatient mortality, 13.9% vs 11.0%, p = 0.507 and \n(v) all-cause mortality within 90 days post-IVT, 15.2% vs \n14.6%, p = 0.910. Causes of death were listed in Table II. The \nmost common causes of death in both groups were fatal ICH, \npneumonia and acute coronary syndrome (Table II). \n \nSubgroups Analyses \nAmong the 313 study patients, 148 patients (47.3%) had \nfavourable functional outcomes (mRS \u22641) whereas 165 \npatients (52.7%) had unfavourable functional outcomes \n(mRS \u22652) at 3 months post-IVT. Patients with favourable \n\n\n\nfunctional outcomes demonstrated significantly (i) younger \nage, (ii) lower NIHSS at presentation, (iii) higher ASPECTS at \npresentation, (iv) shorter DNT, (v) greater proportion with \nDNT <60 minutes and (vi) lower rates of ICH. These two \ngroups of patients are comparable in terms of gender, \nethnicity, comorbidities/vascular risk factors, and TOAST \nsubtype (Table III). \n \nUnivariable and Multivariable Logistic Regression \nAnalyses \nAmong the overall cohort of 313 patients, factors that were \nsignificantly associated with favourable functional outcomes \n(Table IV) include (i) younger age, (ii) lower NIHSS at \npresentation, shorter DNT and (iv) absence of sICH. Notably, \nfunctional outcomes were independent of the role of PSCs or \nASRHs, gender, ethnicity and comorbidities/vascular risk \nfactors. \n \nFactors significantly associated with any type of post-IVT ICH \namong the overall cohort of 313 patients (refer \nSupplementary Table I) included (i) older age and (ii) higher \nNIHSS at presentation. Meanwhile, factors significantly \nassociated with sICH (refer Supplementary Table II) included \n(i) lower ASPECTS at presentation and (ii) longer DNT. The \nrole of PSCs versus ASRHs, age, gender, ethnicity, \ncomorbidities/vascular risk factors, NIHSS at presentation \nand antiplatelet or anticoagulant use were not significantly \nassociated with ICH.  \n \nIn addition, factors significantly associated with 90-day all-\ncause mortality among the overall cohort of 313 patients \n(refer Supplementary Table III) included (i) longer DNT and \n(ii) presence of sICH, regardless of the role of PSCs vs ASRHs, \nage, gender, ethnicity, comorbidities/vascular risk factors, \nNIHSS and ASPECTS at presentation. \n \nIn the PSC cohort, (i) factors significantly associated with \nfavourable functional outcomes (refer Supplementary Table \nIV) included lower NIHSS at presentation, shorter DNT and \nabsence of sICH;  (ii) factors significantly associated with any \ntype of post-IVT ICH (refer Supplementary Table V) included \nlower ASPECTS at presentation and longer DNT; (iv) factors \nsignificantly associated with post-IVT sICH (refer \nSupplementary Table VI) included female gender, lower \nASPECTS at presentation, and longer DNT and (v) factor \nsignificantly associated with overall 90-day all-cause \nmortality (refer Supplementary Table VII) included older age \nand longer DNT. \n \nIn the ASRH cohort, (i) factors significantly associated with \nfavourable functional outcomes (refer Supplementary Table \nVIII) included younger age and lower NIHSS at presentation \nand (ii) factors significantly correlated with overall 90-day \nall-cause mortality (refer Supplementary Table IX) was lower \nASPECTS at presentation.  \n \nDNT \u226460 Minutes Versus DNT >60 Minutes \nAlmost equal proportion of patients, namely 30.7% in PSCs \nand 30.5% in ASRHs, recorded DNT \u226460 minutes. Among the \noverall cohort of 313 study patients, 96 (30.7%) recorded DNT \n\u226460 minutes while 217 (69.3%) recorded DNT >60 minutes. \nSubsequently, 59 (61.5%) of the 96 patients with DNT \u226460 \n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 596\n\n\n\n\n\n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                597 \n\n\n\nminutes recorded favourable functional outcomes while only \n89 (41.0%) of the 217 patients with DNT >60 minutes \nrecorded favourable functional outcomes at 3 months, p = \n0.001. At 3 months, patients with DNT \u226460 minutes recorded \nmedian mRS of 1 (IQR: 0\u20132) while patients with DNT >60 \nminutes recorded median mRS of 2 (IQR: 1\u20134), p < 0.001. \n \n \nDISCUSSION \nComparison of the efficiency, effectiveness and safety of IVT \nadministration in public primary versus acute stroke-ready \nhospitals were reflected in this real-world study through \nperformance metrics in DNT, functional outcomes by mRS, \nmortality and rates of intracerebral haemorrhages. Our \npatients in both public PSC and ASRH cohorts demonstrated \nsimilar demographics and baseline clinical characteristics, \nstroke subtypes as defined by TOAST classifications and \nstroke severity upon presentation in terms of NIHSS and \nASPECTS. Comparable efficiency (DNT), effectiveness \n(functional outcomes) and safety (ICH and mortality rates) \nprofiles of IVT were recorded in both groups. This may imply \nthat IVT service can be equally safe, effective and efficiently \ndelivered in ASRHs.  \n \nAs of date, there were only 138 registered neurologists in \nMalaysia (both public and private sectors), which translates \n\n\n\nto 1 neurologist to almost 250,000 populations. Thus, there \nare critical shortage of neurologists to support the IVT service \nnationwide, especially in East Malaysia. Majority of the rural \nand remote hospitals are not equipped with in-house \nneurologists. Hence, there was an increasing need to establish \nASRH to extend the benefits of IVT to a greater proportion of \nstroke patients. In Malaysia, physicians (specialists in \nInternal Medicine) have taken the initiative to initiate IVT \nservice in some of these centres, guided by telemedicine \nconsultation with neurologists. These physicians are tasked to \ndraft acute stroke protocols and workflows while ensuring \nstrict adherence to the protocol in daily practice. \n \nChallenges and limitations in Malaysian ASRHs include (i) \nlack of certified expertise namely in-house neurologists; (ii) \nlack of stroke centres and regional stroke networks in close \nproximity; (iii) logistic constraints which limit inter-hospital \ntransfer; (iv) lack of established telestroke network or \nteleradiography system; (v) limited healthcare facilities and \n(vi) lack of advanced neuroimaging. \n \nThe results of our study may proactively advocate the \nestablishment of more ASRHs despite the current challenges \nand limitations. A few collaborative efforts and initiatives are \nneeded, which includes (i) establishing structured training \nand certification programme to equip physicians in offering \n\n\n\nPatient\u2019s characteristics                                                        PSCs (n = 231)                         ASRHs (n = 82)                          P value \nAge (mean \u00b1 S.D.)                                                                       57.4 \u00b1 13.1                                56.4 \u00b1 12.6                               0.540I \nGender (male:female)                                                                    150:81                                        54:28                                   0.881II \n\n\n\n                                                                                            64.9%:35.1%                            65.9%:34.1%                                   \nEthnicity (Malay:Chinese:Indian:Others)                                  129:31:14:57                               41:14:8:19                               0.537II \n\n\n\n                                                                                  55.8%:13.4%:6.1%:24.7%       50.0%:17.1%:9.8%:23.2%                        \nDiabetes mellitus                                                                     80/231 (34.6%)                          28/82 (34.1%)                            0.937II \nHypertension                                                                          152/231 (65.8%)                         58/82 (70.7%)                            0.414II \nDyslipidemia                                                                            63/231 (27.3%)                          29/82 (35.4%)                            0.167II \nCoronary artery disease                                                          46/231 (19.9%)                          15/82 (18.3%)                            0.750II \nAtrial fibrillation/flutter                                                          39/231 (16.9%)                          13/82 (15.9%)                            0.830II \nValvular heart diseases                                                             5/231 (2.2%)                              1/82 (1.2%)                              1.000III \nHistory of previous CVA/TIA                                                   33/231 (14.3%)                          12/82 (14.6%)                            0.938II \nSmoking (active smokers)                                                       87/231 (37.7%)                          43/82 (52.4%)                            0.020II \nPrior antiplatelet/anticoagulant use                                      67/231 (29.0%)                          24/82 (29.3%)                            0.964II \n\n\n\nI.   Aspirin                                                                                  52/67                                         18/24 \nII.  Clopidogrel                                                                            3/67                                           1/24                                          \nIII. Warfarin                                                                                7/67                                           4/24 \nIV. NOACs                                                                                   2/67                                           1/24 \nV.  Aspirin + clopidogrel                                                            2/67                                           0/24 \nVI. Aspirin + warfarin                                                                1/67                                           0/24                                          \n\n\n\nStroke characteristics \nSubtype (TOAST classification) \n\n\n\nI.   Large artery atherosclerosis                                       102/231 (44.2%)                         35/82 (42.7%) \nII.  Small vessel occlusion                                                  68/231 (29.4%)                          24/82 (29.3%)                              N/A \nIII. Cardioembolism                                                           40/231 (17.3%)                          17/82 (20.7%) \nIV. Other determined aetiologies                                      2/231 (0.9%)                                0/82 (0%) \nV. Undetermined aetiology                                               19/231 (8.2%)                             6/82 (7.3%)                                    \n\n\n\nMedian NIHSS at presentation                                                    11 (8-17)                                    12 (9-16)                                0.833IV \nMedian ASPECTS at presentation                                                 9 (8-10)                                      9 (8-10)                                 0.879IV \n \nI. Independent sample t test \nII. Pearson\u2019s chi square \nIII. Fisher\u2019s exact test \nIV. Mann\u2013Whitney U test \n \nOthers = natives/indigenous populations of Southeast Asia.  \nASRH, acute stroke-ready hospital; CVA, TIA, \n\n\n\nTable I: Baseline Demographic, Clinical and Stroke Characteristics\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 597\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n598                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nEfficiency of IVT delivery                                                       PSCs (n = 231)                         ASRHs (n = 82)                          P value \nMedian onset-to-needle time (minutes)                                 190 (155\u2013225)                           185 (139\u2013226)                            0.276IV \nMedian door-to-needle time (minutes)                                    85 (56\u2013118)                               93 (60\u2013125)                              0.470IV \nDoor-to-needle time <60 minutes                                         71/231 (30.7%)                          25/82 (30.5%)                            0.967II \nPost-IVT clinical outcomes                                                                                                                                                                \nMedian 3 months mRS                                                                   2 (1\u20134)                                       2 (1\u20133)                                  0.707IV \nFavourable functional outcomes                                                  108/231                                       40/82                                   0.752II \n(3 months mRS \u22641)                                                                        (46.8%)                                     (48.8%)                                       \nPoor functional outcomes                                                             40/231                                        14/82                                   0.960II \n(3 months mRS \u22655)                                                                        (17.3%)                                     (17.1%)                                       \nHaemorrhages and mortality                                                                                                                                                             \nAny intra-cranial haemorrhages (ICH)                                          41/231                                        15/82                                   0.912II \n(including haemorrhagic transformation)                                   (17.7%)                                     (18.3%)                                       \nSymptomatic ICH (ECASS III definition)                                        24/231                                         6/82                                    0.417II \n\n\n\n                                                                                                 (10.4%)                                      (7.3%)                                        \nFatal ICH                                                                                           9/231                                          4/82                                    0.749III \n\n\n\n                                                                                                  (3.9%)                                       (4.9%)                                        \nInpatient mortality                                                                         32/231                                         9/82                                    0.507II \n\n\n\n                                                                                                 (13.9%)                                     (11.0%) \nI.   Fatal ICH                                                                                9/32                                            4/9 \nII.  Pneumonia                                                                            9/32                                            3/9                                           \nIII. ACS and cardiac failure                                                        7/32                                            1/9 \nIV. Severe stroke/massive infarct                                               4/32                                            1/9 \nV.  Other stroke-related complications                                    3/32                                            0/9 \n\n\n\n90 days all-cause mortality                                                            35/231                                        12/82                                   0.910II \n                                                                                                 (15.2%)                                     (14.6%) \nI.    Fatal ICH                                                                               9/35                                           4/12 \nII.   Pneumonia                                                                          10/35                                          4/12 \nIII.  ACS and cardiac failure                                                       9/35                                           3/12 \nIV.  Severe stroke/massive infarct                                             4/35                                           1/12 \nV.  Other stroke-related complications                                    3/35                                           0/12                                          \n\n\n\n \nV. Independent sample t test \nVI. Pearson\u2019s chi square \nVII. Fisher\u2019s exact test \nVIII. Mann\u2013Whitney U test \nASRH, acute stroke-ready hospital; IVT, intravenous thrombolysis; mRS, Modified Rankin Scale; PSC, primary stroke centres. \n\n\n\nTable II: Efficiency of IVT delivery,Post-IVT clinical outcomes, Incidence of haemorrhages and mortality \n\n\n\nIVT, (ii) establishing and enhancing telestroke networks and \nteleradiography system, hence allowing more neurologists \nand radiologists to remotely support IVT service, (iii) \nimproving inter-hospital patient transfer system and (iv) \nincreasing availability of CT machine in rural/remote areas. \nThe national clinical practice guidelines on stroke \nmanagement is an essential tool to supplement these efforts \nas well. \n \nEssentially, there are multiple unmet needs in the provision \nof IVT in resource-limited settings, namely number of trained \nprofessionals, supporting staffs, facilities and information \ntechnology (IT) services. However, there are certain measures \nwhich can be carried out in the short run, for example, by \nincreasing the number of training platforms/resources \nonline, stroke simulation training or hands-on workshop \norganised by tertiary stroke centres to address the knowledge \ngap. Meanwhile, with regards to longer term planning, an \nincrease in budget allocation to procure basic equipments, \nsuch as scan machine, beds, blood pressure/cardiac \nmonitoring devices should be prioritised. \n \nFindings of our regression analyses highlight the importance \nof shortening DNT as it is a modifiable factor significantly \nassociated with favourable functional outcomes. Longer DNT \nis significantly associated with poorer functional outcomes, \nsICH and overall 90-day all-cause mortality. Results \npresented in \u201cSubgroups Analyses\u201d and \u201cDNT \u226460 Minutes \n\n\n\nVersus DNT >60 Minutes\u201d further supplement such findings. \nAlmost 70% of study patients recorded DNT >60 minutes in \nboth PSCs and ASRHs. Comprehensive data on door-to-CT \ntime and CT-to-needle time was not consistently available \nacross all centres. Hence it is not feasible to determine \nwhether our long DNT was caused by either or both \ncomponents. However, the causes of our long DNT in general \nmay include (i) delay in decision making and offering \nconsent by patients and/or family (ii) delay in organising \nneuroimaging due to limited infrastructure and (iii) stroke \ncode workflow unfamiliarity among healthcare personnel. \n \nWe hereby propose measures which can be undertaken to \nshorten DNT: (i) increase public awareness regarding the \navailability and benefits of IVT in acute stroke through \nwidespread campaign and education nationwide. (ii) equip \nhigh-volume public centres with more CT machines to \naccommodate the increasing patient\u2019s loads locally. (iii) \nminimise delay between steps during stroke code activation \nby introducing better-structured training and refresher course \nfor stroke care personnel nationwide, (iv) conduct regular \nquality improvement projects and clinical audits to improve \nperformance and consequentially quality of care and (v) \nestablish telestroke networks involving dedicated neurologists \nand neuroradiologists in respective states nationwide. This \nmay assist physicians in swift decision-making on IVT with \ngreater confidence, especially in ASRHs. \n \n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 598\n\n\n\n\n\n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                599 \n\n\n\nThe strengths of this study include (i) inclusion of 12 public \ncentres nationwide, namely both East Malaysia and \nPeninsular Malaysia; (ii) inclusion of multi-ethnic Asian \npatients and (iii) inclusion of all consecutive patients who \nreceived IVT in all PSCs and ASRHs in Malaysia. Furthermore, \nprospective local stroke registries at study centres offer \nreliable real-world data. Despite not performing propensity \nscore matching, there were no statistically significant \ndifferences in demographic, clinical and stroke characteristics \nupon comparing patients in both PSC and ASRH cohorts. In \naddition, univariable and multivariable logistic regression \nanalyses with appropriate adjustments were performed to \nassess the role of ethnicity and types of centres (i.e. PSCs vs \nASRHs) in clinical outcomes while identifying factors \nassociated with various outcomes of interest.  \n \nLimitations of this study include (i) the observational nature \nof study; however, this real-world study still offers valuable \ninsights on the benefits of IVT in both PSCs and ASRHs,  (ii) \nlack of comprehensive data on extra-cranial haemorrhages \nin some study centres; however, there was no significant \nmorbidity or mortality resulted from extra-cranial \nhaemorrhages among all study patients and (iii) lack of \ndetailed data on door-to-CT and CT-to-needle time, however, \ndefinite DNT was clearly documented and (iv) lack of detailed \nstandardised blood pressure recording in some patients as the \ntimings of blood pressure measurements were varied (any \n\n\n\npoint from upon arrival to Emergency Department to \nimmediately prior to Alteplase bolus); however, it has been a \nnationwide standard practice (as per national clinical \npractice guidelines) that blood pressure must be <185/110 \nmmHg prior to IVT initiation.  \n                                                                                                   \nGiven the inherent bias in an observational study, statistical \nadjustment techniques, i.e. logistic regression, have been \nemployed to produce unbiased estimates of effects. Moreover, \nthe findings from this study were replicated in other studies \ninternationally.10-12 Additional evidence to bolster the \npotential causal association with longer DNT would be an \nunderstanding of the Malaysia\u2019s healthcare landscape by the \nauthors and inputs/reviews from the local stroke experts. \n \nEvidence on the provision of IVT by non-neurologists is not \nexpansive so far, especially in resource-limited regions (low-\nmiddle income countries) where the neurologist:population \nratio is low and substantial proportions of acute stroke \npatients receive emergency care by non-neurologists. This \nproject, with strengths and limitations as stated,  is still \namong the largest real-world study providing real-world \nevidence which may suggest comparable IVT safety, \neffectiveness and service efficiency when administered by \nnon-neurologists in ASRHs as compared to administration by \nneurologists in PSCs, in a resource-limited setting. \n \n\n\n\nOverall (n = 313) \nModified Rankin Scale (mRS)                                                      mRS \u22641                                     mRS \u22652                               p values \nN (%)                                                                                       148/313 (47.3%)                       165/313 (52.7%)                               - \nMean age \u00b1 SD (years)                                                               53.6 \u00b1 12.3                                60.3 \u00b1 12.8                              <0.001 \nGender (Male:Female)                                                                     90:58                                        114:51                                   0.125  \n\n\n\n                                                                                               61%:39%                                  69%:31%                                      \nEthnicity                                                                                       73:24:8:43                                97:21:14:33                               0.131 \n(Malay:Chinese:Indian:Others)                                            49%:16%:6%:29%                   59%:13%:8%:20%                              \nDM                                                                                             50/148 (34%)                            58/165 (35%)                             0.799 \nHypertension                                                                             96/148 (65%)                           114/165 (69%)                            0.427 \nDyslipidaemia                                                                            45/148 (30%)                            47/165 (28%)                             0.710 \nCAD                                                                                            26/148 (18%)                            35/165 (21%)                             0.416 \nAF                                                                                             23/148 (16%)                            29/165 (18%)                             0.629 \nValvular CD                                                                                 5/148 (3%)                                1/165 (1%)                               0.074 \nHx of TIA/CVA                                                                           26/148 (18%)                            19/165 (12%)                             0.128 \nActive smoking                                                                         64/148 (43%)                            66/165 (40%)                             0.561 \nPrior antiplatelet/anticoagulant use                                       47/148 (32%)                            44/165 (27%)                             0.322 \nTOAST subtypes \n\n\n\nI.   Large artery atherosclerosis                                        47/148 (31.8%)                         90/165 (54.5%) \nII.  Small vessel occlusion                                                  62/148 (41.9%)                         30/165 (18.2%)                                 \nIII. Cardioembolism                                                           24/148 (16.2%)                         33/165 (20.0%) \nIV. Other determined aetiology                                        1/148 (0.7%)                             1/165 (0.6%) \nV. Undetermined aetiology                                               14/148 (9.4%)                           11/165 (6.7%)                                  \n\n\n\nMedian NIHSS (at presentation)                                                  10 (7\u201313)                                  13 (10\u201320)                               <0.001 \nMedian ASPECTS (at presentation)                                              9 (8\u201310)                                     9 (8\u20139.5)                                <0.001 \nMedian onset-to-needle time (minutes)                                 190 (160\u2013225)                           190 (150\u2013230)                             0.986 \nMedian door-to-needle time (minutes)                                  75 (50\u2013104.5)                              98 (65\u2013132)                              <0.001 \nDNT <60 minutes                                                                     59/148 (39.9%)                         37/165 (22.4%)                            0.001 \nAny ICH                                                                                     10/148 (6.8%)                          46/165 (27.9%)                           <0.001 \nsICH                                                                                            3/148 (2.0%)                           27/165 (16.4%)                           <0.001 \nFatal ICH                                                                                      0/148 (0%)                              13/165 (7.9%)                            <0.001 \nInpatient mortality                                                                     0/148 (0%)                             41/165 (24.8%)                           <0.001 \n90 days all-cause mortality                                                         0/148 (0%)                             47/165 (28.5%)                           <0.001 \n \nICH, intra-cranial haemorrhage. \n \n\n\n\nTable III: Distribution of Modified Rankin Scale (mRS)\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 599\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n600                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nOdd ratios                                                        Crude OR (95% CI)                        p value                     Adj OR (95% CI)             p value \nCentre  \n     ASRH                                                              1.09 (0.66\u20131.80)                            0.752 \n     PSC                                                                            Ref                                          \u2013                                                                           \nAge                                                                      0.96 (0.94\u20130.98)                           <0.001                       0.97 (0.95\u20130.99)                0.012 \nGender  \n     Female                                                           1.44 (0.90\u20132.30)                            0.125 \n     Male                                                                         Ref                                          \u2013                                                                           \nEthnicity  \n     Malays                                                           0.58 (0.34\u20130.997)                           0.049                        0.52 (0.27\u20131.02)                0.055 \n     Chinese                                                          0.88 (0.42\u20131.84)                            0.729                        0.95 (0.38\u20132.36)                0.916 \n     Indians                                                           0.44 (0.17\u20131.17)                            0.099                        0.43 (0.14\u20131.33)                0.143 \n     Others                                                                       Ref                                          \u2013                                      Ref                                \nDiabetes mellitus  \n     Yes                                                                  0.94 (0.59\u20131.50)                            0.799                                      \n     No                                                                             Ref                                          \u2013                                                                           \nHypertension  \n     Yes                                                                  0.83 (0.52\u20131.32)                            0.427 \n     No                                                                             Ref                                          \u2013                                                                           \nDyslipidaemia  \n     Yes                                                                  1.10 (0.67\u20131.79)                            0.710 \n     No                                                                             Ref                                          \u2013                                                                           \nCAD  \n     Yes                                                                  0.79 (0.45\u20131.39)                            0.417 \n     No                                                                             Ref                                          \u2013                                                                           \nAtrial \n     Yes                                                                  0.86 (0.47\u20131.57)                            0.629 \n     No                                                                             Ref                                          \u2013                                                                           \nVHD \n     Yes                                                                  5.73 (0.66\u201349.7)                            0.113 \n     No                                                                             Ref                                          \u2013                                                                           \nCVA /TIA  \n     Yes                                                                  1.64 (0.87\u20133.10)                            0.130 \n     No                                                                             Ref                                          \u2013                                                                           \nAnti-platelet/anti-coagulant  \n     Yes                                                                  1.28 (0.79\u20132.09)                            0.323 \n     No                                                                             Ref                                          \u2013                                                                           \nSmoking status : \n     Current/Ex Smoker                                        1.14 (0.73\u20131.79)                            0.561 \n     Non                                                                           Ref                                          \u2013                                                                           \nNIHSS at presentation                                       0.85 (0.81\u20130.90)                           <0.001                       0.85 (0.81\u20130.91)               <0.001 \nASPECTS                                                              1.67 (1.33\u20132.11)                           <0.001                      1.28 (0.997\u20131.65)               0.053 \nOnset-to-needle time                                        1.00 (0.99\u20131.004)                           0.998                                                                       \nDoor-to-needle time                                       0.988 (0.983\u20130.994)                        <0.001                   0.988 (0.981\u20130.995))            0.001 \nSymptomatic ICH  \n     Yes                                                                  0.11 (0.03\u20130.36)                           <0.001                       0.13 (0.04\u20130.48)                0.002 \n     No                                                                             Ref                                          \u2013                                      Ref                              \u2013 \n \n1. Younger age \n2. Lower NIHSS at presentation \n3. Shorter DNT \n4. No sICH \nASRH, acute stroke-ready hospital; AF, atrial fibrillation; CAD, coronary artery disease; CVA, cerebrovascular disease; TIA, transient \nischaemic attack; sICH, symptomatic intracranial haemorrhage; VHD, valvular heart disease; PSC, primary stroke centres. \n \n\n\n\nTable IV: Factors associated with favourable outcomes\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 600\n\n\n\n\n\n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                601 \n\n\n\nCONCLUSION \nThis real-world study may provide translational real-world \nevidence which suggests that IVT in AIS can be equally safe, \neffective and efficiently delivered in both PSCs and ASRHs. \nThis may further encourage the establishment of IVT service \nin some centres without in-house neurologists, hence \nextending the benefits of IVT to a greater proportion of stroke \npopulations. Accordingly, through collaborative efforts and \ninitiatives, the development of more ASRHs equipped with \ntrained stroke teams should be proactively advocated to \nenhance regional and international acute stroke care. \n \n \nDECLARATION OF INTEREST \nAll authors report no disclosure or conflict of interest with \nrespect to the research, authorship and publication of this \narticle. \n \n \nREFERENCES \n1. National Institute of Neurological Disorders and Stroke rt-PA \n\n\n\nStroke Study Group. Tissue plasminogen activator for acute \nischemic stroke. N Engl J Med 1995; 333(24): 1581\u20137. \n\n\n\n2. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase \n3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; \n359(13): 1317\u201329. \n\n\n\n3. Wahlgren N, Ahmed N, D\u00e1valos A, et al. Thrombolysis with \nalteplase for acute ischaemic stroke in the Safe Implementation \nof Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an \nobservational study. Lancet 2007; 369(9558): 275\u201382. \n\n\n\n4. Hacke W, Donnan G, Fieschi C, et al. Association of outcome \nwith early stroke treatment: pooled analysis of ATLANTIS, \nECASS, and NINDS rt-PA stroke trials. Lancet 2004; 363(9411): \n768\u201374. \n\n\n\n5. Lees KR, Bluhmki E, von Kummer R, et al; ECASS, ATLANTIS, \nNINDS and EPITHET rt-PA Study Group. Time to treatment with \nintravenous alteplase and outcome in stroke: an updated pooled \nanalysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet \n2010; 375: 1695\u20131703. \n\n\n\n6. Wardlaw JM, Murray V, Berge E, et al. Thrombolysis for acute \nischaemic stroke. Cochrane Database Syst Rev 2014; (7): \nCD000213 \n\n\n\n7. Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue \nplasminogen activator for acute ischaemic stroke: an updated \nsystematic review and meta-analysis. Lancet 2012; 379(9834): \n2364\u201372. \n\n\n\n8. Lees KR, Emberson J, Blackwell L, et al; on behalf of the Stroke \nThrombolysis Trialists\u2019 Collaborators Group. Effects of alteplase \nfor acute stroke on the distribution of functional outcomes: a \npooled analysis of 9 trials. Stroke 2016;47:2373\u201379. \n\n\n\n9. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the \nEarly Management of Patients With Acute Ischemic Stroke: 2019 \nUpdate to the 2018 Guidelines for the Early Management of \nAcute Ischemic Stroke: A Guideline for Healthcare Professionals \nFrom the American Heart Association/American Stroke \nAssociation. Stroke 2019; 50(12): e344\u2013e418. \n\n\n\n10. Lee A, Gaekwad A, Bronca M, et al. Stroke physician versus \nstroke neurologist: can anyone thrombolyse? Intern Med J 2015; \n45(3): 305\u20139. \n\n\n\n11. Kongbunkiat K, Kasemsap N, Tiamkao S, et al. Thrombolysis in \nischaemic stroke in rural North East Thailand by neurologist and \nnon-neurologists. Neurology Asia. 2016; 21(4): 325\u201331. \n\n\n\n12. Akins PT, Delemos C, Wentworth D, et al. Can emergency \ndepartment physicians safely and effectively initiate \nthrombolysis for acute ischemic stroke? Neurology 2000; 55(12): \n1801\u20135. \n\n\n\n13. Aho K, Harmsen P, Hatano S, et al. Cerebrovascular disease in \nthe community: results of a WHO collaborative study. Bull World \nHealth Organ 1980; 58: 113\u201330.  \n\n\n\n14. HP Adams Jr, BH Bendixen, LJ Kappelle, et al. Classification of \nsubtype of acute ischemic stroke. Definitions for use in a \nmulticenter clinical trial. TOAST. Trial of Org 10172 in Acute \nStroke Treatment. Stroke 1993; 24(1): 35\u201341. \n\n\n\n15. Barber PA, Demchuk AM, Zhang J, et al. Validity and reliability \nof a quantitative computed tomography score in predicting \noutcome of hyperacute stroke before thrombolytic therapy. \nASPECTS Study Group. Alberta Stroke Programme Early CT Score. \nLancet 2000; 355: 1670\u20134. \n\n\n\n16. JH Pexman, PA Barber, MD Hill, et al. Use of the Alberta Stroke \nProgram Early CT Score (ASPECTS) for assessing CT scans in \npatients with acute stroke. AJNR Am J Neuroradiol. 2001; 22(8): \n1534\u201342. \n\n\n\n\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 601\n\n\n\n\n\n\n\n\n602                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Previous trials and real-world studies have \nshown that nirmatrelvir/ritonavir (Paxlovid\u00ae) reduces \nhospitalisation and deaths in symptomatic, high-risk, non-\nsevere COVID-19 patients. However, there was a scarcity of \ndata on its effectiveness in the local setting. This study \naimed to determine the effectiveness of Paxlovid\u00ae in \nreducing hospitalisation and mortality among COVID-19 \npatients and to identify the types of adverse events that \noccur after taking Paxlovid\u00ae. \n \nMaterials and Methods: A two-arm prospective cohort study \nwas conducted among adult patients with COVID-19 \ncategories 2 and 3 treated with Paxlovid\u00ae and a matched \ncontrol group. A standard risk-stratified scoring system was \nused to establish Paxlovid\u00ae eligibility. All patients who were \nprescribed Paxlovid\u00ae and took at least one dose of \nPaxlovid\u00ae were included in the study. The control patients \nwere selected from a centralised COVID-19 patient registry \nand matched based on age, gender and COVID-19 stage \nseverity. \n \nResults:  A total of 552 subjects were included in the study \nand evenly allocated to the treatment and control groups. \nThere was no statistically significant difference in 28-day \nhospitalisation after diagnosis [Paxlovid\u00ae: 26 (9.4%), \nControl: 34 (12.3%), OR: 0.74; 95%CI, 0.43-1.27; p=0.274] or \nall-cause death [Paxlovid\u00ae: 2 (0.7%), Control: 3 (1.1%), OR \n1.51; 95%CI, 0.25-9.09; p=0.999]. There was no significant \nreduction in hospitalisation duration, intensive care unit \nadmission events or supplementary oxygen requirement in \nthe treatment arm. Ethnicity, COVID-19 severity at diagnosis, \ncomorbidities and vaccination status were predictors of \nhospitalisation events. \n \nConclusion: In this two-arm study, Paxlovid\u00ae did not \nsignificantly lower the incidence of hospitalisation, all-cause \ndeath and the need for supplemental oxygen. Adverse \neffects were frequent but not severe. Paxlovid\u00ae efficacy \nvaried across settings and populations, warranting further \nreal-world investigations. \n \n\n\n\nKEYWORDS:  \neffectiveness; nirmatrelvir/ritonavir; hospitalisation; death; \nCOVID-19; real-world; Malaysia  \n \n \nINTRODUCTION \nAs of December 2022, the coronavirus disease 2019 (COVID-\n19) has killed 7.5 million people globally, with more than \n650 million positive cases.1 Between January 24 and February \n7, 2022, the predominant COVID-19 variant in Malaysia was \nOmicron, accounting for 92% of cases, followed by Delta at \n8%. On February 7, 2022, the Ministry of Health declared \nOmicron as the dominant strain in Malaysia.2 As of June 1, \n2022, Malaysia had reported 5.10 million confirmed COVID-\n19 cases and 37,087 deaths related to COVID-19.3  \n \nIn April 2022, WHO recommended the use of \nNirmatrelvir/Ritonavir (Paxlovid\u00ae) for high-risk patients \nwith non-severe COVID-19 based on the available evidence \nfrom two randomised controlled trials (EPIC-SR and EPIC-\nHR).4 Nirmatrelvir is a novel SARS-CoV-2 major protease \ninhibitor targeting SARS-CoV-2 3CL, while ritonavir is an \nHIV-1 protease inhibitor that inhibits the CYP3A-mediated \nmetabolism of nirmatrelvir.5  \n \nHammond et al. found that managing symptomatic Covid-\n19 with nirmatrelvir/ritonavir (Paxlovid\u00ae) reduced the risk of \nprogression to severe Covid-19 by 89% compared to placebo, \nwith no apparent safety issues.6 Nirmatrelvir/ritonavir \n(Paxlovid\u00ae) significantly reduced death and hospitalisation \nin the 65 and older group, with adjusted hazard ratios of 0.21 \n(95% CI, 0.05 to 0.82) and 0.74 (95% CI, 0.35 to 1.58), \nrespectively.7 \n \nIn a large-scale retrospective observational cohort study of \nnon-hospitalised adult patients infected with COVID-19, \ntreatment with Paxlovid\u00ae was associated with a lower rate of \n28-day all-cause hospitalisation and 28-day all-cause death \ncompared to no antiviral treatment.8 Another retrospective \ncohort study conducted in Hong Kong found that the use of \nPaxlovid\u00ae was associated with decreased risks of death, \nhospitalisation and in-hospital disease progression.9  \n\n\n\nEffectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) in \npreventing hospitalisation and death among COVID-19 \npatients: a prospective cohort study \n \nChew Lan Sim1, Lim Xin Jie2, Chang Chee Tao2,3, Ros Sakinah Kamaludin1, Leow Hon Lunn1, Ong Su Yin4, \nNorirmawath Saharuddin4, Nor Aida Sanusi4, Normi Kamaruzaman1, Zaiton Kamarruddin4, Philip Rajan2,5 \n\n\n\n     \n1Pharmacy Department, Hospital Raja Permaisuri Bainun, Ministry of Health Malaysia, Ipoh, Malaysia, 2Clinical Research \nCentre, Hospital Raja Permaisuri Bainun, Ministry of Health Malaysia, Ipoh, Malaysia, 3School of Pharmacy, Monash University \nMalaysia, Subang Jaya, Malaysia, 4Perak Pharmaceutical Services Division, Ministry of Health Malaysia, Perak, Malaysia, \n5School of Medicine, Faculty of Health and Medical Sciences, Taylor\u2019s University, Subang Jaya, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 06 July 2023                                                                                                                                                                              \nCorresponding Author: Philip Rajan                                                                                                                                                                                    \nEmail: prajan333@yahoo.com \n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 602\n\n\n\n\n\n\n\n\nEffectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                603 \n\n\n\nDespite a few studies demonstrating the effectiveness of \nPaxlovid\u00ae in real-world settings,7-10 there remains a notable \ngap in the existing evidence, particularly in the South East \nAsia setting. This study provides insights regarding the use of \nPaxlovid\u00ae specifically for the Omicron variant, compared to \nstudies with larger populations and considering the diverse \nethnic populations found in countries like Malaysia. \n \nThis study aims to assess the effectiveness of Paxlovid\u00ae in \nreducing hospitalisations and death among COVID-19 \npatients and determine the occurrence of adverse events \nassociated with its use. \n \n \nMATERIALS AND METHODS \nThis prospective cohort study included adult patients with \ncategory 2 and category 3 COVID-19 who received treatment \nwith Paxlovid\u00ae and a matched control group. The study was \nconducted across 24 study sites, comprising 13 hospitals and \n11 District Health District Offices in the Perak state of \nMalaysia. \n \nPaxlovid\u00ae Regimen \nThe recommended dose for patients with normal renal \nfunction (eGFR > 60ml/min) is 300 mg of nirmatrelvir (two \n150 mg tablets) and 100 mg of ritonavir (one 100 mg tablet), \ntaken orally twice daily for 5 days. Adjusted dosage for renal \nimpaired (eGFR 30\u201360 ml/min) patients is nirmatrelvir 150 \nmg (1 tablet) and ritonavir 100 mg twice daily. \n \nPaxlovid\u00ae Eligibility \nA standard risk-stratified scoring system was used to prioritise \nPaxlovid\u00ae among patients with COVID-19. One point was \ngiven to each of the following characteristics: age \u2265 60 years, \nimmunocompromised, presence of comorbidities, incomplete \nvaccination (did not complete booster dose or unvaccinated), \nobesity and radiographic abnormalities in chest X-ray. The \nscores were summed up and recorded in the Paxlovid\u00ae \ninitiation criteria checklist. Patients who scored equal or more \nthan 2 were eligible for Paxlovid\u00ae.  \n \nPatients were not eligible for Paxlovid\u00ae if they were less than \n18 years old, asymptomatic (Category 1), with symptoms \nonset more than 5 days, started on oxygen, diagnosed liver \ndisease (Child-Pugh Class C) or end-stage renal failure (eGFR \n<30 ml/min), pregnant or breastfeeding, with the inherent \nrisk of hypersensitivity and taking interacting medications, \nincluding carbamazepine, phenobarbital, phenytoin, \nvoriconazole, warfarin, rivaroxaban, colchicine, atazanavir, \ndarunavir, rifampicin,  quetiapine, amlodipine, felodipine, \ndiltiazem, nifedipine, digoxin, lovastatin, simvastatin, \natorvastatin, rosuvastatin, ethinyl oestradiol, cyclosporine, \ntacrolimus, sirolimus, salmeterol, methadone, sildenafil, \ndexamethasone and methylprednisolone. \n \nStudy Inclusion and Exclusion \nWe included all patients prescribed Paxlovid\u00ae in May and \nJune 2022 who consumed at least one dose of Paxlovid\u00ae. We \nexcluded those lost to follow-up (self-reported as having \nCOVID-19 through the Malaysian contact-tracing mobile \napplication MySejahtera but did not seek treatment at clinics \nor hospitals) and did not consume any dose of Paxlovid\u00ae \nafter receiving the medication.  \n\n\n\nMatched Control \nPatients not prescribed Paxlovid\u00ae in March and April 2022 \nwere included in the control arm in a 1:1 ratio. Control \npatients could not be attained in the same period as the \ntreatment group because all eligible patients were started \nwith Paxlovid\u00ae from May onwards. The control patients were \nidentified and retrieved from the state-centralised COVID-19 \npatients registry and matched using age, gender and pre-\ntreatment COVID-19 stage severity.  \n \nSample Size and Sampling Method \nThe sample size was calculated using G-Power (proportion \ndifference from constant, binomial test, one sample case) \nsample size calculator. Based on Hammond et al. 2022, 0.7% \nof Paxlovid\u00ae patients were hospitalised until Day 28, \ncompared to 6.5% of placebo patients who were hospitalised \nor died.6 To detect a difference of 5.8% between the two arms, \nan alpha error of 0.05, a power of 99% and a minimum \nsample size of 117 were required. Assuming 30% incomplete \ndata, each arm's final sample size was 167. Consecutive \nsampling was employed, where all cases which fulfilled the \ninclusion and exclusion criteria were sampled. \n \nOutcome Measures \nThe primary effectiveness measure was an event of 28-day \nhospitalisation post-COVID-19 diagnosis. Paxlovid\u00ae-related \nadverse events and 28-day post-diagnosis death were the \nsecondary outcome measures. \n \nData Collection \nThe data of patients who were prescribed Paxlovid\u00ae were \nentered into the state centralised Paxlovid\u00ae initiation \nregistry, and eligible patients were identified through the \nregistry. Data retrieved included patients\u2019 age, gender, \nethnicity, COVID-19 category during the first encounter, \ntypes and severity of adverse events (Days 1 to 5 post-\ninitiation), and the total doses ingested. We solicited patients\u2019 \nadmission or readmission outcomes, oxygen requirement \nand adverse events (Days 6\u201328) through phone follow-up on \nDay 28 post-initiation.  \n \nSeveral sources of secondary data supplemented this: (i) \nPaxlovid\u00ae initiation criteria checklist containing \ncomorbidities, obesity, immunocompromised status, dose \nprescribed, radiographic abnormalities in chest X-ray; (ii) \nCentralised COVID-19 vaccine database containing \nvaccination status and types of vaccines administered; (iii) \nNational Registration Department, which provided the death \ndata; (iv) electronic hospital information system containing \nthe admission duration, oxygen requirement and intensive \ncare unit (ICU) admission status.  \n \nControl group data retrieved included patients' age, gender, \nethnicity and COVID-19 severity category during the first \nencounter from the state-centralised COVID-19 patients \nregistry and supplemented with data from the Centralised \nCOVID-19 vaccine database, National Registration \nDepartment and hospital information system.  \n \nData Analysis \nThe demographic characteristics of the patients in both the \ntreatment and control arm were descriptively analysed. \nEvents and duration of hospitalisation, ICU admission, \n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 603\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n604                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nsupplemental oxygen requirement and all-cause death \noutcomes for Paxlovid\u00ae recipients were compared with \nmatched controls using the Chi-square (\u03c72) statistic and \nFisher\u2019s exact test for categorical variables and the Mann\u2013\nWhitney U test for continuous variables. Multiple logistic \nregression analysis was performed to determine the \nindependent predictors of hospital admissions and death. \nThe model was constructed consisting of variables significant \nat the 0.25 level. Inferential data were expressed in odd ratios \nand 95% confidence intervals, and a p-value of 0.05 indicates \nstatistical significance.  \n \nEthics Approval \nThis study was registered in the National Medical Research \nRegistry (NMRR ID-22-01372-NIL) and approved by Medical \n\n\n\nResearch Ethical Committee [22-01372-NIL(1)]. Consent was \nobtained from the treatment group patients during the first \nencounter regarding the 28-day phone call follow-up. \n \n \nRESULTS \nBaseline Patient Characteristics \n552 subjects were evenly divided into both arms and \nanalysed. Of 276 patients who received Paxlovid\u00ae treatment, \nthe median age was 53 years (IQR: 40-66 years); 142 (51.4%) \nwere women, and 157 (56.9%) were Malay individuals. The \nmost common comorbidities were hypertension (54.0%) and \ndiabetes (32.6%). The baseline demographic and clinical \ncharacteristics were generally similar in both arms. Of those \nwho received Paxlovid\u00ae, 259 (93.8%) completed the 5-day \n\n\n\n                                                                                         Paxlovid\u00ae group                        Control group                           p value \n                                                                                                (n = 276)                                   (n = 276)                                       \n\n\n\nAge, median (IQR)                                                                       53 (40-66)                                  53 (40-63)                                0.242a \nGender, n (%)                                                                                                                                                                                      \n\n\n\nMale                                                                                       134 (48.6)                                  128 (46.4)                                0.282 \nFemale                                                                                    142 (51.4)                                  148 (53.6)                                      \n\n\n\nEthnicity, n (%)                                                                                                                                                                                    \nMalay                                                                                     157 (56.9)                                  171 (62.0)                                0.189 \nChinese                                                                                    66 (22.5)                                    61 (22.1)                                       \nIndian                                                                                      51 (18.5)                                    43 (15.6)                                       \nOthers                                                                                       6 (2.2)                                        1 (0.4)                                         \n\n\n\nCovid severity at  \n(before treatment), n (%)                                                                                                                                                                   \n\n\n\n2A                                                                                           258 (93.5)                                  258 (93.5)                                0.999 \n2B                                                                                             10 (3.6)                                      10 (3.6)                                        \n3                                                                                                 8 (2.9)                                        8 (2.9)                                         \n\n\n\nComorbidities, n (%)                                                                                                                                                                            \nHypertension                                                                         149 (54.0)                                  160 (58.0)                                0.346 \nDiabetes                                                                                  90 (32.6)                                   101 (36.6)                                0.325 \nDyslipidaemia                                                                           8 (2.9)                                       20 (7.2)                                  0.020 \nChronic kidney disease                                                            6 (2.2)                                       11 (4.0)                                  0.218 \nRespiratory disease                                                                  24 (8.7)                                      26 (9.4)                                  0.767 \nCancer                                                                                       6 (2.2)                                        2 (0.7)                                   0.154 \nCardiovascular disease                                                           29 (10.5)                                    32 (11.6)                                 0.684 \nOthers                                                                                      13 (4.7)                                     32 (11.6)                                 0.003 \n\n\n\nCOVID-19 vaccination status, n (%)                                                                                                                                              0.237 \nCompleted booster dose                                                      202 (73.5)                                  186 (67.4)                                0.119 \nCompleted primary doses                                                      67 (24.4)                                    85 (30.8)                                 0.091 \nUnvaccinated                                                                            6 (2.2)                                        5 (1.8)                                   0.756 \n\n\n\nAdherence, n (%)                                                                                                                                                                                 \nCompleted regimen (10 doses)                                            259 (93.8)                                                                                        \nTaken at least one dose                                                          17 (6.2)                                             \n \n\n\n\na Mann-Whitney U test performed \nb Reason of non-adherence: intolerable adverse events (n=9), patient refusal (n=5), progression to severe COVID-19 (n=1), others (n=2). \n\n\n\nTable I: Characteristics of patients who received Paxlovid\u00ae and matched population controls (n=552)\n\n\n\n                                                                                          Overall           Control             Paxlovid\u00ae            Odds ratio              p-value \n                                                                                         (n=552)            (n=276)                (n=276)                 (95%CI)                       \n\n\n\nHospitalisation, n (%)                                                           60 (10.9)          34 (12.3)               26 (9.4)          0.74 (0.43\u20131.27)           0.274a \nDuration of hospitalisation in days, median (IQR)             4.0 (2\u20136)          4.0 (2\u20137)              5.0 (3\u20136)                      -                        0.952b \nICU admission, n (%)                                                               5 (8.3)              3 (8.8)                  2 (7.7)           1.51 (0.25\u20139.09)           0.999c \nSupplemental oxygen requirement, N (%)                          13(21.7)          10 (29.0)               3(11.5)          3.41 (0.93\u201312.52)           0.05a \nAll-cause death, n (%)                                                            5 (0.9)              3 (1.1)                  2 (0.7)           1.51 (0.25\u20139.09)           0.999c \n \naChi-square test. \nbMann\u2013Whitney U test.  \ncFisher\u2019s exact test. \n\n\n\nTable II: Comparison of hospitalisation, ICU admissions, oxygen requirement and all-cause death outcomes between Paxlovid\u00ae \nrecipients and matched controls (n=552)\n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 604\n\n\n\n\n\n\n\n\nEffectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                605 \n\n\n\nVariable                                                                      Crude OR (95% CI)                   p value            Adjusted OR (95%CI)            p value \nAge (year)                                                                     1.01 (1.00\u20131.03)                        0.129                                                                     \nGender                                                                                                                                                                                                          \n Female                                                                    1.21 (0.70\u20132.07)                         0.50                                                                      \n Male                                                                                 1.00                                                                                                               \nEthnicity                                                                                                                                                                                                        \n Non-Malay                                                              2.08 (1.21\u20133.57)                        0.008                   2.04 (1.10\u20133.80)                   0.024 \n Malay                                                                               1.00                                                                       1.00                                  \nSeverity of COVID-19 at diagnosis                                                                               <0.001                                                              <0.001 \n 2a                                                                            0.02 (0.01\u20130.07)                       <0.001                  0.03 (0.01\u20130.10)                  <0.001 \n 2b                                                                            0.12 (0.03\u20130.59)                        0.009                   0.13 (0.02\u20130.69)                   0.016 \n 3                                                                                        1.00                                                                       1.00                                  \nHypertension                                                                                                                                                                                                \n Yes                                                                          1.11 (0.65\u20131.92)                        0.697                                                                     \n No                                                                                     1.00                                                                                                               \nDM                                                                                                                                                                            \n Yes                                                                          0.94 (0.53\u20131.66)                        0.827                                                                     \n No                                                                                     1.00                                                                                                               \nDyslipidaemia                                                                                                                                                                                               \n Yes                                                                          1.85 (0.68\u20135.07)                        0.229                                                                     \n No                                                                                     1.00                                                                                                               \nCKD                                                                                                                                                                                                               \n Yes                                                                          2.63 (0.83\u20138.35)                         0.10                                                                      \n No                                                                                     1.00                                                                                                               \nRespiratory                                                                                                                                                                                                   \n Yes                                                                          3.40 (1.69\u20136.85)                       <0.001                  0.40 (0.18\u20130.93)                   0.032 \n No                                                                                     1.00                                                                       1.00                                  \nCancer                                                                                                                                                                                                           \n Yes                                                                          2.79 (0.55\u201314.2)                        0.215                                                                     \n No                                                                                     1.00                                                                                                               \nCVS                                                                                                                                                                                                                \n Yes                                                                          2.26 (1.13\u20134.54)                        0.022                   0.43 (0.20\u20130.95)                   0.036 \n No                                                                                     1.00                                                                       1.00                                  \nOthers                                                                                                                                                                                                           \n Yes                                                                          1.89 (0.84\u20134.28)                        0.126                                                                     \n No                                                                                     1.00                                                                                                               \nVaccination status                                                                                                          0.004                                                                0.015 \n Unvaccinated                                                         6.15 (1.71\u201322.1)                        0.005                  6.33 (1.39\u201328.82)                  0.017 \n Complete primary                                                  1.92 (1.09\u20133.39)                        0.025                   1.97 (1.00\u20133.88)                   0.049 \n Complete booster                                                            1.00                                                                       1.00                                  \nPaxlovid\u00ae                                                                                                                                                                                                     \n No                                                                           1.35 (0.79\u20132.32)                        0.275                                                                     \n Yes                                                                                    1.00                                                                                                               \n \nBackward LR method was applied; No multicollinearity and no interaction; Hosmer Lemeshow test, p value=0.506; Classification table 90.9% correctly \nclassified; area under receiver operating characteristics (ROC) curve was 78%.  OR: Odd ratios; DM: Diabetes mellitus; CKD: Chronic kidney disease; CVS: \nCardiovascular disease \n\n\n\nTable III: Univariate and multivariate binary logistic regression for day 28 post-diagnosis hospitalisation event (n=552)\n\n\n\ncourse treatment.  Overall, 73.5% of the patients had received \na booster dose, 24.4% received the primary series, and 2.2% \nwere unvaccinated (Table I). \n \nHospitalisation, ICU Admission, Oxygen Requirement and \nAll-Cause Death  \nFrom the first day of diagnosis to day 28 post-diagnosis, 60 \n(10.9%) patients required hospitalisation. There were no \nstatistically significant differences in day 28 post-diagnosis \nhospitalisation events between the two arms [Paxlovid\u00ae: 26 \n(9.4%), Control: 34 (12.3%), OR: 0.74; 95% confidence \nintervals, 0.43\u20131.27; p=0.274]. The median duration of \nhospitalisation was 4.0 days (IQR: 2\u20136 days). There were no \nsignificant differences in total ICU admissions and \nsupplemental oxygen requirement in the treatment arm. Five \ndeaths were reported at day 28 post-diagnosis, with no \nsignificant differences across both arms [Paxlovid\u00ae: 2 (0.7%), \nControl: 3 (1.1%), OR: 1.51; 95%CI 0.25-9.09; p=0.999] (Table \nII). \n \n\n\n\nPredictive Factors of Hospitalisation  \nNon-Malays had 2.04 times greater odds of hospitalisation \nthan Malays. [OR: 2.04; 95%CI 1.10\u20133.80; p=0.024]. \nIronically, patients with underlying respiratory [OR: 0.40; \n95%CI, 0.18\u20130.93; p=0.032] and cardiovascular disease [OR: \n0.43; 95%CI, 0.20\u20130.95; p=0.036] demonstrated lower risks of \nhospitalisation.  \n \nThe odds of hospitalisation for COVID-19 varied based on the \nstatus of vaccination. Patients vaccinated with the primary \nseries without a booster dose were more likely to be \nhospitalised than boosted patients [OR 1.97; 95%CI 1.00\u2013\n3.88; p=0.049]. The odds of hospitalisation were 6.3 times \nhigher in unvaccinated patients compared to those who were \nboosted [OR: 6.33; 95%CI, 1.39\u201328.82; p=0.017]. \n \nA milder stage of COVID-19 at diagnosis was associated with \ndecreased odds of hospitalisation. Patients who were \ndiagnosed with Stage 2a [OR: 0.03; 95%CI, 0.01\u20130.10; \np<0.001] and Stage 2b [OR: 0.13; 95%CI, 0.02\u20130.69; p=0.016] \n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 605\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n606                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nwere associated with a lower risk of hospitalisation compared \nto stage 3 (Table III). \n \nAdverse Events  \nThe reported adverse events after Paxlovid\u00ae ingestion was as \nfollows: dysgeusia (96, 61.1%), diarrhoea (49, 31.2%), nausea \nand vomiting (11, 7.0%), myalgia (7, 4.5%), abdominal pain \n(5, 3.2%), hypertension (3,1.9%) and others (41, 26.1%). \nThere was no life-threatening adverse event reported.  \n \n \nDISCUSSION \nThis was a real-world study in a multiracial country within \nthe ASEAN region to evaluate the effectiveness of Paxlovid\u00ae \nin reducing hospitalisation and all-cause death. Our study \nfound hospitalisation and all-cause death occurred in 9% \nand 0.8% of Paxlovid\u00ae patients, respectively, which was \nhigher than what was reported by previous studies.6,11,12 \nHammond et al. reported 0.77% of hospitalisation with no \ndeath,6 while Shah et al. reported 0.47% of hospitalisation \nand 0.01% of death in patients receiving Paxlovid\u00ae.11 \n\n\n\nFurthermore, Malden and colleagues discovered that \nemergency department visits or hospitalisations were less \nthan 1% in the 5\u201315 days following Paxlovid\u00ae treatment.12  \nSimilarly, larger real-world cohort studies7-10 carried out \nduring Omicron domination reported a reduction of \nhospitalisation and death in the Paxlovid\u00ae group, but with a \nlower magnitude than Hammond et al. In contrast with \n\n\n\nprevious studies, we did not find a significant reduction in \nhospitalisation and all-cause death in patients who took \nPaxlovid\u00ae. Also, we did not observe any significant reduction \nin intensive care unit (ICU) admission and supplemental \noxygen requirement among patients taking Paxlovid\u00ae. \nAlthough previous studies did not find a reduction in ICU \nadmission among patients who took Paxlovid\u00ae, a \nsignificantly lower need for oxygen therapy was reported.9,10 \nThe insignificant results might be explained by several \ndifferences between the studies, including the study \npopulation and settings.  \n \nFirst, the population's natural immunity may have risen over \ntime due to previous strain infections, contributing to lower \nseverity, hospitalisation and death.13 Second, about 7% of our \nstudy population did not adhere to the Paxlovid\u00ae regimen, \nwhich may reduce the effectiveness of Paxlovid\u00ae.10 \n \nNotably, the EPIC-HR trial6 included only unvaccinated \npatients, whereas our study included merely 2% \nunvaccinated subjects, and 70% had received the booster \ndose. Similarly, two previous studies found no significant \nreduction in hospitalisation or all-cause death among \nvaccinated inpatients who received Paxlovid\u00ae.9,14 The action \nof Paxlovid\u00ae could be masked by COVID-19 vaccinations, \nwhich effectively reduce disease severity and death.10,15 Hence, \nour findings may rationalise the prioritisation of Paxlovid\u00ae \namong unvaccinated patients, especially in resource-poor \n\n\n\n                                                                                           Control group                        Paxlovid\u00ae group                        p value \n                                                                                                  (n=34)                                        (n=26)                                         \n\n\n\nAge, median (IQR)                                                                  55.5 (33.3\u201372.3)                        58.5 (36.8\u201369.3)                           0.715a \nGender, n (%)                                                                                                                                                                                      \n Male                                                                                        13 (38.2)                                    13 (50.0)                                 0.362 \n Female                                                                                     21 (61.8)                                    13 (50.0)                                       \nEthnicity, n (%)                                                                                                                                                                                    \n Malay                                                                                      13 (38.2)                                    13 (50.0)                                 0.631 \n Chinese                                                                                    14 (41.2)                                     8 (30.8)                                        \n Indian                                                                                       7 (20.6)                                      5 (19.2)                                        \n Others                                                                                                                                                                                             \nCovid severity at  \n(before treatment), n (%)                                                                                                                                                                   \n 2A                                                                                            25 (73.5)                                    15 (57.7)                                 0.282b \n 2B                                                                                              2 (5.9)                                       5 (19.2)                                        \n 3                                                                                                7 (20.6)                                      6 (23.1)                                        \nComorbidities, n (%)                                                                                                                                                                            \n Hypertension                                                                          19 (55.9)                                    16 (61.5)                                  0.66 \n Diabetes                                                                                  10 (29.4)                                    10 (38.5)                                 0.582 \n Dyslipidaemia                                                                          4 (11.8)                                       1 (3.8)                                   0.377b \n Chronic kidney disease                                                            2 (5.9)                                        2 (7.7)                                   0.999b \n Respiratory disease                                                                  8 (23.5)                                      5 (19.2)                                   0.76 \n Cancer                                                                                       1 (2.9)                                        1 (3.8)                                   0.999b \n Cardiovascular disease                                                            6 (17.6)                                      6 (23.1)                                  0.747 \n Others                                                                                      6 (17.6)                                       2 (7.7)                                   0.446b \nCOVID-19 vaccination status, n (%)                                                                                                                                                    \n Completed booster dose                                                        18(52.9)                                     15(57.7)                                  0.92b \n Completed primary doses                                                      14(41.2)                                      9(34.6)                                        \n Unvaccinated                                                                             2(5.9)                                         2(7.7)                                         \nAdherence, n (%)                                                                                                                                                                                 \n Completed regimen (10 doses)                                                                                                22 (84.6)                                       \n Taken at least one dose                                                                                                            4(15.4)                                        \n \naMann\u2013Whitney U test was performed. \nbFisher\u2019s exact test was performed. \n \n\n\n\nSupplementary Table I:  Demographic and clinical characteristics of the hospitalised patients (n = 60)\n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 606\n\n\n\n\n\n\n\n\nEffectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                607 \n\n\n\nsettings. Lastly, the fact that we included fewer subjects in the \nover-65 age group in which Paxlovid\u00ae was found to be more \nefficacious7 may have contributed to the underestimation of \nits efficacy. \n \nOur analysis showed non-Malays had higher hospitalisation \nodds than Malays, suggesting the potential association \nbetween ethnicity and COVID-19 severity.10,16,17 It is important \nto note that genetic polymorphisms may affect drug \nmetabolism and medication response.18 Variations in allelic \nfrequencies of the CYP2D6*10 gene have been observed \namong the Chinese, Malay and Indian populations.19 Apart \nfrom different drug metabolism profiles, ethnicity could be \nthe surrogate for underlying factors, including socioeconomic \nstatus, exposure to virus-related- environments and access to \nhealth care.20 Further investigation is needed in this area to \nreduce health inequalities across different ethnic groups.17 \n \nThe most commonly reported Paxlovid\u00ae-related adverse \nevents in this study were dysgeusia, diarrhoea, and vomiting, \nwhich mirrored previous findings.6,14 While the reported \nadverse events were not severe, they might lead to patients\u2019 \nnon-adherence, causing drug resistance and treatment \nfailure.21 Therefore, medication counselling, compliance \nfollow-up, and pharmacovigilance are essential components \nof Paxlovid\u00ae dispensing.22 \n \nWe did not observe a significant difference in the odds of \ndeath between both arms. Two deaths were reported in the \nPaxlovid\u00ae arm, unrelated to COVID-19 infection or \nPaxlovid\u00ae treatment. There were three deaths in the control \ngroup, of which two were related to COVID-19 pneumonia. In \ncontrast, Hammond et al. reported a significant difference in \nall-cause death outcomes, in which no death occurred in the \ntreatment arm and 13 deaths in the placebo arm, of which \nall were COVID-19 related.4 Nonetheless, the high number \nneeded to treat in preventing one death suggests the need to \ninvestigate the cost-effectiveness of Paxlovid\u00ae, particularly in \na low-resource health setting.  \n \nThis study reflected the real-world efficacy of Paxlovid\u00ae using \na matched cohort, which includes both outpatients and \ninpatients, vaccinated and unvaccinated populations. \nInitiation of Paxlovid\u00ae was performed using a standard risk-\nstratified scoring system and closely reflected clinical practice \nin Malaysian health settings. Several limitations should be \nconsidered when interpreting the findings of this study. The \nsmall sample size and the exclusion of lost to follow-up cases \ncould restrict the generalisability of the study findings. \nFurthermore, there was a limited representation of subjects in \nthe over-65 age group. Matching participants based on \nlimited characteristics may introduce bias if other unknown \nfactors influence the outcomes studied.  \n \n \nCONCLUSION \nThe use of Paxlovid\u00ae to treat symptomatic Covid-19 did not \nsignificantly reduce the risk of hospitalisation, all-cause \ndeath and supplemental oxygen requirement compared to \nthe control group. Adverse events were common but non-\nsevere. The efficacy of Paxlovid\u00ae in real-world settings and \ndifferent populations remains inconsistent and warrants \nfurther investigations. \n\n\n\nREFERENCES \n1. World Health Organization (WHO). WHO Coronavirus (COVID-\n\n\n\n19) Dashboard. 2022. https://covid19.who.int. Accessed 25 \nDecember 2022. \n\n\n\n2. Tan KT, Benedict SLH, Chang CY, Chidambaram SK, Abd Jamil \nI, Bahrudin MS, et al. Clinical severity of COVID-19 with omicron \nvariant predominance in relation to vaccination status, age, \ncomorbidities- a single center in Selangor, Malaysia. Med J \nMalaysia 2022; 77: 558-63. \n\n\n\n3. Our World in Data. Malaysia: Coronavirus Pandemic Country \nProfile. 2022. https://ourworldindata.org/coronavirus/ \ncountry/malaysia. Accessed 10 Jun 2023. \n\n\n\n4. World Health Organization (WHO). WHO recommends highly \nsuccessful COVID-19 therapy and calls for wide geographical \ndistribution and transparency from originator. 2022. \nhttps://www.who.int/news/item/22-04-2022-who-recommends-\nhighly-successful-covid-19-therapy-and-calls-for-wide-\ngeographical-distribution-and-transparency-from-originator. \nAccessed 13 Feb 2023. \n\n\n\n5. Pfizer. Pfizer shares in vitro efficacy of novel COVID-19 oral \ntreatment against omicron variant | Pfizer. 2022. \nhttps://www.pfizer.com/news/press-release/press-release-\ndetail/pfizer-shares-vitro-efficacy-novel-covid-19-oral-treatment. \nAccessed 13 Feb 2023. \n\n\n\n6. Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, \nWisemandle W, et al. Oral nirmatrelvir for high-risk, \nnonhospitalized adults with Covid-19. New Engl J Med. 2022; \n386: 1397-408. \n\n\n\n7. Arbel R, Sagy YW, Hoshen M, Battat E, Lavie G, Sergienko R, et \nal. Nirmatrelvir use and severe Covid-19 outcomes during the \nomicron surge. N Engl J Med 2022; 387: 790-8. \n\n\n\n8. Aggarwal NR, Molina KC, Beaty LE, Bennett TD, Carlson NE, \nMayer DA, et al. Real-world use of nirmatrelvir-ritonavir in \noutpatients with COVID-19 during the era of omicron variants \nincluding BA.4 and BA.5 in Colorado, USA: a retrospective cohort \nstudy. Lancet Infect Dis 2023; 23: 696-705. \n\n\n\n9. Wong CKH, Au ICH, Lau KTK, Lau EHY, Cowling BJ, Leung GM. \nReal-world effectiveness of early molnupiravir or nirmatrelvir\u2013\nritonavir in hospitalised patients with COVID-19 without \nsupplemental oxygen requirement on admission during Hong \nKong\u2019s omicron BA.2 wave: a retrospective cohort study. Lancet \nInfectious Dis. 2022; 22: 1681-93. \n\n\n\n10. Najjar-Debbiny R, Gronich N, Weber G, Khoury J, Amar M, Stein \nN, et al. Effectiveness of paxlovid in reducing severe coronavirus \ndisease 2019 and mortality in high-risk patients. Clin Infect Dis. \n2023; 76: e342-9. \n\n\n\n11. Shah MM, Joyce B, Plumb ID, Sahakian S, Feldstein LR, Barkley \nE, et al. Paxlovid associated with decreased hospitalization rate \namong adults with COVID-19 \u2014 United States, April\u2013September \n2022. MMWR Morb Mortal Wkly Rep 2022; 71: 1531-7. \n\n\n\n12. Malden DE, Hong V, Lewin BJ, Ackerson BK, Lipsitch M, Lewnard \nJA, et al. Hospitalization and emergency department encounters \nfor COVID-19 after paxlovid treatment - California, December \n2021-May 2022. MMWR Morb Mortal Wkly Rep 2022; 71: 830\u20133. \n\n\n\n13. Ridgway JP, Tideman S, Wright B, Robicsek A. Decreased risk of \ncoronavirus disease 2019-related hospitalization associated with \nthe omicron variant of severe acute respiratory syndrome \ncoronavirus 2. Open Forum Infect Dis 2022; 9: ofac288. \n\n\n\n14. Tiseo G, Barbieri C, Galfo V, Occhineri S, Matucci T, Almerigogna \nF, et al. Efficacy and safety of nirmatrelvir/ritonavir, \nmolnupiravir, and remdesivir in a real-world cohort of \noutpatients with COVID-19 at high risk of progression: the PISA \noutpatient clinic experience. Infect Dis Ther 2023; 12: 257-71. \n\n\n\n15. Rosenberg ES, Holtgrave DR, Dorabawila V, Conroy M, Greene D, \nLutterloh E, et al. New COVID-19 cases and hospitalizations \namong adults, by vaccination status - New York, May 3-July 25, \n2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1150-5. \n\n\n\n16. Magesh S, John D, Li WT, Li Y, Mattingly-app A, Jain S, et al. \nDisparities in COVID-19 outcomes by race, ethnicity, and \nsocioeconomic status: a systematic review and meta-analysis. \nJAMA Netw Open 2021; 4: e2134147. \n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 607\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n608                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n17. Sze S, Pan D, Nevill CR, Gray LJ, Martin CA, Nazareth J, et al. \nEthnicity and clinical outcomes in COVID-19: a systematic \nreview and meta-analysis. EClinicalMed 2020; 29\u201330: 100630. \n\n\n\n18. Shenfield GM. Genetic polymorphisms, drug metabolism and \ndrug concentrations. Clin Biochem Rev 2004; 25: 203-6. \n\n\n\n19. Runcharoen C, Fukunaga K, Sensorn I, Iemwimangsa N, \nKlumsathian S, Tong H, et al. Prevalence of pharmacogenomic \nvariants in 100 pharmacogenes among Southeast Asian \npopulations under the collaboration of the Southeast Asian \nPharmacogenomics Research Network (SEAPharm). Hum \nGenome Var 2021; 8: 7. \n\n\n\n\n\n\n\n20. CDC. Risk for COVID-19 Infection, Hospitalization, and Death By \nRace/Ethnicity. Centers for Disease Control and Prevention. 2020. \nh t tp s : / /www.cdc .gov/co ronav i rus /2019 -ncov/cov id -\ndata/investigations-discovery/hospitalization-death-by-race-\nethnicity.html. Accessed 13 Feb 2023. \n\n\n\n21. Bezabhe WM, Chalmers L, Bereznicki LR, Peterson GM. \nAdherence to antiretroviral therapy and virologic failure: a meta-\nanalysis. Medicine 2016; 95: e3361. \n\n\n\n22. Chang CT, Ong SY, Lim XJ, Chew LS, Rajan P. Managing \nnirmatrelvir/ritonavir during COVID-19: pharmacists\u2019 \nexperiences from the Perak state of Malaysia. J Pharm Policy \nPract 2022; 15: 70.\n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 608\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                609 \n\n\n\nABSTRACT \nIntroduction: Interleukin (IL)-40 is a recently identified \ncytokine with a novel role in the pathogenesis of \ninflammatory diseases. Since systemic lupus \nerythematosus (SLE) is an autoimmune disease \ncharacterised by a pro-inflammatory response, it is likely \nthat IL-40 contributes to the underlying disease processes \nof this disorder. The aim of the current study was to evaluate \nthe potential of IL-40 to act as a diagnostic biomarker for \nSLE.  \n \nMatrrials and methods: The study included 99 patients with \nSLE who attended the Rheumatology Unit at Baghdad \nTeaching Hospital. These subjects were divided into three \nsubgroups according to disease status: inactive, n = 33; \nactive moderate, n = 33; and active severe, n = 33. \nAdditionally, 33 matched controls were studied. Full medical \nhistories, body mass index, gender and clinical disease \nactivity, the latter evaluated with the SLE disease activity \nindex, were collected. Laboratory parameters measured \nincluded anti-dsDNA antibodies, C3 and C4 levels, \nerythrocyte sedimentation rate and C-reactive protein titres. \nSerum IL-40 levels were quantified using an enzyme-linked \nimmunosorbent assay. \n \nResults: IL-40 levels were significantly higher in patients \n(12.5420 \u00b1 3.00575 ng/L) than in controls (6.1138 \u00b1 0.59452 \nng/L; p < 0.01). Mean serum IL-40 concentration was highest \nin the active severe group (15.2291 \u00b1 2.26540 ng/L) and \ndecreased, in order of disease severity, in the remaining \ncohorts: active moderate, 13.0643 \u00b1 1.23927 ng/L; inactive, \n9.3325 \u00b1 1.62807 ng/L (P < 0.01); controls, 6.1138 \u00b1 0.59452 \nng/L. Serum IL-40 levels showed excellent validity for the \ndiagnosis of SLE with a cut-off value of \u2265 9.3 ng/ml and area \nunder the curve of 0.987. Sensitivity, specificity and \naccuracy were 99%, 90.9% and 96.97%, respectively (P < \n0.001). \n \nConclusions: Serum IL-40 levels were elevated in SLE \npatients. It is therefore proposed that IL-40 is a novel \ncytokine which is associated with SLE and positively linked \nwith disease severity. \n \nKEYWORDS:  \nSystemic lupus erythematosus; SLE; IL-40; autoimmune condition; \ninflammation  \n \n \n \n\n\n\nINTRODUCTION \nSystemic lupus erythematosus (SLE) is a condition that \ndevelops owing to the abnormal immune-mediated \ndestruction of healthy tissues1,2 caused by B and T-cell \nhyperactivity and coincides with reactivity to self-antigens.3 \nIncreased production of antibodies, defective antibody \nclearance and complement and cytokine stimulation are \nsome of the typical characteristics that result in the symptoms \nof SLE. There is up to a 3-fold increase in mortality in patients \nliving with SLE compared to the general population. \nImproved treatment options may reduce mortality rates; \nhowever, superior diagnostic methods which allow for earlier \nor more sensitive detection of the disease are also essential.  \n \nThe earliest signs of SLE reflect constitutional symptoms, \nwhich may be accompanied by mild to moderate joint pain, \nsuggestive of arthritis. However, the presence of an \naccompanying skin rash or skin lesions at various \nanatomical sites supports a diagnosis of SLE.1  \n \nSince SLE is a heterogenous condition, to date, establishing a \ndiagnosis has proved difficult as the presentation often \nreflects the symptoms of alternative conditions, e.g., cancers \nor infectious diseases, such as human immunodeficiency \nvirus and acquired immunodeficiency syndrome.3 Viral \nserological tests and tissue histopathological testing may be \nperformed to exclude other causes. The American College of \nRheumatology (ACR) and the European League Against \nRheumatism (EULAR) have proposed criteria for the \ndiagnosis of SLE. However, as patients with mild diseases are \ncommonly unrecognised by this classification, more rigorous \ntesting is essential.3  \n \nCurrent diagnostic methods for the diagnosis of SLE rely on \nclinical symptom manifestations and are complemented by \nlaboratory tests, such as viral or tissue investigations. The \nlatter includes the anti-nuclear antibody (ANA) test; a \npositive ANA result is supported by an antigen-specific ANA \nfor extractable nuclear antigens, which has a specificity of \napproximately 66% for these complexes. It is recommended \nthat consultants collaborate with a SLE rheumatologist in \norder to attain a more reliable diagnosis. Only a few \nbiomarkers have been recognised as being of value in the \ndiagnosis of SLE, but as none of these can be utilised with \nconfidence in disease management, novel biomarkers are \nurgently required in the field. Elucidation of more precise \nbiomarkers for SLE could greatly improve detection sensitivity \nand reduce the time taken to diagnose patients. However, \nthere has been little success to date. \n\n\n\nSerum interleukin-40: an innovative diagnostic biomarker \nfor patients with systemic lupus erythematosus \n \nAmal Mahdi Al Rubaye, MSc1, Inas K. Sharquie, PhD1, Faiq I. Gorial, FIBMS2 \n\n\n\n     \n1Department of Microbiology and Immunology, College of Medicine, University of Baghdad, Baghdad, Iraq, 2Department of \nMedicine, College of Medicine, University of Baghdad, Baghdad, Iraq  \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 21 July 2023                                                                                                                                                                              \nCorresponding Author: Inas K. Sharquie                                                                                                                                                                             \nEmail:  iksharquie@yahoo.com,  inasksharquie@comed.uobaghdad.edu.iq\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 609\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n610                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nPrevious attempts to elucidate cytokine profiling in SLE have \nincluded the analysis of tumour necrosis factor-\u03b1 (TNF-\u03b1), a \npro-inflammatory cytokine which evidences increased \nexpression in a variety of autoimmune diseases.4 In one \nstudy, no differences between serum TNF-\u03b1 levels in healthy \nand SLE groups were determined, although another study \nsuggested that TNF-\u03b1 was a useful biomarker for SLE. Thus, at \npresent, the role of TNF-\u03b1 in the diagnosis of SLE is unclear.5 \n \nA potentially superior approach is to quantify the levels of \ncytokines secreted by B cells, since SLE is predominantly \nmediated by aberrant B-cell activity, with autoimmune \ndiseases, such as SLE, characterised by the presence of \nautoantibodies. At least one study has demonstrated \naberrant B-cell-associated cytokine profiles in which IL-4 was \nvirtually undetectable in the serum of SLE patients and \ncoincided with a rise in IL-6.6 The recent discovery of the B-\ncell-associated cytokine, IL-40, may also be utilised to \nimprove the diagnosis of SLE, as exemplified in other \ninflammatory conditions.  \n \nIL-40 is a B-cell-associated orphan cytokine encoded by the \ngene, C17orf99, which is secreted via activated B-cells. This \ngene regulates IgG production in order to maintain the \nphysiological function of B-cells.7 Studies have demonstrated \nthat IL-40 accumulates in the synovial joints of patients with \nrheumatoid arthritis (RA); serum IL-40 concentrations in \npatients with RA are substantially increased compared to \nthose detected in healthy controls.8 In RA, IL-40 propagates \npro-inflammatory cytokine release and autoantibody \nproduction; extracellular IL-40 enhances the synthesis of \ntissue-degrading enzymes.9 In one study, the depletion of B-\ncells reduced IL-40 production by 70%, suggesting that B-cell \ntargeted therapies may offer relief from autoimmune \nconditions mediated by IL-40. However, other immune cells \nmay synthesise residual IL-40. IL-40 has also been suggested \nto be a useful biomarker for the detection of type II diabetes \nmellitus and Sj\u00f6gren's syndrome, underscoring its role in the \npathogenesis of inflammatory and autoimmune diseases.10-12  \n \nSince SLE is an autoimmune condition characterised by a \npro-inflammatory response, the detection of IL-40 may be a \nuseful strategy for the identification of individuals with SLE as \naberrant B-cell activity is a hallmark of the disease. However, \nconflicting evidence suggests that IL-40 only regulates local \ninflammation and does not underlie the systemic \ninflammatory response observed in patients with SLE in \nwhom IL-40 levels were comparable to those measured in \ncontrols.10 Before the utility of IL-40 in the diagnosis of SLE \ncan be realised, further studies are required in order to \ninvestigate whether IL-40 plays a role in SLE or whether it is \nsimply a local inflammatory mediator.  \n \nThe principal objective of this present study was to \nthoroughly evaluate and ascertain the potential efficacy of \nIL-40 as a reliable diagnostic biomarker for SLE. \n \n \nMATERIALS AND METHODS \nThis study included 99 patients, aged over 18 years, who were \ndiagnosed with SLE according to the 2019 EULAR/ACR \nclassification criteria.13 They were divided into three \nsubgroups: inactive, n=33; active moderate, n=33; and active \n\n\n\nsevere, n=33. Thirty-three age- and sex-matched healthy \ncontrols were also included. Participants were recruited \nbetween November 2022 and January 2023 from the \nRheumatology Unit at the Baghdad Teaching Hospital. \nExclusion criteria were: concurrent overlapping \ninflammatory arthritis, connective tissue disease or \nseronegative spondyloarthritis; malignancy; pregnancy; \nevidence of infection and patient refusal. Under the direction \nof the rheumatologist, the full patient information page data \nand consent form were completed, and the Committee of \nScientific Ethics from the College of Medicine, University of \nBaghdad approved the study. The ethics committee\u2019s \napproval number was 023.  For each patient, gathered \nbaseline data encompassed blood investigations, full medical \nhistories, body mass index (BMI), gender and clinical disease \nactivity as evaluated with the SLE disease activity index. \nDisease-related laboratory parameters included anti-dsDNA \nantibodies, C3 and C4 levels, erythrocyte sedimentation rate \n(ESR) and C-reactive protein (CRP).  \n \nThe SLE disease activity scoring system consists of 24 \nvariables which cover 9 organ systems and yield a total score \nof 105. A total score \u2264 3 suggests that no flare is present, a \ntotal score > 3 and \u2264 12 is considered to reflect a mild to \nmoderate flare, and a total score > 12 represents a severe \nflare.14 Serum was obtained by centrifuging blood specimens \nfor 10 to 15 minutes at 1000\u20133000 rpm. Serum samples were \nthen frozen at \u221220\u00b0C. The enzyme-linked immunosorbent \nassay technique (Sun Long Biotech Company, China) was \nused to measure serum IL-40 in keeping with the \nmanufacturer\u2019s instructions. A plate reader was used to \ndetermine the absorbance at 450 nm. The immunological \ntesting was done at the International Centre for Research and \nDevelopment. \n \nStatistical Analysis \nStatistical analysis was performed using the Statistical \nPackage for the Social Sciences, version 21 (IBM). Student\u2019s t \ntests, analysis of variance (ANOVA) and the less significant \ndifference (LSD) test were performed for comparisons of \nquantitative variables, i.e. age, BMI and serum IL\u201340 levels, \nbetween studied groups. Normally distributed data are \nexpressed as mean \u00b1 standard deviation. Pearson\u2019s chi-\nsquare test (\u03c72) was used for comparisons of qualitative \nvariables between studied groups, i.e. age groups and BMI. A \nbinomial Z-test was performed for a comparison of gender \nand treatment intake. Pearson\u2019s correlation test was applied \nin order to detect the relationships between serum IL\u201340 \nlevels and age, BMI, duration of SLE disease, ESR and C3 and \nC4 concentrations. The validity of the ELISA test was \nestimated with a ROC curve, cut-off value, area under curve \n(AUC), sensitivity, specificity, positive predictive value (PPV), \nnegative predictive value (NPV) and accuracy. The statistical \nsignificance threshold was deemed to be a P-value < 0.05.  \n \n \nRESULTS \nThe age ranges of the 99 SLE patients and 33 control subjects \nwere 18 to 58 years and 19 to 55 years, respectively. Table I \nillustrate the similarities between the two cohorts with respect \nto the demographic parameters of gender, age group and \nBMI. \n \n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 610\n\n\n\n\n\n\n\n\nSerum interleukin 40: an innovative diagnostic biomarker for patients with systemic lupus erythematosus\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                611 \n\n\n\nFemales were predominant within both studied groups, \ncomprising 93 (93.94%) SLE patients and 30 (90.4%) controls \n(p=0.037).  \n \nThe frequency of subjects was highest within the age range, \n31\u201340 years, in both controls (13, 39.4%) and SLE patients \n(40, 40.4%), followed by the age range 18\u201330 years, i.e. \ncontrols (12, 36.4%) and SLE patients (36, 36.4%) (p=0.991). \nThe mean ages of the two studied groups were similar, i.e. \ncontrols, 35.35 \u00b1 11.783 years, and SLE patients, 34.69 \u00b1 \n9.074 years (p=0.789). \n \nThe frequency of subjects assigned to the BMI classifications \nin the two cohorts was as follows: overweight: controls, 19 \n(57.6%), SLE patients, 40 (40.4%); obese: controls, 8 (24.2%), \nSLE patients, 34 (34.3%); normal weight: controls, 6 (18.2%), \nSLE patients, 25 (25.3%) (p=0.359).  \n \nMean BMI showed a trend towards being greater in the SLE \npatient cohort when compared to the control group, i.e. \n28.1342 \u00b1 5.5956 kg/m2 and 25.8926 \u00b1 3.87481 kg/m2, \nrespectively, but this failed to reach statistical significance \n(p=0.161). \n \nWhen the variables were compared with respect to disease \nactivity using ANOVA, no differences were identified (Table \nII). The mean BMI values of the SLE patients within all three \ngroups of disease activity were similar: active severe, 28.7406 \n\u00b1 6.27527 kg/m2; active moderate, 28.3613 \u00b1 6.04078 kg/m2; \ninactive 27.8319 \u00b1 4.66821 kg/m2 (p=0.101). \n \nLSD test values were also similar between the various levels of \ndisease activity: inactive vs. active moderate, p=0.691; \ninactive vs. active severe, p=0.494; active moderate vs. active \nsevere, p=0.775. \n \nMean disease durations were similar between the different \ndisease activity groups: active moderate, 6.836 \u00b1 5.3956 \nyears; active severe, 5.994 \u00b1 4.2940 years; inactive, 4.306 \u00b1 \n4.7466 years (p=0.185). A within-group comparison of the \nLSD test data demonstrated no differences: inactive vs. active \nmoderate, p=0.072; inactive vs. active severe, p=0.228; active \nmoderate vs. active severe, p=0.546. \n \nMean serum ESR values were higher, the greater the disease \nactivity: active severe disease, 47.18 \u00b1 30.304; active \nmoderate, 40.79 \u00b1 26.415; inactive disease, 21.70 \u00b1 11.509 \n(p<0.001). Similar results were obtained for the LSD test, with \nthe exception of active moderate vs. active severe disease \nstates (p=0.221).  \n \nMean anti-dsDNA levels were modestly elevated in SLE \npatients with active severe disease (92.812 \u00b1 143.821) when \ncompared with those with active moderate disease (30.297 \u00b1 \n24.2616); anti-dsDNA titres were decreased in patients with \ninactive disease (19.233 \u00b1 3.7611, p=0.00). \n \nWithin-group comparisons were shown to be identical by the \nLSD test, with the exception of inactive vs. active moderate \n(p=0.539).  \n \n \n\n\n\nMean C3 levels were lower in SLE patients within the active \nsevere cohort (0.5858 \u00b1 0.37691) compared to those with \nactive moderate disease (0.6973 \u00b1 0.39807) and increased in \nthe inactive group (1.0548 \u00b1 0.49356, p<0.001).  \n \nSignificant differences (P < 0.01) were noted following the LSD \ntest, with the exception of active moderate vs. active severe \n(p=0.253).  \n \nMean C4 levels were diminished in SLE patients with active \nsevere (0.0543 \u00b1 0.05139) compared to those with active \nmoderate (0.2642 \u00b1 0.21645) and inactive disease (0.2812 \u00b1 \n0.08521); these differences were significant (p<0.01) for all \ncomparisons apart from inactive vs. active moderate \n(p=0.528).  \n \nTable III presents the distribution of the CRP data and \ntreatment intake according to the severity of SLE disease. This \nwas non-significant (p=0.164) for DMARDs intake: inactive: \nyes, 31 (93.9%), no, 2 (6.1%); active moderate: yes, 26 \n(78.8%), no, 7 (21.2%); active severe: yes, 25 (75.8%), no, 8 \n(24.2%).   \n \nThe data showed a significant difference (p=0.033) for CRP: \ninactive: positive, 1 (3.03%) negative, 32 (96.97%); active \nmoderate: positive, 2 (6.06%), negative, 31 (93.94%); active \nsevere: positive, 6 (18.18%), negative, 27 (81.82%).  \n \nSignificant differences (p<0.01) were observed for other types \nof treatment intakes: (i) steroid intake: inactive: yes, 12 \n(36.4%), no, 21 (63.6%); active moderate: yes, 25 (75.8%), no, \n8 (24.2%); active severe: yes, 28 (84.85%), no, 5 (15.15%) (P < \n0.001); and (ii) biologics intake: active moderate: yes, 1 (3%), \nno, 32 (97%); active severe, yes, 12 (36.4%), no, 21 (63.6%) \n(p=0.008). \n \nResult indicates that the mean serum IL-40 ng/ml titre in SLE \npatients (n=99) was higher than in controls (n=33), i.e. \n12.5420 \u00b1 3.00575 ng/L vs. 6.1138 \u00b1 0.59452 ng/L (p<0.01). \n \nIt can be clearly observed from the ANOVA and LSD tests \npresented in Table IV that the mean IL-40 levels in the sera of \nSLE patients in the active severe cohort are higher (15.2291 \u00b1 \n2.26540 ng/L) than in those patients in the active moderate \ngroup (13.0643 \u00b1 1.23927 ng/L). The latter values are \nelevated compared to the inactive (9.3325 \u00b1 1.62807 ng/L) \nand control groups (6.1138 \u00b1 0.59452 ng/L) (p<0.01 in all \ncases). \n \nResults also show the mean distributions of IL-40 levels in the \nsera of SLE patients according to the type of treatment intake. \nFor DMARDs intake, mean IL-40 values were lower in those \npatients taking this medication: Yes, 12.2198 \u00b1 2.96423 ng/L; \nNo, 14.0959 \u00b1 2.78502 ng/L (p=0.018). Mean IL-40 levels were \nsimilar amongst patients who were or were not on steroid \ntherapy: Yes, 12.2301 \u00b1 2.72639 ng/L; No, 13.1383 \u00b1 3.44324 \nng/L (p=0.154), and between patients who were or were not \nreceiving biologics: Yes, 14.2086 \u00b1 2.74526 ng/L; No, 14.1315 \n\u00b1 1.96211 ng/L (p=0.907). \n \nA correlation study between IL-40 levels and the other SLE \npatient parameters revealed that there were inverse \n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 611\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n612                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nParameters                                                                                                 Studied groups                                                  p value \n                                                                                                Controls                                   Patients \n                                                                                                  (n=33)                                       (n=99) \n\n\n\nGender                                        Male                                           3 (9.1%)                                   6 (6.06%)                                 0.337 \n                                             Female                                     30 (90.9%)                               93 (93.94%)                                 NS  \n\n\n\nAge-groups                                 18\u201330                                        12 (36.4%)                                36 (36.4%)                               0.991 \n(years)                                         31\u201340                                        13 (39.4%)                                40 (40.4%)                                  NS  \n\n\n\n                                             41\u201350                                         7 (21.2%)                                 21 (21.2%)                                     \n                                             51\u201360                                           1 (3%)                                       2 (2%)                                        \n\n\n\nBMI groups                                 Normal weight                         6 (18.2%)                                 25 (25.3%)                               0.359 \n                                             Overweight                              19 (57.6%)                                40 (40.4%)                                     \n                                             Obese                                        8 (24.2%)                                 34 (34.3%)                                     \n\n\n\nAge (years)                                  Mean                                            35.35                                         34.69                                    0.786 \n                                                                                                                                                                                                    NS \n                                             Std. deviation                              11.783                                        9.074                                         \n                                             Std. error                                      1.915                                         1.074                                         \n\n\n\nBMI (kg/m2)                                 Mean                                          25.8926                                     28.1342                                  0.161 \n                                                                                                                                                                                                    NS \n                                             Std. deviation                             3.87481                                      5.5956                                        \n                                             Std. error                                    0.63942                                      0.5483                                        \n\n\n\n \nNS: non-significant (p>0.05), BMI: body mass index. \n\n\n\nTable I: Demographics and other parameters: distributions within the two studied groups, i.e., SLE patients and controls.\n\n\n\nSLE patient groups                                             Mean                             Std.                          Std.                    LSD test (p value) \n                                                                                                                Deviation                     Error                                     \nBMI                   Inactive                                      27.8319                        4.66821                    0.81263                   A                       0.691 \n                         Active moderate                        28.3613                        6.04078                    1.05156                   B                        0.494 \n                         Active severe                             28.7406                        6.27527                    1.09238                   C                       0.775 \n                                                  ANOVA test  (p value):            p=0.101 \nDuration          Inactive                                        4.306                           4.7466                      0.8263                    A                        0.072 \n(years)              Active moderate                          6.836                           7.3956                      1.2874                    B                        0.228 \n                         Active severe                               5.994                           4.2940                      0.7475                    C                        0.546 \n                                                  ANOVA test (p value):             p=0.185 \nESR                   Inactive                                        21.70                           11.509                       2.004                     A                         0.00 \n                         Active moderate                          40.79                           26.415                       4.598                     B                         0.00 \n                         Active severe                               47.18                           30.304                       5.275                     C                       0.221 \n                                                 ANOVA test (p value):               p<0.001 \nAnti-dsDNA     Inactive                                       19.233                          3.7611                      0.6547                    A                        0.539 \n                         Active moderate                         30.297                         24.2616                     4.2234                    B                         0.00 \n                         Active severe                              92.812                         143.821                    25.0362                   C                        0.001 \n                                                 ANOVA test (p value):               p<0.001 \nC3                     Inactive                                       1.0548                         0.49356                    0.08592                   A                         0.00 \n                         Active moderate                         0.6973                         0.39807                    0.06929                   B                        0.00 \n                         Active severe                              0.5858                         0.37691                    0.06561                   C                        0.253 \n                                                 ANOVA test (p value):                p<0.001 \nC4                     Inactive                                       0.2812                         0.08521                    0.01483                   A                        0.582 \n                         Active moderate                         0.2642                         0.21645                    0.03768                   B                         0.00 \n                         Active severe                              0.0543                         0.05139                    0.00895                   C                         0.00 \n                                                    ANOVA test (p value):         p<0.001 \n \nBMI: body mass index, ESR: erythrocyte sedimentation rate, Anti-ds DNA: Anti-double  \nstranded DNA, C3 and C4: Complement components 3 and 4, LSD: Least Significant \nDifference, A = inactive vs. active moderate, B = inactive vs. active severe,  \nC = active moderate vs. active severe. \n \n \n\n\n\nTable II: Mean distributions of parameters within SLE patient groups\n\n\n\nParameters                                                                                           SLE patient groups                                                          p value \n                                                                          Inactive                   Active moderate                   Active severe \n                                                                           (n=33)                             (n=33)                                  (n=33) \n\n\n\nCRP                                Positive                            1 (3.03%)                       2 (6.06%)                           6 (18.18%)                      **0.033 \n                                Negative                       32 (96.97%)                   31 (93.94%)                        27 (81.82%)                            \n\n\n\nDMARDs intake            Yes                                  31 (93.9%)                     26 (78.8%)                          25 (75.8%)                        0.164 \n                                                                                                                                                                                                       NS \n                                No                                     2 (6.1%)                        7 (21.2%)                            8 (24.2%)                              \n\n\n\nSteroid intake               Yes                                  12 (36.4%)                     25 (75.8%)                         28 (84.85%)                     **<0.01 \n                                No                                   21 (63.6%)                      8 (24.2%)                           5 (15.15%)                             \n\n\n\nBiologics intake            Yes                                                                             1 (3%)                              12 (36.4%)                      **0.008 \n                                No                                                                            32 (97%)                            21 (63.6%)                             \n\n\n\n          \n**p<0.01. NS: non-significant (p>0.05), CRP: C-Reactive Protein, DMARDs: \nDisease- Modifying Anti-Rheumatic Drugs \n\n\n\nTable III: C-reactive protein values and treatment intake distributions within SLE patient groups\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 612\n\n\n\n\n\n\n\n\nSerum interleukin 40: an innovative diagnostic biomarker for patients with systemic lupus erythematosus\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                613 \n\n\n\nrelationships between serum IL-40 titres and C3 (r = \u22120.420, \np<0.01) and C4 levels (r=\u22120.396, p<0.01), and a positive \nrelationship between serum IL-40 levels and ESR values \n(r=0.344, p<0.01). \n \nThe remaining variables demonstrated a weakly positive \ncorrelation which was insignificant (Table V).  \n \nValidity of Tests \nThe results given prove that serum IL-40 levels have excellent \nvalidity for use in the diagnosis or follow-up of SLE patients \nat a cut-off value of 9.3 ng/ml. The performance parameters \nwere: AUC, 0.987; sensitivity, 99%; specificity, 90.9%; PPV, \n97%; NPV, 96.8%; accuracy, 96.97% (p<0.001). \n \n \nDISCUSSION \nIt is well-established that SLE arises from a complicated, \nmultifactorial interaction between various genetic factors. \nMultiple genes contribute towards patient disease \nsusceptibility, which is further refined and controlled by \nenvironmental triggers.15-18 Research has been ongoing for \nseveral decades in order to identify relevant biomarkers for \nSLE,19-22 and although some have shown promising results, no \nsingle biomarker has been able to detect SLE completely and \nreliably in every case. This issue arises as a result of the \nheterogeneous characteristics of SLE, the differing symptom \npresentations observed in practice,23 and the complex \npatterns of hereditability and genetic variation associated \nwith the disease.24   \n\n\n\n \nNonetheless, previous research has indicated that IL-40 plays \na central role in biological disease processes,7-8,10,25 and the \n\n\n\ncytokine has recently been proposed as a contributing factor \nto the development of SLE-associated nephritis.26 In this study, \nmultiple blood markers were evaluated, including IL-40 titres, \nin order to investigate whether or not they played a role in \nthe development and expression of SLE in the selected study \npopulation.  \n \nIt was established that serum IL-40 concentrations differed \nsignificantly between patients with SLE and the controls. A \npositive association between IL-40 levels and lupus severity \nwas identified, in that serum IL-40 titres increased in parallel \nwith the severity and duration of lupus symptoms. Previous \nstudies which have analysed serum IL-40 levels have shown \na similar trend in relation to the identification of RA and \nconcluded that IL-40 is a reliable indicator for the disease 25.  \nIL-40 is a cytokine that plays a central role in the regulation \nand secretion of IgG which, in turn, supports the normal \nfunctioning of B cells and enables the body\u2019s immune system \nto effectively respond to antibodies.7-8,27 IL-40 has not been \nwidely studied, but it appears to be expressed only in \nmammals. It has a unique structure, which makes it \nincomparable to most cytokine families.7,8 The cytokine has \nbeen shown to exert its most potent regulatory influence over \nB cells, acting during foetal development, and within the liver \nand bone marrow.7,28-29 Studies of IL-40 knockout mice \ndemonstrated an effect on B cell development, resulting in \nimpaired and non-functioning cells.8,25 Given that SLE is \nrecognised as an autoimmune disease,6,25 the current results \nsupport the hypothesis that IL-40 could be used to determine \nand diagnose autoimmune dysfunction.    \n \nThe role of IL-40 and its efficacy as a biomarker for detecting \ndisease have now been identified for a range of pathologies \n\n\n\n                                                                                                         IL-40 levels (ng/L) \nSeverity of SLE                                           Mean                                 SD                          Std. error                      LSD test (P value) \nControl                                                        6.1138                            0.59452                        0.07475                      A                     **<0.01 \nInactive                                                        9.3325                            1.62807                        0.28341                       B                      **<0.01 \nActive moderate                                        13.0643                           1.23927                        0.21573                       C                     **<0.01 \nActive severe                                             15.2291                           2.26540                        0.39436                      D                     **<0.01 \nANOVA test (p value);   p=0.00                                                                                                                                E                      **<0.01 \n\n\n\n                                                                                                                                                                             F                      **<0.01 \n \n**(p< 0.01), SD: Standard Deviation, LSD: Least Significant Difference \n\n\n\nTable IV: Mean distributions of IL-40 levels within SLE patient groups and controls\n\n\n\n                                                                              SLE patients (n = 99) \nPearson Correlation                                                                                      IL40 ng/L \nBMI                                                                   r                                                  0.069 \n                                                                   p value                                            0.495  \nAge                                                                  r                                                  0.139 \n                                                                   p value                                            0.171  \nDuration                                                          r                                                  0.181 \n                                                                   p value                                            0.073  \nESR                                                                   r                                                  0.344 \n                                                                   p value                                             0.00  \nAnti-dsDNA                                                     r                                                  0.166 \n                                                                   p value                                            0.101  \nC3                                                                     r                                                 -0.420 \n                                                                   p value                                             0.00  \nC4                                                                     r                                                 -0.396 \n                                                                   p value                                             0.00  \n\n\n\nTable V: Correlation study between IL-40 levels and other SLE patient parameters\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 613\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n614                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nincluding RA8,25 type II diabetes,10 hepatocellular carcinoma30 \nand lupus.11 The present results also imply that IL-40 is an \nimportant biomarker for the detection of SLE, and it is \nsuggested that further work should be targeted towards the \npart played by IL-40 in disease development processes. \nMonitoring serum IL-40 levels could support future clinical \ndiagnosis. Additionally, higher IL-40 titres were associated \nwith SLE symptom severity and so serum IL-40 level \nmonitoring in individuals suspected of having SLE could \nprovide opportunities for early diagnosis and intervention. \n \nIt was determined that the complement indicators, C3 and \nC4, were both negatively correlated with IL-40 levels, \nindicating that a higher titre of IL-40, which is indicative of a \npositive SLE diagnosis, is associated with reduced C3 and C4 \nlevels. This finding supports previous studies which have \nreported diminished blood serum complement factors in \ncases of lupus.9,11  \n \nWhen compared to the cohort of patients with inactive SLE, \nESR values were elevated in the groups with active severe and \nactive moderate disease, which supports existing literature \nshowing that a high ESR indicates active lupus.19 Elevated \nanti-dsDNA antibody levels were also measured in the active \nsevere group as opposed to in SLE patients with active \nmoderate or inactive disease, a finding which supports \nprevious studies that suggest a high level of serum anti-\ndsDNA antibodies are strongly associated with lupus.  \n \nCRP has a complex role in lupus, with modest CRP elevations \noften seen in patients with SLE. In the current study, the \ninactive group exhibited more negative than positive test \noutcomes. Conversely, both types of active SLE patient \ncohorts demonstrated more positive than negative test \noutcomes. The reason for the variation in proportions of \npositive and negative tests across the different SLE types is not \nclear. However, these findings support previous observations, \ni.e. that CRP involvement in lupus appears to be part of a \ncomplex set of processes.19  \n \nA negative association between the use of DMARDs and IL-40 \nlevels was observed, i.e. patients who did not take DMARDs \nhad significantly higher serum IL-40 levels. This suggested \nthat DMARDs may provide a protective effect against rising \nIL-40 levels in cases of SLE. \n \nThis study is the first to demonstrate the positive association \nbetween IL-40 levels and SLE symptom severity, adding \nevidence to suggest that IL-40 plays a role in SLE, and could \nbe used as part of the diagnostic process. A robust sample size \nof 99 SLE and 33 controls was studied. However, it was \nrecognised that when filtering patients by certain variables, \nthe sample size was reduced to a less than ideal number. For \ninstance, the sample size for SLE patients not taking DMARDs \nwas small, i.e. 17 patients, when compared to the sample of \n82 patients who were taking DMARDs. Nonetheless, it is \nconsidered that the results offer robust evidence that \nDMARDs may be protective against the development of SLE \nand support the role of IL-40 in this autoimmune condition. \nSample sizes will always be a challenge in such studies, but it \nis recommended that, where possible, future studies should \ntake all available steps to maximise sample sizes.  \n\n\n\nThe link between IL-40 titres, and SLE symptom severity and \nduration, needs to be confirmed in a larger sample size, and \nin patient populations with greater ethnic diversity. Previous \nstudies have highlighted that Black, Hispanic and Asian \npopulations demonstrate higher rates of SLE,31,32 and it is well-\nestablished that SLE is linked to genetic heritage and \nancestry.24 Furthermore, women are disproportionately \naffected over men.23 A logical next step would therefore be to \nunderstand how the role and function of IL-40 may differ \nbetween different ethnic and geo-spatially distinct \npopulations of individuals with SLE. The majority of studies \nhave been conducted in the Western or developed world,14-\n\n\n\n15,31,32 and a need for further studies to investigate the \nprevalence and presence of SLE in developing nations is \nrecognised. This is especially relevant given that White \npopulations appear to be at a lower risk of the condition.31,32 \n \n \nCONCLUSIONS \nIt was established that serum IL-40 measurements \ndemonstrated strong validity for the identification and \ndiagnosis of SLE, and exhibited greater accuracy than \nrecognised in relation to other disease indications. IL-40 \nlevels were positively correlated with SLE symptom severity \nand duration, indicating that this cytokine could be a \npromising biomarker for SLE, and play a role in early \ndiagnosis and intervention monitoring. This study adds \nfurther evidence to support the observation that IL-40 is \nimportant with respect to the immune response and immune \nsystem regulation. It is hoped that it inspires further studies \nwhich are designed to improve the understanding of the \ncytokine\u2019s potential as a biomarker for SLE and other \nautoimmune diseases.   \n \n \nCONFLICTS OF INTEREST  \nNo conflicts of interest. \n \n \nFUNDING \nThis research article is entirely funded by the authors.  \n \n \nREFERENCES \n1. Kiriakidou M, Ching CL. Systemic lupus erythematosus. Ann \n\n\n\nIntern Med. 2020; 172(11) :ITC81-ITC96. \n2. Justiz Vaillant AA, Goyal A, Varacallo M. Systemic lupus \n\n\n\nerythematosus. In: Stat Pearls. Treasure Island (FL): StatPearls \nPublishing. 2023. \n\n\n\n3. Abdulridha RH, Saud AM, Alosami MH. Evaluation of interferon \nalpha (IFN-\u03b1) in women with systemic lupus erythematosus in \nIraq. Iraqi J Sci 2022; 63(10): 4225\u201333.  \n\n\n\n4. Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, et al. The \nrole of tumor necrosis factor alpha (TNF-\u03b1) in autoimmune \ndisease and current TNF-\u03b1 inhibitors in therapeutics. 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Annals of the Rheumatic Diseases. 2022; \n81(Suppl 1): 273.  \n\n\n\n27. Lissoni P, Messina G, Pelizzoni F, Rovelli F, Brivio F, Monzon A, et \nal., editors. The fascination of cytokine immunological science. \n2020. \n\n\n\n28. Lee J, Hever A, Willhite D, Zlotnik A, Hevezi P. Effects of RNA \ndegradation on gene expression analysis of human postmortem \ntissues. Faseb J 2005; 19(10): 1356-8. \n\n\n\n29. Roth RB, Hevezi P, Lee J, Willhite D, Lechner SM, Foster AC, et al. \nGene expression analyses reveal molecular relationships among \n20 regions of the human CNS. Neurogenetics 2006; 7(2): 67\u201380. \n\n\n\n30. Said Nm, Yassin F, Esh AM, Saeed E. Association between serum \nlevel of pentraxin-3 and interleukin-40 with HCC disease in \nEgypt. Biochem Lett 2020; 16(1): 50-62.  \n\n\n\n31. Dall'Era M, Cisternas MG, Snipes K, Herrinton LJ, Gordon C, \nHelmick CG. The incidence and prevalence of systemic lupus \nerythematosus in San Francisco County, California: The \nCalifornia Lupus Surveillance Project. Arthritis Rheumatol. 2017; \n69(10): 1996-2005. \n\n\n\n32. Izmirly PM, Wan I, Sahl S, Buyon JP, Belmont HM, Salmon JE, et \nal. The incidence and prevalence of systemic lupus \nerythematosus in New York County (Manhattan), New York: The \nManhattan Lupus Surveillance Program. Arthritis Rheumatol. \n2017; 69(10): 2006-17 \n\n\n\n\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 615\n\n\n\n\n\n\n\n\n616                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Gastric cancer (GC) is one of the leading \ncauses of all new cancer cases globally. Although it is no \nlonger reported in the top 10th most common cancer in \nMalaysia, geographical distribution and ethnic influences \nstill obviously exist.  \n \nMaterials and Methods: This is a retrospective analysis of \nhistopathological records in a public tertiary health care \ncentre in Malaysia. The computerised laboratory information \nsystem from the histopathology department of the hospital \nwas retrieved for the period of 2005\u20132018. Descriptive \nanalysis was done using Microsoft Excel.  \n \nResults: There was a total of 233 histologically confirmed \nGC cases. The burden of GC was observed to be an \nincreasing trend from 2016 onwards. Among them, 64% were \nmale and 36% were female. The youngest age of diagnosis \nwas 19, while the oldest one was 93. Malaysian Chinese were \nfound to have the highest incidences (41.63%), followed by \nMalays (32.19%) and Malaysian Indians (23.61%). All cases \nwere of adenocarcinoma cell types and were found to have \npoorly differentiated in majority at the time of diagnosis.  \n \nConclusion: Although this report only represents one \ntertiary health care centre in Malaysia, the Indian Enigma \nwas still observed, as stated in other literatures. Over time, \nthe incidence of GC in Malays has increased. Consideration \nof lifestyle modifications, health education and Helicobacter \npylori eradication in various nations' National Health \nInsurance plans, are encouraged as prevention is always \nbetter than treatment or cure, including the cost load. \n \nKEYWORDS:  \nStomach neoplasms, Malaysia, Ethnic, Geographical, Enigma \n \n \nINTRODUCTION \nGastric cancer (GC) is the fifth leading cause of all newly \ndiagnosed cancer globally and the fourth leading cause of \ncancer-related death in 2020.1 The incidence rate, mortality \nrate and the 5-year prevelance rate of GC were the highest in \nAsia compared to other regions.1 In addition, around 1 in 12 \ncancer-related deaths were attributable to GC in 2018.2 \nAlthough nearly a million new GC cases are diagnosed \nglobally every year, GC is one of the most preventable cancer \ndue to its highly behaviourally influenced nature.2 \n\n\n\nHowever, the incidence, the age-standardized incidence and \nmortality of GC also declined globally.3 Although GC was \nreported as the second-highest incidence and mortality \nworldwide according to the Global Cancer Observatory \n(GLOBOCAN) 1998, GC was reported as the fifth most \ncommon neoplasm of all new cancer cases in GLOBOCAN \n2018.3 New GC cases are still detected, especially in the \nEastern Asian countries and these countries still have a high \nrisk of GC.3 GC was ranked as the 10th most common cancer \nin Malaysia in 2007\u20132011 (Malaysia National Cancer \nRegistry) MNCR report but it was not reported in the top 10 \nlist in the 2012\u20132016 MNCR report.4,5 \n \nIncidence and mortality of GC are highly variable by \ngeography as well as are greatly influenced by diet, \nenvironmental factors, and Helicobacter pylori (H. pylori) \ninfection in the community. GC was common in the United \nStates in previous centuries, but now it is no longer \nprevalent.2 This decreasing trend was most obvious in \ncountries such as Japan and South Korea.2 More than 50% of \nnew incident cases were reported from developing countries.  \nThis downward trend in some regions could be due to the \nearlier detection of GC using screening procedures such as \nupper gastrointestinal endoscopy or radiography and might \nbe due to the reduced H.  pylori infection in some countries.2 \n \nThe age-standardized 5-year net survival rate for GC is still \nbetween 20% and 40%, where 33.1% for the USA and 20.7% \nfor the UK.2 In these countries, although being the well-\ndeveloped countries, GC tends to be diagnosed at an \nadvanced stage.2 In contrast, the age-standardized 5-year net \nsurvival rate for Eastern Asian countries such as South Korea \nand Japan also has higher rates. The 5-year survival rate for \nGC in 2010\u20132014 was reported as 68.9% for South Korea and \n60.3% for Japan. It was strongly believed that the early \ndetection of GC had contributed to these favourable health \noutcomes. However, the median survival rate of GC is less \nthan 12 months in the advanced stage of GC.6 \n \nThe survival rate of GC has improved globally over the \ndecades due to improved case detection, early diagnosis, and \nbetter treatment strategies.2 However, there is still room for \nimprovement to achieve a favourable survival rate \nworldwide.2 Early diagnosis of GC plays an important role in \nachieving a better survival outcome of GC and an \nunderstanding of its epidemiology, variation in ethnicity, \nage, gender and genetic predispositions are crucial. The \n\n\n\nClinicopathological study of gastric cancer in a Malaysian \ntertiary public health care centre \n \nHtet Htet, MMedSc1, Thin Thin Win, MMedSc1, Wong Siew Tung, PhD1, Noor Hasni Bt Shamsudin, MMedSc2, \nKandasami Palayan, FRCS1 \n\n\n\n     \n1School of Medicine, International Medical University, Kuala Lumpur, Malaysia, 2Department of Histopathology, Hospital \nTuanku Ja'afar, Seremban, Ministry of Health, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 13 August 2023                                                                                                                                                                         \nCorresponding Author: Htet Htet                                                                                                                                                                                        \nEmail: hhnoel@gmail.com\n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 616\n\n\n\n\n\n\n\n\nClinicopathological study of gastric cancer in a Malaysian tertiary public health care centre\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                617 \n\n\n\nobjective of this study is to investigate the incidence and \ntrend of GC in Malaysia at one of the tertiary health care \ncentres, i.e., Hospital Tuanku Ja'afar (HTJ), Seremban, Negeri \nSembilan state, Malaysia from 2005 to 2018.  \n \n \nMATERIALS AND METHODS \nThis is a retrospective cross-sectional study of the \nhistologically confirmed GC data from 2008 to 2018. All \npatient records of histologically confirmed GC cases during \nthe study period at the Hospital Tuanku Ja\u2019afer (HTJ), \nSeremban, Negeri Sembilan, Malaysia were reviewed. Data \ncollected were clinicopathological parameters which included \nhistopathological diagnosis, age, gender, identification card \nnumber, patient registration number, ethnic group, date of \nbiopsy and histological diagnosis. Inclusion criteria included \nthat the patients must have attended HTJ between 2005 and \n2018 and paraffin-embedded gastric biopsy must be \navailable. The patients diagnosed with GC before 1 January  \n2005 or after 31 December 2018, patients who were \ndiagnosed with oesophageal cancer alone were excluded \nfrom the study. The index date was defined as the date of the \nfirst outpatient or inpatient visit with a diagnosis of GC. \nRecords of the patients who were first diagnosed with GC \nbefore 1st January 2005 were excluded from the study. Data \nwere analysed using Microsoft Excel. Confidentiality of the \ncollected information was maintained by strict measures. The \nnames, ethnic groups and ages of the patients were kept \nprivate and confidential apart from the research team. The \nidentities of patients were not revealed in this report.   \n \n \n \n\n\n\nRESULTS \nThere was a total of 233 cases reported as histologically \nconfirmed GC cases in HTJ, Seremban from 2005 to 2018. The \nnumber of annual reported cases of GC from 2005 to 2018 \nwas found to be varied. The number of reported GC cases in \nHTJ was observed as an increasing trend starting from 2016 \nonwards (Table I). \n \nThe youngest reported case was a 19-year-old Malaysian \nIndian man, and the oldest reported case was a 93-year-old \nMalaysian Chinese woman. The mean age of diagnosis is \n62.24 \u00b1 14.04 years. However, there were 38 cases whose ages \nwere not included in the report, and the estimated age was \ncalculated from the identification card (IC) number of the \npatient (which usually starts with the birth year of the person \nin Malaysia) and the year of the biopsy report. The number \nof reported and confirmed GC cases was found to be highest \namong the age group of 61\u201370, 51\u201360 and 71\u201380, respectively \n(Table II).   \n \nAmong 233 cases, 64% (n = 150) cases were males and 36% \n(n = 83) were females. The youngest age of reported GC cases \nfor females was 23, and the oldest one was 92. The youngest \nage of reported GC case for men was 19 and the oldest was \n93. Malaysian Chinese ethnic group has the highest \nincidence of GC with 41.63% (n = 97), followed by Malays \nwith 32.2% (n = 75) and Malaysian Indians with 23.61% (n \n= 55). There were a few cases reported from ethnic minorities \n1 case each (0.43%) from Orang Asli, Singh and others (Table \nII). \n \nAll reported cases were adenocarcinoma 100% (n = 233). In \nterms of histopathological grading, 45% (n = 104) were \n\n\n\nYear reported       2005         2006       2007       2008      2009        2010      2011     2012       2013       2014       2015     2016     2017    2018 \nNumber of             13             11           13            5           17             23          23         12           12           17           15         22         21        29 \nGC cases                    \n \nNote: GC = gastric cancer  \n\n\n\nTable I: Number of GC cases reported annually at the HTJ, Seremban, Negeri Sembilan, Malaysia from 2005\u20132018\n\n\n\nGender                  Ethnicity                       Number of cases                    Mean age of GC cases a                     Age in years (range) \n                                                                              n (%)                                at the time of diagnosis \n                                                                                                                            Age in years \u00b1 SD                                             \nFemale                    Chinese                              31 (37.35)                                     68.41 \u00b1 12.77                                           45\u201392 \n                                Indian                                26 (31.33)                                     59.38 \u00b1 14.04                                           23\u201380 \n                                 Malay                                24 (28.92)                                     57.76 \u00b1 14.06                                           34\u201383 \n                                others                                 2 (2.41)                                            60 \u00b1 20                                                40\u201380 \n                          Female (Total)                          83 (100)                                       61.99 \u00b1 14.64                                           23\u201392 \nMale                       Chinese                                 66 (44)                                        66.67 \u00b1 10.84                                           42\u201393 \n                                Indian                                29 (19.33)                                     54.63 \u00b1 12.74                                          30\u201383.2 \n                                 Malay                                  51 (34)                                        63.42 \u00b1 13.33                                           28\u201391 \n                                others                                 4 (2.67)                                       43.25 \u00b1 10.96                                           31\u201361 \n                           Male (Total)                           150 (100)                                       62.38 \u00b1 13.7                                            19\u201393 \nTotal                       Chinese                              97 (41.63)                                        67.23 \u00b1 12                                              42\u201393 \n                                Indian                                55 (23.61)                                     55.74 \u00b1 14.29                                          19\u201383.2 \n                                 Malay                                75 (32.19)                                     61.61 \u00b1 13.83                                           28\u201391 \n                                others                                 6 (2.58)                                       48.83 \u00b1 16.61                                           31\u201380 \n                                 Total                                 233 (100)                                      62.24 \u00b1 14.04                                           19\u201393 \n \nNote: SD = standard deviation \n \n\n\n\nTable II. Age, gender, and ethnic incidences of GC cases reported annually at the HTJ, Seremban, Negeri Sembilan, Malaysia from \n2005 to 2018\n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 617\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n618                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\npoorly differentiated type, 21% (n = 21) were moderately \ndifferentiated type, 3% (n = 7) were well-differentiated type, \nwhile there were 1 moderate to poorly differentiated type and \n1 moderate to well-differentiated type, 30% (n = 70) were not \nreported. According to Lauren\u2019s classification, 13% (n = 31) \nwere intestinal type, 15% (n = 34) were diffuse type and 1% \n(n = 2) were mixed type, while 74% (n = 172) did not find a \nreport for pathological subtype. Seven reported cases with \nsignet ring cell types which were considered as diffused type. \n \n \nDISCUSSION \nComparison with Previous Findings   \nThe shifting pattern of ethnic incidence of GC in Malaysia is \nthe most noticeable characteristic of this study. Among the \n233 laboratory-confirmed GC cases from the HTJ, Seremban \nfrom 2005 to 2018, 41.6% of diagnostically confirmed GC \ncases were Malaysian Chinese population, 31.8% were Malay \npopulation and 23.6% were Malaysian Indian population. \nAn earlier study which was done at the HTJ in 2013 showed \n55.0% Malaysian Chinese, 27.8% Malaysian Indian and \n16.6% Malay population.7 The second study which was \ncarried out at the Hospital Ipoh, Perak state, Malaysia also \nshowed 53.6% Malaysian Chinese, 36% Malaysian Indian \nand 26% Malay population. The study represented data from \n1988 to 1998.8 It indicates the increasing incidence of GC in  \nMalay population.  \n \nThe age-standardized rate for GC was 4\u20135 times lower in \nMalay than in the Malaysian Chinese and Malaysian Indian \npopulations. This gap seemed to be narrower due to the \nincreased number of GC cases in the Malay population and \ndecreased the number of cases in the other two populations.9 \nThe findings from this study agrees with the fact of the \nincreased number of GC cases in the Malay population. \nHowever, the incidence rate in the Malaysian Chinese and \nMalaysian Indian populations does not seem to decline \nsignificantly. This partly agrees with the MNCR report (2012\u2013\n2016), which stated as the Malaysian Chinese have the \nhighest incidence rate in both genders.4 According to MNCR \n2012\u20132016, the rate of GC was declined in Malaysia and was \nno longer listed as the 10th most common cancer. However, \nthe incidence of GC in Seremban, Negeri Sembilan state does \nnot seem to be declining until 2018. Globally, the highest \nnumber of cases was observed in Asia, specifically in China.10 \n \nThe mean age of diagnosis for GC was 62.75 \u00b1 13.95 years \nand only 9.8% of them (n = 23) are diagnosed under the age \nof 45 in this study. This agrees with the previous reports 60.8 \n\u00b1 14.744 years (19\u201391) and 65 years (male 65.3 years and \nfemale 63.2 years, p > 0.05).7,8 In our study, 9.8% of the \nreported cases were early-onset GC (45 years or younger) and \nthe remaining 91.2% were conventional GC (older than 45). \nThis finding agrees with the data from Machlowska et al (6), \nwhich stated that GC is not prevalent in younger age groups \nwho are <45 years of age.6 Early-onset GC was rare and not \nmore than 10% of patients underwent disease development.6 \n\n\n\nHowever, the youngest reported case in this study was a 19-\nyear-old Malaysian Indian male patient, and such cases \ncould have a genetic influence as a big role in the \ndevelopment of GC.  \n \n\n\n\nThere were 56.3% male patients in the study by Tata et al (7) \nwhereas our current study indicates that 63% male, \nindicating male predominance in GC.7 Both studies were \ndone in HTJ, Seremban, Negeri Sembilan state, Malaysia. In \nanother study done at the Hospital Ipoh, 68.4% (171 out of \n250 GC patients) were male patients.8 This clearly \ndemonstrates the male predominance in the incidence of GC. \nIn our study, among different populations, men had a higher \nincidence than women (68%, 68% and 52.7%) in all \nMalaysian populations: Malaysian Chinese, Malay and \nMalaysian Indian, respectively. The findings of our study \nagree with the previous reports, that there is a male \npreponderance in all main ethnic groups of Malaysia.4,6 \n\n\n\nGlobally, men have higher incidence than women, and \ndouble the number of cases were reported.9 \n \nAround the 1980s, only 3% of GC patients are diagnosed with \nearly GC but this was increased to 27% as stages 1 and 2 in \nthe twenty-first century, indicating an earlier diagnosis \ntrend.9 The mortality to an incidence rate (MIR) for GC in \nSouth East Asia (SEA) was reported as 0.88 and a similar rate \nwas observed for Malaysia.10 Incidence of GC in Malaysia was \ndeclined by 48% among males and 31% among females in \ntheir last reported period of 13 years.10 \n \nAll 233 cases in our review reported as adenocarcinoma type, \nand this agrees with the previous study.7 Most of the reported \ncases 45% were diagnosed as poorly differentiated, 21% were \nreported as moderately differentiated and only 3% were \nreported as well-differentiated. The site of the tumour was not \nconsistently informed. In the previous study, 45.6% were \ndiagnosed with stage 4B; 36% with stage 4A; and only 3.6% \nwith stage 1.8 This implied the late diagnosis nature of the \ndisease. Survival rate of the studied cases in this report was \nnot traced. The survival rate of GC has improved globally \nover the decades due to improved case detection, early \ndiagnosis, and better treatment strategies.2 However, there is \nstill room for improvement to achieve a favourable survival \nrate worldwide.2 \n \nIn addition, GC can be classified into intestinal type and \ndiffuse type depending on the histopathology.2,4 There was a \ndecline in the sporadic intestinal-type GC, but in contrast, the \nincidence of diffuse-type GC has reportedly increased.6 This \nstudy does not have any prior data to explore further. \n \nGeographic Diversity of GC \nThe incidence of GC displays immense geographical \ndiversity.6,9 This study only represents the data from the \nNegeri Sembilan state, Malaysia. Geographically, Kelantan \nstate, which is northeast of the Peninsular Malaysia, was \nobserved as having the lowest incidence of GC and Kelantan \nMalays were probably having the lowest rates of GC \nglobally.9 Thailand Enigma was reported where the Southern \npart of Thailand, was also observed as a lower incidence of H. \npylori infection compared to North, Northeast and Central \nThailand.11 Geographically, Kelantan state and the Southern \npart of Thailand are neighbouring states and share a \nsignificant pattern of similarity in diet and the abundance of \nsea foods, vegetables and deep-sea water.12 \n \n \n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 618\n\n\n\n\n\n\n\n\nClinicopathological study of gastric cancer in a Malaysian tertiary public health care centre\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                619 \n\n\n\nThe Indian enigma had reported by Misra in 2014.13 The \ngeographical distribution of GC differs widely in the different \nregions of India.13 Southern and Eastern India had shown a \nhigh incidence of GC frequency approximately four times \ncompared to North India.13 Non-vegetarian foods, \nparticularly, spicy and salty meat, fish, pickled food, high rice \nintake, excess chilli consumption, high-temperature foods, \nsmoked dried salted meat, use of soda and consumption of \ndried salted fish were observed as significant risk factors for \nGC compared to North India, where diet is mainly wheat-\nbased, a greater proportion of vegetarians and a higher \nintake of fruits and spices such as turmeric, garlic etc. These \ndietary habits were proposed as one of the explanations for \nthe Indian enigma.13  \n \nGlobally, the age-adjusted incidence rate was observed as a \ndownward trend in Japan which was probably due to \nimproved early diagnosis efforts and improved treatment \noutcomes in Japan.2,10 However, due to the increased number \nof elderly populations, the crude incidence rate of GC \ncontinued to increase, and GC was more frequently detected \nin Japan. After the two peaks in 2030\u20132034 (in men) and \n2025\u20132029 (in women), the decreasing trend of GC could be \nobserved as the younger generation in Japan was more aware \nof health, and they tend to adopt a healthy lifestyle \ncompared to the older generation.2 In February 2013, Japan \nbecame the first country in the world to cover H. pylori \neradication for chronic gastritis under its National Health \nInsurance (NHI) system.10 H. pylori eradication reduces the \nrisk of second GC to approximately one-third that of patients \nwho do not undergo eradication therapy (JAPANGAST study). \nThis indicates the benefit of H. pylori eradication in \npreventing GC.14,15 \n \nRisk Factors of GC \nAs known, H. pylori is classified as a type I carcinogen and is \nreported as a major risk factor for GC, especially for non-\ncardia GC. The reduction of the H. pylori infection rate in the \npopulation has contributed to the decline in the incidence of \nnon-cardia GC. In addition, this trend could be explained by \nthe increased standard of hygiene, better food conservation \nand a high intake of fruits and vegetables.2,4 For cardia GC, it \nis more related to risk factors such as body fat. It was expected \nthat cardia GC might be more frequent in future.2 Most of the \ncases are non-cardia GC in Malaysia, except in Kelantan, \nwhere the main site of involvement is cardia.9 The site of the \ntumour of GC, either cardia or non-cardia did not report \nconsistently and hence, we do not have a precise data \nregarding the cardia and non-cardia types in this study.  \n \nFive-Year Survival Rate of GC \nThe 5-year survival rate for GC in 2010\u20132014 was reported as \n68.9% for South Korea and 60.3% for Japan. However, the 5-\nyear survival rate of GC globally is still around 20%.10 It was \nstrongly believed that the early detection of GC had \ncontributed to these favourable health outcomes. However, \nthe median survival rate of GC is less than 12 months in the \nadvanced stage of GC.6 Due to its high aggressiveness and \nheterogeneous in nature, even with early diagnosis, GC will \nstill constitute as a global health issue.6 \n\n\n\n\n\n\n\nAccessing the trend of GC from one hospital data is not \nsufficient despite the data obtained are more than a decade. \nSome data, such as the age of the patients from certain \nreports, were not included. Confounding factors such as \nfamily history, occupation, comorbidities (e.g., diabetes \nmellitus, history of gastritis), social history (alcohol drinking, \nsmoking etc), dietary history, body mass index (BMI), status \nof H. pylori infection and physical activity were unable to \ninclude in this analysis.  \n \nThe epidemiology of GC in different geographical locations \ncan be sought out in future. The trend and the changes in the \nincidence of GC in previous low-incidence areas such as \nKelantan should also be studied along with the dietary and \nlifestyle changes. The prevalence of H. pylori infections and \nthe incidence of GC in different geographic locations could be \nstudied for Malaysia as well as for Asia and globally. \n \n \nCONCLUSION  \nIn this retrospective study, we studied the clinicopathological \ndata of GC, although the data we reported represented only \none hospital. The incidence of GC cases in Malay population \nwas observed to be increased. Late-onset GC cases were found \nto be more common than early-onset cases, while all reported \ncases were adenocarcinoma types. Globally, it was estimated \nthat there could be 1.8 million new cases and 1.3 million \ndeaths related to GC by 2040.16 And a higher incidence will be \nfound in medium and low HDI (Human Development Index) \ncountries compared to high HDI countries, hence, the SEA \ncountries should be observant on the burden of GC.16 \nAlthough GC showed a downward trend in Malaysia, it could \nagain lead to an increasing trend of GC. Because of the \nnature of high aggressiveness, late diagnosis, association \nwith lifestyle and non-communicable diseases such as \ndiabetes mellitus, the prevalence of H. pylori infection, \nvariation in responsiveness and awareness of the eradication \nregimens, GC could still constitute a local and global health \nissue. Consideration of lifestyle changes, health education, \ndetection and eradication of H. pylori infection and early \ndiagnosis of GC by health check-ups should be encouraged \nby the authorities. Hence, the authorities should consider \nadapting the H. pylori eradication regimen as a part of the \ninsurance scheme; detection of H. pylori as a part of routine \nhealth check-ups; early referral and an exploration of upper \nGI endoscopy of middle-aged people who are above 50 with \ndyspeptic symptoms should be considered. Since certain \ncountries and regions are estimated to have more burden of \nGC, health authorities should plan cancer control initiatives \nwithout delay. \n \n \nDISCLOSURE \nThe authors have no other relevant affiliations or financial \ninvolvement with any organisation or entity with a financial \ninterest in or financial conflict with the subject matter or \nmaterials discussed in the manuscript apart from those \ndisclosed. No writing assistance was utilised in the production \nof this manuscript. \n \n \n \n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 619\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n620                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nACKNOWLEDGEMENTS \nWe would like to thank the Director General of Health \nMalaysia for his permission to publish this article. This study \nis a part of the Fundamental Research Grant Scheme \nFRGS/1/2018/ SKK03/IMU/02/1. The projects and methods \nhad been granted ethical approval by the International \nMedical University, Malaysia with the project ID No: PHMS \n1/2020(04). The authors thank the Head of Department and \nstaff from the Histopathology Department, Hospital Tuanku \nJa'afar, Seremban, Negeri Sembilan State, Malaysia and the \nDirector and staff from the Institute For Research, \nDevelopment & Innovation, International Medical \nUniversity, Kuala Lumpur, Malaysia for their kind permission \nand assistance to retrieve the required data and support of \nthe project.  \n \n \nREFERENCES \n1. Globocan 2020. Cancer Today. Global Cancer Observatory. \n\n\n\nInternational Agency on Research on Cancer. World Health \nOrganization. March 2021. [cited 2023 April 28]. Available from: \nhttps://gco.iarc.fr/today/ \n\n\n\n2. Rawla P, Barsouk A. Epidemiology of gastric cancer: Global \ntrends, risk factors and prevention. Prz Gastroenterol. 2019; \n14(1): 26-38.  \n\n\n\n3. Sekiguchi M, Oda I, Matsuda T, Saito Y. Epidemiological trends \nand future perspectives of gastric cancer in Eastern Asia. \nDigestion 2022; 103(1): 22-8.  \n\n\n\n4. Azizah AM, Hashimah B, Nirmal K, Siti Zubaidah AR, Puteri NA, \nNabihah A et al. Malaysia National Cancer Registry Report \n(MNCR) 2012-2016. National Cancer Registry, National Cancer \nInstitute. Ministry of Health, Malaysia. [cited 2023 April 23] \nAvailable from: https://www.moh.gov.my/moh/resources/ \nPenerbitan/Laporan/Umum/2012-2016%20(MNCRR) \n\n\n\n5. Azizah Ab M, Nor Saleha IT, Noor Hashimah A, Asmah ZA, \nMastulu W. Malaysia National Cancer Registry Report (MNCR) \n2007-2011. National Cancer Registry, National Cancer Institute. \nMinistry of Health, Malaysia. [cited 2023 April 23] Available \nfrom: https://www.crc.gov.my/wp-content/uploads/documents/ \nreport/MNCRRrepor2007-2011.pdf \n\n\n\n6. Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric \ncancer: epidemiology, risk factors, classification, genomic \ncharacteristics and treatment strategies. Int J Mol Sci 2020; \n21(11): 4012.  \n\n\n\n7. Tata MD, Ratnasingam D, Gurunathan R, Palayan K. Delay in \ndiagnosis of upper gastrointestinal cancer: whose fault, is it? Med \nJ Malaysia 2013; 68(3): 275-7.  \n\n\n\n8. Kandasami P, Tan WJ, Norain K. Gastric cancer in Malaysia: the \nneed for early diagnosis. Med J Malaysia. 2003; 58(5): 758-62.  \n\n\n\n9. Lim KG, Palayan K A review of gastric cancer research in \nMalaysia. Asian Pacif J Cancer Prev 2019; 20(1): 5-11.  \n\n\n\n10. Ilic M, Ilic I. Epidemiology of stomach cancer. World J \nGastroenterol 2022; 28(12): 1187-203.  \n\n\n\n11. Pratoomchat B, Tongtawee T. Helicobacter pylori and gastric \ncancer \u201cThailand Enigma\u201d. (Poster presentation) Ann Oncol \n2018; 29 (supplementary 7).  \n\n\n\n12. Takeuchi H, Trang VT, Morimoto N, Nishida Y, Matsumura Y, \nSugiura T. Natural products and food components with anti-\nHelicobacter pylori activities. World J Gastroenterol 2014; 20(27): \n8971-8.  \n\n\n\n13. Misra V, Pandey R, Misra SP, Dwivedi M. Helicobacter pylori and \ngastric cancer: Indian enigma. World J Gastroenterol 2014; 20(6): \n1503-9.  \n\n\n\n14. Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of \nHelicobacter pylori on incidence of metachronous gastric \ncarcinoma after endoscopic resection of early gastric cancer: an \nopen-label, randomised controlled trial. Lancet 2008; 372: 392\u2013\n97.  \n\n\n\n15. Asaka M, Kobayashi M, Kudo T, Akino K, Asaka Y, Fujimori K, \nKikuchi S, Kawai S, Kato M. Gastric cancer deaths by age group \nin Japan: Outlook on preventive measures for elderly adults. \nCancer Sci 2020; 111(10): 3845-53.  \n\n\n\n16. Morgan E, Arnold M, Camargo MC, Gini A, Kunzmann AT, \nMatsuda T, et al. The current and future incidence and mortality \nof gastric cancer in 185 countries, 2020\u201340: a population-based \nmodelling study. eClinicalMedicine 2022; 47: 101404.  \n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 620\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                621 \n\n\n\nABSTRACT \nIntroduction: Financial affordability to purchase \ncommodities for disease prevention is an important public \nhealth issue. The objective of this paper is to report the \nfinancial affordability and willingness to pay amongst the \nparents of government students for their children\u2019s non-\nmedical mask use, using a newly created Household Face \nMask Affordability Questionnaire (MAQ). \n \nMaterials and Methods: This was a cross-sectional study \ninvolving the parents or guardians of 50.6%  (44/87) \ngovernment schools in the whole of Kuching Division of \nSarawak. The sampling method was multistage cluster \nsampling, whereby stage one involved random sampling of \n49.2%  (30/61) primary schools and  53.8% (14/46) secondary \nschools in the Kuching Division, followed by stage two \ncluster sampling of one class per non-examination standard \nin each randomly sampled school. All students in the \nsampled classes were asked to bring a face-validated \nquestionnaire (MAQ) back home to be answered by one of \ntheir parents or a guardian. A total of 2559 out of 3661 \ndistributed questionnaires were collected, with a response \nrate of 70%. The data collection period was between April \nand June of 2022 so as the recall bias of the information \ncollected, especially on the actual spending on the face \nmasks for the school going students, was minimised. The \nrelevant summary statistics for self-perceived face masks \ncharacteristics, face mask expenses, affordability and \nwillingness to pay were calculated. We regress separately \nthe monthly affordability and willingness to pay amount \nagainst age, occupation, marital status, total number of \nchildren, monthly income and monthly saving to build \npredictive models for affordability and willingness to pay \namount per child per month. \n \nResults: The average Scale-level Face Validity Indexes for all \naspects of validity (clarity, comprehension, relevancy, \nrepresentativeness) are high (0.91 to 1.00) for MAQ. Most of \nthe respondents were mothers, married, working as private \nemployees with a mean age of 41 and belonged to the B40 \nand M40 group. The average monthly saving per family was \nRM540, which was about 15% of the total income. The \naverage actual monthly spending to purchase face masks \nfor one child is RM24. On average, a family can afford to pay \nRM23.80 for one child per month to purchase face masks. \n\n\n\nThe willingness to pay for the same was RM25.27. The \nmedian affordability, willingness to pay and actual spending \nfor face masks per child was RM16.67 per month. Taking \n75th percentile as the reasonable maximum expenses per \nchild for face masks per month, the affordable amount by \nmost parents is RM30, with the willingness to pay at 10% \nhigher. Affordability to purchase a face mask is influenced \nby the marital status, occupation, income, saving and the \nnumber of dependent of the breadwinner of a household. \nThe most important face mask characteristics expected by \nthe parents are better filtration efficiency and easier \nbreathability.  \n \nConclusion: The affordability and willingness to pay the \namount to purchase face masks amongst parents of \ngovernment students in Sarawak were RM30 and RM33 per \nchild per month, respectively.  \n \nKEYWORDS:  \nAffordability, willingness to pay, face mask, universal masking, \nCOVID-19 \n \n \nINTRODUCTION \nThe COVID-19 pandemic forces the world population to \nadopt new norms in life, namely social distancing, wearing \nface masks and frequent sanitising.1 These new norms are \nessential and were made compulsory in Malaysia since 1st \nAugust 2020 to the general population in an effort to prevent \nCOVID-19 transmission in the country.2 Amongst these new \nnorms, the requirement to wear face mask imposes financial \nburden on the population, especially amongst the family \nwith schooling children, because of the shortage in supply \nand single-use feature of most non-medical masks in the \nmarket.3,4 \n \nThe World Health Organization has recommended universal \nmasking, meaning that everyone should wear a mask for \nCOVID-19 source control, rather than protection.5 Source \ncontrol means that if everyone is wearing a mask, then the \nchances of virus transmission from an unknown infected \nperson will be reduced significantly. Hence, Malaysia \ngovernment has implemented universal masking policy, \neither disposable or reusable, from 1st August 2020 for 2 \nyears, to control the COVID-19 cases in the country. \n\n\n\nParental affordability and willingness to pay for universal \nmasking amongst government school students in Kuching, \nSarawak \n \nAnselm Ting Su, PhD1, Jew Win Kuan, PhD1, Musdi Hj Shanat, PhD2, Baderin Osman, BSc3, Haalah Mahmud, \nBSc3 \n\n\n\n     \n1Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia, 2Faculty of Applied and Creative \nArts, Universiti Malaysia Sarawak, Sarawak, Malaysia, 3Dust Mask Laboratory, National Institute of Occupational Safety and \nHealth, Selangor, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 13 August 2023                                                                                                                                                                         \nCorresponding Author: Anselm Ting Su                                                                                                                                                                              \nEmail: stanselm.unimas@gmail.com \n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 621\n\n\n\n\n\n\n\n\n622                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nOriginal Article \n\n\n\nIn view of the potential financial burden to the population on \nthe use of single-use disposable mask in compliance with the \nuniversal masking policy, the authors have embarked on a \nstudy to determine the financial affordability for universal \nmasking amongst the parents of the government school-\ngoing students in Kuching, Sarawak, as well as to develop a \nwashable reusable fabric face mask within the determined \naffordability range for the use of school going students in \nSarawak. Although the indoor universal masking policy has \nbeen scrapped since 7th September 2022,6 the finding of this \nstudy is still important to serve as the basis for setting price \nceiling for face masks and production of affordable reusable \nface masks in the future. \n \nThe objective of this paper is to report results on the \naffordability and willingness to pay for their children\u2019s non-\nmedical mask use amongst the parents of government \nstudents in Kuching division of Sarawak, using a newly \ncreated Household Face Mask Affordability Questionnaire \n(MAQ), as there is no similar readily available questionnaire \nin the market. \n \n \nMATERIALS AND METHODS \nThis was a cross-sectional study involving the parents or \nguardians of  50.6% (44/87) of government schools in the \nwhole of Kuching Division of Sarawak. The sampling method \nwas multistage cluster sampling, whereby stage one involved \nrandom sampling of 49.2% (30/61) primary schools and \n53.8% (14/46) secondary schools in the Kuching Division, \nfollowed by stage two cluster sampling of one class per non-\nexamination standard (namely, Standard 1 to 5, Form 1, 2, 3 \nand Lower 6) in each randomly sampled school. Following \nthe sampling procedure, 54.5% (24/44) of schools were \nclassified as urban schools and the rest were classified as rural \nschools. All students in the sampled classes were asked to \nbring a questionnaire back home to be answered by one of \ntheir parents or a guardian. A total of 2559 out of 3661 \ndistributed questionnaires were collected, with a response rate \nof 70%. The data collection period was between April and \nJune of 2022 so as the recall bias of the information collected, \nespecially on the actual spending on the face masks for the \nschool-going students, was minimised. \n \nThe questionnaire on universal masking affordability and \nwillingness to pay, called Household Face Mask Affordability \nQuestionnaire (MAQ), was created by the authors for this \nstudy. The MAQ is a brief simple-to-use self-administered \nquestionnaire consisting of two parts: Part 1: Demographic \nInformation and Part 2: Affordability and Willingness to Pay. \nPart 1 of the questionnaire asks about the respondent\u2019s age, \noccupation, marital status, relationship with the student, \ntotal number of children and total number of school-going \nchildren. Part 2 of the questionnaire asks about total monthly \nhousehold income and saving, affordability and willingness \nto spend for face masks for all children, self-perceived \nimportant characteristics of face masks, and the actual \nmonthly spent for face masks during the COVID-19 universal \nmasking period where schools were reopened.  \n \nThe questionnaire was designed by a Public Health Physician \nand a parent with school-going children originally in English \n\n\n\nand underwent forward and backward translation into each \nMalay and Chinese language. As the MAQ is not a \npsychological construct questionnaire, we performed face \nvalidation on the questionnaire on the following aspects: \nclarity, comprehension, relevancy and representativeness, for \nquestions in the Part 2 of the questionnaire. The scale of the \nresponses ranges from 1 being \u2018very vague\u2019, \u2018tough to \nunderstand\u2019, \u2018very irrelevant\u2019 and \u2018totally not representing\u2019, \nto 5 being \u2018very clear\u2019, \u2018very easy to understand\u2019, \u2018very \nrelevant\u2019 and \u2018accurately representing\u2019, to the respective \nquestion. The face validation test was carried out on 18 \nconveniently selected parents of variable socio-demographic \nbackgrounds in Kuching before the commencement of the \nactual affordability study. The Raters in Agreement \nfrequency, Universal Agreement (UA), Item-level Face \nValidity Index (I-FVI), Scale-level Face Validity Index (S-FVI), \naverage of S-FVI and S-FVI/UA were calculated to determine \nthe face validity of the questionnaire. \n \nThe data were entered into Microsoft Excel and analysed \nusing RStudio 2023.03.0+386 \"Cherry Blossom\" Release for \nWindows. All continuous data was examined for its \ndistribution, with necessary transformation, if any, and its \nrelationship with categorical variables. The relevant \nsummary statistics for self-perceived face mask \ncharacteristics, face mask expenses, affordability and \nwillingness to pay were calculated. We regress separately the \nmonthly affordability and willingness to pay amount against \nmonthly age, occupation, marital status, total number of \nchildren, monthly income and monthly saving to build \npredictive models for affordability and willingness to pay \namount per child per month. \n \nThe study obtained ethical approval from the Universiti \nMalaysia Sarawak Medical Ethics Committee (Ethics \nReference: FME/21/93) and study approval from the Malaysia \nMinistry of Education (Approval Reference: KPM.600-3/2/3-\neras (11777)). All participating schools were briefed, and \nwritten consents were taken from all respondents before the \ndata collection.  \n \n \nRESULTS \nValidity of the Household Face Mask Affordability \nQuestionnaire \nTable I shows the validity index of the MAQ. The original \nquestionnaire is attached in the Appendix of this paper. The \nI-FVI for all questions are high, ranging from 0.83 to 1.00 for \nall aspects of face validity (clarity, comprehension, relevancy \nand representativeness). Although S-FVI/UA are low for \nrelevancy and representativeness, as some respondents \nclaimed that questions on total income and saving are not \ncrucial, the index is high for clarity and comprehension for \nall questions. The average S-FVIs for all aspects of validity are \nhigh (0.91 to 1.00) for MAQ in general, indicating the face \nvalidity of this questionnaire is good. \n \nSocio-demographic Characteristics of the Respondents \nTable II reports the socio-demographic characteristics of all \nrespondents. The statistics are calculated based on the valid \nresponses for each variable. Most of the respondents come \nfrom families that send their children to urban schools. Most \n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 622\n\n\n\n\n\n\n\n\nParental affordability and willingness to pay for universal masking amongst government school students in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                623 \n\n\n\nof the respondents were mothers, married and working as \nprivate employees, with a mean age of 41. On average, each \nfamily had three school-going children to support.  \n \nAffordability and Willingness to Pay for Children\u2019s \nUniversal Masking \nThe financial profile of the respondents reflects that most of \nthe families of government students belong to the B40 and \nM40 income group. The average monthly saving per family \nwas RM540, which was about 15% of the total income. The \naverage actual monthly spending to purchase face masks for \none child is RM24. On average, a family can afford to pay \nRM23.80 for one child per month to purchase face masks. \nThe willingness to pay for the same was RM25.27.  \n \nIt is undoubtedly that the data in Table III are skewed to the \nright, which is logical, reflecting the economic status of the \n\n\n\nrespondents. Hence, if we consider the median as the \nmeasure of central tendency, the affordability, willingness to \npay and actual spending for face masks per child was \nRM16.67 per month. Logically, if we consider 75th percentile \nas the reasonable maximum expenses per child for face \nmasks per month, the acceptable amount by most parents is \nRM30. \n \nCharacteristics of Face Mask that Affects Purchasing \nDecision \nThe parents\u2019 decision to purchase the type of face mask was \naffected by a face mask\u2019s characteristics as shown in Figure 1. \nThe most important face mask\u2019s characteristics are \u2018ability to \nblock the particles\u2019 and \u2018easier to breath\u2019. The median \nranking for both \u2018ability to block particles\u2019 and \u2018easier to \nbreath\u2019 is 5 (maximum rank is 5 = \u2018Extremely important \ncharacteristics\u2019), followed by \u2018cheaper price\u2019 and \u2018comfortable \n\n\n\nItem                             Clarity                               Comprehension                                Relevancy                             Representativeness \n                      Na           I-FVI          UA             Na          I-FVI           UA               Na           I-FVI            UA              Na           I-FVI          UA  \nQ7                  18           1.00         1.00            18           1.00           1.00               15            0.83            0.00             17            0.94          0.00 \nQ8                  18           1.00         1.00            18           1.00           1.00               16            0.89            0.00             15            0.83          0.00 \nQ9                  18           1.00         1.00            18           1.00           1.00               18            1.00            1.00             18            1.00          1.00 \nQ10                16           0.89         0.00            18           1.00           1.00               16            0.89            0.00             17            0.94          0.00 \nQ11                18           1.00         1.00            18           1.00           1.00               16            0.89            0.00             16            0.89          0.00 \nQ12                18           1.00         1.00            18           1.00           1.00               17            0.94            0.00             18            1.00          1.00 \nS-FVI/Ave                       0.98                                           1.00                                                0.91                                                0.94              \nS-FVI/UA                                        0.83                                            1.00                                                 0.17                                             0.33 \n \nNote:  \n1. Na represents the number of Raters in Agreement, denotes the number of rater scored \u201c1\u201d, represents \u201cYes\u201d, corresponding to the scale of 3 to 5 for \neach aspect of validity (clarity, comprehension, relevancy, representativeness), on a particular question, and \u201c0\u201d, represents \u201cNo\u201d, corresponding to the scale \nof 1 to 2 for each aspect.  \n2. I-FVI = Item-level Face Validity Index, is the Raters in Agreement divided by the number of raters.  \n3. UA = Universal Agreement, indicated by score \u20181\u2019 assigned to the question that achieved 100% raters in agreement in respective to each aspect of validity. \n4. S-FVI/Ave = Average Scale-level Face Validity Index, is the sum of I-FVI divided by the total number of questions. \n \n\n\n\nTable I: The validity indexes of Household Face Mask Affordability Questionnaire\n\n\n\nRespondent's characteristics                     n                 %             Mean             SD          p50             p25             p75           Min          Max  \nAge (years)*                                                                                                                                                                                                     \n   Respondent                                          2461           96.17          41.34            7.36          41               36               46             16             79 \n   Spouse                                                  2231           87.18          41.81            7.17          41               37               46             21             76 \nRelationship to the student (total)          2433          100.00                                                                                                                         \n   Mother                                                 1367           56.19                                                                                                                          \n   Father                                                    963            39.58                                                                                                                          \n   Guardian/relative                                 103             4.23                                                                                                                           \nMarital status (total)                                 2476          100.00                                                                                                                         \n   Married                                                2235           90.27                                                                                                                          \n   Single parent                                        223             9.01                                                                                                                           \n   Unmarried                                             18              0.73                                                                                                                           \nOccupation (total)                                     2483          100.00                                                                                                                         \n   Private employee                                 950            38.26                                                                                                                          \n   Government servant                            616            24.81                                                                                                                          \n   Housewife                                             527            21.22                                                                                                                          \n   Own business                                        263            10.59                                                                                                                          \n   Others                                                   127             5.11                                                                                                                           \nNo of children*                                                                                                                                                                                                \n   Schooling                                             2469           96.48           3.03             1.36           3                 3                 2               1              10 \n   Total                                                     2442           95.43           2.38             1.06           2                 2                 2               1               7 \nSchool type (total)                                     2559          100.00                                                                                                                         \n   Urban                                                   2262           88.39                                                                                                                          \n   Rural                                                      297            11.61                                                                                                                          \n \nNote: n = frequency denotes number of respondents contributing to the statistics, with its respective valid percentage against the total of 2559 respondents. \n \n\n\n\nTable II: Socio-demographic characteristics of respondents\n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 623\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n624                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nto skin\u2019 ranking at 4, and finally \u2018stylish/good looking\u2019 \nranking at 2. \n \nPredictive Factors for Affordability and Willingness to Pay \nThe final predictors retained following multiple linear \nregression for monthly affordability and willingness to pay \namount against monthly age, occupation, marital status, \ntotal number of children, monthly income and monthly \nsaving is shown in Table IV. We used backward stepwise \nanalysis for both outcomes and the adjusted R-squared \nvalues for affordability and willingness to pay models are \n0.2727 and 0.2712, respectively. Diagnostic plots for both \nmodels showed the models are adequate, where the residuals \nversus fitted plot revealed no relationship and all data points \nin the residuals versus leverage plot are within Cook\u2019s \ndistance. \n \nHence, the final model for monthly affordability amount to \npay for the face mask for one child is: \nA = 36.9 \u2013 3.2G \u2013 5.3M + 0.0019I + 0.0064S \u2013 6.3C \n \n \n\n\n\nwhere:                                                                                         \nA = Monthly affordability amount to pay for the face mask \nper child in RM                                                                          \nG = Status as a government servant valued as \u201c1\u201d if yes        \nM = Marital status valued as \u201c1\u201d if married                             \nI = Total monthly income in RM                                               \nS = Total monthly saving in RM                                               \nC = Total number of children in round number \n \nThe final model for monthly willingness to pay amount for \nthe face mask for one child is: \nW = 42.0 \u2013 5.3M + 0.0019I + 0.0064S \u2013 6.3C \n \nwhere: \nW = Monthly willingness to pay for the face mask per child in \nRM                                                                                              \nM = Marital status valued as \u201c1\u201d if married                             \nI = Total monthly income in RM                                               \nS = Total monthly saving in RM                                               \nC = Total number of children in round number \n \n \n\n\n\nVariables (RM)                                              n                 %             Mean             SD             p50           p25            p75           Min         Max  \nMonthly income (I)                                    2310           90.27        3693.33       2930.78      2542.50       1400          5000           80        12430 \nMonthly saving (S)                                     1790           69.95         540.36         566.30        300.00         100           1000            0          2300 \nI - S1729                                                     67.57         3241.67      2607.59       2400.00        1240         4800             0           12130 \nMonthly face mask expenses (E)*            2363           92.34          60.40           45.23          50.00           30             100             0           200 \nE per child                                                  2290           89.49          24.23           22.09          16.67           10              30              0           200 \nTotal monthly affordability (A)                2439           95.31          58.11           45.70          50.00           24             100             0           210 \nTotal monthly willingness to pay (W)      2439           95.31          58.11           45.70          50.00           30             100             0           210 \nA per child                                                  2365           92.42          23.80           23.13          16.67           10              30              0           200 \nW per child                                                 2350           91.83          25.27           24.33          16.67           10              33              0           200 \n \nNote: *This is the actual spending for face masks reported by the parents after schools reopened during COVID-19 pandemic where universal masking is still \nrequired. \n \n\n\n\nTable III: Financial profile, affordability and willingness to pay for children\u2019s universal masking during COVID-19 pandemic\n\n\n\nPredictors                                                              Coefficient (B)                               95% CI for B                                       p-value  \n                                                                                                                 Lower limit                Upper limit                             \n\n\n\n(a) Monthly affordability amount \nIntercept                                                                      36.8993                          32.907                       40.8916                         <0.001 \nOccupation                                                                                                                                                                                       \n   Others (housewife, others)                                        1                                                                                                              \n   Government servant                                             \u22123.1937                         \u22126.1279                      \u22120.2594                         0.0359 \n   Own business                                                         2.5848                          \u22120.7602                       5.9298                          0.1298 \n   Private sector employee                                       \u22121.0984                         \u22123.4995                       1.3026                          0.3697 \nMarital status                                                                                                                                                                                   \n   Single parent/guardian                                              1                                                                                                              \n   Married                                                                  \u22125.335                          \u22128.4874                      \u22122.1825                         0.0009 \nMonthly income                                                           0.0019                           0.0015                        0.0024                         <0.0001 \nMonthly saving                                                            0.0064                           0.0044                        0.0084                         <0.0001 \nTotal children                                                              \u22126.2717                         \u22126.9922                      \u22125.5512                        <0.0001 \n(b) Monthly willingness to pay amount \nIntercept                                                                      42.0269                         38.3693                      45.6846                        <0.0001 \nMarital status                                                                                                                                                                                   \n   Single parent/guardian                                              1                                                                                                              \n   Married                                                                  \u22125.335                               1                                                                        \nMonthly income                                                           0.0019                          \u22127.7034                     \u221210.9924                       \u22124.4144 \nMonthly saving                                                            0.0064                           0.0012                        0.0013                          0.0021 \nTotal children                                                              \u22126.2717                          0.0067                        0.0047                          0.0088\n\n\n\nTable IV.:Predictive factors for monthly (a) affordability (b) willingness to pay amount to purchase face masks for one child\n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 624\n\n\n\n\n\n\n\n\nParental affordability and willingness to pay for universal masking amongst government school students in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                625 \n\n\n\nDISCUSSION \nPrevious studies on non-medical masks use by the population \nfocussed mainly on determinants of willingness to pay or \nwillingness to wear face masks.7-9 No study has been focussing \non the affordability to purchase non-medical masks amongst \nthe population when universal masking is required. \nFinancial affordability to purchase commodities for disease \nprevention is an important public health issue. The current \nstudy reflects the financial affordability of the parents of \ngovernment students in Kuching population to purchase face \nmasks under universal masking policy accurately because of \nthe large sample size and random sampling strategy. The \nfindings of this study could be extrapolated to other states \nwith almost similar monthly household incomes, such as \nSabah, Pahang, Perak, Kedah and Perlis, where these are the \nstates within RM500 difference of monthly household income \nof Sarawak (mean = RM5087 in year 2020).10 \n \nCurrently, the retail ceiling price for face mask in Malaysia is \nRM0.70. It was reduced from the ceiling of RM1.50 before 1st \nMac 2020, further down to RM0.70 on 1 November 2020.11-13 \nThe reduction was likely intuitive based on strong demand \nfrom the population. The affordability amount of RM30 per \nchild per month found in this study is equivalent to the \nexpenditure of RM1 per piece of disposable face mask per \nchild per day. The finding shows that the current retail ceiling \nprice set by the government for face masks is reasonable \nconsidering the variation in different socio-economic levels of \npopulation across the country.  \n \nThe affordability and willingness to pay models derived in \nthis study can be used to determine the ceiling price of face \nmasks by the government in the future should the universal \n\n\n\nmasking policy is required. Although the models may not be \ncomprehensive as independent variables are limited to those \ntaken, they can readily be used for quick estimation. The \naffordability model itself indicates that when policymakers \nwant to set the ceiling price for face masks, they must take \ninto account at least the occupation, income, saving, marital \nstatus and number of dependents of the breadwinner within \na household in the targeted population.  \n \nMost studies focused on the health-related factors such as the \nperceived severity of disease and benefit of masking when it \ncomes to willingness to pay for and wear face mask.14,15 It is \nalso important to understand the perceived expected \ncharacteristics of face mask that would affect the consumer to \npurchase and use the mask. Our study found that the most \nimportant characteristics of the face mask that influence the \nchoice of the parents are filtration efficiency and \nbreathability. This information is important in two aspects, \nfirst to the government and the supplier, to ensure that the \nface masks that are sold legally in the market are of certain \nacceptable standards of filtration efficiency and \nbreathability. Second, the information reflects the knowledge \nlevel of the target population that serves as a benchmark for \nappropriate health education by public health professionals. \n \nThis study also produced the face-validated MAQ, which can \nbe used as a simple and quick questionnaire to determine the \naffordability level of the target population in this country. \nThe questionnaire was purposely made short and simple to \nimprove the accuracy of reporting. Hence, MAQ can be used \nby policymakers or market survey professionals for the \npurpose of policymaking and setting an affordable retail \nprice for face masks. \n\n\n\nFig. 1: Characteristics of face mask that affect purchasing decision by the parents.\n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 625\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n626                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nThe findings of this study are useful to various public health \nstakeholders for comprehensive and timeliness public health \nresponse during pandemic. The Ministry of Health should \nensure the quality of non-medical masks supplied in the \ncountry meeting the population\u2019s demand, namely filtration \nefficiency and breathability. The Ministry of Domestic Trade \nand Consumer Affairs should ensure the market price of non-\nmedical masks within the affordable level of the population, \nby continuous close monitoring of its supply and demand \nand being sensitive to future similar pandemic given the \nlesson learnt from the COVID-19 pandemic. Non-medical \nmask manufacturers should focus on the production of \nefficient and cost-effective masks to meet the population\u2019s \ndemand.  \n \nA major limitation of this study would be the restriction of \nstudy population to Kuching area due to logistic issues. \nNevertheless, since there has been no similar study done \nbefore, the current findings serve as a baseline for future \nextrapolation to other states of Malaysia. Another strength of \nthis research is the creation of validated MAQ, which can be \nused by all researchers in Malaysia for future studies. \n \n \nCONCLUSION \nThe affordability level to purchase face masks amongst the \nparents of government students in Sarawak was RM30 per \nchild per month. The willingness to pay for the same can be \nexpected to increase by 10%. The most important face mask \ncharacteristics expected by the parents are better filtration \nefficiency and easier breathability. Affordability to purchase \na face mask is influenced by the marital status, occupation, \nincome, saving, and number of dependents of the \nbreadwinner of a household.  \n \n \nACKNOWLEDGEMENTS \nThe study is sponsored by the Sarawak Research \nDevelopment Council under the grant number \nRDCRG02/CAT/2020/_4.  \n \n \nDISCLOSURE \nThe Sarawak Research Development Council was not \ninvolved in the planning, conduct and analysis of the study. \nThe authors declare no conflict of interest with the grant \nsponsor in completing this study. \n \n \n \n \n \n \n \n \n \n\n\n\nREFERENCES \n1. Ayenigbara IO, Adeleke OR, Ayenigbara GO, Adegboro JS, \n\n\n\nOlofintuyi OO. COVID-19 (SARS-CoV-2) pandemic: fears, facts, \nand preventive measures. Germs. 2020; 10(4): 218-28. \n\n\n\n2. Jayaraj VJ, Rampal S, Ng CW, Chong DWQ. The epidemiology of \nCOVID-19 in Malaysia. The Lancet Regional Health Western \nPacific. 2021; 17: 100295. \n\n\n\n3. Alcaraz JP, Le Coq L, Pourchez J, Thomas D, Chazelet S, Boudry \nI, et al. Reuse of medical face masks in domestic and community \nsettings without sacrificing safety: Ecological and economical \nlessons from the Covid-19 pandemic. Chemosphere. 2022; \n288(1): 132364. \n\n\n\n4. Chan TK. Universal masking for COVID-19: evidence, ethics and \nrecommendations. BMJ Global Health. 2020; 5: e002819. \n\n\n\n5. World Health Organization. Advice on the use of masks in the \ncontext of COVID-19: interim guidance, 6 April 2020. World \nHealth Organization. 2020. Available from: \nhttps://apps.who.int/iris/handle/10665/331693. \n\n\n\n6. Kaus J. Khairy: Use of face masks indoors now optional. The Star. \n[cited 2022 Sep 7]. Available from: \nhttps://www.thestar.com.my/news/nation/2022/09/07/khairy-\nwearing-facemasks-indoors-is-optional. \n\n\n\n7. Restiatun R, Yani A, Bariyah N, Suradi R. Factors influencing the \nwillingness to pay for masks during the COVID-19 pandemic: \nEmpirical evidence from Indonesia. Asian Development Policy \nReview. 2023; 11(2): 67-8. \n\n\n\n8. Ding Q, Lin S, Wang S. Determinants and willingness to pay for \npurchasing mask against COVID-19: a protection motivation \ntheory perspective. Int J Environ Res Public Health. 2022; 19: \n4268. \n\n\n\n9. Irfan M, Akhtar N, Ahmad M, Shahzad F, Elavarasan RM, Wu H, \net al. Assessing public willingness to wear face masks during the \nCOVID-19 pandemic: fresh insights from the theory of planned \nbehavior. Int J Environ Res Public Health. 2021; 18: 4577. \n\n\n\n10. Mahidin U. Household income estimates and incidence of \npoverty report, Malaysia, 2020. Department of Statistics \nMalaysia. [cited 2021 Aug 6]. Available from: \nh t t p s : / / w w w . d o s m . g o v . m y / p o r t a l - m a i n / r e l e a s e -\ncontent/household-income-estimates-and-incidence-of-poverty-\nreport-malaysia-2020. \n\n\n\n11. Bernama. Face mask ceiling price set a RM1.5 per piece effective \nApril 1. Bernama. [cited 2020 March 30]. Available from:  \nh t tp s : / /www.be rnama.com/en/genera l /news_cov id -\n19.php?id=1826626. \n\n\n\n12. Bernama. Face mask ceiling price set at 70 sen from Nov 1. The \nStar. [cited 2020 Oct 27]. Available from: \nhttps://www.thestar.com.my/news/nation/2020/10/27/face-\nmask-ceiling-price-set-at-70-sen-from-nov-1. \n\n\n\n13. Borneo Post. Domestic Trade Ministry: No plans to remove ceiling \nprice on 3-ply face mask. Malay Mail. [cited 2021 Sep 5]. \nAvailable from: \nhttps://www.malaymail.com/news/malaysia/2021/09/05/domes\ntic-trade-ministry-no-plans-to-remove-ceiling-price-on-3-ply-\nface-mask/2003154. \n\n\n\n14. Lee SE, Kim SJ, Oh KW, Lee KH. Purchase intention toward \nsustainable masks after COVID-19: the moderating role of health \nconcern. Fashion Textiles. 2022; 9(1): 43. \n\n\n\n15. Oreffice S, Quintana-Domeque C. (2021). COVID-19 \nInformation, demand, and willingness to pay for protective gear \nin the UK. Stud Microecon. 2021; 9(2): 180-95. \n\n\n\n\n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 626\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                627 \n\n\n\nABSTRACT \nIntroduction: Poor sleep quality is common among patients \nwith type 2 diabetes mellitus (T2DM). It has detrimental \neffects on physical and psychological health, as well as on \nquality of life. This study aimed to determine the prevalence \nof poor sleep quality among T2DM patients and to \ninvestigate the factors associated with this disorder.  \n \nMaterials and Methods: A cross-sectional study was \nconducted at Klinik Kesihatan Seremban in Seremban \ndistrict, Negeri Sembilan. Data were collected using the \nMalay version of the Pittsburgh Sleep Quality Index (PSQI-M) \nwith a cut-off point of >5 as poor sleep quality. The \nDepression Anxiety Stress Scale-21 (DASS-21) was used to \nmeasure level of psychological distress. Data were collected \nbetween July 2022 until January 2023. \n \nResults: A total of 319 patients with T2DM participated. Their \nmean age was 63 (11) years, 58% were women and 42.9% \nwere of Indian ethnicity. The mean total score of PSQI was \n4.04 (2.21) and 23% of the participants had poor sleep \nquality. Multivariate logistic regression analysis revealed \nthat poor sleep quality was significantly associated with \nIndian ethnicity (Adj. OR = 2.25; 95%CI: 1.05, 4.82; p = 0.037), \nseparated or widowed (Adj. OR = 2.16; 95%CI = 1.15, 4.05; p \n= 0.016), having nocturia (Adj. OR = 2.13; 95%CI = 1.18, 3.84; \np = 0.012) and depressive symptoms (Adj. OR = 3.41; 95%CI: \n1.01, 11.48; p = 0.048).  \n \nConclusion: Poor sleep quality was prevalent in almost a \nquarter of T2DM patients studied. Indian ethnicity, separated \nor widowed, having nocturia, and depressive symptoms \nwere independently associated with poor sleep quality. \nDespite lower prevalence of poor sleep quality compared to \nother studies, identification of those at higher risk warrants \nfurther exploration in lifestyle management of patients with \nT2DM. \n \nKEYWORDS:  \ntype 2 diabetes mellitus, sleep quality, psychological distress \n \n \nINTRODUCTION \nSleep is a physiological need for all human beings as it is \nimportant for both physical and psychological health. Its \nbenefits for vital functions at cellular, metabolic, \nneurological, cardiovascular, cognitive and emotional level \nare extensively studied.1 Despite individual variability with \n\n\n\nage across lifespan, recommended optimal healthy sleep \nduration for adults is 7 to 9 hours a day.1 Some indicators for \ngood sleep quality are shorter sleep latency, fewer \nawakenings, less time needed to wake after sleep onset, and \nhigher sleep efficiency.2 Short sleep duration (< 6 hours per \n24-hour) and long sleep duration (> 9 hours per 24-hour) are \nassociated with multiple morbidities.1,3 Poor sleep quantity \nand quality are implicated for the development and control \nof type 2 diabetes mellitus (T2DM) and obesity.3-5 Inadequate \nsleep causes hormonal imbalance in the body, which induces \nincreases in appetite, blood sugar and insulin resistance \nresulting in obesity and poor glycaemic control.3 Hence, \nhigher prevalence of sleep problem is expected among T2DM \npatients with obesity and poor glycaemic control.   \n \nPrevalence of sleep problems among the general adult \npopulation in Asia Pacific region ranged from 15 to 45%.6-9 \n\n\n\nMeanwhile, approximately 33 to 81% of T2DM patients \nreported sleep problems5,8,10,11 and the proportion was \ncomparatively higher than the general population.8 Diabetes \nmellitus (DM) is a growing public health concern worldwide. \nGlobally in 2021, International Diabetes Federation reported \naround 537 million people live with diabetes12, while in \nMalaysia it was estimated that 3.9 million (18.3%) of the \nadult population had deranged glycaemic index in 2019; \ncompared to only 13.4% in 2015.13 These numbers are \nforecasted to expand further in the future. Studies showed \nthat higher age, female gender, high BMI, poor glycaemic \ncontrol, longer duration of diabetes, diabetic complications \nand psychological factors increased the risk for poor sleep \nquality among T2DM patients.5,8,10,11,14 Some of the factors are \nmodifiable with multiple benefits such as weight \nmanagement, glycaemic control and better mental health. In \nMalaysia, there is a dearth of information reported on sleep \nquality and its associated factors among T2DM patients. This \nstudy aimed to identify the prevalence of poor sleep quality \nand determine its associated factors among patients with \nT2DM. \n \n \nMATERIALS AND METHODS \nStudy design, location, and population \nThis is a cross-sectional study conducted from July 2022 until \nJanuary 2023 at a non-communicable diseases (NCD) clinic, \nKlinik Kesihatan Seremban in the Seremban district of Negeri \nSembilan. Participants of this study were National Diabetes \nRegistry (NDR) patients from the clinic. Until June 2021, this \nclinic had a total of 5445 registered diabetic patients \n\n\n\nA cross-sectional study on the sleep quality among type 2 \ndiabetes mellitus patients and its associated factors \n \nNorhazimah Saparwan, MBBS1,2, Noorlaili Mohd Tohit, PhD2, Salmiah Md Sharif, MMed Fam Med3 \n\n\n\n     \n1Klinik Kesihatan Seremban 2, Ministry of Health Malaysia, Negeri Sembilan, Malaysia,  2Department of Family Medicine, \nFaculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak, Kuala Lumpur, Malaysia, 3Klinik Kesihatan \nSeremban, Ministry of Health Malaysia, Negeri Sembilan, Malaysia\n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 13 August 2023                                                                                                                                                                         \nCorresponding Author: Noorlaili Mohd Tohit                                                                                                                                                                      \nEmail: laili@ppukm.ukm.edu.my\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 627\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n628                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nconsisting of 38.7% Indians, 38.5% Chinese, 22.1% Malay \nand 0.7% other ethnics (unpublished data). \n \nSample Size  \nSample size was calculated using the population proportion \nformula with a population size of 5445 registered T2DM \npatients in the clinic, 95% confidence interval, 5% margin of \nerror and 32% population proportion from a local sleep \nquality study among T2DM patients.15  Sample size needed \nwas 316. Considering 10% non-response rate, 347 \nparticipants should be recruited. Each answered \nquestionnaire was immediately checked for completion to \nreduce non-responder. \n \nData Collection and Sampling Method \nSystematic random sampling was carried out with a \nsampling interval of two, based on the T2DM patient \nappointment list extracted from the tele-primary care (TPC) \nsystem with up to 90 patients listed per day. Each patient is \nnumbered, and a computer-generated random number was \nused to select the first patient followed by every other patient \nin the list to intensify recruitment. \n \nData collection was only done for a fixed day in a week for \n24 weeks as the main researcher (NS) had clinical duties in \nthe clinic. Recruitments were challenging as some listed \npatients were affected by Covid19 infection or close contact or \nthere were other reasons hindering clinic visit. \n \nMalaysian citizens aged 18 years and above, diagnosed with \nT2DM of at least six months duration, having attended \ndiabetic follow-up at Klinik Kesihatan Seremban, having \nlatest HbA1c result within one year and literate in Malay or \nEnglish were invited to participate. Those  having conditions \nor illness that do not permit completion of the self-\nadministered questionnaire, working in night shifts or \ntravelling across time zones within one month, pregnant \nwomen, breastfeeding mothers, those with type 1 diabetes \nmellitus (T1DM), having mental illness or use of any kind of \npsychotropic medication, having sleep disorder diagnosed \nprior to diabetes, having endocrine disorders (for example \nthyroid disease), chronic use of glucocorticoid and having \nheart failure were excluded from selection. A brief \nintroduction about the study was given to those recruited, \nand written informed consent was obtained. A self-\nadministered questionnaire was given to the participants \nwhich took about 15 minutes to be completed. A researcher \nwas available on-site for further assistance if necessary. \n \nStudy Instruments  \nData was collected using a structured questionnaire \nconsisting of four parts: sociodemographic data, clinical \nprofile, sleep quality questionnaire and Depression, Anxiety \nand Stress Scale 21-Item questionnaire (DASS-21). It was \navailable in dual language, in Malay and English.  \n \nPart I comprised of personal data of participant such as age, \ngender, ethnicity, marital status, educational level, \nemployment status, and estimated household income.  \n \n \n \n\n\n\nPart II documented their clinical profiles such as duration of \nT2DM, body mass index (BMI), HbA1c level, nocturia, \ncomorbidities and diabetic complications. Body mass index \nwas calculated using the weight and height measured by the \nstandardized stadiometer with a weighing scale during     the \nday of follow-up. The most recent HbA1c levels within the \npast one year were documented from the electronic medical \nrecord system. Other clinical information was collected from \nparticipants\u2019 home-based follow-up cards and confirmed \nwith the electronic medical record system. \n \nPart III was the Pittsburgh Sleep Quality Index (PSQI). This \nself-administered questionnaire developed in 1989 with the \nmain goal of differentiating between people who slept well \nand poorly over the past one month.16 It was locally \ntranslated to Malay (PSQI-M) and validated with Cronbach \nalpha of 0.74 for internal consistency and test-retest \nreliability of 0.58.17 The PSQI is a self-reported questionnaire \nwith 19 items from seven components that assesses subjective \nsleep quality. The seven components are (1) sleep quality (1 \nitem), (2) sleep latency (2 items), (3) sleep duration (1 item), \n(4) sleep efficiency (3 items), (5) sleep disturbance (9 items), \n(6) sleep medication (1 item) and (7) daily dysfunction (2 \nitems). Each component is given a value between 0 and 3, \nand the aggregate of the individual components results in a \nPSQI global score between 0 and 21. A score of 5 or less \nindicates \"good sleepers,\" whereas a score of greater than 5 \nindicates \"poor sleepers\".16 \n \nFor  Part IV, depression, anxiety, and stress were measured \nusing the Depression, Anxiety and Stress Scale (DASS 21).18 \nPart IV contains 21 items divided into three subscales of \ndepression, anxiety, and stress, with seven items allocated for \neach subscale. It inquired about recent experiences in the \npast week and the items were scored on a 4-point scale \nranging from 0 (did not apply to me at all) to 3 (applied to \nme very much, or most of the time). The range of score a \nparticipant could get for each subscale varied from 0 to 21. \nThe total scores were summed up and multiplied by 2.18 The \nrecommended cut-off points were used to classify participants \ninto normal, mild, moderate, severe, and extremely severe in \nterms of depression, anxiety, and stress as in Table I. \nParticipants were classified as having depressive or anxiety or \nstress symptoms if they scored above the cutoff point for \nnormal in the respective subscale. The validated Malay \nversion of DASS21 used in this study reported Cronbach's \nalpha of 0.84, 0.74 and 0.79 for depression, anxiety, and \nstress, respectively.19 \n \nData Analysis \nData were analysed using the SPSS software version 27. \nDescriptive analysis was performed using frequencies and \npercentages for categorical variables and mean \u00b1 standard \ndeviation (SD) for continuous variables. Simple and multiple \nlogistic regression analyses were used to determine factors \nindependently associated with sleep quality. Variables with p \n< 0.25 in the simple logistic regression and important \nvariables from literature were further assessed in multiple \nlogistic regression. p-value of < 0.05 was set as level of \nsignificant. \n \n \n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 628\n\n\n\n\n\n\n\n\nA cross-sectional study on the sleep quality among type 2 diabetes mellitus patients and its associated factors\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                629 \n\n\n\nSeverity                                                Depression                                         Anxiety                                                       Stress \nNormal                                                         0-9                                                    0-7                                                            0-14 \nMild                                                            10-13                                                  8-9                                                           15-18 \nModerate                                                   14-20                                                10-14                                                         19-25 \nSevere                                                        21-27                                                15-19                                                         26-33 \nExtremely severe                                         28+                                                   20+                                                            34+ \n\n\n\nTable I: Cutoff points for DASS-21 scale 18\n\n\n\nFactors                                                                                                                  Sleep quality, n (%)                                             n (%) \n                                                                                                        Poor sleep                        Good sleep \n                                                                                                           (n = 74)                             (n = 245) \n\n\n\nAge (years)*                                                                                            63 (12)                              62 (10)                                 63 (11)             \nGender                                            Female                                            50 (27.0)                           135 (73.0)                              185 (58.0) \n\n\n\n                                                 Male                                                24 (17.9)                           110 (82.1)                              134 (42.0) \nEthnicity                                          Malay                                              14 (18.9)                            60 (81.1)                                74 (23.2) \n\n\n\n                                                 Indian                                            41 (29.9)                            96 (70.1)                               137 (42.9) \n                                                 Chinese                                            19 (17.6)                            89 (82.4)                               108 (33.9) \n\n\n\nMarital Status                                 Single                                               4 (16.0)                             21 (84.0)                                 25 (7.8) \n                                                 Married                                           43 (19.4)                           179 (80.6)                              222 (69.6) \n                                                 Separated                                         5 (45.5)                              6 (54.5)                                  11 (3.4) \n                                                 Widowed                                        22 (36.1)                            39 (63.9)                                61 (19.1) \n\n\n\nEducation level                               No formal education                       7 (43.8)                              9 (56.3)                                  16 (5.0) \n                                                 Primary education                          17 (19.8)                            69 (80.2)                                86 (27.0) \n                                                 Secondary education                     44 (24.4)                           136 (75.6)                              180 (56.4) \n                                                 Tertiary education                           6 (16.2)                             31 (83.8)                                37 (11.6) \n\n\n\nEmployment status                        Employed                                        16 (18.4)                            71 (81.6)                                87 (27.3) \n                                                 Unemployed                                   42 (25.3)                           124 (74.7)                              166 (52.0) \n                                                 Pensioner                                        16 (24.2)                            50 (75.8)                                66 (20.7) \n\n\n\nHousehold income (RM) *                                                                  2122 (3008)                       1778 (2300)                           1858 (2481) \n \n*Mean (SD)  \n\n\n\nTable II: Socio-demographic characteristics of all participants\n\n\n\nFactors                                                                                                                              Sleep quality, n (%)                                 n (%) \n                                                                                                                               Poor sleep                  Good sleep \n                                                                                                                                  (n = 74)                        (n = 245) \nDuration of T2DM(years)*                                                                                     6.8 (6.7)                        7.1 (6.2)                       7 (6.0) \nBMI (kg/m2)*                                                                                                          27.4 (5.7)                        27 (4.5)                     27.1 (4.8) \nBMI categories                             Underweight/normal (BMI \u2264 22.9)                   16 (26.7)                       44 (73.3)                    60 (18.8) \n                                                     Overweight (BMI 23-27.4)                                 27 (22.5)                       93 (77.5)                   120 (37.6) \n                                                     Obese (BMI \u2265 27.5)                                         31 (22.3)                     108 (77.7)                  139 (43.6) \nHbA1c grouping                          Uncontrolled (\u22657 %)                                         42 (23.9)                      134 (76.1)                  176 (55.2) \n                                                     Controlled (< 7%)                                              32 (22.4)                      111 (77.6)                  143 (44.8) \nNocturia                                       Yes                                                                  50 (30.1)                      116 (69.9)                  166 (52.0) \n                                                     No                                                                    24 (15.7)                      129 (84.3)                  153 (48.0) \nComorbidities                              No comorbidities                                              3 (13.0)                        20 (87.0)                     23 (7.2) \n                                                     Hypertension                                                  17 (23.3)                       56 (76.7)                    73 (22.9) \n                                                     Dyslipidemia                                                      13 (28.9)                       32 (71.1)                    45 (14.1) \n                                                     Both                                                                42 (21.6)                      152 (78.4)                  194 (60.8) \nDiabetic complications               No complication                                              58 (22.1)                      205 (77.9)                  263 (82.4)     \n                                                     Retinopathy                                                        0 (0.0)                         4 (100.0)                       4 (1.3) \n                                                     Nephropathy                                                    9 (33.3)                        18 (66.7)                     27 (8.5) \n                                                     Ischemic heart disease                                      5 (27.8)                       13 (72.2)                     18 (5.6) \n                                                     Cerebrovascular accident                                   2 (22.2)                         7 (77.8)                       9 (2.8) \nDepression                                   Normal                                                               63 (21.0)                      237 (79.0)                  300 (94.0) \n                                                     Mild                                                                    5 (50.0)                         5 (50.0)                      10 (3.1) \n                                                     Moderate                                                            2 (40.0)                         3 (60.0)                       5 (1.6) \n                                                     Severe to extremely severe                               4 (100.0)                         0 (0.0)                        4 (1.3) \nAnxiety                                         Normal                                                               64 (21.2)                      238 (78.8)                  302 (94.7) \n                                                     Mild                                                                    4 (44.4)                         5 (55.6)                       9 (2.8) \n                                                     Moderate                                                            4 (80.0)                         1 (20.0)                       5 (1.6) \n                                                     Severe to extremely severe                                2 (66.7)                         1 (33.3)                       3 (0.9) \nStress                                            Normal                                                               63 (20.8)                      240 (79.2)                  303 (95.0) \n                                                     Mild                                                                    4 (50.0)                         4 (50.0)                       8 (2.5) \n                                                     Moderate                                                           5 (100.0)                         0 (0.0)                        5 (1.6) \n                                                     Severe to extremely severe                                2 (66.7)                         1 (33.3)                       3 (0.9) \n \n*Mean (SD) \n\n\n\nTable III: Clinical characteristics of all participants\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 629\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n630                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nEthical Approval \nThis study was approved by Universiti Kebangsaan Malaysia \nResearch Ethics Committee (JEP-2021-800) and Institute of \nMedical Research Ethics Committee. This project was \nregistered with the National Medical Research Registration \n(NMRR ID-21-01986-E44). Permission to conduct the research \nwas also obtained from the Negeri Sembilan State of Health \nDepartment, Seremban District Health Office, and the Family \nMedicine Specialist in Klinik Kesihatan Seremban. \n \n \nRESULTS \nResponse Rate \nA total of 346 T2DM patients were approached, however 15 \npatients refused, and 12 were excluded due to T1DM (one \nparticipant), three had underlying mental problems, four \nhad been working night shift for the past one month and \nanother four had thyroid disorders. All 319 participants \ncompleted the questionnaire making the response rate of \n100%. \n \nCharacteristics of Participants  \nMean age of the participants was 63 years and more than \nhalf of them were women (58%) (Table II). Indians made up \nthe largest ethnic    group (42.9%), more than half of the \nparticipants had at least secondary education levels (56.4%), \ntwo-third were married (69.6%) and half of them were \n\n\n\nunemployed (52%). Slightly more than half of the \nparticipants had uncontrolled T2DM with HbA1c more than \n7% (55.2%) and two fifth of them were obese (43.6%) (Table \nIII). Majority were having comorbidities (97.8%) with nearly \ntwo-third of them having both hypertension and \ndyslipidaemia (60.8%). Most of the participants had no \ndiabetic complications (82.4%) and about half of them (52%) \nexperienced nocturia for the past one month. Nephropathy \nwas the most common complication, followed by Ischemic \nHeart Disease, Cerebrovascular Accident, and lastly Diabetic \nRetinopathy. Participants with depressive, anxiety and stress \nsymptoms were about 6%, 5.3% and 5%, respectively. \n \nPrevalence of poor sleep quality \nThe total mean PSQI score among the participants was 4.04 \n(2.21) with 23% participants had PSQI score of >5, indicating \npoor sleep quality.  \n \nFactors associated with poor sleep quality \nSimple logistic regression revealed p < 0.25 for gender, \nethnicity, marital status, employment, having nocturia and \npsychological distress namely depression, anxiety, and stress \n(Table IV). All the above variables and six other important \nvariables identified from literature, namely age, BMI \ncategory, HbA1c group, duration of T2DM, co-morbidity and \ndiabetic complications were also included for multivariate \nanalysis. \n\n\n\nFactors                                                                                                           \u00df                 Crude OR (95% CI)          Wald test          p value \nAge (years)*                                                                                                 0.01                  1.00 (0.98, 1.03)                 0.51                0.474 \nGender                                         Female                                                    0.52                  1.69 (0.98, 2.93)                 3.58                0.058 \n                                                    Male                                                                                          ref                                                      \nEthnicity                                      Malay                                                                                        ref                                                      \n                                                    Indian                                                    0.60                  1.83 (0.92, 3.63)                 2.97                0.085 \n                                                    Chinese                                                   -0.89                 0.91 (0.42, 1.96)                 0.05                0.820 \nMarital status                              Married                                                                                     ref                                                      \n                                                    Single                                                      -0.28                 0.75 (0.24, 2.29)                 0.24                0.618 \n                                                    Separated/widow                                   0.91                  2.48 (1.38, 4.44)                 9.39                0.002 \nEducation level                           No formal/primary education                0.46                  1.59(0.59, 4.26)                  0.84                0.357 \n                                                    Secondary education                              0.51                  1.67 (0.65, 4.27)                 1.15                0.283 \n                                                    Tertiary education                                                                   ref                                                      \nEmployment status                     Employed                                                                                 ref                                                      \n                                                    Unemployed/pensioner                          0.39                  1.47 (0.79, 2.74)                 1.53                0.215 \nDuration of T2DM (years)*                                                                       -0.009                0.99 (0.95, 1.03)                 0.16                0.687 \nBMI categories                            Underweight/normal (BMI \u2264 22.9)                                            ref                                                         \n                                                    Overweight (BMI 23-27.4)                     -0.22                 0.79 (0.39, 1.63)                 0.38                0.537 \n                                                    Obese (BMI \u2265 27.5)                               -0.23                 0.78 (0.39, 1.58)                 0.44                0.506 \nHbA1c grouping                         Uncontrolled (\u22657 %)                               0.08                  1.08 (0.64, 1.83)                 0.09                0.755 \n                                                    Controlled (< 7%)                                                                      ref                                                         \nNocturia                                       Yes                                                        0.84                  2.31 (1.34, 4.00)                 9.04                0.003 \n                                                    No                                                                                                ref                                                         \nComorbidities                              No comorbidities                                                                      ref                                                         \n                                                    Hypertension                                       -0.01                 0.99 (0.53, 1.84)               <0.001              0.983 \n                                                    Dyslipidemia                                           0.35                  1.41 (0.70, 2.87)                 0.94                0.331 \n                                                    Both                                                     -0.21                 0.80 (0.47, 1.36)                 0.66                0.415 \nDiabetic complications              No complication                                   0.34                  1.41 (0.73, 2.70)                 1.09                0.296 \nDepression                                  Yes                                                           1.64                 5.17 (1.99, 13.40)               11.44               0.001 \n                                                    No                                                                                                ref                                                         \nAnxiety                                        Yes                                                           1.67                 5.31 (1.94, 14.50)               10.61               0.001 \n                                                    No                                                                                                ref                                                         \nStress                                            Yes                                                           2.12                 8.38 (2.81, 25.00)               14.53              <0.001 \n                                                    No                                                                                                ref \n                                                                                                                          \n* Mean (SD)  \n\n\n\nTable IV: Factors associated with sleep quality among participants using simple logistic regression\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 630\n\n\n\n\n\n\n\n\nA cross-sectional study on the sleep quality among type 2 diabetes mellitus patients and its associated factors\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                631 \n\n\n\nIn the multiple logistic regression analysis shown in Table V, \nIndian ethnicity, having nocturia, separated or widowed, and \nhaving depressive symptoms were significant independent \nfactors associated with poor sleep quality. Indian participants \nhad 2.25 times the odds (Adj. OR = 2.25; 95% CI = 1.05, 4.82) \nof having poor sleep quality compared to Malays. Those who \nwere separated or widowed had two times the odds (Adj. OR \n= 2.16; 95% CI = 1.15, 4.05) of having poor sleep quality than \nthose who were married. T2DM patients with nocturia had \n2.13 times the odds (Adj. OR = 2.13; 95% CI = 1.18, 3.84) of \nhaving poor sleep quality than T2DM patients without \nnocturia. Those with depressive symptoms have more than 3 \ntimes higher risk (Adj. OR = 3.41; 95% CI = 1.01, 11.48) of \nhaving poor sleep quality compared to those without \ndepressive symptoms. \n \n \nDISCUSSION \nPrevalence of Poor Sleep Quality \nThe results of the present study demonstrated that 23% of \nT2DM patients participated had poor sleep quality. This \nfinding is the lowest prevalence compared to other studies \namong T2DM patients. \n  \nInternationally, studies showed prevalence of poor sleep \nquality among T2DM patients ranging from 33.6% in \nChina,10 38.1% in Iran,20 47.2% in Ethiopia,21 47.6% in \nKanagawa, Japan5 to 81% in Jordan.11 Another study in \nJapan reported 43.9% poor sleep quality among T2DM \npatients compared to 38.4% among control group.8 \n\n\n\nMeanwhile in east coast Malaysia, a recent study among 350 \nT2DM patients in Kelantan found 32% of them having poor \nsleep quality.15 Lower prevalence in our study could be \nattributed to different socio-demographic and clinical \ncharacteristics of the participants as seen in a study among \nmultiethnic population in Singapore.22 Other local studies \namong various population groups reported higher \nproportion of poor sleep quality such as in working adults \n(45%),17 nurses (57.8%),23 secondary school teachers (61%)24 \nand pre-clinical medical students (63.9%).25  \n \nNevertheless, more importantly the impact of both diabetes \nmellitus and poor sleep was associated with higher risk of all-\ncause mortality compared to either condition alone, as \nreported in UK Biobank cohort data.26  \n \n\n\n\nAssociated Factors for Poor Sleep Quality \nIndian ethnicity, separated or widowed, having nocturia and \nhaving depressive symptoms showed four independent \nfactors of poor sleep quality in this study. Another local study \namong T2DM patients in Kelantan reported nocturia, restless \nleg syndrome and emotional distress were significantly \nassociated with poor sleep.15  \n \nThe ethnic distribution of our study participants were 42.9% \nIndians, 33.9% Chinese and 23.2% Malays, almost similar to \nthe NDR proportion in the clinic. Comparison for ethnicity \nwas limited by unavailability of local study among T2DM \npatients of multiethnic groups. Local studies among \nsecondary school students and elderly population showed \nhigher proportion of poor sleep quality among Indian \nparticipants compared to all participants, though the \ndifference was not statistically significant.27,28 A population \nstudy of sleep quality among Singapore residents with \nmultiethnic representation showed Indian and Malay \nethnicities were at higher odds of poor sleep quality \ncompared to Chinese.22 A review of sleep studies in the United \nStates of America showed that ethnic minorities were at a \ndisadvantage for sleep health disparities compared to White \npopulations.29 Psychosocial stressors, neighbourhood context, \nsocioeconomic status and access to and utilization of health \ncare were some factors attributed to the sleep health \ndisparities which could possibly explained the higher \nprevalence of poor sleep among Indians in our study.29 \n \nIn terms of marital status, a study in Singapore reported that \nthose divorced/separated were at higher risks of poor sleep \nquality compared to married participants, which is consistent \nwith our findings.22 Those divorced and widowed could \npossibly be at socioeconomic disadvantage and under higher \npsychosocial stressor.29,30 \n \nParticipants having nocturia had more than two times the \nodds of experiencing poor sleep compared to those without \nnocturia. Nocturia among T2DM patients was another \nindependent predictor of poor sleep quality in our study \nconsistent with a local study done among T2DM patients in \nKelantan.15 Among Asian population, another study in \nSingapore similarly reported nocturia as the only \nsignificantly associated factor with poor sleep quality among \n199 elderly with T2DM, hyperlipidaemia and hypertension.31 \nA recent large meta-analysis explored the relationship \n\n\n\nFactors                                                                                                    Multiple logistic regression\u1d43                                              p value \n                                                                                            \u00df                        Adjusted OR (95% CI)                Wald test \nEthnic                                  Malay                                     ref                                                                                6.17                          0.046 \n                                            Chinese                                 0.16                           1.18 (0.51, 2.71)                         0.15                          0.701 \n                                            Indian                                   0.81                           2.25 (1.05, 4.82)                         4.37                          0.037 \nMarital                               Married                                  ref                                                                                7.21                          0.027 \n                                            Single                                   -0.46                           0.64 (0.19, 2.05)                         0.58                          0.446 \n                                            Separated/widow                0.77                           2.16 (1.15, 4.05)                         5.81                          0.016 \nNocturia                              Yes                                        0.76                           2.13 (1.18, 3.84)                         6.36                          0.012 \n                                            No                                          ref                                                                                                                       \nDepressive symptoms         Yes                                        1.23                          3.41 (1.01, 11.48)                        3.92                          0.048 \n                                            No                                          ref                                           \n  \naBackward stepwise likelihood ratio multiple logistic regression method was applied.  \nMulticollinearity and interaction terms were checked and not detected. \nHosmer\u2013Lemeshow GOF test (p < 0.001), classification table (overall correctly classified percentage = 76.8%) were applied to check the model fitness. \n\n\n\nTable V: Factors associated with poor sleep quality using multiple logistic regression\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 631\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n632                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nbetween diabetes and nocturia, and found that diabetes itself \nincreased the risk of nocturia by approximately 49%.32 Poor \nglycaemic control has been implicated as a cause for \nnocturia. Nonetheless, in our study, post-hoc analysis showed \nless than a third of the participants (29.7%) with nocturia \nhad poor glycaemic control, which could explain why \nnocturia was significantly associated with poor sleep quality \nbut poor glycaemic control was not. Hence, the presence of \nnocturia should be assessed in people with poor sleep quality \nas it was not necessarily related to poor glycaemic control. \n \nPsychological distress was another factor that showed \nsignificant association with poor sleep quality. National \nHealth Morbidity Survey 2019 reported depression in 2.3% of \nadults in Malaysia with Negeri Sembilan had among the \nhighest prevalence at 5%.13 Similarly the proportion of \nparticipants with possible depression in our study was 6%. In \nthis study, we found that those with depressive symptoms \nhad more than three times the odds of having poor sleep \nquality compared to those without depressive symptoms. The \nassociation between psychological distress and poor sleep \nquality had been consistently reported in many other studies. \nLocal studies on sleep quality among secondary school \nstudents and the elderly attending a primary care clinic \nreported psychological distress was significantly associated \nwith sleep quality.27,28 Studies among T2DM patients locally \nand abroad reported similar association.14,15,21 A study \nconducted among 289 T2DM patients in outpatient diabetic \nclinic of a private hospital setting in Myanmar showed 27.7% \nof participants had depression and it was significantly \nassociated with poor sleep quality (AOR = 7.52, 95%CI = \n3.38\u201314.76).33 Another study  in China among 281 T2DM \npatients with comorbid metabolic syndromes also found \ndepressive symptoms as an independent predictor of poor \nsleep quality and reported further association between \ndepressive symptoms with long sleep latency and short sleep \nduration.34 This association is understandable as insomnia or \nhypersomnia are established symptoms of depression in The \nDiagnostic and Statistical Manual of Mental Disorders (DSM-\n5).35 Emotion regulation, described as various efforts to modify \nthe experience and expression of emotions, has been \nimplicated to sleep quality and depression.36 Impaired \nemotion regulation was reported as a mediator to current \nand prospective relationship between poor sleep quality and \ndepressive symptoms.36 \n \nHigher BMI and poor glycaemic control were two important \nfactors that were not significantly associated with poor sleep \nquality in our study. We postulated, higher BMI, as one of the \ncritical risk factors for the development of Obstructive Sleep \nApnea (OSA) could be associated with poor sleep quality, in \nour study. NHMS 2019 reported overweight (BMI >25 kg/m\u00b2) \nand obesity (BMI>30 kg/m\u00b2) in about 50% of Malaysian \nadults.13 In our study, using lower cut-off point we found \nhigher proportion of overweight (BMI 23-27.4 kg/m\u00b2) and   \nobesity with (BMI \u226527.5 kg/m\u00b2) at 37.6% and 43.6%, \nrespectively. Interestingly both groups with overweight and \nobesity reported lower proportion of poor sleep quality at \n22.5% and 22.3%, respectively. Consistent with our finding, a \nlocal study done among T2DM attending a primary care \nclinic also did not find significant association between higher \nBMI with poor sleep quality even though 91.7% of their \n\n\n\nparticipants were overweight or obese with BMI >23 kg/m\u00b2.15 \nFurther exploration is needed to investigate sleep quality \namong our overweight and obese populations. \n \nStudies reported inconsistent association between poor \nglycaemic control and poor sleep quality. A Japanese study \nfound diabetes patients with higher quartile HbA1c >7.9% \nhad significantly higher global PSQI score than the other \ngroup with better glycaemic index.5 Studies in Jordan and \nEthiopia also found poor glycaemic control was associated \nwith poor sleep quality.11,21 However, another local study and \nother studies in Japan, Iran, Myanmar, and Saudi Arabia \nreported no significant association.8,14,15,33,37 A systematic \nreview and meta-analysis highlighted that short sleep less \nthan 5 hours and long sleep durations more than 8 hours \nwere associated with an increased HbA1c compared to \nnormal sleep.38 Even though in our study more than half of \nparticipants (55.2%) had uncontrolled HbA1c >7%, it was not \nsignificantly associated with poor sleep quality. Hence, \nfurther investigation assessing amount of sleep as well as \nbroader stratification of HbA1c could be useful to see its \nassociation with glycaemic control. Keeping continuous \nvariables such as BMI and HbA1c for continuous analyses \ninstead of categorical analyses could be more meaningful.39  \n \nOne of the limitations in this study was that the sleep quality \nwas subjectively assessed using the PSQI. Apart from its \nacceptance as a standardized tool, it is not an objective \nmeasure like polysomnography. Secondly, a cross-sectional \ndesign of this study can only suggest an association, not the \ncause and effect, for poor sleep quality. In interpreting our \nresults, caution is needed due to the single-centered setting. \nOur findings would be at most, inferred from the local \npopulation attending our primary care clinic. Other than \nthat, mode of treatment especially insulin use, nocturnal \nhypoglycaemia, painful neuropathy and restless leg \nsyndrome which could be related to poor sleep quality among \nT2DM were not assessed in this study. \n \n \nCONCLUSION  \nThis study found that 23% of our studied population have \npoor sleep quality. Indian ethnicity, separated or widowed, \nhaving nocturia and depressive symptoms were independent \nfactors significantly associated with poor sleep quality. \nAssessment of sleep quality should be considered in the \nmanagement of T2DM patients.  Improving sleep quality \nmight involve a simple measure that does not cost much and \nthe ultimate outcome is to maximize the care towards our \ndiabetic patients indirectly improving their quality of life. \n \n \nACKNOWLEDGEMENTS  \nWe would like to thank the Director General of Health \nMalaysia for his permission to publish this article. Our \nhighest appreciation to all patients participated in this study \nand the supportive staffs at Klinik Kesihatan Seremban, \nNegeri Sembilan. We would also like to thank Universiti \nKebangsaan Malaysia and the Ministry of Health Malaysia \nfor ethical approval to conduct this research. \n \n \n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 632\n\n\n\n\n\n\n\n\nA cross-sectional study on the sleep quality among type 2 diabetes mellitus patients and its associated factors\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                633 \n\n\n\nFUNDING AND CONFLICT OF INTEREST  \nThis study was self-funded, and we declare no conflicts of \ninterest.  \n \n \nETHICAL APPROVAL  \nThe ethical approval was obtained from Medical Research & \nEthics Committee\u2019s (MREC), Ministry of Health Malaysia \n(NMRR ID-21-01986-E44), and Research Ethics Committee of \nUniversiti Kebangsaan Malaysia (JEP-2021-800). \n \n \nREFERENCES \n1. 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The association between diabetes \nand nocturia: a systematic review and meta-analysis. Front \nPublic Heal 2022; 10: 924488. \n\n\n\n33. Htut HN, Howteerakul N, Suwannapong N, Rawdaree P. Sleep \nquality among type 2 diabetes mellitus patients in a private \nhospital setting in Yangon, Myanmar. J Heal Res 2021; 35(2): \n186-98.  \n\n\n\n34. Li Y, Buys N, Li L, Sun J. Sleep Quality and Its Determinants \nAmong Type 2 Diabetes Patients with Comorbid Metabolic \nSyndrome. Diabetes, Metab Syndr Obes Targets Ther 2022; 3469\u2013\n82. \n\n\n\n\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 633\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n634                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n35. American Psychiatric Association. 2013. Diagnostic and \nStatistical Manual of Mental Disorders, 5th Edition. American \nPsychiatric Publishing. \n\n\n\n36. O'Leary K, Bylsma LM, Rottenberg J. Why might poor sleep \nquality lead to depression? A role for emotion regulation. Cogn \nEmot 2017; 31(8): 1698-706. \n\n\n\n37. Darraj A, Mahfouz MS, Alsabaani A, Sani M, Alameer A. \nAssessment of sleep quality and its predictors among patients \nwith diabetes in Jazan, Saudi Arabia. Diabetes, Metab Syndr \nObes Targets Ther 2018; 11: 523-31. \n\n\n\n38. Lee SWH, Ng KY, Chin WK. The impact of sleep amount and \nsleep quality on glycemic control in type 2 diabetes: A systematic \nreview and meta-analysis. Sleep Med Rev 2017; 31: 91-101.  \n\n\n\n39. Salis Z, Gallego B, Sainsbury A. Researchers in rheumatology \nshould avoid categorization of continuous predictor variables. \nBMC Med Res Methodol 2023; 23(1): 104. \n\n\n\n\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 634\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                635 \n\n\n\nABSTRACT \nIntroduction: Epilepsy is a neurological disease with high \nglobal prevalence. Almost one-third of epilepsy patients \ncontinue having seizures despite adequate treatment. \nPerampanel has been widely used in the Western countries \nas an adjunctive therapy for both generalized and focal \nseizures. Owing to its high cost, the use of perampanel is \nlimited in our country.  \n \nMaterials and Methods: We conducted a descriptive, \nretrospective study among epilepsy patients treated with \nperampanel. We aimed to assess the efficacy and safety of \nperampanel as an adjunctive in our hospital.  \n \nResults and Conclusions: From our cohort of 25 patients, \nmost of the patients were either on one or three anti-seizure \nmedications (ASMs) prior to initiation of perampanel. \nPerampanel was added in 88% of them due to persistent \nseizures. Twenty-two (88%) patients experienced reduction \nin seizure frequency. 12% experienced mild side effects, \nwhich were leg cramps, hyponatremia and drowsiness. Only \n1 patient stopped perampanel due to its side effects.  \n \nConclusion: Perampanel is a well-tolerated ASM that should \nbe widely used as an adjunctive. More studies with regards \nto its efficacy and safety involving more centres are \nencouraged in Malaysia. \n \nKEYWORDS:  \nEpilepsy, refractory, anti-seizure medication, perampanel, \ndizziness \n \n \nINTRODUCTION \nEpilepsy is a chronic brain disorder, characterised by two or \nmore unprovoked seizures occurring more than 24 hours \napart, due to the abnormal excessive or synchronous \nneuronal activity in the brain. The prevalence of epilepsy \ndiffers in different countries, ethnics, and socioeconomic \nstatuses, with an overall lifetime population prevalence, \nworldwide, of 7.60 per 1,000.1 The overall lifetime prevalence \nof epilepsy in Asian countries correlates with the worldwide \ndata, varying from 1.5 to 14.0 per 1000 population, and it is \nreported as 7.8 per 1000 population in Malaysia.2 \n \nTreatment for epilepsy includes anti-seizure medications \n(ASMs), which are expected to achieve seizure freedom in \n70% of patients. The remaining 30% of patients might need \n\n\n\na substitution or an addition of a second ASM.3 All ASMs can \nbe categorised into broad- and narrow-spectra. Broad-\nspectrum ASMs such as valproic acid are commonly initiated \nin generalized or uncertain type of epilepsy; whereas narrow-\nspectrum ASMs such as carbamazepine and phenytoin are \nused in the treatment of focal seizures.4 Recent years, many \nnew ASMs with a wide variety of mechanisms of action were \nintroduced with high hopes for a better seizure control. \nHowever, prospective audits on new ASMs such topiramate, \nlevetiracetam, zonisamide, pregabalin, and lacosamide as an \nadjunctive therapy were disappointing with a low seizure \nfreedom rate of less than 25%.5 \n \nPerampanel is one of the new ASMs introduced as an \nadjunctive therapy for epilepsy. It is a selective, non-\ncompetitive antagonist of \u03b1-amino-3-hydroxy-5-methyl-4-\nisoxazolepropionic acid (AMPA)-type glutamate receptors on \npost-synaptic neurons.6 Many promising data were reported \nin the Western countries for the use of perampanel as an \nadjunctive therapy in refractory focal-onset seizures as well as \ngeneralized tonic-clonic seizures.7-9 The commonly reported \nside effects of perampanel are dizziness, convulsion, and \nsomnolence, which are statistically insignificant at low \ndoses.10 The utilisation of perampanel in the Asian \npopulation, especially in South East Asia is relatively low as \ncompared to the Western countries, with limited information \non its clinical performance and safety profile. More clinical \nstudies are warranted for better cognizance of perampanel as \nan adjunctive treatment in the Asian population. \n \nThe aim of this study was to determine the change in seizure \nfrequency and responder rate upon initiation of perampanel \nas an adjuntive ASM. We also studied the adverse events \nrelated to perampanel and the reasons for its \ndiscontinuation. \n \n \nMATERIALS AND METHODS \nThis was a single-centre, descriptive, retrospective study done \nat the Hospital Canselor Tuanku Muhriz after obtaining \napproval of the Research Ethics Committee (Project Code: FF-\n2021-422). All patients with epilepsy treated with \nperampanel were included in this study. Those with missing \ndata were excluded.  \n \nTwenty-five epilepsy patients treated with perampanel as an \nadjunctive therapy from January 2015 till December 2020 \n\n\n\nEfficacy and safety of adjunctive treatment with perampanel \nin epilepsy patients \n \nKuan Yee Lim, Dr Int Med1, Ching Soong Khoo, FRCP1,2, Rathika Rajah, Dr Int Med1, Hui Jan Tan, FRCP1,2, Farah \nWaheeda Tajurudin, MPharm3 \n\n\n\n     \n1Department of Medicine, Hospital Canselor Tuanku Muhriz, 2Department of Medicine, Faculty of Medicine, Universiti \nKebangsaan Malaysia, 3Department of Pharmacy, Hospital Canselor Tuanku Muhriz \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 13 August 2023                                                                                                                                                                         \nCorresponding Author: Ching Soong Khoo                                                                                                                                                                          \nEmail: chingsoongkhoo@gmail.com \n\n\n\n13-Efficacy00110.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 635\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n636                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nwere recruited from the Neurology Clinic of our hospital. The \npatients\u2019 demographics and characteristics of their seizures \nwere collated in a data collection sheet. \n \nThe statistical analysis was performed using IBM Statistical \nProduct and Service Solutions (SPSS) version 26.0. Descriptive \nstatistics were used to present the variables recorded. We \ntabulated the descriptive statistics to summarize our data. \nNormally distributed data were expressed using mean \u00b1 \nstandard deviation; whereas data that was not normally \ndistributed were reported using median (inter-quartile range). \n \nIn this study, the efficacy of perampanel (seizure reduction) \nwas taken as at least 50% reduction in seizure frequency \ncompared to the baseline; whereas the safety of perampanel \nwas measured as presence of any side effects among patients \nwho were on perampanel.   \n \n\n\n\nRESULTS \nA total of 25 patients had perampanel as an adjunctive ASM. \nTwelve (48.0%) were Chinese, 11 (44.0%) Malay and 1 (4.0%) \neach, were Indian and other races. The mean age (\u00b1 standard \ndeviation [SD]) of our patients was 37.5 years (\u00b1 13.4 years), \nwith predominantly males (17, 68.0%). Eleven (44.0%) \npatients had other medical illnesses, which included \nmetabolic diseases (3, 12.0%), brain related diseases (3, \n12.0%), genetic diseases (3, 12.0%), malignancy (1, 4.0%) \nand autoimmune diseases (1, 4.0%) (Table I). \n \nThe mean duration of epilepsy in our cohort was 1.6 years (\u00b1 \n0.9 years). Regarding the types of epilepsy, they were almost \nequally distributed between generalised (13, 52.1%) and focal \n(12, 47.9%) epilepsy. The aetiology of epilepsy in most of our \npatients was unknown (12, 48.0%), while a small number \nwere contributed by structural (5, 20.0%) and infectious (5, \n20.0%) causes (Table II). \n\n\n\nCharacteristics                                                                                                   n (%) \nEthnicity                                                                                                                    \n\n\n\nMalay                                                                                                          11 (44.0) \nChinese                                                                                                       12 (48.0) \nIndian                                                                                                           1 (4.0) \nOthers                                                                                                           1 (4.0) \n\n\n\nAge (year)                                                                                                                 \n0-20                                                                                                              3 (12.0) \n21-40                                                                                                           11 (44.0) \n41-60                                                                                                            9 (36.0) \n61-80                                                                                                             2 (8.0) \n\n\n\nGender                                                                                                                      \nMale                                                                                                            17 (68.0) \nFemale                                                                                                         8 (32.0) \n\n\n\nMedical diseases                                                                                                       \nMetabolic                                                                                                    3 (12.0) \nBrain related                                                                                               3 (12.0) \nMalignancy                                                                                                   1 (4.0) \nGenetic                                                                                                        3 (12.0) \nAutoimmune                                                                                                1 (4.0) \nNone                                                                                                           14 (56.0) \n\n\n\n\n\n\n\nTable I: Patients\u2019 demographic characteristics (n = 25)\n\n\n\nCharacteristics                                                                                                   n (%) \nType of epilepsy                                                                                                       \n\n\n\nGeneralised onset                                                                                      13 (52.0) \nFocal onset                                                                                                 12 (48.0) \nUnknown onset                                                                                           0 (0.0) \n\n\n\nDuration of disease (year)                                                                                       \nLess than one                                                                                               2 (8.0) \n1-10                                                                                                             10 (40.0) \n11-20                                                                                                            8 (32.0) \n21 and above                                                                                              5 (20.0) \n\n\n\nAetiology \nStructural                                                                                                     5 (20.0) \nGenetic                                                                                                         2 (8.0) \nInfectious                                                                                                     5 (20.0) \nMetabolic                                                                                                     1 (4.0) \nUnknown                                                                                                   12 (48.0) \n\n\n\nEEG                                                                                                                            \nNormal                                                                                                         3 (12.0) \nAbnormal spikes                                                                                        22 (88.0)                                                            \n\n\n\nMRI                                                                                                                            \nNormal                                                                                                        14 (56.0) \nAbnormal                                                                                                   11 (44.0) \n\n\n\n\n\n\n\nTable II:\u2008Epilepsy characteristics (n = 25)\n\n\n\n13-Efficacy00110.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 636\n\n\n\n\n\n\n\n\nEfficacy and safety of adjunctive treatment with perampanel in epilepsy patients\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                637 \n\n\n\nMost of our patients were on at least one (7, 28.0%) or three \n(7, 28.0%) ASMs (mean \u00b1 SD = 2.4 \u00b1 1.1) prior to the addition \nof perampanel. More than three-quarter (22, 88.0%) had \nperampanel added due to persistent seizures with previous \nASMs. Three (12.0%) patients had both persistent seizures \nand side effects from the previous ASM, which led to the \naddition of perampanel. After adding perampanel, 22 \n(88.0%) experienced at least 50% reduction in seizure \nfrequency from their baseline, and only three (12.0%) had no \nchange in seizure frequency. \n \nThe mean (\u00b1 SD) duration of perampanel use among our \npatients was 1.5 years (\u00b1 1.1 years). Only 3 (12.0%) \ncomplained of side effects, which were leg cramps, \nhyponatremia and drowsiness. Thirteen (52.0%) patients are \nstill on perampanel; 1 (4.0%) on the other hand stopped \ntreatment due to drowsiness. The remaining 11 (44.0%) \npatients were not on perampanel as they defaulted follow up \nor died (Table III). \n \n \nDISCUSSION \nMost of our patients with epilepsy are of Malay (11, 44.0%) \nand Chinese (12, 48.0%) ethnicity. This is representative of \nthe national population whereby Malay and Chinese form \nthe two largest ethnic groups in Malaysia. In the West, whites \nare more prone to having primary generalized epilepsy, \nwhereas no racial differences were seen in temporal or frontal \nlobe epilepsy.11 However in Malaysia, there are no recent \n\n\n\nstudies to suggest ethnic preponderance towards types of \nepilepsy. Our epilepsy patients are predominantly male (17, \n68.0%). This can be explained by the fact that they are more \nvulnerable to head injuries, stroke and CNS infections \nleading to seizures.12 \n \nKeezer et al., mentioned in their paper that almost half of the \nadults with epilepsy have at least one medical comorbidity. \nDiseases such as depression, dementia, anxiety, heart related \ndiseases and peptic ulcer diseases are strongly related to \nepilepsy due it its bidirectional relations.13 In our current \ncohort, they did not have any psychiatric or heart related \nissues. \n \nWhen treating epilepsy, the gold standard is to use \nmonotherapy at its most tolerated dose. Most of the time, a \nsecond or third agent is needed, thus achieving seizure \nfreedom in more than half patients.14 The average ASMs used \nby our patients were two ASMs, prior to addition of \nperampanel. Almost all of them had perampanel added due \nto persistent seizures and/or adverse effects from other ASMs. \nThe recent PERaMpanel pooled analysIs of effecTiveness and \ntolerability (PERMIT) study showed that perampanel can be \nused as mono, or an adjunctive therapy to treat epilepsy, \nowing to its broad-spectrum properties.15,16 The use of \nperampanel contributes to a significant reduction in seizure \nfrequency, similar to our study in which up to 88.0% of the \npatients had seizure reduction. \n \n\n\n\nCharacteristics                                                                                                   n (%) \nNumber of ASMs prior to perampanel                                                                   \n\n\n\n1                                                                                                                   7 (28.0) \n2                                                                                                                   6 (24.0) \n3                                                                                                                   7 (28.0) \n4 and more                                                                                                  5 (20.0) \n\n\n\nIndications for adding perampanel                                                                        \nPersistent seizures with previous ASM                                                     22 (88.0) \nSide effects from previous ASM                                                                 0 (0.0) \nBoth                                                                                                             3 (12.0) \n\n\n\nChanges in seizure frequency                                                                                 \nNo change in seizure frequency                                                               3 (12.0) \nSeizure reduction$                                                                                      22 (88.0) \nIncrease in seizure frequency                                                                     0 (0.0)                                                              \n\n\n\nDuration on perampanel (year)*                                                                            \nLess than 1                                                                                                  5 (23.8) \n1-2                                                                                                                5 (23.8) \n2-3                                                                                                                6 (28.6) \nMore than 3                                                                                                5 (23.8) \n\n\n\nSide effects from perampanel                                                                                 \nYes\u2020                                                                                                              3 (12.0) \nNo                                                                                                               22 (88.0) \n\n\n\nContinuation of perampanel                                                                                  \nYes                                                                                                              13 (52.0) \nNo                                                                                                               12 (48.0) \n\n\n\nReasons discontinuing perampanel (n = 12)                                                          \nDue to side effects                                                                                       1 (8.3) \nOthers#                                                                                                        11 (91.7) \n\n\n\n \n*4 missing data as patients died/defaulted follow up / transferred care to another hospital \n\u2020Side effects reported include leg cramps, hyponatremia, drowsiness. \n#Other causes such as patients died or defaulted follow up. \n$Seizure reduction refers to at least 50% reduction in seizure frequency from baseline (efficacy of perampanel). \nASM = Anti-seizure medication \n\n\n\nTable III: Perampanel and epilepsy (n = 25)\n\n\n\n13-Efficacy00110.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 637\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n638                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nPatients on perampanel commonly reported experiencing \nside effects, namely dizziness, fatigue, somnolence and \nirritability.10 This was seen among those on perampanel 12 \nmg per day and the discontinuation rate among this group \nwas as high as 5% due to its side effects. The incidence of \ndizziness among this group was as high as 20%.17 One of our \npatients had to discontinue perampanel owing to dizziness \naffecting the daily activities. \n \nAlthough the incidence is low, one of the most concerning \nside effects of perampanel is worsening of depression and \naggression when not used in caution in patients with pre-\nexisting psychiatric illness.10 None of our patients suffered \nfrom any neuropsychiatric illnesses. We noted that one \npatient had hyponatremia secondary to perampanel. \nHyponatremia caused by perampanel was rarely reported \nand the incidence is only less than 1% of general \npopulation.18 \n \nOur study has several limitations. The sample size was too \nsmall due to the high cost of perampanel, which most \npatients could not afford.  This is a single-centre and \nretrospective study, the findings of which might not be \ngeneralizable. Many patients also lost to follow up while on \nperampanel. \n \n \nCONCLUSIONS \nPerampanel is a well-tolerated ASM that could be considered \nas an adjunctive treatment among epilepsy patients in \nMalaysia. More studies on the efficacy, retention rate and \nside effects of perampanel involving a larger population are \nencouraged. \n \n \nACKNOWLEDGEMENT \nThe authors would like to thank the staff of the Neurology \nUnit and Department of Pharmacy, Hospital Canselor \nTuanku Muhriz for their help in completing the study.   \n \n \nCONFLICT OF INTEREST \nThe authors declared no potential conflicts of interest with \nrespect to the research, authorship, and/or publication of this \narticle. The authors received no financial support for the \nresearch, authorship, and/or publication for this article.  \n \n \n \n \n\n\n\nREFERENCES \n1. Beghi E. The epidemiology of epilepsy. Neuroepidemiology 2020; \n\n\n\n54(2): 185-91. \n2. Fong SL, Lim KS, Tan L, Zainuddin NH, Ho JH, Chia ZJ, Choo WY, \n\n\n\nPuvanarajah SD, Chinnasami S, Tee SK, Raymond AA. \nPrevalence study of epilepsy in Malaysia. Epilepsy Res 2021; 170: \n106551. \n\n\n\n3. Sander JW. The use of antiepileptic drugs\u2014principles and \npractice. Epilepsia 2004; 45: 28-34. \n\n\n\n4. Subbarao BS, Silverman A, Eapen BC. Seizure Medications. \nStatPearls [Internet]. 2023 Jan. \n\n\n\n5. Brodie MJ, Kelly K, Stephen LJ. Prospective audits with newer \nantiepileptic drugs in focal epilepsy: insights into population \nresponses? Epilepsy Behav 2014; 31: 73-6. \n\n\n\n6. Plosker GL. Perampanel: as adjunctive therapy in patients with \npartial-onset seizures. CNS Drugs 2012; 26: 1085-96. \n\n\n\n7. Franco V, Crema F, Iudice A, Zaccara G, Grillo E. Novel treatment \noptions for epilepsy: focus on perampanel. Pharmacol Res 2013; \n70(1): 35-40. \n\n\n\n8. French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza \nA, Kumar D, Rogawski MA. Adjunctive perampanel for refractory \npartial-onset seizures: randomized phase III study 304. Neurol \n2012; 79(6): 589-96. \n\n\n\n9. French JA, Krauss GL, Wechsler RT, Wang XF, DiVentura B, \nBrandt C, Trinka E, O'Brien TJ, Laurenza A, Patten A, Bibbiani F. \nPerampanel for tonic-clonic seizures in idiopathic generalized \nepilepsy: a randomized trial. Neurol 2015; 85(11): 950-7. \n\n\n\n10. Rugg\u2010Gunn F. Adverse effects and safety profile of perampanel: a \nreview of pooled data. Epilepsia. 2014; 55: 13-5. \n\n\n\n11. Santiago M, Niedermeyer E. Racial factors and epileptic seizure \ndisorders. J Epilepsy 1988; 1(1): 31-3. \n\n\n\n12. McHugh JC, Delanty N. Epidemiology and classification of \nepilepsy: gender comparisons. Int Rev Neurobiol 2008; 83: 11-26. \n\n\n\n13. Keezer MR, Sisodiya SM, Sander JW. Comorbidities of epilepsy: \ncurrent concepts and future perspectives. Lancet Neurol 2016; \n15(1): 106-15. \n\n\n\n14. Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution \nor add-on?. Seizure. 2000; 9(7): 464-8. \n\n\n\n15. Akamatsu N, Kanemoto K, Maehara T. Optimal use of \nperampanel in the treatment of patients with epilepsy based on \nthe clinical evidence and characteristics. Brain and Nerve Shinkei \nKenkyu no Shinpo 2022; 74(7): 927-37. \n\n\n\n16. Villanueva V, D'Souza W, Goji H, Kim DW, Liguori C, McMurray \nR, Najm I, Santamarina E, Steinhoff BJ, Vlasov P, Wu T. PERMIT \nstudy: a global pooled analysis study of the effectiveness and \ntolerability of perampanel in routine clinical practice. J Neurol \n2022; 269(4): 1957-77. \n\n\n\n17. Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for \nfocal epilepsy: insights from early clinical experience. Acta \nNeurologica Scandinavica 2016; 133(3): 160-72. \n\n\n\n18. Morimoto M, Suzaki I, Shimakawa S, Hashimoto T, Nakatsu T, \nHamada S, Kyotani S. Three cases in which drug-induced \nhyponatremia was improved by replacing carbamazepine with \nlacosamide. Clin Case Rep 2020; 8(7): 1166-70. \n\n\n\n\n\n\n\n13-Efficacy00110.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 638\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                639 \n\n\n\nABSTRACT \nIntroduction: There are insufficient data available regarding \nthe outcome of cardiac arrest (CA) resuscitated in the \nemergency department in Malaysia. This study aims to \ndetermine the incidence of CA, the return of spontaneous \ncirculation (ROSC), survival to admission (STA), survival to \ndischarge (STD) and factors influencing the overall outcome \nof CA. \n \nMaterial and Methods: This is a retrospective observational \nstudy done in Hospital Sg Buloh (HSB), a tertiary referral \ncentre in an urban area located north of Kuala Lumpur, \nMalaysia's capital city, from January until December 2018, \ninvolving 289 patients. All cases with CPR and a sustained \nreturn of spontaneous circulation (ROSC) were included in \nthe study and followed up until discharged or died in the \nhospital. \n \nResults: Out of 236 patients recruited, 25.8% achieved \nROSC, 15.7% survived on admission, and 4.2% of patients \nwere discharged alive. Of 74.1% of witnessed OHCA, only \n17.5% received bystander CPR. Factors with favourable \noutcomes include CA in ED (p<0.001), the initial rhythm of \nventricular fibrillation (p=0.003), defibrillation (p=0.024), \nOHCA witnessed by emergency medical services (EMS) \n(p=0.024) and intravenous adrenaline administration \n(p=0.001). When using multivariate regression analysis, \npositive outcomes were associated with the cardiac and \nrespiratory cause of CA (Adjusted Odd Ratio (AOR) 3.66; \n95% Confidence Intervals, 95%CI: 2.52 - 12.61 and AOR 8.76; \n95%CI: 5.76- 15.46, respectively) as well as OHCA witnessed \nby EMS (AOR 10.81; 95%CI: 1.84- 19.52).  \n \nConclusions: Despite being an upper-middle-income \ncountry and having advancements in the healthcare system, \na relatively lower STD rate among survivors of CA in the ED \nwas observed in this study. There was underutilization of the \nEMS among patients with CA. The bystander CPR rate \namong patients with CA in Malaysia is also worryingly low. \nAggressive community participation in cardiac arrest \nawareness programmes is much required. Additionally, in \nachieving better outcomes, implementing standardized \npost-resuscitation care protocols with existing resources \nwill be a challenge for physicians managing cardiac arrest \ncases.  \n \n \n\n\n\nKEYWORDS:  \nCardiac arrest, Cardiopulmonary resuscitation, Emergency \nDepartment, Survival to discharge, In hospital cardiac arrest, Out \nof hospital cardiac arrest, middle-income country \n \n \nINTRODUCTION \nSince the introduction of modern cardiopulmonary \nresuscitation by Peter Safar in the 1950s, the resuscitation \ntechnique has improved with advanced development and \nprotocols.1 Over the years, with a better understanding of the \nbest practice in resuscitation, many countries have advocated \na standardised approach governed by respective societies and \nassociations. \n \nMalaysia has produced its version of cardiac arrest (CA) \nresuscitation protocol through the National Committee on \nResuscitation Training (NCORT) based on the evidence from \nthe International Liason Committee on Resuscitation \n(ILCOR) since 2006.2 Since then, the hospitals in Malaysia \nhave adopted the NCORT recommendation apart from the \nguidelines from American Heart Association. \n \nThe emergency department in Malaysia has developed \nrapidly, from an admission unit for the in-patient ward 20 \nyears ago to advanced acute medical care provided by \nspecialised doctors and equipped with the latest technologies. \nAs a frontline, advanced critical care provider, \ncardiopulmonary resuscitation (CPR) and subsequent \nmanagement are core elements in emergency department \n(ED). However, despite rigorous training among the \nhealthcare staff on standard CPR and resuscitation \ntechniques, there was no official nationwide registry to assess \nthe outcome of post-cardiac arrest management in the \nemergency department. The PAROS database and many \nother studies concentrate on out-of-hospital cardiac arrest \n(OHCA) and their performances without much emphasis on \nthe ED.3,4 \n \nIn a small sample size study on the East Coast of Malaysia, \nthe rate of return of spontaneous circulation (ROSC) post-CPR \nin the ED is 30.2%.5 This is comparable to a study in China \nby Xue et al. (25.8%) and in Pakistan by Moosajee et al. \n(27.4%).6,7 The survival to discharge (STD) ranges between 5.6 \nto 11% in studies outside Malaysia.5-9 Unfortunately, there is \nno data on STD for post-cardiac arrest in the ED or in-hospital \navailable in Malaysia. \n\n\n\nOutcomes of cardiopulmonary resuscitation in the \nemergency department of a tertiary hospital in Malaysia \n \nMohamad Iqhbal Kunji Mohamad, MMedEM, Mohd Amin Mohd Mokhtar, MmedEM, Mohamad Rodi Bin Isa, \nDrPH, Mohd Fazrul Mokhtar, DrEmMed \n\n\n\n     \nFaculty of Medicine, Universiti Teknologi MARA, UITM Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, \nMalaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 23 August 2023                                                                                                                                                                         \nCorresponding Author: Mohamad Iqhbal Bin Kunji Mohamad                                                                                                                                           \nEmail: iqhbal9966@uitm.edu.my\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 639\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n640                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nAmongst the factors affecting the outcome is the initial \nrhythm (shockable vs non-shockable), the aetiology (trauma \nvs non-trauma), witnessed arrest and bystander resuscitation, \nthe age, and the interval between collapse and initiation of \nCPR. 5,7 \n \nAs the nation develops as a model of an upper-middle-\nincome country in Asia, there is an urgent need to assess the \noverall outcome of CA and the factors affecting it in the local \nemergency department. This study aimed to examine this, \nconsisting of out-of-hospital and in-department cardiac \narrests. \n \n \nMATERIALS AND METHODS \nThis is a retrospective study done in Hospital Sg Buloh (HSB), \na 620 bedded tertiary referral centre in an urban area located \nnorth of Kuala Lumpur, Malaysia's capital city. The ED \nreceives nearly 13,000 patients in a month. Consultants and \nspecialists were available 24 hours in the emergency \ndepartment, with 36 beds in yellow, red and observation \nzones. The resuscitation equipment is complete and \nconsidered state-of-the-art. It also encompasses a pre-hospital \nand trauma fellowship training centre for emergency \nphysicians and paramedics. \n \nData were retrieved from the hospital information system \n(HIS) electronic record from January until December 2018. A \ntotal of 289 patients that underwent CPR in ED during the \nstudy period were included. The inclusion criteria consisted of \nall cases of CA in the ED, aged 18 and above. This consists of \nthose whose CA developed in the ED while undergoing \ntreatment and those brought into the ED with active CPR \nongoing. Cases with incomplete data, not-for-active-\nresuscitation (NAR) or existing do-not-resuscitate  (DNR) \nadvance directives and aged less than 18-years-old were \nexcluded from this study. Thus, 236 patients fulfilled the \ninclusion criteria and were included in the study. \n \nThe data collected adhered to the Utstein template, which \nconsisted of core elements of patients variables \n(demographic, comorbidities, initial CA rhythm, location of \ncardiac arrest), pre-event variables (presence of witnessed \ncollapse, presence of bystander CPR), CA variables (initial CA \nrhythm, defibrillation, use of resuscitation medications) and \noutcome variables (return of spontaneous circulation [ROSC], \nsurvival to in-patient admission, and survival to discharge).10 \nThe supplemental elements consisted of the aetiology of \ncardiac arrest. All cases with CPR and a sustained ROSC for \nmore than 30 minutes were considered positive outcomes. \nThose with a sustained ROSC of less than 30 minutes were \nconsidered negative results. The positive outcome was further \ndivided into eventual death in the ED while awaiting transfer \nto the critical care unit or ward, death in the critical care unit \nor ward after admission and those who survived and were \ndischarged alive from the hospital. \n \nEmergency department cardiac arrest (EDCA) was defined as \na CA in the ED. In contrast, OHCA were those with CA \noutside the hospital and brought into the ED with ongoing \nCPR or resuscitation by emergency medical system (EMS) \ntransportation provided by the government (Ministry of \nHealth, Ministry of Education, Ministry of Defense) and \n\n\n\ntrained personnel from Red Cross Malaysia and St John \nAmbulance Malaysia or private ambulances from other \nmodes. \n \nThe CA incidence rate was calculated by dividing that year's \ntotal number of cardiac arrests by the estimated total number \nof ED visits, multiplying by 1000. The estimated total number \nof ED visits is 154,00 \n \nStatistical Package for Social Sciences, version 25.0 (SPSS Inc, \nChicago, IL) was used for data analysis. The descriptive \nstatistics were presented using mean and standard deviation \nfor the numerical variable, whereas the categorical variable \nwas presented using frequency and percentage. The \nnormality of the data was tested statistically using \nKolmogorov-Smirnov Test. The Mann-Whitney U and chi-\nsquare tests were used to assess the p-values for continuous \nand categorical data, respectively. \n \nThe dependent variable was the status of ROSC, divided into \nyes and no ROSC. Patients with ROSC were further divided \ninto discharged alive and died in the ward or the ED. The \nfactors affecting the dependent variable of ROSC were \nanalysed with univariable logistic regression analysis. Crude \nodds ratios (c OR) were reported with 95% confidence \nintervals (95% CI). A manual selection of covariates with a \ncut-off p-value of less than 0.25 were included in the \nmultivariable models. Multivariable stepwise backward \nlogistic regression models were created to control for \nconfounding factors. p-value 0.05 (two-tailed) was set for \nstatistical significance.  \n \n \nRESULTS \nThis study included 236 patients who had CA with CPR in the \nED of HSB in 2018. There were 61 ROSC (25.8%) after CPR. \n83.6% of those with ROSC, or 21.6% of patients who received \nCPR, died in ED or the ward. Only 16.4% of those with ROSC, \nor 4.2% of total CPR, survived and were discharged alive from \nthe hospital. These findings are described in detail in Figure \n1. The incidence of CA, calculated based on yearly ED visits, \nis 1.9 for every 1000 visits.  \n \nThe demographics, clinical and other CPR characteristics of \nthe patient population with stratification by ROSC and no \nROSC were described in Table I. There were more males than \nfemales with CA, with the mean age group equally \ndistributed. The most frequent cause of CA was non-trauma, \nwith the majority being cardiac or presumed cardiac causes. \nMost were OHCA cases compared to EDCA (70.3% vs 29.7%). \nDuring resuscitation, 13.6% had an initial shockable rhythm, \nand 19.5% had defibrillation at least once throughout CPR. \nInterestingly, only 87.3% received intravenous adrenaline. \n \nWhen assessing CPR outcomes, those with CA in ED were \nassociated with ROSC (p < 0.001). A similar significant \nassociation was seen in those with a history of defibrillation \n(p = 0.019) and those who received intravenous adrenaline (p \n= 0.007). There was no association between males and \nfemales and ROSC (p = 0.9). There was also no association \nbetween the mean age for those who attained ROSC and \nthose who did not (p = 0.900). \n \n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 640\n\n\n\n\n\n\n\n\nOutcomes of cardiopulmonary resuscitation in the emergency department of a tertiary hospital in Malaysia\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                641 \n\n\n\nAssessing for predictors of ROSC using a multivariate logistic \nregression model, the non-trauma cause, specifically cardiac \n(aOR 3.66; 95%CI: 2.52 12.61), respiratory cause of CA (aOR \n8.76; 95%CI: 5.76 15.46) and OHCA initial arrest witnessed \nby EMS (aOR 10.81; 95%CI: 1.84 19.52) has a better chance \nof survival compared to other factors (Table II). \n \n \nDISCUSSION \nIn this study, the incidence of CA is comparable with the UK \nNational Cardiac Arrest Audit data of 1.6 for every 1000 in-\nhospital patients.11 The percentage of CA patients receiving \nCPR attaining ROSC in the ED is lower than the study by \nChew et al. (30.2%) but almost similar to other studies by Xue \net al. (25.8%) and Moosajee et al. (27.4%). However, only \n4.2% of cases attained STD, lower than other studies in this \nregion, where the STD ranges from 5.6 to 11%, but is similar \nto the cardiac arrest survivor rate in an ED in Brazil.5\u20139,12 \n \nA crucial data that needs further research is the mean age of \npatients with CA in this study, which is 51.3 years, contrasted \nwith other studies of 66 years in the US and Brazil and 73.9 \nyears in the UK.12\u201314 A similar pattern of the high rate of \n\n\n\nnatural deaths at 41-50 years was also reported in an autopsy \nstudy in Kuala Lumpur in 2007, but not much has been \nexplored further ever since.15 This might be linked to the \nyounger age group in Malaysia diagnosed with coronary \nartery disease as reported in the National Cardiovascular \nDisease Database Registry and a study on East Coast.16,17 \n\n\n\nNevertheless there is need for further research on this, as it \nseems in paradox with the national aim of achieving high \nincome nation.18,19 \n \nThe ROSC rate was significantly better in EDCA compared to \nOHCA, with 1 ROSC for every 2 EDCA vs 1 ROSC for every 6 \nOHCA. The ratio for survival to discharge is also markedly \nbetter in EDCA (1:10 vs 1:55). The 10% rate of STD within \nEDCA is similar to studies conducted on in-hospital CA in \nJapan but lower than rates reported in the US and UK.14-16 \n\n\n\nHowever, there is no available local data for comparison. \nFactors such as pre-hospital response time, early \ndefibrillation, witnessed CPR and bystander CPR could have \ncontributed to the better overall EDCA CPR outcome.20  \n \nAs for OHCA, it is essential to examine the factors affecting \nthis cohort since they comprise of the largest group. Only \n\n\n\n                                                                                                                                   Outcome \n                                                   No ROSC                                                                  ROSC                                                      p value \n                                                     (n=175)                  Discharged alive               Died in ward            Died in ED \n                                                                                             (n=10)                              (n=37)                     (n=14) \n\n\n\nRace: \nMalay                                        101 (57.7%)                     6 (60.0%)                       25 (67.6%)               9 (64.3%)                   0.812** \nChinese                                      20 (11.4%)                      2 (20.0%)                        5 (13.5%)                2 (14.3%) \nIndian                                        37 (21.1%)                      2 (20.0%)                        5 (13.5%)                 1 (7.1%) \nOthers                                         17 (9.7%)                        0 (0.0%)                          2 (5.4%)                 2 (14.3%) \n\n\n\nGender: \nMale                                          122 (69.7%)                     6 (60.0%)                       25 (67.6%)               9 (64.3%)                   0.900** \nFemale                                       53 (30.3%)                      4 (40.0%)                       12 (32.4%)               5 (35.7%) \n\n\n\nAge: \nMean (SD)                               51.39 \u00b1 15.86                50.40 \u00b1 13.45                  53.68 \u00b1 15.37          52.21 \u00b1 12.64                 0.858# \nRange                                            18 - 85                           29 - 79                             22 - 80                     21 - 69 \n\n\n\nComorbidities: \nLess than 3                                59 (61.5%)                      4 (57.1%)                       12 (46.2%)               8 (72.7%)                   0.410** \n3 and more                                37 (38.5%)                      3 (42.9%)                       14 (53.8%)               3 (27.3%) \n\n\n\nInitial rhythm during  \ncardiac arrest: \nArrest location \n\n\n\nED                                              36 (20.6%)                      7 (70.0%)                       17 (45.9%)              10 (71.4%)                  <0.001* \nOHCA                                        139 (79.4%)                     3 (30.0%)                       20 (54.1%)               4 (28.6%) \n\n\n\nAny witness (OHCA)?  \n(n = 166) \n\n\n\nYes                                            103 (74.1%)                     2 (66.7%)                       18 (90.0%)              4 (100.0%)                  0.277** \nNo                                              36 (25.9%)                      1 (33.3%)                        2 (10.0%)                 0 (0.0%) \n\n\n\nWho witnesses the arrest?  \n(OHCA)(n = 127) \n\n\n\nFamily                                        74 (71.8%)                     2 (100.0%)                      10 955.6%)              2 (50.0%)                   0.138** \nEMS                                            15 (14.6%)                       0 (0.0%)                         7 (38.9%)                2 (50.0%) \nLayperson                                  14 (13.6%)                       0 (0.0%)                          1 (5.6%)                  0 (0.0%) \n\n\n\nBystander CPR performed  \nfor OHCA? (n = 72) \n\n\n\nEMS                                            44 (61.1%)                       0 (0.0%)                        9 (100.0%)              2 (100.0%)                    0.083 \nNon EMS                                   28 (38.8 %)                    1 (100.0%)                        0 (0.0%)                  0 (0.0%) \n\n\n\n \n*Chi-Square, **Fisher Exact test, #NOVA \nROSC, Return of spontaneous circulation; ED ,Emergency Department ; SD ,Standard Deviation;PEA, Pulseless Electrical Activities ;VF , Ventricular Fibrillation \n; VT, \nVentricular Tachycardia ; OHCA ,Out of hospital cardiac arrest ;CPR ,cardiopulmonary resuscitation;EMS ,Emergency medical services; CA \u2013 Cardiac arrest\n\n\n\nTable I:\u2008Characteristics of patients with cardiac arrest (CA) with or without return of spontaneous circulation (ROSC)\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 641\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n642                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n17.5% of OHCA received bystander CPR by non-EMS, which \nis at the lower end of the range 10.6 - 41.6% in other Pan \nAsian countries and much lower than 47.4% in Europe.3,21 \nThis might be attributed to the low willingness to perform \nCPR, as portrayed by a study on college students in Malaysia \nby Karuthan et al., which stated that respondents were not \nwilling to perform hands-only CPR due to limited knowledge \nof CPR.22 Additionally, there might be concerns about legal \nliability and lack of confidence while performing CPR.23 As \nbystander CPR is the most amenable factor in improving the \noutcome of OHCA, there is an urgent need for public \neducation on the importance and technique of CPR.24 \n \nMost cases were non-shockable as the initial documented \nrhythm was asystole and PEA compared to VF and VT. This is \nnot much different from the studies on non-shockable \nrhythms in the East Coast of Malaysia (84%), the US (76 \u2013 \n81%%) and Taiwan (87.4%).5,13,25,26 \n \n \n\n\n\nThe low adrenaline administration rate is surprising as it is \none of the core drugs and the standard management for all \ncardiac arrests. However, it is comparable to a study done in \nSweden.27 Perhaps a local study needs to be done to analyse \ncompliance with all the standard cardiac arrest management \nand the factors affecting it.  \n \nRegarding the low rate of STD after ROSC, there might be a \nneed for improvisation of care after cardiac arrest. The lack of \nstandard protocolised post-cardiac-arrest management, as \nrecommended by the American Heart Association in the \nchain of survival, mainly due to limited resources, might be \none of the reasons for the low STD. The paramount issue in \nMalaysia\u2019s ED, i.e., the lack of acute beds and ED \nlongboarding, might also hamper the ideal post-resuscitation \ncare protocols.28 \n \nAs this is a small study, we included and analysed the \ntrauma and non-trauma cohorts together, as were the studies \ndone in Sweden, the UK and Japan.11,29,30 Future studies shall \n\n\n\nVariables                                                                                                          ROSC achieved                     \n                                                                                  p value                         OR (95%CI)                  p value              Adj. OR (95%CI) \n\n\n\nRace: \nMalay                                                                          0.374                       1.68 (0.53, 5.31) \nChinese                                                                       0.344                       1.91 (0.50, 7.33) \nIndian                                                                         0.901                       0.92 (0.24, 3.47) \nOthers                                                                          Ref                                   Ref                                                                    \n\n\n\nGender: \nMale                                                                            0.549                       1.21 (0.65, 2.24) \nFemale                                                                          Ref                                   Ref                                                                    \n\n\n\nAge \n52 and above                                                             0.943                       0.98 (0.55, 1.75) \nLess than 52                                                                 Ref                                   Ref                                                                    \n\n\n\nComorbidities (n = 192): \n0                                                                                    Ref                                     1 \n1\u20133                                                                             0.008*                      2.90 (1.32, 6.36) \nMore then 3                                                               0.216                       1.96 (0.68, 5.69)                      \n\n\n\nInitial rhythm during cardiac arrest: \nAsystole                                                                        Ref                                   Ref \nPEA                                                                             0.067                       2.10 (0.95, 4.66) \nVF                                                                               0.003*                      3.86 (1.60, 9.32) \nVT                                                                                0.764                       1.29 (0.25, 6.65)                                                         \n\n\n\nDefibrillation performed: \nYes                                                                             0.024*                      2.20 (1.11, 4.35) \nNo                                                                                 Ref                                   Ref                                                                    \n\n\n\nNon-trauma cause of CA (n = 191): \nCardiac or presume cardiac                                    <0.001*                     4.24 (2.02, 8.92)                 0.003                 3.66(2.52,12.61)  \nRespiratory                                                                0.001*                     5.59 (1.98, 15.79)                0.001                 8.76 (5.76,15.46) \nOthers                                                                          Ref                                   Ref                             Ref                              Ref \n\n\n\nArrest location: \nED                                                                             < 0.001*                    4.86 (2.61, 9.08)                      \nOHCA                                                                           Ref                                   Ref                                                                    \n\n\n\nAny witness? (n = 169) (OHCA) \nYes                                                                              0.109                       2.80 (0.79, 9.84) \nNo                                                                                 Ref                                   Ref                                                                    \n\n\n\nWho witnessed the arrest? (n = 127) (OHCA \nFamily                                                                           Ref                                   Ref                             Ref                              Ref \nEMS                                                                            0.024*                      3.17 (1.16, 8.66)                 0.008                10.81(1.84,19.52) \nLayperson                                                                   0.365                       0.38 (0.05, 3.11)                 0.227                 8.02(0.27,23.24) \n\n\n\n \nMultivariate analysis was done with the backward method, model fits well (Hosmer & Lemeshow test), Cox & Snell R2 = 0.314 \nROSC, Return of spontaneous circulation; ED, Emergency Department ; SD ,Standard Deviation;PEA, Pulseless Electrical Activities ;VF , Ventricular Fibrillation \n; VT, Ventricular Tachycardia ; OHCA ,Out of hospital cardiac arrest ;CPR ,cardiopulmonary resuscitation;EMS ,Emergency  medical  services; CA \u2013 Cardiac \narrest; OR , Odds ratio, Adj OR , Adjusted odds ratio. \n \n\n\n\nTable II: Univariate and multivariate analysis related to the return of spontaneous circulation (ROSC)  \namong cardiac arrest patients in ED\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 642\n\n\n\n\n\n\n\n\nOutcomes of cardiopulmonary resuscitation in the emergency department of a tertiary hospital in Malaysia\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                643 \n\n\n\nfocus on examining each cohort separately with longer study \nperiods and larger sample sizes to gain a better \nunderstanding. The majority of CA is caused by non-\ntraumatic events, with 26.9% ROSC and 4.8% STD, whereas \nfor trauma cases, 17% ROSC and none with STD. In contrast, \nthe STD for post-traumatic CA in the PROPHET and Epistry \nTrauma registries is 6.8%.31 This result is despite the study \nhospital being a trauma centre with the necessary \nsubspecialist care available.  \n \nWith univariable logistic regression analysis, CA in ED, VF as \nfirst rhythm, history of defibrillation, EMS attended CA and \nIV adrenaline administration were associated with a better \nchance of attaining ROSC. These findings are consistent with \nprevious studies in the literature.6,7,32\u201334  \n \nThrough multivariate analysis, independent predictors for \nROSC were cardiac and respiratory causes of CA, and EMS \nattended CA. Due to the small number of STDs, we chose not \nto perform the multivariate analysis as the result might not \nbe accurate. \n\n\n\nLooking at it from a different perspective, during our \nresearch, we discovered that the main challenge we faced in \ngathering the data was the insufficient information recorded. \nWhilst the Utstein template was introduced in 1990 and \nrevised in 2004, it was never widely adopted in Malaysia.10 \nThe variables, consisting of the patient variables, the hospital \nvariables, the CA variables, and the outcome variables would \nbe comprehensive for documentation and data retrieval \npurposes. Unfortunately, from our observation, until this \narticle was written, there was no standard way of \ndocumenting a CA event, even within a single centre. This is \nthe major reason for the variance in term definitions and the \nmissing important data, including the details during the CA \nand the long-term neurological outcomes. Since this study is \nretrospective, we made every effort to maintain the accuracy \nof the data by adhering to the template. Future registry \nimplementation based on this template will produce robust \nresearch comparisons between nations. For that, official \npolicy and continuous administrative support is needed.  \n \n \n\n\n\nFig. 1: Outcome of cardiopulmonary resuscitation of patients with cardiac arrest in the emergency department. \n \n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 643\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n644                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nAlthough the research has reached its primary aims, there \nwere unavoidable limitations. Our study was performed \nretrospectively in a single tertiary centre for a year. The data \ncollected were limited based on the above reasoning. As more \nhospitals in Malaysia are not tertiary, the result should not be \ngeneralised. Hence, our results should be interpreted \ncautiously. We were also unable to ascertain the factors \ninfluencing the survival to discharge after the patients left the \nED resuscitation area; thus, the patient's actual survival and \nneurological status were not captured. \n \nThere is a need to create a cardiac arrest registry in Malaysia. \nThe ROSC and STD rate will directly imply the quality of the \nhealthcare system and the gap to be addressed. The \nAmerican Heart Association\u2019s Get With The Guidelines- \nResuscitation (GWTG-R) registry and the Danish In-Hospital \nCardiac Arrest Registry (DANARREST) can be emulated to be \nimplemented in Malaysia.35 \n\n\n\n \n \nCONCLUSION  \nDespite being an upper-middle-income country and having \nadvancements in the healthcare system, a relatively lower \nSTD rate among survivors of CA in the ED was observed in \nthis study. There was underutilization of the EMS among \npatients with CA. The bystander CPR rate among patients \nwith CA in Malaysia is also worryingly low. Aggressive \ncommunity participation in cardiac arrest awareness \nprogrammes is much required. Additionally, in achieving \nbetter outcomes, implementing standardized post-\nresuscitation care protocols with existing resources will be a \nchallenge for physicians managing cardiac arrest cases.  \n \n \nACKNOWLEDGMENT \nThe authors would like to thank the Director-General of \nHealth Malaysia for his permission to publish this article. \n \n \nDECLARATION \nThis study was approved by the Malaysian Research Ethics \nCommittee (MREC) (NMRR-19-1766-47833) and Universiti \nTeknologi MARA (UiTM) Research Ethics Committee \n(REC/334/19). All methods were performed according to the \nICH Good Clinical Practice Guidelines, Malaysia Good \nClinical Practice Guidelines and the Declaration of Helsinki. \n \n \nREFERENCES \n1. Oransky I. Peter Safar. Lancet 2003; 362(9385): 749.  \n2. Malaysia. Ministry of Health. National Committee on \n\n\n\nResuscitation Training (NCORT). Guidelines for resuscitation \ntraining : in Ministry of Health Malaysia Hospitals & Healthcare \nFacilities. Medical Development Division, Ministry of Health, \nMalaysia; 2012. 56 p.  \n\n\n\n3. Doctor NE, Ahmad NS, Pek PP, Yap S, ME. O. The Pan-Asian \nResuscitation Outcomes Study (PAROS) clinical research network: \nwhat, where, why and how. Singapore Med J 2017; 58(7): 456\u20138. \n\n\n\n4. Yasin S, Abu Bakar SA, Nurumal MS, Ahmad Arifin S. \nCardiopulmonary resuscitation performed by bystanders: a \nsystematic review. Int J Care Schl 2023; 6(1): 71-91.  \n\n\n\n5. Chew KS, Idzwan ZM, Hisamuddin NA, Kamaruddin J, WA. WA. \nOutcomes of cardiopulmonary resuscitation performed in \nemergency department, Hospital Universiti Sains Malaysia. Med \nJ Malaysia 2008; 63(1): 4-8.  \n\n\n\n6. Xue JK, Leng QY, Gao YZ, Chen SQ, Li ZP, Li HP, et al. Factors \ninfluencing outcomes after cardiopulmonary resuscitation in \nemergency department. World J Emerg Med 2013; 4(3): 183-9. \n\n\n\n7. Moosajee US, Saleem SG, Iftikhar S, Samad L. Outcomes \nfollowing cardiopulmonary resuscitation in an emergency \ndepartment of a low-and middle-income country. Int J Emerg \nMed 2018; 11(1): 40. \n\n\n\n8. Amnuaypattanapon K, Udomsubpayakul U. Evaluation of \nrelated factors and the outcome in cardiac arrest resuscitation at \nThammasat Emergency Department. J Med Assoc Thai 2010; \n1(93): S26-34.  \n\n\n\n9. Sittichanbuncha Y, Prachanukool T, Sawanyawisuth K. A 6-year \nexperience of CPR outcomes in an emergency department in \nThailand. Ther Clin Risk Manag 2013; 9: 377-81. \n\n\n\n10. Jacobs I, Nadkarni V, Bahr J, Berg RA, Billi JE, Bossaert L, et al. \nCardiac arrest and cardiopulmonary resuscitation outcome \nreports: Update and simplification of the Utstein templates for \nresuscitation registries. A statement for healthcare professionals \nfrom a task force of the international liaison committee on \nresuscitation. Resuscitation 2004; 63(3): 233-49.  \n\n\n\n11. Nolan JP, Soar J, Smith GB, Gwinnutt C, Parrott F, Power S, et al. \nIncidence and outcome of in-hospital cardiac arrest in the United \nKingdom National Cardiac Arrest Audit. Resuscitation 2014; \n85(8): 987-92.  \n\n\n\n12. Vancini-Campanharo CR, Vancini RL, de Lira CAB, Andrade M \ndos S, Teixeira Lopes MCB, Okuno MFP, et al. Characterization of \ncardiac arrest in the emergency department of a Brazilian \nUniversity Reference Hospital: A prospective study. Indian J Med \nRes 2016; 144: 552-9.  \n\n\n\n13. Andersen LW, Holmberg MJ, Berg KM, Donnino MW, Granfeldt \nA. In-hospital cardiac arrest: a review. J Am Med Assoc 2019;321: \n1200-10.  \n\n\n\n14. Sandroni C, Nolan J, Cavallaro F, Antonelli M. In-hospital \ncardiac arrest: incidence, prognosis and possible measures to \nimprove survival. Intensive Care Med 2007; 33(2): 237-45.  \n\n\n\n15. Kumar V, San KP, Idwan A, Shah N, Hajar S, Norkahfi M. A study \nof sudden natural deaths in medico legal autopsies in University \nMalaya Medical Centre (UMMC), Kuala Lumpur. J Forensic Leg \nMed 2007; 14(3): 151-4.  \n\n\n\n16. Lu HT, Nordin RB. Ethnic differences in the occurrence of acute \ncoronary syndrome: results of the Malaysian National \nCardiovascular Disease (NCVD) Database Registry (March 2006 - \nFebruary 2010). BMC Cardiovasc Disord. 2013; 13: 97. \n\n\n\n17. Muda Z, Abdul Kadir A, Yusof Z, Husniati Yaacob L. ) 507 \nPremature Coronary Artery Disease among Angiographically \nProven Atherosclerotic Coronary Artery Disease in North East of \nPeninsular Malaysia. Int J Collab Res Intern Med Public 2013; 5. \n\n\n\n18. Malaysia to renew push for high-income goal by 2030 despite \nCOVID - Nikkei Asia [Internet]. [cited 2023 Aug 9]. Available \nfrom: https://asia.nikkei.com/Economy/Malaysia-to-renew-push-\nfor-high-income-goal-by-2030-despite-COVID \n\n\n\n19. World health statistics overview 2019: monitoring health for the \nSDGs, sustainable development goals. Geneva: World Health \nOrganization; 2019 (WHO/DAD/2019.1). Licence: CC BY-NC-SA \n3.0 IGO.  \n\n\n\n20. Ong ME, Ng FS, Anushia P, Tham LP, Leong BS, Ong VY, et al. \nComparison of chest compression only and standard \ncardiopulmonary resuscitation for out-of-hospital cardiac arrest \nin Singapore. Resuscitation 2008; 1(78): 2.  \n\n\n\n21. Gr\u00e4sner JT, Lefering R, Koster RW, Masterson S, B\u00f6ttiger BW, \nHerlitz J, et al. EuReCa ONE-27 Nations, ONE Europe, ONE \nRegistry: A prospective one month analysis of out-of-hospital \ncardiac arrest outcomes in 27 countries in Europe. Resuscitation \n2016; 105: 188-95. \n\n\n\n22. Karuthan SR, Firdaus PJFB, Angampun ADG, Chai XJ, Sagan CD, \nRamachandran M, et al. Knowledge of and willingness to \nperform Hands-Only cardiopulmonary resuscitation among \ncollege students in Malaysia. Medicine (Baltimore) 2019; 98(51): \ne18466. \n\n\n\n\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 644\n\n\n\n\n\n\n\n\nOutcomes of cardiopulmonary resuscitation in the emergency department of a tertiary hospital in Malaysia\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                645 \n\n\n\n23. Nichol G, Rumsfeld J, Eigel B, Abella BS, Labarthe D, Hong Y, et \nal. Essential features of designating out-of-hospital cardiac arrest \nas a reportable event: a scientific statement from the {A}merican \nHeart Association Emergency Cardiovascular Care Committee; \ncouncil on cardiopulmonary, perioperative. and critical care; \ncouncil on cardiovascular nursing; council on clinical cardiology; \nand quality of care and outcomes research interdisciplinary \nworking group. Circulation. 2008; 117(17): 2299-308. \n\n\n\n24. Girotra S, van Diepen S, Nallamothu BK, Carrel M, Vellano K, \nAnderson ML, et al. Regional variation in out-of-hospital cardiac \narrest survival in the United States. Circulation 2016; 31(133): 22.  \n\n\n\n25. Meaney PA, Nadkarni VM, Kern KB, Indik JH, Halperin HR, Berg \nRA. Rhythms and outcomes of adult in-hospital cardiac arrest. \nCrit Care Med 2010; 38(1): 101-8.  \n\n\n\n26. Chi CY, Chen YP, Yang CW, Huang CH, Wang YC, Chong KM, et \nal. Characteristics, prognostic factors, and chronological trends \nof out-of-hospital cardiac arrests with shockable rhythms in \nTaiwan \u2013 A 7-year observational study. J Formos Med Assoc 2022; \n121(10): 1972-80.  \n\n\n\n27. Johansson J, Hammerby R, Oldgren J, Rubertsson S, Gedeborg R. \nAdrenaline administration during cardiopulmonary \nresuscitation: Poor adherence to clinical guidelines. Acta \nAnaesthesiol Scand 2004; 48(7): 909-13.  \n\n\n\n28. Iqhbal KM, Ahmad NH. COVID-19 - How prepared are \nemergency departments in embracing the new norm? Med J \nMalaysia 2020; 75(5): 585-6. \n\n\n\n29. Kimblad H, Marklund J, Riva G, Rawshani A, Lauridsen KG, \nDj\u00e4rv T. Adult cardiac arrest in the emergency department \u2013 A \nSwedish cohort study. Resuscitation 2022 Jun 1; 175: 105-12.  \n\n\n\n30. Ohbe H, Tagami T, Uda K, Matsui H, Yasunaga H. Incidence and \noutcomes of in-hospital cardiac arrest in Japan 2011-2017: a \nnationwide inpatient database study.  J Intensive Care 2022; \n10(1): 10. \n\n\n\n31. Evans CCD, Petersen A, Meier EN, Buick JE, Schreiber M, Kannas \nD, et al. Prehospital traumatic cardiac arrest: Management and \noutcomes from the resuscitation outcomes consortium epistry-\ntrauma and PROPHET registries. J Trauma Acute Care Surg 2016; \n285-93.  \n\n\n\n32. Cooper S, Janghorbani M, Cooper G. A decade of in-hospital \nresuscitation: outcomes and prediction of survival? Resuscitation \n2006; 68(2): 231-7. \n\n\n\n33. Perkins GD, Olasveengen TM, Maconochie I, Soar J, Wyllie J, \nGreif R, et al. Van de Voorde P, Lott C, Monsieurs KG. European \nresuscitation council guidelines for resuscitation: 2018 ; 1(123): \n43-50.  \n\n\n\n34. Ishtiaq O, Iqbal M, Zubair M, Qayyum R, Adil M. Outcome of \ncardiopulmonary resuscitation-predictors of survival. J Coll \nPhysicians Surg Pak 2008; 18(1): 3-7 \n\n\n\n35. Andersen LW, \u00d8stergaard JN, Antonsen S, Weis A, Rosenberg J, \nHenriksen FL, et al. The Danish in-hospital cardiac arrest registry \n(DANARREST). Clin Epidemiol 2019; 11: 397-402.  \n\n\n\n\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 645\n\n\n\n\n\n\n\n\n646                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Sexting refers to the act of sending and \nreceiving sexually explicit content in the form of in the form \nof texts, photos, or videos via the Internet and mobile \nphones. This behaviour is associated with many negative \nhealth consequences among young people. However, there \nis a lack of intervention studies to curb this behaviour. We \nhave developed a new sexting prevention module and tested \nit using a randomised controlled field trial. This paper \nreported the phase one of the study i.e., the development of \nan animated sexting prevention module using the prototype \nwillingness model (PWM) to reduce the intention and \nwillingness to sext amongst diploma students in Malaysia.  \n \nMaterials and Method: The initial phase involved a review of \nprevious interventions, validation from field experts, and the \nprocess of developing video. Then the module pilot was \ntested among 30 diploma students from a public university. \nThey were given access to the newly developed videos \nposted on a private YouTube channel and asked to evaluate \nthe videos quantitatively and qualitatively by using the \nacceptability of the intervention module (AIM), intervention \nappropriateness measure (IAM) and feasibility of the \nintervention measure (FIM). The minimum and maximum \nscores of each measure were 12 and 24 respectively \nwhereby a higher score indicated greater acceptability, \nappropriateness and feasibility.  \n \nResults: The intervention consisted of five sections \naddressing the constructs of PWM, namely attitude, \nperceived norm, prototype perception, as well as intention \nand willingness of sexting. The contents were then \nconverted into five videos with a total duration of 23 \nminutes. Based on the pilot test, the scores of AIM, IAM and \nFIM were not normally distributed and their median and the \ninterquartile range values were 20 (4), 21 (4) and 22 (4) \nrespectively. Most of the respondents gave favourable \nopinions on the intervention besides providing some input \nfor improvement.  \n \nConclusion: This animated sexting intervention module \nbased on PWM to reduce the intention and willingness was \nnovel. The module was acceptable, appropriate and feasible \nto be implemented among undergraduate students. Further \n\n\n\nevaluation of this intervention module can be performed to \nprovide more comprehensive evidence of its effectiveness.  \n \nKEYWORDS:  \nSocial media, intention, Malaysia, students, sexting, pilot projects \n \n \nINTRODUCTION \nThe term sexting is a combination of sex and texting. It refers \nto the act of sending and receiving sexually explicit content \nin the form of texts, photos, or videos via the Internet and \nmobile phones.1,2 \n \nSexting is a new form of sexual communication among the \nyoung population in discovering sexual needs and desires as \nwell as for them to maintain sexual intimacy.3 However, \nrecent studies reported that sexting might cast some adverse \npsychosocial consequences on young people, for example, \ncyberbullying, depression and attempted suicide.4\u20138 \n\n\n\nFurthermore, it is also associated with sexually risky \nbehaviours such as sexual intercourse with multiple partners. \nDue to the profound impact of sexting and its association \nwith other risky behaviours that can burden young people\u2019s \nhealth, sexting must be curtailed. In relation to that, sending \nobscene content via media is a punishable act under \nMalaysian law, and the penalty is more severe if minors were \ninvolved.9,10 \n \nCurrently, interventional studies are scarce on sexting-related \nissues. The majority of previous studies followed a within-\nsubject experimental study design that focused on the effects \nof social images on the prototype perception and willingness \nto sext among adolescents.11 To date, observational studies \nhave asserted that engagement in sexting can be forecasted \nby intention and willingness to sext.12\u201314 By definition, \nintention refers to a deliberately planned behaviour15 while \nwillingness refers to an individual's spontaneous response to \nrisky circumstances.16 Both intention and willingness are \ninvolved in the behaviour that precedes any cognitive \nprocess.17 By focusing on the intention and willingness to \nsext, the intervention aimed at preventing sexting amongst \nthose who have never sexted, reducing the act of sexting \namong those who have sexted and minimising multiple risky \nbehaviours associated with sexting. \n\n\n\nDevelopment of an online animated sexting prevention \nmodule based on the prototype willingness model to reduce \nintention and willingness to sexting among diploma students  \n \nNorain Mansor, DrPH1,2, Norliza Ahmad, PhD1, Salmiah Md Said, MCommMed1, Kit-Aun Tan, PhD3, Rosnah \nSutan, PhD4 \n\n\n\n     \n1Department of Community Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, \nMalaysia, 2Ministry of Health, Malaysia, 3Department of Psychiatry, Faculty of Medicine and Health Sciences, Universiti Putra \nMalaysia, Serdang, Selangor, Malaysia, 4Department of Community Health, Faculty of Medicine, Universiti Kebangsaan \nMalaysia, Jalan Yaacob Latif, Bandar Tun Razak Cheras, Kuala Lumpur, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 24 August 2023                                                                                                                                                                         \nCorresponding Author: Norliza Ahmad                                                                                                                                                                               \nEmail: lizaahmad@upm.edu.my\n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 646\n\n\n\n\n\n\n\n\nDevelopment of an online animated sexting prevention module based on the prototype \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                647 \n\n\n\nThe application of a theory-based intervention is more likely \nto yield a better outcome.18,19 Therefore, we used the prototype \nwillingness model (PWM) theory as the backbone of our \nintervention to reduce the intention and willingness to sext. \nThe PWM has been applied to predict risky behaviours \namongst the adolescents and young adult population.14,20\u201322 \nHowever, this theory has not been applied to sexting \ninterventions to date. To our knowledge, this is the first \nintervention module developed based on PWM for sexting. \nThe evaluation of the effectiveness of this module involved \ntwo phases, i.e., phase one involved the development and \nvalidation of the newly developed module and the second \nphase involved evaluating the effectiveness of this module \nusing randomised controlled trial (RCT). In this paper, we \nreported phase one of the study. The second phase is reported \nelsewhere. \n \n \nMATERIALS AND METHODS \nPhase one involved the identification of the suitable contents \nfor the intervention based on the respective constructs of the \nPWM before matching them with the suitable behavioural \nchange techniques (BCT).18 These processes involved \nreviewing previous literature and consultation with experts in \nthe field. Three public health experts and a clinical \npsychologist were invited to examine the content validity. \nOnce the contents were agreed upon by all the experts, the \nstoryboard and scripts for the animated video was created. A \nprivate multimedia company was then appointed to develop \nthe animated video. The animated video used to deliver the \nintervention was assessed for its objective, structure, \npresentation and relevance as a part of the validation \nprocess. A series of reviews of the scripts and the flow of the \nstoryboard was also conducted by the same experts before it \nwas finalised. The flow of the development of the video as in \nAppendix 1. \n \nLater, a pilot study was conducted at a public university, \nwhich is the same university where phase two of the study \nwas conducted. The university has 13 diploma programmes. \nOne programme was randomly selected for the pilot study. \nThe remaining 12 programmes were involved in phase two of \nthis study, where a randomised controlled field trial (RCT) \nwas conducted to test the effectiveness of this module. Thirty \nvoluntary students who fulfilled the inclusion criteria of the \nRCT but were not included in the main study were invited to \nparticipate in the pilot study. The sample size of 30 was \nderived from 10% of the sample size calculated for the RCT.23 \n \nYouTube channel was utilised as the online medium to \ndistribute the newly developed video as it was convenient and \neasily accessible. The videos were set to be private and only \nthose with access could view them. The pilot study aimed to \ndetermine the acceptability, appropriateness, and feasibility \nof the intervention module by using quantitative measures.24 \nAcceptability is a form of personal judgment made by \nindividuals about the intervention and it can vary according \nto individual needs, preferences or expectations. In \ncomparison, appropriateness refers to the perceived fit, \nrelevance or compatibility of the intervention to be practiced \nin a given setting. In other words, it assesses the technical or \nsocial perspective towards the intervention. Feasibility, on the \n\n\n\nother hand, is the practicality with which the new \nintervention can be successfully carried out in a given setting. \n \nThree quantitative scales were used, namely acceptability of \nintervention measure (AIM), intervention appropriateness \nmeasure (IAM) and feasibility of intervention measure \n(FIM).24 Each of these scales consisted of four-item \nstatements. The response scale for all item statements ranged \nfrom 1 (completely disagree) to 5 (completely agree). The \nminimum and maximum scores of each of the measures are \n12 and 24 respectively. A higher score indicates greater \nacceptability, appropriateness and feasibility. The \nrespondents were also requested to provide opinions and \nfeedback on the videos. \n \nThe studies involving human participants were reviewed and \napproved by the Ethics Committee for Research Involving \nHuman Subjects at Universiti Putra Malaysia (JKEUPM-2020-\n321). The patients/participants provided their written \ninformed consent to participate in this study. The RCT of this \nintervention module was prospectively registered in the Thai \nClinical Trials Registry (TCTR20201002001). The approval \nfrom the administration department of the higher education \ninstitution and the head of the program, as well as \nrespondents\u2019 written consent, were obtained before the \ncommencement of the study.  \n \n \nRESULTS \nThe PWM consists of five constructs, i.e. intention, \nwillingness, attitude, perceived norm and prototype \nperception. Figure 1 illustrates the theoretical construct of the \nPWM.21,25 \n \nThe intervention was developed in the Malay language to \nsuit the target population. It comprises five sections, namely \nSection 1 (Sexting and Z generation), Section 2 (What are the \nimplications of sexting?), Section 3 (Who is behind sexting?), \nSection 4 (What others' opinion?) and Section 5 (What can \nyou do?). The summary of constructs and contents in each \nsection of the intervention is summarised in Table I. \n \nSection 1: Sexting and Z generation \nThis was an introductory session that was delivered via an \nanimated video. Participants were informed of the definition \nof sexting and the population was deemed to be at risk of \nbeing involved in it. \n \nSection 2: What are the implications of sexting? \nParticipants were educated on the consequences of sexting \nfrom four aspects, including sexual and reproductive health, \ncyberbullying, mental health and the legal aspect. The \ncontent of this section was based on the literature review on \nthe implications of sexting.2,6\u20138,26\u201328 In this section, the \nparticipants were also exposed to the real scenario of \nnegative consequences of sexting as reported in the local \nmedia. \n \nSection 3: Who is behind sexting? \nParticipants were exposed to the different personalities of \npeople who are more prone to engage in sexting (for \nexample, individuals with a high sensation-seeking \n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 647\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n648                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nSe\nct\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nPW\nM\n\n\n\n c\non\n\n\n\nst\nru\n\n\n\nct\ns\n\n\n\n\n\n\n\n A\nim\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  B\neh\n\n\n\nav\nio\n\n\n\nur\n c\n\n\n\nha\nng\n\n\n\ne \nte\n\n\n\nch\nni\n\n\n\nqu\nes\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  D\nur\n\n\n\nat\nio\n\n\n\nn \n \n\n\n\nSe\nct\n\n\n\nio\nn\n\n\n\n 1\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n -\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n T\no\n\n\n\n in\ncr\n\n\n\nea\nse\n\n\n\n t\nh\n\n\n\ne \nkn\n\n\n\no\nw\n\n\n\nle\nd\n\n\n\ng\ne \n\n\n\no\nf \n\n\n\nse\nxt\n\n\n\nin\ng\n\n\n\n\n\n\n\n   \n  2\n\n\n\n. P\nro\n\n\n\nvi\nd\n\n\n\ne \nin\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn\n a\n\n\n\nb\no\n\n\n\nu\nt \n\n\n\nth\ne \n\n\n\nse\nxt\n\n\n\nin\ng\n\n\n\n t\nre\n\n\n\nn\nd\n\n\n\n a\nm\n\n\n\no\nn\n\n\n\ng\nst\n\n\n\n t\nh\n\n\n\ne\n   \n\n\n\n\n\n\n\n   \n2.\n\n\n\n4 \nm\n\n\n\nin\nu\n\n\n\nte\ns.\n\n\n\n \nSe\n\n\n\nxt\nin\n\n\n\ng\n a\n\n\n\nn\nd\n\n\n\n Z\n g\n\n\n\nen\ner\n\n\n\nat\nio\n\n\n\nn\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n a\n\n\n\nm\no\n\n\n\nn\ng\n\n\n\nst\n t\n\n\n\nh\ne \n\n\n\np\nar\n\n\n\nti\nci\n\n\n\np\nan\n\n\n\nts\n. \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nZ \ng\n\n\n\nen\ner\n\n\n\nat\nio\n\n\n\nn\n a\n\n\n\nn\nd\n\n\n\n t\nh\n\n\n\ne \nre\n\n\n\nas\no\n\n\n\nn\ns \n\n\n\nw\nh\n\n\n\ny \nit\n\n\n\n is\n c\n\n\n\no\nm\n\n\n\nm\no\n\n\n\nn\n a\n\n\n\nm\no\n\n\n\nn\ng\n\n\n\n t\nh\n\n\n\nem\n. \n\n\n\n Se\nct\n\n\n\nio\nn\n\n\n\n 2\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n A\ntt\n\n\n\nit\nu\n\n\n\nd\ne\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \nTo\n\n\n\n im\np\n\n\n\nro\nve\n\n\n\n t\nh\n\n\n\ne \nat\n\n\n\nti\ntu\n\n\n\nd\ne \n\n\n\nto\nw\n\n\n\nar\nd\n\n\n\ns \nse\n\n\n\nxt\nin\n\n\n\ng\n. \n\n\n\n   \n i.\n\n\n\n P\nro\n\n\n\nvi\nd\n\n\n\ne \nin\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn\n o\n\n\n\nn\n t\n\n\n\nh\ne \n\n\n\nn\neg\n\n\n\nat\niv\n\n\n\ne \nco\n\n\n\nn\nse\n\n\n\nq\nu\n\n\n\nen\nce\n\n\n\ns \no\n\n\n\nf \nse\n\n\n\nxt\nin\n\n\n\ng\n   \n\n\n\n   \n 9\n\n\n\n.3\n m\n\n\n\nin\nu\n\n\n\nte\ns.\n\n\n\nW\nh\n\n\n\nat\n a\n\n\n\nre\n t\n\n\n\nh\ne \n\n\n\nim\np\n\n\n\nlic\nat\n\n\n\nio\nn\n\n\n\ns \no\n\n\n\nf \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \nTo\n\n\n\n r\ned\n\n\n\nu\nce\n\n\n\n t\nh\n\n\n\ne \nin\n\n\n\nte\nn\n\n\n\nti\no\n\n\n\nn\n a\n\n\n\nn\nd\n\n\n\n w\nill\n\n\n\nin\ng\n\n\n\nn\nes\n\n\n\ns \n   \n\n\n\n   \n f\n\n\n\nro\nm\n\n\n\n f\no\n\n\n\nu\nr \n\n\n\nas\np\n\n\n\nec\nts\n\n\n\n w\nh\n\n\n\nic\nh\n\n\n\n a\nre\n\n\n\n s\nex\n\n\n\nu\nal\n\n\n\n a\nn\n\n\n\nd\n r\n\n\n\nep\nro\n\n\n\nd\nu\n\n\n\nct\niv\n\n\n\ne \nh\n\n\n\nea\nlt\n\n\n\nh\n,  \n\n\n\nse\nxt\n\n\n\nin\ng\n\n\n\n? \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  t\no\n\n\n\n s\nex\n\n\n\nt \nam\n\n\n\no\nn\n\n\n\ng\nst\n\n\n\n p\nar\n\n\n\nti\nci\n\n\n\np\nan\n\n\n\nts\n.  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\ncy\nb\n\n\n\ner\nb\n\n\n\nu\nlly\n\n\n\nin\ng\n\n\n\n, m\nen\n\n\n\nta\nl h\n\n\n\nea\nlt\n\n\n\nh\n a\n\n\n\nn\nd\n\n\n\n le\ng\n\n\n\nal\nit\n\n\n\ny.\n  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n ii\n\n\n\n. P\nro\n\n\n\nvi\nd\n\n\n\ne \nre\n\n\n\nal\n w\n\n\n\no\nrl\n\n\n\nd\n n\n\n\n\neg\nat\n\n\n\niv\ne \n\n\n\nan\nd\n\n\n\n le\ng\n\n\n\nis\nla\n\n\n\nti\no\n\n\n\nn\n c\n\n\n\no\nn\n\n\n\nse\nq\n\n\n\nu\nen\n\n\n\nce\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n o\nf \n\n\n\nse\nxt\n\n\n\nin\ng\n\n\n\n t\no\n\n\n\n t\nh\n\n\n\ne \nin\n\n\n\nd\niv\n\n\n\nid\nu\n\n\n\nal\ns \n\n\n\nb\nas\n\n\n\ned\n o\n\n\n\nn\n t\n\n\n\nh\ne \n\n\n\nre\np\n\n\n\no\nrt\n\n\n\ns \nb\n\n\n\ny \nlo\n\n\n\nca\nl m\n\n\n\ned\nia\n\n\n\n.  \n Se\n\n\n\nct\nio\n\n\n\nn\n 3\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n P\n\n\n\nro\nto\n\n\n\nty\np\n\n\n\ne \n   \n\n\n\n\n\n\n\n\n\n\n\n   \nTo\n\n\n\n im\np\n\n\n\nro\nve\n\n\n\n t\nh\n\n\n\ne \np\n\n\n\nro\nto\n\n\n\nty\np\n\n\n\ne \np\n\n\n\ner\nce\n\n\n\np\nti\n\n\n\no\nn\n\n\n\n. \n   \n\n\n\n\n\n\n\ni. \nPr\n\n\n\no\nvi\n\n\n\nd\ne \n\n\n\nin\nfo\n\n\n\nrm\nat\n\n\n\nio\nn\n\n\n\n a\nb\n\n\n\no\nu\n\n\n\nt \nth\n\n\n\ne \nch\n\n\n\nar\nac\n\n\n\nte\nri\n\n\n\nst\nic\n\n\n\ns \no\n\n\n\nr \np\n\n\n\ner\nso\n\n\n\nn\nal\n\n\n\nit\ny\n\n\n\n\n\n\n\n   \n 3\n\n\n\n m\nin\n\n\n\nu\nte\n\n\n\ns.\n \n\n\n\nW\nh\n\n\n\no\n is\n\n\n\n b\neh\n\n\n\nin\nd\n\n\n\n s\nex\n\n\n\nti\nn\n\n\n\ng\n?\n\n\n\n\n\n\n\n\n\n\n\n   \n p\n\n\n\ner\nce\n\n\n\np\nti\n\n\n\no\nn\n\n\n\n\n\n\n\n\n\n\n\n   \n  T\n\n\n\no\n r\n\n\n\ned\nu\n\n\n\nce\n t\n\n\n\nh\ne \n\n\n\nin\nte\n\n\n\nn\nti\n\n\n\no\nn\n\n\n\n a\nn\n\n\n\nd\n w\n\n\n\nill\nin\n\n\n\ng\nn\n\n\n\nes\ns \n\n\n\n\n\n\n\no\nf \n\n\n\nin\nd\n\n\n\niv\nid\n\n\n\nu\nal\n\n\n\ns \nw\n\n\n\nh\no\n\n\n\n a\nre\n\n\n\n a\nss\n\n\n\no\nci\n\n\n\nat\ned\n\n\n\n w\nit\n\n\n\nh\n s\n\n\n\nex\nti\n\n\n\nn\ng\n\n\n\n b\neh\n\n\n\nav\nio\n\n\n\nu\nr.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  t\n\n\n\no\n s\n\n\n\nex\nt \n\n\n\nam\no\n\n\n\nn\ng\n\n\n\nst\n p\n\n\n\nar\nti\n\n\n\nci\np\n\n\n\nan\nts\n\n\n\n. \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  \nSe\n\n\n\nct\nio\n\n\n\nn\n 4\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n P\n\n\n\ner\nce\n\n\n\niv\ned\n\n\n\n n\no\n\n\n\nrm\n   \n\n\n\n\n\n\n\n T\no\n\n\n\n r\ned\n\n\n\nu\nce\n\n\n\n t\nh\n\n\n\ne \np\n\n\n\ner\nce\n\n\n\niv\ned\n\n\n\n n\no\n\n\n\nrm\n, i\n\n\n\nn\nte\n\n\n\nn\nti\n\n\n\no\nn\n\n\n\n\n\n\n\n i.\n P\n\n\n\nro\nvi\n\n\n\nd\ne \n\n\n\no\np\n\n\n\nin\nio\n\n\n\nn\ns \n\n\n\no\nf \n\n\n\np\nar\n\n\n\nen\nts\n\n\n\n a\nn\n\n\n\nd\n o\n\n\n\nth\ner\n\n\n\n y\no\n\n\n\nu\nn\n\n\n\ng\n a\n\n\n\nd\nu\n\n\n\nlt\ns \n\n\n\no\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n2 \n\n\n\nm\nin\n\n\n\nu\nte\n\n\n\ns.\n \n\n\n\nW\nh\n\n\n\nat\n o\n\n\n\nth\ner\n\n\n\ns\u2019\n o\n\n\n\np\nin\n\n\n\nio\nn\n\n\n\n? \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  a\nn\n\n\n\nd\n w\n\n\n\nill\nin\n\n\n\ng\nn\n\n\n\nes\ns \n\n\n\nto\n s\n\n\n\nex\nt \n\n\n\nam\no\n\n\n\nn\ng\n\n\n\nst\n  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nin\nd\n\n\n\niv\nid\n\n\n\nu\nal\n\n\n\ns \nw\n\n\n\nh\no\n\n\n\n a\nre\n\n\n\n in\nvo\n\n\n\nlv\ned\n\n\n\n in\n s\n\n\n\nex\nti\n\n\n\nn\ng\n\n\n\n.  \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  p\n\n\n\nar\nti\n\n\n\nci\np\n\n\n\nan\nts\n\n\n\n. \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nSe\nct\n\n\n\nio\nn\n\n\n\n 5\n: \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  P\ner\n\n\n\nce\niv\n\n\n\ned\n n\n\n\n\no\nrm\n\n\n\n\n\n\n\n   \n T\n\n\n\no\n r\n\n\n\ned\nu\n\n\n\nce\n t\n\n\n\nh\ne \n\n\n\np\ner\n\n\n\nce\niv\n\n\n\ned\n n\n\n\n\no\nrm\n\n\n\n, p\nro\n\n\n\nto\nty\n\n\n\np\ne \n\n\n\n   \n i.\n\n\n\n P\nro\n\n\n\nvi\nd\n\n\n\ne \nin\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn\n o\n\n\n\nn\n p\n\n\n\no\nte\n\n\n\nn\nti\n\n\n\nal\n s\n\n\n\nce\nn\n\n\n\nar\nio\n\n\n\ns \nth\n\n\n\nat\n m\n\n\n\nig\nh\n\n\n\nt \nle\n\n\n\nad\n  \n\n\n\n\n\n\n\n   \n5.\n\n\n\n4 \nm\n\n\n\nin\nu\n\n\n\nte\ns.\n\n\n\n \nW\n\n\n\nh\nat\n\n\n\n y\no\n\n\n\nu\n c\n\n\n\nan\n d\n\n\n\no\n? \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nPr\no\n\n\n\nto\nty\n\n\n\np\ne \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\np\ner\n\n\n\nce\np\n\n\n\nti\no\n\n\n\nn\n, i\n\n\n\nn\nte\n\n\n\nn\nti\n\n\n\no\nn\n\n\n\n, a\nn\n\n\n\nd\n w\n\n\n\nill\nin\n\n\n\ng\nn\n\n\n\nes\ns \n\n\n\nto\n  \n\n\n\n   \n t\n\n\n\no\n s\n\n\n\nex\nti\n\n\n\nn\ng\n\n\n\n. \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n p\n\n\n\ner\nce\n\n\n\np\nti\n\n\n\no\nn\n\n\n\n\n\n\n\n\n\n\n\n   \n  s\n\n\n\nex\nt \n\n\n\nam\no\n\n\n\nn\ng\n\n\n\nst\n p\n\n\n\nar\nti\n\n\n\nci\np\n\n\n\nan\nts\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n ii\n. P\n\n\n\nro\nvi\n\n\n\nd\ne \n\n\n\nin\nfo\n\n\n\nrm\nat\n\n\n\nio\nn\n\n\n\n o\nn\n\n\n\n p\no\n\n\n\nte\nn\n\n\n\nti\nal\n\n\n\n b\nar\n\n\n\nri\ner\n\n\n\ns \no\n\n\n\nf \nre\n\n\n\nsi\nst\n\n\n\nin\ng\n\n\n\n s\nex\n\n\n\nti\nn\n\n\n\ng\n. \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n ii\n\n\n\ni. \nPr\n\n\n\no\nvi\n\n\n\nd\ne \n\n\n\nsk\nill\n\n\n\ns \nto\n\n\n\n r\nes\n\n\n\nis\nt \n\n\n\nse\nxt\n\n\n\n r\neq\n\n\n\nu\nes\n\n\n\nts\n b\n\n\n\ny \no\n\n\n\nth\ner\n\n\n\ns \nan\n\n\n\nd\n in\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn\n  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n o\n\n\n\nn\n w\n\n\n\nh\ner\n\n\n\ne \nto\n\n\n\n g\net\n\n\n\n h\nel\n\n\n\np\n. \n\n\n\n\n\n\n\nTa\nbl\n\n\n\ne \nI: \n\n\n\nSu\nm\n\n\n\nm\nar\n\n\n\ny \nof\n\n\n\n th\ne \n\n\n\nse\nxt\n\n\n\nin\ng \n\n\n\nin\nte\n\n\n\nrv\nen\n\n\n\ntio\nn \n\n\n\nm\nod\n\n\n\nul\ne \n\n\n\n(S\nIM\n\n\n\n)\n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 648\n\n\n\n\n\n\n\n\nDevelopment of an online animated sexting prevention module based on the prototype \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                649 \n\n\n\nItems                 Item statement                                                                                      Responses (n=30) \n                                                                         Completely           Disagree (%)             Neither agree              Agree (%)          Completely \n                                                                        disagree (%)                                          nor disagree (%)                                       agree (%) \nAIM 1      This SIM meets my approval                  0                              0                              17%                          53%                    30% \nAIM 2      This SIM is appealing to me                   0                              0                              20%                          50%                    30% \nAIM 3      I like SIM                                                  0                              0                              23%                          50%                    27% \nAIM 4      I welcome SIM to be given                    0                              0                              10%                          47%                    43% \n                to other students                                      \n\n\n\nTable II: Acceptability intervention measure (AIM)\n\n\n\nItems                 Item statement                                                                                  Responses (n=30) \n                                                                         Completely              Disagree                Neither agree                Agree             Completely  \n                                                                        disagree (%)                  (%)                  nor disagree (%)                 (%)                 agree (%) \nIAM 1      This SIM seems fitting in                        0                              0                              10%                          50%                    40% \n                the sexting prevention effort                  \nIAM 2      This SIM seems suitable for                    0                              0                              13%                          50%                    37% \n                university students                                    \nIAM 3      This SIM seems applicable                      0                              0                              13%                          40%                    47% \nIAM 4      This SIM seems like a good                    0                              0                              13%                          37%                    50% \n                match with the current  \n                technology era.                                         \n \n \n\n\n\nTable III: Appropriateness measure\n\n\n\nItems                 Item statement                                                                                 Responses (n=30) \n                                                                         Completely              Disagree               Neither agree             Agree (%)          Completely  \n                                                                        disagree (%)                  (%)                  nor disagree (%)                                       agree (%) \nFIM 1       Things that we learn from                     0                              0                              13%                          37%                    50% \n                SIM seem implementable                         \nFIM 2       Things that we learn from                     0                              0                              13%                          37%                    50% \n                SIM seem possible                                     \nFIM 3       Things that we learn from                     0                              0                              13%                          37%                    50% \n                SIM seem doable                                      \nFIM 4       Things that we learn from                     0                              0                              13%                          37%                    50% \n                SIM seem easy to apply in  \n                real life                                                       \n \n\n\n\nTable IV: Feasibility of intervention measure\n\n\n\nFig. 1: The theoretical construct of the prototype willingness model.\n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 649\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n650                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\npersonality trait, low agreeableness, neuroticism and \nattachment anxiety). The content of this section was based \non the findings from the literature review on studies of the \nrelationship between personality type and sexting \nbehaviour.28-30 \n \nSection 4: What others' opinion? \nParticipants were provided with relevant information on the \nperceived and actual prevalence of sexting in Western and \nAsian countries as a comparison. Besides, they were also \nprovided with information about the perception and \napproval of others about sexting behaviour, particularly \nparents, friends, religion and culture. The content was \nadapted from the findings of quantitative and qualitative \nstudies obtained during the literature review.31\u201333  \n \nSection 5: What can you do? \nParticipants were provided with the instructions on how to \nresist social pressure to sext, such as a demonstration on how \nto resist sext requests by others. The participants were also \nreminded to use prompts, whereby they are taught to identify \nenvironmental prompts that can be applied as a reminder for \nthem to avoid potential situations that can lead to sexting. \nThe participants were also prompted to think about the \npotential barriers that can prevent them from engaging in \nsexting and to identify ways to overcome the behaviour. \n \nBased on the response of the pilot study, the majority of the \nrespondents found this intervention module to be acceptable \n(Table II). The scores were not normally distributed, giving a \nmedian (interquartile range, IQR) of 20 (4). Qualitatively, \nrespondents suggested improvement in the video\u2019s graphics \nand animation, as well as increasing examples using real-\nworld sexting scenarios. Furthermore, some respondents \nrecommended for the intervention be expanded to school \nchildren. \n \nBased on the response, the majority of the respondents found \nthis intervention to be appropriate (Table III). The scores were \nnot normally distributed, giving a median (IQR) of 21 (4). No \nadditional comment was made qualitatively in this section. \n \nBased on the response, the majority of the respondents found \nthat this intervention was feasible (Table IV). The scores were \nnot normally distributed, giving a median (IQR) of 22 (4). \nQualitatively, the respondents suggested uploading the video \non social media platforms such as TikTok to gain more \nattention.  \n \n \nDISCUSSION \nIn this paper, we reported the development of an online \nanimated sexting intervention module based on the PWM \naimed at reducing the intention and willingness to sext \namong diploma students in Malaysia. The PWM was chosen \nas the model to address the intention and willingness of \nsexting, both of which represented important precursors to \nsexting behaviour. This model has also been used in previous \ninterventions for the reduction of risky behaviours.14,20\u201322 \nTherefore, this intervention module was established based on \nthe previous interventions using PWM, and consultation with \nexperts, before being validated via a pilot study involving a \n\n\n\nsubgroup of the study population who were not participants \nof the main RCT. \n \nSexting is a complex behaviour that has been explained by \nseveral behavioural theories, including PWM. The \napplication of PWM in the design of the intervention video in \nthis study represented a systematic approach to determine its \nefficacy in reducing the sexting intention and willingness \namong young adults. Since most of the published literature \nfocused on the use of PWM for smoking, skin tanning \nprevention and prevention of alcohol consumption, it is \nnecessary to acknowledge how PWM could contribute to the \nreduction of the intention and willingness to sext among \nundergraduate students. \n \nNext, the design of this intervention was adapted from the \nseveral experimental studies that were conducted based on \nPWM.34\u201337 Based on an experimental study, sharing the \nnegative social consequences of having unsafe sex with \nuniversity students has been effective in decreasing their \nwillingness to perform unsafe sex.34 One of the possible \nreasons could be how the information might change their \nattitude with regard to their willingness to have unsafe sex. \nTherefore, we postulated that the provision of relevant \ninformation on possible negative outcomes resulting from \nengagement in sexting behaviour might contribute to the \nchange in attitude and subsequently the willingness to sext \namong young adults. \n \nWith regard to the best approach to improve the perceived \nnorm of sexting, we included information on the pattern of \nsexting behaviour globally and locally, previous opinions on \nsexting prevalence, and others\u2019 opinions on sexting \nbehaviour in the intervention module. These were based on \nan experimental study that provided information on the \ntypical drinking behaviour, average drinking behaviour on \ncampus, and previous thoughts on the average drinking \nbehaviour on campus for undergraduate students in the \nUSA.35 The study outcome showed a successful reduction in \nthe perceived norm regarding drinking among the \nrespondents. Therefore, in our study intervention, we \nprovided the opinions of parents and other young adults on \nindividuals involved in sexting in order to reduce the \nperceived norm among the respondents. \n \nLastly, the review findings of the behavioural change \ntechniques used in PWM were applied to improve the \nprototype perception towards the sexters.38 Several studies \nprovided positive and negative identities for the actors or \nabstainers.34,39 For example, a study has described the \npersonality of people who practiced unsafe or safe sex in a \nbogus survey created for the intervention which in turn, the \ntechnique was found to successfully increase participants\u2019 \nwillingness to wear condoms.34 This technique was considered \nadequate to modify the prototype perception.36 Therefore, in \nour intervention, we provided information on the type of \npersonality associated with sexting behaviour and a brief \nexplanation of why this type of person would be more prone \nto engage in sexting. \n \nBased on the results from the pilot study, the online video was \nconsidered to be a form of acceptable, appropriate and \n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 650\n\n\n\n\n\n\n\n\nDevelopment of an online animated sexting prevention module based on the prototype \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                651 \n\n\n\nfeasible intervention. Furthermore, these videos were \nuploaded to a private YouTube channel, making it \nconvenient for the participants to access during their free \ntime. Besides, the videos were considered to be more \nattractive for the participants because they were in the form \nof animation, easy to understand, with contents that might \nrelate to them and short (only took a few minutes of their \ntime to complete viewing). However, they provided some \ncomments on improving the graphics and animation of the \nvideo, apart from incorporating more examples based on \nreal-world sexting scenarios. In addition, they also suggested \nthat the videos be uploaded to other social media platforms \nonce the effectiveness of this intervention has been \nestablished. Last but not least, they also recommended that \nthe intervention module be expanded to school children. \n \nDespite the positive feedback from this pilot study on our \nmodule, we acknowledge that this module will be one of the \nstrategies to prevent sexting and cannot be a standalone \nstrategy. There are several other factors that could influence \nsexting that are beyond the scope of this module. For \nexample, family dynamics, interrelationships between family \nmembers and peers, and financial constraints. Therefore, \nother strategies could be implemented in parallel with the \nimplementation of this module in order to have a greater \nimpact on sexting prevention. Such strategies include \nparental involvement, peer-to-peer education, digital literacy \nprogrammes, sexting-related legislation awareness, reporting \nmechanisms for sexting victims, religious workshops, moral \nguidance and public campaigns on sexting that emphasise \nthe importance of responsible online behaviour. \n \n \nCONCLUSION  \nThis animated sexting intervention module aimed at \nreducing the intention and willingness to sext represented an \nimportant contribution to the body of literature on the use of \nprototype willingness model (PWM). The intervention was \ndeemed acceptable to the majority of diploma students that \nwere involved in this study. However, a randomised \ncontrolled field trial (RCT) can be undertaken to establish its \neffectiveness. \n \n \nACKNOWLEDGEMENT \nWe are grateful to the HIV/STI Unit of Melaka\u2019s Health \nDepartment for sharing valuable data on sexually \ntransmitted infections. We also would like to express our \ngratitude for the kind cooperation and commitment given by \nthe higher education institution and all the diploma students \ninvolved in this study. \n \n \nCONSENT FOR PUBLICATION \nThe authors would like to thank the Director-General of \nHealth Malaysia and Director-General of National \nPopulation and Family Development Board for their \npermission to publish this article. \n \n \nCONFLICT OF INTEREST \nThe authors declare that they have no competing interest. \n\n\n\nFUNDING \nWe received a grant (GPLPPKN0022) from the National \nPopulation and Family Development \nBoard Malaysia. \n \n \nREFERENCES \n1. Courtice EL, Shaughnessy K. Technology-mediated sexual \n\n\n\ninteraction and relationships: a systematic review of the \nliterature. Sex Relatsh Ther 2017; 32(3/4): 269-90. \n\n\n\n2. Klettke B, Hallford DJ, Mellor DJ. Sexting prevalence and \ncorrelates: A systematic literature review. Clin Psychol Rev 2014; \n34(1): 44-53. \n\n\n\n3. 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Arch Sex Behav. 2015 \nAug; 44(6): 1675-84. \n\n\n\n30. Delevi R, Weisskirch RS. Personality factors as predictors of \nsexting. Comput Human Behav 2013; 29(6): 2589-94 \n\n\n\n31. Walrave M, Heirman W, Hallam L. Under pressure to sext? \nApplying the theory of planned behaviour to adolescent sexting. \nBehav Inf Technol 2014; 33(1): 85-98. \n\n\n\n32. Speno AG, Aubrey JS. Adolescent Sexting: The Roles of Self-\nObjectification and Internalization of Media Ideals. Psychol \nWomen Q 2019; 43(1): 88\u2013104.  \n\n\n\n33. Walker S, Sanci L, Temple-Smith M. Sexting: Young women\u2019s and \nmen\u2019s views on its nature and origins. J Adolesc Heal 2013; 52(6): \n697-701. \n\n\n\n34. Blanton H, VandenEijnden RJJM, Buunk BP, Gibbons FX, Gerrard \nM, Bakker A. Accentuate the negative: Social images in the \nprediction and promotion of condom use. J Appl Soc Psychol. \n2001; 31(2): 274-95 \n\n\n\n35. Lewis M, King K, Litt D, Swanson A, Lee C. Examining daily \nvariability in willingness to drink in relation to underage young \nadult alcohol use. Addict Behav 2016; 61: 62-7. \n\n\n\n36. Dohnke B, Dewitt T, Steinhilber A. A prototype-targeting \nintervention for the promotion of healthy eating in adolescents: \nDevelopment and evaluation using intervention mapping. \nHealth Educ 2011; 118(6): 450-69 \n\n\n\n37. Todd J, Mullan B. Using the theory of planned behaviour and \nprototype willingness model to target binge drinking in female \nundergraduate university students. Addict Behav 2011; 36(10): \n980-6.  \n\n\n\n38. Davies E, Martin J, Foxcroft D. Development of an adolescent \nalcohol misuse intervention based on the Prototype Willingness \nModel: A Delphi study. Health Educ 2016; 116(3): 275-91. \n\n\n\n39. Andrews JA, Gordon JS, Hampson SE, Christiansen SM, Gunn B, \nSlovic P, et al. Shortterm efficacy of Click City\u00ae: Tobacco: \nchanging etiological mechanisms related to the onset of tobacco \nuse. Prev Sci 2011; 12(1): 89-102. \n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 652\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                653 \n\n\n\nABSTRACT \nIntroduction: Healthcare drivers, including ambulance \ndrivers, were less concerned about health and safety during \nthe COVID-19 pandemic, with not only the risk of COVID-19 \ninfection but also a higher risk of prolonged states of \nalertness, stress, burnout, fatigue and road traffic accident. \nThis study aimed to determine the prevalence of stress and \nits associated factors among healthcare drivers, especially \nduring the COVID-19 pandemic.  \n \nMaterials and Methods: This study employs a cross-\nsectional study design and utilises self-reported data \nobtained from locally validated personal stress inventory \nquestionnaires. The data collection period spanned from \nAugust 1 to 31, 2020. The study sample consisted of 163 \nhealthcare drivers affiliated with the Negeri Sembilan State \nHealth Department. The Chi-square test and Fisher\u2019s exact \ntest were the first used to determine the association \nbetween variables prior to conducting multiple logistic \nregression to predict the relationship between dependent \nand independent variables.  \n \nResults: In COVID-19's first year, 7.4% (n = 12) of healthcare \ndrivers reported perceived stress with ambulance drivers \nreporting more stress (10.6%; n = 5) than non-ambulance \ndrivers (6.0%; n = 7). Simple statistical analysis identified \nperceived stress significantly associated with household \nincome, smoking status and performing on-call. Further \nanalysis by multiple logistic regression found that perceived \nstress was significantly related to smoking (aOR 19.9, 95% \nCI: 1.86-213.90), and performing on-call (aOR 8.69, 95% CI \n1.21-62.28). Nevertheless, no association was found \nbetween perceived stress and age, ethnicity, marital status, \neducation, household income, co-morbidities, driving \nassignment, employment duration, needing a part-time job \nor motor vehicle accident history.  \n \nConclusion: The study found that the perceived stress \namongst Malaysian healthcare drivers during the COVID-19 \npandemic was relatively low. This could be due to fewer life-\nthreatening tasks, emergencies, assigned tasks and \nincrease income due to overtime during the COVD-19 \n\n\n\npandemic. The OSH team's efforts to provide consistent \nsafety and health training, including stress management, \nmay have contributed to the healthcare driver\u2019s ability to \neffectively manage the stressful circumstances encountered \nduring the pandemic. In order to enhance salary \ncompetitiveness, employers should provide financial \nmanagement education alongside subsidised housing and \nchildcare provisions. Healthcare drivers who smoke should \nbe taught different stress reduction techniques so that they \ncan handle their stress in a healthy way.  \n \nKEYWORDS:  \nHealthcare; health drivers; ambulance drivers; EMS drivers; stress; \nperceived stress; COVID-19; pandemic; prevalence \n \n \nINTRODUCTION \nThe Global populations have been devastated by the COVID-\n19 epidemic. The impact has existed for almost 2 years since \nthe World Health Organization (WHO) announced the Public \nHealth Emergency of International Concern (PHEIC).1 Every \npart of human life was affected by the COVID-19 epidemic, \nbut economic and social devastation stood out.2,3 \nNevertheless, there are over 8 million confirmed COVID-19 \ninfections worldwide, with two million deaths in 2020, and it \nis increasing day by day.4 Low-income and poor countries \nwere badly affected and had difficulty surviving during the \nCOVID-19 pandemic, as warned by the WHO and the World \nBank Organisation.5,6   \n \nThis pandemic has given a strike to the healthcare system \ncapacity. The occupancy of COVID-19 patients is more than \nthe capacity of healthcare facilities and hospitals worldwide. \nCertain countries (South Africa, the United Kingdom, \nGermany, China and Malaysia) built field hospitals to cope \nwith the pandemic situation.7\u20139 The impacts of the COVID-19 \npandemic are completely different in countries such as Italy, \nSpain and Malaysia, which experienced a surge of cases but \nrelied on the inadequacy of hospital beds and healthcare \nprofessionals.7,10 But, more importantly, during the COVID-19 \npandemic, overwhelmed, short-staffed healthcare facilities \nlead to stress and burnout among healthcare workers, \n\n\n\nStress perceived by drivers in public healthcare facilities \nin Negeri Sembilan during the first year of the COVID-19 \npandemic  \n \nAbdul Aziz Harith, MPH1,2, Zuraida Mohamed, MPH (OH)3, Azyyati Mohammad, MPH3, Lim Kuang Kuay, MSc2, \nNaiemy Reffin, MPH4, Malindawati Mohd Fadzil, MSc4, Shahida Ismail, MPH4, Nofi Yuliani Dahlan, MPH4, \nMuhammad Zulfakhar Zubir, MSc4, Mohd Ihsanuddin Abas, MPH5 \n\n\n\n     \n1Occupational and Aviation Medicine, Department of Medicine, University of Otago Wellington, Wellington New Zealand, New \nZealand, 2Occupational Health Research Centre, Institute for Public Health, National Institutes of Health, Shah Alam, Selangor \nMalaysia, Malaysia, 3Occupational and Environmental Health Unit, Public Health Division, Negeri Sembilan State Health \nDepartment, Negeri Sembilan, Malaysia, 4Department of Community Health, Faculty of Medicine, Universiti Kebangsaan \nMalaysia, Malaysia, 5Community Medicine Unit, Faculty of Medicine, Universiti Sultan Zainal Abidin, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 30 August 2023                                                                                                                                                                         \nCorresponding Author: Abdul Aziz bin Harith                                                                                                                                                                     \nEmail: drazizkpaskkm@gmail.com; abdulaziz.harith@postgrad.otago.ac.nz\n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 653\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n654                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nespecially on the front lines. The WHO has alerted worldwide \nhealthcare organisations and governments to identify and \ntackle the unprecedented issues related to healthcare workers \nduring the COVID-19 pandemic.11  \n \nTiredness, mental stress and burnout are some of the major \nissues among healthcare workers during the COVID-19 \npandemic.12 The well-being of healthcare workers, on the \nother hand, is much more important in maintaining a high \nstandard of quality care for patients because it is directly \nrelated to healthcare worker productivity.13\u201315 Healthcare \nworkers are expected to work intensely because of the high \nburden of COVID-19 patients and a lack of staff (because of \nbeing infected or affected more by the pandemic). The 11th \nRevision of the International Classification of Diseases (ICD-\n11) defined burnout as a syndrome conceptualised as \nresulting from chronic workplace stress that has not been \nsuccessfully managed.16 But tackling stress issues among \nhealthcare workers is crucial and more beneficial to reducing \nburnout among frontline healthcare workers and \nmaintaining the productivity of healthcare services. \n \nFrontline healthcare workers comprise medical physicians, \nnurses, medical doctor assistants, healthcare assistants, \nreceptionists, cleaners and ambulance drivers.17 Ambulance \ndrivers are less concerned with health and safety compared to \ndoctors and nurses during the COVID-19 pandemic. Some \nreports suggest that ambulance workers may be particularly \nvulnerable to first-responder mental health issues.18 \nAmbulance drivers are not only at a higher risk of COVID-19 \ninfection, but they are also at a higher risk of road accidents \ndue to high driving speeds under emergency conditions and \nencountering unpleasant aspects of life.19 They often work \nunder time pressure and at irregular hours, which leads to \nprolonged states of alertness and fatigue.20,21 Afshari et al. \nidentified six main stressors for emergency medical service \n(EMS) drivers: complexity of patients' clinical conditions, \ninterruption of EMS provision, health hazards, interpersonal \nissues, inter-professional interactions and legal conflicts.22 \n \nHealthcare and ambulance drivers are comparable to full-\ntime professional drivers, who are exposed to a variety of \nstressors, such as the behaviour of other drivers, congested \nroads, ergonomic considerations, noise, climate conditions \nand job scheduling, resulting in deteriorating well-being and \nperformance.23,24 John and Linda's 2006 study also revealed \nthat older driver, women and those with a history of reported \naccidents in conditions of limited visibility, adverse weather \nand while performing common driving tasks are more prone \nto experience stress.25 Despite that, according to Maga\u00f1a et \nal.26, the level of stress experienced while driving can be \ninfluenced by four factors: the well-being (physical and \nmental condition) of the driver, the road and traffic \nconditions, the condition of the vehicle and external \ndisturbances.  \n \nThe Institute for Health System Research (IHSR) reported that \n129 ambulance accidents occur in Malaysia on average each \nyear.27 This situation is problematic for the organisation as a \nresult of increased turnover, absenteeism and exposure to \nsubstantial claims for compensation. The majority of \nambulance accidents (70.4%) occurred during the day, and \n55.7% occurred on weekdays. Accidents occurred on straight \nroads in 49.7% of cases and on 35.4% of federal roads. \n\n\n\nAccording to Syazmin et al., health drivers or ambulance \ndrivers were ranked second among Malaysian healthcare \nworkers involved in road traffic accidents, with a 53.7 per \n10,000 worker accident rates.28 The mental health of a driver \nis critical because it directly influences their driving \nbehaviour. Assessment of the stress status of frontline \nhealthcare drivers is critical before it progresses to burnout \nwith increasing mental distance from one's job and feelings \nof isolation especially during the COVID-19 pandemic. Thus, \nthis study aimed to determine the prevalence of stress and its \nassociated factors among healthcare drivers, especially \nduring the COVID-19 pandemic. \n \n \nMATERIALS AND METHODS \nThe Study Design \nThe stress among drivers in public healthcare facilities survey \nwas a cross-sectional study conducted from 1st August until \n31st August 2020. It covers seven district health offices, seven \ndistrict dental offices and seven hospitals under the Negeri \nSembilan State Health Department (SHD). The \nresponsibilities of healthcare drivers within the department \n(ambulance driver or non-ambulance driver) are \ninterchangeable depending on where the driver is posted \n(hospital, district health or dental office or primary care \nclinics). However, all drivers were deployed as front-liners in \nmanaging COVID-19 in the hospital and community. Simple \nrandom sampling was used to select drivers based on the 397 \ndrivers in the list provided by the Negeri Sembilan SHD.  \n \nThe total sample size required was 149 based on the 95% \nconfidence interval (CI), marginal error of 5% and the \nnearest expected stress prevalence among drivers based on \nthe emergency care personnel met posttraumatic stress \ndisorder; 18.6%.29 The sample was increased by 10% to \naccount for the non-response rate, which resulted in 164 but \nrounded into 170 respondents.  \n \nThe inclusion criteria comprise working at the present \nworkplace for at least 6 months, having Malaysian \nnationality, working during the COVID-19 pandemic for at \nleast the last 2 weeks, and being a registered driver under the \nNegeri Sembilan SHD. The selection of a 6-month service \nduration was based on the understanding that individuals \ntypically require a period of 3\u20136 months to adapt to a new \nworkplace environment. Drivers diagnosed with mental \nhealth illnesses and those on long-term sick leave were \nexcluded from this study. \n \nSurvey Instrument \nA validated Malay version of the Personal Stress Inventory \n(PSI) survey was distributed to healthcare drivers. The \ninventory comprised 51 items with 11 subscales using a four-\npoint Likert scale from \u2018never\u2019 (0), \u2018once or twice\u2019 (1), \u2018every \nweek\u2019 (2) and \u2018nearly every day\u2019 (3). The healthcare drivers' \nreplies to each of the 51 items, with scores ranging from 0 to \n153, were added together to create a final score. Rokiah \nvalidated this inventory in Malaysia with a sensitivity of \n95.1%, specificity of 77% and a total score of over 36, \nsignifying respondents were experiencing stress.30 The \nCronbach alpha of this instrument is 0.968. One answered \nthe questionnaires anonymously to maintain the driver's \nprivacy.  \n \n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 654\n\n\n\n\n\n\n\n\nStress perceived by drivers in public healthcare facilities in Negeri Sembilan during the first year of the COVID-19 pandemic\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                655 \n\n\n\nData Variables \nThe questionnaires encompass various categories of data, \nincluding demographic data (age, gender, ethnicity, marital \nstatus, level of education, healthcare facilities), co-\nmorbidities (height, weight, tobacco use, drug use, \nhypertension status, diabetes status) and occupational \ndemography (employment duration in MOH, employment \nyears at unit, number of drivers at working unit, working \nhours, main driving assignment driver, work schedule, on-\ncall status, satisfaction on work schedule, part-time job and \nhad a part-time job).  \n\n\n\nDuring a minimum duration of 1 month amid the COVID-19 \npandemic, the management allocated the principal \nresponsibility, which entailed determining the primary \ndriving assignment. This involved either performing duties as \nan ambulance operator or operating the management \nvehicle to facilitate the transportation of healthcare \npersonnel or the delivery of parcels. The work schedule was \nestablished by considering the driver's availability during \nregular office hours (8 a.m. to 5 p.m.) as well as the three \navailable shift hours (7 a.m. to 3 p.m., 3 p.m. to 11 p.m. and \n11 p.m. to 7 a.m.).  \n\n\n\nVariables                                               n                               %                                                           Frequency (n) \n                                                                                                                                         Stress (%)                         None stress (%) \nHealthcare drivers                             163                           100                                        12 (7.4)                                 141 (92.6) \nAmbulance drivers                               47                            28.8                                        5 (10.6)                                  42 (89.4) \nNon-ambulance drivers                      116                           71.2                                         7 (6.0)                                   109 (94) \n                                                               \n\n\n\nTable I: Prevalence of perceived stress among healthcare drivers (n=163)\n\n\n\nVariables                                                                              n                                        Percentage (%)                               p-value \nDemographic characteristics                                                                                                                                                       \nAge groups                                                                                                                                                                               0.710 \n <30                                                                                    5                                                   3.1                                                 \n 30\u201339                                                                               81                                                 49.7                                                \n 40\u201349                                                                               52                                                 31.9                                                \n >50                                                                                   25                                                 15.3                                                \nHousehold income                                                                                                                                                                  0.044a \n MYR <2000                                                                      76                                                 46.6                                                \n MYR 2000\u20133000                                                              43                                                 26.4                                                \n MYR >3000                                                                      44                                                 27.0                                                \nEthnic                                                                                                                                                                                        0.649 \n Malay                                                                            154                                                95.7                                                \n Chinese                                                                           1                                                   0.6                                                 \n Indian                                                                             6                                                   3.7                                                 \nMarital status                                                                                                                                                                            0.519 \n Single                                                                             12                                                  7.4                                                 \n Married                                                                        145                                                90.1                                                \n Divorced/Widow                                                            4                                                   2.5                                                 \nLevel of education                                                                                                                                                                   0.385 \n High School Certificate                                               145                                                90.1                                                \n Certificate                                                                     12                                                  7.5                                                 \n Diploma                                                                         4                                                   2.5                                                 \nHealth status \nBody mass index (BMI)                                                                                                                                                           0.241 \n Underweight                                                                  3                                                   1.9                                                 \n Normal                                                                          45                                                 28.0                                                \n Overweight                                                                   63                                                 39.1                                                \n Obese                                                                            50                                                 31.1                                                \nNon-communicable diseases                                                                                                                                                       \n Diabetes mellitus                                                          22                                                 13.7                                          0.498 \n Hypertension                                                                14                                                  8.7                                           0.725 \n Hypercholesterolaemia                                                 1                                                   0.6                                           0.926 \n Heart diseases                                                                1                                                   0.6                                           0.926 \nComorbidities                                                                                                                                                                           0.811 \n Single                                                                             28                                                 17.2                                                \n Double                                                                            5                                                   3.1                                                 \n No comorbid                                                                130                                                79.8                                                \nSmoking status                                                                                                                                                                        0.009a \n Smoker                                                                          89                                                 55.3                                                \n None smoker                                                                72                                                 44.7                                                \nAlcoholic status                                                                                                                                                                       0.579 \n Drinker                                                                           2                                                   1.2                                                 \n\n\n\nNone drinker                                                               159                                                98.8                                                \n \naChi-square test. \n\n\n\nTable II: Demographic characteristics of health drivers and association with perceived stress (n=163)\n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 655\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n656                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nVariables                                                                              n                                            Mean (SD)                                   p-value \nEmployment years at Ministry of Health                         163                                           10.6 (7.4)                                      0.120 \nEmployment years at Unit                                                163                                            8.0 (6.8)                                       0.168 \nNum. of driver at working unit                                        163                                            7.9 (7.8)                                       0.073 \nWorking hours (hours/week)                                            163                                          54.7 (20.0)                                     0.313 \nVariables                                                                              n                                        Percentage (%)                                      \nMain driving assignment                                                                                                                                                         0.330 \n\n\n\nAmbulance driver                                                         47                                                 28.8                                                \nNon-ambulance driver                                                116                                                71.2                                                \n\n\n\nWork schedule                                                                                                                                                                         0.435 \nOffice hour                                                                  135                                                82.8                                                \nShift hour                                                                      28                                                 17.2                                                \n\n\n\nOn-call status                                                                                                                                                                           0.032a \nYes                                                                                 83                                                 50.9                                                \nNo                                                                                  80                                                 49.1                                                \n\n\n\nSatisfaction on work schedule                                                                                                                                               0.373 \nYes                                                                                157                                                96.3                                                \nNo                                                                                   6                                                   3.7                                                 \n\n\n\nPart-time job                                                                                                                                                                            0.464 \nRequire                                                                         128                                                78.5                                                \nNot require                                                                   35                                                 21.5                                                \n\n\n\nHad a part-time job                                                                                                                                                                  0.866 \nYes                                                                                 58                                                 35.6                                                \nNo                                                                                 105                                                64.4                                                \n\n\n\nMotor vehicle accident (MVA)                                                                                                                                                      \nMVA with department vehicle                                                                                                                                                 0.446 \n\n\n\nYes                                                                                  7                                                   4.3                                                 \nNo                                                                                 156                                                95.7                                                \n\n\n\nNum. of accidents last 6 months                                                                                                                                           0.446 \nNone                                                                            156                                                95.7                                                \nAt least once                                                                  7                                                   4.3 \n \n\n\n\naFisher\u2019s exact test. \n \n\n\n\nTable III: Occupational characteristic of healthcare drivers (n=163)\n\n\n\nVariables                                                               Simple logistic regression                                         Multiple logistic regression \n                                                              cOR                   95% CI                     p                           aOR                 95% CI                    p \nAge                                                            1.049                 0.97\u20131.12                0.194                        1.06               0.94\u20131.19              0.316 \nMarital status                                                                                                                                                                                                \n\n\n\nSingle/widow/divorce                    1425419.79            0.00\u20130.00                 1.00                     11177.57           0.00\u20130.00              0.998 \nMarried                                                                                                           Reference                                                                    Reference \n\n\n\nBMI                                                       0.96                  0.85\u20131.08                0.490                        0.91               0.78\u20131.05              0.198 \nSmoking status                                                                                                                                                                                             \n\n\n\nYes                                                        9.76                 1.23\u201377.51               0.030                       19.99            1.86\u2013213.90           0.013* \nNo                                                                                                             Reference                                                                    Reference \nComorbidities                                       0.77                  0.16\u20133.71                0.749                        0.71               0.10\u20134.52              0.712 \n\n\n\nEducation level                                                                                                   0.447                                                                            0.665 \nHigh school cert                                   1.24                 0.14\u201310.64               0.841                        1.11              0.07\u201317.21             0.940 \nDiploma                                                4.56                 0.43\u201348.00               0.206                        8.40             0.08\u2013851.18            0.366 \nDegree                                                                                                      Reference                                                                    Reference \n\n\n\nHousehold income                                                                                                                                                                                       \n<MYR 2000                                           0.61                  0.06\u20136.14                0.677                        0.60              0.03\u201311.22             0.737 \nMYR 2000\u20133000                                   2.41                  061\u20139.53                0.209                        3.60              0.48\u201326.73             0.210 \n>MYR 3000                                                                                               Reference                                                                    Reference \n\n\n\nDriving assignment                                                                                                                                                                                      \nAmbulance driver                                1.85                  0.55\u20136.16                0.314                        0.40               0.06\u20132.41              0.317 \nNon-ambulance driver                                                                             Reference                                                                    Reference \nEmployment at unit                            1.07                  1.00\u20131.16                0.044                        1.09               0.98\u20131.21              0.110 \nWorking hours                                    0.595                 0.15\u20132.35                0.460                        1.10               0.16\u20137.14              0.921 \n\n\n\nOn-call status                                             5.342                1.13\u201325.20               0.034                        8.69              1.21\u201362.28            0.031* \nSchedule satisfaction                                                                                                                                                                                    \n\n\n\nYes                                                       0.377                 0.04\u20133.51                0.391                        1.63             0.01\u2013148.54            0.831 \nNo                                                                                                             Reference                                                                    Reference \n\n\n\nHad a part-time job                                                                                                                                                                                     \nYes                                                       0.952                 0.27\u20133.31                0.938                        1.27               0.30\u20135.33              0.741 \nNo                                                                                                             Reference                                                                    Reference \n\n\n\n \n*Significant result. \nCOR = crude odds ratio. \naOR = adjusted odds ratio \n\n\n\nTable IV: Logistic Regressions of perceived stress risk factors among healthcare drivers during the COVID-19 pandemic\n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 656\n\n\n\n\n\n\n\n\nStress perceived by drivers in public healthcare facilities in Negeri Sembilan during the first year of the COVID-19 pandemic\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                657 \n\n\n\nMeanwhile, the designation of on-call status was established \nin response to the need for individuals in a shift-based work \nsystem to be available for post-office hours or double shifts. A \nmotor vehicle accident was operationally defined as an \nincident involving a driver operating a healthcare vehicle \nwho was involved in a collision while carrying out their \nprofessional responsibilities. The health status of the \nhealthcare drivers was determined based on the yearly health \nassessment, either by the Occupational and Environmental \nHealth Unit in district health offices or the Occupational \nSafety and Health Unit in hospitals. \n \nData Collection \nThe questionnaires were distributed and collected by the \nOccupational and Environmental Health Officer in each \ndistrict and hospital. The chosen drivers were approached at \nwork and given a study explanation as well as a participant \ninformation sheet. They were given a week to decide whether \nor not to participate in this study, and informed consent \nforms were given to them after they agreed to participate and \nwere then provided with a series of questionnaires. They had \n3 days to finish the questionnaires. The completed \nquestionnaires were submitted to the Occupational and \nEnvironmental Health Officer in each district and hospital \nupon completion. \n \nData Analysis \nThe Statistical Package for the Social Sciences (SPSS) version \n22 was used to analyse the data. The distribution of the data \nwas not normal. Thus, the association between demographic \ncharacteristics, health status, occupational characteristics \nand stress status was determined using the Chi-square test, \nFisher Exact test, Mann\u2013Whitney test and Kruskal\u2013Wallis test \ndepending on the data variables. Moreover, the collected \ndata underwent multiple logistic regression analysis in order \nto validate the significant risk factors associated with \nperceived stress among healthcare drivers in Negeri Sembilan \nduring the first year of the COVID-19 pandemic. \n \nEthical Consideration \nThis study was registered in the National Medical Research \nRegistry (NMRR-20-2187-56430 (IIR)). The study was \nconducted in accordance with the Declaration of Helsinki \nand was approved by the Medical Research Ethics Committee \n(MREC), Ministry of Health Malaysia (KKM/NIHSEC/ P20-\n2576 (4)), on 25 January 2021. \n \n \nRESULTS \nThe total number of participants in this study was 163, \nresulting in a response rate of 95.8%. In general, non-\nambulance drivers make up 71.2% (n = 116) of the \nhealthcare drivers working for the Negeri Sembilan SHD, \nwhile ambulance drivers make up 28.8% (n = 47) of the \nworkforce. At the end of the first year of the COVID-19 \npandemic, 7.4% of healthcare drivers reported experiencing \nsome degree of perceived stress. Moreover, from the findings \npresented in Table I, ambulance drivers at the Negeri \nSembilan SHD had perceived higher levels of stress (10.6%) \ncompared to non-ambulance drivers (6.0%). \n \n \n\n\n\nAs shown in Table II, the majority of respondents were aged \n30\u201339 (49.7%), had a monthly household income of less than \nMYR 2,000 (46.6%), were Malay (95.7%), were married \n(90.1%) and had their highest education of a high school \ncertificate (90.1%). In addition, 70% of healthcare drivers are \noverweight or obese; 55.2% are smokers and 98.8% do not \nconsume alcohol. The majority of drivers in the SHD are in \ngood health (79.8%), whereas 20.8% have at least one \ncomorbid disease; 13.7% have diabetes, 8.7% have \nhypertension, 0.6% have hypercholesterolaemia and 0.6% \nhave heart disease. A majority of them are smokers (55.3%), \nwhilst only 1.2% consume alcohol. In addition, a correlation \nexists between household income (p = 0.044), smoking status \n(p = 0.009) and perceived stress. However, there is no \nsignificant relationship between other demo-graphic \nparameters (such as age, race, marital status and education \nlevel) and experienced stress, or between perceived stress and \nother health concerns (like BMI, diabetes mellitus, \nhypertension, hypercholesterolaemia, heart diseases, \ncomorbidities and alcoholism). \n \nMore than 7 out of 10 healthcare drivers working with the \nNegeri Sembilan SHD are assigned as non-ambulance drivers \nor department transport service drivers. They have been \nworking with the ministry of health on average for 10.6 \u00b1 7.4 \nyears, and the majority of them work during office hours \n(82.2%). On average, the healthcare drivers in the \ndepartment have been with the ministry of health in the \ncurrent hospital or district health office unit for 8 \u00b1 6.8 years. \nOn average, they worked around 52.6 \u00b1 20 hours per week \nduring the COVID-19 pandemic. More than half of them did \nwork on an on-call basis (50.9%) after office hours and were \nsatisfied with their working schedule (96.3%). Nevertheless, \nperceived stress among healthcare drivers was associated \nwith on-call status (p = 0.032). Having said that, most of \nthem still feel that they need a part-time job (78.5%) on top \nof their full-time job, but only 35.6% of them have a part-\ntime job. On the category of motor vehicle accidents \ninvolving department vehicles, seven healthcare drivers had \na history of motor vehicle accidents involving department \nvehicles during their employment, with 4.3% reported \naccidents during the COVID-19 pandemic. However, there is \nno association found between perceived stress and duration \nof employment, working hour duration, work schedule, \nhaving part-time job and motor vehicle accident.   \n \nA logistic regression analysis was conducted to examine the \nassociation between perceived stress and several variables \namong healthcare drivers during the COVID-19 pandemic. \nThe result indicated that three variables were found to be \nstatistically significant (p<0.05) predictors of perceived stress. \nThese variables included smoking (OR 9.76, 95% CI 1.23\u2013\n77.51), duration of employment at the current unit (OR 1.07, \n95% CI 1.00\u20131.16) and on-call status (OR 5.34, 95% CI 1.13\u2013\n25.20). Meanwhile, the multiple logistic regression revealed \nthat healthcare drivers who are smokers had a significantly \nhigher odds ratio of 19.99 (95% CI 1.86\u2013213.90) compared to \nnon-smokers. In addition, these individuals were found to \nhave 8.69 times the odds (95% CI 1.21\u201362.28) of engaging in \non-call duties compared to healthcare drivers not doing an \non-call. \n \n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 657\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n658                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nDISCUSSION \nDrivers in the healthcare industry play an important role \nbecause their jobs include moving people's lives. Stress level \nof healthcare drivers or ambulance drivers is very dynamic \ndepending on the stressors at the workplace. The level of \nstress among healthcare drivers at the SHD of Negeri \nSembilan remained under control at the end of the first year \nof the COVID-19 pandemic, in contrast to the pool \nprevalence of stress among first responders including \nambulance drivers for medical emergencies, which reported \n17% stress prevalence during the first year of the COVID-19 \npandemic.31 Despite that, the level of perceived stress in \nalmost similar prevalence with the study conducted by \nNordin et al. on healthcare workers in northwest Malaysia, \nwho reported a 6.4%32 with almost a similar study timeframe. \nHowever, with regards to an Asia-Pacific study among \nhealthcare workers in 2020, which involved India, Singapore, \nMalaysia, Vietnam and Indonesia, Malaysia was found to be \nthe second highest (5.7%) after Indonesia, which was 6.8%.33 \nHowever, the prevalence of stress would vary depending on \nthe healthcare facilities and respondents, even though the \nstudies were conducted in a nearly identical timeframe, such \nas a study in the Sarawak Hospital, Malaysia that recorded \n57.1%34 and a study in the primary health clinics of Selangor, \nMalaysia which reported it to be at 2.8%.35 Based on this \nstudy, ambulance drivers experienced higher prevalence \ncompared to non-ambulance drivers, which differ in job \nassignments. \n \nFurthermore, this study also noted that low household \nincome (less than MYR 2,000), performing on-call and \nsmoking were associated with perceived stress among \nhealthcare drivers. Household income of less than 2,000 \nMalaysian Ringgit (MYR) is the lowest of the four categories \nof household income below the B40 threshold in Malaysia.36 \nHowever, further analysis using multiple logistic regression \nrevealed no significant association between stress and \nhousehold income. Nonetheless, employers should prioritise \nhealthcare drivers when allocating resources like \ngovernment-subsidized housing and child care in order to \nmanage their salary competitiveness. Financial management \neducation may be useful for this occupation category as well. \nThe stress of being on call has been established by other \nstudies,37 but prospective healthcare drivers should still be \nreminded of their responsibilities. However, this may also be \nthe result of working excessive hours without taking \nadequate breaks or poorly managing a roaster.38 According to \na study conducted in the USA, medium to high levels of inter-\nshift recovery were highest for shifts over 12 h in length \n(61.6%), lowest for shifts under 12 h in length (47.7%) and \nhighest for shifts of 12 h (40.2%).39 Nevertheless, the \nOccupational Safety and Health (OSH) team must conduct \nlocality assessments of workers to determine safe maximum \nworkweeks and break times, as varying working conditions \nmay have a cumulative effect on employee productivity.40 \n \nDrivers in the healthcare industry play a crucial role, so it is \nimperative that they are in good physical and mental health. \nBased on this study, more than half of the healthcare workers \nin the Negeri Sembilan SHD are smokers. This puts them at \nrisk for cardiovascular diseases and cancers such as \nhypertension, heart disease, peripheral arterial disease and \n\n\n\nlung cancer, despite the fact that the vast majority of them (8 \nout of 10) are healthy and have no other health issues. \nContrarily, a study of Swedish ambulance workers revealed \nthat they had a higher prevalence of heart problems \n(paroxysmal tachycardia, atrial fibrillation, flutter, and other \ncardiac arrhythmias), high blood pressure and dorsopathies \nthan individuals in other occupations.41 As cardiovascular \ndiseases can result in motor vehicle accidents,42 a yearly \nphysical examination and fitness certificate must include a \nheart evaluation, such as an electrocardiogram (ECG). \nFurthermore, continuous awareness and participation in \ninterventional activities at the workplace need to be \nemphasised by the Occupational Safety and Health team. \n \nAdditionally, this study did not find significant associations \nbetween stress among ambulance drivers and other factors \nsuch as gender, age, household income, type of shift work, \nrisk of getting COVID-19 infection, adequacy of personal \nprotective equipment, history of accidents within 1 year and \npressure from family members and patients compared to the \nother studies.43,44 According to the study conducted by Amro et \nal. found that younger female drivers displayed higher levels \nof stress compared to both male and older ambulance \ndrivers.43 In contract to gender, the observation that driving is \npredominantly associated with males in Malaysia is \nexpected, as there is a notable lack of female applicants for \nsuch positions. In contrast to the present study, Pinnalin et al. \nconducted a study that revealed supplementary variables \nlinked to stress levels among ambulance drivers amidst the \nCOVID-19 pandemic. These variables encompassed monthly \nhousehold income, the nature of shift work, the ambulance \ndriver\u2019s accident record within the previous year, as well as \nthe influence exerted by family members and patients.44     \n \nDespite the fact that the perceived stress levels of healthcare \ndrivers appear to be under control, the OSH team must \ncontinue to exert effort to maintain the situation. Because \nstress management training continuously increases drivers\u2019 \nawareness, train them to control, reduce and tolerate the \ninternal and external demands of a certain situation in \nwhich their individual resources are exceeded. Even though, \naccording to a study conducted in Switzerland, paramedics \nrequire less psychological support than other professions due \nto their high level of experience and long-standing training \nin stress management over the course of their careers, they \nare often used to address stressful situations as they are part \nof a coordinated and ordered emergency response and have \nto constantly handle very high levels of stress. According to \nresearch by Lawn et al., the needs of ambulance workers in \nterms of mental health can be classified into four main \ncategories: organisational support, informal support, the use \nof humour and individual ways of coping, such as \ndetachment and external support.18 In a general way, \nstopping unpleasant emotions and thoughts is the most \neffective coping strategy for the reduction of stress levels and \nan increase in positive mental states.                                       \n \nA limitation of this study is that it was unable to identify the \nfactors associated with each driver, as the sample size may \nnot have been adequate given that the study was conducted \nin a single stratum and addressed the study objective, as the \nstress associated with ambulance drivers may differ from that \n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 658\n\n\n\n\n\n\n\n\nStress perceived by drivers in public healthcare facilities in Negeri Sembilan during the first year of the COVID-19 pandemic\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                659 \n\n\n\nof other drivers. In addition, this is a cross-sectional study \nthat only reflects the assessment conducted during the study. \nFollowing up from this study, the OSH team could initiate \nanother research on the adaptability of healthcare drivers in \nMalaysia to varying working hours in terms of \nenvironmental adaptation, which would help policymakers, \nset the working hours limit for healthcare drivers, especially \nin relation to adequate breaks for on-call drivers. In addition, \nan interventional study based on the healthcare driver's \nbehaviour therapy could enhance the overall performance of \ndrivers in terms of occupational safety and health as it \nincreases the driver\u2019s insight. \n \n \nCONCLUSION \nThe study found that perceived stress among Malaysian \nhealthcare drivers during the OVID-19 pandemic was \nrelatively low. The implementation of movement control \norders during the COVID-19 pandemic in Malaysia resulted \nin a reduction in the frequency of life-threatening tasks, \nemergencies and assigned tasks. The consistent provision of \nsafety and health training by the OSH team, which includes \nstress management and a smoking cessation programme, \npotentially contributed to the healthcare driver\u2019s ability to \nmanage the stressful situation. In order to enhance salary \ncompetitiveness, employers ought to offer financial \nmanagement education alongside subsidised housing and \nchildcare provisions. \n \n \nACKNOWLEDGMENTS \nThe authors would also like to offer their appreciation to the \nDirector General of Health Malaysia for permitting this paper \nto be published. This study has been presented at the 28th \nInternational Symposium on Epidemiology in Occupational \nHealth (EPICOH) on October 25\u201328, 2021 through virtual \nplatform. \n \n \nDECLARATION OF INTEREST \nThe authors would like to disclose that they have no conflict \nof interests to declare and have no competing interests in this \nstudy. This research was self-funded and received no external \nfunding. \n \n \nREFERENCES \n1. World Health Organization. COVID 19, Public Health Emergency \n\n\n\nof International Concern (PHEIC) WHO Web page: World Health \nOrganization; 2020. Available from: \nhttps://www.who.int/publications/m/item/covid-19-public-\nhealth-emergency-of-international-concern-(pheic)-global-\nresearch-and-innovation-forum. \n\n\n\n2. 2. Scapaticci S, Neri CR, Marseglia GL, Staiano A, Chiarelli F, \nVerduci E. The impact of the COVID-19 pandemic on lifestyle \nbehaviors in children and adolescents: an international \noverview. 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Evans GW, Johansson G, Rydstedt L. Hassles on the job: A study \nof a job intervention with urban bus drivers. J Organ Behav. \n1999; 20: 199-208. \n\n\n\n24. Useche SA, Cendales B, Montoro L, Esteban C. Work stress and \nhealth problems of professional drivers: a hazardous formula for \ntheir safety outcomes. PeerJ. 2018; 6: e6249. \n\n\n\n25. Hill JD, Boyle LN. Driver stress as influenced by driving \nmaneuvers and roadway conditions. Transport Res. 2007; 10(3): \n177-86. \n\n\n\n\n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 659\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n660                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n26. Maga\u00f1a VC, Scherz WD, Seepold R, Madrid NM, Pa\u00f1eda XG, \nGarcia R. The effects of the driver's mental state and passenger \ncompartment conditions on driving performance and driving \nstress. Sensors (Basel). 2020; 20(18): 5274. \n\n\n\n27. Abu Bakar NS, Zaimi NA, Mahaletchumy S, Shabadin A, Roslan \nA, Manual A, et al. Trends of ambulance accidents in Malaysia: \nimplications to public health.  5th Asia Pacific Conference on \nPublic Health; 10\u201314 September; Kuching, Sarawak. Med J \nMalaysia 2017; 72(Supp 1): 90. \n\n\n\n28. Zuwairy MS, Harith AA, Nobuyaki H, Naim NM, Yon R. Road \ntraffic accidents: a descriptive study of commuting injury among \nhealthcare workers in Malaysia 2014-2016. Int J Public Health \nClin Sci. 2020; 7(1): 58-71. \n\n\n\n29. Trudgill DIN, Gorey KM, Donnelly EA. Prevalent posttraumatic \nstress disorder among emergency department personnel: rapid \nsystematic review. Human Soc Sci Commun. 2020; 7(1): 89. \n\n\n\n30. M. R. Prevalens tekanan dan penyebab tekanan kerja di \nkalangan jururawat terlatih hospital Kuala Lumpur [prevalence \nand causes of occupational stress among staff nurses in HKL] \n(Kuala Lumpur, Malaysia: National University of Malaysia; \n1994. \n\n\n\n31. Huang G, Chu H, Chen R, Liu D, Banda KJ, O'Brien AP, et al. \nPrevalence of depression, anxiety, and stress among first \nresponders for medical emergencies during COVID-19 pandemic: \na meta-analysis. J Glob Health. 2022; 12: 05028. \n\n\n\n32. Nordin S, Yaacob NA, Kelak J, Ilyas AH, Daud A. The Mental \nHealth of Malaysia's Northwest healthcare workers during the \nrelaxation of COVID-19 restrictions and its associated Factors. Int \nJ Environ Res Public Health. 2022; 19(13): 7794. \n\n\n\n33. Chew NWS, Ngiam JN, Tan BY-Q, Tham S-M, Tan CY-S, Jing M, \net al. Asian-Pacific perspective on the psychological well-being of \nhealthcare workers during the evolution of the COVID-19 \npandemic. BJPsych Open. 2020; 6(6): e116. \n\n\n\n34. Sim SK, Lau BL, Zaila SR, Hazira N, Aniqah NM, Panicker J, et al. \nPsychological symptoms among healthcare workers handling \nCOVID-19 patients. Med J Malaysia. 2021; 76(2): 138-44. \n\n\n\n35. Salaton NF, Bulgiba A. depression, anxiety, and stress among \nfrontline primary health care workers during the COVID-19 \npandemic. Asia Pacif J Public Health. 2022; 34(4): 416-9. \n\n\n\n36. Department of Statistics M. Household income and basic \namenities survey report 2019 Putrajaya; 2020. \n\n\n\n37. Nicol AM, Botterill JS. On-call work and health: a review. Environ \nHealth. 2004; 3(1): 15. \n\n\n\n38. Willis E, Lawn S, Roberts L, Couzner L, Mohammadi LM, Goble E. \nThe impact of emergency call taking on the mental health and \nwellbeing of ambulance call-takers: a systematic thematic \nnarrative of qualitative research. Austral J Paramed. 2020; 17: 1-\n11. \n\n\n\n39. Patterson PD, Buysse DJ, Weaver MD, Callaway CW, Yealy DM. \nRecovery between work shifts among emergency medical services \nclinicians. Prehosp Emerg Care. 2015; 19(3): 365-75. \n\n\n\n40. Thielmann B, Schnell J, B\u00f6ckelmann I, Schumann H. Analysis of \nwork related factors, behavior, well-being outcome, and job \nsatisfaction of workers of emergency medical service: a \nsystematic review. Int J Environ Res Public Health. 2022; 19(11): \n6660. \n\n\n\n41. Karlsson K, Nasic S, Lundberg L, M\u00e5rtensson J, Jonsson A. Health \nproblems among Swedish ambulance personnel: long-term risks \ncompared to other professions in Sweden - a longitudinal register \nstudy. Int J Occup Saf Ergon. 2022; 28(2): 1130\u201335.  \n\n\n\n42. Ronna BB, Thiese MS, Ott U, Effiong A, Murtaugh M, Kapellusch \nJ, Garg A, Hegmann K. The association between cardiovascular \ndisease risk factors and motor vehicle crashes among \nprofessional truck drivers. J Occup Environ Med. 2016; 58(8): \n828\u201332.  \n\n\n\n43. Amro TM, Arcos Gonz\u00e1lez P, Montero Vi\u00f1uales E, Castro Delgado \nR. Impact of COVID-19 pandemic on stress and burnout levels \namongst emergency medical technicians: a cross-sectional study \nin Spain. Ann Med. 2022; 54(1): 3007\u20133016.  \n\n\n\n44. Pinalin P, Chaiyanun T, Sara A, Suchinda Jarupat M, Jutatip S. \nThe stress level and stress related factors among ambulance \ndrivers. Nurs J CMU 2021; 48(4): 2021.  \n\n\n\n16-Stress00246.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 660\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023 661 \n\n\n\nABSTRACT \nIntroduction: Burn injuries incur not just significant \nmorbidity but also long-term psychosocial impact. This \nstudy aims to identify the clinico-demographics of children \nhospitalised for burns and factors associated with \nprolonged hospitalisation.  \n\n\n\nMaterials and Methods: Written medical records of burn \npatients admitted to the Sultanah Aminah Hospital \npaediatric surgical ward, from January 2016 to December \n2018, were retrospectively reviewed. Details on the patients\u2019 \nsocio-demographic background, burn injuries, management \nand outcomes were recorded and analysed with logistic \nregression.  \n\n\n\nResults and Conclusion:  Of the 255 children included in the \nstudy, the majority were males (62.7%), children aged \nbetween 1 to 3 years (43.1%), and of the Malay ethnic group \n(83.1%). The commonest injury mechanism was scalds \nburns (81.2%). Staphylococcus aureus remained the \ncommonest organism cultured from paediatric burn \nwounds. Most patients (66.4%) were hospitalised for less \nthan 1 week. A significant number of patients experienced \ncomplications from their injuries. Multivariate analysis \nshowed burns affecting total body surface area > 10% \n(adjusted OR, 13.45 [95% CI 6.25 - 28.96]; p = < 0.001) and \nnon-scald burns (adjusted OR, 2.70 [95% CI 1.12 - 6.50]; p = \n0.027) were the two main factors associated with prolonged \nhospitalisation of more than 1 week. These findings \ndescribing the epidemiology and outcomes of paediatric \nburn cases in a tertiary centre in Malaysia may inform future \npractice. More importantly, the information may contribute \nto the identification of at-risk populations and advise the \ndevelopment of effective prevention strategies to reduce the \nincidence and morbidity associated with paediatric burns in \nthis region. \n\n\n\nKEYWORDS: \nEpidemiology, paediatric,  burns,  Malaysia,  prevention \n\n\n\nINTRODUCTION \nBurns are a significant cause of mortality and morbidity for \npatients and incur high economic burden on healthcare \nsystems.1 Burn injuries in the paediatric population are \npotentially more severe compared to adults as children have \nseveral physiological disadvantages, such as thinner layers of \n\n\n\nskin, less subcutaneous tissue and a larger surface area to \nvolume ratio, which gives rise to increased risk of rapid \npercentage of fluid loss.2 It is clear that paediatric burns are \nlargely preventable injuries, as various primary prevention \ncampaigns have been effective in reducing the incidence of \nburn-related hospitalisation.3,4 However, the ability to \nformulate an effective campaign requires the availability of \nepidemiological data on the various socio-demographic and \nclinical factors surrounding paediatric burns. \n\n\n\nThrough our literature search, only three small studies \nproduced epidemiological data on paediatric burn patients in \nthe Malaysian setting. Two out of the three papers included \nboth adults and children, with the most recent study on \npaediatric burns being published almost 20 years ago in \n2002.5-7 In addition, the total combined number of patients \n(adults and children) from the three studies only amounted to \n379 patients. More recent data is available in the form of a \nposter presentation, which provided some descriptive \nstatistics on 94 paediatric patients who were admitted into \nthe Malacca Hospital from January 2016 to December 2018.8 \nIt is clear that epidemiological data with larger sample sizes \nare needed to inform burns prevention strategies. \n\n\n\nThis study aims to collect the epidemiological data on the \nclinic-demographic factors of hospitalised paediatric burn \npatients from the main tertiary burns referral centre in the \nSouthern part of Peninsula Malaysia in order to identify the \nparameters associated with the patients. In addition, we aim \nto determine factors associated with poorer outcomes by \nusing prolonged hospitalisation, defined as hospital stay \ngreater than 7 days, as the measurement tool. \n\n\n\nMATERIALS AND METHODS \nThis is a retrospective observational study. Ethical approval \nhas been obtained from the Medical Research Ethics \nCommittee (MREC) of the Malaysian Ministry of Health \n(Approval no: NMRR-19-1111-48223) as well as the Monash \nUniversity Human Research Ethics Committee (MUHREC). All \nchildren less than 12 years of age who were admitted to \nHospital Sultanah Aminah Johor Bahru for burn injuries \nfrom January 2016 to December 2018 were included in this \nstudy. This study excluded burn patients treated in the \nemergency department, outpatient setting and patients with \nmissing medical records. Details on the patients\u2019 socio-\ndemographic background, management measures and \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 02 September 2023\nCorresponding Author: Chuen Xian Low\nEmail: kelvinlcx@gmail.com \n\n\n\nThree-year epidemiology of hospitalised paediatric burn \npatients in a Malaysian Tertiary Hospital 2016 \u2013 2018 \n\n\n\nChuen Xian Low1, Ying Quan Kok1, Xuan Song Loo1, Chin Fang Ngim1, Raymond Zhun Ming Lim2, Soong Yuen \nQuah2\n\n\n\n1Jeffrey Cheah School of Medicine Health Sciences, Monash University Malaysia, Malaysia, 2Sultanah Aminah Hospital, Johor \nBahru, Malaysia (HSAJB), Ministry of Health Malaysia, Malaysia \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 661\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n662                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\noutcomes of each individual burn case, such as demographic \nfactors (age, sex, ethnicity), circumstances surrounding the \ninjury (mechanism of burns, location of burns, provision of \nfirst aid), clinical presentation (extent of burns) and \noutcomes (length of hospitalisation, need for surgical \ndebridement, need for blood product transfusion, need for \nICU admission, wound culture results and mortality) were \nrecorded in the case report forms (CRF).  \n \nSultanah Aminah Hospital is the largest referral hospital in \nthe State of Johor and the main paediatric burn referral \ncentre for patients in the Southern region of Peninsula \nMalaysia. All the patients under 12 years of were managed \nby paediatric surgeons in the general paediatric surgical unit. \nAlthough patients were not routinely screened for methicillin \nresistant staphylococcus aureus (MRSA) or extended \u2013 \nspectrum beta lactamase (ESBL) organisms, those with \nknown MRSA or ESBL organisms were placed under contact \nprecautions. Burn patients generally receive management in \nterms of analgesia, dressings and/or fluid resuscitation. The \ntotal burn surface area (TBSA) was estimated using the Lund \nand Browder chart. Patients with TBSA > 10% are \nautomatically given fluid resuscitation using Parkland \nformula with Hartmann\u2019s solution with a goal to maintain \nend organ perfusion. Adequacy of perfusion and fluid \nresuscitation was monitored via urine output, mean arterial \npressure and occasionally blood gas measurements. \nCommon dressings regimes used at the study centre included \nthe following: silver sulfadiazine, carboxymethylcellulose \n(CMC), Bactigras\u2122, Jelonet\u2122 or Intrasite\u2122.  \n \nWound swabs, blood cultures, blood products administration \nand antibiotics administration were not routinely performed \nunless deemed clinically indicated by the treating consultant \npaediatric surgeon. Wound swabs were performed in \ncircumstances where the burn wounds demonstrated signs of \ninfection, such as pus or persistent slough. Blood cultures \nwere generally done in patients who developed signs of \nsepsis. The local practice was for antibiotics to be prescribed \nin suspected burn wound infections, evidenced by occurrence \nof fever 3 days after the date of injury. The first-line antibiotic \nis intravenous cloxacillin, with intravenous ceftazidime \nand/or amikacin as second-line therapies. In addition, blood \ntransfusions were considered in patients with haemoglobin \nlevels less than 8 g/dL, undergoing debridement procedures \nor were septic. Patients with burns affecting joint areas, \nhands or face, severe extensive burns with TBSA > 10% and \nsecond- or third-degree burns were referred to the plastic \nsurgery unit for review and consideration of split skin \ngrafting. Patients with extensive burns with TBSA > 10% were \nalso referred for dietetics input for high protein formula and \ninpatient dietary modifications. \n \nData was analysed using SPSS\u00ae Statistics 26 (IBM \nCorporation, Armonk, NY). Descriptive statistics were used to \npresent the clinico-demographics of patients. Univariate \nanalyses were carried out to identify possible associations \nbetween factors and eventual outcome of burn patients. \nBinary logistic regression was performed on the factors which \nproduced a significant result to assess the impact of those \nindividual factors on the dependent variable (prolonged \nhospitalisation defined as stay greater than seven days). \nStatistical significance was attained when p <0.05. \n \n\n\n\nRESULTS \nPatients\u2019 Description \nAll of the patients in this study were aged 12 and below. \nRecords from the Burns Registry on the paediatrics surgical \nward showed that a total of 327 patients were admitted \nbetween 2016 to 2018. Despite limitations of a paper-based \nrecord, 80% of the patient records (255 out of 327 patients) \nwere included while others were excluded due to missing \ndata. Descriptive statistics were derived from the 255 patient \nrecords that we have identified, after removing the second \nand third admissions for those with numerous admissions. \nFrom the 255 patients, a further five patients were discharged \nagainst medical advice and 14 patients who were transferred \nin/out to/from other hospitals. After excluding these patients, \na total of 236 patients were included in the association \nanalysis to identify factors associated with prolonged \nhospitalisation to enhance the accuracy of results.  \n \nDescriptive Statistics: Clinico-demographic Factors \nData from a total of 255 patients were analysed. Table I \nshows the statistics for the clinic-demographic factors of the \npatients. \n \nGender, Ethnicity, Age Group and Past Medical \nConditions \nThe majority of burn victims were males (n = 160, 62.7%). \nThe breakdown of burn victims by ethnicity are as follows: \nMalay (n = 212, 83.1%), Chinese (n = 21, 8.2%), Indian (n = \n14, 5.5%), others (n = 8, 3.1%). Burn victims were categorised \ninto four different age groups: Infants < 1 years old (n = 62, \n24.3%); toddlers aged 1 to 2.99 years (n = 110, 43.1%); pre-\nschooler aged 3 to 6.99 years (n = 47, 18.4%) and school \ngoing aged 7 to 12 years (n = 36, 14.1%). Only 12 patients \nwere noted to have pre-existing medical condition(s), which \nincluded Tetralogy of Fallot (n = 1), epilepsy (n = 1), G6PD (n \n= 2), bronchial asthma (n = 3), unspecified congenital heart \ndisease (n = 1), neonatal jaundice (n = 1), drug allergies (n = \n3).  \n \nMechanism of Burns, Location of Burns and Extent of \nBurns \nScalds were the commonest cause of injury (n = 207, 81.5%) \nfollowed by direct flame (n = 27, 10.6%) and contact burns (n \n= 12, 4.7%). The most common description leading to the \nscalding episodes describes the behaviour of the child \nreaching out and pulling onto various objects, such as kettle \nwires, tablecloths or containers with scald agents. Direct \nflame burns usually occurred as a result of accidental child \ncontact with burning rubbish or child\u2019s play with lighter \nand/or petrol. Most of the burns occurred indoors (n = 199, \n86.9%), while the rest of the burns occurred outdoors. The \nextent of burns sustained were divided based on their TBSA \ninto the following groups: TBSA 0 to 10% (n = 189, 75.3%); \nTBSA 10 to 20% (n = 57, 22.7%) and TBSA > 20% (n = 5, 2%). \nThe highest TBSA sustained in a child was 36%. \n \nPatterns of Burns Mechanism in Age Groups \nThis is highlighted in Figure 1. In the infant group, scald \nburns represented 95.2% (n = 59) of burn injuries and contact \nburns represented 4.8% of burn injuries (n = 3). The \npercentage of scald burns remained at 92.7% in the toddler \nage group (n = 101), with direct flame burns at 2.8% (n = 3), \ncontact burns are 2.8% (n = 3) and other burns at 1.7% (n = \n2). In the pre-school age group, scald burns decreased to \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 662\n\n\n\n\n\n\n\n\nThree-year epidemiology of hospitalised paediatric burn patients in a Malaysian Tertiary Hospital 2016 \u2013 2018\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                663 \n\n\n\n68.1% (n = 32), direct flame burns increased to 25.6% (n = \n12), contact burns at 4.2% (n = 2) and other burns at 2.1% (n \n= 1). In the school age children, scald burns decreased to \n41.7% (n = 15), direct flame burns increased to 33.3% (n = \n12), contact burns represented 11.1% (n = 4) and other burns \nrepresented 13.9% (n = 5). \n \nProvision of First Aid \nHalf of the patients who sustained burn injuries did not \nreceive any first aid (n = 114, 50.4%). Only one-third of the \npatients had their injuries under running tap water for a \nvariable duration of time (n = 76, 33.6%). Alternative agents \nused by caregivers included toothpaste, aloe vera, traditional \noil, ointments, soy sauce and cream. One caregiver even \nplaced flour onto the child\u2019s wound, while another used egg \nwhite as first aid. \n \nDescriptive Statistics: Outcomes \nTable II shows the statistics for the various outcomes in our \nstudy population. \n \nDuration of hospitalisation \nThis data was synthesised from a total of 236 patients. The \nmedian length of hospitalisation was 4 days (IQR = 8 days). \nUsing 7 days as a cut-off point, one-third of the patients \nexperienced prolonged hospitalisation (n = 80, 33.6%). \n \nWound cultures \nOut of the 255 patients, wound cultures were done on 48 \npatients. Out of the 48 wound swabs, 24 were positive for \norganisms. There were nine patients who had multiple \norganisms cultured from their wounds.  A total of four \npatients cultured drug-resistant organisms (three cases of \nMRSA, one case of ESBL Escherichia coli) The most common \norganism cultured was Staphylococcus aureus (n = 17). Other \norganisms include: Enterococcus sp (n = 6), Pseudomonas sp (n \n= 3), Streptococcus sp (n = 2), E coli (n = 1), Acinetobacter \nbaumannii (n = 1), Enterobacter sp (n = 1).  \n \nBlood culture \nBlood cultures were done on 38 patients, of which only four \npatients had positive results. Two of the patients who were \nadmitted to ICU had consistent organisms cultured from both \ntheir blood and wound samples. The first patient sustained \nTBSA of 36% and had MRSA cultured; whereas the second \npatient sustained TBSA of 18% and had methicillin-sensitive \nStaphylococcus aureus (MSSA) cultured. The other two patients \nhad the following organisms in the blood culture: \nElizabethkingia meningoseptica in one patient and \ncombination of Micrococcus sp. and Enterococcus sp. in the \nother patient. All the four patients sustained burn injuries \nfrom the scalding mechanism. \n \nWound debridement and blood product transfusions \nApproximately one-fifth of the patients required surgical \nwound debridement (n = 45, 17.6%) whereas only a small \nportion of the patients required blood product transfusion (n \n= 19, 7.5%). \n \nICU admissions and mortality \nA total of eight (3.1%) patients required ICU admission for \nthe following reasons: four due to extensive TBSA > 15%, two \n\n\n\ndue to bacteraemia; one due to corneal abrasion; one due to \nshock requiring central venous line insertion and albumin \ninfusion. The patient who sustained a TBSA of 36% and \nMRSA bacteraemia was the only patient who required \nintubation in our study and was intubated for a total period \nof 18 days. There were no mortalities recorded among the \nsubjects within the study period. \n \nFactors Associated with Prolonged Hospitalisation \nThe main parameter utilised as the indicator of poor outcome \nin this study is prolonged hospitalisation. A Chi-squared test \nfor independence (with Yates\u2019 Continuity Correction) \nindicated that the paediatric burn patients with TBSA > 10% \nare 12.4 times more likely to experience prolonged \nhospitalisation (OR, 12.46 [95% CI 5.96 - 26.05]; p = <0.001). \nIn addition, children aged more than 3 years (pre-schooler \nand school going age children) are 2.4 times more likely to \nexperience prolonged hospitalisation compared to infants \nand toddlers (OR, 2.37 [95% CI 1.34 - 4.19]; p = 0.004). \nPatients with non-scald burns are also associated with 2.4 \ntimes increase in odds of experiencing prolonged \nhospitalisation compared to scald burns (OR, 2.46 [95% CI \n1.24 - 4.89]; p = 0.015). \n \nGiven that scalding was the most common mechanism of \ninjury, our team performed further analysis if there were any \nsignificant differences in outcomes from scalding from \ndifferent types of liquid. The scalding mechanism was divided \ninto two categories: plain water scalds and scalds from other \nliquids (curry, oil, etc). There was no significant association \nbetween type of scald fluids and prolonged hospitalisation \n(OR, 1.00 [95% CI 0.53 - 1.90]; p = 1.000). Other factors such \nas gender and ethnicity were also not significantly associated \nwith increase in risk of prolonged hospitalisation. \n \nDirect logistics regression was performed to assess the impact \nof the individual factors on the likelihood that paediatric \nburn patients would experience prolonged hospitalisation. \nThe model contained three independent variables (age \ngreater than 3, TBSA > 10% and non-scald burns). The full \nmodel containing all predictors was statistically significant (p \n<0.001), indicating that the model was able to distinguish \nbetween those who experience prolonged hospitalisation \nversus those who did not experience prolonged \nhospitalisation. The model as a whole explained between \n24.9% (Cox and Snell R square) and 34.5% (Nagelkerke R \nsquared) of variance in hospitalisation duration, and \ncorrectly classified 78.8% of cases. Only two of the three \nindependent variables made a unique statistically significant \ncontribution to the model (TBSA > 10%, non-scald burns). \nThe strongest predictor of prolonged hospitalisation was \nTBSA > 10% where patients were 13 times more likely to \nexperience prolonged hospitalization than those with TBSA \n10% or less, controlling for all other factors in the model \n(Adjusted OR 13.45 [95% CI 6.25 - 28.96]; p = < 0.001). \nPatients with TBSA > 10% are associated with higher \npercentage of antibiotics use (67.7% vs 20.6%), positive \nwound cultures (58.3% vs 41.7%), bacteraemia (13% vs \n6.7%), blood product transfusions (25.8% vs 1.6%), wound \ndebridement (38.7% vs 10.6%) and ICU admission (12.9% vs \n0%) compared to patients with TBSA 10% or less, as outlined \nin Supplementary Table I. Patients who sustained non-scald \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 663\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n664                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nClinico-demographic factors                                                                                                                               n (%) \nSex                                                                 Male                                                                                            160 (62.7%) \n                                                                      Female                                                                                         95 (37.3%) \nEthnicity                                                        Malay                                                                                          212 (83.1%) \n                                                                      Chinese                                                                                         21 (8.2%) \n                                                                      Indian                                                                                           14 (5.5%) \n                                                                      Others                                                                                            8 (3.1%) \nAge group                                                    Infants (< 1 years old)                                                                62 (24.3%) \n                                                                      Toddlers (1\u20132.99 years old)                                                       110 (43.1%) \n                                                                      Pre-schooler (3\u20136.99 years old)                                                  47 (18.4%) \n                                                                      School going (7\u201312 years old)                                                    36 (14.1%) \nMechanism of burns                                    Scald                                                                                           207 (81.5%) \n                                                                      Direct flames                                                                               27 (10.6%) \n                                                                      Contact                                                                                         12 (4.7%) \n                                                                      Others                                                                                            8 (3.2%) \n                                                                      Missing data                                                                                        1 \nType of scald fluids                                      Plain water                                                                                 133 (64.3%) \n                                                                      Others                                                                                          74 (35.2%) \nLocation of burns                                         Indoors                                                                                       199 (86.9%) \n                                                                      Outdoors                                                                                     30 (13.1%) \n                                                                      Missing data                                                                                       26 \nExtent of burns (TBSA)                                0 \u2013 10%                                                                                      189 (75.3%) \n                                                                      10.1 \u2013 20%                                                                                  57 (22.7%) \n                                                                      > 20%                                                                                             5 (2%) \n                                                                      Missing data                                                                                        4 \nProvision of first aid                                    Not given                                                                                   114 (50.4%) \n                                                                      Running water                                                                            76 (33.6%) \n                                                                      Toothpaste                                                                                   15 (6.6%) \n                                                                      Aloe vera                                                                                       3 (1.3%) \n                                                                      Others                                                                                           18 (7.9%) \n                                                                      Missing data                                                                                       29 \n\n\n\nTable I: Patient characteristics\n\n\n\nOutcomes                                                                                                                                                              n (%) \nDuration of hospitalisation                         Prolonged (> 7 days)                                                                  80 (33.6%) \n                                                                      Not prolonged (\u2264 7 days)                                                          156 (66.4%) \nProvision of antibiotics                                Yes                                                                                               82 (32.2%) \n                                                                      No                                                                                               173 (67.8%) \nResults of wound culture                            No growth                                                                                    24 (9.4%) \n                                                                      Positive                                                                                         24 (9.4%) \n                                                                      Not done                                                                                    207 (81.2%) \nResults of blood culture                              No growth                                                                                   34 (13.3%) \n                                                                      Positive                                                                                          4 (1.6%) \n                                                                      Not done                                                                                    217 (85.1%) \nNeed for wound debridement                    Yes                                                                                               45 (17.6%) \n                                                                      No                                                                                               210 (82.4%) \nNeed for blood products                             Yes                                                                                                19 (7.5%) \n                                                                      No                                                                                               236 (92.5%) \nNeed for ICU admission                               Yes                                                                                                 8 (3.1%) \n                                                                      No                                                                                               247 (96.9%) \nMortality                                                       Alive                                                                                            255 (100%) \n                                                                      Deceased                                                                                         0 (0%)\n\n\n\nTable II: Outcomes of paediatric burn patients between 2016 \u2013 2018\n\n\n\nburns were 2.7 times more likely to experience prolonged \nhospitalisation compared to scald burns (adjusted OR, 2.70 \n[95% CI 1.12 - 6.50]; p = 0.027). \n \n \nDISCUSSION \nThere remains a lack of universal definition on the age cut-\noff point for being considered a child. The cut-off points range \nbetween 9 to 20 years of age. Our study provides data for \npatients aged 12 years and below as this was the criteria for \npaediatrics surgical ward admission for our centre. This cut-\n\n\n\noff point is consistent with studies previously performed in \nthe Southeast Asian region.9-11 \n \nMale children accounted for roughly two-thirds of the overall \nadmission, which can be attributed to their risk-taking \nbehaviour.2 It is not surprising that Malay children accounted \nfor the majority of admissions, as Malays are the ethnic \nmajority in the catchment area. The categorisation of \nchildren into various age groups was based on the child\u2019s \nlevel of education, which age ranges consistent with \nclassification from previous studies to allow ease of data \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 664\n\n\n\n\n\n\n\n\nThree-year epidemiology of hospitalised paediatric burn patients in a Malaysian Tertiary Hospital 2016 \u2013 2018\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                665 \n\n\n\nVariables                                 n (%)             Prolonged hospitalisation              Crude OR                  p                Adjusted OR             p \n                                                                              > 7 days                               (95% CI)                                          (95% CI) \n                                                                       Yes                      No \n\n\n\nGender (N = 236)                                                                                                                                                                                                 \nMales                            146 (62.9%)        51 (34.9%)         95 (65.1%)         1.13 (0.65 \u2013 1.97)          0.775                                                 \nFemales                         90 (38.1%)         29 (32.2%)         61 (67.8%)                    Ref                         -                                                     \n\n\n\nEthnicity (N = 236)                                                                                                                                                                                               \nMalay                           198 (83.9%)        68 (34.3%)        130 (65.7%)        1.13 (0.54 \u2013 2.39)          0.887                                                 \nNon-Malay                    38 (16.1%)         12 (31.6%)         26 (68.4%)                    Ref                         -                                                     \n\n\n\nAge (N = 236)                                                                                                                                                                                                      \n> 3                                 76 (32.2%)         36 (47.4%)         40 (52.6%)         2.37 (1.34 \u2013 4.19)          0.004         1.63 (0.79 \u2013 3.40)      0.189 \n\u2264 3                                 160 (67.8%)        44 (27.5%)        116 (72.5%)                   Ref                         -                                                     \n\n\n\nBurns mechanism  \n(N = 235)                                                                                                                                                                                                              \n\n\n\nNon - scalds                   41 (17.4%)         21 (51.2%)         20 (48.8%)        2.462 (1.24 \u2013 4.89)         0.015         2.70 (1.12 \u2013 6.50)      0.027 \nScalds                            194 (82.6%)        58 (29.9%)        136 (70.1%)                   Ref                         -                                                     \n\n\n\nScald injuries  \n(N = 193)                                                                                                                                                                                                              \n\n\n\nPlain water                   123 (63.7%)        37 (30.1%)         86 (69.9%)         1.00 (0.53 \u2013 1.90)          1.000                                                 \nNon-plain water           70 (36.3%)         21 (30.0%)         49 (70.0%)                    Ref                         -                                                     \n\n\n\nDelayed presentation  \n(N = 156)                                                                                                                                                                                                              \n\n\n\n> 2 hours                       52 (33.3%)         16 (30.8%)         36 (69.2%)         0.77 (0.38 \u2013 1.57)          0.592                                                 \n< 2 hours                      104 (66.7%)        38 (36.5%)         66 (63.5%)                    Ref                         -                                                     \n\n\n\nTBSA (N = 232)                                                                                                                                                                                                     \n> 10%                            52 (22.4%)         40 (76.9%)         12 (23.1%)       12.5 (5.96 \u2013 26 .05)       < 0.001     13.45 (6.25 \u2013 28.96)   <0.001 \n10% or less                  180 (77.6%)        38 (21.1%)        142 (78.9%)                   Ref                         -                                                     \n\n\n\n \n*p values presented are extracted from the Yates Continuity Correction as it is a 2 x 2 table \n \n\n\n\nTable III: Factors associated with prolonged length of hospitalisation\n\n\n\nOutcomes                                                                  TBSA 10% or less, n (%)                                             TBSA > 10%, n (%) \nProvision of antibiotics                                                                                                                                                     \n\n\n\nYes                                                                                   39 (20.6%)                                                                42 (67.7%) \nNo                                                                                   150 (79.4%)                                                               20 (32.3%) \n\n\n\nWound culture                                                                                                                                                                  \nNot done                                                                        165 (87.3%)                                                               38 (61.3%) \nDone                                                                                24 (12.7%)                                                                24 (38.7%) \nPositive                                                                            10 (41.7%)                                                                14 (58.3%) \nNo growth                                                                      14 (58.3%)                                                                10 (41.7%) \n\n\n\nBlood culture                                                                                                                                                                    \nNot done                                                                        174 (92.1%)                                                               39 (62.9%) \nDone                                                                                 15 (7.9%)                                                                 23 (37.1%) \nPositive                                                                              1 (6.7%)                                                                   3 (13.0%) \nNo growth                                                                      14 (93.3%)                                                                20 (87.0%) \n\n\n\nBlood transfusion                                                                                                                                                             \nYes                                                                                     3 (1.6%)                                                                  16 (25.8%) \nNo                                                                                   186 (98.4%)                                                               46 (74.2%) \n\n\n\nWound debridement                                                                                                                                                        \nYes                                                                                   20 (10.6%)                                                                24 (38.7%) \nNo                                                                                   169 (89.4%)                                                               38 (61.3%) \n\n\n\nICU admission                                                                                                                                                                    \nYes                                                                                           -                                                                          8 (12.9%) \nNo                                                                                   189 (100%)                                                                54 (87.1%) \n\n\n\n \n*N = 251 \n \n\n\n\nSupplementary Table I: Extent of burns (TBSA) vs outcomes\n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 665\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n666                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\ncomparison.7,11-13 Our study found that toddlers (aged 1\u20132.99 \nyears) were the most vulnerable age group as they \nrepresented the highest number of admissions.  \n \nVarious data uncovered in this study would be crucial in the \ndevelopment of an effective burn prevention campaign. Our \ndata confirms that scalding remains the main mechanism of \nburns injury among young children, with most injuries \noccurring at home.2,14 This is related to the normal \ndevelopmental stages of the children, as most of them start to \nreach for objects and crawl by the age of 6 months followed \nby becoming fully mobile by the age of 18 months.15 This \ntendency for young children to reach out and pull onto \nobjects that cause scalding episodes are crucial intervention \npoints for injury prevention by caregivers. It is also \ninteresting to note that children become more prone to direct \nflame burns as they approach the school age group. This \ntrend was observed in other studies worldwide and was \nattributed to fires from children\u2019s play.15,16 Drawing upon \npaediatric burn prevention measures employed worldwide, \nexamples of prevention strategies to reduce scald and flame \nburns that are relevant to the local population include short \nradio messages on burns prevention, raising height of \ncooking surfaces, safe storage of flammable substances, \nguarding of open fires and home visits with counselling on \nhome hazards.17 The introduction of \u201cChild Safe Home\u201d \nconcept with online information disseminated in the local \nlanguage may be considered. \n \nIt is also evident that there is a lack of awareness on the \nappropriate provision of first aid for burns as only one-third \n\n\n\nof the children had their wounds under running water post-\ninjury. It is unclear if other alternatives, such as toothpaste, \nsoy sauce and egg white, placed on the wound may \npotentially aggravate or contaminate the wound further \nleading to poorer outcomes. However, numerous studies \nbelow have proven the effectiveness of immediate running \nwater lavage for burn injuries. Large scale data from the New \nSouth Wales Agency for Clinical Innovation State-wide Burn \nInjury Service showed initial treatment with running water \nup to 20 minutes was associated with reduction in burn \nwound depth, wound healing time and graft area \nrequirements.18 The seven-year study in Taiwan on over \n12,000 patients demonstrated proper first aid resulted in a \nreduction in length of stay for burns with TBSA less than \n30%.19 A small study in Nigeria observed that burn patients \nwho received water lavage as first aid had a 50% reduction in \nthe development of complications compared to those who did \nnot received it (35.3% vs 18.4%).20 Overall, this highlights the \nutmost importance of emphasising adequate first aid with at \nleast 20 minutes of running water in any burns prevention \ncampaign. Additional first aid strategies include immediate \nremoval of child from burn source and prevention of \nhypothermia by wrapping unaffected areas of child in clean \ndry blankets prior to arrival of the emergency medical \nservices team.21 \n \nThe majority of the paediatric patients (75.3%) who were \nadmitted had TBSA < 10%. This was consistent with various \nlocal and international data.7,11,12,22,23 Comparing our data \nwith the data presented in 1995 by Ibrahim et al based on a \ntertiary burn referral in the capital city of Kuala Lumpur, \n\n\n\nFig. 1: Patterns of burns mechanism in age groups.\n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 666\n\n\n\n\n\n\n\n\nThree-year epidemiology of hospitalised paediatric burn patients in a Malaysian Tertiary Hospital 2016 \u2013 2018\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                667 \n\n\n\nMalaysia, we found that there is a significant reduction in \nproportion of patients requiring hospitalisation greater than \n7days (33.6% in our study vs 49% in Ibrahim et al\u2019s study). \nThis improvement in outcome is thought to be attributed to \nrecent advancements in management of paediatric burns \nand improvements in healthcare infrastructure throughout \nthe years.24  \n \nOur study also provided some preliminary data on the local \nbacteriological profile of burn wounds in children. S. aureus \nremains the predominant organism cultured from wounds of \nour study patients, which was consistent with data from the \nstudy by Ibrahim et. al.7 This is in contrast to studies in \nTurkey and Iran, where coagulase-negative Staphylococcus \nsp. was shown to be the main organism.23,25 In a study \nconducted in India, Acinetobacter baumannii was presented \nas the main organism cultured from paediatric burn \nwounds.26 This variability in reported organisms suggests that \nbacteriological profiles of pathogens vary between region to \nregion. The trend in adult burn patients is more predictable, \nwith S. aureus and Pseudomonas aeruginosa being the two \nmost common pathogens isolated from overall burn wound \nsamples; whereas Acinetobacter baumannii, MRSA and \nPseudomonas aeruginosa were the common organisms \ncultured from wounds of severe burn victims.27 31 It is unclear \nif this bacteriological trend is similar in paediatric burns. \nHence, the data provided by our study may suggest S. aureus \nas the most common organism implicated in local paediatric \nburn wound infections. However, this remains to be proven in \nfuture studies given that only 48 patients in our study had \nwound swabs sent for cultures and the possibility of S. aureus \nbeing a contaminant rather than an infective organism as it \nis a common skin commensal. \n \nGenerally, the mortality rates in paediatric burn patients are \nrather low worldwide. In Malaysia, Ibrahim et al recorded 1% \nmortality rate in 1995, whereas a 3-year study conducted \nbetween 2016 to 2018 at the Malacca Hospital did not record \nany deaths.7,8 Data from Singapore suggested mortality rates \nof 0.28 to 0.4%, and studies in China and Saudi Arabia \nprovided rates of 0.24% and 0.76% respectively.10,11,13,16 In a \nstudy, which analysed 57 years of paediatric burns data from \na single centre in South Australia, it was found that all the \nchildren with TBSA < 40% survived, whereas those with TBSA \n> 40% had a mortality rate of 34%.32 It is worth noting that \nstudies which included older children up to 18 years of age \nrecorded a higher mortality rate.26 This could be due to older \nchildren having higher risk of sustaining severe burns, \nespecially from flame injuries, where flame injuries were \nobserved to be significant predictors of mortality in numerous \nstudies.33,34 We were unable to provide the accurate mortality \nrate for paediatric burns at our centre as none of our patients \ndied during the course of this study. \n \nTBSA > 10% and non-scald burns are the two strongest \npredictors for prolonged hospitalisation based on data from \nour study. This corresponds to data presented in known \nliterature on the influence of these two factors on other \nmeasures of poor outcomes, such as increased risk of \ninfections and mortality.26,33-37 This information would be \nuseful in guiding clinicians to triage paediatric burn patients\u2019 \npresentations, provide rapid care and close monitoring for \n\n\n\nthose with TBSA > 10% and non-scald burns. Burn depth is \nalso important in the initial assessment process given that \ndeeper wounds carry higher risk of complications and may \nrequire surgical intervention. However, there remains \ninaccuracies in burn depth approximation even in large \nexperienced burn centres.21 Hence, it may be more practical \nfor centres to adopt TBSA measurements in favour of burn \ndepth evaluation to guide initial triaging protocols and \nresuscitative efforts with fluid therapy. \n \nDue to the retrospective nature of our study, there were some \nlimitations such as an inadequate account of additional \nsociodemographic variables (e. g., family size and income \ngroup), clinical data such as burn depth and long-term \ncomplications such as scarring and psychological trauma. As \nthis study was based on hospitalised children, the findings \nmay be less applicable to children with milder burns injuries \ntreated in an outpatient setting. This study was conducted on \nsubject prior to COVID-19 pandemic when there were likely \nchanges to the demographics and management approaches \nadopted by healthcare systems.38,39 Nevertheless, as we \nemerged from the COVID-19 pandemic, the study findings \nare likely relevant to the current post-pandemic population.   \n \n \nCONCLUSIONS \nThe findings mentioned above provide a recent update on the \nepidemiology and outcomes of paediatric burn cases based \non a single tertiary centre in Malaysia in the pre-COVID-19 \nera. Data collected on the demography of paediatric burns \npatients would contribute to the identification of at-risk \npopulations, development of effective prevention strategies \nand inform clinical practice and research in the future.   \n \n \nAUTHOR CONTRIBUTIONS \nC.X.L, R.Z.M.L, S.Y.Q and C.F.N performed the relevant \nliterature search, conceived and designed this retrospective \nstudy. Y.Q.K, X.S.L and C.X.L organised rigorous data \ncollection and critical data analysis. C.X.L, Y.Q.K and X.S.L \nperformed the manuscript writing. R.Z.M.L, S.Y.Q, and C.F.N \nprovided conceptualisation, technical support, and \nproofreading. All authors have read and agreed to all the \ninformation and conclusions in the submitted version of the \nmanuscript. \n \n \nFUNDING \nThis research did not receive any specific grant from funding \nagencies in the public, commercial, or not-for-profit sectors. \n \n \nDISCLAIMER \nThe views expressed in the submitted article are based upon \nthe consensus of all authors and do not necessarily represent \nthe official position of the affiliated institutions. \n \n \nACKNOWLEDGEMENTS \nThe authors would like to thank the Director General of \nHealth Malaysia for permission to publish this paper. The \nauthors would also like to express our gratitude towards the \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 667\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n668                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nMedical Director of Sultanah Aminah Hospital for his \npermission and support to conduct this research. \n \n \nDECLARATION OF INTERESTS \nThe authors declare that there is no conflict of interest. \n \n \nREFERENCES \n1. Pellatt RA, Williams A, Wright H, Young AE. The cost of a major \n\n\n\npaediatric burn. Burns 2010;36(8): 1208-14. \n2. Alnababtah K, Khan S, Ashford R. Socio-demographic factors \n\n\n\nand the prevalence of burns in children: an overview of the \nliterature. Paediatr Int Child Health 2016; 36(1): 45-51. \n\n\n\n3. Edelman LS. Social and economic factors associated with the risk \nof burn injury. Burns 2007; 33(8): 958-65. \n\n\n\n4. Emery CA. Parenting interventions for the prevention of \nunintentional injuries in childhood. Paediatr Child Health 2017; \n22(4): 220-2. \n\n\n\n5. Chan KY, Hairol O, Imtiaz H, Zailani M, Kumar S, \nSomasundaram S, et al. A review of burns patients admitted to \nthe Burns Unit of Hospital Universiti Kebangsaan Malaysia. Med \nJ Malaysia 2002; 57(4): 418-25. \n\n\n\n6. Ghani AN, Ibrahim SH. Burns in the Malaysian population: two \nyears of burns admissions for burns at the general hospital, \nKuala Lumpur. Med J Malaysia 1987; 42(4): 238-41. \n\n\n\n7. Ibrahim SB, Omar MB, Gan EC, Rauf A, Johari NB, Yusof HB. \nChildhood burns at the Paediatric Institute Kuala Lumpur. Med J \nMalaysia 1995; 50(3): 221-5. \n\n\n\n8. Mohd Said MT, Hussin I, Ahmad Zaidi AI, Noran IS. E - Poster - \nPaediatric Burn in Hospital Melaka. 1st National Paediatric \nPlastic Surgery Woman and Child Hospital Kuala Lumpur. 2020. \n\n\n\n9. Chong SJ, Song C, Tan TW, Kusumawijaja G, Chew KY. Multi-\nvariate analysis of burns patients in the Singapore General \nHospital Burns Centre (2003-2005). Burns 2009; 35(2): 215-20. \n\n\n\n10. Song C, Chua A. Epidemiology of burn injuries in Singapore from \n1997 to 2003. Burns 2005; 31 Suppl 1:S18-26. \n\n\n\n11. Ngim RC. Epidemiology of burns in Singapore children--an 11-\nyear study of 2288 patients. Ann Acad Med Singap 1992; 21(5): \n667-71. \n\n\n\n12. Tse T, Poon CH, Tse KH, Tsui TK, Ayyappan T, Burd A. Paediatric \nburn prevention: an epidemiological approach. Burns 2006; \n32(2): 229-34. \n\n\n\n13. Li H, Wang S, Tan J, Zhou J, Wu J, Luo G. Epidemiology of \npediatric burns in southwest China from 2011 to 2015. Burns \n2017; 43(6): 1306-17. \n\n\n\n14. Kubilius D, Smailyt\u0117 G, Rimdeikien\u0117 I, Malcius D, Kaikaris V, \nRimdeika R. Epidemiology of paediatric burns in Lithuania: focus \non a vulnerable population exposed to the risk of scalds at home \nwithout hot tap water supply. Burns 2014; 40(3): 506-10. \n\n\n\n15. Peck MD. Epidemiology of burns throughout the world. Part I: \nDistribution and risk factors. Burns 2011; 37(7): 1087-100. \n\n\n\n16. Almarghoub MA, Alotaibi AS, Alyamani A, Alfaqeeh FA, \nAlmehaid FF, Al-Qattan MM, et al. The Epidemiology of Burn \nInjuries in Saudi Arabia: A Systematic Review. J Burn Care Res \n2020; 41(5): 1122-7. \n\n\n\n17. Parbhoo A, Louw QA, Grimmer-Somers K. Burn prevention \nprograms for children in developing countries require urgent \nattention: a targeted literature review. Burns 2010; 36(2): 164-75. \n\n\n\n18. Harish V, Tiwari N, Fisher OM, Li Z, Maitz PKM. First aid \nimproves clinical outcomes in burn injuries: Evidence from a \ncohort study of 4918 patients. Burns 2019; 45(2): 433-9. \n\n\n\n19. Tung KY, Chen ML, Wang HJ, Chen GS, Peck M, Yang J, et al. A \nseven-year epidemiology study of 12,381 admitted burn patients \nin Taiwan--using the Internet registration system of the \nChildhood Burn Foundation. Burns 2005; 31 Suppl 1: S12-7. \n\n\n\n20. Fadeyibi IO, Ibrahim NA, Mustafa IA, Ugburo AO, Adejumo AO, \nBuari A. Practice of first aid in burn related injuries in a \ndeveloping country. Burns 2015; 41(6): 1322-32. \n\n\n\n21. Jeschke MG, van Baar ME, Choudhry MA, Chung KK, Gibran NS, \nLogsetty S. Burn injury. Nat Rev Dis Primers 2020; 6(1): 11. \n\n\n\n22. Zvizdic Z, Be\u0107irovi\u0107 K, Salihagi\u0107 S, Milisic E, Jonuzi A, \nKaramustafic A. Epidemiology and clinical pattern of paediatric \nburns requiring hospitalization in sarajevo canton, bosnia and \nherzegovina, 2012-2016. Ann Burns Fire Disasters 2017; 30(4): \n250-5. \n\n\n\n23. Asena M, Aydin Ozturk P, Ozturk U. Sociodemographic and \nculture results of paediatric burns. Int Wound J 2020; 17(1): 132-\n6. \n\n\n\n24. Lee SZ, Halim AS. Superior long term functional and scar \noutcome of Meek micrografting compared to conventional split \nthickness skin grafting in the management of burns. Burns 2019; \n45(6): 1386-400. \n\n\n\n25. Karimi H, Montevalian A, Motabar AR, Safari R, Parvas MS, \nVasigh M. Epidemiology of paediatric burns in Iran. Annals of \nburns and fire disasters 2012; 25(3): 115-20. \n\n\n\n26. Dhopte A, Bamal R, Tiwari VK. A prospective analysis of risk \nfactors for pediatric burn mortality at a tertiary burn center in \nNorth India. Burns Trauma 2017; 5: 30. \n\n\n\n27. Bahemia IA, Muganza A, Moore R, Sahid F, Menezes CN. \nMicrobiology and antibiotic resistance in severe burns patients: A \n5 year review in an adult burns unit. Burns 2015; 41(7): 1536-42. \n\n\n\n28. Mater ME, Yamani AE, Aljuffri AA, Binladen SA. Epidemiology of \nburn-related infections in the largest burn unit in Saudi Arabia. \nSaudi Med J 2020; 41(7): 726-32. \n\n\n\n29. Miranda BH, Ali SN, Jeffery SL, Thomas SS. Two stage study of \nwound microorganisms affecting burns and plastic surgery \ninpatients. J Burn Care Res 2008; 29(6): 927-32. \n\n\n\n30. Chaudhary NA, Munawar MD, Khan MT, Rehan K, Sadiq A, \nTameez-Ud-Din A, et al. Epidemiology, Bacteriological Profile, \nand Antibiotic Sensitivity Pattern of Burn Wounds in the Burn \nUnit of a Tertiary Care Hospital. Cureus 2019; 11(6): e4794. \n\n\n\n31. Bhat VG, Vasaikar SD. Bacteriological profile and antibiogram of \naerobic burn wound isolates in Mthatha, Eastern Cape, South \nAfrica : original research. South Afr J Epidemiol Infect 2010; \n25(4): 16-9. \n\n\n\n32. Chong HP, Quinn L, Cooksey R, Molony D, Jeeves A, Lodge M, et \nal. Mortality in paediatric burns at the Women's and Children's \nHospital (WCH), Adelaide, South Australia: 1960-2017. Burns \n2020; 46(1): 207-12. \n\n\n\n33. Sharma PN, Bang RL, Al-Fadhli AN, Sharma P, Bang S, Ghoneim \nIE. Paediatric burns in Kuwait: incidence, causes and mortality. \nBurns 2006; 32(1): 104-11. \n\n\n\n34. Purcell LN, Banda W, Akinkuotu A, Phillips M, Hayes-Jordan A, \nCharles A. Characteristics and predictors of mortality in-hospital \nmortality following burn injury in infants in a resource-limited \nsetting. Burns 2021; 48(3): 602 \u2013 607. \n\n\n\n35. Saritas A, Cakir ZG, Ak\u00e7ay MN, Kandis H, Ersunan G, Ozt\u00fcrk G, \net al. Predictors of mortality in childhood burns: an 8-year \nreview. J Child Health Care 2014; 18(1): 84-95. \n\n\n\n36. Rodgers GL, Mortensen J, Fisher MC, Lo A, Cresswell A, Long SS. \nPredictors of infectious complications after burn injuries in \nchildren. Pediatr Infect Dis J 2000; 19(10): 990-5. \n\n\n\n37. Fadeyibi IO, Mustapha IA, Ibrahim NA, Faduyile FI, Faboya MO, \nJewo PI, et al. Characteristics of paediatric burns seen at a \ntertiary centre in a low income country: a five year (2004-2008) \nstudy. Burns 2011; 37(3): 528-34. \n\n\n\n38. Ilenghoven D, Hisham A, Ibrahim S, Mohd Yussof SJ. \nRestructuring burns management during the COVID-19 \npandemic: A Malaysian experience. Burns 2020; 46(5): 1236-9. \n\n\n\n39. Tatar R, Enescu DM. The impact of COVID-19 pandemic on the \nactivity of a pediatric burn center in Bucharest, Romania. Burns \n2020; 46(8): 1977-8. \n\n\n\n\n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 668\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                669 \n\n\n\nABSTRACT \nAppendicular mass is considered as one of the \ncomplications of acute appendicitis but there is no \nconsensus on the optimal management of this condition. \nThe management of this condition has always been \nconservative management with interval appendectomy as \npopularized by Oschner and Sheerin. The need for interval \nappendectomy has now been questioned, and an emerging \ntrend has been early appendectomy by laparoscopic \nmethod. There are no guidelines on the management of \nappendicular mass and treatment is decided by the surgeon. \nWe have conducted a narrative review to investigate what is \nthe current practice in the management of appendicular \nmass.     \n \nKEYWORDS:  \nAppendicular mass, appendicular phlegmon, appendicular lump, \ninterval appendectomy \n \n \nINTRODUCTION \nAcute appendicitis is one of the most common acute \nabdominal conditions that is seen in surgical practice and \nappendicular mass accounts for up to 10% of cases. The \npathological spectrum can range from Phlegmon to abscess \nformation. The appendicular mass is composed of the \ninflamed appendix, omentum and bowel loops, and it forms \nafter about 24 to 48 hours after the initial symptoms. This is \na protective mechanism to prevent the spread of infection. \nThe treatment of appendicular mass has been debated over \nthe past 80 years. The diagnosis of appendicular mass is \nmade clinically, but ultrasonography is the most popular \ninvestigation of choice, although computerized tomography \n(CT), is more sensitive. The presentation is more acute in \nchildren, whereas in the adults the mass tends to take longer \nto form.1 \n \nThe management of appendicular mass can be divided into \nthree treatment approaches 1) Conservative management \nwith broad spectrum antibiotics and intravenous fluids \nfollowed by interval appendectomy in 6 - 8 weeks. This was \nproposed by Oschner and Sheeren in 1901 and is the most \npopular treatment option for appendicular mass and is \nwidely practiced worldwide. 2) Conservative management \nwithout interval appendectomy, as this option is proposed \ndue to low infection rates and low recurrence rates and hence \nthere is no need for interval appendectomy. For patients \nabove the age of 40, follow up treatment with investigations \nlike colonoscopy and computerized tomography (CT) is \nrequired. 3) Immediate appendectomy which is emerging as \n\n\n\nan alternative treatment option, and this option eliminates \nthe risk of recurrence and the need for interval \nappendectomy. The operative options are open \nappendectomy and laparoscopic appendectomy. Open \nappendectomy was the treatment of choice, but laparoscopic \nappendectomy is emerging as an alternative treatment \noption due to decreased post operative pain, early recovery, \nand earlier discharge to home. Currently conservative \ntreatment of appendicular mass is the most favored by most \nsurgeons. However, the pressing question is the need for \ninterval appendectomy after conservative treatment, as there \nis a growing trend to opt against interval appendectomy. The \nargument for this is the low rate of recurrent infection and \nthe early return to work.2,3 \n\n\n\n \n \nMATERIALS AND METHODS \nCurrently there is no uniform consensus on the management \nof appendicular mass, and we have conducted this review \narticle to investigate the various management options. We \nconducted a literature review using PUBMED, Cochrane \ndatabase of clinical reviews and Google scholar looking for \nclinical trial, observational studies, cohort studies systemic \nreviews, and meta-analysis from 1990 to 2022.We used the \nfollowing keywords, \u201cAppendicular Mass\u201d, \u201cAppendicular \nPhlegmon\u201d, \u201cAppendicular Lump\u201d, \u201cInterval Appendectomy \n\u201cand, \u201cComplicated Appendectomy\u201d. All articles were in \nEnglish language only. Further articles were obtained by \nmanual cross referencing of the literature. Case reports and \nstudies with less than 10 patients and editorials were \nexcluded. \n \n \nDISCUSSION \nConservative management followed by interval \nappendectomy. \nOschner and Sherren proposed this management for \nappendicular mass in 1901, during the era of limited \nantibiotics and imaging technologies. This approach \ninvolved keeping the patient nil by mouth and starting intra- \nvenous antibiotics and measuring the size of the \nappendicular mass. This treatment is continued for 24 to 48 \nhours, and it involves monitoring of the vital signs.2 This \nmethod removes the risk of complications that can occur \nduring the acute phase of surgery and interval \nappendectomy eliminates the risk of recurrence.3 Interval \nappendectomy will help to give a histological diagnosis and \nto prevent recurrence. The complication rates from interval \nappendectomy are low.4  \n \n\n\n\nCurrent management of appendicular mas - a narrative \nreview \n \nKumar Hari Rajah, Somanathan Menon and Ganesh Ramachandran \n\n\n\n     \nDepartment of Surgery, School of Medicine, Faculty of Health and Medical Science, Taylor University, Subang Jaya, Malaysia\n\n\n\nSYSTEMATIC / NARRATIVE REVIEW ARTICLE\n\n\n\n This article was accepted: 12 July 2023                                                                                                                                                                              \nCorresponding Author: Kumar Hari Rajah                                                                                                                                                                          \nEmail: kharirajah@yahoo.com.my \n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 669\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n670                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nOlsen et al                         Systematic review        3,772 patients                  70 to 80% success rate                        Most of the studies  \n                                                                                                                                                                                 were retrospective in nature \nVan Amstel et al                  Meta-analysis            1,355 patients                     12% complication in                     Most of the studies were  \n                                                                                                                             conservative group                        retrospective in nature \nGillick et al                      Retrospective study        427 patients                          85% success rate                          Retrospective in nature \nRavichandran et al            Prospective study          116 patients            Decreased wound infection rates                 Low patient load \nDemetrashvilli et al         Retrospective study         48 patients                    Complication rates were                   Retrospective in nature \n                                                                                                                         the same in both groups                                        \nKim et al                          Retrospective study         76 patients                Outcomes and complications               Retrospective in nature \n                                                                                                                    were the same in both groups                                   \n \n \n\n\n\nTable \u2160: Table of contents of the retrospective studies\n\n\n\nFugazolla et al             Meta-analysis         1,288 patients           90% success rate for conservative        Most studies were retrospective \n                                                                                                         treatment.15% recurrence rate                             in nature \nAnderson et al             Meta-analysis        59,488 patients                    93%success rate with                        Most of the studies were  \n                                                                                                                   10%recurrence rate                            retrospective in nature \nDemetashivilli et al        Prospective             74 patients             High success rate for conservative                 Low patient numbers \n                                      cohort study                                                                treatment                                                        \nYilmt et al                    Retrospective          126 patients           Lower morbidity and infection rate         Retrospective study in nature \n                                            study                             \n\n\n\nTable II: Table of contents of the studies for conservative treatment\n\n\n\nKhan et al            Randomized control trials          300 patients                       5-8% complication rate                     Low patient numbers \nArshad et al               Comparative study                176 patients                     Low wound infection rate                   Low patient numbers \nDas et al                     Retrospective study               112 patients                     Low wound infection rate                  Retrospective in nature \nPathan et al                 Prospective study                 100 patients                       Reduced infection rate                      Low patient numbers \nIshar et al                  Observational study                60 patients            Reduced mean hospital stay at 4 days          Low patient numbers \nEl-sood et al              Retrospective study                40 patients                    Reduced mean hospital stay                  Low patient numbers \nKumar et al                 Prospective study                  50 patients                    Reduced mean hospital stay                  Low patient numbers \n\n\n\nTable III: Table of contents for studies that favor early appendectomy\n\n\n\nFig. 1: Flow chart for the management of appendicular mass.\n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 670\n\n\n\n\n\n\n\n\nCurrent management of appendicular mass-narrative review article\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                671 \n\n\n\nA retrospective study by Koirala et al evaluated conservative \ntherapy for appendicular mass where 173 patients were \ntreated. Of this number, 10 patients developed complications \nthat required emergency appendectomy, but the rest were \nmanaged conservatively. Only 35 patients returned for \ninterval appendectomy. Bhandari et al in their study of 75 \npatients with appendicular mass were managed \nconservatively and only five patients developed appendicular \nabscess, but only 13 patients came back for interval \nappendectomy. Although these were retrospective studies, it \nshowed the success of conservative treatment but highlighted \nthe problem of patient\u2019s attendance for interval \nappendectomy. Further retrospective studies by Gillick and \ndemetrashvili also showed the benefit of conservative \ntreatment in the management of appendicular.5\u20137 \n \nIn a prospective study by Elsaady, a total of 169 cases of \nappendicular mass 121 patients were treated conservatively. \nOf this total 106 were successfully treated and treatment \nfailure was seen in 15 cases. This showed that the \nconservative method with interval appendectomy was an \neffective and safe treatment method. This was also confirmed \nby a prospective study by Ravichandran et al and ahmed et \nal which showed the success of conservative treatment \nfollowed by interval appendectomy.8\u201310 \n \nA systemic review by Olsen et al reviewed the literature in 48 \nstudies and a total of 3,772 patients and they concluded that \nconservative management of appendicular mass was safe \nand associated with a Success rate of 80%-90% and there \nwere no major complications. Another systemic review by \nTeixeira et al also concluded that conservative management \nof appendicular mass was safe and the risk of detecting \nneoplasms of the appendix was low.11,12 \n \nA meta-analysis by van Amstel, which included 14 studies \nand 1355 patients, for which 1022 were treated with \nconservative therapy and 333 underwent emergency \nappendectomy, complications were seen in 12.2% of the \nconservative therapy group and 25.5% in the emergency \nappendectomy group. The most common complication was \nwound infection. This showed that conservative therapy \nfollowed by interval appendectomy should be the treatment \nof choice for appendicular mass but the drawback from this \nmeta-analysis was that the majority of the studies were small \nretrospective studies.13      \n \nAn audit by Ahmed et al in the mid trent region in the United \nKingdom, concluded that 75% of surgeons there conducted \nconservative therapy with interval appendectomy on patients \nwith appendicular mass and that there was no present \nprotocol for the treatment of appendicular mass.14   \n \nAnother survey of hospitals in the south coast of the United \nKingdom showed the diverse practice in the management of \nappendicular mass, where senior surgeons would manage \nthese patients conservatively, but surgical registrars were \nmore inclined to perform interval appendectomy.15  \n \nKim et al did a retrospective analysis on 76 patients who were \ndiagnosed with appendicular mass, 48 underwent \nconservative therapy followed by interval appendectomy and \n\n\n\n28 underwent emergency appendectomy, the recurrence rate \nwas low and the outcomes after surgery were the same in all \nthe groups hence conservative therapy followed by interval \nappendectomy is still the primary choice of therapy for \nappendicular mass, but the choice of therapy will usually be \ndecided by the surgeon.16 \n \nGarba et al., conducted a review on the treatment \napproaches for the management of appendicular mass and \nconcluded that conservative management followed by \ninterval appendectomy is still the primary treatment of \nchoice for the management of appendicular mass and follow- \nup of patients are essential while waiting for interval \nappendectomy.17 Simillis et al conducted a meta-analysis \ncomparing conservative therapy versus immediate \nappendectomy on the treatment of appendicular mass,21 \nstudies were included, and the conclusion was that \nconservative therapy followed by interval appendectomy was \nassociated with decreased wound complication ,abscess \nformation and intestinal obstruction. The duration of \nhospital stay was also the same between the groups.18   \n \nThe European Association of Emergency Surgeons consensus \ndevelopment conference 2015 still recommends conservative \nmanagement followed by interval appendectomy in the \nmanagement of appendicular mass. Interval appendectomy \nis done to reduce the chance of recurrence and to not miss \nany under lying malignancy.19  The World Society of \nEmergency Surgeons Jerusalem guidelines also recommends \nconservative treatment as the initially therapy of \nappendicular mass in the event of non-availability of \nlaparoscopic surgery.20 \n \nMost of the studies that were done on conservative \nmanagement of appendicular mass with interval \nappendectomy were retrospective in nature and this \ninfluenced the outcomes of wound infection and recurrence \nrate. An area of issue is the number of patients who are lost \nto follow- up and hence did not come for interval \nappendectomy. The number of patients in most of the studies \nwas rather low in number. For future research it is hoped that \nrandomized control trials can be used to investigate the \nconservative management of appendicular mass, but sample \nsize may be a problem. \n \nConservative management without interval \nappendectomy \nThere are some in the surgical fraternity who oppose interval \nappendectomy as they point out that the rate of recurrence \nattacks is low and the complication rates from interval \nappendectomy are not low. A study by Noori et al, on 65 \npatients with appendicular mass who underwent \nconservative management with no interval appendectomy, \nthe rate of recurrence was 10% and wound infection was seen \nin 4% of the cases. Hence upon completion of conservative \nmanagement, interval appendectomy is not necessary as the \nrecurrence rate is low.21 \n \nDemetrashivili et al also had conducted a cohort study on 74 \npatients with appendicular mass, where 47 had undergone \nconservative therapy and 27 underwent immediate \nappendectomy, and there were no significant differences in \n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 671\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n672                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nthe treatment for both groups, hence conservative treatment \nwithout interval appendectomy was still the preferred \ntreatment of choice. Patients who present with recurrence can \nbe operated and Computerised Tomography and \ncolonoscopy can be done to investigate patients who present \nwith recurrence.22 \n \nYilmaz et al in his retrospective study on 126 patients with \nappendicular mass were divided into two groups one was \nmanaged with appendectomy and another group with \nconservative therapy alone.43 underwent appendectomy and \n72 underwent conservative therapy, the morbidity and \ninfection rate was higher in the appendectomy group .Based \non this study conservative appendectomy without interval \nappendectomy should be the treatment of choice and \npatients with recurrence can be followed up by investigations \nlike colonoscopy and computed tomography. The drawback \nof this study was the fact that it was retrospective in nature.23 \nPanahi et al in his study did a literature search on the best \nmanagement option of appendicular mass, and after \nfiltration a total of 5 papers were identified to provide the best \nevidence. Based on this, conservative management without \ninterval appendectomy was considered the best treatment \noption for appendicular mass and to prevent recurrence, \npatients should be followed up with investigations like \ncolonoscopy and imaging like ultrasound or computed \ntomography. Meshikhes also looked in the literature and \nconcluded that interval appendectomy can be safely \nexcluded, and that recurrence can be managed by \nlaparoscopic appendectomy. Quartey investigated the need \nfor interval appendectomy and concluded that it was not \nnecessary and that concluded that recurrence can be \ninvestigated by colonoscopy or computerized tomography.24\u2013\n\n\n\n26 \n \nMalik et al conducted a retrospective study on 220 patients \nwith conservative management and 213 patients were \ntreated successfully, the recurrence rate was 13% with a \nmedian follow up of 6 months. He concluded that interval \nappendectomy was not necessarily due to the low recurrence \nrates. Another retrospective study by Tingstedt also confirmed \nthis.27,28 \n  \nIn a meta-analysis done by Anderson et al, which \ninvestigated the conservative management of appendicular \nlump and upon successful treatment interval appendectomy \nwas not indicated. There was a success rate of 93% but \npercutaneous drainage of abscess was seen in 20% of cases. \nThe risk of recurrence was seen in less than 10% of cases and \nwas also associated with a risk of missing other diagnosis like \nmalignancy or Crohn \u2018s disease in about 2% of cases. Follow- \nup of patients above the age of 40 was suggested with \ncolonoscopy and Computed Tomography to not miss other \ndiagnosis.29 \n \nA meta-analysis by Fugazolla et al on 14 studies with 1288 \npatients, where 622 were treated with conservative \nmanagement and 666 with appendectomy, the success rate \nwas 90% and the recurrence rate was 15.4%. This showed \nthat conservative therapy should be the treatment of choice \nfor patients with appendicular mass.30 \n \n\n\n\nThe drawback from these studies was that most of them were \nretrospective in nature and due to the low recurrence rate and \npost operative infection rates the need of interval \nappendectomy was questioned. With better investigations \nlike computerized tomography and colonoscopy, the need for \ninterval appendectomy is being questioned. For future \nresearch, more randomized control trials should be \nconducted in the conservative management of appendicular \nmass and more prospective studies should be done, with \nbetter sample size. \n \nImmediate appendectomy either by open or laparoscopic \nmethod \nThere are surgeons who advocate for immediate \nappendectomy for patients who present with an \nappendicular mass, as this approach excludes the need for \nreadmission, cures the condition and reaches a definitive \ndiagnosis.  A prospective study by Bahram on 46 patients \nwith appendicular mass who were subjected to immediate \nappendectomy. The infection rates were 8% and the mean \nhospital stay was 3 days. This showed that immediate \nappendectomy was feasible and safe in the management of \nappendicular mass.31 \n \nAli et al in his literature review, stated that emergency \nappendectomy in the management of appendicular mass is \nemerging as an alternative treatment than conservative \nmanagement. It is safe and cost- effective and reduces \nhospital stay.32 \n \nKhan et al conducted randomized control trials on 300 \npatients with appendicular mass,150 had undergone \nimmediate appendectomy and 150 conservative treatments. \nThe wound infection rates among the groups were 5% and \n8% respectively and the frequency of intra-abdominal \nabscess was less than 2%. This study concluded that \nimmediate appendectomy was more effective option in the \nmanagement of appendicular mass.33 \n \nArshad et al in his comparative study on 176 patients of \nappendicular mass ,88 patients underwent immediate \nappendectomy and 88 underwent conservative treatment. \nThe wound infection rate was higher in the immediate \nappendectomy group but the stay in hospital was less than in \nthe conservative treatment group, but the rate was not high \nto exclude immediate appendectomy. Immediate \nappendectomy in the treatment of appendicular mass is a \nsafe and effective treatment option.34 \n \nDas et al conducted a retrospective analysis on 112 patients \nof appendicular mass who were divided into 56 patients who \nunderwent immediate appendectomy and 56 underwent \nconservative treatment. The length of hospital stay was less \nin the appendectomy group. They were discharged home \nsooner than the group that underwent conservative \ntreatment. Early appendectomy is curative, cost- effective and \nreduces hospital stay in the management of appendicular \nmass. This was also confirmed by obaidi et al who came with \nthe same conclusions in his study.35,36  \n \nTiwary et al in their study of 54 patients with appendicular \nmass were divided into 2 groups of 27 patients each who \n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 672\n\n\n\n\n\n\n\n\nCurrent management of appendicular mass-narrative review article\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                673 \n\n\n\nunderwent immediate appendectomy and conservative \ntreatment. The infection rates were the same in both groups \nbut the stay in hospital was shorter in the appendectomy \ngroup. Early appendectomy is better in the treatment of \nappendicular mass as it is associated with shorter stay and \nreduced cost and eliminates the need for a second \nadmission.37   \n \nPathan et al in his prospective observational study of 100 \npatients of appendicular mass also noted that the length of \nhospital stay was reduced in the immediate appendectomy \ngroup. It was also associated with faster return to work and \nlow economic burden. This conclusion was also observed by \nIsrar in his observational study that immediate \nappendectomy was safe and effective.38,39   \n \nLaparoscopic appendectomy has been emerging as an \nalternative to the management of appendicular mass. \nSeveral retrospective studies were done on the role of \nlaparoscopic appendectomy in the management of \nappendicular mass. The mean operation time was longer but \nthe use of postoperative analgesia and the stay in the \nhospital was reduced. The advantage of laparoscopic \nappendectomy was adequate access and visualisation of the \nperitoneum, lower risk of adhesion and faster mobility. Hence \nlaparoscopic appendectomy is a feasible option in the \nmanagement of appendicular mass.40\u201344 \n \nThe World Society of Emergency Surgeons Jerusalem \nguidelines of 2020 recommended that in the management of \nappendicular mass, laparoscopic surgery is a safe and \nfeasible treatment option if it is done in experienced hands. \nIt is associated with fewer admissions and fewer additional \ninterventions.21 \n \nThe drawback of most of these studies is that they are \nretrospective in nature with small sample sizes. There were \nalso concerns that acute appendicitis is an emergency \nprocedure and most of the appendectomies were performed \nby junior specialists and registrars which could account for \nthe higher post operative wound infection rates. Most of the \nstudies that used laparoscopic appendectomy in the \nmanagement of appendicular used senior surgeons who had \nexperience in laparoscopic surgery, and this could account \nfor the better outcomes. It is hoped that future randomized \ncontrol trials can be conducted in terms of the use of \nlaparoscopic appendectomy in the management of \nappendicular mass. \n \n \nCONCLUSION \nBased on the available evidence, the management of \nappendicular mass should be done with immediate \nappendectomy and laparoscopic appendectomy should be \nthe surgery of choice. If facilities for laparoscopic \nappendectomy are not available then conservative treatment \nshould be done for the patient and for patients above the age \nof 40 years, they can be followed by computerised \ntomography and colonoscopy. Interval appendectomy is not \nrequired, and it is only indicated for patients who present \nwith recurrent symptoms. \n \n \n\n\n\nCONFLICT OF INTEREST \nThere is no conflict of interest related to this review article. \n \n \nREFERENCES \n1. Sartelli M, Baiocchi GL, Di Saverio S, Ferrara F, Labricciosa FM, \n\n\n\nAnsaloni L, et al. Prospective Observational Study on acute \nAppendicitis Worldwide (POSAW). World J Emerg Surg 2018; 13: \n19.  \n\n\n\n2. Bailey H. The Ochsner-Sherren (Delayed) Treatment of acute \nappendicitis: Indications and technique. Br Med J 1930; 1(3603): \n140-3.  \n\n\n\n3. Dhanasekharan N, Raj P, Ganeshram P, Venkatesan V. Does \nOchsner-Sherren Regimen Still Hold True in the Management of \nAppendicular Mass? Ochsner-Sherren Rejimi Halen Apendik\u00fcler \nKitle Tedavisinin D\u00fczenlenmesinde Ge\u00e7erli Midir? Ulus Travma \nAcil Cerrahi Derg 2010; 16(1): 43-6. \n\n\n\n4. Arshad M, Noshad AS. 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Sajid MS, Ray K, Hebbar M, Riaz W, Baig MK, Sains P, et al. South \nCoast appendicular mass management (SCAM) survey. Transl \nGastroenterol Hepatol 2020; 5: 4.  \n\n\n\n16. Kim JK, Ryoo S, Oh HK, et al. Management of appendicitis \npresenting with abscess or mass. J Korean Soc Coloproctol 2010; \n26(6): 413-9.  \n\n\n\n17. Garba ES, Ahmed A. Management of appendiceal mass. Ann Afr \nMed 2008; 7(4): 200-4.  \n\n\n\n18. Simillis C, Symeonides P, Shorthouse AJ, Tekkis PP. A meta-\nanalysis comparing conservative treatment versus acute \nappendectomy for complicated appendicitis (abscess or \nphlegmon). Surgery 2010; 147(6): 818-29.  \n\n\n\n19. Gorter RR, Eker HH, Gorter-Stam MAW, et al. Diagnosis and \nmanagement of acute appendicitis. EAES consensus development \nconference 2015. Surg Endosc 2016; 30(11): 4668-90.  \n\n\n\n20. Di Saverio S, Podda M, De Simone B, Ceresoli M, Augustin G, \nGori A, et al. 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Y\u0131lmaz Y, Kamer E, Acar N, Etlik MN, G\u00fcng\u00f6r M, Kar H, et al. \nApproach to appendiceal masses due to acute appendicitis: \nAnalysis of 126 Cases. Turkish J Colorectal 2020; 30: 134-7. \n\n\n\n24. Panahi P, Ibrahim R, Veeralakshmanan P, Ackah J, Coleman M. \nAppendiceal phlegmon in adults: Do we know how to manage it \nyet? Ann Med Surg (Lond) 2020; 59: 274-7.  \n\n\n\n25. Malik AA, Wani ML, Wani SN, Parray FQ, Nayeem-Ul-Hassan, \nIrshad I. Appendiceal mass: Is interval appendicectomy \n\u201csomething of the past\u201d? World J Gastroenterol 2011; 17(25): \n2977-80.  \n\n\n\n26. Quartey B. Interval appendectomy in adults: A necessary evil. J \nEmerg Trauma Shock 2012; 5(3): 213-6.  \n\n\n\n27. Malik AA, Wani ML, Wani SN, Parray FQ, Nayeem-Ul-Hassan, \nIrshad I. Evaluating conservative treatment for acute \nappendicitis with lump formation. J Emerg Trauma Shock 2012; \n5(1): 33-5.  \n\n\n\n28. Tingstedt B, Bexe-Lindskog E, Ekelund M, Anderson R. \nManagement of Appendiceal Masses.  \n\n\n\n29. Andersson RE, Petzold MG. Nonsurgical treatment of \nappendiceal abscess or phlegmon: A systematic review and \nmeta-analysis. Ann Surg 2007; 246(5): 741-8.  \n\n\n\n30. Fugazzola P, Coccolini F, Tomasoni M, Stella M, Ansaloni L. Early \nappendectomy vs. conservative management in complicated \nacute appendicitis in children: A meta-analysis. J Pediatr Surg \n2019; 54(11): 2234-41.  \n\n\n\n31. Bahram MA. Evaluation of early surgical management of \ncomplicated appendicitis by appendicular mass. International \nJournal of Surgery 2011; 9(1): 101-3.  \n\n\n\n32. Ali M, Jahan KI. Early appendicectomy in appendicular mass-\nreview of literature. Journal of Surgical Science 2016; 20(1): 33-\n35.   \n\n\n\n33. Ali Khan S, Ali M, Seerat MI. Efficacy of early exploration in \nappendicular mass. Pakistan Journal of Medical & Health \nSciences 2016; 10(3): 781-3. \n\n\n\n34. Arshad M, Aziz LA, Qasim M, Altaf K, Talpur H. Early \nappendicectomy in appendicular mass--a Liaquat University \nHospital experience. J Ayub Med Coll Abbottabad 2008; 20(1): \n70-2. \n\n\n\n35. Das BB, Nayak KN, Mohanty SK, Sahoo AK. A retrospective \nanalysis of conservative management versus early surgical \nintervention in appendicular lump. Cureus 2022; 14(1): e21784. \n\n\n\n36. Hussein Al-Obaidi J. Early appendectomy in appendicular mass. \nBionatura 2022; 7(4): 1-4.  \n\n\n\n37. Tiwary A, Huda T, Bansal V, Mishra N. Redefining management \nstrategy for an appendicular lump. Int J Surg Med 2020; 6(5): 33-\n7. \n\n\n\n38. Fahad Pathan M, Irfan Nizammani M, Elfattah Atieh A, \nShahabuddin Memon M, Shaikh S. Comparative study of \nimmediate surgical intervention versus conservative treatment in \nappendicular lump. Indo American Journal of Pharmaceutical \nSciences 2018; 5(1): 606-10. \n\n\n\n39. Israr S, Akhtar J, Taqvi SMRH, Zamir N. Early surgical \nmanagement of appendicular mass in pediatric patients. J Coll \nPhysicians Surg Pak. 2021; 31(3): 302-6. \n\n\n\n40. Shindholimath V, Thinakaran K, Rao T, Veerappa Y. \nLaparoscopic management of appendicular mass. J Minim \nAccess Surg 2011; 7(2): 136-40.  \n\n\n\n41. Prasad BH, Prasanth G. Laparoscopic management of \nappendicular mass. International Surgery Journal 2018; 5(4): \n1259-62. \n\n\n\n42. Deba Kumar C, Abhijit S, Arupjyoti B, Kumar Choudhury D. \nLaparoscopic Appendicectomy in Appendicular Lump. \nInternational Journal of Pharmaceutical Science Invention, \n2013; 2(12): 1-2. \n\n\n\n43. Chowdhury MZ, Farooq MA Al, Rahman MAM, Chowdhury TK. \nManagement of early appendicular lump in children - \nLaparoscopic technique versus open surgery: A comparative \nstudy in low-middle income country perspective. World J Pediatr \nSurg 2020; 3(2).  \n\n\n\n44. Garg CP, Vaidya BB, Chengalath MM. Efficacy of laparoscopy in \ncomplicated appendicitis. Int J Surg 2009; 7(3): 250-2.  \n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 674\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                675 \n\n\n\nABSTRACT \nIntroduction: Postpartum depression (PPD) is a mental and \nemotional condition that can affect women during their first \npostnatal year and concern globally. This study aimed to \ndetermine the overall prevalence and determinants of \npostpartum depression (PPD) in Association of Southeast \nAsian Nations (ASEAN) countries. \n \nMaterials and Methods: A systematic search of \nobservational studies conducted in ASEAN countries \nbetween 1 January 2010 and 31 December 2020 was \nperformed in the Medline, PubMed and Google Scholar \ndatabases. The quality of studies was evaluated based on \nThe Joanna Briggs Institute Checklist. The analysis was \nperformed with Review Manager software version 5.4. Meta-\nanalysis of the estimates from primary studies was \nconducted by adjusting for possible publication bias and \nheterogeneity.  \n \nResults: Twenty-five studies including 19924 postnatal \nmothers were included in this review. The pooled prevalence \nof PPD is 22.32% (95% CI: 18.48, 26.17). Thailand has the \nhighest prevalence of PPD with a pooled prevalence of \n74.1% (95% CI: 64.79, 83.41). The prevalence of PPD was \nhighest when the assessment for PPD was conducted up to \n6 weeks postpartum with a pooled prevalence of 25.24% \n(95% CI: 14.08, 36.41). The identified determinants of PPD \nwere unplanned pregnancy, term pregnancy, lack of family \nsupport and physical violence. There were limited studies \ndone and high heterogeneity in terms of quality, \nmethodology, culture, screening method and time of PPD \nmeasurement. \n \nConclusions: Approximately one in five postpartum women \nin ASEAN countries had PPD. The risk factor that lowers the \nrisk of PPD is unplanned and term pregnancies, while \nwomen with a lack of family support and experienced \nphysical violence increase the risk of PPD. Robust \nprevalence studies are needed to assess the magnitude of \nthis problem in ASEAN countries.     \n \nKEYWORDS:  \nPostnatal depression, postpartum depression, ASEAN countries, \nrisk of postpartum depression \n \n\n\n\nINTRODUCTION \nPostpartum depression (PPD) is a mental and emotional \ncondition that can affect women during their first postnatal \nyear and is a concern globally.1 It involves the woman herself \nand the family institution and, subsequently, the economy of \nthe family itself.2 PPD is often overlooked and causes \nmorbidity to new mothers and their families. PPD is defined \nas a major depressive episode \u2018with peripartum onset if the \nonset of mood symptoms occurs during pregnancy or within \nfour weeks following deliveries\u2019 based on the Diagnostic and \nStatistical Manual of Mental Disorders, fifth edition (DSM-5). \nMultiple studies and clinical practices define PPD as \noccurring within 4 weeks after childbirth, 3 months, 6 months \nor up to 12 months after delivery. \n \nA recent systematic review and meta-analysis by Abel et al.3 \non 58 studies conducted between 2007 and 2017 reported \nthat the PPD prevalence ranged between 18.2% and 25.6%. \nThey also highlighted that the prevalence was higher in low-\nincome countries, with a pooled prevalence of 25.8%, \ncompared to middle-income countries, which was 20.7%. \nWang et al.4 conducted a systematic review and meta-\nanalysis among 565 studies involving 1,236 365 women from \ninception and July 2021 found that the global prevalence of \nPPD is 17.22% (95% CI: 16.00, 18.51). They reported that \nSouth Africa has the highest prevalence, which is 39.96%.  \n \nThe literature on PPD revealed several risk factors that can \ncontribute to women\u2019s PPD. The risk factors are different \namong the developed and developing countries. It can be \ndivided into socio-demographic categories, marital and \npregnancy factors and psychosocial factors. The examples of \nsocio-demographic factors are unintended or birth5\u20137, \noccupation and marital status8 and low socio-economic and \neducation status.6,9,10 For marital and pregnancy factors such \nas intimate partner violence,11 domestic violence5,12,13 \n\n\n\npsychosocial factors identified were partner conflict, \nperfectionism, lack of family and parental support, reduced \nsocial support,6,10,14 and depression during pregnancy or \nhistory of depression before pregnancy.5,10 \n \nASEAN countries comprise an intergovernmental \norganisation of 10 Southeast Asian countries: Brunei, \nCambodia, Indonesia, Laos, Malaysia, Myanmar, the \nPhilippines, Singapore, Thailand and Vietnam. The most \n\n\n\nA 10-year systematic review and meta-analysis of \ndeterminants of postpartum depression in the Association \nof Southeast Asian Nations countries \n \nSiti Syafiqah Sainuddin, MMed, Norhayati Mohd Noor, PhD, Azidah Abdul Kadir, PhD, Rosnani Zakaria, \nFRACGP \n\n\n\n     \nDepartment of Family Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia\n\n\n\nSYSTEMATIC / NARRATIVE REVIEW ARTICLE\n\n\n\n This article was accepted: 17 August 2023                                                                                                                                                                         \nCorresponding Author: Prof Azidah Abdul Kadir                                                                                                                                                                 \nEmail: azidahkb@usm.my \n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 675\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n676                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nstriking characteristic of ASEAN countries is that it has a wide \ndiversity of socio-cultural, hence different socio-economic \nstatuses. We find many studies related to PPD in developed \nand other developing countries but very limited studies \nrelated to ASEAN countries. This can be due to a lack of \nexposure and intervention about PPD in women.  \n \nTherefore, in this systematic review and meta-analyses, we \naimed to estimate the overall prevalence of PPD and its \ndeterminants in ASEAN countries. Findings from this study \nwill be used to identify the need for early screening and \ndetection, encourage the development of an intervention to \nreduce its occurrence and support women with PPD. \n\n\n\n \n \nMATERIALS AND METHODS \nA systematic review and meta-analysis of studies were \nconducted according to the Preferred Reporting Items for \nSystematic Reviews and Meta-Analyses (PRISMA) \nguidelines.15 The protocol for this systematic review and \nmeta-analysis has been registered in the PROSPERO (Protocol \nNo. CRD42021234127), and the protocol includes only the \ndeterminants of PPD in ASEAN countries. The inclusion \ncriteria are studies conducted in ASEAN countries that report \nthe prevalence and determinants of PPD over 10 years from \n1st January 2010 to 31st December 2020. Studies with cross-\nsectional, case\u2013control and cohort designs published in \nEnglish were included. Case series/reports, conference papers, \nproceedings, articles available only in abstract form, editorial \nreviews, letters of communication, commentaries and \nqualitative studies were excluded. \n \nA systematic search was performed in the Medline (PubMed) \nand Google Scholar databases for articles between 1st \nJanuary 2010 and 31st December 2020. The investigation \nwas done using the Medical Subject Headings (MeSH) search \nterms: \u2018determinants,\u2019 \u2018risk factors,\u2019 \u2018postnatal depression,\u2019 \n\u2018perinatal depression,\u2019 \u2018maternal depression\u2019 and \u2018maternal \nblues\u2019. Reference lists of included citations were cross-checked \nto find additional potentially eligible studies. \n \nAll records identified by our search strategy were exported to \nEndNote X8 software. Duplicate articles were removed. Two \nindependent reviewers screened the titles and abstracts of the \nidentified themes. The full texts of eligible studies were \nobtained and read thoroughly to assess their suitability. In a \nconflict between the two reviewers, a consensus discussion \nwas held, and a third reviewer was consulted.  \n \nThe data were extracted into Microsoft Excel. This included \nfirst author, year of publication, study location, study design, \nsetting, study population, sample size, PPD definition, risk \nfactors and data for the calculation of effect estimates. Data \nfor risk factors included physical and biological, \npsychological, obstetric, paediatrics, socio-demographic and \ncultural factors. \n \nA critical appraisal was done to assess the data quality using \nthe Joanna Briggs Institute Meta-Analysis for cross-sectional, \ncase\u2013control and cohort studies (Aromataris and Munn, \n2020). The risk of bias was considered low when more than \n70% of the answers were \u2018yes,\u2019 moderate when 50\u201369% of the \nresponses were \u2018yes\u2019 and high when up to 0%\u201349% of the \n\n\n\nanswers were \u2018yes.\u2019 The risk factors were reported as an odds \nratio with a 95% confidence interval. The analysis was \nperformed with Review Manager software version 5.4 (Nordic \nCochrane Centre). We used a random-effects model to pool \ndata. The I2 statistic was used to assess heterogeneity and use \nthe guide as outlined: 0%\u201340% might not be necessary; 30%\u2013\n60% may represent moderate heterogeneity; 50%\u201390% may \nrepresent substantial heterogeneity and 75%\u2013100% would be \nconsiderable heterogeneity; 50%\u201390% may represent \nsignificant heterogeneity 17Subgroup analysis was \nperformed based on ASEAN countries and the time of \nassessment of the study design. Funnel plots were used to \nassess the publication bias. \n \n \nRESULTS \nCharacteristics of the Included Studies \nA total of 7609 articles were retrieved through an electronic \nsearch, of which 7559 were eligible for assessment after \nremoving ten duplicate records. Of the 7559 articles screened \nfor eligibility, 7250 were excluded. A total of 349 articles \nunderwent full-text evaluation for eligibility, of which 312 \nwere excluded because articleswere not from ASEAN \ncountries (n = 293) but only prenatal depression (n = 19). In \nthis review, 37 articles underwent quality assessment, of \nwhich 25 articles with low risk of bias were included in the \nfinal analysis, as shown in Fig 1, whereas four studies with a \nmoderate risk of bias and six studies with a high risk of bias \nwere excluded. \n \nTable I shows 25 studies included in this review: Malaysia (n \n= 4),11,16\u201318 Singapore (n = 3),19\u201321 Thailand (n = 5),14,22\u201325  \nIndonesia (n = 6),26\u201331, Vietnam (n = 5),32\u201336, Philippines \n(n = 1)8 and Laos (n = 1)37. Fifteen studies were cross-\nsectional,8,11,14,16,22,23,26,28\u201332,34,36,37 two were case\u2013control,19,24 and \neight were cohort studies.17,18,20,21,25,27,33,35 According to the data, \nthe smallest sample size was 31 women, and the largest was \n6636 women. The majority of the included studies used \nEdinburgh Postnatal Depression Scale (EPDS), which is 21 \nstudies out of 25.8,11,14,17,18,20,21,23\u201331,33\u201337 From this, nine studies \nusing cut-off points \u226512,11,14,17,18,23,28,30,34,36 seven studies using cut-\noff points \u226510,8,21,25,26,29,35,37 two studies using cut-off point \n\u226513,20,27 one study using cut-off point \u2265433 and \u22651124, \nrespectively, and one study not explicitly mentioned the cut-\noff point.31 Other than that, four studies using different types \nof measures of PPD, which are Mini International \nNeuropsychiatric Interview (MINI),16 The Diagnostic and \nStatistical Manual of Mental Disorders, fourth edition (DSM-\nIV),19 Center for Epidemiological Studies Depression Scale \n(CES-D)22 and Case-Finding Instruments for Depression.32  \n \nPrevalence of PPD in ASEAN Countries \nA total of 25 studies were included, with a total of 19,924 \nsamples size. The pooled prevalence of PPD was 22.32% (95% \nCI: 18.48, 26.17). Figures 2 and 3 show a funnel plot. A \nsubgroup analysis based on countries was performed in \nFigure 4. Thailand showed the highest pooled prevalence of \nwomen with PPD, which is 74.10% (95% CI: 64.79, 83.41). \nThis is because the study22 was done among a particular \ngroup population of women with human immunodeficiency \nvirus and a small sample size of 85 mothers. Apart from that, \na limited number of studies are available, such as Laos37 and \nThe Philippines.8 \n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 676\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                677 \n\n\n\nN\no.\n\n\n\n   \nA\n\n\n\nut\nho\n\n\n\nr \n   \n\n\n\n\n\n\n\n\n\n\n\n   \nSt\n\n\n\nud\ny \n\n\n\nar\nea\n\n\n\n\n\n\n\n\n\n\n\n   \n S\n\n\n\ntu\ndy\n\n\n\n\n\n\n\n\n\n\n\n  S\nam\n\n\n\npl\ne \n\n\n\n   \n  M\n\n\n\nea\nsu\n\n\n\nre\ns \n\n\n\n\n\n\n\n P\nre\n\n\n\nva\nle\n\n\n\nnc\ne \n\n\n\n\n\n\n\n   \n T\n\n\n\nim\ne \n\n\n\nof\n a\n\n\n\nss\nes\n\n\n\nsm\nen\n\n\n\nt  \n   \n\n\n\n\n\n\n\n\n\n\n\nFa\nct\n\n\n\nor\ns \n\n\n\nas\nso\n\n\n\nci\nat\n\n\n\ned\n w\n\n\n\nith\n P\n\n\n\nPD\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(R\neg\n\n\n\nio\nn)\n\n\n\n\n\n\n\n\n\n\n\n   \n d\n\n\n\nes\nig\n\n\n\nn\n   \n\n\n\n\n\n\n\n\n\n\n\nSi\nze\n\n\n\n\n\n\n\n\n\n\n\nof\n P\n\n\n\nPD\n   \n\n\n\n\n\n\n\n o\nf P\n\n\n\nPD\n (%\n\n\n\n) \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n1\n   \n\n\n\n   \nZa\n\n\n\nin\nal\n\n\n\n e\nt \n\n\n\nal\n.16\n\n\n\n\n\n\n\n   \n  M\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\n\n\n\n\n\n\n\n\nC\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 4\n\n\n\n11\n   \n\n\n\n\n\n\n\n   \n M\n\n\n\nIN\nI \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n6.\n8\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n6\u2013\n\n\n\n8 \nw\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n H\no\n\n\n\nu\nse\n\n\n\nw\nif\n\n\n\ne \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nC\n\n\n\nae\nsa\n\n\n\nri\nan\n\n\n\n s\nec\n\n\n\nti\no\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPr\nev\n\n\n\nio\nu\n\n\n\ns \nh\n\n\n\nis\nto\n\n\n\nry\n o\n\n\n\nf \nd\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nN\no\n\n\n\nn\n-e\n\n\n\nxc\nlu\n\n\n\nsi\nve\n\n\n\n b\nre\n\n\n\nas\ntf\n\n\n\nee\nd\n\n\n\nin\ng\n\n\n\n \n2\n\n\n\n\n\n\n\nY\nu\n\n\n\nsu\nff\n\n\n\n e\nt \n\n\n\nal\n.17\n\n\n\n\n\n\n\n   \n M\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\n\n\n\n\n\n\n\n\nC\no\n\n\n\nh\no\n\n\n\nrt\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  2\n\n\n\n07\n2\n\n\n\n\n\n\n\n   \n  E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n14\n.3\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 1\n, 3\n\n\n\n a\nn\n\n\n\nd\n 6\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n W\no\n\n\n\nm\nen\n\n\n\n d\nep\n\n\n\nre\nss\n\n\n\ned\n d\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n W\n\n\n\no\nm\n\n\n\nen\n w\n\n\n\nit\nh\n\n\n\n c\no\n\n\n\nn\nsi\n\n\n\nst\nen\n\n\n\nt \nw\n\n\n\no\nrr\n\n\n\nie\ns \n\n\n\no\nf \n\n\n\nn\new\n\n\n\nb\no\n\n\n\nrn\n \n\n\n\n3\n   \n\n\n\n   \nN\n\n\n\no\nrh\n\n\n\nay\nat\n\n\n\ni \n   \n\n\n\n\n\n\n\n\n\n\n\nM\nal\n\n\n\nay\nsi\n\n\n\na\n   \n\n\n\n\n\n\n\n   \nC\n\n\n\no\nh\n\n\n\no\nrt\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  7\n42\n\n\n\n\n\n\n\n\n\n\n\n E\nPD\n\n\n\nS\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n4.\n\n\n\n8\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n1 \nan\n\n\n\nd\n 6\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n   \n -\n\n\n\n M\no\n\n\n\nth\ner\n\n\n\n w\nit\n\n\n\nh\n S\n\n\n\nM\nM\n\n\n\n\n\n\n\n   \n  e\n\n\n\nt \nal\n\n\n\n.18\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  2\n\n\n\n.1\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n1 \nan\n\n\n\nd\n 6\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n   \n -\n\n\n\n M\no\n\n\n\nth\ner\n\n\n\n w\nit\n\n\n\nh\no\n\n\n\nu\nt \n\n\n\nSM\nM\n\n\n\n \n4\n\n\n\n\n\n\n\nA\nh\n\n\n\nm\nad\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \nM\n\n\n\nal\nay\n\n\n\nsi\na\n\n\n\n\n\n\n\n\n\n\n\nC\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 6\n\n\n\n63\n9\n\n\n\n\n\n\n\n   \n  E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n4\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n6\u2013\n\n\n\n16\n w\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n  -\n E\n\n\n\nxp\no\n\n\n\nse\nd\n\n\n\n t\no\n\n\n\n in\nti\n\n\n\nm\nat\n\n\n\ne \np\n\n\n\nar\ntn\n\n\n\ner\n v\n\n\n\nio\nle\n\n\n\nn\nce\n\n\n\n\n\n\n\n   \n  e\n\n\n\nt \nal\n\n\n\n.11\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n E\nm\n\n\n\no\nti\n\n\n\no\nn\n\n\n\nal\n v\n\n\n\nio\nle\n\n\n\nn\nce\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nU\n\n\n\nn\np\n\n\n\nla\nn\n\n\n\nn\ned\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLa\n\n\n\nck\n o\n\n\n\nf \nfa\n\n\n\nm\nily\n\n\n\n s\nu\n\n\n\np\np\n\n\n\no\nrt\n\n\n\n d\nu\n\n\n\nri\nn\n\n\n\ng\n c\n\n\n\no\nn\n\n\n\nfi\nn\n\n\n\nem\nen\n\n\n\nt \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPa\n\n\n\nrt\nn\n\n\n\ner\n\u2019s\n\n\n\n u\nse\n\n\n\n o\nf \n\n\n\nal\nco\n\n\n\nh\no\n\n\n\nl \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nB\n\n\n\nei\nn\n\n\n\ng\n f\n\n\n\nro\nm\n\n\n\n h\no\n\n\n\nu\nse\n\n\n\nh\no\n\n\n\nld\n w\n\n\n\nit\nh\n\n\n\n a\n lo\n\n\n\nw\n in\n\n\n\nco\nm\n\n\n\ne \n5\n\n\n\n\n\n\n\nSu\nh\n\n\n\nit\nh\n\n\n\nar\nan\n\n\n\n\n\n\n\n\n\n\n\n   \nSi\n\n\n\nn\ng\n\n\n\nap\no\n\n\n\nre\n   \n\n\n\n\n\n\n\n C\nas\n\n\n\ne\u2013\nco\n\n\n\nn\ntr\n\n\n\no\nl \n\n\n\n\n\n\n\n   \n74\n\n\n\n4\n   \n\n\n\n\n\n\n\n   \n D\n\n\n\nSM\n-I\n\n\n\nV\n   \n\n\n\n\n\n\n\n   \n  1\n\n\n\n2.\n9\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 4\n\u20138\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n -\n A\n\n\n\nb\nse\n\n\n\nn\nce\n\n\n\n o\nf \n\n\n\nla\nb\n\n\n\no\nu\n\n\n\nr \nep\n\n\n\nid\nu\n\n\n\nra\nl a\n\n\n\nn\nal\n\n\n\ng\nes\n\n\n\nia\n \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n.19\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n In\n\n\n\ncr\nea\n\n\n\nsi\nn\n\n\n\ng\n a\n\n\n\ng\ne \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nFa\nm\n\n\n\nily\n h\n\n\n\nis\nto\n\n\n\nry\n o\n\n\n\nf \nd\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nH\nis\n\n\n\nto\nry\n\n\n\n o\nf \n\n\n\nd\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPr\n\n\n\nev\nio\n\n\n\nu\ns \n\n\n\nh\nis\n\n\n\nto\nry\n\n\n\n o\nf \n\n\n\nPP\nD\n\n\n\n \n6\n\n\n\n\n\n\n\nTh\nam\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nSi\nn\n\n\n\ng\nap\n\n\n\no\nre\n\n\n\n\n\n\n\n   \n C\n\n\n\no\nh\n\n\n\no\nrt\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  1\n24\n\n\n\n7\n   \n\n\n\n\n\n\n\n  E\nPD\n\n\n\nS\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n20\n\n\n\n.1\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 3\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nB\no\n\n\n\nrd\ner\n\n\n\nlin\ne \n\n\n\nh\nig\n\n\n\nh\n d\n\n\n\nep\nre\n\n\n\nss\niv\n\n\n\ne/\n a\n\n\n\nn\nxi\n\n\n\net\ny \n\n\n\nsy\nm\n\n\n\np\nto\n\n\n\nm\ns \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n.24\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n P\n\n\n\no\no\n\n\n\nr \nsu\n\n\n\nb\nje\n\n\n\nct\niv\n\n\n\ne \nsl\n\n\n\nee\np\n\n\n\n q\nu\n\n\n\nal\nit\n\n\n\ny \nd\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n \n7\n\n\n\n\n\n\n\nTe\no\n\n\n\n e\nt \n\n\n\nal\n.20\n\n\n\n\n\n\n\n\n\n\n\n   \nSi\n\n\n\nn\ng\n\n\n\nap\no\n\n\n\nre\n   \n\n\n\n\n\n\n\n C\no\n\n\n\nh\no\n\n\n\nrt\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  1\n\n\n\n24\n9\n\n\n\n\n\n\n\n   \n  E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n9.\n8\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n1 \n\n\n\nm\no\n\n\n\nn\nth\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n -\n T\n\n\n\nra\nd\n\n\n\nit\nio\n\n\n\nn\nal\n\n\n\n-I\nn\n\n\n\nd\nia\n\n\n\nn\n-C\n\n\n\no\nn\n\n\n\nfi\nn\n\n\n\nem\nen\n\n\n\nt \nd\n\n\n\nie\nt \n\n\n\nas\nso\n\n\n\nci\nat\n\n\n\ned\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \nw\n\n\n\nit\nh\n\n\n\n le\nss\n\n\n\n P\nPD\n\n\n\n s\nym\n\n\n\np\nto\n\n\n\nm\ns \n\n\n\n8\n   \n\n\n\n   \nR\n\n\n\no\nss\n\n\n\n e\nt \n\n\n\nal\n.22\n\n\n\n\n\n\n\n\n\n\n\n  T\nh\n\n\n\nai\nla\n\n\n\nn\nd\n\n\n\n\n\n\n\n\n\n\n\nC\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 8\n\n\n\n5\n   \n\n\n\n\n\n\n\n\n\n\n\nC\nES\n\n\n\n-D\n   \n\n\n\n\n\n\n\n\n\n\n\n  7\n4.\n\n\n\n1\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 6\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n L\no\n\n\n\nw\n s\n\n\n\nel\nf-\n\n\n\nes\nte\n\n\n\nem\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nIn\nfa\n\n\n\nn\nt \n\n\n\nh\nea\n\n\n\nlt\nh\n\n\n\n s\nta\n\n\n\ntu\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLo\nw\n\n\n\n e\nd\n\n\n\nu\nca\n\n\n\nti\no\n\n\n\nn\n le\n\n\n\nve\nl \n\n\n\n9\n   \n\n\n\n   \nPa\n\n\n\nn\nya\n\n\n\nyo\nn\n\n\n\ng\n  \n\n\n\n\n\n\n\n\n\n\n\nTh\nai\n\n\n\nla\nn\n\n\n\nd\n   \n\n\n\n\n\n\n\n   \nC\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 1\n73\n\n\n\n1\n   \n\n\n\n\n\n\n\n  E\nPD\n\n\n\nS\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n8.\n\n\n\n4\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n12\n m\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n M\nat\n\n\n\ner\nn\n\n\n\nal\n h\n\n\n\nea\nlt\n\n\n\nh\n \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n.23\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n M\n\n\n\nar\nit\n\n\n\nal\n c\n\n\n\no\nn\n\n\n\nfl\nic\n\n\n\nt \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nEc\n\n\n\no\nn\n\n\n\no\nm\n\n\n\nic\n b\n\n\n\nu\nrd\n\n\n\nen\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nSt\nre\n\n\n\nss\nfu\n\n\n\nl l\nif\n\n\n\ne \nev\n\n\n\nen\nts\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPr\n\n\n\nev\nio\n\n\n\nu\ns \n\n\n\nd\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n \n10\n\n\n\n   \n R\n\n\n\no\no\n\n\n\nm\nru\n\n\n\nan\ng\n\n\n\nw\no\n\n\n\nn\ng\n\n\n\n   \nTh\n\n\n\nai\nla\n\n\n\nn\nd\n\n\n\n\n\n\n\n\n\n\n\nC\nas\n\n\n\ne\u2013\nco\n\n\n\nn\ntr\n\n\n\no\nl \n\n\n\n\n\n\n\n   \n31\n\n\n\n3\n   \n\n\n\n\n\n\n\n   \n E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n16\n.9\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 4\n\u20136\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n -\n H\n\n\n\nis\nto\n\n\n\nry\n o\n\n\n\nf \nlif\n\n\n\net\nim\n\n\n\ne \nm\n\n\n\naj\no\n\n\n\nr \nd\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n &\n\n\n\n P\nPD\n\n\n\n\n\n\n\n   \n  e\n\n\n\nt \nal\n\n\n\n.24\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n H\nis\n\n\n\nto\nry\n\n\n\n o\nf \n\n\n\nd\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n d\nu\n\n\n\nri\nn\n\n\n\ng\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nM\nu\n\n\n\nlt\nip\n\n\n\nar\nit\n\n\n\ny \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nU\n\n\n\nn\nw\n\n\n\nan\nte\n\n\n\nd\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nC\nh\n\n\n\nild\nca\n\n\n\nre\n s\n\n\n\ntr\nes\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPr\n\n\n\nem\nen\n\n\n\nst\nru\n\n\n\nal\n s\n\n\n\nyn\nd\n\n\n\nro\nm\n\n\n\ne \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nPa\n\n\n\nin\n s\n\n\n\nym\np\n\n\n\nto\nm\n\n\n\ns \nd\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n e\nar\n\n\n\nly\n p\n\n\n\nu\nrp\n\n\n\ner\niu\n\n\n\nm\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nU\nse\n\n\n\n o\nf \n\n\n\nca\nff\n\n\n\nei\nn\n\n\n\n d\nu\n\n\n\nri\nn\n\n\n\ng\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nB\nab\n\n\n\ny \nfe\n\n\n\ned\nin\n\n\n\ng\n p\n\n\n\nro\nb\n\n\n\nle\nm\n\n\n\n \n11\n\n\n\n   \n H\n\n\n\nas\nse\n\n\n\nrt\n e\n\n\n\nt \nal\n\n\n\n.14\n   \n\n\n\n\n\n\n\nTh\nai\n\n\n\nla\nn\n\n\n\nd\n   \n\n\n\n\n\n\n\n   \nC\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 2\n25\n\n\n\n\n\n\n\n\n\n\n\n E\nPD\n\n\n\nS\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n36\n\n\n\n.0\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n2 \nm\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n P\nar\n\n\n\ntn\ner\n\n\n\n c\no\n\n\n\nn\nfl\n\n\n\nic\nt \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPe\nrf\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nis\nm\n\n\n\n  \n12\n\n\n\n   \n P\n\n\n\nh\no\n\n\n\no\nsu\n\n\n\nw\nan\n\n\n\n\n\n\n\n\n\n\n\n  T\nh\n\n\n\nai\nla\n\n\n\nn\nd\n\n\n\n\n\n\n\n\n\n\n\nC\no\n\n\n\nh\no\n\n\n\nrt\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  4\n\n\n\n49\n   \n\n\n\n\n\n\n\n   \n E\n\n\n\nPD\nS\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n47\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 1\n a\n\n\n\nn\nd\n\n\n\n 3\n m\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n -\n L\n\n\n\no\nw\n\n\n\n in\nco\n\n\n\nm\ne \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n.25\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  -\n L\n\n\n\nim\nit\n\n\n\ned\n s\n\n\n\no\nci\n\n\n\nal\n s\n\n\n\nu\np\n\n\n\np\no\n\n\n\nrt\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLo\nw\n\n\n\n p\nsy\n\n\n\nch\no\n\n\n\nlo\ng\n\n\n\nic\nal\n\n\n\n w\nel\n\n\n\nl b\nei\n\n\n\nn\ng\n\n\n\n\n\n\n\nTa\nbl\n\n\n\ne \nI: \n\n\n\nSu\nm\n\n\n\nm\nar\n\n\n\ny \nof\n\n\n\n re\nse\n\n\n\nar\nch\n\n\n\n a\nrti\n\n\n\ncl\nes\n\n\n\n in\ncl\n\n\n\nud\ned\n\n\n\n in\n s\n\n\n\nys\nte\n\n\n\nm\nat\n\n\n\nic\n re\n\n\n\nvi\new\n\n\n\n a\nnd\n\n\n\n m\net\n\n\n\na-\nan\n\n\n\nal\nys\n\n\n\nis\n fo\n\n\n\nr P\nPD\n\n\n\n in\n A\n\n\n\nSE\nAN\n\n\n\n c\nou\n\n\n\nnt\nrie\n\n\n\ns\n\n\n\nco\nn\n\n\n\nt.\n...\n\n\n\n. p\ng\n\n\n\n 6\n78\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 677\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n678                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nN\no.\n\n\n\n   \nA\n\n\n\nut\nho\n\n\n\nr \n   \n\n\n\n\n\n\n\n\n\n\n\n   \nSt\n\n\n\nud\ny \n\n\n\nar\nea\n\n\n\n\n\n\n\n\n\n\n\n   \n S\n\n\n\ntu\ndy\n\n\n\n\n\n\n\n\n\n\n\n  S\nam\n\n\n\npl\ne \n\n\n\n   \n  M\n\n\n\nea\nsu\n\n\n\nre\ns \n\n\n\n\n\n\n\n P\nre\n\n\n\nva\nle\n\n\n\nnc\ne \n\n\n\n\n\n\n\n   \n T\n\n\n\nim\ne \n\n\n\nof\n a\n\n\n\nss\nes\n\n\n\nsm\nen\n\n\n\nt  \n   \n\n\n\n\n\n\n\n\n\n\n\nFa\nct\n\n\n\nor\ns \n\n\n\nas\nso\n\n\n\nci\nat\n\n\n\ned\n w\n\n\n\nith\n P\n\n\n\nPD\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(R\neg\n\n\n\nio\nn)\n\n\n\n\n\n\n\n\n\n\n\n   \n d\n\n\n\nes\nig\n\n\n\nn\n   \n\n\n\n\n\n\n\n\n\n\n\nSi\nze\n\n\n\n\n\n\n\n\n\n\n\nof\n P\n\n\n\nPD\n   \n\n\n\n\n\n\n\n o\nf P\n\n\n\nPD\n (%\n\n\n\n) \n13\n\n\n\n   \n D\n\n\n\nir\na \n\n\n\net\n a\n\n\n\nl.26\n   \n\n\n\n\n\n\n\n   \n  I\n\n\n\nn\nd\n\n\n\no\nn\n\n\n\nes\nia\n\n\n\n\n\n\n\n   \n  C\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 4\n4 \n\n\n\n\n\n\n\n   \n E\n\n\n\nPD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 2\n\n\n\n0.\n5\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 2\n m\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n- \nLo\n\n\n\nw\n m\n\n\n\nat\ner\n\n\n\nn\nal\n\n\n\n e\nd\n\n\n\nu\nca\n\n\n\nti\no\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPr\nim\n\n\n\nip\nar\n\n\n\nit\ny \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nM\nat\n\n\n\ner\nn\n\n\n\nal\n a\n\n\n\ng\ne \n\n\n\n<\n23\n\n\n\n y\nea\n\n\n\nrs\n o\n\n\n\nld\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nH\nav\n\n\n\ne \na \n\n\n\nh\nis\n\n\n\nto\nry\n\n\n\n o\nf \n\n\n\nch\nild\n\n\n\nre\nn\n\n\n\n d\nea\n\n\n\nth\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nU\nn\n\n\n\nw\nan\n\n\n\nte\nd\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n  \n14\n\n\n\n   \n N\n\n\n\nu\nrb\n\n\n\nae\nti\n\n\n\n e\nt \n\n\n\nal\n.27\n\n\n\n\n\n\n\nIn\nd\n\n\n\no\nn\n\n\n\nes\nia\n\n\n\n\n\n\n\n   \n  C\n\n\n\no\nh\n\n\n\no\nrt\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  2\n83\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n8.\n37\n\n\n\n\n\n\n\n\n\n\n\n   \n  1\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n -\n C\n\n\n\nh\nild\n\n\n\nca\nre\n\n\n\n s\ntr\n\n\n\nes\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n15\n\n\n\n.1\n9\n\n\n\n\n\n\n\n\n\n\n\n   \n  2\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nM\nar\n\n\n\nit\nal\n\n\n\n s\nat\n\n\n\nis\nfa\n\n\n\nct\nio\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n26\n\n\n\n.1\n5\n\n\n\n\n\n\n\n\n\n\n\n   \n  3\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLi\nfe\n\n\n\n s\ntr\n\n\n\nes\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nN\no\n\n\n\nn\n a\n\n\n\ncc\nep\n\n\n\nta\nn\n\n\n\nce\n o\n\n\n\nf \nb\n\n\n\nab\ny \n\n\n\ng\nen\n\n\n\nd\ner\n\n\n\n \n15\n\n\n\n   \n P\n\n\n\nu\ntr\n\n\n\nia\nrs\n\n\n\nih\n e\n\n\n\nt \nal\n\n\n\n, \n   \n\n\n\n   \nIn\n\n\n\nd\no\n\n\n\nn\nes\n\n\n\nia\n   \n\n\n\n\n\n\n\n  C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 2\n\n\n\n00\n   \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 1\n8.\n\n\n\n5\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 2\n\n\n\n\u20136\n w\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n L\nab\n\n\n\no\nr \n\n\n\nco\nm\n\n\n\np\nlic\n\n\n\nat\nio\n\n\n\nn\n \n\n\n\n\n\n\n\n  2\n01\n\n\n\n8\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n -\n U\n\n\n\nn\nw\n\n\n\nan\nte\n\n\n\nd\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLo\nw\n\n\n\n f\nam\n\n\n\nily\n in\n\n\n\nco\nm\n\n\n\ne \n16\n\n\n\n   \n N\n\n\n\nu\nrb\n\n\n\nae\nti\n\n\n\n e\nt \n\n\n\nal\n.28\n\n\n\n\n\n\n\nIn\nd\n\n\n\no\nn\n\n\n\nes\nia\n\n\n\n\n\n\n\n   \n  C\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 1\n66\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n9.\n88\n\n\n\n\n\n\n\n\n\n\n\n   \n  6\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n  -\n\n\n\n S\ntr\n\n\n\nes\nsf\n\n\n\nu\nl l\n\n\n\nif\ne \n\n\n\nev\nen\n\n\n\nts\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nC\nh\n\n\n\nild\nca\n\n\n\nre\n s\n\n\n\ntr\nes\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nM\n\n\n\nar\nit\n\n\n\nal\n s\n\n\n\nat\nis\n\n\n\nfa\nct\n\n\n\nio\nn\n\n\n\n \n17\n\n\n\n   \n U\n\n\n\nsn\naw\n\n\n\nat\ni e\n\n\n\nt \nal\n\n\n\n.31\n   \n\n\n\n  I\nn\n\n\n\nd\no\n\n\n\nn\nes\n\n\n\nia\n   \n\n\n\n\n\n\n\n  C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 1\n\n\n\n00\n   \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 4\n9.\n\n\n\n0\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n2 \nm\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n S\nm\n\n\n\nal\nle\n\n\n\nr \np\n\n\n\nar\nit\n\n\n\ny \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nW\n\n\n\no\nrk\n\n\n\nin\ng\n\n\n\n m\no\n\n\n\nth\ner\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLo\n\n\n\nw\ner\n\n\n\n h\nu\n\n\n\nsb\nan\n\n\n\nd\n s\n\n\n\nu\np\n\n\n\np\no\n\n\n\nrt\n \n\n\n\n18\n   \n\n\n\n P\nu\n\n\n\ntr\na \n\n\n\net\n a\n\n\n\nl.30\n   \n\n\n\n\n\n\n\n   \nIn\n\n\n\nd\no\n\n\n\nn\nes\n\n\n\nia\n   \n\n\n\n\n\n\n\n  C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 3\n\n\n\n1 \n   \n\n\n\n\n\n\n\n E\nPD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 3\n2.\n\n\n\n3\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n2 \nm\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n -\n\n\n\n M\nat\n\n\n\ner\nn\n\n\n\nal\n a\n\n\n\ng\ne \n\n\n\no\nf \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n \n\n\n\n19\n   \n\n\n\n S\nu\n\n\n\nzu\nki\n\n\n\n e\nt \n\n\n\nal\n.32\n\n\n\n\n\n\n\n   \n V\n\n\n\nie\ntn\n\n\n\nam\n   \n\n\n\n\n\n\n\n   \n C\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 3\n00\n\n\n\n\n\n\n\n   \nC\n\n\n\nas\ne-\n\n\n\nFi\nn\n\n\n\nd\nin\n\n\n\ng\n  \n\n\n\n\n\n\n\n  2\n3.\n\n\n\n1\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 3\n\n\n\n m\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPa\nre\n\n\n\nn\nta\n\n\n\nl a\nn\n\n\n\nd\n f\n\n\n\nam\nili\n\n\n\nal\n c\n\n\n\no\nn\n\n\n\nfl\nic\n\n\n\nt \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  I\n\n\n\nn\nst\n\n\n\nru\nm\n\n\n\nen\nts\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nR\n\n\n\nec\nen\n\n\n\nt \nm\n\n\n\no\nvi\n\n\n\nn\ng\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  f\n\n\n\no\nr \n\n\n\nD\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n -\n L\n\n\n\nac\nk \n\n\n\no\nf \n\n\n\nco\nn\n\n\n\nfi\nd\n\n\n\nen\nce\n\n\n\n in\n c\n\n\n\nh\nild\n\n\n\nre\nar\n\n\n\nin\ng\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLe\n\n\n\nss\n r\n\n\n\nel\nax\n\n\n\ned\n f\n\n\n\nee\nin\n\n\n\ng\n t\n\n\n\no\nw\n\n\n\nar\nd\n\n\n\n t\nh\n\n\n\ne \nch\n\n\n\nild\n \n\n\n\n20\n   \n\n\n\n F\nis\n\n\n\nh\ner\n\n\n\n e\nt \n\n\n\nal\n.33\n\n\n\n\n\n\n\n   \n  V\n\n\n\nie\ntn\n\n\n\nam\n   \n\n\n\n\n\n\n\n   \n C\n\n\n\no\nh\n\n\n\no\nrt\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  4\n97\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 0\n\n\n\n.9\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n8 \nw\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n  -\n E\n\n\n\nxp\no\n\n\n\nsu\nre\n\n\n\n t\no\n\n\n\n e\nit\n\n\n\nh\ner\n\n\n\n li\nfe\n\n\n\nti\nm\n\n\n\ne \no\n\n\n\nr \np\n\n\n\ner\nin\n\n\n\nat\nal\n\n\n\n IP\nV\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n4\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n6 \n\n\n\nm\no\n\n\n\nn\nth\n\n\n\ns \np\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n(e\n\n\n\nm\no\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n a\nb\n\n\n\nu\nse\n\n\n\n, p\nh\n\n\n\nys\nic\n\n\n\nal\n a\n\n\n\nn\nd\n\n\n\n s\nex\n\n\n\nu\nal\n\n\n\n v\nio\n\n\n\nle\nn\n\n\n\nce\n  \n\n\n\n21\n   \n\n\n\n M\nu\n\n\n\nrr\nay\n\n\n\n e\nt \n\n\n\nal\n.34\n\n\n\n\n\n\n\n   \nV\n\n\n\nie\ntn\n\n\n\nam\n   \n\n\n\n\n\n\n\n   \n C\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 4\n31\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n8.\n1\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 6\n m\n\n\n\no\nn\n\n\n\nth\ns \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n- \nPo\n\n\n\nve\nrt\n\n\n\ny \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nFo\n\n\n\no\nd\n\n\n\n in\nse\n\n\n\ncu\nri\n\n\n\nty\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nB\nei\n\n\n\nn\ng\n\n\n\n f\nri\n\n\n\ng\nh\n\n\n\nte\nn\n\n\n\ned\n o\n\n\n\nf \nfa\n\n\n\nm\nily\n\n\n\n m\nem\n\n\n\nb\ner\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nIn\n\n\n\nti\nm\n\n\n\nat\ne \n\n\n\np\nar\n\n\n\ntn\ner\n\n\n\n v\nio\n\n\n\nle\nn\n\n\n\nce\n \n\n\n\n22\n   \n\n\n\n T\nh\n\n\n\no\n T\n\n\n\nra\nn\n\n\n\n e\nt \n\n\n\nal\n.35\n\n\n\n\n\n\n\nV\nie\n\n\n\ntn\nam\n\n\n\n\n\n\n\n\n\n\n\n C\no\n\n\n\nh\no\n\n\n\nrt\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n  1\n\n\n\n27\n4 \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 8\n.2\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n12\n\n\n\n w\nee\n\n\n\nks\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nW\no\n\n\n\nm\nen\n\n\n\n e\nxp\n\n\n\no\nse\n\n\n\nd\n t\n\n\n\no\n e\n\n\n\nm\no\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n v\nio\n\n\n\nle\nn\n\n\n\nce\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nTy\np\n\n\n\ne \no\n\n\n\nf \nem\n\n\n\np\nlo\n\n\n\nym\nen\n\n\n\nt \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLa\n\n\n\nck\n o\n\n\n\nf \nfa\n\n\n\nm\nily\n\n\n\n s\nu\n\n\n\np\np\n\n\n\no\nrt\n\n\n\n a\nft\n\n\n\ner\n d\n\n\n\nel\niv\n\n\n\ner\ny \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nLo\nw\n\n\n\ner\n le\n\n\n\nve\nl o\n\n\n\nf \ned\n\n\n\nu\nca\n\n\n\nti\no\n\n\n\nn\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nH\nu\n\n\n\nsb\nan\n\n\n\nd\n p\n\n\n\nre\nfe\n\n\n\nre\nn\n\n\n\nce\n f\n\n\n\no\nr \n\n\n\na \nsp\n\n\n\nec\nif\n\n\n\nic\n s\n\n\n\nex\n o\n\n\n\nf \nch\n\n\n\nild\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n- \n\n\n\nPr\nes\n\n\n\nen\nce\n\n\n\n o\nf \n\n\n\nm\nen\n\n\n\nta\nl d\n\n\n\nis\no\n\n\n\nrd\ner\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nD\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n d\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n \n23\n\n\n\n   \n D\n\n\n\no\n e\n\n\n\nt \nal\n\n\n\n, 2\n01\n\n\n\n8\n   \n\n\n\n\n\n\n\nV\nie\n\n\n\ntn\nam\n\n\n\n\n\n\n\n\n\n\n\n C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 1\n\n\n\n16\n   \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 2\n7.\n\n\n\n6\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n <\n\n\n\n 1\n y\n\n\n\nea\nr \n\n\n\np\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n  -\n L\n\n\n\no\nw\n\n\n\n le\nve\n\n\n\nl o\nf \n\n\n\ned\nu\n\n\n\nca\nti\n\n\n\no\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nB\n\n\n\nei\nn\n\n\n\ng\n t\n\n\n\nh\ne \n\n\n\nfi\nrs\n\n\n\nt-\nti\n\n\n\nm\ne \n\n\n\nm\no\n\n\n\nth\ner\n\n\n\ns \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nD\n\n\n\nis\nsa\n\n\n\nti\nsf\n\n\n\nac\nti\n\n\n\no\nn\n\n\n\n a\nb\n\n\n\no\nu\n\n\n\nt \nfa\n\n\n\nm\nily\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nLi\n\n\n\nm\nit\n\n\n\ned\n c\n\n\n\no\nm\n\n\n\nm\nu\n\n\n\nn\nic\n\n\n\nat\nio\n\n\n\nn\n a\n\n\n\nn\nd\n\n\n\n in\nte\n\n\n\nra\nct\n\n\n\nio\nn\n\n\n\n w\nit\n\n\n\nh\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \no\n\n\n\nth\ner\n\n\n\ns \n24\n\n\n\n   \n L\n\n\n\nab\nra\n\n\n\ng\nu\n\n\n\ne \net\n\n\n\n a\nl.8\n\n\n\n\n\n\n\nPh\nili\n\n\n\np\np\n\n\n\nin\nes\n\n\n\n\n\n\n\n   \nC\n\n\n\nro\nss\n\n\n\n-s\nec\n\n\n\nti\no\n\n\n\nn\nal\n\n\n\n\n\n\n\n 1\n65\n\n\n\n\n\n\n\n   \nEP\n\n\n\nD\nS \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n 1\n\n\n\n6.\n4\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 6\n w\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n\n\n\n\n  -\n O\n\n\n\ncc\nu\n\n\n\np\nat\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nM\n\n\n\nar\nit\n\n\n\nal\n s\n\n\n\nta\ntu\n\n\n\ns \n25\n\n\n\n   \n S\n\n\n\no\nu\n\n\n\np\nh\n\n\n\nal\nak\n\n\n\n\n\n\n\n\n\n\n\n   \n L\n\n\n\nao\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n C\nro\n\n\n\nss\n-s\n\n\n\nec\nti\n\n\n\no\nn\n\n\n\nal\n   \n\n\n\n   \n 4\n\n\n\n28\n   \n\n\n\n\n\n\n\nEP\nD\n\n\n\nS \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n 3\n1.\n\n\n\n8\n   \n\n\n\n\n\n\n\n\n\n\n\n   \n 6\n\n\n\n-8\n w\n\n\n\nee\nks\n\n\n\n p\no\n\n\n\nst\np\n\n\n\nar\ntu\n\n\n\nm\n   \n\n\n\n\n\n\n\n   \n  -\n\n\n\n U\nn\n\n\n\nin\nte\n\n\n\nn\nd\n\n\n\ned\n p\n\n\n\nre\ng\n\n\n\nn\nan\n\n\n\ncy\n \n\n\n\n\n\n\n\n  e\nt \n\n\n\nal\n, 2\n\n\n\n02\n0\n\n\n\n\n\n\n\n\n\n\n\n   \nLa\n\n\n\no\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n -\n L\n\n\n\no\nw\n\n\n\n b\nir\n\n\n\nth\n s\n\n\n\nat\nis\n\n\n\nfa\nct\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n- \nD\n\n\n\nep\nre\n\n\n\nss\nio\n\n\n\nn\n d\n\n\n\nu\nri\n\n\n\nn\ng\n\n\n\n p\nre\n\n\n\ng\nn\n\n\n\nan\ncy\n\n\n\n \n N\n\n\n\no\nte\n\n\n\n: P\nPD\n\n\n\n =\n p\n\n\n\no\nst\n\n\n\np\nar\n\n\n\ntu\nm\n\n\n\n d\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n, M\nIN\n\n\n\nI: \nM\n\n\n\nin\ni I\n\n\n\nn\nte\n\n\n\nrn\nat\n\n\n\nio\nn\n\n\n\nal\n N\n\n\n\neu\nro\n\n\n\np\nsy\n\n\n\nch\nia\n\n\n\ntr\nic\n\n\n\n In\nte\n\n\n\nrv\nie\n\n\n\nw\n, E\n\n\n\nPD\nS:\n\n\n\n E\nd\n\n\n\nin\nb\n\n\n\nu\nrg\n\n\n\n P\no\n\n\n\nst\nn\n\n\n\nat\nal\n\n\n\n D\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n S\nca\n\n\n\nle\n, D\n\n\n\nSM\n-I\n\n\n\nV\n: D\n\n\n\nia\ng\n\n\n\nn\no\n\n\n\nst\nic\n\n\n\n a\nn\n\n\n\nd\n S\n\n\n\nta\nti\n\n\n\nst\nic\n\n\n\nal\n M\n\n\n\nan\nu\n\n\n\nal\n o\n\n\n\nf \nM\n\n\n\nen\nta\n\n\n\nl D\nis\n\n\n\no\nrd\n\n\n\ner\ns,\n\n\n\n f\no\n\n\n\nu\nrt\n\n\n\nh\n e\n\n\n\nd\nit\n\n\n\nio\nn\n\n\n\n, C\nES\n\n\n\n-D\n: C\n\n\n\nen\nte\n\n\n\nr \nfo\n\n\n\nr \nEp\n\n\n\nid\nem\n\n\n\nio\nlo\n\n\n\ng\nic\n\n\n\nal\n S\n\n\n\ntu\nd\n\n\n\nie\ns \n\n\n\nD\nep\n\n\n\nre\nss\n\n\n\nio\nn\n\n\n\n S\nca\n\n\n\nle\n, I\n\n\n\nPV\n: I\n\n\n\nn\nti\n\n\n\nm\nat\n\n\n\ne \np\n\n\n\nar\ntn\n\n\n\ner\n v\n\n\n\nio\nle\n\n\n\nn\nce\n\n\n\n\n\n\n\nTa\nbl\n\n\n\ne \nI: \n\n\n\nSu\nm\n\n\n\nm\nar\n\n\n\ny \nof\n\n\n\n re\nse\n\n\n\nar\nch\n\n\n\n a\nrti\n\n\n\ncl\nes\n\n\n\n in\ncl\n\n\n\nud\ned\n\n\n\n in\n s\n\n\n\nys\nte\n\n\n\nm\nat\n\n\n\nic\n re\n\n\n\nvi\new\n\n\n\n a\nnd\n\n\n\n m\net\n\n\n\na-\nan\n\n\n\nal\nys\n\n\n\nis\n fo\n\n\n\nr P\nPD\n\n\n\n in\n A\n\n\n\nSE\nAN\n\n\n\n c\nou\n\n\n\nnt\nrie\n\n\n\ns\nco\n\n\n\nn\nt \n\n\n\nfr\no\n\n\n\nm\n...\n\n\n\n.. \np\n\n\n\ng\n 6\n\n\n\n77\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 678\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                679 \n\n\n\nFactors Affecting PPD \nA total of 25 studies reported risk factors for PPD. Similar \nfactors were searched for in each study. The selected studies \nidentified 23 risk factors, which were then divided into five \ngroups as shown in Table II: (1) Physical and biological \nfactors which include gestational diabetes in pregnancy,19,36 \nhypertension in pregnancy,19,36 health of the mothers;19,23,32 (2) \nPsychological factor such as history of family death,8,36 lack of \nfamily support,17,23,24,35 little family attachment,8,23,36 spouse \nassistance for child rearing,8,17,23,31 physical violence;23,35 (3) \nObstetric and paediatric factor which were unplanned \npregnancy,8,16,17,19,23,24,37 term pregnancy,8,23,35,37 low birth \nweight,8,32,37 types of delivery,8,16,17,19,37 labour difficulty,8,19,37 \nparity8,16,31,36,37 and breastfeeding;8,16,23,36 (4) Socio-demographic \nfactor which were mother age,8,16,17,23,26,30,31,35\u201337 mother \neducation level,8,17,19,26,30\u201332,35\u201337 marital status,8,19,23,37 \noccupational status of the mother,817,19,30\u201332,35,37 economic \nburden,23,32,37 type of family,8,36 urban area36,37 and (5) cultural \nfactor which include gender preferences.8,17,37  \n \nIn the meta-analyses, four factors were significantly \nassociated with PPD, as shown in Figures 6\u20139. There was an \nunplanned pregnancy, term pregnancy, poor family support \nand physical violence. Seven studies8,16,1719,23,24,37 with 5864 \nwomen were included to analyse the relationship between \nunplanned pregnancy and PPD. The pooled result showed \nthat women with unplanned pregnancies had a lower risk of \nPPD with an odd of 0.69 compared to women with planned \npregnancies (OR: 0.69, 95% CI: 0.53, 0.91). In comparison, \nfour studies8,23,35,37 with a total of 3598 women were included \nin this analysis for the association of term pregnancy with \nPPD. The pooled analysis showed that women with term \n\n\n\npregnancy had a lower risk of PPD with an odds of 0.55 \ncompared to women with preterm pregnancy (OR: 0.55, 95% \nCI: 0.40, 0.74). For the association of family support and PPD, \nfour studies17,23,24,35 were included for analysis, with a total of \n5390 women involved. The pooled result showed that women \nlacking family support had a higher risk of PPD with odds of \n5.10 compared to women with good family support (OR: \n5.10, 95% CI: 1.95, 13.38). Meanwhile, two studies23,35 were \nincluded with a total of 3005 women to assess the association \nbetween physical violence and PPD, which showed that \nwomen who experienced physical violence had a higher risk \nof PPD with the odds of 2.16 compared to women without \n(OR: 2.16, 95% CI:1.56, 2.99). \n \n \nDISCUSSION \nIn this study, we found that the pooled prevalence of PPD in \nASEAN countries was 22.32%, comparable with middle-\nincome countries, which were 20.8%;3 but lower than Middle \nEast countries, which were 27%.6 The prevalence of PPD in \nASEAN countries was higher than the recently reported \nglobal prevalence estimates of 17.22%.4 This estimated \nprevalence could be related to the limited number of research \navailable in ASEAN countries and the fact that most ASEAN \ncountries are from middle- and low-income countries.  \n \nBesides that, the pooled prevalence based on the subgroup \nanalysis of the time of assessment showed a higher \nprevalence in the first 6 weeks of postpartum, which was \n25.24%. This is slightly similar to the study3 whereby the \nprevalence of PPD was higher in the first ten weeks of \npostpartum. This is possibly due to women\u2019s attempts to \n\n\n\nVariables                                                                                                                      Number of studies \nPhysical and biological factors \n Gestational diabetes in pregnancy                                                                                    2 \n Hypertension in pregnancy                                                                                                2 \n Health of the mothers                                                                                                        3 \nPsychological factor \n History of family death                                                                                                       2 \n Lack of family support                                                                                                        4 \n Little family attachment                                                                                                     3 \n Spouse assistance for child-rearing                                                                                    4 \n Physical violence                                                                                                                  2 \nObstetric and paediatric factor \n Unplanned pregnancy                                                                                                         7 \n Term pregnancy                                                                                                                   4 \n Low birth weight                                                                                                                 3 \n Types of delivery                                                                                                                 5 \n Labour difficulty                                                                                                                  3 \n Parity                                                                                                                                    5 \n Breastfeeding                                                                                                                      4 \nSocio-demographic factor \n Mother age                                                                                                                         10 \n Mother education level                                                                                                      10 \n Marital status                                                                                                                       4 \n Occupation of the mothers                                                                                                8 \n Economic burden                                                                                                                 3 \n Type of family                                                                                                                      2 \n Urban area                                                                                                                           2 \nCultural factor \n Gender preferences                                                                                                             3 \n\n\n\nTable II: Summary of risk factors included in systematic review and meta-analysis for PPD in ASEAN countries\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 679\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n680                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nFig. 1: PRISMA flow diagram.\n\n\n\nadjust for babysitting and transition into motherhood. Other \nthan that, the possibility of hormone dysregulation following \nchildbirth also contributes to the depression.3 \n \nFrom our study, we found four significant risk factors \nassociated with PPD. There were unplanned pregnancy, term \npregnancy, poor family support and physical violence. \nAccording to current study findings, women experiencing \nphysical violence and lack or poor family support were at \nincreased risk of PPD. In this situation, usually after delivery, \nthe mother will go through a new phase and transition \nwhereby the mother needs support from the family to help, \nteach and manage the newborn. Hence, if they had a lack of \nsupport from family members or experienced physical \nviolence, it could aggravate women\u2019s condition and \ncontribute to PPD. These findings were similar to various \nsystematic reviews/meta-analysis as described below.3,38\u201340 \n\n\n\n\n\n\n\n\n\n\n\nAccording to a systematic review and meta-analysis on PPD \nand its association with adverse infant health outcomes in \nlow- and middle-income countries,3 a mother's stress and \ndepression symptoms could be worsened by a lack of social \nsupport because it affects the mother's self-confidence. Sawyer \net al.38 highlighted in a systematic review of postnatal \npsychological well-being in Africa that women who have \npoor support and marital/family conflict were associated \nwith depression. Domestic violence has been associated with \nperinatal mental disorders, including antenatal and PPD.39 A \nsystematic review and meta-analysis on domestic violence \nand perinatal mental disorders39 highlighted that women \nwith PPD reported a high prevalence and risk for intimate \npartner violence during the lifetime (OR 2.9, 95% CI 1.8\u20134.8), \nduring the past year (OR 2.8, 95% CI 1.7\u20134.6) and during \npregnancy (OR 4.4, 95% CI 2.9\u20136.5). These findings are \nconsistent with our results that demonstrated poor family \nsupport and intimate physical violence was associated with \nPPD.  \n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 680\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                681 \n\n\n\nFig. 2: Forest plot of the prevalence of PPD in ASEAN countries.\n\n\n\nFig. 3: Funnel plot for assessing publication bias.\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 681\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n682                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nFig. 4: Forest plot of a subgroup based on the countries for PPD.\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 682\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                683 \n\n\n\nFig. 5: Forest plot of the subgroup analysis based at different assessment time points for PPD.\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 683\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n684                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nFig. 6: Forest plot for association between unplanned pregnancy and PPD. \n\n\n\nFig. 7: Forest plot for association between term pregnancy and PPD.\n\n\n\nFig. 8: Forest plot for association between poor family support and PPD.\n\n\n\nFig. 9: Forest plot for association between physical violence and PPD.\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 684\n\n\n\n\n\n\n\n\nA 10-year systematic review and meta-analysis of determinants of postpartum depression \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                685 \n\n\n\nFor unplanned and preterm pregnancies, our study showed a \nlower risk of PPD and was in contrast with other studies,3,4,40 \nwhereby these risk factors favour PPD. This is probably due to \nthe minimal study from ASEAN countries, different tools in \nPPD assessment method, a wide range of PPD assessment \ntime, greater variety of sample size and cultural and \nbackground factors.  \n \nBased on the measurement tools used for diagnosis of PPD, \nabout 84% of included studies used EPDS, whereas 16% used \ndifferent diagnostic tools: MINI, DSM-IV, CES-D and Case-\nFinding Instruments for Depression. Out of 84%, eight \nstudies11,17,18,24,25,33,35,36 used validated EPDS, five studies14,27,28,34,37 \nused back-to-back translation and another eight \nstudies8,20,21,23,26,29\u201331 not mentioned about validation of EPDS. \nAll this has a significant impact on the result because of the \nconsiderable disparities, and the result is difficult to interpret. \nFurthermore, different cut-off points for EPDS also \nsignificantly impacted the result. According to Levis et al.40 a \ncut-off value of 11 or higher showed maximised sensitivity \nand specificity, and 12 of the included \nstudies11,14,17,18,20,23,24,27,28,30,34,36 using cut-off point \u226511. \n \nMore research on PPD would be beneficial in identifying \npostnatal depression in mothers as soon as possible after \ngiving birth and acting immediately to prevent morbidity, \ndeath, disabilities and negative impacts on the child's future \ndevelopment. This is especially crucial for the development of \nmaternal health care in ASEAN countries. Aside from that, \nthis research is limited to papers published in English and \nlimited studies about PPD in ASEAN countries. \n \n \nCONCLUSION \nThe prevalence of PPD in ASEAN countries was 22.32%. \nUnplanned and term pregnancies lower the risk of PPD, while \npoor family support and women who have experienced \nphysical violence increase the risk of PPD. This review also \nfound a very limited study among ASEAN countries and a \nscarcity of high-quality studies in ASEAN that can be used to \ngenerate generalisability evidence. More studies are needed \nto assess this problem\u2019s magnitude and plan a proper \nintervention program. Apart from that, the findings can be \nused to identify the need for early detection, encourage the \ndevelopment of an intervention to reduce its occurrence and \nsupport mothers with PPD. \n \n \nREFERENCES \n1. Almond P. Postnatal depression: a global public health \n\n\n\nperspective. Perspect Public Health. 2009; 129(5): 221\u20137. \n2. Klainin P, Arthur DG. Postpartum depression in Asian cultures: a \n\n\n\nliterature review. Int J Nurs Stud. 2009; 46(10): 1355\u201373. \n3. Dadi AF, Miller ER, Mwanri L. Postnatal depression and its \n\n\n\nassociation with adverse infant health outcomes in low- and \nmiddle-income countries: a systematic review and meta-analysis. \nBMC Pregnancy Childbirth. 2020; 20(1): 416. \n\n\n\n4. Wang Z, Liu J, Shuai H, Cai Z, Fu X, Liu Y, et al. Mapping global \nprevalence of depression among postpartum women. Transl \nPsychiatry. 2021; 11(1): 543. \n\n\n\n5. Tolossa T, Fetensa G, Yilma MT, Abadiga M, Wakuma B, Besho \nM, et al. Postpartum depression and associated factors among \npostpartum women in Ethiopia: a systematic review and meta-\nanalysis, 2020. Public Health Rev. 2020; 41(1): 21. \n\n\n\n6. Alshikh Ahmad H, Alkhatib A, Luo J. Prevalence and risk factors \nof postpartum depression in the Middle East: a systematic review \nand meta\u2013analysis. BMC Pregnancy Childbirth. 2021; 21(1): 542. \n\n\n\n7. Upadhyay AK, Singh A, Singh A. Association between \nunintended births and risk of postpartum depression: evidence \nfrom Ethiopia, India, Peru and Vietnam. SSM. 2019; 9: 100495. \n\n\n\n8. Labrague LJ, McEnroe-Petitte D, Tsaras K, Yboa BC, Rosales RA, \nTizon MM, et al. Predictors of postpartum depression and the \nutilization of postpartum depression services in rural areas in the \nPhilippines. Perspect Psychiatr Care. 2020; 56(2): 308\u201315. \n\n\n\n9. Ayoub K, Shaheen A, Hajat S. Postpartum depression in the Arab \nRegion: a systematic literature review. Clin Pract Epidemiol Ment \nHealth. 2020; 16(Suppl-1): 142\u201355. \n\n\n\n10. \u00d6zcan NK, Boyac\u0131o\u011flu NE, Din\u00e7 H. Postpartum depression \nprevalence and risk factors in Turkey: a systematic review and \nmeta-analysis. Arch Psychiatr Nurs. 2017; 31(4): 420\u20138. \n\n\n\n11. Ahmad NA, Silim UA, Rosman A, Mohamed M, Chan YY, Mohd \nKasim N, et al. Postnatal depression and intimate partner \nviolence: a nationwide clinic-based cross-sectional study in \nMalaysia. BMJ Open. 2018; 8(5): e020649. \n\n\n\n12. Zhao XH, Zhang ZH. Risk factors for postpartum depression: an \nevidence-based systematic review of systematic reviews and \nmeta-analyses. Asian J Psychiatry. 2020; 53: 102353. \n\n\n\n13. Upadhyay RP, Chowdhury R, Aslyeh S, Sarkar K, Singh SK, Sinha \nB, et al. Postpartum depression in India: a systematic review and \nmeta-analysis. Bull World Health Organ. 2017; 95(10): 706-17C. \n\n\n\n14. Hassert S, Sharon SR, Payakkakom A, Kody\u0161ov\u00e1 E. Postpartum \ndepressive symptoms: risks for Czech and Thai mothers. J Perinat \nEduc. 2018; 27(1): 38\u201349. \n\n\n\n15. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, \nMulrow CD, et al. The PRISMA 2020 statement: an updated \nguideline for reporting systematic reviews. BMJ. 2021; 372: n71. \n\n\n\n16. Zainal NZ, Kaka AS, Ng CG, Jawan R, Singh Gill J. Prevalence of \npostpartum depression in a hospital setting among Malaysian \nmothers. Asia Pac Psychiatry. 2012; 4(2): 144\u20139. \n\n\n\n17. Yusuff MAS, Tang L, Binns CW, Lee AH. Prevalence and risk \nfactors for postnatal depression in Sabah, Malaysia: a cohort \nstudy. Women Birth J Austral College Midwives. 2015; 28(1): 25\u2013\n9. \n\n\n\n18. Norhayati MN, Nik Hazlina NH, Aniza AA, Asrenee AR. Severe \nmaternal morbidity and postpartum depressive \nsymptomatology: a prospective double cohort comparison study. \nRes Nurs Health. 2016; 39(6): 415\u201325. \n\n\n\n19. Suhitharan T, Pham TP, Chen H, Assam PN, Sultana R, Han NL, \net al. Investigating analgesic and psychological factors \nassociated with risk of postpartum depression development: a \ncase-control study. Neuropsychiatr Dis Treatment. 2016; 12: \n1333\u20139. \n\n\n\n20. Teo C, Chia AR, Colega MT, Chen LW, Fok D, Pang WW, et al. \nProspective associations of maternal dietary patterns and \npostpartum mental health in a Multi-Ethnic Asian Cohort: the \ngrowing up in Singapore towards Healthy Outcomes (GUSTO) \nStudy. Nutrients. 2018; 10(3):415-425. \n\n\n\n21. Tham EK, Tan J, Chong YS, Kwek K, Saw SM, Teoh OH, et al. \nAssociations between poor subjective prenatal sleep quality and \npostnatal depression and anxiety symptoms. J Affect Disord. \n2016; 202: 91\u20134. \n\n\n\n22. Ross R, Sawatphanit W, Mizuno M, Takeo K. Depressive \nsymptoms among HIV-positive postpartum women in Thailand. \nArch Psychiatr Nurs. 2011; 25(1): 36\u201342. \n\n\n\n23. Panyayong B. Postpartum depression among Thai women: a \nnational survey. J Med Assoc Thailand. 2013; 96(7): 761\u20137. \n\n\n\n24. Roomruangwong C, Withayavanitchai S, Maes M. Antenatal \nand postnatal risk factors of postpartum depression symptoms in \nThai women: a case-control study. Sexual Reprod Healthcare. \n2016; 10: 25\u201331. \n\n\n\n25. Phoosuwan N, Manwong M, Eriksson L, Lundberg PC. Perinatal \ndepressive symptoms among Thai women: a hospital-based \nlongitudinal study. Nursing Health Sci. 2020; 22(2): 309\u201317. \n\n\n\n\n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 685\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n686                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n26. Dira AIKP, Wahyuni AAS. Prevalence and risk factors of \npostpartum depression in the city of Denpasar using Edinburg \nPostnatal Depression Scale Jurnal Midwifery Update (MU) 2020; \n2(2):100-109.  \n\n\n\n27. Nurbaeti I, Deoisres W, Hengudomsub P. Postpartum depression \nin Indonesian mothers: its changes and predicting factors. Pacific \nRim Int J Nurs Res. 2018; 22(2): 93-105. \n\n\n\n28. Nurbaeti I, Deoisres W, Hengudomsub P. Association between \npsychosocial factors and postpartum depression in South \nJakarta, Indonesia. Sexual Reprod Healthcare. 2019; 20:72-76.. \n\n\n\n29. Ryanawati P, Uki Retno B, Bhisma M. Prevalence and \ndeterminants of postpartum depression in Sukoharjo district, \nCentral Java. J Maternal Child Health. 2018; 3(1): 11\u201324. \n\n\n\n30. Putra AJE, Nurrobi R, Prasetyo D, Akbar M, Oktaviana N, \nFatimah A, et al. Determinants of perinatal depression in Licin \nBanyuwangi 2019. J Commun Med Public Health Res. 2020; 1: \n14. \n\n\n\n31. Usnawati N, Nuryani N. Risk factors of postpartum depression. \nAlliance Health Activists (AloHA) 2019; 2(6): 131\u20137. \n\n\n\n32. Suzuki Y, Mph M, Goto A, Vinh N, Msc M, Thi N, et al. Postnatal \ndepression and associated parenting indicators among \nVietnamese women. Asia-Pacific Psychiatry. 2011; 3:-227 \n\n\n\n33. Fisher J, Tran TD, Biggs B, Dang TH, Nguyen TT, Tran T. Intimate \npartner violence and perinatal common mental disorders among \nwomen in rural Vietnam. Int Health. 2013; 5(1): 29\u201337. \n\n\n\n34. Murray L, Dunne MP, Van Vo T, Anh PNT, Khawaja NG, Cao TN. \nPostnatal depressive symptoms amongst women in Central \nVietnam: a cross-sectional study investigating prevalence and \nassociations with social, cultural and infant factors. BMC \nPregnancy Childbirth. 2015; 15(1): 234. \n\n\n\n35. Tho Tran N, Nguyen HTT, Nguyen HD, Ngo TV, Gammeltoft T, \nRasch V, et al. Emotional violence exerted by intimate partners \nand postnatal depressive symptoms among women in Vietnam: \na prospective cohort study. PLoS One. 2018; 13(11): e0207108-e. \n\n\n\n36. Do TKL, Nguyen TTH, Pham TTH. Postpartum depression and \nrisk factors among Vietnamese women. Biomed Res Int. 2018; \n2018: 4028913. \n\n\n\n37. Inthaphatha S, Yamamoto E, Louangpradith V, Takahashi Y, \nPhengsavanh A, Kariya T, et al. Factors associated with \npostpartum depression among women in Vientiane Capital, Lao \nPeople\u2019s Democratic Republic: a cross-sectional study. PLoS One. \n2020; 15(12): e0243463. \n\n\n\n38. Sawyer A, Ayers S, Smith H. Pre- and postnatal psychological \nwellbeing in Africa: a systematic review. J Affective Disord. 2010; \n123(1-3): 17\u201329. \n\n\n\n39. Howard LM, Oram S, Galley H, Trevillion K, Feder G. Domestic \nviolence and perinatal mental disorders: A systematic review and \nmeta-analysis. PLoS Med. 2013; 10(5): e1001452. \n\n\n\n40. Levis B, Negeri Z, Sun Y, Benedetti A, Thombs BD. Accuracy of \nthe Edinburgh Postnatal Depression Scale (EPDS) for screening to \ndetect major depression among pregnant and postpartum \nwomen: systematic review and meta-analysis of individual \nparticipant data. BMJ. 2020; 371: m4022. \n\n\n\n19-A 10-year00068.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 686\n\n\n\n\n\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                687 \n\n\n\nDear Editor, \n \nAs we know, propolis is a natural resinous material produced \nby bees from various plants. This material is used to seal and \nline the beehives. The quality of propolis depends on \nchemical compositions, geographical region and botanical \norigin. Propolis contains resin, wax, essential oil, pollen, \nminerals, phenolic acid, flavonoids, terpenes, aromatic \naldehydes, alcohols, fatty acids and stilbenes. It has many \nbenefits for human health, for instance, antioxidant, \nantimicrobial, antiproliferative, antitumoral, anti-\ninflammatory and immunomodulatory capacity. Currently, \nthere are many types of products made from propolis, \nincluding tablets, liquids and capsules but they are quite \nexpensive in Vietnam (15\u201320 USD/120 capsules). Customers \ncan use either the original propolis or propolis extract \ndepending on the application. In Vietnam, beekeepers are \nnot very interested in propolis due to the low yield \n(approximately 0.2 kg/herd/year). \n \nThe biggest problem for propolis is its low solubility in water \nand poor bioavailability. Therefore, scientists must use \norganic solvents (acetone, ethanol, etc.) to extract the \nbioactive compounds. In addition, to resolve these problems, \nmany previous studies pointed out that nanoparticles (NPs) \nproduced from propolis extract could be used as drug delivery \nsystems to facilitate drug absorption and are relatively safe \n(low toxicity) and compatible with the human body.1 \nPropolis extract NPs could improve the biological activities \ncompared to the control. In fact, there are many ways to \nencapsulate propolis, for instance, lipid NPs, polymeric NPs, \nand inorganic NPs with various diameters. \n \nIn general, all studies about propolis extract NPs are very \ninteresting; however, they only have focused on the \nantiproliferative, antimicrobial, immunomodulatory \nactivities, cytotoxicity and phytochemical profiles. Those are \nhighlights of medicine, but it is a pity that these experiments \nwere performed in vitro.1 In my opinion, there are some \nmajor issues that need to be resolved when researching the \nhuman body. Firstly, the interaction of unintended NPs and \nimmune cells may create some molecular responses that \n\n\n\nnegatively affect human health, stimulate infectious \ndiseases, induce autoimmune disorders and promote cancer \ndevelopment.2 Secondly, plant extract NPs can be undetected \nby the immune system.3 Lastly, the data on the toxicity of \nplant extract NPs (both carriers and phytochemical \ncomponents of extract from plants) are inadequate. So, the \nimpact of nanoparticles on the immune system is still a grey \nzone. Determination of the toxicity of propolis extract NPs \nand evaluation of their interaction with the human immune \nsystem are quite necessary. Based on the issues mentioned \nabove, the applications of propolis extract NPs in the human \nbody are huge challenges for the medical field and \nnanotechnology, however, future studies are necessary for in \nvivo models. Therefore, the perspective being proposed in this \nstudy is indeed feasible. Although the development of \nnanomedicine is still a long way off, it looks bright and may \nattain great achievements in the future. For NPs produced \nfrom propolis extract, I believe that there are many exciting \nthings to discover with this nanomaterial and they are surely \nadvantageous for human health, at least for in vitro \nexperiments. \n \n \nCONFLICT OF INTEREST \nNone. \n \n \nFUNDS \nNone. \n \n \nREFERENCES \n1. Botteon CEA, Silva LB, Ccana Ccapatinta GV, Silva TS, Ambrosio \n\n\n\nSR,Veneziani RCS, et al. Biosynthesis and characterization of \ngold nanoparticles using Brazilian red propolis and evaluation of \nits antimicrobial and anticancer activities. Sci Rep 2021; 11: \n1974. \n\n\n\n2. Kononenko V, Narat M, Drobne D. Nanoparticle interaction with \nthe immune system. Arh Hig Rada Toksikol 2015; 66: 97-108 \n\n\n\n3. Ernst LM, Casals E, Italiani P, Boraschi D, Puntes V. The \ninteractions between nanoparticles and the innate immune \nsystem from a nanotechnologist perspective. Nanomater 2021; \n11: 2991. \n\n\n\n\n\n\n\nNanoparticles produced from propolis extract: Their \napplications in medicine, why not? \n \nLe Pham Tan Quoc, PhD \n\n\n\n     \nInstitute of Biotechnology and Food Technology, Industrial University of Ho Chi Minh City, Ho Chi Minh City, Vietnam \n\n\n\nLETTER TO EDITOR\n\n\n\n This article was accepted: 04 August 2023                                                                                                                                                                         \nCorresponding Author: Le Pham Tan Quoc \nEmail: lephamtanquoc@iuh.edu.vn \n\n\n\n20-Nanoparticles00065.qxp_3-PRIMARY.qxd  25/09/2023  4:29 PM  Page 687\n\n\n\n\n\n\n\n\n688                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nAcknowledgement \nSeptember Issue 2023 \n\n\n\n \nThe Editorial Board of The Medical Journal of Malaysia gratefully acknowledge the following \nindividuals for reviewing the papers submitted for publication: \n \n                                                                                                                                                                                                              1. Assoc Prof Dr Abdelkareem A.Ahmed \n\n\n\n2. Dr Aida Abdul Aziz \n3. Prof Dr Anselm Ting Su \n4. Datin Dr Asmah Binti Johar \n5. Dr Azhar Md Zain \n6. Dr Azlan Helmy Abd Samat \n7. Dr Chai Zhen Hoo \n8. Dr Chan Tha A Hing \n9. Dr Chern Phei Ming \n10. Dr Chua Hock Hin \n11. Dr Davinder Singh Bagh \n12. Dr Fauzi Abdul Rani \n13. Dr Gerald Henry \n14. Dr Hana Maizuliana Solehan \n15. Prof Dr Jafri Malin Abdullah \n16. Dr Khadijah Poh \n17. Dr Krishna Kumar G \n18. Dr Kumar Harirajah \n19. Assoc Prof Dr Leelavathi Muthupalaniappen \n20. Dr Mazlin Baseri \n21. Dr Mohd Aizuddin Abd Rahman \n22. Dr Mohd Azmarul A Aziz \n23. Dr Mohd Azmi Bin Suliman \n24. Dr Muhd Siv Azhar Merican Abdullah \n25. Dr Navin Kumar Devaraj \n26. Dr Noor Dina Hashim \n27. Dr Rama Krishna Supramanian \n28. Dr Sanihah Abdul Halim \n29. Dr Sanjiv Rampal \n30. Dr Shaik Farid Abdull Wahab \n31. Dr Suhaila Abd Muid \n32. Dr Sufian Adenan \n33. Prof Dr Thameen Ansari \n34. Dr Thien Thien Lim \n35. Dr Vasu Pillai Letchumanan \n36. Dr Zahir Izuan Azhar \n37. Dr Zainab Abdul Majeed \n\n\n\n \n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                559 \n\n\n\nABSTRACT \nIntroduction: Noise-induced hearing loss (NIHL) is a \ncommon problem worldwide. Increased globalisation, as \nwell as industrialisation, gives rise to an increase in the \nincidence of NIHL worldwide. Malaysia is not spared from \nthis problem, either. The objectives were to determine the \nprevalence of NIHL and its associated factors among \nmanufacturing factory workers. \n \nMaterial and Methods: A cross-sectional study was done in \nKuching, Sarawak, involving 173 randomly selected \nrespondents among manufacturing factory workers. Data \ncollected were respondents' workplace monitoring data and \ntheir audiometry records obtained from the factory record, \nand the otoscopy examinations performed. In addition, \nrespondents were required to fill up an interviewer-guided \nquestionnaire.  \n \nResults: The prevalence of NIHL was high (49.7%). The \nfactors which were found to have a significant association \nwith NIHL in bivariate analysis were age (p < 0.05, 95% CI), \nmale gender (p < 0.05; OR \u2013 7.60; CI 3.34 \u201318.38), duration of \nemployment (p <0.05), knowledge of noise level (p < 0.05; OR \n\u2013 4.11; CI 1.10 \u2013 15.28), working at polishing department (p < \n0.05; OR \u2013 4.23; CI  2.13 \u2013 8.43), and smoking (p < 0.05; OR \u2013 \n39.6; CI 16.5 \u2013 94.8). Pack\u2013years of smoking were also found \nto have a significant association with p < 0.05. However, only \nsmoking was statistically significant in multivariate analysis, \nwhere the risk of developing NIHL was 27.55 (p < 0.005; CI \n10.74 \u2013 70.64) among smokers. \n \nConclusion: The high prevalence of NIHL despite the \nexisting Hearing Conservation Program (HCP) may indicate \nthat there may be some elements in HCP that require close \nmonitoring by the factory management, and the importance \nof smoking cessation among the workers exposed to noise \nat the workplace should be highlighted. \n \nKEYWORDS:  \nNoise-induced hearing loss, manufacturing factory, audiometry, \nprevalence, Sarawak \n \n \nINTRODUCTION \nOccupational noise-induced hearing loss (NIHL) is a \nprevalent occupational disorder, and hearing loss caused by \n\n\n\nworkplace noise exposure is a significant health issue \nglobally.1 NIHL occurs due to long-term exposure to excessive \nnoise, usually over the years. Therefore, continuous or \nintermittent noise in the workplace that exceeds 85dB(A) \nduring an 8-hour shift, or impact noise that exceeds \n120dB(A) , is deemed dangerous.1,2 \n \nGlobally, NIHL is responsible for 16% of cases of debilitating \nhearing loss in adults, indicating that it does not directly \ncause early death but does result in significant disability.2,3 In \nMalaysia, occupational NIHL, which includes NIHL, hearing \nimpairment, and Permanent Standard Threshold Shift, was \nthe most frequently reported occupational disease in 2021, \naccounting for 3648 cases (68.9%).4 Although the data may \nnot reflect the entire Malaysian population, it is clear that \nNIHL is a significant concern impacting many employees in \nMalaysia.  \n \nNIHL is related to multiple factors, and the risk factors for \ndeveloping NIHL can be non-modifiable such as age and \ngender, or can be modifiable. In addition to occupational \nnoise, other causes (such as organic solvents, high \ntemperatures, lack of hearing protection devices, smoking, \nalcohol, heredity, comorbidities) may serve independently or \nsynergistic effects with noise to increase the risk of NIHL.5-6 \n\n\n\nTobacco smoking is a risk factor for various diseases, and \nseveral scientific literatures has shown that it may be related \nto NIHL.7-9 Some toxic and harmful substances like nicotine \nfrom tobacco burning may affect hearing.10 Smokers were \nalmost twice as likely as non-smokers to develop hearing loss. \nThis association persisted in studies that excluded those with \nnon-age-related hearing loss and those with no history of \noccupational noise exposure.10,11 Several meta-analysis \nstudies have found evidence of an association between \ncigarette smoke and hearing loss.10-12 \n \nThe intensity, frequency, duration of exposure, and type of \nnoise significantly impact the risk of health hazards, notably \noccupational hearing loss. Individuals with NIHL may \nendure severe morbidity due to hearing loss, concomitant \ntinnitus, and poor speech discrimination.13 Non-auditory \neffects may impacts workplace communication and safety. \nThe non-auditory reaction to noise may be affected by sound \nqualities such as the rate, loudness, consistency, complexity, \nduration (period of exposure) and noise meaning.14 Noise has \nbeen linked to increased stress, cardiovascular health \n\n\n\nNoise-induced hearing loss among manufacturing factory \nworkers in Kuching, Sarawak: Prevalence and associated \nrisk factors \n \nHalim Ismail, DrPH, Azizul Idris, MScCH, David Chan Chee Hoong, MPH, Hanis Ahmad, MPH, Hafiz Baharudin, \nMPH, Naiemy Reffin, MScCH, Hibatul Hakimi Jamaludin, MD, Nor Azila Aris, MD, Huam Zhe Shen, MD \n\n\n\n     \nDepartment of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 26 June 2023                                                                                                                                                                             \nCorresponding Author: David Chan Chee Hoong                                                                                                                                                                \nEmail: davidcch10@gmail.com\n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 559\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n560                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n(hypertension, changes in heart rate), irritation, poor sleep \nand mental health issues. Because of this broad spectrum of \nimpacts, experts believe noise can interact as a general, non-\nspecific stressor.14-15 Studies have proved that a sound pressure \nlevel of 95-90 dB(A) can induce hearing loss of more than 25 \ndB(A), whereas a sound pressure level of 85-90 dB(A) can \ncause hearing loss of less than 2dB(A).16 The risk of NIHL can \nbe minimised if noise is decreased to below 80 dB(A). \nRegulation six of the Occupational Safety and Health (Noise \nExposure) Regulations 2019 states that the NEL as the daily \nnoise exposure level should not exceed 85dB(A) or daily \npersonal dose (cumulative noise exposure of an employee \ncorrected for a typical working day of eight hours) a hundred \nper cent (100%). The criterion for maximum sound level \npressure (SPL) exceeding 115dB(A) at any time or the peak \nSPL exceeding 140dB(C) necessitates the implementation of \nactivities to reduce risk of NIHL. This dose limit uses a 3-dB \ntime-intensity trade-off as the exchange rate.2,18  \n \nA thorough medical history can assist in establishing whether \nany of these disorders may be contributing to an individual's \nhearing loss.2,17,18 Poor knowledge and awareness among \nemployees and a lack of enforcement by governing bodies \nwere cited as factors for the risk of NIHL. In addition, hearing \nprotection is not often adequately fitted, and even when it is, \nit wears out and fails to provide the specified laboratory \nvalues of attenuation in the field.17,18  \n \nResearch showed that occupational noise exposure is a \nsignificant concern and pervasive in the industrial industry.19 \nProcessing tasks are a significant aspect of the manufacturing \nindustry, and the complexity of process noise such as forging, \ngrinding, cutting, polishing, and welding is very noticeable.20 \nAlthough the reported NILH cases have dramatically \nincreased since 2010, there is a significant disparity between \nthe number of cases diagnosed and the number of workers \nexposed to hazardous noise. In addition, there is no \nestablished data on NIHL among manufacturing sector \nworkers in Sarawak. Therefore, this study aims to determine \nthe proportion of NIHL and its associated factors among \nmanufacturing factory workers.  \n \n \nMATERIALS AND METHODS \nStudy design \nThis retrospective cross-sectional study was conducted among \nmanufacturing factory workers in Sarawak to evaluate the \nmedical record, area monitoring, personal monitoring, and \nworkers' audiometry assessment from the factory records.  \n \nThis research has been approved by UKM ethical committee \n(UKM FPR.4/244/FF-2016-219) and the manufacturing \ncompany management board. \n \nStudy subject and methods \nThis study included all workers from the polishing and \nplating department of the manufacturing factory who went \nfor an annual audiometry assessment and were exposed to \nnoise at work above noise exposure limits (NEL) of 85 dB(A). \nHowever, workers who have underlying medical diseases that \nmay compromise blood flow to organs and increase viscosity, \nlike diabetes mellitus, hyperlipidaemia, and hypothyroidism, \n\n\n\nhistory of usage of the ototoxic drug, history of severe and \nfrequent ear infections with or without ear surgery were \nexcluded from the study. Additionally, workers with a history \nof exposure to non-occupational noise, such as involvement \nin the war, and loud explosion activities, such as hunting, \nwere excluded.  \n \nEligible workers were selected by a simple random sampling \nmethod, where each subject was chosen randomly and by \nchance.  \n \nSelected respondents then undergo an otoscopic examination \nand audiometric assessment. Those with abnormal otoscopic \nfindings such as ear wax, ear discharge, perforated tympanic \nmembrane, and ear infection were ruled out from the study. \nAn audiometry assessment was conducted for selected \nworkers after they were not exposed to noise for 14 hours \nbefore the test. Furthermore, all respondents were using \nhearing protective devices uniformly as they worked in an \narea requiring hearing protection before entry.  \n \nFactors such as age, gender, duration of working, working \ndepartment in the company, smoking habits (packed year), \nknowledge of noise level of the workplace unit, and usage of \nhearing protective devices were obtained through a \nsociodemographic questionnaire.   \n \nWritten and oral informed consent was obtained from all \nparticipants. They were assured anonymity as well as \nconfidentiality. \n \nDiagnosis of NIHL \n1. History taking and physical examination \nTo ensure that the NIHL was caused by the current \nemployment and not due to previous job exposure or other \nnon-occupational exposure, several histories such as \nmedical, non-occupational, previous employment, drugs, \nrecreational and social histories of exposure risk in the \nhistory taking were included in the sociodemographic \nquestionnaire. History of hearing loss, ear pain, ear \ndischarge, head injury, history of tinnitus, recent surgery on \near, nose, and throat, or head surgery was considered. \nHobbies that involve noise exposure, such as loud music, \nclubbing, hunting, and scuba diving as a hobby were \ndocumented.   \n \nRespondents underwent a thorough head, ear, neck and \ncranial nerve examination and an otoscopic examination.  \n \n2. Audiometric assessment \nThere must be a positive history of exposure to noise at the \nworkplace. Audiometric examination results were used to \ndetermine hearing loss among the respondents. The \naudiometric results should have a hearing threshold of more \nthan 25 dB(A) at 4 kHz with a characteristic dip followed by \nrecovery at higher frequencies to determine whether hearing \nloss was related to noise exposure. The dip depth in NIHL \nalone should not be more than 75 dB(A) in higher \nfrequencies and should not be more than 40 dB(A) in lower \nfrequencies. If those dips were not consistent with the \ncharacteristic of noise exposure, then the hearing loss could \nbe due to other factors such as presbycusis.  \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 560\n\n\n\n\n\n\n\n\nNoise-induced hearing loss among manufacturing factory workers in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                561 \n\n\n\n   Variables                                                         Frequency (n)                                      Percentage (%) \nAge group                                                                                                                                              \n\n\n\n20 \u2013 24.9                                                                        51                                                          29.5 \n25 \u2013 29.9                                                                        54                                                          31.2 \n30 \u2013 34.9                                                                        42                                                          24.3 \n35 \u2013 39.9                                                                        21                                                          12.1 \n40 \u2013 44.9                                                                         2                                                            1.2 \n\u2265 45                                                                                 3                                                            1.7 \n\n\n\nGender                                                                                                                                                   \nMale                                                                              131                                                         75.7 \nFemale                                                                           42                                                          24.3 \n\n\n\nDuration of employment \n1 \u2013 4.9                                                                           116                                                         67.1 \n5 \u2013 9.9                                                                            38                                                          22.0 \n10 \u2013 14.9                                                                        10                                                           5.8 \n15 \u2013 19.9                                                                         2                                                            1.2 \n\u2265 20                                                                                 7                                                            4.0 \n\n\n\nDepartment                                                                                                                                           \nPlating                                                                           58                                                          33.5 \nPolishing                                                                       115                                                         66.5 \n\n\n\nNoise level knowledge \nYes                                                                                 14                                                           8.1 \nNo                                                                                 159                                                         91.9 \n\n\n\nHPD usage \nYes                                                                                 36                                                          20.8 \nNo                                                                                 137                                                         79.2 \n\n\n\nSmoking history \nYes                                                                                 82                                                          47.4 \nNo                                                                                  91                                                          52.6 \n\n\n\nPack \u2013 years+ \n< 0.9                                                                              106                                                         61.3 \n1 \u2013 4.9                                                                            37                                                          21.4 \n5 \u2013 9.9                                                                            25                                                          14.5 \n10 \u2013 14.9                                                                         3                                                            1.7 \n\u2265 15                                                                                 2                                                            1.2 \n\n\n\n \nHPD = Hearing protective device \n+ smoking was quantified based on pack years which are calculated based on the number of cigarettes per day times the years of cigarette consumption. \n \n\n\n\nTable I: Sociodemographic characteristics of respondents (n = 173)\n\n\n\n                                                                         Frequency (n)                                                     Percent (%) \nYes                                                                              86                                                                      49.7 \nNo                                                                               87                                                                      50.3 \nTotal                                                                          173                                                                    100.0 \n \n\n\n\nTable II: Prevalence of NIHL\n\n\n\nVariables                                                                                                                 NIHL (%)                                 c2 value                p value \n                                                                                                                  Yes                                No \n\n\n\nGender                                                                   Male                     79 (60.3%)                   52 (39.7%)              24.22                 < 0.001* \n                                                                             Female                    7 (16.7%)                    35 (83.3%)                                                \nPrevious employment                                             Yes                       5 (45.5%)                     6 (54.5%)               0.085                     0.77 \n                                                                                 No                       81(50.0%)                     81(50.0%)                                                 \nDepartment                                                         Plating                   42 (72.4%)                   16 (27.6%)              17.99                < 0.0005* \n                                                                            Polishing                 44 (38.3%)                   71 (61.7%)                                                \nNoise level knowledge                                           Yes                      11 (78.6%)                    3 (21.4%)                5.08                    0.024* \n                                                                                 No                      75 (47.2%)                   84 (52.8%)                                                \nHearing protective device usage                           Yes                      20 (55.6%)                   16 (44.4%)               0.62                      0.43 \n                                                                                 No                      66 (48.2%)                   71 (51.8%)                                                \nSmoking                                                                  Yes                      72 (87.8%)                   10 (12.2%)              90.49                <0.0005* \n                                                                                 No                      14 (15.4%)                   77 (84.6%)                                                \n \n* Statistically significant p < 0.05\n\n\n\nTable III: Association between gender, previous employment, department, noise level knowledge, hearing protective device usage, \nsmoking, and NIHL\n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 561\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n562                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nVariables                                             NIHL                          N                    Mean \u00b1 Std. deviation               t-test, (t)                     p value \nAge                                                       Yes                          86                            30.69 \u00b1 7.19                          3.902                       <0.001* \n                                                              No                           87                            27.02 \u00b1 4.97                                                                  \nDuration of employment                    Yes                          86                             5.71 \u00b1 5.39                                                                   \n                                                              No                           87                             3.15 \u00b1 2.37                            4.05                       <0.0005* \nPack-years                                             Yes                          86                             3.44 \u00b1 3.36                            8.62                       <0.0005* \n                                                              No                           87                             0.22 \u00b1 0.86                                 \n                                                                  \n*Statistically significant p < 0.05 \n \n\n\n\nTable IV: Association between age, duration of employment, pack-years and NIHL\n\n\n\nVariables                                                     aOR                              p value                                                   95% C.I. for OR \n                                                                                                                                                        Lower                                Upper \nAge                                                              0.98                                 0.70                                      0.91                                   1.07 \nSmoking*                                                    27.55                                0.00                                     10.74                                 70.64 \nGender                                                         2.42                                 0.13                                     0.778                                  7.50 \nNoise level knowledge                               1.37                                 0.72                                     0.242                                  7.73 \nDepartment                                                 2.37                                 0.09                                     0.874                                  6.43 \n \n*Statistically significant p < 0.05 \n\n\n\nTable V:\u2008Multiple logistic regression between variables and NIHL\n\n\n\nStatistical analysis \nData analysis was done with Statistical Package for Social \nSciences (SPSS) version 22. The statistical test used was \nPearson's Chi-Square test, and if there were any cells with an \nexpected value less than 5, a Chi-square test with Yates \ncorrection was performed. For qualitative data with \nquantitative binominal data, student t-tests were done. Two-\ntailed p values were calculated, and the p value of <0.05 were \nconsidered to have a significant association. Multivariate \nanalysis using multiple logistic regression (MLR) with forward \nand backward stepwise analysis was used to determine the \nfinal model of this study.  \n \n \nRESULTS \nA total of 298 respondents participated in this study. Of these \n298 respondents, 125 were excluded from further analysis \nbecause they did not fulfil the inclusion criteria.  \n \nRegarding sociodemographic characteristics, as shown in \nTable I, most respondents were in the 25 to 30 age group \n(31.2%). The mean age of the respondents was 28.84 \u00b1 6.42 \nyears, where the youngest respondent was 21 years of age \nand the oldest was 54 years of age. Most were male workers \n(75.7%), the majority with a duration of employment \nbetween 1 to 5 years. Most respondents were from polishing \ndepartment (115, 65%), while the rest were from plating \ndepartment. These represent two of the significant activities \nin the manufacturing company.  \n \nRegarding duration of smoking, less than half of the \nrespondents were smokers, 82 respondents (47.4%), and their \nmean duration of smoking was 3.94 \u00b1 5.54 years. On the \nother hand, the mean pack \u2013 years calculated was 1.82 \u00b1 \n2.92, and the majority of the respondents (61.3%) had pack \u2013 \nyears of less than 0.99.  \n \nA high percentage of the workers (80.5%) have a normal \notoscopy finding, and only 2% have perforated ear drums. \n\n\n\nThe overall prevalence of hearing loss in this manufacturing \ncompany was 49.7%, as shown in Table II. \n \nThe bivariate analysis has shown that males workers \n(c2=24.22, p<0.001) in the plating department c2=17.99, \np<0.05) are more likely to develop NIHL (Table III). Smokers \nwere found to have a higher risk (unadjusted Odds Ratios, OR \n= 39.6; CI = 16.5 94.8) of developing NIHL than those who did \nnot smoke. The difference was statistically significant (p value \n< 0.05). In pack -years, those with the higher pack\u2013years of \nsmoking were likelier to develop NIHL than those with lower \npack \u2013 years (Table IV). \n \nIn the multiple logistic regression, only smoking was \nstatistically significant with an adjusted OR of 27.55 (95%CI \n10.74 \u2013 70.64). Despite other variables having statistically \nnon-significant results, males are two times more likely to \ndevelop NIHL than females. In addition, those who do not \nknow the noise level are one time more likely to develop \nNIHL than those who know the noise level, and those in \npolishing department are twice more likely to develop NIHL \ncompared to plating department after adjusting with others \nrisk factors (Table V). \n \n \nDISCUSSION \nThe study was done on a population of manufacturing \nfactory workers involving 298 workers. However, only 173 \nrespondents were eligible to be included after the exclusion. \nThis study found that the prevalence of NIHL in this \ncompany was as high as 49.7%. It was similar to other \nresearchers who found a high prevalence of NIHL in various \nindustries in Asia and Malaysia.23-25 \n \nAge is one of the vital factors found in other research and has \na statistical significance in this research, too. It proves that \nthe older the person, the more likely she or he is to develop \nNIHL. This is consistent with other research showing that \nolder people are more likely to develop NIHL. However, in \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 562\n\n\n\n\n\n\n\n\nNoise-induced hearing loss among manufacturing factory workers in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                563 \n\n\n\nNIHL, it differs from age-related hearing loss (AHL), which \nappears later, as in NIHL, it appears in younger age groups. \nIf other parameters are excluded, age can also be the most \nimportant single factor for NIHL.26 Young age group \ndistribution may be exposed enough to noise higher than PEL \nfor a considerable time, thus giving an early diagnosis of \nNIHL. \n \nFurthermore, the working group is primarily young and fit, \nlikely to get employed and stay employed (Hawthorne's \neffect). NIHL differs as it develops earlier in adults exposed to \nnoise than age-related hearing loss (presbycusis).27 A young \nperson exposed to noise shows a threshold shift compared to \nan older person who does not show any threshold shift, as \npostulated in some research. This explains the younger group \npopulation who developed NIHL in this study.28 \n \nGender is important in developing NIHL, as male workers are \nmore likely to be employed in manufacturing industries. \nHowever, few other studies also replicate that male \npredominance.29,30 Hearing sensitivity also declines in men \ntwice as fast as women of the same age and found \nlongitudinal declines in hearing sensitivity at 30 compared to \nwomen, which is seen at a later age.29 Furthermore, lifestyle \nhabit, such as smoking, is more common in males than in \nfemales.  \n \nDuration of employment indicates when the person is \nexposed to noise and predisposed to NIHL. The longer the \nperson is exposed to noise, the more likely they will develop \nNIHL. Duration of employment indicates dose\u2014response \nrelationship, thus corresponding with this research's \nfindings.28,31 The previous history of employment in a noisy \nenvironment was not statistically significant. This is probably \nbecause most workers employed at this manufacturing \ncompany are young, which is probably their first job. Plating \ndepartment was statistically significant in developing NIHL \ncompared to polishing department, although both \ndepartments are exposed to noise above NEL. That may be \npartly due to lacking control at the source as well. Workers \naware of the NEL are more likely to develop NIHL than those \nnot aware of the NEL. This is because those diagnosed have \nbeen told about their findings and made aware of the noise \nlevel. This contrasts with a study that indicates that those \nunaware of noise levels are more likely to develop NIHL.32 \n \nKnowledge is an essential aspect of the Hearing Conservation \nProgram (HCP). Although some research showed that the \nworkers\u2019 knowledge of hearing conservation was good,32 \nresearch in Malaysia shows that the knowledge, usage of \nHearing Protective Devices (HPD), and attitude towards NIHL \nprevention were low.25,33 Although 23.3% of the workers wore \nHPD at work, they may not have worn it correctly and thus \ndid not offer complete protection compared to properly fit \nHPD. Properly fit HPD may attenuate 15\u201320 dB (A).26 \nFurthermore, this was also proven during the walkthrough \nsurvey that most workers were non-compliant in wearing \nHPD due to a long time of usage and lack of social \ncommunication. However, using HPD on an average of 50% \nof the time also offers protection compared to those who did \nnot wear HPD.34 There could be a lack of knowledge regarding \nthe importance of hearing conservation among the workers, \nand some may not adhere to it entirely\u2014for example, proper \n\n\n\nusage of PPE and exchange of PPE once it is spoiled or \ndamaged.  \n \nThis study proves the hypothesis that there is a significant \nrelationship between smoking and NIHL and pack\u2013years of \ncigarette consumption. Smoking is a lifestyle habit that \npredisposes its users and those surrounding them to multiple \nhealth hazards. Cigarette smoke lacks an antioxidant effect, \nwhere reports that endogenous antioxidants significantly \ninfluences susceptibility to auditory damage.35 Therefore, it is \nprobable that the number of endogenous antioxidants in \nsmokers is reduced, thus predisposing them to cochlear \ndamage. Other researchers also found that smoking and \nhearing loss is statistically significant in those exposed to \noccupational noise with OR 1.85, 95% CI 1.33\u20132.57, and \npack-years of smoking remained significantly associated with \nhearing loss.36 The precise mechanism of smoking and NIHL \nis unknown. A simple additive effect of smoking and noise \nmight be compatible with NIHL potentiation caused by long-\nterm exposure to excessive noise and carbon monoxide \nexposure from smoking. Nicotine and other tobacco \ncompounds could be ototoxic.36,37 The fundamental \npathologic processes are the established vascular changes \n(cochlear hair cells damaged by raising carbon monoxide \nhaemoglobin, cochlear hypoxia, capillary vasoconstriction, \nor decreasing cochlear blood flow volume) associated with \nsmoking as well as long-term exposure to loud noise.36-41 \n\n\n\nEvidence suggests synergistic effects of smoking, noise, and \nage on hearing loss and a multiplicative effect of smoking \nand age on hearing loss. Some other studies also found that \nmedian age\u2013corrected hearing thresholds at 3 and 4 kHz in \nsmokers are significantly higher [7 dB (A)] than in those who \ndo not smoke.36,37  \n \nThis study has achieved its objectives and proved most of its \nhypotheses, as this manufacturing company reveals the \nprevalence of NIHL in almost half of the workforce. This \nstudy also manifests that the HCP, which this manufacturing \ncompany has implemented, may not be as effective as they \nare still weak areas of compliance. Although the seven \nelements of HCP have been adhered to, they may not be \nenough, especially on the worker's part. \n \nThe main limitation of our study was the small sample size. \nThe targeted sample size was not achieved as turnout was not \nas expected, as the study was done during regular working \nhours, and they followed shift and team systems. In addition, \nthe secondary data may influence the audiometric result as it \ncan be operator dependent. Furthermore, the instructions \ngiven to the respondents may not be accurate and thus may \nreflect misclassification bias. Hawthorne's effect, most of the \nemployees are young as the young and fit are most likely to \nbe employed and remain employed. Thus, the sample \npopulation is mainly of the young age group of less than 45 \nyears. \n \n \nCONCLUSION \nThe study found that occupational noise exposure is a severe \nhazard, mainly distributed in the manufacturing industry, \nwith the complexity of the process noise, such as forging, \ngrinding, cutting, and welding, particularly prominent. The \nrising trend in Malaysia over the past few years is probably \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 563\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n564                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\ndue to the increasing nature of investments and government \ninitiatives for small and medium-scale industries. Other than \nthe increasing nature of industries entering Malaysia, other \nfactors could contribute to increased cases, such as poor \ncompliance towards HCP. Smoking cessation programmes \nneed to be incorporated, and the benefits are of a broad \nrange as well. Reward or merit can be given to those who \nsuccessfully stopped smoking and helped reduce the \nincidence and prevalence of NIHL. \n \n \nACKNOWLEDGEMENTS \nWe thank the Department of Public Health Medicine,, \nFaculty of Medicine, National University of Malaysia, for the \ntechnical support. In addition, no external funding was \nreceived for this study. \n \n \nREFERENCES \n\n\n\n1. \u015aliwi\u0144ska-Kowalska M, Zaborowski K. WHO environmental noise \nguidelines for the European region: A systematic review on \nenvironmental noise and permanent hearing loss and tinnitus. \nInt J Environ Res Public Health 2017; 14(10): 1139. \n\n\n\n2. Department of Occupational Safety and Health Malaysia. \nIndustry Code of Practice for Management of Occupational Noise \nExposure and Hearing Conservation 2019. [cited July 2022] \nAvailable from: \nhttps://www.dosh.gov.my/index.php/legislation/codes-of-\npractice/industrial-hygiene/3286-industry-code-of-practice-for-\nmanagement-of-occupational-noise-exposure-and-hearing-\nconservation-2019?path=industrial-hygiene \n\n\n\n3. Kerr MJ, Neitzel RL, Hong O, Sataloff RT. Historical review of \nefforts to reduce noise-induced hearing loss in the United States. \nAm J Ind Med 2017; 60(6): 569\u201377. \n\n\n\n4. Department of Occupational Safety and Health Malaysia. \nGuideline on Management of Occupational Noise-Related \nHearing Disorders 2021. [June 2022]. Available from: \nht tps : / /www.dosh .gov .my/ index .php/guide l ines -on-\nmanagement-of -occupat ional -noise-re lated-hearing-\ndisorders/file \n\n\n\n5. Daniel E. Noise and hearing loss: a review. J Sch Health 2007; \n77(5): 225\u201331. \n\n\n\n6. Li X, Rong, X, Wang, Z, Lin, A. Association between smoking and \nnoise-induced hearing loss: a meta-analysis of observational \nstudies. Int J Environ Res Public Health 2020; 17(4): 1201.  \n\n\n\n7. Dement J, Welch LS, Ringen K, Cranford K, Quinn P. Hearing loss \namong older construction workers: Updated analyses. Am J Ind \nMed 2018; 61: 326\u201335.  \n\n\n\n8. Sari MA, Adnan A, Munir D, Eyanoer PC. The correlation of \nsmoking and noise induced hearing loss on workers at a palm oil \nfactory X in Medan-Indonesia. Bali Med J 2017; 6: 637\u201340.  \n\n\n\n9. Wang DM, Wang ZC, Zhou M, Li WZ, He MA, Zhang XM, Guo \nH, Yuan J, Zhan Y, Zhang K et al. The combined effect of cigarette \nsmoking and occupational noise exposure on hearing loss: \nevidence from the Dongfeng-Tongji Cohort Study. Sci Rep 2017; \n11142-7.  \n\n\n\n10. Kumar A, Gulati R, Singhal S, Hasan A, Khan A. The effect of \nsmoking on the hearing status-a hospital based study. J Clin \nDiagn Res 2013; 7(2): 210-14.  \n\n\n\n11. Cruickshanks KJ, Tweed TS, Wiley TL, Klein BE, Klein R, Chappell \nR, Nondahl DM, Dalton DS. The 5-year incidence and \nprogression of hearing loss: the epidemiology of hearing loss \nstudy. Arch Otolaryngol Head Neck Surg 2003; 129(10): 1041-46. \n\n\n\n12. Cho EK, Yang YR, Cho YH, Ro HS. Relationship between smoking \nand hearing loss in cohort and case-control studies. J Korean \nSociety Health-Sys Pharm 1998; 15(4): 513-17. \n\n\n\n13. Moshammer H, Kundi M, Wallner P, Herbst A, Feuerstein A, \nHutter HP. Early prognosis of noise-induced hearing loss. Occup \nEnviron Med 2015; 72: 83-4. \n\n\n\n14. Government of Canada, Canadian Centre for Occupational \nHealth and Safety. Noise - Non-Auditory Effects, April 5 2023. \n[cited April 2023] Accessed from: \nwww.ccohs.ca/oshanswers/phys_agents/noise/non_auditory.html \n\n\n\n15. Golmohammadi R, Ziad M, Atari S. Assessment of noise \npollution and its effects on stone cut industry workers of Malayer \ndistrict. Iran Occup. Health J 2006; 3 (1): 23-27.  \n\n\n\n16. American Conference on Governmental Industrial Hygienists. \nThresholds limit values and biological indexes. New York: \nACGIH; 2010. Hygienists. \n\n\n\n17. Coles R, Lutman M, Buffin J. Guidelines on the diagnosis of \nnoise-induced hearing loss for medicolegal purposes. Clin \nOtolaryngol Allied Sci 2000; 25: 264-73. \n\n\n\n18. Department of Occupational Safety and Health. Guidelines on \nmanagement of occupational noise-related hearing disorders. \n2021. \n\n\n\n19. Neitzel R, Seixas N. The effectiveness of hearing protection \namong construction workers. J Occup Environ Hyg 2005; 2(4): \n227-38. \n\n\n\n20. Girard SA, Leroux T, Courteau M, Picard M, Turcotte F, Richer O. \nOccupational noise exposure and noise-induced hearing loss are \nassociated with work-related injuries leading to admission to \nhospital. Inj Prev 2015; 21: e88-e92. \n\n\n\n21. Hu Shuangqiu, Hu Weijiang, Yang Shu, et al. Investigation on \nnoise exposure level and health status of workers in \ntransportation equipment manufacturing industry [J]. Chin Jo \nLabor Health Occup 2021; 39(7): 498-502.  \n\n\n\n22. Zhou J, Shi Z, Zhou L, et al Occupational noise-induced hearing \nloss in China: a systematic review and meta-analysis. BMJ Open \n2020; 10: e039576.  \n\n\n\n23. Fuente, A Hickson, L. Noise-induced hearing loss in Asia. Int J \nAudiol 2011; 50(sup1): S3-S10. \n\n\n\n24. Ahmad Kamarudin N, Fredie Robinson, Saupin S, Mohammad \nAH, Domingo O, Salan N hafizah H. Hearing loss among vector \ncontrol unit workers in Bornean Malaysia: a cross sectional risk \nfactors study. MJPHM 2022; 22(2): 61-7. \n\n\n\n25. Ismail, AF, Daud, A, Ismail, Z and Abdullah, B. Noise-induced \nhearing loss among quarry workers in a north-eastern state of \nMalaysia: a study on knowledge, attitude and practice. Oman \nMed J 2013; 28(5): 331. \n\n\n\n26. Toppila, E, Pyykk\u00f6, I, Starck, J. Age and noise-induced hearing \nloss. Scand Audiol 2001; 30(4): 236-44. \n\n\n\n27. Cruickshanks KJ, Klein R, Klein BEK, Wiley TL, Nondahl DM, \nTweed TS. Cigarette smoking and hearing loss: the epidemiology \nof hearing loss study. J Am Med Assoc 1998; 279(21): 1715-9. \n\n\n\n28. Rabonowitz PM, Galusha D, Dixon-Ernst C, Clougherty JE, \nNeitzel RL. The dose-response relationship between in-ear \noccupational noise exposure and hearing loss. Occupational and \nenvironmental medicine vol. 2013; 70(10): 716-21. \n\n\n\n29. Pearson, JD, Morrell, CH, Gordon\u2010Salant, S, Brant, LJ, Metter, EJ, \nKlein, LL and Fozard, JL. Gender differences in a longitudinal \nstudy of age\u2010associated hearing loss. J Acoust Soc Am 1995; \n97(2): 1196-1205. \n\n\n\n30. Xin Sun. Occupational noise exposure and worker's health in \nChina[J]. China CDC Weekly, 2021; 3(18): 375-7. \n\n\n\n31. Shakhatreh, FM, Abdul-Baqi, KJ, Turk, MM. Hearing loss in a \ntextile factory. Saudi Med J 2000; 21(1): 58-60. \n\n\n\n32. Ologe, FE, Akande, TM, Olajide, TG. Noise exposure, awareness, \nattitudes and use of hearing protection in a steel rolling mill in \nNigeria. Occup Medic 2005; 55(6): 487\u201389. \n\n\n\n33. Rus, RM, Daud, A, Musa, KI, Naing, L. Knowledge, attitude and \npractice of sawmill workers towards noise-induced hearing loss in \nkota bharu, kelantan. Malays J Med Sci 2008; 15(4): 28. \n\n\n\n34. Pyykk\u00f6, I, Toppila, E, Zou, J, Kentala, E. Individual susceptibility \nto noise-induced hearing loss. Audiol Medic 2007; 5(1): 41-53. \n\n\n\n35. Le Prell, CG, Yamashita, D, Minami, SB, Yamasoba, T, Miller, JM. \nMechanisms of noise-induced hearing loss indicate multiple \nmethods of prevention. Hea Res 2007; 226(1\u20132): 22-43. \n\n\n\n36. Wild DC, Brewster MJ, Banerjee AR. Noise\u2010induced hearing loss is \nexacerbated by long\u2010term smoking. Clinic Otolaryng 2005; 30(6): \n517-20. \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 564\n\n\n\n\n\n\n\n\nNoise-induced hearing loss among manufacturing factory workers in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                565 \n\n\n\n37. Prignot J. Quantification and chemical markers of tobacco-\nexposure. Eur Respir J 1987; 70(1): 1. \n\n\n\n38. Chen GD. Effect of hypoxia on noise-induced auditory \nimpairment. Hear Res 2002; 172(1 2), 186\u201395.  \n\n\n\n39. Starck J, Toppila E, Pyykko I. Smoking as a risk factor in sensory \nneural hearing loss among workers exposed to occupational \nnoise. Acta Otolaryngol 1999; 119(3), 302\u20135.  \n\n\n\n40. Fechter LD, Thorne PR, Nuttall AL. Effects of carbon monoxide on \ncochlear electrophysiology and blood flow. Hearing Res 1987; \n27(1): 37-45. \n\n\n\n41. Blanchet C, Erostegui C, Sugasawa M, Dulon D. Acetylcholine-\ninduced potassium current of guinea pig outer hair cells: its \ndependence on a calcium influx through nicotinic-like receptors. \nJ Neurosci 1996; 16(8): 2574-84. \n\n\n\n1B-Noise-induced00054.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 565\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023 551 \n\n\n\nINTRODUCTION \nThe Medical Journal of Malaysia (MJM) is the oldest medical \njournal not only in Malaysia but also in the region, serving \nmore than 17,000 doctors, and the wider healthcare \ncommunity. The vision of the MJM is to be the foremost \nmedical journal that promotes the integration of medical \nresearch and scholarly publication across South East Asia \nnations in particular and the world at large. The mission of \nthe MJM is to improve all peoples\u2019 lives by assisting and \nstrengthening the capacities of members of the Malaysian \nMedical Associations (MMA) and Medical Associations of \nSouth East Asian Nations (MASEAN) by training and \npublishing sound scientific articles. MJM is a double-blind \npeer-reviewed scientific journal. It publishes multidisciplinary \nmanuscripts that seek to advance medical and health \nsciences research, including all aspects of clinical and \npreventive medicine; political, economic, environmental \nsocial and technological (PEEST) subjects related to medical \npractice. The journal follows the International Committee of \nMedical Journal Editors (ICMJE) and Committee on \nPublication Ethics (COPE) guidelines with regard to \nconcerning its editorial policies on publication ethics, \nscientific misconduct, consent and peer review criteria. The \naim of this editorial is to record the history of MJM. \n\n\n\nHistory of MJM \nIn this editorial, we trace the history of the MJM from its \ninception. The first medical journal ever published in \nSoutheast Asia was the Journal of Straits Medical Association \n(JStMA). It was the official journal of the Straits Medical \nAssociation (StMA) which was established in 1890 [Figure \n1(A)]1. The StMA was then led by Dr. D. J. Galloway as the \nPresident [Figure 2 (A)]2, with Dr. W. Gilmore Ellis being the \nVice President. The first edition of the journal was under the \neditorship of Dr. Max F, Simon who was then the principal \ncivil medical officer of the Straits Settlements.3 \n\n\n\nThe journal published the minutes of meetings, rules of the \nassociation, reports of the committee and the address by Dr \nGalloway. There were only three manuscripts in the March\u2013\nSeptember 1890 issue, on \u2018Puerperal Eclampsia\u2019, \u2018A case of \nSyphilitic Coma\u2019 and \u2018A type of Puerperal Fever\u2019 in the 48 \npages issue. Dr. Max F. Simon dated 21st November 1892 \nmentioned that nearly all the members of the medical \nprofession in the Straits Settlement which included the whole \nof the Malay Peninsular had joined as corresponding \nmembers of the StMA, which has been recognised as a branch \nof the British Medical Association (BMA). He stated that a \njournal may be established which shall contain contributions \nfrom all the practitioners in the Malay Peninsula. The \nheadquarters of the association was in Singapore. He hoped \n\n\n\nthat the journal would become a means of communication \nbetween all medical men in the whole Peninsular of Malaya, \nnotes of cases and improved methods of treatment which \nmay be forwarded and received for publication, besides as a \nrecord of the proceedings of the association.3 \n\n\n\nAccording to the research work by W.S. Tiew (1999) on \u2018Some \nScholarly English Periodicals In Pre-Independent Malaysia: \nAn Historical Overview\u2019, he found that the JStMA was one of \nthe earliest Pre-independent Malaysian Scholarly English \nPeriodicals, with the Journal of the Indian Archipelago and \nEastern Asia was the first published in 1847, followed by the \nJournal of Eastern Asia (1875), the Journal of the Straits \nBranch of the Royal Asiatic Society (1878) and the \nAgricultural Bulletin of the Malay Peninsula (1891).4 \n\n\n\nThe second issue of the JStMA (October 1890\u2013March 1891) \nwas edited by Dr. Max Frank Simon. There were papers on \n\u2018Parangi disease\u2019, \u2018Case of Myxoedema\u2019, \u2018Beri-beri to \naccompany microscopical specimens\u2019 with notes of \ndiscussion on Beri-beri, notes of cases and a memorandum on \nAncylostomiasis in the 36 pages issue. The third issue (April \n1891\u2013March 1892) was with a new editor, Dr. W. Gilmore \nEliis. There were eight papers including one on Leprosy. \nAccording to the editor (in his editorial), the third number of \nthe JStMA was bulkier than the previous issues with 60 pages. \nThe fourth issue of the JStMA (April 1892\u2013March 1893) was \nedited by Dr. T.S. Kerr. A few interesting papers were papers \non \u2018Disorders of sleep\u2019, \u2018Malarial diarrhea\u2019, \u2018Amok of the \nMalays\u2019, \u2018Treatments of sciatica\u2019 and \u2018Ulcerative tuberculous \nof the lobe of the ear\u2019 in a 75-page issue. \n\n\n\nThe fifth issue of the JStMA (April 1893\u2013December 1894) with \n17 scientific papers was the period of the transaction of the \nStMA until the end of 1894, which thereafter became a \nbranch of the BMA. Interesting papers include topics on \n\u2018Acromegaly\u2019 and \u2018Spinal concussion\u2019 and a paper on \nunqualified practice in Singapore were published in the 158-\npage issue. It was noted in the minutes of the regular \nmonthly meeting on 4th November 1893 that Dr. Middleton, \nthe secretary, reported that 15 out of the 23 circulars sent to \nmembers not residing in Singapore indicated their \nwillingness to join the BMA, with two expressing \nunwillingness. In the annual general meeting dated 16th \nDecember 1893, it was unanimously agreed that the \nsecretary should draw up the necessary requisition of joining \nthe BMA. The annual subscription of the journal was fixed at \n$9 with $3 as the annual subscription to the branch. All the \npapers in the issues were discussed in the monthly meeting \nprior to the publications.5 All the first five volumes were \nprinted by the Government Printing Office in Singapore. \n\n\n\nThe evolution of the Medical Journal of Malaysia - beyond a \ncentury \n\n\n\nLiew Boon Seng, MS (Neurosurgery), Lekhraj Rampal, DrPH\n\n\n\nEDITORIAL \n\n\n\n This article was accepted: 29 August 2023\nCorresponding Author: Prof Datuk Dr Lekhraj Rampal \nEmail: dr_rampal1@hotmail.com\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 551\n\n\n\n\n\n\n\n\nEditorial \n\n\n\n552                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nOn 1st January 1894, the StMA was admitted as a branch of \nBMA, known as the Malaya Branch of the British Medical \nAssociation (MBBMA).6 In their regular monthly meeting \nheld on 6th May 1894, a committee was formed to draft new \nrules and by-laws for the purpose of transmission to the \nbranch organisation committee of the BMA. The membership \nof the new entity was 38 members. The publication of the \nJStMA was discontinued following the formation of this new \nentity.6 \n \nBy 1910, half of 215 registered medical practitioners in British \nMalaya including Singapore joined the association.7 The \nrevival of the journal with a new name, the Journal of the \nMBBMA, occurred in 1904 [Figure 1B(i)]8. The news was \npublished in the Straits Times on 29th June 1904. Dr. J. Kirk, \nas the chairman of the editorial committee, along with the \nassistance of Dr. McDowell, who established the local branch \nof the BMA, ensured the journal's reappearance with greater \nregularity in its issues. Articles on topics such as dengue fever \nby Dr. More and malarial fever by Dr. Galloway were \nconsidered relevant at that time. The second volume was \npublished in 1905. These two volumes were printed by the \nPinang Gazette Press Ltd, located in Penang, Malaya. \n \nThe third volume (Session 1905\u20131906 and January 1907) of \nthe Journal of the MBBMA was published. The 118-page \nvolume contained the minutes of the Council of the Malay \nBranch 1904 and 1905, minutes of meetings of the Singapore \ndivision for 1905 and 1906, the report of the Medical \nRegistration Bill Committee and 14 other papers. [Figure \n1B(ii)]9. However, due to insufficient contributions and \neditorial issues, the journal could not sustain its publication \nin 1907. \n \nThe journal was revived in January 1911 as the Malaya \nMedical Journal (MMJ). It was considered as the IX volume \n(previously five volumes as the JStMA and three volumes as \nthe Journal of the MBBMA).  Dr. Gilbert E Brooke was the \neditor with his last issue in October 1912 [Figure 1C(i)10 and \n1C(ii)11]. The journal was the organ of the MBBMA and the \nMalaya Branch of the Far Eastern Association of Tropical \nMedicine. There were a total of two volumes, each consisting \nof four parts. The first volume, which was published in 1911, \nincludes a 74-page January issue, a 66-page April issue, a 97-\npage July issue and a 74-page October issue. The second \nvolume, which was published in 1912, includes a 68-page \nJanuary issue, a 58-page May issue, a 34-page August issue \nand a 48-page October issue. The two volumes were printed \nby the Methodist Publishing House in Singapore [Price $4.00 \nper annum ($2.00 to BMA members), Single copies $1.00]. \n \nHe was replaced by Dr. J.W. Scharff in 1922, and the journal \nwas given a new name, the Transactions of the MBBMA, with \n56 pages.7 Dr. J.W. Scharff served as the editor until 1923. For \nthe subsequent twelve volumes issued between January 1926 \nand March 1937, the journal was renamed as the Malayan \nMedical Journal, by the MBBMA. There were four editors, \nnamely Dr. T.S. Macaulay (1926), Dr. JR. Kayo-Mouat (1927), \nDr. G.H. Macalister (1928-1929) and Dr. G.V. Allen (1930-\n1937) for those issues [Figure 2(B)]12. \n \nOn 17th December 1926, the quarterly MMJ was officially \nadopted as the official organ of the MBBMA. There were six \n\n\n\noriginal articles in its first January\u2013December 1926 issue, \ncovering topics such as \u2018Epidemic Jaundice\u2019, \u2018Leptospirosis\u2019, \n\u2018A system of Intelligence as a Handmaiden of Hygiene\u2019, \n\u2018Occupational Cancer with Special Reference to the Industries \nof Malaya\u2019, \u2018Epithelioma adenoidescysticum\u2019 and \u2018An \nexperiment with Paris Green as an Anopheles \nludlowaelarvicide\u2019. A special obituary notice of the late Miss \nElizabeth Fletcher, Matron of the General Hospital, Singapore \nwas published too. The subscription rate was six dollars per \nannum. The managing headquarters was located in Kuala \nKrai, Kelantan.13 \n \nThe MMJ reverted to its previous name, the Journal of the \nMBBMA for its five volumes of quarterly publications \nbetween 1937 and 1941 [Figure 1D(i)14 and 1D(ii)15]. The \nAdvertising & Publicity Bureau Ltd, Singapore was the \nprinting company of the journal. A supplementary issue of \nthe Journal of the MBBMA was published in June 1941 which \nconsisted of the names of Asiatic members.16 A study done by \nTeng et al in 2019 showed that out of five medical journals \npublished in pre-independence British Malaya from 1890 to \n1941, the MMJ published 59.5% of the articles.17 \n \nThere was no publication during World War II. However, \nfollowing World War II with the return of the British to \nMalaya and Singapore, the journal reappeared as the \nMedical Journal of Malaya under the same association, the \nMBBMA, from 1946 to 1959. The journal was printed by the \nYoung Advertising & Marketing Ltd, Singapore. The first two \nvolumes published between 1946 and 1947 were under Dr. \nD.W.G. Faris as the editor, while Dr. D.E.C. Mekie was the \neditor for the subsequent seven volumes published between \n1948 and 1954. Dr. H.M. McGladdery was the next editor for \nthe 11th volume (September 1956) through the 15th volume \n(2nd issue in December 1960).  \n \nThe close relationship between MBBMA and BMA can be \nobserved in a correspondence published on 8th January 1949 \nin its parent journal, the British Medical Journal (BMJ). The \ncorrespondence was written by Dr. Webb Johnson, the \nPresident of the Royal Medical Benevolent Fund regarding \ngift parcels sent by MBBMA.18 However in 1958, the situation \nchanged. In November 1958, medical doctors in both the \nFederation of Malaya and Singapore decided to withdraw \nfrom the MBBMA and established a new entity, the Malayan \nMedical Association. On 5th November 1958, an article was \npublished in the Straits Times, stating that \u2018the 1,500 doctors \nin Singapore and Federation will be holding their inaugural \nmeeting of the Malayan Medical Association on 10th \nNovember 1958\u2019. A draft of the constitution with 13 items \nwas introduced.19 However, the drafted constitution of the \nMalayan Medical Association was rejected by the Malaya \nRegistrar of Societies (ROS) as reported in the Straits Times \ndated 7th March 1959. The rejection was on the grounds that \ndoctors from both the Federation of Malaya and Singapore \nwere considered separate political entities before the \nformation of Malaysia and a single association could not \nrepresent doctors in both territories.20 \n \nThe Malayan Medical Association appealed against the \ndecision, arguing that the association is a professional, non-\npolitical body and political objections should therefore not \nimpede the formation of a pan-Malayan organisation for \n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 552\n\n\n\n\n\n\n\n\nThe evolution of the Medical Journal of Malaysia - Beyond a Century\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                553 \n\n\n\nFig. 1: A:First edition of the Journal of Straits Medical Association March\u2013September 1890; B(i): The front page of the Journal of the \nMalaya Branch of the BMA session 1904\u20131905; B(ii): The contents of the Volume 3: Session 1905\u20131906 of the Journal of the \nMalaya Branch of the BMA; C (i): The front page of the Malaya Medical Journal, January 1911, Vol IX. Part 1; C (ii): The front \npage of the Malaya Medical Journal, January 1912, Vol X. Part 1; D (i): The content page of the Journal of the Malaya Branch of \nthe British Medical Association, Volume II, No. 4 (1st March 1939); D(ii): Front page of the Journal of the Malaya Branch of the \nBritish Medical Association, Volume 3, No. 3 (December 1939); E(i): Index page of the Medical Journal of Malaya, Volume 11, \nSeptember 1956\u2013June 1957; E(ii): Front page of the Medical Journal of Malaya, Volume 12, No. 2 December 1957; E(iii): Index \npage of the Medical Journal of Malaya, Volume 14, September 1959\u2013June 1960; E(iv): Front page of the Medical Journal of \nMalaya, Volume 15, No.2 December 1960; F(i) Front page of the Medical Journal of Malaysia, Volume 47, Issue 3 September 1992; \nF(ii) Front page of the Medical Journal of Malaysia, Volume 59, Issue 2 June 2004; F(iii) Front page of the Medical Journal of \nMalaysia, Volume 64, Issue 1 March 2009 \n\n\n\nA B (i) B (ii)\n\n\n\nD (i) D (ii)C (i) C (ii)\n\n\n\nE (iii) E (iV)E (i) E (ii)\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 553\n\n\n\n\n\n\n\n\nEditorial \n\n\n\n554                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nFig. 2: (A): Dr. David James Galloway; (B): Dr. George Vance Allen; (C): Dr. A. A. Sandosham; (D): Dr. Paul C.Y. Chen; (E): Dr. Victor K.E. \nLim; (F): Dr. John T. Arokiasamy; (G): Dr. Azhar M. Zain; (H): Dr. K.G. Lim; (I): Dr. Khoo Kah Lin; (J):Professor Datuk Dr. Lekhraj \nRampal\n\n\n\nA B C D\n\n\n\nE F G\n\n\n\nI J\n\n\n\nH\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 554\n\n\n\n\n\n\n\n\nThe evolution of the Medical Journal of Malaysia - Beyond a Century\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                555 \n\n\n\ndoctors. On 2nd July 1959, the Federation Government again \nturned down the request of 1500 doctors in the Federation \nand Singapore to register their newly formed Malayan \nMedical Association. The decision was made by Mr. J. G. \nAdams, the Registrar of Trade Union and Societies, based on \nthe Federation's interest in having a Federation body with \nFederation citizens as officials.21 \n\n\n\n\n\n\n\nThe Straits Times, dated 4th August 1959, reported that \u2018The \noldest medical organisation in Malaya, the MBBMA, which is \n\n\n\nmore than 50 years old, will be dissolved soon\u2019. The last \npresident of the association was Dr. A.W.S. Thevathasan.22 \nOn 31st August 1959, news regarding the formation of a new \nmedical association, the Singapore Medical Association \n(SMA) was reported. On 15th September 1959, the new \nassociation took over the functions of the present Alumni \nAssociation of the King Edward VII College of Medicine and \nthe Faculty of Medicine, University of Malaya, as well as the \nBritish Medical Centre. This news was announced by Dr. V. \nThambipillai, the President of the Alumni Association. He \n\n\n\nFig. 3: The Medical Journal of Malaysia Metrics 1999\u20132022.\n\n\n\n*Bar graphs using left vertical axis and line graphs using right vertical axis \nSource: Scimago Journal & Country Rank \n\n\n\nFig. 4: The Medical Journal of Malaysia: Number of articles according to the types of articles and number of supplements in 2013\u20132022 \n(including the new 2022 MJM Case Reports journal).\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 555\n\n\n\n\n\n\n\n\nEditorial \n\n\n\n556                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nalso mentioned the formation of a similar body, the Malayan \nMedical Association, in the Federation.23 \n \nTwo medical associations were formed to replace the \nMBBMA: the SMA on 15th September 1959, and the Malayan \nMedical Association on 24th October 1959. Both medical \nassociations were affiliated with the BMA, based in London. \nSince then, the Medical Journal of Malaya has been under \nthe Malayan Medical Association and has been handled by \nthe same editor, Dr. H.M. McGladdery, until 1965 [Figure \n1E(i), 1E(ii) and 1E(iii)]. \n \nThe SMA established its own medical journal, the Singapore \nMedical Journal (SMJ), in 1960.24 The SMJ published an article \nentitled \u2018Galloway Memorial Lecture\u2019 which was written by \nDr. J.W. Scharff in 1960. In that article, it was stated that \u2018Sir \nDr. David Galloway was the first president of the Straits \nMedical Association in 1890. Four years later, he became the \npresident of the newly formed MBBMA. He passed away on \n5th March 1943 at the age of 85 years old\u2019.25 \n \nDr. A.A. Sandosham was the first Malaysian to serve as the \neditor for the Medical Journal of Malaya, appointed by the \n\n\n\nMalayan Medical Association, from 1965 until [Figure 2(C)]26. \nA  total of three volumes, spanning from the 3rd issue of the \nvolume XXIV to the 4th issue of the volume XXVI, were under \nthe editorship of  Dr. A.A. Sandosham. The Straits Times Press \n(S) Sendirian Berhad, Thomson Road, Singapore was the \nprinting company of the journal. \n \nIn 1972, following the formation of Malaysia in 1963, the \njournal was renamed as the Medical Journal of Malaysia \n(MJM) in September 1972, following the renaming of the \nMalayan Medical Association to Malaysia Medical \nAssociation (MMA) (Table I). Dr. A.A. Sandosham continued \nas the honorary editor of the MJM. He was replaced by Dr. \nPaul C.Y. Chen, the honorary editor for the 4th issue of the \n31st volume, in June 1977 [Figure 2(D)]. \n \nIn the 1st issue of the 37th volume of the MJM, published in \nMarch 1982, the honorary editor, Dr. Paul C.Y. Chen wrote \nan editorial titled \u2018The medical journal of Malaysia: Past and \nFuture\u2019. In the editorial, which marks the journal's 92nd year, \nhe stated that \u2018the MJM is the leading medical journal in the \nregion. To maintain the highest level of editorial and medical \nwriting, the journal has acquired the part-time services of an \n\n\n\nName of the journal                                                 Labeled volume                 Published month,                    Editor/Honorary Editor/ \n                                                                              (cumulative volume)                         year                                 Editor-In-Chief [Issue] \nJournal of Straits Medical                                               1,2 (2)                        Mar,1890\u2013Mar,1891                          Dr. Max Simon \nAssociationa                                                                        3 (3)                          Apr,1891\u2013Mar,1892                      Dr. W. Gilmore Ellis \n                                                                                          4,5 (5)                         Apr,1892\u2013Dec,1894                            Dr. T. S. Kerr \nJournal of the Malaya Branch of                                    1-3 (8)                            1904\u2013Jan,1907                                   Dr. J. Kirk \nthe British Medical Associationb                                            \nMalaya Medical Journalb                                                9,10 (10)                       Jan,1911\u2013Oct,1912                       Dr. Gilbert E Brooke \nThe transaction of the Malaya                                         (11)                                  1922\u20131923                                 Dr. J.W. Scharff \nBranch of the British Medical Associationb                           \nMalayan Medical Journalb                                                  (12)                           Jun,1926\u2013Mar,1927                     Dr. J.W. Scharff [1,2];  \n                                                                                                                                                                                  Dr. T.S. Macaulay [3,4] \n                                                                                            (13)                           Jun,1927\u2013Mar,1928                       Dr. JR. Kayo-Mouat \n                                                                                          (14,15)                        Jun,1928\u2013Mar,1930                       Dr. G.H. Macalister \n                                                                                          (16-23)                        Jun,1930\u2013Mar,1937                           Dr. G.V . Allen \nThe Journal of the Malaya Branch of the                     (23-28)                        Jun,1937\u2013Mar,1942 \nBritish Medical Associationb                                                                                                 \nThe Medical Journal of Malayab                                  1,2 (29,30)                     Sep,1946\u2013Jun,1948                          Dr. D.W.G. Faris \n                                                                                     3\u201310 (31-38)                    Sep,1948\u2013Jun,1956                          Dr. D.E.C. Mekie \n                                                                                    11-13 (39-41)                   Sep,1956\u2013Jun,1959                      Dr. H.M. McGladdery \nThe Medical Journal of Malayac                                14-18 (42-46)                   Sep,1959\u2013Jun,1964                      Dr. H.M. McGladdery \n                                                                                          19 (46)                        Sep,1964\u2013Jun,1965                 Dr. H.M. McGladdery [1,2];  \n                                                                                                                                                                               Dr. A.A. Sandosham [3.4] \n                                                                                    20-26 (47-53)                   Sep,1965\u2013Jun,1972                       Dr. A.A. Sandosham \nThe Medical Journal of Malaysiad                              27-30 (48-57)                   Sep,1972\u2013Jun,1976                       Dr. A.A. Sandosham \n                                                                                          31 (58)                        Sep,1976\u2013Jun,1977                  Dr. A.A. Sandosham [1-3]; \n                                                                                                                                                                                  Dr. Paul C.Y. Chen [4] \n                                                                                    32-41 (59-68)                   Sep,1977\u2013Dec,1986                        Dr. Paul C.Y. Chen \n                                                                                    42-45 (69-72)                   Mar,1987\u2013Dec,1990                   Dr. N. Chandrasekharan \n                                                                                    46-53 (73-80)                   Mar,1991\u2013Dec,1998                       Dr. Victor K.E. Lim \n                                                                                    54-63 (81-90)                   Mar,1999\u2013Dec,2008                   Dr. John T. Arokiasamy \n                                                                                    64,65 (91, 92)                  Mar,2009\u2013Dec,2010                        Dr. Azhar M. Zain \n                                                                                     66,67 (93,94)                   Feb,2011\u2013Dec,2012                             Dr. K.G. Lim \n                                                                                          68 (95)                        Feb,2013\u2013Dec,2013                        Dr. K.G. Lim [1-3]; \n                                                                                                                                                                                  Dr. Khoo Kah Lin [4-6] \n                                                                                          69 (96)                        Feb,2014\u2013Dec,2014                         Dr. Khoo Kah Lin \n                                                                                   70-78*(97-105)                   Feb,2015\u2013present                        Dr. Lekhraj Rampal \n \nPublishers of journal: aStraits Medical Association; bBritish Medical Association Malaya Branch; cMalayan Medical Association; dMalaysian Medical Association; \n*Until the 2023 issue \n\n\n\nTable I: Information on Pre- and Current volumes of the Medical Journal of Malaysia, 1890\u2013 Present\n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 556\n\n\n\n\n\n\n\n\nThe evolution of the Medical Journal of Malaysia - Beyond a Century\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                557 \n\n\n\nexecutive assistant, tasked with assisting in maintaining the \ndifficult and meticulous editorial policy of the Journal\u2019. \nDuring his tenure as the honorary editor, the journal faced \nfinancial problems as the cost of publication continued to \nrise.27 \n\n\n\n \nIn 1987, the first BMA Congress was held in Kuala Lumpur to \nrecognise the MMA as one of the former overseas branches of \nBMA. Despite the fact that MMA was an independent \nassociation in sovereign states, the BMA Congress helped to \nmaintain the old ties and create new ones.28 Dr. N. \nChandrasekharan was the honorary editor from 1987 until \n1990. He was replaced by Dr. Victor K.E. Lim in 1990 [Figure \n2(E)]. The second article on the history of the MJM was \npublished in 1995.29 Dr. John T. Arokiasamy [Figure 2(F)] \nserved as the next honorary editor from 1999 until 2008 and \nwas subsequently replaced by Dr. Azhar M. Zain. [Figure \n2(G)]. Dr. K.G. Lim [Figure 2(H)] took over the helm from Dr. \nAzhar M. Zain in 2011. \n \nIn 2011, the Honarary Editor at that time, Dr. Lim Kean Ghee \nwrote an editorial for the 66th volume of the MJM entitled \n\u2018The Medical Journal of Malaysia: Its History and Its \nMission\u2019.30 The first volume is considered to date back to the \npublication of the Medical Journal of Malaya in 1946. \nHowever, according to him, the Medical Journal of Malaysia \ncan claim 121 years of history based on the heritage of the \nforerunning medical associations such as the StMA, which \nwas established in 1890.30 The appearance of the MJM has \nbeen changing over years (Figure 1). \n \nDr. K.G. Lim\u2019s tenure as the Honorary Editor ended after the \n3rd issue of the 68th volume. Dr. Khoo Kah Lin [Figure 2(I)] \nreplaced him and served until the end of 2014 (Table I). His \nposition as the Honorary Editor was taken over by Dr. Lekhraj \nRampal in 2015. At the annual General Meeting of the \nMalaysian Medical Association in 2019, the post of Honorary \nEditor was changed to Editor in Chief. Dr. Lekhraj Rampal \nhas been serving as the EIC of the MJM from 2015 and \nremains the EIC at the present tenure. A summary of all the \nprevious and current versions of MJM and its editors, \nhonorary editors and EICs are shown in Table I. \n \nIn 2019, the EIC, Professor Datuk Dr. Lekhraj Rampal \ninformed the Editorial Board Members, that the time was now \nripe for moving to the next level. He stated that steps need to \nbe taken to improve the quality and quantity and its impact \nfactor on the health sector. MJM editorial board needs to \nidentify the bottlenecks and remove them. During the period \n2019/2021, bottlenecks were identified and removed to \nensure better quality and quantity. Articles that were \naccepted were published in the next issue. The staff was \nreplaced. Criteria were set for applicants to join the in as \neditors. Younger members were admitted as Editorial Board \nmembers. They had to apply and meet certain criteria. In \n2021, the Editorial Board decided to separate the MJM into \ntwo journals, namely, the Medical Journal of Malaysia and \nthe Medical Journal of Malaysia Case Reports (MJM Case \nReports). This policy change explained by Prof Rampal was \nthat the case reports were not well cited and the journal \ncitation index was being affected.  \n \n \n\n\n\nThe first volume of the MJM without case reports was volume \n77, issue no. 4, published in July 2022. However, the need for \na separate journal for case reports was felt for the training of \nyoung doctors. The policy to have a separate journal for case \nreports was approved in the Annual General Meeting of the \nMMA. The first issue of MJM Case Reports was published in \nAugust 2022 with a new International Standard Serial \nNumber (ISSN) 2948-3859. It contained 22 articles. It is being \npublished regularly, three issues per year.  Case reports \nrepresent a relevant form of advancing medical scientific \nknowledge, especially of rare diseases or conditions. They are \nimportant learning resources for doctors. They are usually the \nfirst encounter that trainees or residents will have in their \nearly careers. It serves also as a platform for them to write \nand learn the techniques of scientific writing.  \n \nMJM: The way forward \nCurrently, in 2023, with the 78th volume, we are also \ncelebrating 133rd years anniversary of the journal since the \npublication of its first version of the JStMA in 1890. Over one \ncentury, we have covered many milestones. The most noted \nis that of sustainability and an increased number of scientific \nmanuscripts published in each volume.  \n \nThe MJM continues to provide a scientific platform for \nmedical doctors and scientists to contribute new knowledge \nwhich leads to better healthcare for the population. The \nreviewing and editing of our medical journal have been \nconducted on a voluntary basis by the medical fraternity. The \nMJM follows the COPE Guidelines and a double-blind peer \nreview system. From initially being only the printed version, \nthe MJM has since 2010 been made available online with free \naccess. The MJM can be accessed at the uniform resource \nlocator http://www.e-mjm.org.31 The availability of archives \nof previous issues from 1980 was made available in 2013.32 In \n2020, under the leadership of the EIC, Professor Datuk Dr. \nLekhraj Rampal, he and his team have performed rigorous \nsearches for the availability of non-digitised issues of the \nMJM. Those issues from 1979 were first made available online \nin December 2020. Most of the past issues from 1960 were \nmade available online in February 2022. The MJM is \ncurrently indexed in MEDLINE, EMBASE, PubMed and \nScopus. The MJM is now moving forward to be indexed in the \nDirectory of Open Access Journals (DOAJ) and Science \nCitation Index Expanded (SCIE). \n \nMJM SCImago Journal Rank (SJR) h-index is 39 (Q3) in \n2023.33 The Medical Journal of Malaysia Metrics 1999\u20132022 \nin the SJR website shows a positive linear correlation \ncoefficient between year and number of citations per \ndocument. The same correlation was shown between the year \nand the total citations with almost zero linear correlation \ncoefficient between year and self-citation. These figures \nindicate that the increasing number of total citations was not \ndue to self-citation with the number of self-citations \nremaining low over the past 23 years in the MJM (Figure 3). \nAbrizah reported that MJM was one of the Malaysian \nmedical journals with the highest h-index score based on the \nMalaysian Medical Journals Indexed in MyCite in 2015 \nreport.34 There has been an increasing trend of original \narticles being submitted to the MJM. Despite the separation of \ncase reports and case series from the MJM, there have been \nencouraging numbers of publications in the MJM Case \n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 557\n\n\n\n\n\n\n\n\nEditorial \n\n\n\n558                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nReports. The number of proceedings from meetings held in \nMalaysia has been encouraging due to its high prestige \n(Figure 4). \n \n \nCONCLUSION \nThe MJM has evolved from its initial publications of variously \nnamed as the Journal of Straits Medical Association in 1890, \nJournal of the Malaya Branch of the BMA session in 1904, the \nMalaya Medical Journal in 1911, the Medical Journal of \nMalaya in 1946 and the current MJM since 1972. MJM has \nbeen served by 22 editors since its inception in 1890. \nCurrently, in 2023, with the 78th volume, we are also \ncelebrating 133 years anniversary of the journal since the \npublication of its first version of the JStMA in 1890. Over one \ncentury, we have covered many milestones. The most noted \nis that of sustainability, an increased number of scientific \nmanuscripts published, the number of issues each year and \nincreased citations. The MJM is now the journal of choice \namong clinical researchers in Malaysia to publish their \nresearch findings and is one of the most cited medical \njournals published in Malaysia. It has marched forward to \nensure the MJM remains as an open-access journal with its e-\nversion with limited copies of the printed form. The MJM \ncontinues to improve the lives of all people by assisting and \nstrengthening the capacities of clinicians, academicians, \npractitioners and scientists by publishing sound scientific \narticles. \n \n \nACKNOWLEDGEMENTS \nWe wish to express our sincere gratitude to Dr. Azhar M. Zain \nand Dr. K.G. Lim (former Editors of MJM), Professor Dr. Victor \nHoe and Professor Dr. Pakeer Oothuman for spending their \nprecious time reviewing this paper. We also wish to express \nour sincere appreciation to the MMA EXCO Members \n(2022/2023) led by Dr. Muruga Raj A/L Rajathurai for their \nfull support to the current editorial board of the MJM. \n \n \nREFERENCES \n1. The Journal of the Straits Medical Association. 1890. \n\n\n\nEresources.nlb.gov.sg. [cited August 2023]. Available from: \nhttps://eresources.nlb.gov.sg/  \n\n\n\n2. Singapore Government Agency. Our History of Healthcare. [cited \nAugust 2023]. Accessed from: \nhttps://www.roots.gov.sg/en/stories-landing/stories/history-of-\nhealthcare-sg \n\n\n\n3. Simon MF. Introductory Note. The Journal of the Straits Medical \nAssociation. 1890; 1:i-ii \n\n\n\n4. Tiew WS. Some scholarly English periodicals in pre-independent \nMalaysia: An historical overview. Malaysian Journal of Library \nand Information Science. 1999;4 (1):27-40 \n\n\n\n5. Kerr TS. Annual General Meeting. The Journal of the Straits \nMedical Association. 1894; 5:7-11 \n\n\n\n6. Khoo FY. X-rays in Singapore 1896-1975. Singapore University \nPress for the Radiological Society of Singapore. 1981 \n\n\n\n7. Chia JYJ. Straits Medical Association. Singapore Infopedia. \nEresources.nlb.gov.sg. [cited August 2023]. Accessed from: \nhttps://eresources.nlb.gov.sg/ \n\n\n\n8. The Journal of the Malaya Branch of the BMA. 1904-1905. \nEresources.nlb.gov.sg. [cited August 2023]. Accessed from:  \nhttps://eservice.nlb.gov.sg/  \n\n\n\n9. The Journal of the Malaya Branch of the BMA. 1904-1906; 3. \nEresources.nlb.gov.sg. [ cited August 2023]. Accessed from: \nhttps://eservice.nlb.gov.sg/  \n\n\n\n10. The Malaya Medical Journal. 1911; 9(Part 1). \nEresources.nlb.gov.sg. [cited August 2023]. Accessed from: \nhttps://eservice.nlb.gov.sg/ \n\n\n\n11. The Malaya Medical Journal. 1912;10 (Part 1). \nEresources.nlb.gov.sg. [cited August 2023]. Accessed from:  \nhttps://eservice.nlb.gov.sg/ \n\n\n\n12. Wikimedia Foundation. George Vance Allen. Wikipedia. August \n15, 2023. [cited August 2023]. Accessed from: \nhttps://en.wikipedia.org/wiki/George_Vance_Allen  \n\n\n\n13. Malayan Medical Journal: Adopted as Official Organ of B.M. \nAssociation. The Straits Times. 1926; Dec 17:9 \n\n\n\n14. The Journal of the Malaya Branch of the British Medical \nAssociation. 1939; II (4). Eresources.nlb.gov.sg. [cited August \n2023]. Accessed from: https://eservice.nlb.gov.sg/ \n\n\n\n15. The Journal of the Malaya Branch of the British Medical \nAssociation. 1939;3(3). Eresources.nlb.gov.sg. [cited August \n2023]. Accessed from: https://eservice.nlb.gov.sg/ \n\n\n\n16. Anderson RE. Medical Prisoners in Singapore. Br Med J. \n1945;2(4427):660-1. \n\n\n\n17. Teng CL, Lim KG, Ang CY, Chan SY, Sam EKS, Wee JCS, et al. Pre-\nindependence medical journals in British Malaya: A content \nanalysis. IeJSME 2019 13(2): 23-26 \n\n\n\n18. Webb J. Malaya Branch of B.M.A. and R.M.B.F. Br Med J, \n1949;1:70 \n\n\n\n19. Doctors unite on \u2018service before self\u2019 banner. The Straits Times. \n1958; Nov 5:8 \n\n\n\n20. New association for doctors rejected. The Straits Times. 1959; Mar \n7:8 \n\n\n\n21. A \u2018No\u2019 to A Malayan Medical Body: Federation refuses \nregistration. The Straits Times. 1959; Jul 2:7 \n\n\n\n22. Two local bodies to replace the British Medical Association. The \nStraits Times. 1959; Aug 4:16 \n\n\n\n23. Singapore doctors get all-in-one association. The Straits Times. \n1959; Aug 31:4 \n\n\n\n24. Wikimedia Foundation.  Singapore Medical Journal. Wikipedia. \n2023; May 5. [cited August 2023]. Accessed from: \nhttps://en.wikipedia.org/wiki/ Singapore_Medical_Journal \n\n\n\n25. Scharff JW. The life and times of Sir David Galloway Singapore \nMed J. 1960;1(3):84-6 \n\n\n\n26. Malaysian Society of Parasitology and Tropical Medicine. [cited \nAugust 2023]. Accessed from: https://msptm.org/about/ \n\n\n\n27. Chen CT. The Medical Journal of Malaysia: Past and Future. Med \nJ Malaysia. 1982;37(1):1-6 \n\n\n\n28. Beecham  L,  Smith  T.  Conference  Report:  Minarets  and \nmicrochips: the BMA in Kuala Lumpur. Br Med J (Clin Res Ed). \n1987 Oct 31;295(6606):1126\u20139. PMCID: PMC1248191. \n\n\n\n29. Lim VKE. A short history of the Medical Journal of Malaysia. Med \nJ Malaysia. 1995;50 Suppl A:S11-3. \n\n\n\n30. Lim KG. The Medical Journal of Malaysia: its history and its \nmission. Med J Malaysia. 2011;66(3):173-174. \n\n\n\n31. Lim KG. The e-mjm. Med J Malaysia. 2010 Jun;65(2):97. \n32. Lim KG. The e-mjm goes LIVE to PubMed. Med J Malaysia. 2013 \n\n\n\nJun;68(3):195-4. \n33. Medical Journal of Malaysia. Scimago Journal & Country Rank. \n\n\n\n[cited August 2023]. Accessed from: https://www.scimagojr.com/ \njournalsearch.php?q=17838&tip=sid \n\n\n\n34. Abrizah A. Performance of Malaysian Medical Journals. Malays \nJ Med Sci. 2016 Mar;23(2):1-5. \n\n\n\n1A-The evolution.qxp_3-PRIMARY.qxd  27/09/2023  3:13 PM  Page 558\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\n\n\n\n\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\n594                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Intravenous thrombolysis (IVT) with \nrecombinant tissue plasminogen activator is beneficial in \nacute ischaemic stroke (AIS). We aim to compare the real-\nworld clinical outcomes and service efficiency of IVT in \nMalaysian primary stroke centres (PSCs) versus acute \nstroke ready hospitals (ASRHs). \n \nMaterials and Methods: We conducted a multi-centre cohort \nstudy involving 5 PSCs and 7 ASRHs in Malaysia. Through \nreview of medical records of AIS patients who received IVT \nfrom 01 January 2014 to 30 June 2021, real-world data was \nextracted for analysis. Univariate and multivariate \nregression models were employed to evaluate the role of \nPSCs versus ASRHs in post-IVT outcomes and \ncomplications. Statistical significance was set at p<0.05.  \n \nResults: A total of 313 multi-ethnic Asians, namely 231 from \nPSCs and 82 from ASRHs, were included. Both groups were \ncomparable in baseline demographic, clinical, and stroke \ncharacteristics. The efficiency of IVT delivery (door-to-\nneedle time), functional outcomes (mRS at 3 months post-\nIVT), and rates of adverse events (intracranial haemorrhages \nand mortality) following IVT were comparable between the 2 \ngroups. Notably, 46.8% and 48.8% of patients in PSCs and \nASRHs group respectively (p=0.752) achieved favourable \nfunctional outcome (mRS\u22641 at 3 months post-IVT). \nRegression analyses demonstrated that post-IVT functional \noutcomes and adverse events were independent of the role \nof PSCs or ASRHs. \n \nConclusion: Our study provides real-world evidence which \nsuggests that IVT can be equally safe, effective, and \nefficiently delivered in ASRHs. This may encourage the \nestablishment of more ASRHs to extend the benefits of IVT \nto a greater proportion of stroke populations and enhance \nthe regional stroke care. \n\n\n\nKEYWORDS:  \nAcute ischemic stroke, thrombolysis, stroke ready hospitals, \nfunctional outcomes, efficiency, safety \n \n \nINTRODUCTION \nIntravenous thrombolysis (IVT) with recombinant tissue \nplasminogen activator (rt-PA) has been a well-established \nemergency intervention in acute ischaemic stroke (AIS) since \n1995.1-9 However, such therapy may not be readily available \nin district/community hospitals, especially in countries with \nlower neurologist: population ratio. We hypothesise that as \n(i) the efficacy of IV rt-PA has been extensively proven,1-7 (ii) \ncoupled with the presence of objective, internationally \nstandardised indications and contraindications of IV rt-PA in \nAIS,1-2,9 (iii) in addition to the availability of local evidence-\nbased protocol and (iv) the growing use of telemedicine to \nguide decision-making, IVT can potentially be administered \nin these district/community hospitals without neurologist in \na timely, safe and effective manner. \n \nAccordingly, evidence has consistently shown the beneficial \neffects of IVT in AIS even when administered by non-\nneurologists in non-stroke centres.10-12 However, similar \ntargeted research involving multi-ethnic Asian populations \nin this region is scarce. We aim to appraise and compare the \nreal-world efficiency, effectiveness and safety of IVT among \nmulti-ethnic Asians in Malaysian public primary stroke \ncentres (PSCs) versus acute stroke-ready hospitals (ASRHs). \n \n \nMATERIALS AND METHODS \nWe conducted a multi-centre cohort study (combination of \nhistorical, retrospective and prospective cohort) involving \nanalyses of real-world data. This real-world study involved \nfive public PSCs and seven public ASRHs in Malaysia. \nQualifying criteria of PSCs and ASRHs were in accordance \n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute \nischaemia stroke in Malaysian public primary stroke centres \nversus acute stroke ready hospitals: Comparison of real-\nworld clinical outcomes \n \nSchee Jie Ping1,2, Ang Chai Liang1, Crystal Teoh Sing Chiek3, Tan Hui Jieh4, Chew Sin Hong5, Anderson Steven3, \nHii Ding Wei3, Chin Yen Theng6, Loh Ee Wen7, Desmond Samuel8, Pravind Narayanan9, Mazlina Husin6, Linda \nThen Yee Yen3, Cheah Chun Fai4, Cheah Wee Kooi10, Zainura Che Isa11, Aznita Ibrahim11, Chia Yuen Kang5, \nKhairul Azmi Ibrahim6, Looi Irene12, Law Wan Chung3, Zariah Abdul Aziz6 \n\n\n\n     \n1Department of Medicine, Tawau Hospital, Sabah, Malaysia, 2Division of Neurology, Department of Medicine, Faculty of \nMedicine, University of Malaya, Malaysia, 3Department of Medicine, Sarawak General Hospital, Sarawak, Malaysia, \n4Department of Medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia, 5Department of Medicine, Queen Elizabeth \nHospital, Sabah, Malaysia, 6Department of Medicine, Sultanah Nur Zahirah Hospital, Terengganu, Malaysia, 7Department of \nMedicine, Bintulu Hospital, Sarawak, Malaysia, 8Department of Medicine, Miri Hospital, Sarawak, Malaysia, 9Department of \nMedicine, Sarikei Hospital, Sarawak, Malaysia, 10Department of Medicine, Taiping Hospital, Perak, Malaysia, 11Department of \nMedicine, Sultan Abdul Halim Hospital, Kedah, Malaysia, 12Department of Medicine, Seberang Jaya Hospital, Penang, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 05 July 2023                                                                                                                                                                              \nCorresponding Author: Crystal Teoh Sing Chiek                                                                                                                                                                  \nEmail: crystalteoh13@gmail.com\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 594\n\n\n\n\n\n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                595 \n\n\n\nwith the American Stroke Association & The Joint \nCommission Stroke Certification criteria. The five PSCs were \nSarawak General Hospital, Queen Elizabeth Hospital, \nSultanah Nur Zahirah Hospital, Seberang Jaya Hospital and \nRaja Permaisuri Bainun Hospital. Meanwhile, the seven \nASRHs were Tawau Hospital, Taiping Hospital, Bintulu \nHospital, Miri Hospital, Sarikei Hospital, Sultan Abdul Halim \nHospital and Lahad Datu Hospital. Clinical data were \ncollected through a review of medical records and extracted \nfrom the local stroke registry. \n \nThe data collection period was from December 2019 to \nDecember 2021. All patients who received IVT from 1 January \n2016 to 31 December 2021 in these 12 study centres were \npotential subjects. These patients were being followed up for \nfunctional outcomes in Modified Rankin Scale (mRS) and \nmortality status. Assessments findings were documented \ncontemporaneously in their medical records and stroke \nregistries. This study was a combination of historical, \nretrospective and prospective cohort study as we included \npatients who (i) received IVT and had at least 3 months of \nfollow-up post-IVT at the beginning of data collection period \n(historical cohort); (ii) received IVT and were still under \nongoing follow-up at the beginning of data collection period \n(retrospective cohort); (iii) received IVT within the data \ncollection period, followed by the standard follow-up for at \nleast 3 months (prospective cohort). \n \nThe first author (S.J.P.), who is also the principal and \ncoordinating investigator of the study, had full access to the \ndata. The authors vouch for the accuracy and completeness \nof data, in addition to strict adherence to study protocol and \nstatistical analysis. \n \nStudy Populations/Patients \nOur inclusion criteria were patients (i) with clinical diagnosis \nof AIS according to WHO criteria13, (ii) age of \u226518 years at the \ntime of receiving IVT, (iii) received IVT within 4.5 hours from \nAIS onset, at a dose of 0.9 mg/kg and maximum 90 mg, (iv) \n\u22653 months of follow-up after IVT. Patients who died within 3 \nmonths post-IVT were included in the analyses on mortality \noutcome. Exclusion criteria were patients (i) aged <18 years \nat the time of receiving IVT, (ii) received IVT in an extended \nwindow, i.e., >4.5 hours after AIS onset, (iii) received other \nreperfusion therapies (e.g. intra-arterial thrombolysis,  \nmechanical/endovascular thrombectomy) within 90 days \npost-IVT, (iv) no data on door-to-needle time (DNT), \nintracranial haemorrhages following IVT, mRS at 3 months \npost-IVT and   mortality up to 3 months post-IVT.  \nAnonymized real-world data were collected through a review \nof medical records and local stroke registry. Informed consent \nwas obtained from all study subjects, approving the use of \ntheir anonymised data in analyses and publication of \nfindings. \n \nClinical Assessments and Outcome Measures \nSubtypes of AIS among study patients were grouped \naccording to the TOAST classification.14 These five subtypes \nwere (i) large artery atherosclerosis, (ii) small vessel occlusion, \n(iii) cardioembolism, (iv) other determined aetiologies and (v) \nundetermined aetiologies.  Stroke severity upon presentation, \nmeasured by National Institutes of Health Stroke Scale \n(NIHSS), was assessed by neurologists in PSCs and trained \n\n\n\nphysicians in ASRHs, respectively. The Alberta Stroke \nProgram Early CT Score (ASPECTS) were evaluated and \nreported by radiologists.15,16 \n \nThe onset-to-needle time (ONT) was defined as the duration \nfrom the onset of AIS symptoms to the time of IVT \nadministration. The DNT was defined as the duration from \nthe time of patient\u2019s arrival at emergency department to the \ntime of first bolus dose of thrombolytic. mRS was employed to \nmeasure the degree of disability. Intracranial haemorrhages \n(ICH) following IVT, namely   (i)   any ICH, (ii) symptomatic \nICH (sICH) as per ECASS III definition2 and (iii) fatal ICH were \nrecorded. Mortality following IVT, namely (i) inpatient \nmortality, i.e., mortality within the same/index hospital \nadmission and (ii) all-cause mortality within 3 months (90 \ndays) post-IVT, were recorded. \n \nAIS characteristics and severity upon presentation were \nevaluated by using TOAST subtypes, NIHSS and ASPECTS \nscore. The efficiency of IVT delivery was evaluated through \nDNT and proportion of patients with DNT <60 minutes. The \neffectiveness of IVT was assessed through mRS at 3 months \n(90 \u00b1 5 days), number of patients with favourable functional \noutcomes (mRS \u22641 at 3 months) and unfavourable functional \noutcomes (mRS \u2265 2 at 3 months). Meanwhile, safety of IVT \nwas assessed by rates of any ICH, sICH, fatal ICH, inpatient \nmortality and 90 days all-cause mortality. \n \nStatistical Analysis \nStatistical Package of Social Sciences (SPSS) for Windows \nversion 28.0 (IBM Corporation, Armonk, NY, USA) was \nemployed. Baseline demographic and clinical characteristics \nwere presented as absolute numbers and percentage for \ncategorical variables, mean and standard deviation (SD) for \nnormally distributed continuous variables, and median and \ninterquartile ranges for continuous variables with skewed \ndistribution or ordinal data. Shapiro\u2013Wilk test was used to \nassess the normality of data distribution. \n \nUpon comparing the variables between two groups (PSCs \nversus ASRHs), the independent sample t test and Mann\u2013\nWhitney U test were used for the analyses of continuous \nvariables, while Pearson\u2019s chi-square and Fisher\u2019s exact test \nwere used for the analyses of categorical variables.   A two-\nsided P value of <0.05 was considered statistically significant. \nUnivariable and multivariable logistic regression analyses \nwere conducted to investigate the association between \nvarious outcomes of interest and independent variables. All \nvariables with p value of <0.1 in the univariable analyses \nwere included in the final multivariable analyses. The results \nwere presented in the form of crude odds ratios (OR) and \nadjusted OR with the respective 95% confidence interval (CI). \nP value of <0.05 signifies statistical significance. \n \nStandard Protocol Approvals and Study Registrations \nThis study was registered with the Malaysian National \nMedical Research Register (study ID: NMRR-19-3731-52272). \nStudy protocol was approved and supported by the National \nInstitutes of Health Malaysia. Ethical approval was obtained \nfrom the Malaysian Medical Research and Ethics Committee. \nApproval for publication was granted by the Director-\nGeneral of Health Malaysia. \n \n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 595\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n596                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nThis study followed the Strengthening the Reporting of \nObservational Studies in Epidemiology (STROBE) reporting \nguideline. This study was conducted in strict compliance with \nethical principles outlined in the Declaration of Helsinki and \nMalaysian Good Clinical Practice Guideline. Strictly no minor \nnor vulnerable subjects were enrolled in the study. Only \nanonymised, non-identifying data were extracted/collected. \n \n \nRESULTS \nA total of 313 multi-ethnic Asian patients, namely 231 \n(73.8%) from PSCs and 82 (26.2%) from ASRHs were \nincluded. The baseline demographic (age, gender, ethnicity) \nand clinical characteristics (comorbidities/vascular risk \nfactors) of these two groups of patients were comparable, with \nthe exception of the proportions of active smokers. Rates of \nprior antiplatelet and/or anticoagulant use within 7 days \nprior to stroke onset were similar in both PSCs and ASRHs \ngroups (29.0% vs 29.3%) as well. Types of antiplatelets and \nanticoagulants used were listed in Table I. \n \nStroke Characteristics and Severity at Presentation \nThese two groups of patients demonstrated similar \nproportions in each TOAST subtype. Both groups recorded \ncomparable NIHSS upon presentation, namely a median \nNIHSS of 11 (IQR: 8\u201317) in PSCs and a median NIHSS of 12 \n(IQR: 9\u201316) in ASRHs (p = 0.833).  Both groups also have \ncomparable ASPECTS, with a median ASPECTS of 9 (IQR: 8\u2013\n10) in both PSCs and ASRHs (p = 0.879) groups (Table I). \n \nEfficiency of Delivery of IVT \nBoth groups recorded similar ONT. Notably, the DNT was \ncomparable between the two groups as well, namely a \nmedian of 85 (IQR: 56\u2013118) minutes in PSCs and a median of \n93 (IQR: 60\u2013125) minutes in ASRHs, p = 0.470. In addition, \nthe proportion of patients with DNT <60 minutes was similar, \nnamely 30.7% in PSCs and 30.5% in ASRHs, p = 0.967 (Table \nII). \n                                                                                                    \nClinical Outcomes Following IVT  \nmRS at 3 months was identical between the two groups, with \na median of 2 (IQR: 1\u20134) in PSCs and  2 (IQR: 1\u20133) in ASRHs, \np = 0.707. Percentage of patients with favourable functional \noutcomes, i.e., mRS \u2264 1 at 3 months post-IVT, was \ncomparative as well, namely 46.8% in PSCs and 48.8% in \nASRHs, p = 0.752 (Table II and Figure 1 mRS bar chart). \n \nHaemorrhages and Mortality following IVT \nBoth PSCs and ASRHs groups demonstrated similar rates of (i)   \nany ICH, 17.7% vs 18.3%, p = 0.912; (ii) symptomatic ICH, \n10.4% vs 7.3%, p = 0.417; (iii) fatal ICH, 3.9% vs 4.9%, p = \n0.749, (iv) inpatient mortality, 13.9% vs 11.0%, p = 0.507 and \n(v) all-cause mortality within 90 days post-IVT, 15.2% vs \n14.6%, p = 0.910. Causes of death were listed in Table II. The \nmost common causes of death in both groups were fatal ICH, \npneumonia and acute coronary syndrome (Table II). \n \nSubgroups Analyses \nAmong the 313 study patients, 148 patients (47.3%) had \nfavourable functional outcomes (mRS \u22641) whereas 165 \npatients (52.7%) had unfavourable functional outcomes \n(mRS \u22652) at 3 months post-IVT. Patients with favourable \n\n\n\nfunctional outcomes demonstrated significantly (i) younger \nage, (ii) lower NIHSS at presentation, (iii) higher ASPECTS at \npresentation, (iv) shorter DNT, (v) greater proportion with \nDNT <60 minutes and (vi) lower rates of ICH. These two \ngroups of patients are comparable in terms of gender, \nethnicity, comorbidities/vascular risk factors, and TOAST \nsubtype (Table III). \n \nUnivariable and Multivariable Logistic Regression \nAnalyses \nAmong the overall cohort of 313 patients, factors that were \nsignificantly associated with favourable functional outcomes \n(Table IV) include (i) younger age, (ii) lower NIHSS at \npresentation, shorter DNT and (iv) absence of sICH. Notably, \nfunctional outcomes were independent of the role of PSCs or \nASRHs, gender, ethnicity and comorbidities/vascular risk \nfactors. \n \nFactors significantly associated with any type of post-IVT ICH \namong the overall cohort of 313 patients (refer \nSupplementary Table I) included (i) older age and (ii) higher \nNIHSS at presentation. Meanwhile, factors significantly \nassociated with sICH (refer Supplementary Table II) included \n(i) lower ASPECTS at presentation and (ii) longer DNT. The \nrole of PSCs versus ASRHs, age, gender, ethnicity, \ncomorbidities/vascular risk factors, NIHSS at presentation \nand antiplatelet or anticoagulant use were not significantly \nassociated with ICH.  \n \nIn addition, factors significantly associated with 90-day all-\ncause mortality among the overall cohort of 313 patients \n(refer Supplementary Table III) included (i) longer DNT and \n(ii) presence of sICH, regardless of the role of PSCs vs ASRHs, \nage, gender, ethnicity, comorbidities/vascular risk factors, \nNIHSS and ASPECTS at presentation. \n \nIn the PSC cohort, (i) factors significantly associated with \nfavourable functional outcomes (refer Supplementary Table \nIV) included lower NIHSS at presentation, shorter DNT and \nabsence of sICH;  (ii) factors significantly associated with any \ntype of post-IVT ICH (refer Supplementary Table V) included \nlower ASPECTS at presentation and longer DNT; (iv) factors \nsignificantly associated with post-IVT sICH (refer \nSupplementary Table VI) included female gender, lower \nASPECTS at presentation, and longer DNT and (v) factor \nsignificantly associated with overall 90-day all-cause \nmortality (refer Supplementary Table VII) included older age \nand longer DNT. \n \nIn the ASRH cohort, (i) factors significantly associated with \nfavourable functional outcomes (refer Supplementary Table \nVIII) included younger age and lower NIHSS at presentation \nand (ii) factors significantly correlated with overall 90-day \nall-cause mortality (refer Supplementary Table IX) was lower \nASPECTS at presentation.  \n \nDNT \u226460 Minutes Versus DNT >60 Minutes \nAlmost equal proportion of patients, namely 30.7% in PSCs \nand 30.5% in ASRHs, recorded DNT \u226460 minutes. Among the \noverall cohort of 313 study patients, 96 (30.7%) recorded DNT \n\u226460 minutes while 217 (69.3%) recorded DNT >60 minutes. \nSubsequently, 59 (61.5%) of the 96 patients with DNT \u226460 \n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 596\n\n\n\n\n\n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                597 \n\n\n\nminutes recorded favourable functional outcomes while only \n89 (41.0%) of the 217 patients with DNT >60 minutes \nrecorded favourable functional outcomes at 3 months, p = \n0.001. At 3 months, patients with DNT \u226460 minutes recorded \nmedian mRS of 1 (IQR: 0\u20132) while patients with DNT >60 \nminutes recorded median mRS of 2 (IQR: 1\u20134), p < 0.001. \n \n \nDISCUSSION \nComparison of the efficiency, effectiveness and safety of IVT \nadministration in public primary versus acute stroke-ready \nhospitals were reflected in this real-world study through \nperformance metrics in DNT, functional outcomes by mRS, \nmortality and rates of intracerebral haemorrhages. Our \npatients in both public PSC and ASRH cohorts demonstrated \nsimilar demographics and baseline clinical characteristics, \nstroke subtypes as defined by TOAST classifications and \nstroke severity upon presentation in terms of NIHSS and \nASPECTS. Comparable efficiency (DNT), effectiveness \n(functional outcomes) and safety (ICH and mortality rates) \nprofiles of IVT were recorded in both groups. This may imply \nthat IVT service can be equally safe, effective and efficiently \ndelivered in ASRHs.  \n \nAs of date, there were only 138 registered neurologists in \nMalaysia (both public and private sectors), which translates \n\n\n\nto 1 neurologist to almost 250,000 populations. Thus, there \nare critical shortage of neurologists to support the IVT service \nnationwide, especially in East Malaysia. Majority of the rural \nand remote hospitals are not equipped with in-house \nneurologists. Hence, there was an increasing need to establish \nASRH to extend the benefits of IVT to a greater proportion of \nstroke patients. In Malaysia, physicians (specialists in \nInternal Medicine) have taken the initiative to initiate IVT \nservice in some of these centres, guided by telemedicine \nconsultation with neurologists. These physicians are tasked to \ndraft acute stroke protocols and workflows while ensuring \nstrict adherence to the protocol in daily practice. \n \nChallenges and limitations in Malaysian ASRHs include (i) \nlack of certified expertise namely in-house neurologists; (ii) \nlack of stroke centres and regional stroke networks in close \nproximity; (iii) logistic constraints which limit inter-hospital \ntransfer; (iv) lack of established telestroke network or \nteleradiography system; (v) limited healthcare facilities and \n(vi) lack of advanced neuroimaging. \n \nThe results of our study may proactively advocate the \nestablishment of more ASRHs despite the current challenges \nand limitations. A few collaborative efforts and initiatives are \nneeded, which includes (i) establishing structured training \nand certification programme to equip physicians in offering \n\n\n\nPatient\u2019s characteristics                                                        PSCs (n = 231)                         ASRHs (n = 82)                          P value \nAge (mean \u00b1 S.D.)                                                                       57.4 \u00b1 13.1                                56.4 \u00b1 12.6                               0.540I \nGender (male:female)                                                                    150:81                                        54:28                                   0.881II \n\n\n\n                                                                                            64.9%:35.1%                            65.9%:34.1%                                   \nEthnicity (Malay:Chinese:Indian:Others)                                  129:31:14:57                               41:14:8:19                               0.537II \n\n\n\n                                                                                  55.8%:13.4%:6.1%:24.7%       50.0%:17.1%:9.8%:23.2%                        \nDiabetes mellitus                                                                     80/231 (34.6%)                          28/82 (34.1%)                            0.937II \nHypertension                                                                          152/231 (65.8%)                         58/82 (70.7%)                            0.414II \nDyslipidemia                                                                            63/231 (27.3%)                          29/82 (35.4%)                            0.167II \nCoronary artery disease                                                          46/231 (19.9%)                          15/82 (18.3%)                            0.750II \nAtrial fibrillation/flutter                                                          39/231 (16.9%)                          13/82 (15.9%)                            0.830II \nValvular heart diseases                                                             5/231 (2.2%)                              1/82 (1.2%)                              1.000III \nHistory of previous CVA/TIA                                                   33/231 (14.3%)                          12/82 (14.6%)                            0.938II \nSmoking (active smokers)                                                       87/231 (37.7%)                          43/82 (52.4%)                            0.020II \nPrior antiplatelet/anticoagulant use                                      67/231 (29.0%)                          24/82 (29.3%)                            0.964II \n\n\n\nI.   Aspirin                                                                                  52/67                                         18/24 \nII.  Clopidogrel                                                                            3/67                                           1/24                                          \nIII. Warfarin                                                                                7/67                                           4/24 \nIV. NOACs                                                                                   2/67                                           1/24 \nV.  Aspirin + clopidogrel                                                            2/67                                           0/24 \nVI. Aspirin + warfarin                                                                1/67                                           0/24                                          \n\n\n\nStroke characteristics \nSubtype (TOAST classification) \n\n\n\nI.   Large artery atherosclerosis                                       102/231 (44.2%)                         35/82 (42.7%) \nII.  Small vessel occlusion                                                  68/231 (29.4%)                          24/82 (29.3%)                              N/A \nIII. Cardioembolism                                                           40/231 (17.3%)                          17/82 (20.7%) \nIV. Other determined aetiologies                                      2/231 (0.9%)                                0/82 (0%) \nV. Undetermined aetiology                                               19/231 (8.2%)                             6/82 (7.3%)                                    \n\n\n\nMedian NIHSS at presentation                                                    11 (8-17)                                    12 (9-16)                                0.833IV \nMedian ASPECTS at presentation                                                 9 (8-10)                                      9 (8-10)                                 0.879IV \n \nI. Independent sample t test \nII. Pearson\u2019s chi square \nIII. Fisher\u2019s exact test \nIV. Mann\u2013Whitney U test \n \nOthers = natives/indigenous populations of Southeast Asia.  \nASRH, acute stroke-ready hospital; CVA, TIA, \n\n\n\nTable I: Baseline Demographic, Clinical and Stroke Characteristics\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 597\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n598                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nEfficiency of IVT delivery                                                       PSCs (n = 231)                         ASRHs (n = 82)                          P value \nMedian onset-to-needle time (minutes)                                 190 (155\u2013225)                           185 (139\u2013226)                            0.276IV \nMedian door-to-needle time (minutes)                                    85 (56\u2013118)                               93 (60\u2013125)                              0.470IV \nDoor-to-needle time <60 minutes                                         71/231 (30.7%)                          25/82 (30.5%)                            0.967II \nPost-IVT clinical outcomes                                                                                                                                                                \nMedian 3 months mRS                                                                   2 (1\u20134)                                       2 (1\u20133)                                  0.707IV \nFavourable functional outcomes                                                  108/231                                       40/82                                   0.752II \n(3 months mRS \u22641)                                                                        (46.8%)                                     (48.8%)                                       \nPoor functional outcomes                                                             40/231                                        14/82                                   0.960II \n(3 months mRS \u22655)                                                                        (17.3%)                                     (17.1%)                                       \nHaemorrhages and mortality                                                                                                                                                             \nAny intra-cranial haemorrhages (ICH)                                          41/231                                        15/82                                   0.912II \n(including haemorrhagic transformation)                                   (17.7%)                                     (18.3%)                                       \nSymptomatic ICH (ECASS III definition)                                        24/231                                         6/82                                    0.417II \n\n\n\n                                                                                                 (10.4%)                                      (7.3%)                                        \nFatal ICH                                                                                           9/231                                          4/82                                    0.749III \n\n\n\n                                                                                                  (3.9%)                                       (4.9%)                                        \nInpatient mortality                                                                         32/231                                         9/82                                    0.507II \n\n\n\n                                                                                                 (13.9%)                                     (11.0%) \nI.   Fatal ICH                                                                                9/32                                            4/9 \nII.  Pneumonia                                                                            9/32                                            3/9                                           \nIII. ACS and cardiac failure                                                        7/32                                            1/9 \nIV. Severe stroke/massive infarct                                               4/32                                            1/9 \nV.  Other stroke-related complications                                    3/32                                            0/9 \n\n\n\n90 days all-cause mortality                                                            35/231                                        12/82                                   0.910II \n                                                                                                 (15.2%)                                     (14.6%) \nI.    Fatal ICH                                                                               9/35                                           4/12 \nII.   Pneumonia                                                                          10/35                                          4/12 \nIII.  ACS and cardiac failure                                                       9/35                                           3/12 \nIV.  Severe stroke/massive infarct                                             4/35                                           1/12 \nV.  Other stroke-related complications                                    3/35                                           0/12                                          \n\n\n\n \nV. Independent sample t test \nVI. Pearson\u2019s chi square \nVII. Fisher\u2019s exact test \nVIII. Mann\u2013Whitney U test \nASRH, acute stroke-ready hospital; IVT, intravenous thrombolysis; mRS, Modified Rankin Scale; PSC, primary stroke centres. \n\n\n\nTable II: Efficiency of IVT delivery,Post-IVT clinical outcomes, Incidence of haemorrhages and mortality \n\n\n\nIVT, (ii) establishing and enhancing telestroke networks and \nteleradiography system, hence allowing more neurologists \nand radiologists to remotely support IVT service, (iii) \nimproving inter-hospital patient transfer system and (iv) \nincreasing availability of CT machine in rural/remote areas. \nThe national clinical practice guidelines on stroke \nmanagement is an essential tool to supplement these efforts \nas well. \n \nEssentially, there are multiple unmet needs in the provision \nof IVT in resource-limited settings, namely number of trained \nprofessionals, supporting staffs, facilities and information \ntechnology (IT) services. However, there are certain measures \nwhich can be carried out in the short run, for example, by \nincreasing the number of training platforms/resources \nonline, stroke simulation training or hands-on workshop \norganised by tertiary stroke centres to address the knowledge \ngap. Meanwhile, with regards to longer term planning, an \nincrease in budget allocation to procure basic equipments, \nsuch as scan machine, beds, blood pressure/cardiac \nmonitoring devices should be prioritised. \n \nFindings of our regression analyses highlight the importance \nof shortening DNT as it is a modifiable factor significantly \nassociated with favourable functional outcomes. Longer DNT \nis significantly associated with poorer functional outcomes, \nsICH and overall 90-day all-cause mortality. Results \npresented in \u201cSubgroups Analyses\u201d and \u201cDNT \u226460 Minutes \n\n\n\nVersus DNT >60 Minutes\u201d further supplement such findings. \nAlmost 70% of study patients recorded DNT >60 minutes in \nboth PSCs and ASRHs. Comprehensive data on door-to-CT \ntime and CT-to-needle time was not consistently available \nacross all centres. Hence it is not feasible to determine \nwhether our long DNT was caused by either or both \ncomponents. However, the causes of our long DNT in general \nmay include (i) delay in decision making and offering \nconsent by patients and/or family (ii) delay in organising \nneuroimaging due to limited infrastructure and (iii) stroke \ncode workflow unfamiliarity among healthcare personnel. \n \nWe hereby propose measures which can be undertaken to \nshorten DNT: (i) increase public awareness regarding the \navailability and benefits of IVT in acute stroke through \nwidespread campaign and education nationwide. (ii) equip \nhigh-volume public centres with more CT machines to \naccommodate the increasing patient\u2019s loads locally. (iii) \nminimise delay between steps during stroke code activation \nby introducing better-structured training and refresher course \nfor stroke care personnel nationwide, (iv) conduct regular \nquality improvement projects and clinical audits to improve \nperformance and consequentially quality of care and (v) \nestablish telestroke networks involving dedicated neurologists \nand neuroradiologists in respective states nationwide. This \nmay assist physicians in swift decision-making on IVT with \ngreater confidence, especially in ASRHs. \n \n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 598\n\n\n\n\n\n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                599 \n\n\n\nThe strengths of this study include (i) inclusion of 12 public \ncentres nationwide, namely both East Malaysia and \nPeninsular Malaysia; (ii) inclusion of multi-ethnic Asian \npatients and (iii) inclusion of all consecutive patients who \nreceived IVT in all PSCs and ASRHs in Malaysia. Furthermore, \nprospective local stroke registries at study centres offer \nreliable real-world data. Despite not performing propensity \nscore matching, there were no statistically significant \ndifferences in demographic, clinical and stroke characteristics \nupon comparing patients in both PSC and ASRH cohorts. In \naddition, univariable and multivariable logistic regression \nanalyses with appropriate adjustments were performed to \nassess the role of ethnicity and types of centres (i.e. PSCs vs \nASRHs) in clinical outcomes while identifying factors \nassociated with various outcomes of interest.  \n \nLimitations of this study include (i) the observational nature \nof study; however, this real-world study still offers valuable \ninsights on the benefits of IVT in both PSCs and ASRHs,  (ii) \nlack of comprehensive data on extra-cranial haemorrhages \nin some study centres; however, there was no significant \nmorbidity or mortality resulted from extra-cranial \nhaemorrhages among all study patients and (iii) lack of \ndetailed data on door-to-CT and CT-to-needle time, however, \ndefinite DNT was clearly documented and (iv) lack of detailed \nstandardised blood pressure recording in some patients as the \ntimings of blood pressure measurements were varied (any \n\n\n\npoint from upon arrival to Emergency Department to \nimmediately prior to Alteplase bolus); however, it has been a \nnationwide standard practice (as per national clinical \npractice guidelines) that blood pressure must be <185/110 \nmmHg prior to IVT initiation.  \n                                                                                                   \nGiven the inherent bias in an observational study, statistical \nadjustment techniques, i.e. logistic regression, have been \nemployed to produce unbiased estimates of effects. Moreover, \nthe findings from this study were replicated in other studies \ninternationally.10-12 Additional evidence to bolster the \npotential causal association with longer DNT would be an \nunderstanding of the Malaysia\u2019s healthcare landscape by the \nauthors and inputs/reviews from the local stroke experts. \n \nEvidence on the provision of IVT by non-neurologists is not \nexpansive so far, especially in resource-limited regions (low-\nmiddle income countries) where the neurologist:population \nratio is low and substantial proportions of acute stroke \npatients receive emergency care by non-neurologists. This \nproject, with strengths and limitations as stated,  is still \namong the largest real-world study providing real-world \nevidence which may suggest comparable IVT safety, \neffectiveness and service efficiency when administered by \nnon-neurologists in ASRHs as compared to administration by \nneurologists in PSCs, in a resource-limited setting. \n \n\n\n\nOverall (n = 313) \nModified Rankin Scale (mRS)                                                      mRS \u22641                                     mRS \u22652                               p values \nN (%)                                                                                       148/313 (47.3%)                       165/313 (52.7%)                               - \nMean age \u00b1 SD (years)                                                               53.6 \u00b1 12.3                                60.3 \u00b1 12.8                              <0.001 \nGender (Male:Female)                                                                     90:58                                        114:51                                   0.125  \n\n\n\n                                                                                               61%:39%                                  69%:31%                                      \nEthnicity                                                                                       73:24:8:43                                97:21:14:33                               0.131 \n(Malay:Chinese:Indian:Others)                                            49%:16%:6%:29%                   59%:13%:8%:20%                              \nDM                                                                                             50/148 (34%)                            58/165 (35%)                             0.799 \nHypertension                                                                             96/148 (65%)                           114/165 (69%)                            0.427 \nDyslipidaemia                                                                            45/148 (30%)                            47/165 (28%)                             0.710 \nCAD                                                                                            26/148 (18%)                            35/165 (21%)                             0.416 \nAF                                                                                             23/148 (16%)                            29/165 (18%)                             0.629 \nValvular CD                                                                                 5/148 (3%)                                1/165 (1%)                               0.074 \nHx of TIA/CVA                                                                           26/148 (18%)                            19/165 (12%)                             0.128 \nActive smoking                                                                         64/148 (43%)                            66/165 (40%)                             0.561 \nPrior antiplatelet/anticoagulant use                                       47/148 (32%)                            44/165 (27%)                             0.322 \nTOAST subtypes \n\n\n\nI.   Large artery atherosclerosis                                        47/148 (31.8%)                         90/165 (54.5%) \nII.  Small vessel occlusion                                                  62/148 (41.9%)                         30/165 (18.2%)                                 \nIII. Cardioembolism                                                           24/148 (16.2%)                         33/165 (20.0%) \nIV. Other determined aetiology                                        1/148 (0.7%)                             1/165 (0.6%) \nV. Undetermined aetiology                                               14/148 (9.4%)                           11/165 (6.7%)                                  \n\n\n\nMedian NIHSS (at presentation)                                                  10 (7\u201313)                                  13 (10\u201320)                               <0.001 \nMedian ASPECTS (at presentation)                                              9 (8\u201310)                                     9 (8\u20139.5)                                <0.001 \nMedian onset-to-needle time (minutes)                                 190 (160\u2013225)                           190 (150\u2013230)                             0.986 \nMedian door-to-needle time (minutes)                                  75 (50\u2013104.5)                              98 (65\u2013132)                              <0.001 \nDNT <60 minutes                                                                     59/148 (39.9%)                         37/165 (22.4%)                            0.001 \nAny ICH                                                                                     10/148 (6.8%)                          46/165 (27.9%)                           <0.001 \nsICH                                                                                            3/148 (2.0%)                           27/165 (16.4%)                           <0.001 \nFatal ICH                                                                                      0/148 (0%)                              13/165 (7.9%)                            <0.001 \nInpatient mortality                                                                     0/148 (0%)                             41/165 (24.8%)                           <0.001 \n90 days all-cause mortality                                                         0/148 (0%)                             47/165 (28.5%)                           <0.001 \n \nICH, intra-cranial haemorrhage. \n \n\n\n\nTable III: Distribution of Modified Rankin Scale (mRS)\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 599\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n600                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nOdd ratios                                                        Crude OR (95% CI)                        p value                     Adj OR (95% CI)             p value \nCentre  \n     ASRH                                                              1.09 (0.66\u20131.80)                            0.752 \n     PSC                                                                            Ref                                          \u2013                                                                           \nAge                                                                      0.96 (0.94\u20130.98)                           <0.001                       0.97 (0.95\u20130.99)                0.012 \nGender  \n     Female                                                           1.44 (0.90\u20132.30)                            0.125 \n     Male                                                                         Ref                                          \u2013                                                                           \nEthnicity  \n     Malays                                                           0.58 (0.34\u20130.997)                           0.049                        0.52 (0.27\u20131.02)                0.055 \n     Chinese                                                          0.88 (0.42\u20131.84)                            0.729                        0.95 (0.38\u20132.36)                0.916 \n     Indians                                                           0.44 (0.17\u20131.17)                            0.099                        0.43 (0.14\u20131.33)                0.143 \n     Others                                                                       Ref                                          \u2013                                      Ref                                \nDiabetes mellitus  \n     Yes                                                                  0.94 (0.59\u20131.50)                            0.799                                      \n     No                                                                             Ref                                          \u2013                                                                           \nHypertension  \n     Yes                                                                  0.83 (0.52\u20131.32)                            0.427 \n     No                                                                             Ref                                          \u2013                                                                           \nDyslipidaemia  \n     Yes                                                                  1.10 (0.67\u20131.79)                            0.710 \n     No                                                                             Ref                                          \u2013                                                                           \nCAD  \n     Yes                                                                  0.79 (0.45\u20131.39)                            0.417 \n     No                                                                             Ref                                          \u2013                                                                           \nAtrial \n     Yes                                                                  0.86 (0.47\u20131.57)                            0.629 \n     No                                                                             Ref                                          \u2013                                                                           \nVHD \n     Yes                                                                  5.73 (0.66\u201349.7)                            0.113 \n     No                                                                             Ref                                          \u2013                                                                           \nCVA /TIA  \n     Yes                                                                  1.64 (0.87\u20133.10)                            0.130 \n     No                                                                             Ref                                          \u2013                                                                           \nAnti-platelet/anti-coagulant  \n     Yes                                                                  1.28 (0.79\u20132.09)                            0.323 \n     No                                                                             Ref                                          \u2013                                                                           \nSmoking status : \n     Current/Ex Smoker                                        1.14 (0.73\u20131.79)                            0.561 \n     Non                                                                           Ref                                          \u2013                                                                           \nNIHSS at presentation                                       0.85 (0.81\u20130.90)                           <0.001                       0.85 (0.81\u20130.91)               <0.001 \nASPECTS                                                              1.67 (1.33\u20132.11)                           <0.001                      1.28 (0.997\u20131.65)               0.053 \nOnset-to-needle time                                        1.00 (0.99\u20131.004)                           0.998                                                                       \nDoor-to-needle time                                       0.988 (0.983\u20130.994)                        <0.001                   0.988 (0.981\u20130.995))            0.001 \nSymptomatic ICH  \n     Yes                                                                  0.11 (0.03\u20130.36)                           <0.001                       0.13 (0.04\u20130.48)                0.002 \n     No                                                                             Ref                                          \u2013                                      Ref                              \u2013 \n \n1. Younger age \n2. Lower NIHSS at presentation \n3. Shorter DNT \n4. No sICH \nASRH, acute stroke-ready hospital; AF, atrial fibrillation; CAD, coronary artery disease; CVA, cerebrovascular disease; TIA, transient \nischaemic attack; sICH, symptomatic intracranial haemorrhage; VHD, valvular heart disease; PSC, primary stroke centres. \n \n\n\n\nTable IV: Factors associated with favourable outcomes\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 600\n\n\n\n\n\n\n\n\nIntravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                601 \n\n\n\nCONCLUSION \nThis real-world study may provide translational real-world \nevidence which suggests that IVT in AIS can be equally safe, \neffective and efficiently delivered in both PSCs and ASRHs. \nThis may further encourage the establishment of IVT service \nin some centres without in-house neurologists, hence \nextending the benefits of IVT to a greater proportion of stroke \npopulations. Accordingly, through collaborative efforts and \ninitiatives, the development of more ASRHs equipped with \ntrained stroke teams should be proactively advocated to \nenhance regional and international acute stroke care. \n \n \nDECLARATION OF INTEREST \nAll authors report no disclosure or conflict of interest with \nrespect to the research, authorship and publication of this \narticle. \n \n \nREFERENCES \n1. National Institute of Neurological Disorders and Stroke rt-PA \n\n\n\nStroke Study Group. Tissue plasminogen activator for acute \nischemic stroke. N Engl J Med 1995; 333(24): 1581\u20137. \n\n\n\n2. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase \n3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; \n359(13): 1317\u201329. \n\n\n\n3. Wahlgren N, Ahmed N, D\u00e1valos A, et al. Thrombolysis with \nalteplase for acute ischaemic stroke in the Safe Implementation \nof Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an \nobservational study. 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Lees KR, Emberson J, Blackwell L, et al; on behalf of the Stroke \nThrombolysis Trialists\u2019 Collaborators Group. Effects of alteplase \nfor acute stroke on the distribution of functional outcomes: a \npooled analysis of 9 trials. Stroke 2016;47:2373\u201379. \n\n\n\n9. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the \nEarly Management of Patients With Acute Ischemic Stroke: 2019 \nUpdate to the 2018 Guidelines for the Early Management of \nAcute Ischemic Stroke: A Guideline for Healthcare Professionals \nFrom the American Heart Association/American Stroke \nAssociation. Stroke 2019; 50(12): e344\u2013e418. \n\n\n\n10. Lee A, Gaekwad A, Bronca M, et al. Stroke physician versus \nstroke neurologist: can anyone thrombolyse? Intern Med J 2015; \n45(3): 305\u20139. \n\n\n\n11. Kongbunkiat K, Kasemsap N, Tiamkao S, et al. Thrombolysis in \nischaemic stroke in rural North East Thailand by neurologist and \nnon-neurologists. Neurology Asia. 2016; 21(4): 325\u201331. \n\n\n\n12. Akins PT, Delemos C, Wentworth D, et al. Can emergency \ndepartment physicians safely and effectively initiate \nthrombolysis for acute ischemic stroke? Neurology 2000; 55(12): \n1801\u20135. \n\n\n\n13. Aho K, Harmsen P, Hatano S, et al. Cerebrovascular disease in \nthe community: results of a WHO collaborative study. Bull World \nHealth Organ 1980; 58: 113\u201330.  \n\n\n\n14. HP Adams Jr, BH Bendixen, LJ Kappelle, et al. Classification of \nsubtype of acute ischemic stroke. Definitions for use in a \nmulticenter clinical trial. TOAST. Trial of Org 10172 in Acute \nStroke Treatment. Stroke 1993; 24(1): 35\u201341. \n\n\n\n15. Barber PA, Demchuk AM, Zhang J, et al. Validity and reliability \nof a quantitative computed tomography score in predicting \noutcome of hyperacute stroke before thrombolytic therapy. \nASPECTS Study Group. Alberta Stroke Programme Early CT Score. \nLancet 2000; 355: 1670\u20134. \n\n\n\n16. JH Pexman, PA Barber, MD Hill, et al. Use of the Alberta Stroke \nProgram Early CT Score (ASPECTS) for assessing CT scans in \npatients with acute stroke. AJNR Am J Neuroradiol. 2001; 22(8): \n1534\u201342. \n\n\n\n\n\n\n\n7-Intravenous00112.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 601\n\n\n\n\n\n\n\n\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                621 \n\n\n\nABSTRACT \nIntroduction: Financial affordability to purchase \ncommodities for disease prevention is an important public \nhealth issue. The objective of this paper is to report the \nfinancial affordability and willingness to pay amongst the \nparents of government students for their children\u2019s non-\nmedical mask use, using a newly created Household Face \nMask Affordability Questionnaire (MAQ). \n \nMaterials and Methods: This was a cross-sectional study \ninvolving the parents or guardians of 50.6%  (44/87) \ngovernment schools in the whole of Kuching Division of \nSarawak. The sampling method was multistage cluster \nsampling, whereby stage one involved random sampling of \n49.2%  (30/61) primary schools and  53.8% (14/46) secondary \nschools in the Kuching Division, followed by stage two \ncluster sampling of one class per non-examination standard \nin each randomly sampled school. All students in the \nsampled classes were asked to bring a face-validated \nquestionnaire (MAQ) back home to be answered by one of \ntheir parents or a guardian. A total of 2559 out of 3661 \ndistributed questionnaires were collected, with a response \nrate of 70%. The data collection period was between April \nand June of 2022 so as the recall bias of the information \ncollected, especially on the actual spending on the face \nmasks for the school going students, was minimised. The \nrelevant summary statistics for self-perceived face masks \ncharacteristics, face mask expenses, affordability and \nwillingness to pay were calculated. We regress separately \nthe monthly affordability and willingness to pay amount \nagainst age, occupation, marital status, total number of \nchildren, monthly income and monthly saving to build \npredictive models for affordability and willingness to pay \namount per child per month. \n \nResults: The average Scale-level Face Validity Indexes for all \naspects of validity (clarity, comprehension, relevancy, \nrepresentativeness) are high (0.91 to 1.00) for MAQ. Most of \nthe respondents were mothers, married, working as private \nemployees with a mean age of 41 and belonged to the B40 \nand M40 group. The average monthly saving per family was \nRM540, which was about 15% of the total income. The \naverage actual monthly spending to purchase face masks \nfor one child is RM24. On average, a family can afford to pay \nRM23.80 for one child per month to purchase face masks. \n\n\n\nThe willingness to pay for the same was RM25.27. The \nmedian affordability, willingness to pay and actual spending \nfor face masks per child was RM16.67 per month. Taking \n75th percentile as the reasonable maximum expenses per \nchild for face masks per month, the affordable amount by \nmost parents is RM30, with the willingness to pay at 10% \nhigher. Affordability to purchase a face mask is influenced \nby the marital status, occupation, income, saving and the \nnumber of dependent of the breadwinner of a household. \nThe most important face mask characteristics expected by \nthe parents are better filtration efficiency and easier \nbreathability.  \n \nConclusion: The affordability and willingness to pay the \namount to purchase face masks amongst parents of \ngovernment students in Sarawak were RM30 and RM33 per \nchild per month, respectively.  \n \nKEYWORDS:  \nAffordability, willingness to pay, face mask, universal masking, \nCOVID-19 \n \n \nINTRODUCTION \nThe COVID-19 pandemic forces the world population to \nadopt new norms in life, namely social distancing, wearing \nface masks and frequent sanitising.1 These new norms are \nessential and were made compulsory in Malaysia since 1st \nAugust 2020 to the general population in an effort to prevent \nCOVID-19 transmission in the country.2 Amongst these new \nnorms, the requirement to wear face mask imposes financial \nburden on the population, especially amongst the family \nwith schooling children, because of the shortage in supply \nand single-use feature of most non-medical masks in the \nmarket.3,4 \n \nThe World Health Organization has recommended universal \nmasking, meaning that everyone should wear a mask for \nCOVID-19 source control, rather than protection.5 Source \ncontrol means that if everyone is wearing a mask, then the \nchances of virus transmission from an unknown infected \nperson will be reduced significantly. Hence, Malaysia \ngovernment has implemented universal masking policy, \neither disposable or reusable, from 1st August 2020 for 2 \nyears, to control the COVID-19 cases in the country. \n\n\n\nParental affordability and willingness to pay for universal \nmasking amongst government school students in Kuching, \nSarawak \n \nAnselm Ting Su, PhD1, Jew Win Kuan, PhD1, Musdi Hj Shanat, PhD2, Baderin Osman, BSc3, Haalah Mahmud, \nBSc3 \n\n\n\n     \n1Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia, 2Faculty of Applied and Creative \nArts, Universiti Malaysia Sarawak, Sarawak, Malaysia, 3Dust Mask Laboratory, National Institute of Occupational Safety and \nHealth, Selangor, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 13 August 2023                                                                                                                                                                         \nCorresponding Author: Anselm Ting Su                                                                                                                                                                              \nEmail: stanselm.unimas@gmail.com \n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 621\n\n\n\n\n\n\n\n\n622                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nOriginal Article \n\n\n\nIn view of the potential financial burden to the population on \nthe use of single-use disposable mask in compliance with the \nuniversal masking policy, the authors have embarked on a \nstudy to determine the financial affordability for universal \nmasking amongst the parents of the government school-\ngoing students in Kuching, Sarawak, as well as to develop a \nwashable reusable fabric face mask within the determined \naffordability range for the use of school going students in \nSarawak. Although the indoor universal masking policy has \nbeen scrapped since 7th September 2022,6 the finding of this \nstudy is still important to serve as the basis for setting price \nceiling for face masks and production of affordable reusable \nface masks in the future. \n \nThe objective of this paper is to report results on the \naffordability and willingness to pay for their children\u2019s non-\nmedical mask use amongst the parents of government \nstudents in Kuching division of Sarawak, using a newly \ncreated Household Face Mask Affordability Questionnaire \n(MAQ), as there is no similar readily available questionnaire \nin the market. \n \n \nMATERIALS AND METHODS \nThis was a cross-sectional study involving the parents or \nguardians of  50.6% (44/87) of government schools in the \nwhole of Kuching Division of Sarawak. The sampling method \nwas multistage cluster sampling, whereby stage one involved \nrandom sampling of 49.2% (30/61) primary schools and \n53.8% (14/46) secondary schools in the Kuching Division, \nfollowed by stage two cluster sampling of one class per non-\nexamination standard (namely, Standard 1 to 5, Form 1, 2, 3 \nand Lower 6) in each randomly sampled school. Following \nthe sampling procedure, 54.5% (24/44) of schools were \nclassified as urban schools and the rest were classified as rural \nschools. All students in the sampled classes were asked to \nbring a questionnaire back home to be answered by one of \ntheir parents or a guardian. A total of 2559 out of 3661 \ndistributed questionnaires were collected, with a response rate \nof 70%. The data collection period was between April and \nJune of 2022 so as the recall bias of the information collected, \nespecially on the actual spending on the face masks for the \nschool-going students, was minimised. \n \nThe questionnaire on universal masking affordability and \nwillingness to pay, called Household Face Mask Affordability \nQuestionnaire (MAQ), was created by the authors for this \nstudy. The MAQ is a brief simple-to-use self-administered \nquestionnaire consisting of two parts: Part 1: Demographic \nInformation and Part 2: Affordability and Willingness to Pay. \nPart 1 of the questionnaire asks about the respondent\u2019s age, \noccupation, marital status, relationship with the student, \ntotal number of children and total number of school-going \nchildren. Part 2 of the questionnaire asks about total monthly \nhousehold income and saving, affordability and willingness \nto spend for face masks for all children, self-perceived \nimportant characteristics of face masks, and the actual \nmonthly spent for face masks during the COVID-19 universal \nmasking period where schools were reopened.  \n \nThe questionnaire was designed by a Public Health Physician \nand a parent with school-going children originally in English \n\n\n\nand underwent forward and backward translation into each \nMalay and Chinese language. As the MAQ is not a \npsychological construct questionnaire, we performed face \nvalidation on the questionnaire on the following aspects: \nclarity, comprehension, relevancy and representativeness, for \nquestions in the Part 2 of the questionnaire. The scale of the \nresponses ranges from 1 being \u2018very vague\u2019, \u2018tough to \nunderstand\u2019, \u2018very irrelevant\u2019 and \u2018totally not representing\u2019, \nto 5 being \u2018very clear\u2019, \u2018very easy to understand\u2019, \u2018very \nrelevant\u2019 and \u2018accurately representing\u2019, to the respective \nquestion. The face validation test was carried out on 18 \nconveniently selected parents of variable socio-demographic \nbackgrounds in Kuching before the commencement of the \nactual affordability study. The Raters in Agreement \nfrequency, Universal Agreement (UA), Item-level Face \nValidity Index (I-FVI), Scale-level Face Validity Index (S-FVI), \naverage of S-FVI and S-FVI/UA were calculated to determine \nthe face validity of the questionnaire. \n \nThe data were entered into Microsoft Excel and analysed \nusing RStudio 2023.03.0+386 \"Cherry Blossom\" Release for \nWindows. All continuous data was examined for its \ndistribution, with necessary transformation, if any, and its \nrelationship with categorical variables. The relevant \nsummary statistics for self-perceived face mask \ncharacteristics, face mask expenses, affordability and \nwillingness to pay were calculated. We regress separately the \nmonthly affordability and willingness to pay amount against \nmonthly age, occupation, marital status, total number of \nchildren, monthly income and monthly saving to build \npredictive models for affordability and willingness to pay \namount per child per month. \n \nThe study obtained ethical approval from the Universiti \nMalaysia Sarawak Medical Ethics Committee (Ethics \nReference: FME/21/93) and study approval from the Malaysia \nMinistry of Education (Approval Reference: KPM.600-3/2/3-\neras (11777)). All participating schools were briefed, and \nwritten consents were taken from all respondents before the \ndata collection.  \n \n \nRESULTS \nValidity of the Household Face Mask Affordability \nQuestionnaire \nTable I shows the validity index of the MAQ. The original \nquestionnaire is attached in the Appendix of this paper. The \nI-FVI for all questions are high, ranging from 0.83 to 1.00 for \nall aspects of face validity (clarity, comprehension, relevancy \nand representativeness). Although S-FVI/UA are low for \nrelevancy and representativeness, as some respondents \nclaimed that questions on total income and saving are not \ncrucial, the index is high for clarity and comprehension for \nall questions. The average S-FVIs for all aspects of validity are \nhigh (0.91 to 1.00) for MAQ in general, indicating the face \nvalidity of this questionnaire is good. \n \nSocio-demographic Characteristics of the Respondents \nTable II reports the socio-demographic characteristics of all \nrespondents. The statistics are calculated based on the valid \nresponses for each variable. Most of the respondents come \nfrom families that send their children to urban schools. Most \n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 622\n\n\n\n\n\n\n\n\nParental affordability and willingness to pay for universal masking amongst government school students in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                623 \n\n\n\nof the respondents were mothers, married and working as \nprivate employees, with a mean age of 41. On average, each \nfamily had three school-going children to support.  \n \nAffordability and Willingness to Pay for Children\u2019s \nUniversal Masking \nThe financial profile of the respondents reflects that most of \nthe families of government students belong to the B40 and \nM40 income group. The average monthly saving per family \nwas RM540, which was about 15% of the total income. The \naverage actual monthly spending to purchase face masks for \none child is RM24. On average, a family can afford to pay \nRM23.80 for one child per month to purchase face masks. \nThe willingness to pay for the same was RM25.27.  \n \nIt is undoubtedly that the data in Table III are skewed to the \nright, which is logical, reflecting the economic status of the \n\n\n\nrespondents. Hence, if we consider the median as the \nmeasure of central tendency, the affordability, willingness to \npay and actual spending for face masks per child was \nRM16.67 per month. Logically, if we consider 75th percentile \nas the reasonable maximum expenses per child for face \nmasks per month, the acceptable amount by most parents is \nRM30. \n \nCharacteristics of Face Mask that Affects Purchasing \nDecision \nThe parents\u2019 decision to purchase the type of face mask was \naffected by a face mask\u2019s characteristics as shown in Figure 1. \nThe most important face mask\u2019s characteristics are \u2018ability to \nblock the particles\u2019 and \u2018easier to breath\u2019. The median \nranking for both \u2018ability to block particles\u2019 and \u2018easier to \nbreath\u2019 is 5 (maximum rank is 5 = \u2018Extremely important \ncharacteristics\u2019), followed by \u2018cheaper price\u2019 and \u2018comfortable \n\n\n\nItem                             Clarity                               Comprehension                                Relevancy                             Representativeness \n                      Na           I-FVI          UA             Na          I-FVI           UA               Na           I-FVI            UA              Na           I-FVI          UA  \nQ7                  18           1.00         1.00            18           1.00           1.00               15            0.83            0.00             17            0.94          0.00 \nQ8                  18           1.00         1.00            18           1.00           1.00               16            0.89            0.00             15            0.83          0.00 \nQ9                  18           1.00         1.00            18           1.00           1.00               18            1.00            1.00             18            1.00          1.00 \nQ10                16           0.89         0.00            18           1.00           1.00               16            0.89            0.00             17            0.94          0.00 \nQ11                18           1.00         1.00            18           1.00           1.00               16            0.89            0.00             16            0.89          0.00 \nQ12                18           1.00         1.00            18           1.00           1.00               17            0.94            0.00             18            1.00          1.00 \nS-FVI/Ave                       0.98                                           1.00                                                0.91                                                0.94              \nS-FVI/UA                                        0.83                                            1.00                                                 0.17                                             0.33 \n \nNote:  \n1. Na represents the number of Raters in Agreement, denotes the number of rater scored \u201c1\u201d, represents \u201cYes\u201d, corresponding to the scale of 3 to 5 for \neach aspect of validity (clarity, comprehension, relevancy, representativeness), on a particular question, and \u201c0\u201d, represents \u201cNo\u201d, corresponding to the scale \nof 1 to 2 for each aspect.  \n2. I-FVI = Item-level Face Validity Index, is the Raters in Agreement divided by the number of raters.  \n3. UA = Universal Agreement, indicated by score \u20181\u2019 assigned to the question that achieved 100% raters in agreement in respective to each aspect of validity. \n4. S-FVI/Ave = Average Scale-level Face Validity Index, is the sum of I-FVI divided by the total number of questions. \n \n\n\n\nTable I: The validity indexes of Household Face Mask Affordability Questionnaire\n\n\n\nRespondent's characteristics                     n                 %             Mean             SD          p50             p25             p75           Min          Max  \nAge (years)*                                                                                                                                                                                                     \n   Respondent                                          2461           96.17          41.34            7.36          41               36               46             16             79 \n   Spouse                                                  2231           87.18          41.81            7.17          41               37               46             21             76 \nRelationship to the student (total)          2433          100.00                                                                                                                         \n   Mother                                                 1367           56.19                                                                                                                          \n   Father                                                    963            39.58                                                                                                                          \n   Guardian/relative                                 103             4.23                                                                                                                           \nMarital status (total)                                 2476          100.00                                                                                                                         \n   Married                                                2235           90.27                                                                                                                          \n   Single parent                                        223             9.01                                                                                                                           \n   Unmarried                                             18              0.73                                                                                                                           \nOccupation (total)                                     2483          100.00                                                                                                                         \n   Private employee                                 950            38.26                                                                                                                          \n   Government servant                            616            24.81                                                                                                                          \n   Housewife                                             527            21.22                                                                                                                          \n   Own business                                        263            10.59                                                                                                                          \n   Others                                                   127             5.11                                                                                                                           \nNo of children*                                                                                                                                                                                                \n   Schooling                                             2469           96.48           3.03             1.36           3                 3                 2               1              10 \n   Total                                                     2442           95.43           2.38             1.06           2                 2                 2               1               7 \nSchool type (total)                                     2559          100.00                                                                                                                         \n   Urban                                                   2262           88.39                                                                                                                          \n   Rural                                                      297            11.61                                                                                                                          \n \nNote: n = frequency denotes number of respondents contributing to the statistics, with its respective valid percentage against the total of 2559 respondents. \n \n\n\n\nTable II: Socio-demographic characteristics of respondents\n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 623\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n624                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nto skin\u2019 ranking at 4, and finally \u2018stylish/good looking\u2019 \nranking at 2. \n \nPredictive Factors for Affordability and Willingness to Pay \nThe final predictors retained following multiple linear \nregression for monthly affordability and willingness to pay \namount against monthly age, occupation, marital status, \ntotal number of children, monthly income and monthly \nsaving is shown in Table IV. We used backward stepwise \nanalysis for both outcomes and the adjusted R-squared \nvalues for affordability and willingness to pay models are \n0.2727 and 0.2712, respectively. Diagnostic plots for both \nmodels showed the models are adequate, where the residuals \nversus fitted plot revealed no relationship and all data points \nin the residuals versus leverage plot are within Cook\u2019s \ndistance. \n \nHence, the final model for monthly affordability amount to \npay for the face mask for one child is: \nA = 36.9 \u2013 3.2G \u2013 5.3M + 0.0019I + 0.0064S \u2013 6.3C \n \n \n\n\n\nwhere:                                                                                         \nA = Monthly affordability amount to pay for the face mask \nper child in RM                                                                          \nG = Status as a government servant valued as \u201c1\u201d if yes        \nM = Marital status valued as \u201c1\u201d if married                             \nI = Total monthly income in RM                                               \nS = Total monthly saving in RM                                               \nC = Total number of children in round number \n \nThe final model for monthly willingness to pay amount for \nthe face mask for one child is: \nW = 42.0 \u2013 5.3M + 0.0019I + 0.0064S \u2013 6.3C \n \nwhere: \nW = Monthly willingness to pay for the face mask per child in \nRM                                                                                              \nM = Marital status valued as \u201c1\u201d if married                             \nI = Total monthly income in RM                                               \nS = Total monthly saving in RM                                               \nC = Total number of children in round number \n \n \n\n\n\nVariables (RM)                                              n                 %             Mean             SD             p50           p25            p75           Min         Max  \nMonthly income (I)                                    2310           90.27        3693.33       2930.78      2542.50       1400          5000           80        12430 \nMonthly saving (S)                                     1790           69.95         540.36         566.30        300.00         100           1000            0          2300 \nI - S1729                                                     67.57         3241.67      2607.59       2400.00        1240         4800             0           12130 \nMonthly face mask expenses (E)*            2363           92.34          60.40           45.23          50.00           30             100             0           200 \nE per child                                                  2290           89.49          24.23           22.09          16.67           10              30              0           200 \nTotal monthly affordability (A)                2439           95.31          58.11           45.70          50.00           24             100             0           210 \nTotal monthly willingness to pay (W)      2439           95.31          58.11           45.70          50.00           30             100             0           210 \nA per child                                                  2365           92.42          23.80           23.13          16.67           10              30              0           200 \nW per child                                                 2350           91.83          25.27           24.33          16.67           10              33              0           200 \n \nNote: *This is the actual spending for face masks reported by the parents after schools reopened during COVID-19 pandemic where universal masking is still \nrequired. \n \n\n\n\nTable III: Financial profile, affordability and willingness to pay for children\u2019s universal masking during COVID-19 pandemic\n\n\n\nPredictors                                                              Coefficient (B)                               95% CI for B                                       p-value  \n                                                                                                                 Lower limit                Upper limit                             \n\n\n\n(a) Monthly affordability amount \nIntercept                                                                      36.8993                          32.907                       40.8916                         <0.001 \nOccupation                                                                                                                                                                                       \n   Others (housewife, others)                                        1                                                                                                              \n   Government servant                                             \u22123.1937                         \u22126.1279                      \u22120.2594                         0.0359 \n   Own business                                                         2.5848                          \u22120.7602                       5.9298                          0.1298 \n   Private sector employee                                       \u22121.0984                         \u22123.4995                       1.3026                          0.3697 \nMarital status                                                                                                                                                                                   \n   Single parent/guardian                                              1                                                                                                              \n   Married                                                                  \u22125.335                          \u22128.4874                      \u22122.1825                         0.0009 \nMonthly income                                                           0.0019                           0.0015                        0.0024                         <0.0001 \nMonthly saving                                                            0.0064                           0.0044                        0.0084                         <0.0001 \nTotal children                                                              \u22126.2717                         \u22126.9922                      \u22125.5512                        <0.0001 \n(b) Monthly willingness to pay amount \nIntercept                                                                      42.0269                         38.3693                      45.6846                        <0.0001 \nMarital status                                                                                                                                                                                   \n   Single parent/guardian                                              1                                                                                                              \n   Married                                                                  \u22125.335                               1                                                                        \nMonthly income                                                           0.0019                          \u22127.7034                     \u221210.9924                       \u22124.4144 \nMonthly saving                                                            0.0064                           0.0012                        0.0013                          0.0021 \nTotal children                                                              \u22126.2717                          0.0067                        0.0047                          0.0088\n\n\n\nTable IV.:Predictive factors for monthly (a) affordability (b) willingness to pay amount to purchase face masks for one child\n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 624\n\n\n\n\n\n\n\n\nParental affordability and willingness to pay for universal masking amongst government school students in Kuching, Sarawak\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                625 \n\n\n\nDISCUSSION \nPrevious studies on non-medical masks use by the population \nfocussed mainly on determinants of willingness to pay or \nwillingness to wear face masks.7-9 No study has been focussing \non the affordability to purchase non-medical masks amongst \nthe population when universal masking is required. \nFinancial affordability to purchase commodities for disease \nprevention is an important public health issue. The current \nstudy reflects the financial affordability of the parents of \ngovernment students in Kuching population to purchase face \nmasks under universal masking policy accurately because of \nthe large sample size and random sampling strategy. The \nfindings of this study could be extrapolated to other states \nwith almost similar monthly household incomes, such as \nSabah, Pahang, Perak, Kedah and Perlis, where these are the \nstates within RM500 difference of monthly household income \nof Sarawak (mean = RM5087 in year 2020).10 \n \nCurrently, the retail ceiling price for face mask in Malaysia is \nRM0.70. It was reduced from the ceiling of RM1.50 before 1st \nMac 2020, further down to RM0.70 on 1 November 2020.11-13 \nThe reduction was likely intuitive based on strong demand \nfrom the population. The affordability amount of RM30 per \nchild per month found in this study is equivalent to the \nexpenditure of RM1 per piece of disposable face mask per \nchild per day. The finding shows that the current retail ceiling \nprice set by the government for face masks is reasonable \nconsidering the variation in different socio-economic levels of \npopulation across the country.  \n \nThe affordability and willingness to pay models derived in \nthis study can be used to determine the ceiling price of face \nmasks by the government in the future should the universal \n\n\n\nmasking policy is required. Although the models may not be \ncomprehensive as independent variables are limited to those \ntaken, they can readily be used for quick estimation. The \naffordability model itself indicates that when policymakers \nwant to set the ceiling price for face masks, they must take \ninto account at least the occupation, income, saving, marital \nstatus and number of dependents of the breadwinner within \na household in the targeted population.  \n \nMost studies focused on the health-related factors such as the \nperceived severity of disease and benefit of masking when it \ncomes to willingness to pay for and wear face mask.14,15 It is \nalso important to understand the perceived expected \ncharacteristics of face mask that would affect the consumer to \npurchase and use the mask. Our study found that the most \nimportant characteristics of the face mask that influence the \nchoice of the parents are filtration efficiency and \nbreathability. This information is important in two aspects, \nfirst to the government and the supplier, to ensure that the \nface masks that are sold legally in the market are of certain \nacceptable standards of filtration efficiency and \nbreathability. Second, the information reflects the knowledge \nlevel of the target population that serves as a benchmark for \nappropriate health education by public health professionals. \n \nThis study also produced the face-validated MAQ, which can \nbe used as a simple and quick questionnaire to determine the \naffordability level of the target population in this country. \nThe questionnaire was purposely made short and simple to \nimprove the accuracy of reporting. Hence, MAQ can be used \nby policymakers or market survey professionals for the \npurpose of policymaking and setting an affordable retail \nprice for face masks. \n\n\n\nFig. 1: Characteristics of face mask that affect purchasing decision by the parents.\n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 625\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n626                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nThe findings of this study are useful to various public health \nstakeholders for comprehensive and timeliness public health \nresponse during pandemic. The Ministry of Health should \nensure the quality of non-medical masks supplied in the \ncountry meeting the population\u2019s demand, namely filtration \nefficiency and breathability. The Ministry of Domestic Trade \nand Consumer Affairs should ensure the market price of non-\nmedical masks within the affordable level of the population, \nby continuous close monitoring of its supply and demand \nand being sensitive to future similar pandemic given the \nlesson learnt from the COVID-19 pandemic. Non-medical \nmask manufacturers should focus on the production of \nefficient and cost-effective masks to meet the population\u2019s \ndemand.  \n \nA major limitation of this study would be the restriction of \nstudy population to Kuching area due to logistic issues. \nNevertheless, since there has been no similar study done \nbefore, the current findings serve as a baseline for future \nextrapolation to other states of Malaysia. Another strength of \nthis research is the creation of validated MAQ, which can be \nused by all researchers in Malaysia for future studies. \n \n \nCONCLUSION \nThe affordability level to purchase face masks amongst the \nparents of government students in Sarawak was RM30 per \nchild per month. The willingness to pay for the same can be \nexpected to increase by 10%. The most important face mask \ncharacteristics expected by the parents are better filtration \nefficiency and easier breathability. Affordability to purchase \na face mask is influenced by the marital status, occupation, \nincome, saving, and number of dependents of the \nbreadwinner of a household.  \n \n \nACKNOWLEDGEMENTS \nThe study is sponsored by the Sarawak Research \nDevelopment Council under the grant number \nRDCRG02/CAT/2020/_4.  \n \n \nDISCLOSURE \nThe Sarawak Research Development Council was not \ninvolved in the planning, conduct and analysis of the study. \nThe authors declare no conflict of interest with the grant \nsponsor in completing this study. \n \n \n \n \n \n \n \n \n \n\n\n\nREFERENCES \n1. Ayenigbara IO, Adeleke OR, Ayenigbara GO, Adegboro JS, \n\n\n\nOlofintuyi OO. COVID-19 (SARS-CoV-2) pandemic: fears, facts, \nand preventive measures. Germs. 2020; 10(4): 218-28. \n\n\n\n2. Jayaraj VJ, Rampal S, Ng CW, Chong DWQ. The epidemiology of \nCOVID-19 in Malaysia. The Lancet Regional Health Western \nPacific. 2021; 17: 100295. \n\n\n\n3. Alcaraz JP, Le Coq L, Pourchez J, Thomas D, Chazelet S, Boudry \nI, et al. Reuse of medical face masks in domestic and community \nsettings without sacrificing safety: Ecological and economical \nlessons from the Covid-19 pandemic. Chemosphere. 2022; \n288(1): 132364. \n\n\n\n4. Chan TK. Universal masking for COVID-19: evidence, ethics and \nrecommendations. BMJ Global Health. 2020; 5: e002819. \n\n\n\n5. World Health Organization. Advice on the use of masks in the \ncontext of COVID-19: interim guidance, 6 April 2020. World \nHealth Organization. 2020. Available from: \nhttps://apps.who.int/iris/handle/10665/331693. \n\n\n\n6. Kaus J. Khairy: Use of face masks indoors now optional. The Star. \n[cited 2022 Sep 7]. Available from: \nhttps://www.thestar.com.my/news/nation/2022/09/07/khairy-\nwearing-facemasks-indoors-is-optional. \n\n\n\n7. Restiatun R, Yani A, Bariyah N, Suradi R. Factors influencing the \nwillingness to pay for masks during the COVID-19 pandemic: \nEmpirical evidence from Indonesia. Asian Development Policy \nReview. 2023; 11(2): 67-8. \n\n\n\n8. Ding Q, Lin S, Wang S. Determinants and willingness to pay for \npurchasing mask against COVID-19: a protection motivation \ntheory perspective. Int J Environ Res Public Health. 2022; 19: \n4268. \n\n\n\n9. Irfan M, Akhtar N, Ahmad M, Shahzad F, Elavarasan RM, Wu H, \net al. Assessing public willingness to wear face masks during the \nCOVID-19 pandemic: fresh insights from the theory of planned \nbehavior. Int J Environ Res Public Health. 2021; 18: 4577. \n\n\n\n10. Mahidin U. Household income estimates and incidence of \npoverty report, Malaysia, 2020. Department of Statistics \nMalaysia. [cited 2021 Aug 6]. Available from: \nh t t p s : / / w w w . d o s m . g o v . m y / p o r t a l - m a i n / r e l e a s e -\ncontent/household-income-estimates-and-incidence-of-poverty-\nreport-malaysia-2020. \n\n\n\n11. Bernama. Face mask ceiling price set a RM1.5 per piece effective \nApril 1. Bernama. [cited 2020 March 30]. Available from:  \nh t tp s : / /www.be rnama.com/en/genera l /news_cov id -\n19.php?id=1826626. \n\n\n\n12. Bernama. Face mask ceiling price set at 70 sen from Nov 1. The \nStar. [cited 2020 Oct 27]. Available from: \nhttps://www.thestar.com.my/news/nation/2020/10/27/face-\nmask-ceiling-price-set-at-70-sen-from-nov-1. \n\n\n\n13. Borneo Post. Domestic Trade Ministry: No plans to remove ceiling \nprice on 3-ply face mask. Malay Mail. [cited 2021 Sep 5]. \nAvailable from: \nhttps://www.malaymail.com/news/malaysia/2021/09/05/domes\ntic-trade-ministry-no-plans-to-remove-ceiling-price-on-3-ply-\nface-mask/2003154. \n\n\n\n14. Lee SE, Kim SJ, Oh KW, Lee KH. Purchase intention toward \nsustainable masks after COVID-19: the moderating role of health \nconcern. Fashion Textiles. 2022; 9(1): 43. \n\n\n\n15. Oreffice S, Quintana-Domeque C. (2021). COVID-19 \nInformation, demand, and willingness to pay for protective gear \nin the UK. Stud Microecon. 2021; 9(2): 180-95. \n\n\n\n\n\n\n\n11-Parental00090.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 626\n\n\n\n\n\n\n\n\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                669 \n\n\n\nABSTRACT \nAppendicular mass is considered as one of the \ncomplications of acute appendicitis but there is no \nconsensus on the optimal management of this condition. \nThe management of this condition has always been \nconservative management with interval appendectomy as \npopularized by Oschner and Sheerin. The need for interval \nappendectomy has now been questioned, and an emerging \ntrend has been early appendectomy by laparoscopic \nmethod. There are no guidelines on the management of \nappendicular mass and treatment is decided by the surgeon. \nWe have conducted a narrative review to investigate what is \nthe current practice in the management of appendicular \nmass.     \n \nKEYWORDS:  \nAppendicular mass, appendicular phlegmon, appendicular lump, \ninterval appendectomy \n \n \nINTRODUCTION \nAcute appendicitis is one of the most common acute \nabdominal conditions that is seen in surgical practice and \nappendicular mass accounts for up to 10% of cases. The \npathological spectrum can range from Phlegmon to abscess \nformation. The appendicular mass is composed of the \ninflamed appendix, omentum and bowel loops, and it forms \nafter about 24 to 48 hours after the initial symptoms. This is \na protective mechanism to prevent the spread of infection. \nThe treatment of appendicular mass has been debated over \nthe past 80 years. The diagnosis of appendicular mass is \nmade clinically, but ultrasonography is the most popular \ninvestigation of choice, although computerized tomography \n(CT), is more sensitive. The presentation is more acute in \nchildren, whereas in the adults the mass tends to take longer \nto form.1 \n \nThe management of appendicular mass can be divided into \nthree treatment approaches 1) Conservative management \nwith broad spectrum antibiotics and intravenous fluids \nfollowed by interval appendectomy in 6 - 8 weeks. This was \nproposed by Oschner and Sheeren in 1901 and is the most \npopular treatment option for appendicular mass and is \nwidely practiced worldwide. 2) Conservative management \nwithout interval appendectomy, as this option is proposed \ndue to low infection rates and low recurrence rates and hence \nthere is no need for interval appendectomy. For patients \nabove the age of 40, follow up treatment with investigations \nlike colonoscopy and computerized tomography (CT) is \nrequired. 3) Immediate appendectomy which is emerging as \n\n\n\nan alternative treatment option, and this option eliminates \nthe risk of recurrence and the need for interval \nappendectomy. The operative options are open \nappendectomy and laparoscopic appendectomy. Open \nappendectomy was the treatment of choice, but laparoscopic \nappendectomy is emerging as an alternative treatment \noption due to decreased post operative pain, early recovery, \nand earlier discharge to home. Currently conservative \ntreatment of appendicular mass is the most favored by most \nsurgeons. However, the pressing question is the need for \ninterval appendectomy after conservative treatment, as there \nis a growing trend to opt against interval appendectomy. The \nargument for this is the low rate of recurrent infection and \nthe early return to work.2,3 \n\n\n\n \n \nMATERIALS AND METHODS \nCurrently there is no uniform consensus on the management \nof appendicular mass, and we have conducted this review \narticle to investigate the various management options. We \nconducted a literature review using PUBMED, Cochrane \ndatabase of clinical reviews and Google scholar looking for \nclinical trial, observational studies, cohort studies systemic \nreviews, and meta-analysis from 1990 to 2022.We used the \nfollowing keywords, \u201cAppendicular Mass\u201d, \u201cAppendicular \nPhlegmon\u201d, \u201cAppendicular Lump\u201d, \u201cInterval Appendectomy \n\u201cand, \u201cComplicated Appendectomy\u201d. All articles were in \nEnglish language only. Further articles were obtained by \nmanual cross referencing of the literature. Case reports and \nstudies with less than 10 patients and editorials were \nexcluded. \n \n \nDISCUSSION \nConservative management followed by interval \nappendectomy. \nOschner and Sherren proposed this management for \nappendicular mass in 1901, during the era of limited \nantibiotics and imaging technologies. This approach \ninvolved keeping the patient nil by mouth and starting intra- \nvenous antibiotics and measuring the size of the \nappendicular mass. This treatment is continued for 24 to 48 \nhours, and it involves monitoring of the vital signs.2 This \nmethod removes the risk of complications that can occur \nduring the acute phase of surgery and interval \nappendectomy eliminates the risk of recurrence.3 Interval \nappendectomy will help to give a histological diagnosis and \nto prevent recurrence. The complication rates from interval \nappendectomy are low.4  \n \n\n\n\nCurrent management of appendicular mas - a narrative \nreview \n \nKumar Hari Rajah, Somanathan Menon and Ganesh Ramachandran \n\n\n\n     \nDepartment of Surgery, School of Medicine, Faculty of Health and Medical Science, Taylor University, Subang Jaya, Malaysia\n\n\n\nSYSTEMATIC / NARRATIVE REVIEW ARTICLE\n\n\n\n This article was accepted: 12 July 2023                                                                                                                                                                              \nCorresponding Author: Kumar Hari Rajah                                                                                                                                                                          \nEmail: kharirajah@yahoo.com.my \n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 669\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n670                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nOlsen et al                         Systematic review        3,772 patients                  70 to 80% success rate                        Most of the studies  \n                                                                                                                                                                                 were retrospective in nature \nVan Amstel et al                  Meta-analysis            1,355 patients                     12% complication in                     Most of the studies were  \n                                                                                                                             conservative group                        retrospective in nature \nGillick et al                      Retrospective study        427 patients                          85% success rate                          Retrospective in nature \nRavichandran et al            Prospective study          116 patients            Decreased wound infection rates                 Low patient load \nDemetrashvilli et al         Retrospective study         48 patients                    Complication rates were                   Retrospective in nature \n                                                                                                                         the same in both groups                                        \nKim et al                          Retrospective study         76 patients                Outcomes and complications               Retrospective in nature \n                                                                                                                    were the same in both groups                                   \n \n \n\n\n\nTable \u2160: Table of contents of the retrospective studies\n\n\n\nFugazolla et al             Meta-analysis         1,288 patients           90% success rate for conservative        Most studies were retrospective \n                                                                                                         treatment.15% recurrence rate                             in nature \nAnderson et al             Meta-analysis        59,488 patients                    93%success rate with                        Most of the studies were  \n                                                                                                                   10%recurrence rate                            retrospective in nature \nDemetashivilli et al        Prospective             74 patients             High success rate for conservative                 Low patient numbers \n                                      cohort study                                                                treatment                                                        \nYilmt et al                    Retrospective          126 patients           Lower morbidity and infection rate         Retrospective study in nature \n                                            study                             \n\n\n\nTable II: Table of contents of the studies for conservative treatment\n\n\n\nKhan et al            Randomized control trials          300 patients                       5-8% complication rate                     Low patient numbers \nArshad et al               Comparative study                176 patients                     Low wound infection rate                   Low patient numbers \nDas et al                     Retrospective study               112 patients                     Low wound infection rate                  Retrospective in nature \nPathan et al                 Prospective study                 100 patients                       Reduced infection rate                      Low patient numbers \nIshar et al                  Observational study                60 patients            Reduced mean hospital stay at 4 days          Low patient numbers \nEl-sood et al              Retrospective study                40 patients                    Reduced mean hospital stay                  Low patient numbers \nKumar et al                 Prospective study                  50 patients                    Reduced mean hospital stay                  Low patient numbers \n\n\n\nTable III: Table of contents for studies that favor early appendectomy\n\n\n\nFig. 1: Flow chart for the management of appendicular mass.\n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 670\n\n\n\n\n\n\n\n\nCurrent management of appendicular mass-narrative review article\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                671 \n\n\n\nA retrospective study by Koirala et al evaluated conservative \ntherapy for appendicular mass where 173 patients were \ntreated. Of this number, 10 patients developed complications \nthat required emergency appendectomy, but the rest were \nmanaged conservatively. Only 35 patients returned for \ninterval appendectomy. Bhandari et al in their study of 75 \npatients with appendicular mass were managed \nconservatively and only five patients developed appendicular \nabscess, but only 13 patients came back for interval \nappendectomy. Although these were retrospective studies, it \nshowed the success of conservative treatment but highlighted \nthe problem of patient\u2019s attendance for interval \nappendectomy. Further retrospective studies by Gillick and \ndemetrashvili also showed the benefit of conservative \ntreatment in the management of appendicular.5\u20137 \n \nIn a prospective study by Elsaady, a total of 169 cases of \nappendicular mass 121 patients were treated conservatively. \nOf this total 106 were successfully treated and treatment \nfailure was seen in 15 cases. This showed that the \nconservative method with interval appendectomy was an \neffective and safe treatment method. This was also confirmed \nby a prospective study by Ravichandran et al and ahmed et \nal which showed the success of conservative treatment \nfollowed by interval appendectomy.8\u201310 \n \nA systemic review by Olsen et al reviewed the literature in 48 \nstudies and a total of 3,772 patients and they concluded that \nconservative management of appendicular mass was safe \nand associated with a Success rate of 80%-90% and there \nwere no major complications. Another systemic review by \nTeixeira et al also concluded that conservative management \nof appendicular mass was safe and the risk of detecting \nneoplasms of the appendix was low.11,12 \n \nA meta-analysis by van Amstel, which included 14 studies \nand 1355 patients, for which 1022 were treated with \nconservative therapy and 333 underwent emergency \nappendectomy, complications were seen in 12.2% of the \nconservative therapy group and 25.5% in the emergency \nappendectomy group. The most common complication was \nwound infection. This showed that conservative therapy \nfollowed by interval appendectomy should be the treatment \nof choice for appendicular mass but the drawback from this \nmeta-analysis was that the majority of the studies were small \nretrospective studies.13      \n \nAn audit by Ahmed et al in the mid trent region in the United \nKingdom, concluded that 75% of surgeons there conducted \nconservative therapy with interval appendectomy on patients \nwith appendicular mass and that there was no present \nprotocol for the treatment of appendicular mass.14   \n \nAnother survey of hospitals in the south coast of the United \nKingdom showed the diverse practice in the management of \nappendicular mass, where senior surgeons would manage \nthese patients conservatively, but surgical registrars were \nmore inclined to perform interval appendectomy.15  \n \nKim et al did a retrospective analysis on 76 patients who were \ndiagnosed with appendicular mass, 48 underwent \nconservative therapy followed by interval appendectomy and \n\n\n\n28 underwent emergency appendectomy, the recurrence rate \nwas low and the outcomes after surgery were the same in all \nthe groups hence conservative therapy followed by interval \nappendectomy is still the primary choice of therapy for \nappendicular mass, but the choice of therapy will usually be \ndecided by the surgeon.16 \n \nGarba et al., conducted a review on the treatment \napproaches for the management of appendicular mass and \nconcluded that conservative management followed by \ninterval appendectomy is still the primary treatment of \nchoice for the management of appendicular mass and follow- \nup of patients are essential while waiting for interval \nappendectomy.17 Simillis et al conducted a meta-analysis \ncomparing conservative therapy versus immediate \nappendectomy on the treatment of appendicular mass,21 \nstudies were included, and the conclusion was that \nconservative therapy followed by interval appendectomy was \nassociated with decreased wound complication ,abscess \nformation and intestinal obstruction. The duration of \nhospital stay was also the same between the groups.18   \n \nThe European Association of Emergency Surgeons consensus \ndevelopment conference 2015 still recommends conservative \nmanagement followed by interval appendectomy in the \nmanagement of appendicular mass. Interval appendectomy \nis done to reduce the chance of recurrence and to not miss \nany under lying malignancy.19  The World Society of \nEmergency Surgeons Jerusalem guidelines also recommends \nconservative treatment as the initially therapy of \nappendicular mass in the event of non-availability of \nlaparoscopic surgery.20 \n \nMost of the studies that were done on conservative \nmanagement of appendicular mass with interval \nappendectomy were retrospective in nature and this \ninfluenced the outcomes of wound infection and recurrence \nrate. An area of issue is the number of patients who are lost \nto follow- up and hence did not come for interval \nappendectomy. The number of patients in most of the studies \nwas rather low in number. For future research it is hoped that \nrandomized control trials can be used to investigate the \nconservative management of appendicular mass, but sample \nsize may be a problem. \n \nConservative management without interval \nappendectomy \nThere are some in the surgical fraternity who oppose interval \nappendectomy as they point out that the rate of recurrence \nattacks is low and the complication rates from interval \nappendectomy are not low. A study by Noori et al, on 65 \npatients with appendicular mass who underwent \nconservative management with no interval appendectomy, \nthe rate of recurrence was 10% and wound infection was seen \nin 4% of the cases. Hence upon completion of conservative \nmanagement, interval appendectomy is not necessary as the \nrecurrence rate is low.21 \n \nDemetrashivili et al also had conducted a cohort study on 74 \npatients with appendicular mass, where 47 had undergone \nconservative therapy and 27 underwent immediate \nappendectomy, and there were no significant differences in \n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 671\n\n\n\n\n\n\n\n\nSystematic / Narrative Review Article\n\n\n\n672                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nthe treatment for both groups, hence conservative treatment \nwithout interval appendectomy was still the preferred \ntreatment of choice. Patients who present with recurrence can \nbe operated and Computerised Tomography and \ncolonoscopy can be done to investigate patients who present \nwith recurrence.22 \n \nYilmaz et al in his retrospective study on 126 patients with \nappendicular mass were divided into two groups one was \nmanaged with appendectomy and another group with \nconservative therapy alone.43 underwent appendectomy and \n72 underwent conservative therapy, the morbidity and \ninfection rate was higher in the appendectomy group .Based \non this study conservative appendectomy without interval \nappendectomy should be the treatment of choice and \npatients with recurrence can be followed up by investigations \nlike colonoscopy and computed tomography. The drawback \nof this study was the fact that it was retrospective in nature.23 \nPanahi et al in his study did a literature search on the best \nmanagement option of appendicular mass, and after \nfiltration a total of 5 papers were identified to provide the best \nevidence. Based on this, conservative management without \ninterval appendectomy was considered the best treatment \noption for appendicular mass and to prevent recurrence, \npatients should be followed up with investigations like \ncolonoscopy and imaging like ultrasound or computed \ntomography. Meshikhes also looked in the literature and \nconcluded that interval appendectomy can be safely \nexcluded, and that recurrence can be managed by \nlaparoscopic appendectomy. Quartey investigated the need \nfor interval appendectomy and concluded that it was not \nnecessary and that concluded that recurrence can be \ninvestigated by colonoscopy or computerized tomography.24\u2013\n\n\n\n26 \n \nMalik et al conducted a retrospective study on 220 patients \nwith conservative management and 213 patients were \ntreated successfully, the recurrence rate was 13% with a \nmedian follow up of 6 months. He concluded that interval \nappendectomy was not necessarily due to the low recurrence \nrates. Another retrospective study by Tingstedt also confirmed \nthis.27,28 \n  \nIn a meta-analysis done by Anderson et al, which \ninvestigated the conservative management of appendicular \nlump and upon successful treatment interval appendectomy \nwas not indicated. There was a success rate of 93% but \npercutaneous drainage of abscess was seen in 20% of cases. \nThe risk of recurrence was seen in less than 10% of cases and \nwas also associated with a risk of missing other diagnosis like \nmalignancy or Crohn \u2018s disease in about 2% of cases. Follow- \nup of patients above the age of 40 was suggested with \ncolonoscopy and Computed Tomography to not miss other \ndiagnosis.29 \n \nA meta-analysis by Fugazolla et al on 14 studies with 1288 \npatients, where 622 were treated with conservative \nmanagement and 666 with appendectomy, the success rate \nwas 90% and the recurrence rate was 15.4%. This showed \nthat conservative therapy should be the treatment of choice \nfor patients with appendicular mass.30 \n \n\n\n\nThe drawback from these studies was that most of them were \nretrospective in nature and due to the low recurrence rate and \npost operative infection rates the need of interval \nappendectomy was questioned. With better investigations \nlike computerized tomography and colonoscopy, the need for \ninterval appendectomy is being questioned. For future \nresearch, more randomized control trials should be \nconducted in the conservative management of appendicular \nmass and more prospective studies should be done, with \nbetter sample size. \n \nImmediate appendectomy either by open or laparoscopic \nmethod \nThere are surgeons who advocate for immediate \nappendectomy for patients who present with an \nappendicular mass, as this approach excludes the need for \nreadmission, cures the condition and reaches a definitive \ndiagnosis.  A prospective study by Bahram on 46 patients \nwith appendicular mass who were subjected to immediate \nappendectomy. The infection rates were 8% and the mean \nhospital stay was 3 days. This showed that immediate \nappendectomy was feasible and safe in the management of \nappendicular mass.31 \n \nAli et al in his literature review, stated that emergency \nappendectomy in the management of appendicular mass is \nemerging as an alternative treatment than conservative \nmanagement. It is safe and cost- effective and reduces \nhospital stay.32 \n \nKhan et al conducted randomized control trials on 300 \npatients with appendicular mass,150 had undergone \nimmediate appendectomy and 150 conservative treatments. \nThe wound infection rates among the groups were 5% and \n8% respectively and the frequency of intra-abdominal \nabscess was less than 2%. This study concluded that \nimmediate appendectomy was more effective option in the \nmanagement of appendicular mass.33 \n \nArshad et al in his comparative study on 176 patients of \nappendicular mass ,88 patients underwent immediate \nappendectomy and 88 underwent conservative treatment. \nThe wound infection rate was higher in the immediate \nappendectomy group but the stay in hospital was less than in \nthe conservative treatment group, but the rate was not high \nto exclude immediate appendectomy. Immediate \nappendectomy in the treatment of appendicular mass is a \nsafe and effective treatment option.34 \n \nDas et al conducted a retrospective analysis on 112 patients \nof appendicular mass who were divided into 56 patients who \nunderwent immediate appendectomy and 56 underwent \nconservative treatment. The length of hospital stay was less \nin the appendectomy group. They were discharged home \nsooner than the group that underwent conservative \ntreatment. Early appendectomy is curative, cost- effective and \nreduces hospital stay in the management of appendicular \nmass. This was also confirmed by obaidi et al who came with \nthe same conclusions in his study.35,36  \n \nTiwary et al in their study of 54 patients with appendicular \nmass were divided into 2 groups of 27 patients each who \n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 672\n\n\n\n\n\n\n\n\nCurrent management of appendicular mass-narrative review article\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                673 \n\n\n\nunderwent immediate appendectomy and conservative \ntreatment. The infection rates were the same in both groups \nbut the stay in hospital was shorter in the appendectomy \ngroup. Early appendectomy is better in the treatment of \nappendicular mass as it is associated with shorter stay and \nreduced cost and eliminates the need for a second \nadmission.37   \n \nPathan et al in his prospective observational study of 100 \npatients of appendicular mass also noted that the length of \nhospital stay was reduced in the immediate appendectomy \ngroup. It was also associated with faster return to work and \nlow economic burden. This conclusion was also observed by \nIsrar in his observational study that immediate \nappendectomy was safe and effective.38,39   \n \nLaparoscopic appendectomy has been emerging as an \nalternative to the management of appendicular mass. \nSeveral retrospective studies were done on the role of \nlaparoscopic appendectomy in the management of \nappendicular mass. The mean operation time was longer but \nthe use of postoperative analgesia and the stay in the \nhospital was reduced. The advantage of laparoscopic \nappendectomy was adequate access and visualisation of the \nperitoneum, lower risk of adhesion and faster mobility. Hence \nlaparoscopic appendectomy is a feasible option in the \nmanagement of appendicular mass.40\u201344 \n \nThe World Society of Emergency Surgeons Jerusalem \nguidelines of 2020 recommended that in the management of \nappendicular mass, laparoscopic surgery is a safe and \nfeasible treatment option if it is done in experienced hands. \nIt is associated with fewer admissions and fewer additional \ninterventions.21 \n \nThe drawback of most of these studies is that they are \nretrospective in nature with small sample sizes. There were \nalso concerns that acute appendicitis is an emergency \nprocedure and most of the appendectomies were performed \nby junior specialists and registrars which could account for \nthe higher post operative wound infection rates. Most of the \nstudies that used laparoscopic appendectomy in the \nmanagement of appendicular used senior surgeons who had \nexperience in laparoscopic surgery, and this could account \nfor the better outcomes. It is hoped that future randomized \ncontrol trials can be conducted in terms of the use of \nlaparoscopic appendectomy in the management of \nappendicular mass. \n \n \nCONCLUSION \nBased on the available evidence, the management of \nappendicular mass should be done with immediate \nappendectomy and laparoscopic appendectomy should be \nthe surgery of choice. If facilities for laparoscopic \nappendectomy are not available then conservative treatment \nshould be done for the patient and for patients above the age \nof 40 years, they can be followed by computerised \ntomography and colonoscopy. Interval appendectomy is not \nrequired, and it is only indicated for patients who present \nwith recurrent symptoms. \n \n \n\n\n\nCONFLICT OF INTEREST \nThere is no conflict of interest related to this review article. \n \n \nREFERENCES \n1. Sartelli M, Baiocchi GL, Di Saverio S, Ferrara F, Labricciosa FM, \n\n\n\nAnsaloni L, et al. Prospective Observational Study on acute \nAppendicitis Worldwide (POSAW). World J Emerg Surg 2018; 13: \n19.  \n\n\n\n2. Bailey H. The Ochsner-Sherren (Delayed) Treatment of acute \nappendicitis: Indications and technique. Br Med J 1930; 1(3603): \n140-3.  \n\n\n\n3. Dhanasekharan N, Raj P, Ganeshram P, Venkatesan V. Does \nOchsner-Sherren Regimen Still Hold True in the Management of \nAppendicular Mass? Ochsner-Sherren Rejimi Halen Apendik\u00fcler \nKitle Tedavisinin D\u00fczenlenmesinde Ge\u00e7erli Midir? Ulus Travma \nAcil Cerrahi Derg 2010; 16(1): 43-6. \n\n\n\n4. Arshad M, Noshad AS. 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Int J Surg 2009; 7(3): 250-2.  \n\n\n\n18-Current00013.qxp_3-PRIMARY.qxd  25/09/2023  4:28 PM  Page 674\n\n\n\n\n\n\n\n\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023 627 \n\n\n\nABSTRACT \nIntroduction: Poor sleep quality is common among patients \nwith type 2 diabetes mellitus (T2DM). It has detrimental \neffects on physical and psychological health, as well as on \nquality of life. This study aimed to determine the prevalence \nof poor sleep quality among T2DM patients and to \ninvestigate the factors associated with this disorder.  \n\n\n\nMaterials and Methods: A cross-sectional study was \nconducted at Klinik Kesihatan Seremban in Seremban \ndistrict, Negeri Sembilan. Data were collected using the \nMalay version of the Pittsburgh Sleep Quality Index (PSQI-M) \nwith a cut-off point of >5 as poor sleep quality. The \nDepression Anxiety Stress Scale-21 (DASS-21) was used to \nmeasure level of psychological distress. Data were collected \nbetween July 2022 until January 2023. \n\n\n\nResults: A total of 319 patients with T2DM participated. Their \nmean age was 63 (11) years, 58% were women and 42.9% \nwere of Indian ethnicity. The mean total score of PSQI was \n4.04 (2.21) and 23% of the participants had poor sleep \nquality. Multivariate logistic regression analysis revealed \nthat poor sleep quality was significantly associated with \nIndian ethnicity (Adj. OR = 2.25; 95%CI: 1.05, 4.82; p = 0.037), \nseparated or widowed (Adj. OR = 2.16; 95%CI = 1.15, 4.05; p \n= 0.016), having nocturia (Adj. OR = 2.13; 95%CI = 1.18, 3.84; \np = 0.012) and depressive symptoms (Adj. OR = 3.41; 95%CI: \n1.01, 11.48; p = 0.048).  \n\n\n\nConclusion: Poor sleep quality was prevalent in almost a \nquarter of T2DM patients studied. Indian ethnicity, separated \nor widowed, having nocturia, and depressive symptoms \nwere independently associated with poor sleep quality. \nDespite lower prevalence of poor sleep quality compared to \nother studies, identification of those at higher risk warrants \nfurther exploration in lifestyle management of patients with \nT2DM. \n\n\n\nKEYWORDS: \ntype 2 diabetes mellitus, sleep quality, psychological distress \n\n\n\nINTRODUCTION \nSleep is a physiological need for all human beings as it is \nimportant for both physical and psychological health. Its \nbenefits for vital functions at cellular, metabolic, \nneurological, cardiovascular, cognitive and emotional level \nare extensively studied.1 Despite individual variability with \n\n\n\nage across lifespan, recommended optimal healthy sleep \nduration for adults is 7 to 9 hours a day.1 Some indicators for \ngood sleep quality are shorter sleep latency, fewer \nawakenings, less time needed to wake after sleep onset, and \nhigher sleep efficiency.2 Short sleep duration (< 6 hours per \n24-hour) and long sleep duration (> 9 hours per 24-hour) are\nassociated with multiple morbidities.1,3 Poor sleep quantity\nand quality are implicated for the development and control\nof type 2 diabetes mellitus (T2DM) and obesity.3-5 Inadequate\nsleep causes hormonal imbalance in the body, which induces\nincreases in appetite, blood sugar and insulin resistance\nresulting in obesity and poor glycaemic control.3 Hence,\nhigher prevalence of sleep problem is expected among T2DM\npatients with obesity and poor glycaemic control.\n\n\n\nPrevalence of sleep problems among the general adult \npopulation in Asia Pacific region ranged from 15 to 45%.6-9\n\n\n\nMeanwhile, approximately 33 to 81% of T2DM patients \nreported sleep problems5,8,10,11 and the proportion was \ncomparatively higher than the general population.8 Diabetes \nmellitus (DM) is a growing public health concern worldwide. \nGlobally in 2021, International Diabetes Federation reported \naround 537 million people live with diabetes12, while in \nMalaysia it was estimated that 3.9 million (18.3%) of the \nadult population had deranged glycaemic index in 2019; \ncompared to only 13.4% in 2015.13 These numbers are \nforecasted to expand further in the future. Studies showed \nthat higher age, female gender, high BMI, poor glycaemic \ncontrol, longer duration of diabetes, diabetic complications \nand psychological factors increased the risk for poor sleep \nquality among T2DM patients.5,8,10,11,14 Some of the factors are \nmodifiable with multiple benefits such as weight \nmanagement, glycaemic control and better mental health. In \nMalaysia, there is a dearth of information reported on sleep \nquality and its associated factors among T2DM patients. This \nstudy aimed to identify the prevalence of poor sleep quality \nand determine its associated factors among patients with \nT2DM. \n\n\n\nMATERIALS AND METHODS \nStudy design, location, and population \nThis is a cross-sectional study conducted from July 2022 until \nJanuary 2023 at a non-communicable diseases (NCD) clinic, \nKlinik Kesihatan Seremban in the Seremban district of Negeri \nSembilan. Participants of this study were National Diabetes \nRegistry (NDR) patients from the clinic. Until June 2021, this \nclinic had a total of 5445 registered diabetic patients \n\n\n\nA cross-sectional study on the sleep quality among type 2 \ndiabetes mellitus patients and its associated factors \n\n\n\nNorhazimah Saparwan, MBBS1,2, Noorlaili Mohd Tohit, PhD2, Salmiah Md Sharif, MMed Fam Med3\n\n\n\n1Klinik Kesihatan Seremban 2, Ministry of Health Malaysia, Negeri Sembilan, Malaysia,  2Department of Family Medicine, \nFaculty of Medicine, Universiti Kebangsaan Malaysia, Bandar Tun Razak, Kuala Lumpur, Malaysia, 3Klinik Kesihatan \nSeremban, Ministry of Health Malaysia, Negeri Sembilan, Malaysia\n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 13 August 2023\nCorresponding Author: Noorlaili Mohd Tohit\nEmail: laili@ppukm.ukm.edu.my\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 627\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n628                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nconsisting of 38.7% Indians, 38.5% Chinese, 22.1% Malay \nand 0.7% other ethnics (unpublished data). \n \nSample Size  \nSample size was calculated using the population proportion \nformula with a population size of 5445 registered T2DM \npatients in the clinic, 95% confidence interval, 5% margin of \nerror and 32% population proportion from a local sleep \nquality study among T2DM patients.15  Sample size needed \nwas 316. Considering 10% non-response rate, 347 \nparticipants should be recruited. Each answered \nquestionnaire was immediately checked for completion to \nreduce non-responder. \n \nData Collection and Sampling Method \nSystematic random sampling was carried out with a \nsampling interval of two, based on the T2DM patient \nappointment list extracted from the tele-primary care (TPC) \nsystem with up to 90 patients listed per day. Each patient is \nnumbered, and a computer-generated random number was \nused to select the first patient followed by every other patient \nin the list to intensify recruitment. \n \nData collection was only done for a fixed day in a week for \n24 weeks as the main researcher (NS) had clinical duties in \nthe clinic. Recruitments were challenging as some listed \npatients were affected by Covid19 infection or close contact or \nthere were other reasons hindering clinic visit. \n \nMalaysian citizens aged 18 years and above, diagnosed with \nT2DM of at least six months duration, having attended \ndiabetic follow-up at Klinik Kesihatan Seremban, having \nlatest HbA1c result within one year and literate in Malay or \nEnglish were invited to participate. Those  having conditions \nor illness that do not permit completion of the self-\nadministered questionnaire, working in night shifts or \ntravelling across time zones within one month, pregnant \nwomen, breastfeeding mothers, those with type 1 diabetes \nmellitus (T1DM), having mental illness or use of any kind of \npsychotropic medication, having sleep disorder diagnosed \nprior to diabetes, having endocrine disorders (for example \nthyroid disease), chronic use of glucocorticoid and having \nheart failure were excluded from selection. A brief \nintroduction about the study was given to those recruited, \nand written informed consent was obtained. A self-\nadministered questionnaire was given to the participants \nwhich took about 15 minutes to be completed. A researcher \nwas available on-site for further assistance if necessary. \n \nStudy Instruments  \nData was collected using a structured questionnaire \nconsisting of four parts: sociodemographic data, clinical \nprofile, sleep quality questionnaire and Depression, Anxiety \nand Stress Scale 21-Item questionnaire (DASS-21). It was \navailable in dual language, in Malay and English.  \n \nPart I comprised of personal data of participant such as age, \ngender, ethnicity, marital status, educational level, \nemployment status, and estimated household income.  \n \n \n \n\n\n\nPart II documented their clinical profiles such as duration of \nT2DM, body mass index (BMI), HbA1c level, nocturia, \ncomorbidities and diabetic complications. Body mass index \nwas calculated using the weight and height measured by the \nstandardized stadiometer with a weighing scale during     the \nday of follow-up. The most recent HbA1c levels within the \npast one year were documented from the electronic medical \nrecord system. Other clinical information was collected from \nparticipants\u2019 home-based follow-up cards and confirmed \nwith the electronic medical record system. \n \nPart III was the Pittsburgh Sleep Quality Index (PSQI). This \nself-administered questionnaire developed in 1989 with the \nmain goal of differentiating between people who slept well \nand poorly over the past one month.16 It was locally \ntranslated to Malay (PSQI-M) and validated with Cronbach \nalpha of 0.74 for internal consistency and test-retest \nreliability of 0.58.17 The PSQI is a self-reported questionnaire \nwith 19 items from seven components that assesses subjective \nsleep quality. The seven components are (1) sleep quality (1 \nitem), (2) sleep latency (2 items), (3) sleep duration (1 item), \n(4) sleep efficiency (3 items), (5) sleep disturbance (9 items), \n(6) sleep medication (1 item) and (7) daily dysfunction (2 \nitems). Each component is given a value between 0 and 3, \nand the aggregate of the individual components results in a \nPSQI global score between 0 and 21. A score of 5 or less \nindicates \"good sleepers,\" whereas a score of greater than 5 \nindicates \"poor sleepers\".16 \n \nFor  Part IV, depression, anxiety, and stress were measured \nusing the Depression, Anxiety and Stress Scale (DASS 21).18 \nPart IV contains 21 items divided into three subscales of \ndepression, anxiety, and stress, with seven items allocated for \neach subscale. It inquired about recent experiences in the \npast week and the items were scored on a 4-point scale \nranging from 0 (did not apply to me at all) to 3 (applied to \nme very much, or most of the time). The range of score a \nparticipant could get for each subscale varied from 0 to 21. \nThe total scores were summed up and multiplied by 2.18 The \nrecommended cut-off points were used to classify participants \ninto normal, mild, moderate, severe, and extremely severe in \nterms of depression, anxiety, and stress as in Table I. \nParticipants were classified as having depressive or anxiety or \nstress symptoms if they scored above the cutoff point for \nnormal in the respective subscale. The validated Malay \nversion of DASS21 used in this study reported Cronbach's \nalpha of 0.84, 0.74 and 0.79 for depression, anxiety, and \nstress, respectively.19 \n \nData Analysis \nData were analysed using the SPSS software version 27. \nDescriptive analysis was performed using frequencies and \npercentages for categorical variables and mean \u00b1 standard \ndeviation (SD) for continuous variables. Simple and multiple \nlogistic regression analyses were used to determine factors \nindependently associated with sleep quality. Variables with p \n< 0.25 in the simple logistic regression and important \nvariables from literature were further assessed in multiple \nlogistic regression. p-value of < 0.05 was set as level of \nsignificant. \n \n \n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 628\n\n\n\n\n\n\n\n\nA cross-sectional study on the sleep quality among type 2 diabetes mellitus patients and its associated factors\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                629 \n\n\n\nSeverity                                                Depression                                         Anxiety                                                       Stress \nNormal                                                         0-9                                                    0-7                                                            0-14 \nMild                                                            10-13                                                  8-9                                                           15-18 \nModerate                                                   14-20                                                10-14                                                         19-25 \nSevere                                                        21-27                                                15-19                                                         26-33 \nExtremely severe                                         28+                                                   20+                                                            34+ \n\n\n\nTable I: Cutoff points for DASS-21 scale 18\n\n\n\nFactors                                                                                                                  Sleep quality, n (%)                                             n (%) \n                                                                                                        Poor sleep                        Good sleep \n                                                                                                           (n = 74)                             (n = 245) \n\n\n\nAge (years)*                                                                                            63 (12)                              62 (10)                                 63 (11)             \nGender                                            Female                                            50 (27.0)                           135 (73.0)                              185 (58.0) \n\n\n\n                                                 Male                                                24 (17.9)                           110 (82.1)                              134 (42.0) \nEthnicity                                          Malay                                              14 (18.9)                            60 (81.1)                                74 (23.2) \n\n\n\n                                                 Indian                                            41 (29.9)                            96 (70.1)                               137 (42.9) \n                                                 Chinese                                            19 (17.6)                            89 (82.4)                               108 (33.9) \n\n\n\nMarital Status                                 Single                                               4 (16.0)                             21 (84.0)                                 25 (7.8) \n                                                 Married                                           43 (19.4)                           179 (80.6)                              222 (69.6) \n                                                 Separated                                         5 (45.5)                              6 (54.5)                                  11 (3.4) \n                                                 Widowed                                        22 (36.1)                            39 (63.9)                                61 (19.1) \n\n\n\nEducation level                               No formal education                       7 (43.8)                              9 (56.3)                                  16 (5.0) \n                                                 Primary education                          17 (19.8)                            69 (80.2)                                86 (27.0) \n                                                 Secondary education                     44 (24.4)                           136 (75.6)                              180 (56.4) \n                                                 Tertiary education                           6 (16.2)                             31 (83.8)                                37 (11.6) \n\n\n\nEmployment status                        Employed                                        16 (18.4)                            71 (81.6)                                87 (27.3) \n                                                 Unemployed                                   42 (25.3)                           124 (74.7)                              166 (52.0) \n                                                 Pensioner                                        16 (24.2)                            50 (75.8)                                66 (20.7) \n\n\n\nHousehold income (RM) *                                                                  2122 (3008)                       1778 (2300)                           1858 (2481) \n \n*Mean (SD)  \n\n\n\nTable II: Socio-demographic characteristics of all participants\n\n\n\nFactors                                                                                                                              Sleep quality, n (%)                                 n (%) \n                                                                                                                               Poor sleep                  Good sleep \n                                                                                                                                  (n = 74)                        (n = 245) \nDuration of T2DM(years)*                                                                                     6.8 (6.7)                        7.1 (6.2)                       7 (6.0) \nBMI (kg/m2)*                                                                                                          27.4 (5.7)                        27 (4.5)                     27.1 (4.8) \nBMI categories                             Underweight/normal (BMI \u2264 22.9)                   16 (26.7)                       44 (73.3)                    60 (18.8) \n                                                     Overweight (BMI 23-27.4)                                 27 (22.5)                       93 (77.5)                   120 (37.6) \n                                                     Obese (BMI \u2265 27.5)                                         31 (22.3)                     108 (77.7)                  139 (43.6) \nHbA1c grouping                          Uncontrolled (\u22657 %)                                         42 (23.9)                      134 (76.1)                  176 (55.2) \n                                                     Controlled (< 7%)                                              32 (22.4)                      111 (77.6)                  143 (44.8) \nNocturia                                       Yes                                                                  50 (30.1)                      116 (69.9)                  166 (52.0) \n                                                     No                                                                    24 (15.7)                      129 (84.3)                  153 (48.0) \nComorbidities                              No comorbidities                                              3 (13.0)                        20 (87.0)                     23 (7.2) \n                                                     Hypertension                                                  17 (23.3)                       56 (76.7)                    73 (22.9) \n                                                     Dyslipidemia                                                      13 (28.9)                       32 (71.1)                    45 (14.1) \n                                                     Both                                                                42 (21.6)                      152 (78.4)                  194 (60.8) \nDiabetic complications               No complication                                              58 (22.1)                      205 (77.9)                  263 (82.4)     \n                                                     Retinopathy                                                        0 (0.0)                         4 (100.0)                       4 (1.3) \n                                                     Nephropathy                                                    9 (33.3)                        18 (66.7)                     27 (8.5) \n                                                     Ischemic heart disease                                      5 (27.8)                       13 (72.2)                     18 (5.6) \n                                                     Cerebrovascular accident                                   2 (22.2)                         7 (77.8)                       9 (2.8) \nDepression                                   Normal                                                               63 (21.0)                      237 (79.0)                  300 (94.0) \n                                                     Mild                                                                    5 (50.0)                         5 (50.0)                      10 (3.1) \n                                                     Moderate                                                            2 (40.0)                         3 (60.0)                       5 (1.6) \n                                                     Severe to extremely severe                               4 (100.0)                         0 (0.0)                        4 (1.3) \nAnxiety                                         Normal                                                               64 (21.2)                      238 (78.8)                  302 (94.7) \n                                                     Mild                                                                    4 (44.4)                         5 (55.6)                       9 (2.8) \n                                                     Moderate                                                            4 (80.0)                         1 (20.0)                       5 (1.6) \n                                                     Severe to extremely severe                                2 (66.7)                         1 (33.3)                       3 (0.9) \nStress                                            Normal                                                               63 (20.8)                      240 (79.2)                  303 (95.0) \n                                                     Mild                                                                    4 (50.0)                         4 (50.0)                       8 (2.5) \n                                                     Moderate                                                           5 (100.0)                         0 (0.0)                        5 (1.6) \n                                                     Severe to extremely severe                                2 (66.7)                         1 (33.3)                       3 (0.9) \n \n*Mean (SD) \n\n\n\nTable III: Clinical characteristics of all participants\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 629\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n630                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nEthical Approval \nThis study was approved by Universiti Kebangsaan Malaysia \nResearch Ethics Committee (JEP-2021-800) and Institute of \nMedical Research Ethics Committee. This project was \nregistered with the National Medical Research Registration \n(NMRR ID-21-01986-E44). Permission to conduct the research \nwas also obtained from the Negeri Sembilan State of Health \nDepartment, Seremban District Health Office, and the Family \nMedicine Specialist in Klinik Kesihatan Seremban. \n \n \nRESULTS \nResponse Rate \nA total of 346 T2DM patients were approached, however 15 \npatients refused, and 12 were excluded due to T1DM (one \nparticipant), three had underlying mental problems, four \nhad been working night shift for the past one month and \nanother four had thyroid disorders. All 319 participants \ncompleted the questionnaire making the response rate of \n100%. \n \nCharacteristics of Participants  \nMean age of the participants was 63 years and more than \nhalf of them were women (58%) (Table II). Indians made up \nthe largest ethnic    group (42.9%), more than half of the \nparticipants had at least secondary education levels (56.4%), \ntwo-third were married (69.6%) and half of them were \n\n\n\nunemployed (52%). Slightly more than half of the \nparticipants had uncontrolled T2DM with HbA1c more than \n7% (55.2%) and two fifth of them were obese (43.6%) (Table \nIII). Majority were having comorbidities (97.8%) with nearly \ntwo-third of them having both hypertension and \ndyslipidaemia (60.8%). Most of the participants had no \ndiabetic complications (82.4%) and about half of them (52%) \nexperienced nocturia for the past one month. Nephropathy \nwas the most common complication, followed by Ischemic \nHeart Disease, Cerebrovascular Accident, and lastly Diabetic \nRetinopathy. Participants with depressive, anxiety and stress \nsymptoms were about 6%, 5.3% and 5%, respectively. \n \nPrevalence of poor sleep quality \nThe total mean PSQI score among the participants was 4.04 \n(2.21) with 23% participants had PSQI score of >5, indicating \npoor sleep quality.  \n \nFactors associated with poor sleep quality \nSimple logistic regression revealed p < 0.25 for gender, \nethnicity, marital status, employment, having nocturia and \npsychological distress namely depression, anxiety, and stress \n(Table IV). All the above variables and six other important \nvariables identified from literature, namely age, BMI \ncategory, HbA1c group, duration of T2DM, co-morbidity and \ndiabetic complications were also included for multivariate \nanalysis. \n\n\n\nFactors                                                                                                           \u00df                 Crude OR (95% CI)          Wald test          p value \nAge (years)*                                                                                                 0.01                  1.00 (0.98, 1.03)                 0.51                0.474 \nGender                                         Female                                                    0.52                  1.69 (0.98, 2.93)                 3.58                0.058 \n                                                    Male                                                                                          ref                                                      \nEthnicity                                      Malay                                                                                        ref                                                      \n                                                    Indian                                                    0.60                  1.83 (0.92, 3.63)                 2.97                0.085 \n                                                    Chinese                                                   -0.89                 0.91 (0.42, 1.96)                 0.05                0.820 \nMarital status                              Married                                                                                     ref                                                      \n                                                    Single                                                      -0.28                 0.75 (0.24, 2.29)                 0.24                0.618 \n                                                    Separated/widow                                   0.91                  2.48 (1.38, 4.44)                 9.39                0.002 \nEducation level                           No formal/primary education                0.46                  1.59(0.59, 4.26)                  0.84                0.357 \n                                                    Secondary education                              0.51                  1.67 (0.65, 4.27)                 1.15                0.283 \n                                                    Tertiary education                                                                   ref                                                      \nEmployment status                     Employed                                                                                 ref                                                      \n                                                    Unemployed/pensioner                          0.39                  1.47 (0.79, 2.74)                 1.53                0.215 \nDuration of T2DM (years)*                                                                       -0.009                0.99 (0.95, 1.03)                 0.16                0.687 \nBMI categories                            Underweight/normal (BMI \u2264 22.9)                                            ref                                                         \n                                                    Overweight (BMI 23-27.4)                     -0.22                 0.79 (0.39, 1.63)                 0.38                0.537 \n                                                    Obese (BMI \u2265 27.5)                               -0.23                 0.78 (0.39, 1.58)                 0.44                0.506 \nHbA1c grouping                         Uncontrolled (\u22657 %)                               0.08                  1.08 (0.64, 1.83)                 0.09                0.755 \n                                                    Controlled (< 7%)                                                                      ref                                                         \nNocturia                                       Yes                                                        0.84                  2.31 (1.34, 4.00)                 9.04                0.003 \n                                                    No                                                                                                ref                                                         \nComorbidities                              No comorbidities                                                                      ref                                                         \n                                                    Hypertension                                       -0.01                 0.99 (0.53, 1.84)               <0.001              0.983 \n                                                    Dyslipidemia                                           0.35                  1.41 (0.70, 2.87)                 0.94                0.331 \n                                                    Both                                                     -0.21                 0.80 (0.47, 1.36)                 0.66                0.415 \nDiabetic complications              No complication                                   0.34                  1.41 (0.73, 2.70)                 1.09                0.296 \nDepression                                  Yes                                                           1.64                 5.17 (1.99, 13.40)               11.44               0.001 \n                                                    No                                                                                                ref                                                         \nAnxiety                                        Yes                                                           1.67                 5.31 (1.94, 14.50)               10.61               0.001 \n                                                    No                                                                                                ref                                                         \nStress                                            Yes                                                           2.12                 8.38 (2.81, 25.00)               14.53              <0.001 \n                                                    No                                                                                                ref \n                                                                                                                          \n* Mean (SD)  \n\n\n\nTable IV: Factors associated with sleep quality among participants using simple logistic regression\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 630\n\n\n\n\n\n\n\n\nA cross-sectional study on the sleep quality among type 2 diabetes mellitus patients and its associated factors\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                631 \n\n\n\nIn the multiple logistic regression analysis shown in Table V, \nIndian ethnicity, having nocturia, separated or widowed, and \nhaving depressive symptoms were significant independent \nfactors associated with poor sleep quality. Indian participants \nhad 2.25 times the odds (Adj. OR = 2.25; 95% CI = 1.05, 4.82) \nof having poor sleep quality compared to Malays. Those who \nwere separated or widowed had two times the odds (Adj. OR \n= 2.16; 95% CI = 1.15, 4.05) of having poor sleep quality than \nthose who were married. T2DM patients with nocturia had \n2.13 times the odds (Adj. OR = 2.13; 95% CI = 1.18, 3.84) of \nhaving poor sleep quality than T2DM patients without \nnocturia. Those with depressive symptoms have more than 3 \ntimes higher risk (Adj. OR = 3.41; 95% CI = 1.01, 11.48) of \nhaving poor sleep quality compared to those without \ndepressive symptoms. \n \n \nDISCUSSION \nPrevalence of Poor Sleep Quality \nThe results of the present study demonstrated that 23% of \nT2DM patients participated had poor sleep quality. This \nfinding is the lowest prevalence compared to other studies \namong T2DM patients. \n  \nInternationally, studies showed prevalence of poor sleep \nquality among T2DM patients ranging from 33.6% in \nChina,10 38.1% in Iran,20 47.2% in Ethiopia,21 47.6% in \nKanagawa, Japan5 to 81% in Jordan.11 Another study in \nJapan reported 43.9% poor sleep quality among T2DM \npatients compared to 38.4% among control group.8 \n\n\n\nMeanwhile in east coast Malaysia, a recent study among 350 \nT2DM patients in Kelantan found 32% of them having poor \nsleep quality.15 Lower prevalence in our study could be \nattributed to different socio-demographic and clinical \ncharacteristics of the participants as seen in a study among \nmultiethnic population in Singapore.22 Other local studies \namong various population groups reported higher \nproportion of poor sleep quality such as in working adults \n(45%),17 nurses (57.8%),23 secondary school teachers (61%)24 \nand pre-clinical medical students (63.9%).25  \n \nNevertheless, more importantly the impact of both diabetes \nmellitus and poor sleep was associated with higher risk of all-\ncause mortality compared to either condition alone, as \nreported in UK Biobank cohort data.26  \n \n\n\n\nAssociated Factors for Poor Sleep Quality \nIndian ethnicity, separated or widowed, having nocturia and \nhaving depressive symptoms showed four independent \nfactors of poor sleep quality in this study. Another local study \namong T2DM patients in Kelantan reported nocturia, restless \nleg syndrome and emotional distress were significantly \nassociated with poor sleep.15  \n \nThe ethnic distribution of our study participants were 42.9% \nIndians, 33.9% Chinese and 23.2% Malays, almost similar to \nthe NDR proportion in the clinic. Comparison for ethnicity \nwas limited by unavailability of local study among T2DM \npatients of multiethnic groups. Local studies among \nsecondary school students and elderly population showed \nhigher proportion of poor sleep quality among Indian \nparticipants compared to all participants, though the \ndifference was not statistically significant.27,28 A population \nstudy of sleep quality among Singapore residents with \nmultiethnic representation showed Indian and Malay \nethnicities were at higher odds of poor sleep quality \ncompared to Chinese.22 A review of sleep studies in the United \nStates of America showed that ethnic minorities were at a \ndisadvantage for sleep health disparities compared to White \npopulations.29 Psychosocial stressors, neighbourhood context, \nsocioeconomic status and access to and utilization of health \ncare were some factors attributed to the sleep health \ndisparities which could possibly explained the higher \nprevalence of poor sleep among Indians in our study.29 \n \nIn terms of marital status, a study in Singapore reported that \nthose divorced/separated were at higher risks of poor sleep \nquality compared to married participants, which is consistent \nwith our findings.22 Those divorced and widowed could \npossibly be at socioeconomic disadvantage and under higher \npsychosocial stressor.29,30 \n \nParticipants having nocturia had more than two times the \nodds of experiencing poor sleep compared to those without \nnocturia. Nocturia among T2DM patients was another \nindependent predictor of poor sleep quality in our study \nconsistent with a local study done among T2DM patients in \nKelantan.15 Among Asian population, another study in \nSingapore similarly reported nocturia as the only \nsignificantly associated factor with poor sleep quality among \n199 elderly with T2DM, hyperlipidaemia and hypertension.31 \nA recent large meta-analysis explored the relationship \n\n\n\nFactors                                                                                                    Multiple logistic regression\u1d43                                              p value \n                                                                                            \u00df                        Adjusted OR (95% CI)                Wald test \nEthnic                                  Malay                                     ref                                                                                6.17                          0.046 \n                                            Chinese                                 0.16                           1.18 (0.51, 2.71)                         0.15                          0.701 \n                                            Indian                                   0.81                           2.25 (1.05, 4.82)                         4.37                          0.037 \nMarital                               Married                                  ref                                                                                7.21                          0.027 \n                                            Single                                   -0.46                           0.64 (0.19, 2.05)                         0.58                          0.446 \n                                            Separated/widow                0.77                           2.16 (1.15, 4.05)                         5.81                          0.016 \nNocturia                              Yes                                        0.76                           2.13 (1.18, 3.84)                         6.36                          0.012 \n                                            No                                          ref                                                                                                                       \nDepressive symptoms         Yes                                        1.23                          3.41 (1.01, 11.48)                        3.92                          0.048 \n                                            No                                          ref                                           \n  \naBackward stepwise likelihood ratio multiple logistic regression method was applied.  \nMulticollinearity and interaction terms were checked and not detected. \nHosmer\u2013Lemeshow GOF test (p < 0.001), classification table (overall correctly classified percentage = 76.8%) were applied to check the model fitness. \n\n\n\nTable V: Factors associated with poor sleep quality using multiple logistic regression\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 631\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n632                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nbetween diabetes and nocturia, and found that diabetes itself \nincreased the risk of nocturia by approximately 49%.32 Poor \nglycaemic control has been implicated as a cause for \nnocturia. Nonetheless, in our study, post-hoc analysis showed \nless than a third of the participants (29.7%) with nocturia \nhad poor glycaemic control, which could explain why \nnocturia was significantly associated with poor sleep quality \nbut poor glycaemic control was not. Hence, the presence of \nnocturia should be assessed in people with poor sleep quality \nas it was not necessarily related to poor glycaemic control. \n \nPsychological distress was another factor that showed \nsignificant association with poor sleep quality. National \nHealth Morbidity Survey 2019 reported depression in 2.3% of \nadults in Malaysia with Negeri Sembilan had among the \nhighest prevalence at 5%.13 Similarly the proportion of \nparticipants with possible depression in our study was 6%. In \nthis study, we found that those with depressive symptoms \nhad more than three times the odds of having poor sleep \nquality compared to those without depressive symptoms. The \nassociation between psychological distress and poor sleep \nquality had been consistently reported in many other studies. \nLocal studies on sleep quality among secondary school \nstudents and the elderly attending a primary care clinic \nreported psychological distress was significantly associated \nwith sleep quality.27,28 Studies among T2DM patients locally \nand abroad reported similar association.14,15,21 A study \nconducted among 289 T2DM patients in outpatient diabetic \nclinic of a private hospital setting in Myanmar showed 27.7% \nof participants had depression and it was significantly \nassociated with poor sleep quality (AOR = 7.52, 95%CI = \n3.38\u201314.76).33 Another study  in China among 281 T2DM \npatients with comorbid metabolic syndromes also found \ndepressive symptoms as an independent predictor of poor \nsleep quality and reported further association between \ndepressive symptoms with long sleep latency and short sleep \nduration.34 This association is understandable as insomnia or \nhypersomnia are established symptoms of depression in The \nDiagnostic and Statistical Manual of Mental Disorders (DSM-\n5).35 Emotion regulation, described as various efforts to modify \nthe experience and expression of emotions, has been \nimplicated to sleep quality and depression.36 Impaired \nemotion regulation was reported as a mediator to current \nand prospective relationship between poor sleep quality and \ndepressive symptoms.36 \n \nHigher BMI and poor glycaemic control were two important \nfactors that were not significantly associated with poor sleep \nquality in our study. We postulated, higher BMI, as one of the \ncritical risk factors for the development of Obstructive Sleep \nApnea (OSA) could be associated with poor sleep quality, in \nour study. NHMS 2019 reported overweight (BMI >25 kg/m\u00b2) \nand obesity (BMI>30 kg/m\u00b2) in about 50% of Malaysian \nadults.13 In our study, using lower cut-off point we found \nhigher proportion of overweight (BMI 23-27.4 kg/m\u00b2) and   \nobesity with (BMI \u226527.5 kg/m\u00b2) at 37.6% and 43.6%, \nrespectively. Interestingly both groups with overweight and \nobesity reported lower proportion of poor sleep quality at \n22.5% and 22.3%, respectively. Consistent with our finding, a \nlocal study done among T2DM attending a primary care \nclinic also did not find significant association between higher \nBMI with poor sleep quality even though 91.7% of their \n\n\n\nparticipants were overweight or obese with BMI >23 kg/m\u00b2.15 \nFurther exploration is needed to investigate sleep quality \namong our overweight and obese populations. \n \nStudies reported inconsistent association between poor \nglycaemic control and poor sleep quality. A Japanese study \nfound diabetes patients with higher quartile HbA1c >7.9% \nhad significantly higher global PSQI score than the other \ngroup with better glycaemic index.5 Studies in Jordan and \nEthiopia also found poor glycaemic control was associated \nwith poor sleep quality.11,21 However, another local study and \nother studies in Japan, Iran, Myanmar, and Saudi Arabia \nreported no significant association.8,14,15,33,37 A systematic \nreview and meta-analysis highlighted that short sleep less \nthan 5 hours and long sleep durations more than 8 hours \nwere associated with an increased HbA1c compared to \nnormal sleep.38 Even though in our study more than half of \nparticipants (55.2%) had uncontrolled HbA1c >7%, it was not \nsignificantly associated with poor sleep quality. Hence, \nfurther investigation assessing amount of sleep as well as \nbroader stratification of HbA1c could be useful to see its \nassociation with glycaemic control. Keeping continuous \nvariables such as BMI and HbA1c for continuous analyses \ninstead of categorical analyses could be more meaningful.39  \n \nOne of the limitations in this study was that the sleep quality \nwas subjectively assessed using the PSQI. Apart from its \nacceptance as a standardized tool, it is not an objective \nmeasure like polysomnography. Secondly, a cross-sectional \ndesign of this study can only suggest an association, not the \ncause and effect, for poor sleep quality. In interpreting our \nresults, caution is needed due to the single-centered setting. \nOur findings would be at most, inferred from the local \npopulation attending our primary care clinic. Other than \nthat, mode of treatment especially insulin use, nocturnal \nhypoglycaemia, painful neuropathy and restless leg \nsyndrome which could be related to poor sleep quality among \nT2DM were not assessed in this study. \n \n \nCONCLUSION  \nThis study found that 23% of our studied population have \npoor sleep quality. Indian ethnicity, separated or widowed, \nhaving nocturia and depressive symptoms were independent \nfactors significantly associated with poor sleep quality. \nAssessment of sleep quality should be considered in the \nmanagement of T2DM patients.  Improving sleep quality \nmight involve a simple measure that does not cost much and \nthe ultimate outcome is to maximize the care towards our \ndiabetic patients indirectly improving their quality of life. \n \n \nACKNOWLEDGEMENTS  \nWe would like to thank the Director General of Health \nMalaysia for his permission to publish this article. Our \nhighest appreciation to all patients participated in this study \nand the supportive staffs at Klinik Kesihatan Seremban, \nNegeri Sembilan. We would also like to thank Universiti \nKebangsaan Malaysia and the Ministry of Health Malaysia \nfor ethical approval to conduct this research. \n \n \n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 632\n\n\n\n\n\n\n\n\nA cross-sectional study on the sleep quality among type 2 diabetes mellitus patients and its associated factors\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                633 \n\n\n\nFUNDING AND CONFLICT OF INTEREST  \nThis study was self-funded, and we declare no conflicts of \ninterest.  \n \n \nETHICAL APPROVAL  \nThe ethical approval was obtained from Medical Research & \nEthics Committee\u2019s (MREC), Ministry of Health Malaysia \n(NMRR ID-21-01986-E44), and Research Ethics Committee of \nUniversiti Kebangsaan Malaysia (JEP-2021-800). \n \n \nREFERENCES \n1. 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Sleep health of Australian adults in 2016: results of the \n2016 Sleep Health Foundation national survey. Sleep Health \n2017; 3(1): 35-42. \n\n\n\n10. Lou P, Qin Y, Zhang P, Chen P, Zhang L, Chang G, et al. \nAssociation of sleep quality and quality of life in type 2 diabetes \nmellitus: A cross-sectional study in China. Diabetes Res Clin Pract \n2015; 107(1); 69-76. \n\n\n\n11. Barakat S, Abujbara M, Banimustafa R, Batieha A, Ajlouni K. \nSleep quality in patients with type 2 diabetes mellitus. J Clin Med \nRes. 2019; 11(4): 261-6. \n\n\n\n12. International Diabetes Federation, Brussels, Belgium. 2021. IDF \nDiabetes Atlas, 10th Edition. Available from:  \nhttps://www.diabetesatlas.org  \n\n\n\n13. Institute for Public Health. National Health and Morbidity \nSurvey (NHMS) 2019: Non-communicable diseases, healthcare \ndemand, and health literacy\u2014Key Findings. 2020. \n\n\n\n14. Shamshirgaran SM, Ataei J, Malek A, Iranparvar-Alamdari M, \nAminisani N. Quality of sleep and its determinants among \npeople with type 2 diabetes mellitus in Northwest of Iran. World \nJ Diabetes 2017; 8(7): 358-64. \n\n\n\n15. Nasir NFM, Draman N, Zulkifli MM, Muhamad R, Draman S. \nSleep quality among patients with type 2 diabetes: a cross-\nsectional study in the east coast region of Peninsular Malaysia. \nInt J Environ Res Public Health 2022; 19(9): 5211. \n\n\n\n\n\n\n\n16. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The \nPittsburgh Sleep Quality Index: a new instrument for psychiatric \npractice and research. Psychiatry Res 1989; 28(2): 193-213.  \n\n\n\n17. Farah NMF, Yee TS, Rasdi HFM. Self-reported sleep quality using \nthe malay version of the pittsburgh sleep quality index (PSQI-M) \nin Malaysian adults. Int J Environ Res Public Health 2019; \n16(23): 4750.  \n\n\n\n18. Lovibond SH Lovibond PF. 1995. Manual for the Depression \nAnxiety Stress Scales. 2nd Edition. School of Psychology \nUniversity of New South Wales. \n\n\n\n19. Ramli Musa, Ariff MF, Zaini Z. Translation, validation and \npsychometric properties of Bahasa Malaysia version of the \nDepression Anxiety and Stress Scales (DASS). ASEAN J Psychiatry \n2007; 8(2): 82-9.  \n\n\n\n20. Modarresnia L, Golgiri F, Madani NH, Emami Z, Tanha K. \nRestless Legs Syndrome in Iranian People with type 2 diabetes \nmellitus: the role in quality of life and quality of sleep. J Clin \nSleep Med 2018; 14(2): 223-8. \n\n\n\n21. Birhanu TT, Salih MH, Abate HK. Sleep quality and associated \nfactors among diabetes mellitus patients in a follow-up clinic at \nthe University of Gondar Comprehensive Specialized Hospital in \nGondar, Northwest Ethiopia: A cross-sectional study. Diabetes \nMetab Syndr Obes. 2020; 13: 4859\u201368.                                           \n\n\n\n22. Lee YY, Lau JH, Vaingankar JA, Sambasivam R, Shafie S, Chua \nBY, et al. Sleep quality of Singapore residents: findings from the \n2016 Singapore mental health study. Sleep Med X 2022; 4: \n100043. \n\n\n\n23. Nazatul SM, Saimy I, Moy FM, Nabila AS. Prevalence of sleep \ndisturbance among nurses in a malaysian government Hospital \nand its association with work characteristics. J Heal Transl Med \n2008; 11(2): 66-71. \n\n\n\n24. Musa NA, Moy FM, Wong LP. Prevalence and factors associated \nwith poor sleep quality among secondary school teachers in a \ndeveloping country. Ind Health 2018; 56(5): 407-18. \n\n\n\n25. Ngu ST, Masalamany K, Abd Manan N, Adam SK. Sleep quality \namong pre-clinical medical students in Universiti Putra Malaysia \nand Universiti Malaya, Malaysia. Educ Med J 2017; 9(3): 23-31.  \n\n\n\n26. von Schantz M, Ong JC, Knutson KL. Associations between sleep \ndisturbances, diabetes and mortality in the UK Biobank cohort: A \nprospective population-based study. J Sleep Res 2021; 30(6): \ne13392. \n\n\n\n27. Kesintha A, Rampal L, Sidik SM, Thevandran K. Prevalence and \npredictors of poor sleep quality among secondary school students \nin Gombak District, Selangor. Med J Malaysia 2018; 73(1): 31-40.  \n\n\n\n28. Razali R, Ariffin J, Aziz AFA, Puteh SEW, Wahab S, Daud TIM. \nSleep quality and psychosocial correlates among elderly \nattendees of an urban primary care centre in Malaysia. Neurol \nAsia 2016; 21(3): 265-73. \n\n\n\n29. Johnson DA, Jackson CL, Williams NJ, Alc\u00e1ntara C. Are sleep \npatterns influenced by race/ethnicity - a marker of relative \nadvantage or disadvantage? Evidence to date. Nat Sci Sleep 2019; \n11: 79-95.  \n\n\n\n30. Arber S. Gender, marital status and sleep problems in Britain. \nPrzegl Lek 2012; 69(2): 54-60. \n\n\n\n31. Chiang GSH, Sim BLH, Lee JJM, Quah JHM. Determinants of poor \nsleep quality in elderly patients with diabetes mellitus, \nhyperlipidemia and hypertension in Singapore. Prim Heal Care \nRes Dev 2018; 19(6): 610-5.  \n\n\n\n32. Fu Z, Wang F, Dang X, Zhou T. The association between diabetes \nand nocturia: a systematic review and meta-analysis. Front \nPublic Heal 2022; 10: 924488. \n\n\n\n33. Htut HN, Howteerakul N, Suwannapong N, Rawdaree P. Sleep \nquality among type 2 diabetes mellitus patients in a private \nhospital setting in Yangon, Myanmar. J Heal Res 2021; 35(2): \n186-98.  \n\n\n\n34. Li Y, Buys N, Li L, Sun J. Sleep Quality and Its Determinants \nAmong Type 2 Diabetes Patients with Comorbid Metabolic \nSyndrome. Diabetes, Metab Syndr Obes Targets Ther 2022; 3469\u2013\n82. \n\n\n\n\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 633\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n634                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n35. American Psychiatric Association. 2013. Diagnostic and \nStatistical Manual of Mental Disorders, 5th Edition. American \nPsychiatric Publishing. \n\n\n\n36. O'Leary K, Bylsma LM, Rottenberg J. Why might poor sleep \nquality lead to depression? A role for emotion regulation. Cogn \nEmot 2017; 31(8): 1698-706. \n\n\n\n37. Darraj A, Mahfouz MS, Alsabaani A, Sani M, Alameer A. \nAssessment of sleep quality and its predictors among patients \nwith diabetes in Jazan, Saudi Arabia. Diabetes, Metab Syndr \nObes Targets Ther 2018; 11: 523-31. \n\n\n\n38. Lee SWH, Ng KY, Chin WK. The impact of sleep amount and \nsleep quality on glycemic control in type 2 diabetes: A systematic \nreview and meta-analysis. Sleep Med Rev 2017; 31: 91-101.  \n\n\n\n39. Salis Z, Gallego B, Sainsbury A. Researchers in rheumatology \nshould avoid categorization of continuous predictor variables. \nBMC Med Res Methodol 2023; 23(1): 104. \n\n\n\n\n\n\n\n12-A cross-sectional00086.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 634\n\n\n\n\n\n\n\n\n\n"
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"\n\n570                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Thoracic surgery procedures evolved \nenormously over time from open surgery to video assisted \nthoracoscopic surgery (VATS) and now non-intubated \nuniportal VATS. At our centre, the initial approach for \nbullectomy was by uniportal intubated VATS (iVATS) for \nmost cases. Only in mid-2020, in the midst of COVID-19 \npandemic, uniportal non-intubated VATS (NiVATS) took \nprecedence. We compared the outcome of bullectomy via \niVATS versus NiVATS for a period of 5 years. \n \nMaterials and Methods: We reviewed the medical records of \nall patients that underwent bullectomy from 1st June 2017 to \n31st May 2022. Mann Whitney U-test was completed for all \nvariables. Primary objective was to compare operating time \n(OT), global operating time (GOT), post-operative length of \nstay (LOS) and complication rate.  \n \nResults: A total of 90 bullectomies performed in which 36 \nwere approached via iVATS and 54 NiVATS. It was found that \nthe post-operative LOS, GOT, and OT were significantly \nshorter in the NiVATS as compared to iVATS. Complication \nrate between both groups showed no significant difference.  \n \nConclusion: NiVATS bullectomy demonstrated a safe and \nreliable alternative surgical approach with superior surgical \noutcome than iVATS bullectomy.  \n \nKEYWORDS:  \nThoracic surgery, bullectomy, NIVATS \n \n \nINTRODUCTION \nTraditionally thoracic cases are performed intubated with \neither double lumen or bronchial blocker to achieve single \nlung ventilation. The associated risk of intubation primarily \nled to transition to non-intubated approach.1,2 The likely \nreason of the slow transition to non-intubated is both the \nfamiliarity of surgeon with the cases and a supportive \nanaesthesia team. Challenges faced during the surgery led to \nmany cases being performed with intubated general \nanaesthesia. With the advancement of good regional \nblockade and intravenous anaesthesia, non-intubated \nthoracic surgery has become feasible and is an option for \nmost thoracic procedures in recent times.1-5 \n\n\n\nThere is no doubt that the COVID-19 pandemic brought \nmany changes to the way institutionalised medicine has \nbeen practiced.6 For the most part of the pandemic, it resulted \nin a generalised cessation of elective non-emergent \nprocedures across specialties worldwide, leading to a backlog \nof cases. Being an aerosol generating procedure (AGP), non-\nurgent thoracic surgery procedures were put on hold. The \nadvantage of non-intubated video assisted thoracoscopic \nsurgery (NiVATS) not requiring intubation and hence the \nreduction in augmentation of the airway reduced the AGP \nexposure risk of healthcare personnel, in specific our \nanaesthesia colleagues. This is especially during the \nextubation period when patients cough.7 Hence, selective \nthoracic surgery procedures were continued to be performed \nin our centre with the introduction of non-intubated \ntechnique. Bullectomy cases were regularly performed as we \nserve as the regional referral centre for thoracic cases.  \n \nThis retrospective cohort study aimed to examine the \ndifferences in outcome for those who underwent uniportal \nintubated video assisted thoracoscopic surgery (iVATS) versus \nNiVATS bullectomy in the aspects of post-operative length of \nstay (LOS), global operating time (GOT), operating time (OT) \nand complication rate. \n \n \nMATERIALS AND METHODS \nWe retrospectively reviewed the medical records of all \npatients that underwent iVATS and NiVATS bullectomy from \n1st June 2017 to 31st May 2022 in the Thoracic Unit of \nHospital Kuala Lumpur. All patients with spontaneous \npneumothorax within the age group of 12-80 years and with \npre-operative Contrast Enhanced Computed Tomography of \nThorax showing evidence of bullae or bleb were included in \nthe study. Exclusion criteria were if patients underwent more \nthan one procedure in the same sitting or if other pathology \nwere identified during the surgery. All patients were given \nregional anaesthetic block by anaesthetists prior to \ninduction. The surgical procedures were explained in detail to \nthe patient and a written consent obtained.  \n \nDemographic data and pertinent information were gathered \nfrom the medical records and analysed. The primary \noutcome of post-operative LOS in the hospital, OT, GOT and \ncomplications were analysed. Complications were \n\n\n\nNon-intubated vs. intubated video-assisted thoracoscopic \nbullectomy \u2013 a retrospective cohort study \n \nPalaniappa Meiyappan Palaniappan, MRCS1, Diong Nguk Chai, MMed(Surg)1, Benedict Dharmaraj, \nMMed(Surg)1, Amiruddin Nik Mohamed Kamil, MMed(Anaesthesiology)2, Narasimman Sathiamurthy, \nMMed(Surg)1 \n\n\n\n     \n1Thoracic Surgery Unit, Department of General Surgery, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia, \n2Department of Anaesthesia, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 03 July 2023                                                                                                                                                                              \nCorresponding Author: Narasimmman Sathiamurthy                                                                                                                                                         \nEmail: drnara@hotmail.com\n\n\n\n3-Non-intubated00111.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 570\n\n\n\n\n\n\n\n\nNon-intubated vs. intubated video-assisted thoracoscopic bullectomy \u2013 a retrospective cohort study\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                571 \n\n\n\nMeasure                                                         Number of patients (%)                                             U                                 p value \n                                                       iVATS                                      NiVATS \n                                                       (n=36)                                      (n=54) \n\n\n\nGender \n Male                                               31 (84)                                      48 (89)                                    -                                        - \n\n\n\nFemale                                            5 (16)                                        6 (11)                                     -                                        -  \nAge (Median, year)                               27.0                                          25.0                                 1148.5                               0.146 \nSmoking/vaping                                   21(58)                                      29 (53)                                927.0                                0.667 \n\n\n\nTable I: Demographic summary of iVATS versus NiVATS bullectomy. \n\n\n\nMeasure                                                                       Median                                                           U                                 p value \n                                                       iVATS                                      NiVATS \n\n\n\nLOS (days)                                               4.5                                            3.0                                   660.0                               0.008* \nGOT (minutes)                                      149.0                                         90.0                                  256.5                             < 0.001* \nOT (minutes)                                          91.0                                          60.0                                  274.5                             < 0.001* \nComplications, N                                      3                                               2                                    1017.0                                0.35 \n\n\n\nChest drain >5 days                           2                                               2 \n     Surgical site infection                        1                                               0 \n \nNote \n*Statistical significance p < .05 \nN: Number of participants \nLOS (days): Post-operative length of stay \nGOT (minutes): Global operating time \nOT (minutes): Operating time \n\n\n\nTable II: Outcome summary of iVATS versus NiVATS bullectomy \n\n\n\nProcedures                                                                                                NiTS cases, n = 94 (%) \nBullectomy                                                                                                              54 (57) \nDecortication                                                                                                             7 (7) \nLymph node biopsy                                                                                                  7 (7) \nEndoscopic thoracic sympathectomy                                                                       7 (7) \nWedge resection                                                                                                       6 (6) \nLobectomy                                                                                                                 3 (3) \nTracheal resection and reconstruction                                                                    3 (3) \nPleurodesis                                                                                                                3 (3) \nPleural                                                                                                                        3 (3) \nMediastinal biopsy                                                                                                    1 (1) \n\n\n\nTable III: Non-intubated thoracic surgery (NITS) cases performed\n\n\n\nFirst author (year)                    Type of study           Number of patients                                  Outcomes (p value) \n                                                                                                                                   LOS                    GOT         Complications        Recurrence \nAhmed et al. (2022) 12                Retrospective                         140                      <0.0001*           <0.0001*                0.79                     0.49 \nNoda et al. (2012)13                    Retrospective                          16                            0.7                   0.006*                 0.02*                     - \nPompeo et al. (2017)14                       RCT                                  43                       <0.0001*           <0.0001*                 -                             - \nIrons et al. (2016)15                     Retrospective                          62                        <0.001*            <0.0001*                 -                        N = 0 \nLiu, J et al. (2014)16                            RCT                                 194                      < 0.001*                     -                  0.004*                        - \nPalaniappa et al. (2022)            Retrospective                          90                         0.008*               <0.001*               0.35                     N = 0 \n \nNote. \n*Statistical significance p < .05 \nLOS (days): Post-operative length of stay \nGOT (minutes): Global operating time \n \n\n\n\nTable IV:\u2008Summary of Bullectomy Studies Performed Comparing NiVATS versus iVATS\n\n\n\ndocumented and classified as per Clavein-Dindo \nclassification. \n \nNiVATS in our study is defined as cases that are performed \nwith the patient having spontaneous breathing without \nmuscle relaxant, under deep sedation via intravenous \nanaesthesia and without an endotracheal tube (ETT) across \nthe glottis.8 iVATS is when a patient is on muscle relaxant \nand inhalational anaesthesia under mechanical ventilation \nwith an ETT across the glottis.8 \n\n\n\n\n\n\n\nLOS was defined as the post-operative  hospitalisation \nduration. OT was defined as the time taken for the surgical \nprocedure (skin-to-skin) whereas GOT involved operating \ntime and anaesthesia period from induction to the time \npatient reaches recovery bay post-operatively.9 All patients \nwere followed up for a period of 1 year, after which they were \ndischarged. Chest X-ray was performed during the first visit to \nthe clinic at two weeks after discharge. No chest X-rays were \nperformed in subsequent visits unless indicated. All data were \nstatistically analysed via SPSS statistics v27. Mann Whitney \nU-test was performed for all variables. \n\n\n\n3-Non-intubated00111.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 571\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n572                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nRESULTS \nThroughout the study duration, 90 patients underwent \nuniportal VATS bullectomy, out of which 36 cases via iVATS \nand 54 cases via NiVATS. Table I below summarises the \ndemographic data. \n \nAll the outcome variables of the study violated the normality \nassumption test of Kolmogorov-Smirnov test and hence the \nMann-Whitney U test was utilised. Demographically, age \nand incidence of smoking showed no statistical significance \n(Table I ). \n \nThe test revealed that the post-operative LOS was \nsignificantly shorter in the NiVATS group as compared to the \niVATSgroup (p = 0.008) with a small effect size. As for GOT \nand OT, it was found that patients in the NiVATS group had \na significantly shorter time compared to the iVATS group \nwith large effect size (p < 0.001) as shown in Table II below. \n \nOut of the 90 cases, Five patients (5.56%) were found to have \ncomplications. Two patients (3.7%) in the NiVATS group had \npoor lung expansion post-operatively, requiring prolonged \nchest drain of more than 5 days. This was also seen in the \niVATS group with an additional recorded case (8.3%) of \nsurgical site infection. No statistical significance was seen \ncomparing complications between patients in the NiVATS \nand iVATS group (p = 0.35). All the complications fall under \nthe category of Clavein-Dindo Classification Grade II. There \nwas no procedure related mortality. \n \n \nDISCUSSION \nSince the start of thoracic services in June 2017, thus far 1200 \nthoracic surgical procedures have been performed by a rather \nsmall unit (one thoracic consultant with two thoracic \nsurgeons). Only in June 2020 did the concept of non-\nintubated thoracic surgery (NITS) take precedence and till \ndate a total of 94 (8%) cases of various pathologies have been \nperformed as shown in Table III below. \n \nNiVATS bullectomy was the commonest NITS procedure \nperformed (57%), hence it was chosen to be used as a \ncomparison with iVATS bullectomy in this study.Criteria for \nNITS surgery are short procedure of <2 hours, simple surgery, \nEastern Cooperative Oncology Group (ECOG) score of <1, \nAmerican Society of Anesthesiologists (ASA) class one or two, \nwith a good airway, a body mass index less than 30, and no \nsignificant cardiopulmonary issues.10 However with progress \namong surgeons and anaesthetist and as the learning curve \nimproves; these criteria have expanded further to include \nmore complex surgeries as the indication arises. \n \nOur centre has been performing bullectomy surgery by \nuniportal iVATS from June 2017 to May 2020 and after which \ntill to date, NiVATS technique is used. Savitsky et al. reported \nthe incidence of spontaneous pneumothorax to be estimated \nat 17 to 24/100 000 in the male population and 1 to \n6/100 000 in the female population.11 This is in line with \nmale preponderance in our case series. Both the groups \ncomprise of smokers or vapers without significant difference, \nwhich could be the cause of the bullae or bleb formation. \nThere were no comorbid to report in this young cohort with \nthe median age between 25 to 27 years. \n\n\n\nFocusing on literature search comparing bullectomies \nperformed via NiVATS and iVATS, a few centres have \nembarked and published their findings. Summary of these \nstudies are shown in Table IV below. \n \nBased on Table IV, it is evident that NiVATS ensures a shorter \nLOS and reduced GOT. Recurrence and complications rates \nare similar. Noda et al. showed statistical in-significant result \ncomparing the length of stay and this could be due to the \nsmall population size of that study. Our study showed \nsignificant results for all three primary outcomes of LOS, GOT \nand OT. Complications showed no significant difference (p = \n0.35). This is in accordance to previous studies done. \n \nThe shorter LOS is highly attributable to the reduced \nanaesthesia effect post-surgery and faster recovery. All the \npatients received regional anaesthesia and this helps to \ncontrol immediate post-operative pain as well.16,17 GOT and \nOT are lower in the NiVATS group in line with the papers \npublished. Shorter GOT is due to the reduction of anaesthesia \nhours as patients are non-intubated and recovery is faster. OT \non the other hand comprises only the time of procedure \nperformed by a surgeon. The shorter time needed is likely due \nto the familiarity of surgeons rather than the type of \nanaesthesia. The steep learning curve of NiVATS requires one \nto adapt the skill and hence the initial cases performed may \ntake a longer operating time.16 18 The process of transition \nfrom iVATS to NiVATS has to be in a stepwise manner. It is \nencouraged for thoracic surgeons to have performed at least \n50 iVATS procedures including complex lobectomies and \nsuccessful handling of intraoperative bleeding prior to \nembarking on NiVATS.18 \n \nIt has to be highlighted that there was no conversion to \nintubated or open thoracotomy as far as NiVATS bullectomy \nis concerned and our pneumothorax recurrence rate at 1 year \nfollow-up is zero as well. This is likely due to surgeon \nfamiliarity with bullectomy under iVATS hence the transition \n(NiVATS) outcome was excellent. Similarly, a meta-analysis \nby Tacconi et al. comprising of 1,441 participants showed a \nlow conversion rate of 2.4%, majority being for adhesions \n(1.31%) followed by major bleeding (0.34%).19 This indicates \nNiVATS is a safe alternative option for bullectomy in a well \nselected population. \n \nIn handling complications intra-operatively, the surgical and \nanaesthetic team should be alert and prepared for an \nunfavourable situation that may need conversion to iVATS or \neven thoracotomy. Preparation of instruments for an open \nsurgery as well as preparedness for lateral intubation by \nanaesthetist has to be ensured prior to start of the case. \nLimitations during NiVATS must be clear with low threshold \nfor conversion to ensure patient safety. \n \nIn our study, the complications rate was found to be \ninsignificant, however there are reported papers with a lower \ncomplication rate in NiVATS compared to iVATS (Table IV). \nThe likelihood of our finding is due to small sample size in \nboth arms and short follow-up duration. \n \n \n \n \n\n\n\n3-Non-intubated00111.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 572\n\n\n\n\n\n\n\n\nNon-intubated vs. intubated video-assisted thoracoscopic bullectomy \u2013 a retrospective cohort study\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                573 \n\n\n\nCONCLUSION \nThoracic surgery has always been deemed as a surgery with \nhigh morbidity. NiVATS bullectomy in selected group of \npatients is a viable safe alternative with superior outcomes \ncompared to iVATS. Keeping the benefits in mind, the \nmanaging teams, both surgeons and anaesthetists, must also \nbe prepared to handle crisis situation intraoperatively. The \nlong-term efficacy of non-intubated VATS remains to be \ninvestigated via a well-designed, large-scale, multi-centred \nRCT. \n \n \nCONFLICT OF INTEREST  \nNone \n \n \nREFERENCES \n1. Sesma J, \u00c1lvarez M, G\u00e1lvez C, Bolufer S, Lirio F, Maf\u00e9 JJ, et al. \n\n\n\nNon-intubated vats for the management in primary \nspontaneous pneumothorax. Video-assist Thorac Surg 2019; 4: \n23. \n\n\n\n2. Starke H, Zinne N, Leffler A, Zardo P, Karsten J. Developing a \nminimally-invasive anaesthesiological approach to non-\nintubated uniportal video-assisted thoracoscopic surgery in \nminor and major thoracic surgery. J Thorac Dis 2020; 12(12): \n7202-17.  \n\n\n\n3. Chuang JH, Hung WT, Chen JS. Narrative review of non-\nintubated video-assisted thoracic surgery (NI-VATS) for lung \ncancer: A focus on lobectomy. Video-Assist Thorac Surg 2021; 6: \n25.  \n\n\n\n4. Fur\u00e1k J, Par\u00f3czai D, Buri\u00e1n K, Szab\u00f3 Z, Zombori T. Oncological \nadvantage of nonintubated thoracic surgery: Better Compliance \nof adjuvant treatment after lung lobectomy. Thorac Canc 2020; \n11(11): 3309-16.  \n\n\n\n5. Wang ML, How CH, Hung MH, Huang HH, Hsu HH, Cheng YJ, et \nal. Long-term outcomes after nonintubated versus intubated \nthoracoscopic lobectomy for clinical stage I non-small cell lung \ncancer: A propensity-matched analysis. J Formos Med Assoc \n2021; 120(11): 1949-56. \n\n\n\n6. Wang R, Zhong R, Liang H, Zhang T, Zhou X, Huo Z, et al. \nThoracic surgery and COVID-19: Changes and managements \nduring the pandemic. J Thorac Dis 2021; 13(3): 1507-16.  \n\n\n\n7. Brown J, Gregson F, Shrimpton A, Cook T, Bzdek B, Reid J, et al. \nA quantitative evaluation of aerosol generation during tracheal \nintubation and extubation. Anaesthesia 2020; 76(2): 174-81. \n\n\n\n8. Anile M, Vannucci J, Ferrante F, Bruno K, De Paolo D, Bassi M, et \nal. Non-intubated thoracic surgery: Standpoints and \nperspectives. Front Surg 2022; 9. \n\n\n\n9. Zhang K, Chen HG, Wu WB, Li XJ, Wu YH, Xu JN, et al. Non-\nintubated video-assisted Thoracoscopic Surgery vs. intubated \nvideo-assisted thoracoscopic surgery for thoracic disease: A \nsystematic review and meta-analysis of 1,684 cases. J Thorac Dis \n2019; 11(8): 3556-68. \n\n\n\n10. Gelzinis T. The anesthetic management of patients undergoing \nnon intubated video-assisted Thorac Surg Cur Anesthes Rep \n2021; 11(4): 437-45. \n\n\n\n11. Savitsky E, Oh SS, Lee JM. The evolving epidemiology and \nmanagement of spontaneous pneumothorax. J Am Med Assoc \n2018; 320(14): 1441.  \n\n\n\n12. Elkhouly AG, Karamustafaoglu YA, Galvez C, Rao M, Lerut P, \nGrimonprez A, et al. Nonintubated versus intubated \nthoracoscopic bullectomy for primary spontaneous \npneumothorax: A multicenter propensity-matched analysis. \nAsian Cardiovascular and Thoracic Annals 2022; 30(9): 1010\u20136. \n\n\n\n13. Noda M, Okada Y, Maeda S, Sado T, Sakurada A, Hoshikawa Y, \net al. Is there a benefit of awake thoracoscopic surgery in patients \nwith secondary spontaneous pneumothorax? J Thorac Cardio \nSurg 2012; 143(3): 613-6.  \n\n\n\n14. Pompeo E, Tacconi F, Mineo D, Mineo TC. The role of awake \nvideo-assisted thoracoscopic surgery in spontaneous \npneumothorax. J Thorac Cardio Surg 2007; 133(3): 786-90.  \n\n\n\n15. Irons JF, Miles LF, Joshi KR, Klein AA, Scarci M, Solli P, et al. \nIntubated versus nonintubated general anesthesia for video-\nassisted Thoracoscopic Surgery\u2014a case-control study. J \nCardiothorac Vasc Anesth 2017; 31(2): 411-7. \n\n\n\n16. Liu J, Cui F, Li S, Chen H, Shao W, Liang L, et al. Nonintubated \nvideo-assisted thoracoscopic surgery under epidural anesthesia \ncompared with conventional anesthetic option. Surg Innov 2014; \n22(2): 123-30. \n\n\n\n17. Navarro-Mart\u00ednez J, Galiana-Ivars M, Rivera-Cogollos MJ, \nG\u00e1lvez C, Nadal SB, Lamaign\u00e8re MO, et al. Management of intra \noperative crisis during non intubated thoracic surgery. Thorac \nSurg Clin 2020; 30(1): 101-10.  \n\n\n\n18. Grott M, Eichhorn M, Eichhorn F, Schmidt W, Kreuter M, Winter \nH. Thoracic surgery in the non-intubated spontaneously \nbreathing patient. Respir Res 2022; 23(1). \n\n\n\n19. Tacconi F, Pompeo E. Non-intubated video-assisted Thoracic \nSurgery: Where Does Evidence Stand? J Thorac Dis 2016; 8(S4). \n\n\n\n3-Non-intubated00111.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 573\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                687 \n\n\n\nDear Editor, \n \nAs we know, propolis is a natural resinous material produced \nby bees from various plants. This material is used to seal and \nline the beehives. The quality of propolis depends on \nchemical compositions, geographical region and botanical \norigin. Propolis contains resin, wax, essential oil, pollen, \nminerals, phenolic acid, flavonoids, terpenes, aromatic \naldehydes, alcohols, fatty acids and stilbenes. It has many \nbenefits for human health, for instance, antioxidant, \nantimicrobial, antiproliferative, antitumoral, anti-\ninflammatory and immunomodulatory capacity. Currently, \nthere are many types of products made from propolis, \nincluding tablets, liquids and capsules but they are quite \nexpensive in Vietnam (15\u201320 USD/120 capsules). Customers \ncan use either the original propolis or propolis extract \ndepending on the application. In Vietnam, beekeepers are \nnot very interested in propolis due to the low yield \n(approximately 0.2 kg/herd/year). \n \nThe biggest problem for propolis is its low solubility in water \nand poor bioavailability. Therefore, scientists must use \norganic solvents (acetone, ethanol, etc.) to extract the \nbioactive compounds. In addition, to resolve these problems, \nmany previous studies pointed out that nanoparticles (NPs) \nproduced from propolis extract could be used as drug delivery \nsystems to facilitate drug absorption and are relatively safe \n(low toxicity) and compatible with the human body.1 \nPropolis extract NPs could improve the biological activities \ncompared to the control. In fact, there are many ways to \nencapsulate propolis, for instance, lipid NPs, polymeric NPs, \nand inorganic NPs with various diameters. \n \nIn general, all studies about propolis extract NPs are very \ninteresting; however, they only have focused on the \nantiproliferative, antimicrobial, immunomodulatory \nactivities, cytotoxicity and phytochemical profiles. Those are \nhighlights of medicine, but it is a pity that these experiments \nwere performed in vitro.1 In my opinion, there are some \nmajor issues that need to be resolved when researching the \nhuman body. Firstly, the interaction of unintended NPs and \nimmune cells may create some molecular responses that \n\n\n\nnegatively affect human health, stimulate infectious \ndiseases, induce autoimmune disorders and promote cancer \ndevelopment.2 Secondly, plant extract NPs can be undetected \nby the immune system.3 Lastly, the data on the toxicity of \nplant extract NPs (both carriers and phytochemical \ncomponents of extract from plants) are inadequate. So, the \nimpact of nanoparticles on the immune system is still a grey \nzone. Determination of the toxicity of propolis extract NPs \nand evaluation of their interaction with the human immune \nsystem are quite necessary. Based on the issues mentioned \nabove, the applications of propolis extract NPs in the human \nbody are huge challenges for the medical field and \nnanotechnology, however, future studies are necessary for in \nvivo models. Therefore, the perspective being proposed in this \nstudy is indeed feasible. Although the development of \nnanomedicine is still a long way off, it looks bright and may \nattain great achievements in the future. For NPs produced \nfrom propolis extract, I believe that there are many exciting \nthings to discover with this nanomaterial and they are surely \nadvantageous for human health, at least for in vitro \nexperiments. \n \n \nCONFLICT OF INTEREST \nNone. \n \n \nFUNDS \nNone. \n \n \nREFERENCES \n1. Botteon CEA, Silva LB, Ccana Ccapatinta GV, Silva TS, Ambrosio \n\n\n\nSR,Veneziani RCS, et al. Biosynthesis and characterization of \ngold nanoparticles using Brazilian red propolis and evaluation of \nits antimicrobial and anticancer activities. Sci Rep 2021; 11: \n1974. \n\n\n\n2. Kononenko V, Narat M, Drobne D. Nanoparticle interaction with \nthe immune system. Arh Hig Rada Toksikol 2015; 66: 97-108 \n\n\n\n3. Ernst LM, Casals E, Italiani P, Boraschi D, Puntes V. The \ninteractions between nanoparticles and the innate immune \nsystem from a nanotechnologist perspective. Nanomater 2021; \n11: 2991. \n\n\n\n\n\n\n\nNanoparticles produced from propolis extract: Their \napplications in medicine, why not? \n \nLe Pham Tan Quoc, PhD \n\n\n\n     \nInstitute of Biotechnology and Food Technology, Industrial University of Ho Chi Minh City, Ho Chi Minh City, Vietnam \n\n\n\nLETTER TO EDITOR\n\n\n\n This article was accepted: 04 August 2023                                                                                                                                                                         \nCorresponding Author: Le Pham Tan Quoc \nEmail: lephamtanquoc@iuh.edu.vn \n\n\n\n20-Nanoparticles00065.qxp_3-PRIMARY.qxd  25/09/2023  4:29 PM  Page 687\n\n\n\n\n\n\n\n\n\n"
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"\n\n602                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Previous trials and real-world studies have \nshown that nirmatrelvir/ritonavir (Paxlovid\u00ae) reduces \nhospitalisation and deaths in symptomatic, high-risk, non-\nsevere COVID-19 patients. However, there was a scarcity of \ndata on its effectiveness in the local setting. This study \naimed to determine the effectiveness of Paxlovid\u00ae in \nreducing hospitalisation and mortality among COVID-19 \npatients and to identify the types of adverse events that \noccur after taking Paxlovid\u00ae. \n \nMaterials and Methods: A two-arm prospective cohort study \nwas conducted among adult patients with COVID-19 \ncategories 2 and 3 treated with Paxlovid\u00ae and a matched \ncontrol group. A standard risk-stratified scoring system was \nused to establish Paxlovid\u00ae eligibility. All patients who were \nprescribed Paxlovid\u00ae and took at least one dose of \nPaxlovid\u00ae were included in the study. The control patients \nwere selected from a centralised COVID-19 patient registry \nand matched based on age, gender and COVID-19 stage \nseverity. \n \nResults:  A total of 552 subjects were included in the study \nand evenly allocated to the treatment and control groups. \nThere was no statistically significant difference in 28-day \nhospitalisation after diagnosis [Paxlovid\u00ae: 26 (9.4%), \nControl: 34 (12.3%), OR: 0.74; 95%CI, 0.43-1.27; p=0.274] or \nall-cause death [Paxlovid\u00ae: 2 (0.7%), Control: 3 (1.1%), OR \n1.51; 95%CI, 0.25-9.09; p=0.999]. There was no significant \nreduction in hospitalisation duration, intensive care unit \nadmission events or supplementary oxygen requirement in \nthe treatment arm. Ethnicity, COVID-19 severity at diagnosis, \ncomorbidities and vaccination status were predictors of \nhospitalisation events. \n \nConclusion: In this two-arm study, Paxlovid\u00ae did not \nsignificantly lower the incidence of hospitalisation, all-cause \ndeath and the need for supplemental oxygen. Adverse \neffects were frequent but not severe. Paxlovid\u00ae efficacy \nvaried across settings and populations, warranting further \nreal-world investigations. \n \n\n\n\nKEYWORDS:  \neffectiveness; nirmatrelvir/ritonavir; hospitalisation; death; \nCOVID-19; real-world; Malaysia  \n \n \nINTRODUCTION \nAs of December 2022, the coronavirus disease 2019 (COVID-\n19) has killed 7.5 million people globally, with more than \n650 million positive cases.1 Between January 24 and February \n7, 2022, the predominant COVID-19 variant in Malaysia was \nOmicron, accounting for 92% of cases, followed by Delta at \n8%. On February 7, 2022, the Ministry of Health declared \nOmicron as the dominant strain in Malaysia.2 As of June 1, \n2022, Malaysia had reported 5.10 million confirmed COVID-\n19 cases and 37,087 deaths related to COVID-19.3  \n \nIn April 2022, WHO recommended the use of \nNirmatrelvir/Ritonavir (Paxlovid\u00ae) for high-risk patients \nwith non-severe COVID-19 based on the available evidence \nfrom two randomised controlled trials (EPIC-SR and EPIC-\nHR).4 Nirmatrelvir is a novel SARS-CoV-2 major protease \ninhibitor targeting SARS-CoV-2 3CL, while ritonavir is an \nHIV-1 protease inhibitor that inhibits the CYP3A-mediated \nmetabolism of nirmatrelvir.5  \n \nHammond et al. found that managing symptomatic Covid-\n19 with nirmatrelvir/ritonavir (Paxlovid\u00ae) reduced the risk of \nprogression to severe Covid-19 by 89% compared to placebo, \nwith no apparent safety issues.6 Nirmatrelvir/ritonavir \n(Paxlovid\u00ae) significantly reduced death and hospitalisation \nin the 65 and older group, with adjusted hazard ratios of 0.21 \n(95% CI, 0.05 to 0.82) and 0.74 (95% CI, 0.35 to 1.58), \nrespectively.7 \n \nIn a large-scale retrospective observational cohort study of \nnon-hospitalised adult patients infected with COVID-19, \ntreatment with Paxlovid\u00ae was associated with a lower rate of \n28-day all-cause hospitalisation and 28-day all-cause death \ncompared to no antiviral treatment.8 Another retrospective \ncohort study conducted in Hong Kong found that the use of \nPaxlovid\u00ae was associated with decreased risks of death, \nhospitalisation and in-hospital disease progression.9  \n\n\n\nEffectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) in \npreventing hospitalisation and death among COVID-19 \npatients: a prospective cohort study \n \nChew Lan Sim1, Lim Xin Jie2, Chang Chee Tao2,3, Ros Sakinah Kamaludin1, Leow Hon Lunn1, Ong Su Yin4, \nNorirmawath Saharuddin4, Nor Aida Sanusi4, Normi Kamaruzaman1, Zaiton Kamarruddin4, Philip Rajan2,5 \n\n\n\n     \n1Pharmacy Department, Hospital Raja Permaisuri Bainun, Ministry of Health Malaysia, Ipoh, Malaysia, 2Clinical Research \nCentre, Hospital Raja Permaisuri Bainun, Ministry of Health Malaysia, Ipoh, Malaysia, 3School of Pharmacy, Monash University \nMalaysia, Subang Jaya, Malaysia, 4Perak Pharmaceutical Services Division, Ministry of Health Malaysia, Perak, Malaysia, \n5School of Medicine, Faculty of Health and Medical Sciences, Taylor\u2019s University, Subang Jaya, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 06 July 2023                                                                                                                                                                              \nCorresponding Author: Philip Rajan                                                                                                                                                                                    \nEmail: prajan333@yahoo.com \n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 602\n\n\n\n\n\n\n\n\nEffectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                603 \n\n\n\nDespite a few studies demonstrating the effectiveness of \nPaxlovid\u00ae in real-world settings,7-10 there remains a notable \ngap in the existing evidence, particularly in the South East \nAsia setting. This study provides insights regarding the use of \nPaxlovid\u00ae specifically for the Omicron variant, compared to \nstudies with larger populations and considering the diverse \nethnic populations found in countries like Malaysia. \n \nThis study aims to assess the effectiveness of Paxlovid\u00ae in \nreducing hospitalisations and death among COVID-19 \npatients and determine the occurrence of adverse events \nassociated with its use. \n \n \nMATERIALS AND METHODS \nThis prospective cohort study included adult patients with \ncategory 2 and category 3 COVID-19 who received treatment \nwith Paxlovid\u00ae and a matched control group. The study was \nconducted across 24 study sites, comprising 13 hospitals and \n11 District Health District Offices in the Perak state of \nMalaysia. \n \nPaxlovid\u00ae Regimen \nThe recommended dose for patients with normal renal \nfunction (eGFR > 60ml/min) is 300 mg of nirmatrelvir (two \n150 mg tablets) and 100 mg of ritonavir (one 100 mg tablet), \ntaken orally twice daily for 5 days. Adjusted dosage for renal \nimpaired (eGFR 30\u201360 ml/min) patients is nirmatrelvir 150 \nmg (1 tablet) and ritonavir 100 mg twice daily. \n \nPaxlovid\u00ae Eligibility \nA standard risk-stratified scoring system was used to prioritise \nPaxlovid\u00ae among patients with COVID-19. One point was \ngiven to each of the following characteristics: age \u2265 60 years, \nimmunocompromised, presence of comorbidities, incomplete \nvaccination (did not complete booster dose or unvaccinated), \nobesity and radiographic abnormalities in chest X-ray. The \nscores were summed up and recorded in the Paxlovid\u00ae \ninitiation criteria checklist. Patients who scored equal or more \nthan 2 were eligible for Paxlovid\u00ae.  \n \nPatients were not eligible for Paxlovid\u00ae if they were less than \n18 years old, asymptomatic (Category 1), with symptoms \nonset more than 5 days, started on oxygen, diagnosed liver \ndisease (Child-Pugh Class C) or end-stage renal failure (eGFR \n<30 ml/min), pregnant or breastfeeding, with the inherent \nrisk of hypersensitivity and taking interacting medications, \nincluding carbamazepine, phenobarbital, phenytoin, \nvoriconazole, warfarin, rivaroxaban, colchicine, atazanavir, \ndarunavir, rifampicin,  quetiapine, amlodipine, felodipine, \ndiltiazem, nifedipine, digoxin, lovastatin, simvastatin, \natorvastatin, rosuvastatin, ethinyl oestradiol, cyclosporine, \ntacrolimus, sirolimus, salmeterol, methadone, sildenafil, \ndexamethasone and methylprednisolone. \n \nStudy Inclusion and Exclusion \nWe included all patients prescribed Paxlovid\u00ae in May and \nJune 2022 who consumed at least one dose of Paxlovid\u00ae. We \nexcluded those lost to follow-up (self-reported as having \nCOVID-19 through the Malaysian contact-tracing mobile \napplication MySejahtera but did not seek treatment at clinics \nor hospitals) and did not consume any dose of Paxlovid\u00ae \nafter receiving the medication.  \n\n\n\nMatched Control \nPatients not prescribed Paxlovid\u00ae in March and April 2022 \nwere included in the control arm in a 1:1 ratio. Control \npatients could not be attained in the same period as the \ntreatment group because all eligible patients were started \nwith Paxlovid\u00ae from May onwards. The control patients were \nidentified and retrieved from the state-centralised COVID-19 \npatients registry and matched using age, gender and pre-\ntreatment COVID-19 stage severity.  \n \nSample Size and Sampling Method \nThe sample size was calculated using G-Power (proportion \ndifference from constant, binomial test, one sample case) \nsample size calculator. Based on Hammond et al. 2022, 0.7% \nof Paxlovid\u00ae patients were hospitalised until Day 28, \ncompared to 6.5% of placebo patients who were hospitalised \nor died.6 To detect a difference of 5.8% between the two arms, \nan alpha error of 0.05, a power of 99% and a minimum \nsample size of 117 were required. Assuming 30% incomplete \ndata, each arm's final sample size was 167. Consecutive \nsampling was employed, where all cases which fulfilled the \ninclusion and exclusion criteria were sampled. \n \nOutcome Measures \nThe primary effectiveness measure was an event of 28-day \nhospitalisation post-COVID-19 diagnosis. Paxlovid\u00ae-related \nadverse events and 28-day post-diagnosis death were the \nsecondary outcome measures. \n \nData Collection \nThe data of patients who were prescribed Paxlovid\u00ae were \nentered into the state centralised Paxlovid\u00ae initiation \nregistry, and eligible patients were identified through the \nregistry. Data retrieved included patients\u2019 age, gender, \nethnicity, COVID-19 category during the first encounter, \ntypes and severity of adverse events (Days 1 to 5 post-\ninitiation), and the total doses ingested. We solicited patients\u2019 \nadmission or readmission outcomes, oxygen requirement \nand adverse events (Days 6\u201328) through phone follow-up on \nDay 28 post-initiation.  \n \nSeveral sources of secondary data supplemented this: (i) \nPaxlovid\u00ae initiation criteria checklist containing \ncomorbidities, obesity, immunocompromised status, dose \nprescribed, radiographic abnormalities in chest X-ray; (ii) \nCentralised COVID-19 vaccine database containing \nvaccination status and types of vaccines administered; (iii) \nNational Registration Department, which provided the death \ndata; (iv) electronic hospital information system containing \nthe admission duration, oxygen requirement and intensive \ncare unit (ICU) admission status.  \n \nControl group data retrieved included patients' age, gender, \nethnicity and COVID-19 severity category during the first \nencounter from the state-centralised COVID-19 patients \nregistry and supplemented with data from the Centralised \nCOVID-19 vaccine database, National Registration \nDepartment and hospital information system.  \n \nData Analysis \nThe demographic characteristics of the patients in both the \ntreatment and control arm were descriptively analysed. \nEvents and duration of hospitalisation, ICU admission, \n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 603\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n604                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nsupplemental oxygen requirement and all-cause death \noutcomes for Paxlovid\u00ae recipients were compared with \nmatched controls using the Chi-square (\u03c72) statistic and \nFisher\u2019s exact test for categorical variables and the Mann\u2013\nWhitney U test for continuous variables. Multiple logistic \nregression analysis was performed to determine the \nindependent predictors of hospital admissions and death. \nThe model was constructed consisting of variables significant \nat the 0.25 level. Inferential data were expressed in odd ratios \nand 95% confidence intervals, and a p-value of 0.05 indicates \nstatistical significance.  \n \nEthics Approval \nThis study was registered in the National Medical Research \nRegistry (NMRR ID-22-01372-NIL) and approved by Medical \n\n\n\nResearch Ethical Committee [22-01372-NIL(1)]. Consent was \nobtained from the treatment group patients during the first \nencounter regarding the 28-day phone call follow-up. \n \n \nRESULTS \nBaseline Patient Characteristics \n552 subjects were evenly divided into both arms and \nanalysed. Of 276 patients who received Paxlovid\u00ae treatment, \nthe median age was 53 years (IQR: 40-66 years); 142 (51.4%) \nwere women, and 157 (56.9%) were Malay individuals. The \nmost common comorbidities were hypertension (54.0%) and \ndiabetes (32.6%). The baseline demographic and clinical \ncharacteristics were generally similar in both arms. Of those \nwho received Paxlovid\u00ae, 259 (93.8%) completed the 5-day \n\n\n\n                                                                                         Paxlovid\u00ae group                        Control group                           p value \n                                                                                                (n = 276)                                   (n = 276)                                       \n\n\n\nAge, median (IQR)                                                                       53 (40-66)                                  53 (40-63)                                0.242a \nGender, n (%)                                                                                                                                                                                      \n\n\n\nMale                                                                                       134 (48.6)                                  128 (46.4)                                0.282 \nFemale                                                                                    142 (51.4)                                  148 (53.6)                                      \n\n\n\nEthnicity, n (%)                                                                                                                                                                                    \nMalay                                                                                     157 (56.9)                                  171 (62.0)                                0.189 \nChinese                                                                                    66 (22.5)                                    61 (22.1)                                       \nIndian                                                                                      51 (18.5)                                    43 (15.6)                                       \nOthers                                                                                       6 (2.2)                                        1 (0.4)                                         \n\n\n\nCovid severity at  \n(before treatment), n (%)                                                                                                                                                                   \n\n\n\n2A                                                                                           258 (93.5)                                  258 (93.5)                                0.999 \n2B                                                                                             10 (3.6)                                      10 (3.6)                                        \n3                                                                                                 8 (2.9)                                        8 (2.9)                                         \n\n\n\nComorbidities, n (%)                                                                                                                                                                            \nHypertension                                                                         149 (54.0)                                  160 (58.0)                                0.346 \nDiabetes                                                                                  90 (32.6)                                   101 (36.6)                                0.325 \nDyslipidaemia                                                                           8 (2.9)                                       20 (7.2)                                  0.020 \nChronic kidney disease                                                            6 (2.2)                                       11 (4.0)                                  0.218 \nRespiratory disease                                                                  24 (8.7)                                      26 (9.4)                                  0.767 \nCancer                                                                                       6 (2.2)                                        2 (0.7)                                   0.154 \nCardiovascular disease                                                           29 (10.5)                                    32 (11.6)                                 0.684 \nOthers                                                                                      13 (4.7)                                     32 (11.6)                                 0.003 \n\n\n\nCOVID-19 vaccination status, n (%)                                                                                                                                              0.237 \nCompleted booster dose                                                      202 (73.5)                                  186 (67.4)                                0.119 \nCompleted primary doses                                                      67 (24.4)                                    85 (30.8)                                 0.091 \nUnvaccinated                                                                            6 (2.2)                                        5 (1.8)                                   0.756 \n\n\n\nAdherence, n (%)                                                                                                                                                                                 \nCompleted regimen (10 doses)                                            259 (93.8)                                                                                        \nTaken at least one dose                                                          17 (6.2)                                             \n \n\n\n\na Mann-Whitney U test performed \nb Reason of non-adherence: intolerable adverse events (n=9), patient refusal (n=5), progression to severe COVID-19 (n=1), others (n=2). \n\n\n\nTable I: Characteristics of patients who received Paxlovid\u00ae and matched population controls (n=552)\n\n\n\n                                                                                          Overall           Control             Paxlovid\u00ae            Odds ratio              p-value \n                                                                                         (n=552)            (n=276)                (n=276)                 (95%CI)                       \n\n\n\nHospitalisation, n (%)                                                           60 (10.9)          34 (12.3)               26 (9.4)          0.74 (0.43\u20131.27)           0.274a \nDuration of hospitalisation in days, median (IQR)             4.0 (2\u20136)          4.0 (2\u20137)              5.0 (3\u20136)                      -                        0.952b \nICU admission, n (%)                                                               5 (8.3)              3 (8.8)                  2 (7.7)           1.51 (0.25\u20139.09)           0.999c \nSupplemental oxygen requirement, N (%)                          13(21.7)          10 (29.0)               3(11.5)          3.41 (0.93\u201312.52)           0.05a \nAll-cause death, n (%)                                                            5 (0.9)              3 (1.1)                  2 (0.7)           1.51 (0.25\u20139.09)           0.999c \n \naChi-square test. \nbMann\u2013Whitney U test.  \ncFisher\u2019s exact test. \n\n\n\nTable II: Comparison of hospitalisation, ICU admissions, oxygen requirement and all-cause death outcomes between Paxlovid\u00ae \nrecipients and matched controls (n=552)\n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 604\n\n\n\n\n\n\n\n\nEffectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                605 \n\n\n\nVariable                                                                      Crude OR (95% CI)                   p value            Adjusted OR (95%CI)            p value \nAge (year)                                                                     1.01 (1.00\u20131.03)                        0.129                                                                     \nGender                                                                                                                                                                                                          \n Female                                                                    1.21 (0.70\u20132.07)                         0.50                                                                      \n Male                                                                                 1.00                                                                                                               \nEthnicity                                                                                                                                                                                                        \n Non-Malay                                                              2.08 (1.21\u20133.57)                        0.008                   2.04 (1.10\u20133.80)                   0.024 \n Malay                                                                               1.00                                                                       1.00                                  \nSeverity of COVID-19 at diagnosis                                                                               <0.001                                                              <0.001 \n 2a                                                                            0.02 (0.01\u20130.07)                       <0.001                  0.03 (0.01\u20130.10)                  <0.001 \n 2b                                                                            0.12 (0.03\u20130.59)                        0.009                   0.13 (0.02\u20130.69)                   0.016 \n 3                                                                                        1.00                                                                       1.00                                  \nHypertension                                                                                                                                                                                                \n Yes                                                                          1.11 (0.65\u20131.92)                        0.697                                                                     \n No                                                                                     1.00                                                                                                               \nDM                                                                                                                                                                            \n Yes                                                                          0.94 (0.53\u20131.66)                        0.827                                                                     \n No                                                                                     1.00                                                                                                               \nDyslipidaemia                                                                                                                                                                                               \n Yes                                                                          1.85 (0.68\u20135.07)                        0.229                                                                     \n No                                                                                     1.00                                                                                                               \nCKD                                                                                                                                                                                                               \n Yes                                                                          2.63 (0.83\u20138.35)                         0.10                                                                      \n No                                                                                     1.00                                                                                                               \nRespiratory                                                                                                                                                                                                   \n Yes                                                                          3.40 (1.69\u20136.85)                       <0.001                  0.40 (0.18\u20130.93)                   0.032 \n No                                                                                     1.00                                                                       1.00                                  \nCancer                                                                                                                                                                                                           \n Yes                                                                          2.79 (0.55\u201314.2)                        0.215                                                                     \n No                                                                                     1.00                                                                                                               \nCVS                                                                                                                                                                                                                \n Yes                                                                          2.26 (1.13\u20134.54)                        0.022                   0.43 (0.20\u20130.95)                   0.036 \n No                                                                                     1.00                                                                       1.00                                  \nOthers                                                                                                                                                                                                           \n Yes                                                                          1.89 (0.84\u20134.28)                        0.126                                                                     \n No                                                                                     1.00                                                                                                               \nVaccination status                                                                                                          0.004                                                                0.015 \n Unvaccinated                                                         6.15 (1.71\u201322.1)                        0.005                  6.33 (1.39\u201328.82)                  0.017 \n Complete primary                                                  1.92 (1.09\u20133.39)                        0.025                   1.97 (1.00\u20133.88)                   0.049 \n Complete booster                                                            1.00                                                                       1.00                                  \nPaxlovid\u00ae                                                                                                                                                                                                     \n No                                                                           1.35 (0.79\u20132.32)                        0.275                                                                     \n Yes                                                                                    1.00                                                                                                               \n \nBackward LR method was applied; No multicollinearity and no interaction; Hosmer Lemeshow test, p value=0.506; Classification table 90.9% correctly \nclassified; area under receiver operating characteristics (ROC) curve was 78%.  OR: Odd ratios; DM: Diabetes mellitus; CKD: Chronic kidney disease; CVS: \nCardiovascular disease \n\n\n\nTable III: Univariate and multivariate binary logistic regression for day 28 post-diagnosis hospitalisation event (n=552)\n\n\n\ncourse treatment.  Overall, 73.5% of the patients had received \na booster dose, 24.4% received the primary series, and 2.2% \nwere unvaccinated (Table I). \n \nHospitalisation, ICU Admission, Oxygen Requirement and \nAll-Cause Death  \nFrom the first day of diagnosis to day 28 post-diagnosis, 60 \n(10.9%) patients required hospitalisation. There were no \nstatistically significant differences in day 28 post-diagnosis \nhospitalisation events between the two arms [Paxlovid\u00ae: 26 \n(9.4%), Control: 34 (12.3%), OR: 0.74; 95% confidence \nintervals, 0.43\u20131.27; p=0.274]. The median duration of \nhospitalisation was 4.0 days (IQR: 2\u20136 days). There were no \nsignificant differences in total ICU admissions and \nsupplemental oxygen requirement in the treatment arm. Five \ndeaths were reported at day 28 post-diagnosis, with no \nsignificant differences across both arms [Paxlovid\u00ae: 2 (0.7%), \nControl: 3 (1.1%), OR: 1.51; 95%CI 0.25-9.09; p=0.999] (Table \nII). \n \n\n\n\nPredictive Factors of Hospitalisation  \nNon-Malays had 2.04 times greater odds of hospitalisation \nthan Malays. [OR: 2.04; 95%CI 1.10\u20133.80; p=0.024]. \nIronically, patients with underlying respiratory [OR: 0.40; \n95%CI, 0.18\u20130.93; p=0.032] and cardiovascular disease [OR: \n0.43; 95%CI, 0.20\u20130.95; p=0.036] demonstrated lower risks of \nhospitalisation.  \n \nThe odds of hospitalisation for COVID-19 varied based on the \nstatus of vaccination. Patients vaccinated with the primary \nseries without a booster dose were more likely to be \nhospitalised than boosted patients [OR 1.97; 95%CI 1.00\u2013\n3.88; p=0.049]. The odds of hospitalisation were 6.3 times \nhigher in unvaccinated patients compared to those who were \nboosted [OR: 6.33; 95%CI, 1.39\u201328.82; p=0.017]. \n \nA milder stage of COVID-19 at diagnosis was associated with \ndecreased odds of hospitalisation. Patients who were \ndiagnosed with Stage 2a [OR: 0.03; 95%CI, 0.01\u20130.10; \np<0.001] and Stage 2b [OR: 0.13; 95%CI, 0.02\u20130.69; p=0.016] \n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 605\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n606                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nwere associated with a lower risk of hospitalisation compared \nto stage 3 (Table III). \n \nAdverse Events  \nThe reported adverse events after Paxlovid\u00ae ingestion was as \nfollows: dysgeusia (96, 61.1%), diarrhoea (49, 31.2%), nausea \nand vomiting (11, 7.0%), myalgia (7, 4.5%), abdominal pain \n(5, 3.2%), hypertension (3,1.9%) and others (41, 26.1%). \nThere was no life-threatening adverse event reported.  \n \n \nDISCUSSION \nThis was a real-world study in a multiracial country within \nthe ASEAN region to evaluate the effectiveness of Paxlovid\u00ae \nin reducing hospitalisation and all-cause death. Our study \nfound hospitalisation and all-cause death occurred in 9% \nand 0.8% of Paxlovid\u00ae patients, respectively, which was \nhigher than what was reported by previous studies.6,11,12 \nHammond et al. reported 0.77% of hospitalisation with no \ndeath,6 while Shah et al. reported 0.47% of hospitalisation \nand 0.01% of death in patients receiving Paxlovid\u00ae.11 \n\n\n\nFurthermore, Malden and colleagues discovered that \nemergency department visits or hospitalisations were less \nthan 1% in the 5\u201315 days following Paxlovid\u00ae treatment.12  \nSimilarly, larger real-world cohort studies7-10 carried out \nduring Omicron domination reported a reduction of \nhospitalisation and death in the Paxlovid\u00ae group, but with a \nlower magnitude than Hammond et al. In contrast with \n\n\n\nprevious studies, we did not find a significant reduction in \nhospitalisation and all-cause death in patients who took \nPaxlovid\u00ae. Also, we did not observe any significant reduction \nin intensive care unit (ICU) admission and supplemental \noxygen requirement among patients taking Paxlovid\u00ae. \nAlthough previous studies did not find a reduction in ICU \nadmission among patients who took Paxlovid\u00ae, a \nsignificantly lower need for oxygen therapy was reported.9,10 \nThe insignificant results might be explained by several \ndifferences between the studies, including the study \npopulation and settings.  \n \nFirst, the population's natural immunity may have risen over \ntime due to previous strain infections, contributing to lower \nseverity, hospitalisation and death.13 Second, about 7% of our \nstudy population did not adhere to the Paxlovid\u00ae regimen, \nwhich may reduce the effectiveness of Paxlovid\u00ae.10 \n \nNotably, the EPIC-HR trial6 included only unvaccinated \npatients, whereas our study included merely 2% \nunvaccinated subjects, and 70% had received the booster \ndose. Similarly, two previous studies found no significant \nreduction in hospitalisation or all-cause death among \nvaccinated inpatients who received Paxlovid\u00ae.9,14 The action \nof Paxlovid\u00ae could be masked by COVID-19 vaccinations, \nwhich effectively reduce disease severity and death.10,15 Hence, \nour findings may rationalise the prioritisation of Paxlovid\u00ae \namong unvaccinated patients, especially in resource-poor \n\n\n\n                                                                                           Control group                        Paxlovid\u00ae group                        p value \n                                                                                                  (n=34)                                        (n=26)                                         \n\n\n\nAge, median (IQR)                                                                  55.5 (33.3\u201372.3)                        58.5 (36.8\u201369.3)                           0.715a \nGender, n (%)                                                                                                                                                                                      \n Male                                                                                        13 (38.2)                                    13 (50.0)                                 0.362 \n Female                                                                                     21 (61.8)                                    13 (50.0)                                       \nEthnicity, n (%)                                                                                                                                                                                    \n Malay                                                                                      13 (38.2)                                    13 (50.0)                                 0.631 \n Chinese                                                                                    14 (41.2)                                     8 (30.8)                                        \n Indian                                                                                       7 (20.6)                                      5 (19.2)                                        \n Others                                                                                                                                                                                             \nCovid severity at  \n(before treatment), n (%)                                                                                                                                                                   \n 2A                                                                                            25 (73.5)                                    15 (57.7)                                 0.282b \n 2B                                                                                              2 (5.9)                                       5 (19.2)                                        \n 3                                                                                                7 (20.6)                                      6 (23.1)                                        \nComorbidities, n (%)                                                                                                                                                                            \n Hypertension                                                                          19 (55.9)                                    16 (61.5)                                  0.66 \n Diabetes                                                                                  10 (29.4)                                    10 (38.5)                                 0.582 \n Dyslipidaemia                                                                          4 (11.8)                                       1 (3.8)                                   0.377b \n Chronic kidney disease                                                            2 (5.9)                                        2 (7.7)                                   0.999b \n Respiratory disease                                                                  8 (23.5)                                      5 (19.2)                                   0.76 \n Cancer                                                                                       1 (2.9)                                        1 (3.8)                                   0.999b \n Cardiovascular disease                                                            6 (17.6)                                      6 (23.1)                                  0.747 \n Others                                                                                      6 (17.6)                                       2 (7.7)                                   0.446b \nCOVID-19 vaccination status, n (%)                                                                                                                                                    \n Completed booster dose                                                        18(52.9)                                     15(57.7)                                  0.92b \n Completed primary doses                                                      14(41.2)                                      9(34.6)                                        \n Unvaccinated                                                                             2(5.9)                                         2(7.7)                                         \nAdherence, n (%)                                                                                                                                                                                 \n Completed regimen (10 doses)                                                                                                22 (84.6)                                       \n Taken at least one dose                                                                                                            4(15.4)                                        \n \naMann\u2013Whitney U test was performed. \nbFisher\u2019s exact test was performed. \n \n\n\n\nSupplementary Table I:  Demographic and clinical characteristics of the hospitalised patients (n = 60)\n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 606\n\n\n\n\n\n\n\n\nEffectiveness of nirmatrelvir/ritonavir (Paxlovid\u00ae) \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                607 \n\n\n\nsettings. Lastly, the fact that we included fewer subjects in the \nover-65 age group in which Paxlovid\u00ae was found to be more \nefficacious7 may have contributed to the underestimation of \nits efficacy. \n \nOur analysis showed non-Malays had higher hospitalisation \nodds than Malays, suggesting the potential association \nbetween ethnicity and COVID-19 severity.10,16,17 It is important \nto note that genetic polymorphisms may affect drug \nmetabolism and medication response.18 Variations in allelic \nfrequencies of the CYP2D6*10 gene have been observed \namong the Chinese, Malay and Indian populations.19 Apart \nfrom different drug metabolism profiles, ethnicity could be \nthe surrogate for underlying factors, including socioeconomic \nstatus, exposure to virus-related- environments and access to \nhealth care.20 Further investigation is needed in this area to \nreduce health inequalities across different ethnic groups.17 \n \nThe most commonly reported Paxlovid\u00ae-related adverse \nevents in this study were dysgeusia, diarrhoea, and vomiting, \nwhich mirrored previous findings.6,14 While the reported \nadverse events were not severe, they might lead to patients\u2019 \nnon-adherence, causing drug resistance and treatment \nfailure.21 Therefore, medication counselling, compliance \nfollow-up, and pharmacovigilance are essential components \nof Paxlovid\u00ae dispensing.22 \n \nWe did not observe a significant difference in the odds of \ndeath between both arms. Two deaths were reported in the \nPaxlovid\u00ae arm, unrelated to COVID-19 infection or \nPaxlovid\u00ae treatment. There were three deaths in the control \ngroup, of which two were related to COVID-19 pneumonia. In \ncontrast, Hammond et al. reported a significant difference in \nall-cause death outcomes, in which no death occurred in the \ntreatment arm and 13 deaths in the placebo arm, of which \nall were COVID-19 related.4 Nonetheless, the high number \nneeded to treat in preventing one death suggests the need to \ninvestigate the cost-effectiveness of Paxlovid\u00ae, particularly in \na low-resource health setting.  \n \nThis study reflected the real-world efficacy of Paxlovid\u00ae using \na matched cohort, which includes both outpatients and \ninpatients, vaccinated and unvaccinated populations. \nInitiation of Paxlovid\u00ae was performed using a standard risk-\nstratified scoring system and closely reflected clinical practice \nin Malaysian health settings. Several limitations should be \nconsidered when interpreting the findings of this study. The \nsmall sample size and the exclusion of lost to follow-up cases \ncould restrict the generalisability of the study findings. \nFurthermore, there was a limited representation of subjects in \nthe over-65 age group. Matching participants based on \nlimited characteristics may introduce bias if other unknown \nfactors influence the outcomes studied.  \n \n \nCONCLUSION \nThe use of Paxlovid\u00ae to treat symptomatic Covid-19 did not \nsignificantly reduce the risk of hospitalisation, all-cause \ndeath and supplemental oxygen requirement compared to \nthe control group. Adverse events were common but non-\nsevere. The efficacy of Paxlovid\u00ae in real-world settings and \ndifferent populations remains inconsistent and warrants \nfurther investigations. \n\n\n\nREFERENCES \n1. World Health Organization (WHO). WHO Coronavirus (COVID-\n\n\n\n19) Dashboard. 2022. https://covid19.who.int. Accessed 25 \nDecember 2022. \n\n\n\n2. Tan KT, Benedict SLH, Chang CY, Chidambaram SK, Abd Jamil \nI, Bahrudin MS, et al. Clinical severity of COVID-19 with omicron \nvariant predominance in relation to vaccination status, age, \ncomorbidities- a single center in Selangor, Malaysia. Med J \nMalaysia 2022; 77: 558-63. \n\n\n\n3. Our World in Data. Malaysia: Coronavirus Pandemic Country \nProfile. 2022. https://ourworldindata.org/coronavirus/ \ncountry/malaysia. Accessed 10 Jun 2023. \n\n\n\n4. World Health Organization (WHO). WHO recommends highly \nsuccessful COVID-19 therapy and calls for wide geographical \ndistribution and transparency from originator. 2022. \nhttps://www.who.int/news/item/22-04-2022-who-recommends-\nhighly-successful-covid-19-therapy-and-calls-for-wide-\ngeographical-distribution-and-transparency-from-originator. \nAccessed 13 Feb 2023. \n\n\n\n5. Pfizer. Pfizer shares in vitro efficacy of novel COVID-19 oral \ntreatment against omicron variant | Pfizer. 2022. \nhttps://www.pfizer.com/news/press-release/press-release-\ndetail/pfizer-shares-vitro-efficacy-novel-covid-19-oral-treatment. \nAccessed 13 Feb 2023. \n\n\n\n6. Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, \nWisemandle W, et al. Oral nirmatrelvir for high-risk, \nnonhospitalized adults with Covid-19. New Engl J Med. 2022; \n386: 1397-408. \n\n\n\n7. Arbel R, Sagy YW, Hoshen M, Battat E, Lavie G, Sergienko R, et \nal. Nirmatrelvir use and severe Covid-19 outcomes during the \nomicron surge. N Engl J Med 2022; 387: 790-8. \n\n\n\n8. Aggarwal NR, Molina KC, Beaty LE, Bennett TD, Carlson NE, \nMayer DA, et al. Real-world use of nirmatrelvir-ritonavir in \noutpatients with COVID-19 during the era of omicron variants \nincluding BA.4 and BA.5 in Colorado, USA: a retrospective cohort \nstudy. Lancet Infect Dis 2023; 23: 696-705. \n\n\n\n9. Wong CKH, Au ICH, Lau KTK, Lau EHY, Cowling BJ, Leung GM. \nReal-world effectiveness of early molnupiravir or nirmatrelvir\u2013\nritonavir in hospitalised patients with COVID-19 without \nsupplemental oxygen requirement on admission during Hong \nKong\u2019s omicron BA.2 wave: a retrospective cohort study. Lancet \nInfectious Dis. 2022; 22: 1681-93. \n\n\n\n10. Najjar-Debbiny R, Gronich N, Weber G, Khoury J, Amar M, Stein \nN, et al. Effectiveness of paxlovid in reducing severe coronavirus \ndisease 2019 and mortality in high-risk patients. Clin Infect Dis. \n2023; 76: e342-9. \n\n\n\n11. Shah MM, Joyce B, Plumb ID, Sahakian S, Feldstein LR, Barkley \nE, et al. Paxlovid associated with decreased hospitalization rate \namong adults with COVID-19 \u2014 United States, April\u2013September \n2022. MMWR Morb Mortal Wkly Rep 2022; 71: 1531-7. \n\n\n\n12. Malden DE, Hong V, Lewin BJ, Ackerson BK, Lipsitch M, Lewnard \nJA, et al. Hospitalization and emergency department encounters \nfor COVID-19 after paxlovid treatment - California, December \n2021-May 2022. MMWR Morb Mortal Wkly Rep 2022; 71: 830\u20133. \n\n\n\n13. Ridgway JP, Tideman S, Wright B, Robicsek A. Decreased risk of \ncoronavirus disease 2019-related hospitalization associated with \nthe omicron variant of severe acute respiratory syndrome \ncoronavirus 2. Open Forum Infect Dis 2022; 9: ofac288. \n\n\n\n14. Tiseo G, Barbieri C, Galfo V, Occhineri S, Matucci T, Almerigogna \nF, et al. Efficacy and safety of nirmatrelvir/ritonavir, \nmolnupiravir, and remdesivir in a real-world cohort of \noutpatients with COVID-19 at high risk of progression: the PISA \noutpatient clinic experience. Infect Dis Ther 2023; 12: 257-71. \n\n\n\n15. Rosenberg ES, Holtgrave DR, Dorabawila V, Conroy M, Greene D, \nLutterloh E, et al. New COVID-19 cases and hospitalizations \namong adults, by vaccination status - New York, May 3-July 25, \n2021. MMWR Morb Mortal Wkly Rep 2021; 70: 1150-5. \n\n\n\n16. Magesh S, John D, Li WT, Li Y, Mattingly-app A, Jain S, et al. \nDisparities in COVID-19 outcomes by race, ethnicity, and \nsocioeconomic status: a systematic review and meta-analysis. \nJAMA Netw Open 2021; 4: e2134147. \n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 607\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n608                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n17. Sze S, Pan D, Nevill CR, Gray LJ, Martin CA, Nazareth J, et al. \nEthnicity and clinical outcomes in COVID-19: a systematic \nreview and meta-analysis. EClinicalMed 2020; 29\u201330: 100630. \n\n\n\n18. Shenfield GM. Genetic polymorphisms, drug metabolism and \ndrug concentrations. Clin Biochem Rev 2004; 25: 203-6. \n\n\n\n19. Runcharoen C, Fukunaga K, Sensorn I, Iemwimangsa N, \nKlumsathian S, Tong H, et al. Prevalence of pharmacogenomic \nvariants in 100 pharmacogenes among Southeast Asian \npopulations under the collaboration of the Southeast Asian \nPharmacogenomics Research Network (SEAPharm). Hum \nGenome Var 2021; 8: 7. \n\n\n\n\n\n\n\n20. CDC. Risk for COVID-19 Infection, Hospitalization, and Death By \nRace/Ethnicity. Centers for Disease Control and Prevention. 2020. \nh t tp s : / /www.cdc .gov/co ronav i rus /2019 -ncov/cov id -\ndata/investigations-discovery/hospitalization-death-by-race-\nethnicity.html. Accessed 13 Feb 2023. \n\n\n\n21. Bezabhe WM, Chalmers L, Bereznicki LR, Peterson GM. \nAdherence to antiretroviral therapy and virologic failure: a meta-\nanalysis. Medicine 2016; 95: e3361. \n\n\n\n22. Chang CT, Ong SY, Lim XJ, Chew LS, Rajan P. Managing \nnirmatrelvir/ritonavir during COVID-19: pharmacists\u2019 \nexperiences from the Perak state of Malaysia. J Pharm Policy \nPract 2022; 15: 70.\n\n\n\n8-Effectiveness00128.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 608\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\n646                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Sexting refers to the act of sending and \nreceiving sexually explicit content in the form of in the form \nof texts, photos, or videos via the Internet and mobile \nphones. This behaviour is associated with many negative \nhealth consequences among young people. However, there \nis a lack of intervention studies to curb this behaviour. We \nhave developed a new sexting prevention module and tested \nit using a randomised controlled field trial. This paper \nreported the phase one of the study i.e., the development of \nan animated sexting prevention module using the prototype \nwillingness model (PWM) to reduce the intention and \nwillingness to sext amongst diploma students in Malaysia.  \n \nMaterials and Method: The initial phase involved a review of \nprevious interventions, validation from field experts, and the \nprocess of developing video. Then the module pilot was \ntested among 30 diploma students from a public university. \nThey were given access to the newly developed videos \nposted on a private YouTube channel and asked to evaluate \nthe videos quantitatively and qualitatively by using the \nacceptability of the intervention module (AIM), intervention \nappropriateness measure (IAM) and feasibility of the \nintervention measure (FIM). The minimum and maximum \nscores of each measure were 12 and 24 respectively \nwhereby a higher score indicated greater acceptability, \nappropriateness and feasibility.  \n \nResults: The intervention consisted of five sections \naddressing the constructs of PWM, namely attitude, \nperceived norm, prototype perception, as well as intention \nand willingness of sexting. The contents were then \nconverted into five videos with a total duration of 23 \nminutes. Based on the pilot test, the scores of AIM, IAM and \nFIM were not normally distributed and their median and the \ninterquartile range values were 20 (4), 21 (4) and 22 (4) \nrespectively. Most of the respondents gave favourable \nopinions on the intervention besides providing some input \nfor improvement.  \n \nConclusion: This animated sexting intervention module \nbased on PWM to reduce the intention and willingness was \nnovel. The module was acceptable, appropriate and feasible \nto be implemented among undergraduate students. Further \n\n\n\nevaluation of this intervention module can be performed to \nprovide more comprehensive evidence of its effectiveness.  \n \nKEYWORDS:  \nSocial media, intention, Malaysia, students, sexting, pilot projects \n \n \nINTRODUCTION \nThe term sexting is a combination of sex and texting. It refers \nto the act of sending and receiving sexually explicit content \nin the form of texts, photos, or videos via the Internet and \nmobile phones.1,2 \n \nSexting is a new form of sexual communication among the \nyoung population in discovering sexual needs and desires as \nwell as for them to maintain sexual intimacy.3 However, \nrecent studies reported that sexting might cast some adverse \npsychosocial consequences on young people, for example, \ncyberbullying, depression and attempted suicide.4\u20138 \n\n\n\nFurthermore, it is also associated with sexually risky \nbehaviours such as sexual intercourse with multiple partners. \nDue to the profound impact of sexting and its association \nwith other risky behaviours that can burden young people\u2019s \nhealth, sexting must be curtailed. In relation to that, sending \nobscene content via media is a punishable act under \nMalaysian law, and the penalty is more severe if minors were \ninvolved.9,10 \n \nCurrently, interventional studies are scarce on sexting-related \nissues. The majority of previous studies followed a within-\nsubject experimental study design that focused on the effects \nof social images on the prototype perception and willingness \nto sext among adolescents.11 To date, observational studies \nhave asserted that engagement in sexting can be forecasted \nby intention and willingness to sext.12\u201314 By definition, \nintention refers to a deliberately planned behaviour15 while \nwillingness refers to an individual's spontaneous response to \nrisky circumstances.16 Both intention and willingness are \ninvolved in the behaviour that precedes any cognitive \nprocess.17 By focusing on the intention and willingness to \nsext, the intervention aimed at preventing sexting amongst \nthose who have never sexted, reducing the act of sexting \namong those who have sexted and minimising multiple risky \nbehaviours associated with sexting. \n\n\n\nDevelopment of an online animated sexting prevention \nmodule based on the prototype willingness model to reduce \nintention and willingness to sexting among diploma students  \n \nNorain Mansor, DrPH1,2, Norliza Ahmad, PhD1, Salmiah Md Said, MCommMed1, Kit-Aun Tan, PhD3, Rosnah \nSutan, PhD4 \n\n\n\n     \n1Department of Community Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, \nMalaysia, 2Ministry of Health, Malaysia, 3Department of Psychiatry, Faculty of Medicine and Health Sciences, Universiti Putra \nMalaysia, Serdang, Selangor, Malaysia, 4Department of Community Health, Faculty of Medicine, Universiti Kebangsaan \nMalaysia, Jalan Yaacob Latif, Bandar Tun Razak Cheras, Kuala Lumpur, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 24 August 2023                                                                                                                                                                         \nCorresponding Author: Norliza Ahmad                                                                                                                                                                               \nEmail: lizaahmad@upm.edu.my\n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 646\n\n\n\n\n\n\n\n\nDevelopment of an online animated sexting prevention module based on the prototype \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                647 \n\n\n\nThe application of a theory-based intervention is more likely \nto yield a better outcome.18,19 Therefore, we used the prototype \nwillingness model (PWM) theory as the backbone of our \nintervention to reduce the intention and willingness to sext. \nThe PWM has been applied to predict risky behaviours \namongst the adolescents and young adult population.14,20\u201322 \nHowever, this theory has not been applied to sexting \ninterventions to date. To our knowledge, this is the first \nintervention module developed based on PWM for sexting. \nThe evaluation of the effectiveness of this module involved \ntwo phases, i.e., phase one involved the development and \nvalidation of the newly developed module and the second \nphase involved evaluating the effectiveness of this module \nusing randomised controlled trial (RCT). In this paper, we \nreported phase one of the study. The second phase is reported \nelsewhere. \n \n \nMATERIALS AND METHODS \nPhase one involved the identification of the suitable contents \nfor the intervention based on the respective constructs of the \nPWM before matching them with the suitable behavioural \nchange techniques (BCT).18 These processes involved \nreviewing previous literature and consultation with experts in \nthe field. Three public health experts and a clinical \npsychologist were invited to examine the content validity. \nOnce the contents were agreed upon by all the experts, the \nstoryboard and scripts for the animated video was created. A \nprivate multimedia company was then appointed to develop \nthe animated video. The animated video used to deliver the \nintervention was assessed for its objective, structure, \npresentation and relevance as a part of the validation \nprocess. A series of reviews of the scripts and the flow of the \nstoryboard was also conducted by the same experts before it \nwas finalised. The flow of the development of the video as in \nAppendix 1. \n \nLater, a pilot study was conducted at a public university, \nwhich is the same university where phase two of the study \nwas conducted. The university has 13 diploma programmes. \nOne programme was randomly selected for the pilot study. \nThe remaining 12 programmes were involved in phase two of \nthis study, where a randomised controlled field trial (RCT) \nwas conducted to test the effectiveness of this module. Thirty \nvoluntary students who fulfilled the inclusion criteria of the \nRCT but were not included in the main study were invited to \nparticipate in the pilot study. The sample size of 30 was \nderived from 10% of the sample size calculated for the RCT.23 \n \nYouTube channel was utilised as the online medium to \ndistribute the newly developed video as it was convenient and \neasily accessible. The videos were set to be private and only \nthose with access could view them. The pilot study aimed to \ndetermine the acceptability, appropriateness, and feasibility \nof the intervention module by using quantitative measures.24 \nAcceptability is a form of personal judgment made by \nindividuals about the intervention and it can vary according \nto individual needs, preferences or expectations. In \ncomparison, appropriateness refers to the perceived fit, \nrelevance or compatibility of the intervention to be practiced \nin a given setting. In other words, it assesses the technical or \nsocial perspective towards the intervention. Feasibility, on the \n\n\n\nother hand, is the practicality with which the new \nintervention can be successfully carried out in a given setting. \n \nThree quantitative scales were used, namely acceptability of \nintervention measure (AIM), intervention appropriateness \nmeasure (IAM) and feasibility of intervention measure \n(FIM).24 Each of these scales consisted of four-item \nstatements. The response scale for all item statements ranged \nfrom 1 (completely disagree) to 5 (completely agree). The \nminimum and maximum scores of each of the measures are \n12 and 24 respectively. A higher score indicates greater \nacceptability, appropriateness and feasibility. The \nrespondents were also requested to provide opinions and \nfeedback on the videos. \n \nThe studies involving human participants were reviewed and \napproved by the Ethics Committee for Research Involving \nHuman Subjects at Universiti Putra Malaysia (JKEUPM-2020-\n321). The patients/participants provided their written \ninformed consent to participate in this study. The RCT of this \nintervention module was prospectively registered in the Thai \nClinical Trials Registry (TCTR20201002001). The approval \nfrom the administration department of the higher education \ninstitution and the head of the program, as well as \nrespondents\u2019 written consent, were obtained before the \ncommencement of the study.  \n \n \nRESULTS \nThe PWM consists of five constructs, i.e. intention, \nwillingness, attitude, perceived norm and prototype \nperception. Figure 1 illustrates the theoretical construct of the \nPWM.21,25 \n \nThe intervention was developed in the Malay language to \nsuit the target population. It comprises five sections, namely \nSection 1 (Sexting and Z generation), Section 2 (What are the \nimplications of sexting?), Section 3 (Who is behind sexting?), \nSection 4 (What others' opinion?) and Section 5 (What can \nyou do?). The summary of constructs and contents in each \nsection of the intervention is summarised in Table I. \n \nSection 1: Sexting and Z generation \nThis was an introductory session that was delivered via an \nanimated video. Participants were informed of the definition \nof sexting and the population was deemed to be at risk of \nbeing involved in it. \n \nSection 2: What are the implications of sexting? \nParticipants were educated on the consequences of sexting \nfrom four aspects, including sexual and reproductive health, \ncyberbullying, mental health and the legal aspect. The \ncontent of this section was based on the literature review on \nthe implications of sexting.2,6\u20138,26\u201328 In this section, the \nparticipants were also exposed to the real scenario of \nnegative consequences of sexting as reported in the local \nmedia. \n \nSection 3: Who is behind sexting? \nParticipants were exposed to the different personalities of \npeople who are more prone to engage in sexting (for \nexample, individuals with a high sensation-seeking \n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 647\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n648                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nSe\nct\n\n\n\nio\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nPW\nM\n\n\n\n c\non\n\n\n\nst\nru\n\n\n\nct\ns\n\n\n\n\n\n\n\n A\nim\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  B\neh\n\n\n\nav\nio\n\n\n\nur\n c\n\n\n\nha\nng\n\n\n\ne \nte\n\n\n\nch\nni\n\n\n\nqu\nes\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  D\nur\n\n\n\nat\nio\n\n\n\nn \n \n\n\n\nSe\nct\n\n\n\nio\nn\n\n\n\n 1\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n -\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n T\no\n\n\n\n in\ncr\n\n\n\nea\nse\n\n\n\n t\nh\n\n\n\ne \nkn\n\n\n\no\nw\n\n\n\nle\nd\n\n\n\ng\ne \n\n\n\no\nf \n\n\n\nse\nxt\n\n\n\nin\ng\n\n\n\n\n\n\n\n   \n  2\n\n\n\n. P\nro\n\n\n\nvi\nd\n\n\n\ne \nin\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn\n a\n\n\n\nb\no\n\n\n\nu\nt \n\n\n\nth\ne \n\n\n\nse\nxt\n\n\n\nin\ng\n\n\n\n t\nre\n\n\n\nn\nd\n\n\n\n a\nm\n\n\n\no\nn\n\n\n\ng\nst\n\n\n\n t\nh\n\n\n\ne\n   \n\n\n\n\n\n\n\n   \n2.\n\n\n\n4 \nm\n\n\n\nin\nu\n\n\n\nte\ns.\n\n\n\n \nSe\n\n\n\nxt\nin\n\n\n\ng\n a\n\n\n\nn\nd\n\n\n\n Z\n g\n\n\n\nen\ner\n\n\n\nat\nio\n\n\n\nn\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n a\n\n\n\nm\no\n\n\n\nn\ng\n\n\n\nst\n t\n\n\n\nh\ne \n\n\n\np\nar\n\n\n\nti\nci\n\n\n\np\nan\n\n\n\nts\n. \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nZ \ng\n\n\n\nen\ner\n\n\n\nat\nio\n\n\n\nn\n a\n\n\n\nn\nd\n\n\n\n t\nh\n\n\n\ne \nre\n\n\n\nas\no\n\n\n\nn\ns \n\n\n\nw\nh\n\n\n\ny \nit\n\n\n\n is\n c\n\n\n\no\nm\n\n\n\nm\no\n\n\n\nn\n a\n\n\n\nm\no\n\n\n\nn\ng\n\n\n\n t\nh\n\n\n\nem\n. \n\n\n\n Se\nct\n\n\n\nio\nn\n\n\n\n 2\n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n A\ntt\n\n\n\nit\nu\n\n\n\nd\ne\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \nTo\n\n\n\n im\np\n\n\n\nro\nve\n\n\n\n t\nh\n\n\n\ne \nat\n\n\n\nti\ntu\n\n\n\nd\ne \n\n\n\nto\nw\n\n\n\nar\nd\n\n\n\ns \nse\n\n\n\nxt\nin\n\n\n\ng\n. \n\n\n\n   \n i.\n\n\n\n P\nro\n\n\n\nvi\nd\n\n\n\ne \nin\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn\n o\n\n\n\nn\n t\n\n\n\nh\ne \n\n\n\nn\neg\n\n\n\nat\niv\n\n\n\ne \nco\n\n\n\nn\nse\n\n\n\nq\nu\n\n\n\nen\nce\n\n\n\ns \no\n\n\n\nf \nse\n\n\n\nxt\nin\n\n\n\ng\n   \n\n\n\n   \n 9\n\n\n\n.3\n m\n\n\n\nin\nu\n\n\n\nte\ns.\n\n\n\nW\nh\n\n\n\nat\n a\n\n\n\nre\n t\n\n\n\nh\ne \n\n\n\nim\np\n\n\n\nlic\nat\n\n\n\nio\nn\n\n\n\ns \no\n\n\n\nf \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \nTo\n\n\n\n r\ned\n\n\n\nu\nce\n\n\n\n t\nh\n\n\n\ne \nin\n\n\n\nte\nn\n\n\n\nti\no\n\n\n\nn\n a\n\n\n\nn\nd\n\n\n\n w\nill\n\n\n\nin\ng\n\n\n\nn\nes\n\n\n\ns \n   \n\n\n\n   \n f\n\n\n\nro\nm\n\n\n\n f\no\n\n\n\nu\nr \n\n\n\nas\np\n\n\n\nec\nts\n\n\n\n w\nh\n\n\n\nic\nh\n\n\n\n a\nre\n\n\n\n s\nex\n\n\n\nu\nal\n\n\n\n a\nn\n\n\n\nd\n r\n\n\n\nep\nro\n\n\n\nd\nu\n\n\n\nct\niv\n\n\n\ne \nh\n\n\n\nea\nlt\n\n\n\nh\n,  \n\n\n\nse\nxt\n\n\n\nin\ng\n\n\n\n? \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  t\no\n\n\n\n s\nex\n\n\n\nt \nam\n\n\n\no\nn\n\n\n\ng\nst\n\n\n\n p\nar\n\n\n\nti\nci\n\n\n\np\nan\n\n\n\nts\n.  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\ncy\nb\n\n\n\ner\nb\n\n\n\nu\nlly\n\n\n\nin\ng\n\n\n\n, m\nen\n\n\n\nta\nl h\n\n\n\nea\nlt\n\n\n\nh\n a\n\n\n\nn\nd\n\n\n\n le\ng\n\n\n\nal\nit\n\n\n\ny.\n  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n ii\n\n\n\n. P\nro\n\n\n\nvi\nd\n\n\n\ne \nre\n\n\n\nal\n w\n\n\n\no\nrl\n\n\n\nd\n n\n\n\n\neg\nat\n\n\n\niv\ne \n\n\n\nan\nd\n\n\n\n le\ng\n\n\n\nis\nla\n\n\n\nti\no\n\n\n\nn\n c\n\n\n\no\nn\n\n\n\nse\nq\n\n\n\nu\nen\n\n\n\nce\ns \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n o\nf \n\n\n\nse\nxt\n\n\n\nin\ng\n\n\n\n t\no\n\n\n\n t\nh\n\n\n\ne \nin\n\n\n\nd\niv\n\n\n\nid\nu\n\n\n\nal\ns \n\n\n\nb\nas\n\n\n\ned\n o\n\n\n\nn\n t\n\n\n\nh\ne \n\n\n\nre\np\n\n\n\no\nrt\n\n\n\ns \nb\n\n\n\ny \nlo\n\n\n\nca\nl m\n\n\n\ned\nia\n\n\n\n.  \n Se\n\n\n\nct\nio\n\n\n\nn\n 3\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n P\n\n\n\nro\nto\n\n\n\nty\np\n\n\n\ne \n   \n\n\n\n\n\n\n\n\n\n\n\n   \nTo\n\n\n\n im\np\n\n\n\nro\nve\n\n\n\n t\nh\n\n\n\ne \np\n\n\n\nro\nto\n\n\n\nty\np\n\n\n\ne \np\n\n\n\ner\nce\n\n\n\np\nti\n\n\n\no\nn\n\n\n\n. \n   \n\n\n\n\n\n\n\ni. \nPr\n\n\n\no\nvi\n\n\n\nd\ne \n\n\n\nin\nfo\n\n\n\nrm\nat\n\n\n\nio\nn\n\n\n\n a\nb\n\n\n\no\nu\n\n\n\nt \nth\n\n\n\ne \nch\n\n\n\nar\nac\n\n\n\nte\nri\n\n\n\nst\nic\n\n\n\ns \no\n\n\n\nr \np\n\n\n\ner\nso\n\n\n\nn\nal\n\n\n\nit\ny\n\n\n\n\n\n\n\n   \n 3\n\n\n\n m\nin\n\n\n\nu\nte\n\n\n\ns.\n \n\n\n\nW\nh\n\n\n\no\n is\n\n\n\n b\neh\n\n\n\nin\nd\n\n\n\n s\nex\n\n\n\nti\nn\n\n\n\ng\n?\n\n\n\n\n\n\n\n\n\n\n\n   \n p\n\n\n\ner\nce\n\n\n\np\nti\n\n\n\no\nn\n\n\n\n\n\n\n\n\n\n\n\n   \n  T\n\n\n\no\n r\n\n\n\ned\nu\n\n\n\nce\n t\n\n\n\nh\ne \n\n\n\nin\nte\n\n\n\nn\nti\n\n\n\no\nn\n\n\n\n a\nn\n\n\n\nd\n w\n\n\n\nill\nin\n\n\n\ng\nn\n\n\n\nes\ns \n\n\n\n\n\n\n\no\nf \n\n\n\nin\nd\n\n\n\niv\nid\n\n\n\nu\nal\n\n\n\ns \nw\n\n\n\nh\no\n\n\n\n a\nre\n\n\n\n a\nss\n\n\n\no\nci\n\n\n\nat\ned\n\n\n\n w\nit\n\n\n\nh\n s\n\n\n\nex\nti\n\n\n\nn\ng\n\n\n\n b\neh\n\n\n\nav\nio\n\n\n\nu\nr.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  t\n\n\n\no\n s\n\n\n\nex\nt \n\n\n\nam\no\n\n\n\nn\ng\n\n\n\nst\n p\n\n\n\nar\nti\n\n\n\nci\np\n\n\n\nan\nts\n\n\n\n. \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  \nSe\n\n\n\nct\nio\n\n\n\nn\n 4\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n P\n\n\n\ner\nce\n\n\n\niv\ned\n\n\n\n n\no\n\n\n\nrm\n   \n\n\n\n\n\n\n\n T\no\n\n\n\n r\ned\n\n\n\nu\nce\n\n\n\n t\nh\n\n\n\ne \np\n\n\n\ner\nce\n\n\n\niv\ned\n\n\n\n n\no\n\n\n\nrm\n, i\n\n\n\nn\nte\n\n\n\nn\nti\n\n\n\no\nn\n\n\n\n\n\n\n\n i.\n P\n\n\n\nro\nvi\n\n\n\nd\ne \n\n\n\no\np\n\n\n\nin\nio\n\n\n\nn\ns \n\n\n\no\nf \n\n\n\np\nar\n\n\n\nen\nts\n\n\n\n a\nn\n\n\n\nd\n o\n\n\n\nth\ner\n\n\n\n y\no\n\n\n\nu\nn\n\n\n\ng\n a\n\n\n\nd\nu\n\n\n\nlt\ns \n\n\n\no\nn\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n2 \n\n\n\nm\nin\n\n\n\nu\nte\n\n\n\ns.\n \n\n\n\nW\nh\n\n\n\nat\n o\n\n\n\nth\ner\n\n\n\ns\u2019\n o\n\n\n\np\nin\n\n\n\nio\nn\n\n\n\n? \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  a\nn\n\n\n\nd\n w\n\n\n\nill\nin\n\n\n\ng\nn\n\n\n\nes\ns \n\n\n\nto\n s\n\n\n\nex\nt \n\n\n\nam\no\n\n\n\nn\ng\n\n\n\nst\n  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nin\nd\n\n\n\niv\nid\n\n\n\nu\nal\n\n\n\ns \nw\n\n\n\nh\no\n\n\n\n a\nre\n\n\n\n in\nvo\n\n\n\nlv\ned\n\n\n\n in\n s\n\n\n\nex\nti\n\n\n\nn\ng\n\n\n\n.  \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n  p\n\n\n\nar\nti\n\n\n\nci\np\n\n\n\nan\nts\n\n\n\n. \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nSe\nct\n\n\n\nio\nn\n\n\n\n 5\n: \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n  P\ner\n\n\n\nce\niv\n\n\n\ned\n n\n\n\n\no\nrm\n\n\n\n\n\n\n\n   \n T\n\n\n\no\n r\n\n\n\ned\nu\n\n\n\nce\n t\n\n\n\nh\ne \n\n\n\np\ner\n\n\n\nce\niv\n\n\n\ned\n n\n\n\n\no\nrm\n\n\n\n, p\nro\n\n\n\nto\nty\n\n\n\np\ne \n\n\n\n   \n i.\n\n\n\n P\nro\n\n\n\nvi\nd\n\n\n\ne \nin\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn\n o\n\n\n\nn\n p\n\n\n\no\nte\n\n\n\nn\nti\n\n\n\nal\n s\n\n\n\nce\nn\n\n\n\nar\nio\n\n\n\ns \nth\n\n\n\nat\n m\n\n\n\nig\nh\n\n\n\nt \nle\n\n\n\nad\n  \n\n\n\n\n\n\n\n   \n5.\n\n\n\n4 \nm\n\n\n\nin\nu\n\n\n\nte\ns.\n\n\n\n \nW\n\n\n\nh\nat\n\n\n\n y\no\n\n\n\nu\n c\n\n\n\nan\n d\n\n\n\no\n? \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nPr\no\n\n\n\nto\nty\n\n\n\np\ne \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\np\ner\n\n\n\nce\np\n\n\n\nti\no\n\n\n\nn\n, i\n\n\n\nn\nte\n\n\n\nn\nti\n\n\n\no\nn\n\n\n\n, a\nn\n\n\n\nd\n w\n\n\n\nill\nin\n\n\n\ng\nn\n\n\n\nes\ns \n\n\n\nto\n  \n\n\n\n   \n t\n\n\n\no\n s\n\n\n\nex\nti\n\n\n\nn\ng\n\n\n\n. \n   \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n p\n\n\n\ner\nce\n\n\n\np\nti\n\n\n\no\nn\n\n\n\n\n\n\n\n\n\n\n\n   \n  s\n\n\n\nex\nt \n\n\n\nam\no\n\n\n\nn\ng\n\n\n\nst\n p\n\n\n\nar\nti\n\n\n\nci\np\n\n\n\nan\nts\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n ii\n. P\n\n\n\nro\nvi\n\n\n\nd\ne \n\n\n\nin\nfo\n\n\n\nrm\nat\n\n\n\nio\nn\n\n\n\n o\nn\n\n\n\n p\no\n\n\n\nte\nn\n\n\n\nti\nal\n\n\n\n b\nar\n\n\n\nri\ner\n\n\n\ns \no\n\n\n\nf \nre\n\n\n\nsi\nst\n\n\n\nin\ng\n\n\n\n s\nex\n\n\n\nti\nn\n\n\n\ng\n. \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n ii\n\n\n\ni. \nPr\n\n\n\no\nvi\n\n\n\nd\ne \n\n\n\nsk\nill\n\n\n\ns \nto\n\n\n\n r\nes\n\n\n\nis\nt \n\n\n\nse\nxt\n\n\n\n r\neq\n\n\n\nu\nes\n\n\n\nts\n b\n\n\n\ny \no\n\n\n\nth\ner\n\n\n\ns \nan\n\n\n\nd\n in\n\n\n\nfo\nrm\n\n\n\nat\nio\n\n\n\nn\n  \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n   \n o\n\n\n\nn\n w\n\n\n\nh\ner\n\n\n\ne \nto\n\n\n\n g\net\n\n\n\n h\nel\n\n\n\np\n. \n\n\n\n\n\n\n\nTa\nbl\n\n\n\ne \nI: \n\n\n\nSu\nm\n\n\n\nm\nar\n\n\n\ny \nof\n\n\n\n th\ne \n\n\n\nse\nxt\n\n\n\nin\ng \n\n\n\nin\nte\n\n\n\nrv\nen\n\n\n\ntio\nn \n\n\n\nm\nod\n\n\n\nul\ne \n\n\n\n(S\nIM\n\n\n\n)\n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 648\n\n\n\n\n\n\n\n\nDevelopment of an online animated sexting prevention module based on the prototype \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                649 \n\n\n\nItems                 Item statement                                                                                      Responses (n=30) \n                                                                         Completely           Disagree (%)             Neither agree              Agree (%)          Completely \n                                                                        disagree (%)                                          nor disagree (%)                                       agree (%) \nAIM 1      This SIM meets my approval                  0                              0                              17%                          53%                    30% \nAIM 2      This SIM is appealing to me                   0                              0                              20%                          50%                    30% \nAIM 3      I like SIM                                                  0                              0                              23%                          50%                    27% \nAIM 4      I welcome SIM to be given                    0                              0                              10%                          47%                    43% \n                to other students                                      \n\n\n\nTable II: Acceptability intervention measure (AIM)\n\n\n\nItems                 Item statement                                                                                  Responses (n=30) \n                                                                         Completely              Disagree                Neither agree                Agree             Completely  \n                                                                        disagree (%)                  (%)                  nor disagree (%)                 (%)                 agree (%) \nIAM 1      This SIM seems fitting in                        0                              0                              10%                          50%                    40% \n                the sexting prevention effort                  \nIAM 2      This SIM seems suitable for                    0                              0                              13%                          50%                    37% \n                university students                                    \nIAM 3      This SIM seems applicable                      0                              0                              13%                          40%                    47% \nIAM 4      This SIM seems like a good                    0                              0                              13%                          37%                    50% \n                match with the current  \n                technology era.                                         \n \n \n\n\n\nTable III: Appropriateness measure\n\n\n\nItems                 Item statement                                                                                 Responses (n=30) \n                                                                         Completely              Disagree               Neither agree             Agree (%)          Completely  \n                                                                        disagree (%)                  (%)                  nor disagree (%)                                       agree (%) \nFIM 1       Things that we learn from                     0                              0                              13%                          37%                    50% \n                SIM seem implementable                         \nFIM 2       Things that we learn from                     0                              0                              13%                          37%                    50% \n                SIM seem possible                                     \nFIM 3       Things that we learn from                     0                              0                              13%                          37%                    50% \n                SIM seem doable                                      \nFIM 4       Things that we learn from                     0                              0                              13%                          37%                    50% \n                SIM seem easy to apply in  \n                real life                                                       \n \n\n\n\nTable IV: Feasibility of intervention measure\n\n\n\nFig. 1: The theoretical construct of the prototype willingness model.\n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 649\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n650                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\npersonality trait, low agreeableness, neuroticism and \nattachment anxiety). The content of this section was based \non the findings from the literature review on studies of the \nrelationship between personality type and sexting \nbehaviour.28-30 \n \nSection 4: What others' opinion? \nParticipants were provided with relevant information on the \nperceived and actual prevalence of sexting in Western and \nAsian countries as a comparison. Besides, they were also \nprovided with information about the perception and \napproval of others about sexting behaviour, particularly \nparents, friends, religion and culture. The content was \nadapted from the findings of quantitative and qualitative \nstudies obtained during the literature review.31\u201333  \n \nSection 5: What can you do? \nParticipants were provided with the instructions on how to \nresist social pressure to sext, such as a demonstration on how \nto resist sext requests by others. The participants were also \nreminded to use prompts, whereby they are taught to identify \nenvironmental prompts that can be applied as a reminder for \nthem to avoid potential situations that can lead to sexting. \nThe participants were also prompted to think about the \npotential barriers that can prevent them from engaging in \nsexting and to identify ways to overcome the behaviour. \n \nBased on the response of the pilot study, the majority of the \nrespondents found this intervention module to be acceptable \n(Table II). The scores were not normally distributed, giving a \nmedian (interquartile range, IQR) of 20 (4). Qualitatively, \nrespondents suggested improvement in the video\u2019s graphics \nand animation, as well as increasing examples using real-\nworld sexting scenarios. Furthermore, some respondents \nrecommended for the intervention be expanded to school \nchildren. \n \nBased on the response, the majority of the respondents found \nthis intervention to be appropriate (Table III). The scores were \nnot normally distributed, giving a median (IQR) of 21 (4). No \nadditional comment was made qualitatively in this section. \n \nBased on the response, the majority of the respondents found \nthat this intervention was feasible (Table IV). The scores were \nnot normally distributed, giving a median (IQR) of 22 (4). \nQualitatively, the respondents suggested uploading the video \non social media platforms such as TikTok to gain more \nattention.  \n \n \nDISCUSSION \nIn this paper, we reported the development of an online \nanimated sexting intervention module based on the PWM \naimed at reducing the intention and willingness to sext \namong diploma students in Malaysia. The PWM was chosen \nas the model to address the intention and willingness of \nsexting, both of which represented important precursors to \nsexting behaviour. This model has also been used in previous \ninterventions for the reduction of risky behaviours.14,20\u201322 \nTherefore, this intervention module was established based on \nthe previous interventions using PWM, and consultation with \nexperts, before being validated via a pilot study involving a \n\n\n\nsubgroup of the study population who were not participants \nof the main RCT. \n \nSexting is a complex behaviour that has been explained by \nseveral behavioural theories, including PWM. The \napplication of PWM in the design of the intervention video in \nthis study represented a systematic approach to determine its \nefficacy in reducing the sexting intention and willingness \namong young adults. Since most of the published literature \nfocused on the use of PWM for smoking, skin tanning \nprevention and prevention of alcohol consumption, it is \nnecessary to acknowledge how PWM could contribute to the \nreduction of the intention and willingness to sext among \nundergraduate students. \n \nNext, the design of this intervention was adapted from the \nseveral experimental studies that were conducted based on \nPWM.34\u201337 Based on an experimental study, sharing the \nnegative social consequences of having unsafe sex with \nuniversity students has been effective in decreasing their \nwillingness to perform unsafe sex.34 One of the possible \nreasons could be how the information might change their \nattitude with regard to their willingness to have unsafe sex. \nTherefore, we postulated that the provision of relevant \ninformation on possible negative outcomes resulting from \nengagement in sexting behaviour might contribute to the \nchange in attitude and subsequently the willingness to sext \namong young adults. \n \nWith regard to the best approach to improve the perceived \nnorm of sexting, we included information on the pattern of \nsexting behaviour globally and locally, previous opinions on \nsexting prevalence, and others\u2019 opinions on sexting \nbehaviour in the intervention module. These were based on \nan experimental study that provided information on the \ntypical drinking behaviour, average drinking behaviour on \ncampus, and previous thoughts on the average drinking \nbehaviour on campus for undergraduate students in the \nUSA.35 The study outcome showed a successful reduction in \nthe perceived norm regarding drinking among the \nrespondents. Therefore, in our study intervention, we \nprovided the opinions of parents and other young adults on \nindividuals involved in sexting in order to reduce the \nperceived norm among the respondents. \n \nLastly, the review findings of the behavioural change \ntechniques used in PWM were applied to improve the \nprototype perception towards the sexters.38 Several studies \nprovided positive and negative identities for the actors or \nabstainers.34,39 For example, a study has described the \npersonality of people who practiced unsafe or safe sex in a \nbogus survey created for the intervention which in turn, the \ntechnique was found to successfully increase participants\u2019 \nwillingness to wear condoms.34 This technique was considered \nadequate to modify the prototype perception.36 Therefore, in \nour intervention, we provided information on the type of \npersonality associated with sexting behaviour and a brief \nexplanation of why this type of person would be more prone \nto engage in sexting. \n \nBased on the results from the pilot study, the online video was \nconsidered to be a form of acceptable, appropriate and \n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 650\n\n\n\n\n\n\n\n\nDevelopment of an online animated sexting prevention module based on the prototype \n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                651 \n\n\n\nfeasible intervention. Furthermore, these videos were \nuploaded to a private YouTube channel, making it \nconvenient for the participants to access during their free \ntime. Besides, the videos were considered to be more \nattractive for the participants because they were in the form \nof animation, easy to understand, with contents that might \nrelate to them and short (only took a few minutes of their \ntime to complete viewing). However, they provided some \ncomments on improving the graphics and animation of the \nvideo, apart from incorporating more examples based on \nreal-world sexting scenarios. In addition, they also suggested \nthat the videos be uploaded to other social media platforms \nonce the effectiveness of this intervention has been \nestablished. Last but not least, they also recommended that \nthe intervention module be expanded to school children. \n \nDespite the positive feedback from this pilot study on our \nmodule, we acknowledge that this module will be one of the \nstrategies to prevent sexting and cannot be a standalone \nstrategy. There are several other factors that could influence \nsexting that are beyond the scope of this module. For \nexample, family dynamics, interrelationships between family \nmembers and peers, and financial constraints. Therefore, \nother strategies could be implemented in parallel with the \nimplementation of this module in order to have a greater \nimpact on sexting prevention. Such strategies include \nparental involvement, peer-to-peer education, digital literacy \nprogrammes, sexting-related legislation awareness, reporting \nmechanisms for sexting victims, religious workshops, moral \nguidance and public campaigns on sexting that emphasise \nthe importance of responsible online behaviour. \n \n \nCONCLUSION  \nThis animated sexting intervention module aimed at \nreducing the intention and willingness to sext represented an \nimportant contribution to the body of literature on the use of \nprototype willingness model (PWM). The intervention was \ndeemed acceptable to the majority of diploma students that \nwere involved in this study. However, a randomised \ncontrolled field trial (RCT) can be undertaken to establish its \neffectiveness. \n \n \nACKNOWLEDGEMENT \nWe are grateful to the HIV/STI Unit of Melaka\u2019s Health \nDepartment for sharing valuable data on sexually \ntransmitted infections. We also would like to express our \ngratitude for the kind cooperation and commitment given by \nthe higher education institution and all the diploma students \ninvolved in this study. \n \n \nCONSENT FOR PUBLICATION \nThe authors would like to thank the Director-General of \nHealth Malaysia and Director-General of National \nPopulation and Family Development Board for their \npermission to publish this article. \n \n \nCONFLICT OF INTEREST \nThe authors declare that they have no competing interest. \n\n\n\nFUNDING \nWe received a grant (GPLPPKN0022) from the National \nPopulation and Family Development \nBoard Malaysia. \n \n \nREFERENCES \n1. Courtice EL, Shaughnessy K. Technology-mediated sexual \n\n\n\ninteraction and relationships: a systematic review of the \nliterature. Sex Relatsh Ther 2017; 32(3/4): 269-90. \n\n\n\n2. Klettke B, Hallford DJ, Mellor DJ. Sexting prevalence and \ncorrelates: A systematic literature review. Clin Psychol Rev 2014; \n34(1): 44-53. \n\n\n\n3. 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Prev Sci 2011; 12(1): 89-102. \n\n\n\n15-Development00118.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 652\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                589 \n\n\n\nABSTRACT \nIntroduction: Monitoring of impedance field telemetry is \ncrucial to maintaining optimal function of cochlear implants. \nThis study aims to investigate impedance changes in \ncochlear implant electrodes one year after switch on. \n \nMaterials and Methods: A retrospective repeated cross-\nsectional study was conducted by recruiting patients with \ncochlear implants presenting to the Dr. Cipto \nMangunkusumo National General Hospital, Jakarta, \nIndonesia between 2017 and 2021. Basal (b1, b2) and apical \n(a1, a2) electrodes, representing the outermost and \ninnermost parts of the cochlear implant electrodes, were \nmeasured at switch on and at 1 year post-implantation. \n \nResults: A total of 123 patients, with a total of 123 cochlear \nimplant samples, were included in the analysis. We found a \nsubstantial change in electrical impedance between switch \non and follow-up periods, where the impedance levels of \nbasal electrodes decreased (b1: mean difference (MD) \u22121.13 \n[95% confidence interval (CI): \u22121.71, \u22120.54], p<0.001; b2: MD \n\u22120.60 [95%CI: \u22121.17, \u22120.03], p=0.041) and those of apical \nelectrodes increased (a1: MD 0.48 [95%CI: \u22120.28, 0.99], \np=0.064; a2: MD 0.67 [95%CI: 0.12, 1.22], p=0.017). We also \nfound that the choice of surgical approaches for implant \ninsertion may affect the electrode impedance. \nCochleostomy approach resulted in a higher impedance \nthan round window in basal (b1) and apical (a2) electrodes \nboth at switch on and follow-up (b1 at switch on and at \nfollow-up: p=0.019 and p=0.004; a2 at follow-up: p=0.012). \nExtended round window approach also resulted in a higher \nimpedance than round window in basal (b1) and apical (a2) \nelectrodes at follow-up (p=0.013 and p=0.003, respectively). \n \nConclusion: Electrical impedance of cochlear implant \nelectrodes may change over time, highlighting the \nimportance of regular impedance assessments for cochlear \nimplant users to ensure optimal device function. The round \nwindow approach resulted in better initial and long-term \nimpedance levels compared to cochleostomy, and better \nlong-term impedance levels than extended round window. \nExtended round window approach also gives better \nimpedance level than cochleostomy. Further research \nshould investigate the potential interplay between surgical \napproach and other factors that may impact impedance \nlevels to confirm our findings. \n \n\n\n\nKEYWORDS:  \nCochlear implant, cross-sectional, electrical impedance, follow-up \nstudies, surgical approach \n \n \nINTRODUCTION \nCochlear implants are widely used for the habilitation and \nrehabilitation of patients with profound sensorineural \nhearing loss (SNHL). Such implants use a software connecting \nan external component, i.e., speech processor, to an internal \ncomponent consisting of an array of electrodes surgically \nimplanted into the cochlea. The electrodes play a crucial role \nin aural habilitation by stimulating the auditory nerve fibers \nin the cochlea, enabling the brain to receive auditory input \nand perceive sound, thereby improving hearing and speech \ndevelopment especially in children with congenital SNHL.  \n \nTo maintain an optimal function, it is essential to regularly \nexamine the electrode impedance in cochlear implants. \nElectrical impedance, a parameter measuring the resistance \nor opposition of electrodes to the flow of electrical current, is \nevaluated both intraoperatively and during mapping \nsessions to describe the integrity of the electrodes and the \nelectrical current between the electrodes and the surrounding \ncochlear tissues.1,2 Any changes in impedance levels may \nindicate issues with the electrodes and/or cochlear implants, \nsuch as short circuits, open circuits, or damaged devices.1,3 \n \nElectrical impedance of a cochlear implant may be affected \nby several factors including electrode placement, tissue \nchanges (e.g., inflammation or damage), electrode corrosion, \nand the duration of use. Long-term use of the device may \nlead to a reduction in its efficiency in delivering electrical \ncurrent to the surrounding cochlear tissues, resulting in an \nincrease in impedance and decreased implant effectiveness.2-4 \nTherefore, it is saliently important to perform follow-up \nexaminations post-implantation to investigate potential \nchanges in the electrical impedance of cochlear implants \nover time. This study aims to investigate changes in \nimpedance levels in patients with cochlear implants one year \nafter implantation at a tertiary referral hospital in Jakarta, \nIndonesia. \n \n \nMATERIALS AND METHODS \nA retrospective repeated cross-sectional study was conducted \nby including patients using cochlear implants presenting to \n\n\n\nImpedance changes in cochlear implant electrodes one year \nafter switch on: A cohort study at a tertiary referral hospital \nin Jakarta, Indonesia \n \nSemiramis Zizlavsky, MD PhD, Rangga Saleh, MD, Harim Priyono, MD PhD \n\n\n\n     \nDepartment of Otorhinolaryngology Head and Neck Surgery (ORL-HNS), Faculty of Medicine Universitas Indonesia/Dr. Cipto \nMangunkusumo Hospital, Jakarta, Indonesia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 04 July 2023                                                                                                                                                                              \nCorresponding Author: Semiramis Zizlavsky                                                                                                                                                                       \nEmail: semiramiszizlavsky@gmail.com\n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 589\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n590                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nthe Ear, Nose, and Throat (ENT) outpatient clinic of the \nDepartment of Otorhinolaryngology and Head and Neck \nSurgery, Dr. Cipto Mangunkusumo National General \nHospital, Jakarta, Indonesia between 2017 and 2021. All \npatients underwent complete electrode insertion using \nimplants manufactured by MED-EL (PULSAR, SONATA, OR \nSYNCHRONY models; Innsbruck, Austria), Cochlear\u00ae (Slim \nStraight\u00ae (CI622) or Contour Advance\u00ae (CI612) models; \nSydney, Australia), or Advanced BionicsTM implants \n(HiFocus\u2122 1J or HiFocus\u2122 Mid-Scala models; Bangalore, \nIndia), and patients with device failures were excluded from \nthis study. The parents or guardians of the children provided \nwritten informed consent for the children to participate in \nthis study. The study protocol has been approved by the \nResearch Ethics Committee, Faculty of Medicine Universitas \nIndonesia and Cipto Mangunkusumo National General \nHospital (ethical no. 22-02-0181). This study is reported \naccording to the Strengthening the Reporting of \nObservational Studies in Epidemiology (STROBE) guidelines.5 \n \nMeasurement of the impedance levels (k\u03a9) of the cochlear \nimplants was performed at switch on and at 1 year post-\nimplantation. The electrodes investigated in this study were \nbasal electrodes (b1, b2) and apical electrodes (a1, a2; Figure \n1). In addition, we also recorded data on cochlear implants \n(type of electrodes, hearing preservation technique, surgical \napproach for implant insertion) and comorbidities (inner ear \nmalformation and obliteration of scala tympani). The round \nwindow insertion was used as the hearing preservation \ngroup, whereas extended round window and cochleostomy \ninsertion were used as the non-hearing preservation group. \nThe cochlear implantation procedures in this study were \nperformed by two surgeons which can be consider as bias and \na limitation to this study. The collected data were then \ntabulated, described narratively and analysed using paired \nsample t tests to compare values from consecutive fitting \nsessions, and one-way analysis of variance (ANOVA) \nfollowed by Tukey\u2019s HSD post hoc tests to compare \nimpedance values between surgical approaches at each \nmapping session, whichever appropriate, to compare values \nfrom consecutive fitting sessions. Dichotomous data were \npresented in frequencies and proportions, while continuous \ndata in mean \u00b1 standard deviation (SD) or mean difference \n(MD) and 95% confidence intervals (95% CI). All statistical \nanalysis were performed using SPSS 24.0 (SPSS Inc., Chicago, \nIL), and a p value of \u22640.05 denotes statistical significance. \n \n \nRESULTS \nA total of 123 patients with ages ranging from 1 to 45 years \nold, cumulating a total of 123 samples of cochlear \nimplantation procedures, were included in the present study. \n50.4% (62/123) patients were female, and about 64.2% \n(79/123) received implantation on the right side. Most of the \nchildren underwent hearing preservation technique (106 \npatients, 86.2%) with lateral wall electrodes (114 patients, \n92.7%). 71.5% (88/123) of the children underwent round \nwindow insertion, followed by an extended round window \napproach (18 patients, 14.6%) and cochleostomy (17 \npatients, 13.8%). No children presented with inner ear \nmalformation (0/123 patients, 0.0%), and two patients \n(1.6%) had obliterated scala tympani (Table I). \n\n\n\nWe found a statistically significant changes in electrical \nimpedance between switch on and 1 year post-implantation \nperiods, where the impedance values of b1 and b2 electrodes \ndecreased at 1 year follow-up (b1: MD \u22121.13 [95%CI: \u22121.71, \n\u22120.54], p<0.001; b2: MD \u22120.60 [95%CI: \u22121.17, \u22120.03], \np=0.041), while those of a2 electrode slightly increased (MD \n0.67 [95%CI: \u22120.12, 1.22], p=0.017; Table II). We also \nobserved a slight increase in the impedance value of a1 \nelectrode, although not statistically significant (MD 0.48 \n[95%CI: 0.28, 0.99], p=0.064). \n \nWe also found that the choice of surgical approaches for \nimplant insertion contributed to the evolution of apical and \nbasal impedance at switch on and 1-year follow-up post-\nimplantation (Table III). In basal (b1) electrodes, \ncochleostomy approach resulted in a higher impedance both \nat switch on and follow-up compared to round window \napproach (p=0.019 and p=0.004, respectively), while the \nextended round window approach resulted in a significantly \nhigher impedance level than round window approach only \nat follow-up (p=0.013). Meanwhile, in apical (a2) electrodes, \nboth extended round window and cochleostomy approaches \nhad a substantially higher/lower impedance levels than the \nround window approach at follow-up (p=0.003 and p=0.012, \nrespectively), but not at switch on (p=0.428 and p>0.999, \nrespectively). \n \n \nDISCUSSION \nImpedance field telemetry is a widely used parameter to \nassess the integrity of a cochlear implant device during \nimplantation and mapping sessions. This enables clinicians \nto ensure the optimal function of cochlear implants in order \nto improve hearing and speech abilities of patients with \nsevere-to-profound SNHL. This study, assessing the \nimpedance levels of basal (b1 and b2) and apical (a1 and a2) \nelectrodes, which represent the outermost and innermost part \nof the cochlear implant electrodes, found that significant \nchanges in impedance levels occur over time, where the \nimpedance values were decreased in basal electrodes and \nincreased in apical electrodes at 1-year post-implantation. \n \nIt is known that impedance levels of a cochlear implant may \nchange over time due to various factors affecting the tissues \nsurrounding the device. Following implantation, fibrous \ntissues, protein exudates, and macrophages may surround \nthe electrodes, caused by inflammation or other tissue \nchanges, thereby potentially altering the electrical properties \nof the surrounding tissues and leading to changes in \nimpedance levels. Additionally, the metal components of the \nimplant may gradually corrode and thus induce further \nchanges in impedance levels of the electrodes.6 Previous \nstudies have shown that the impedance levels of a cochlear \nimplant electrode will increase substantially in the first week \nafter implantation and are expected to plateau within one to \ntwo months.7,8 In addition to wear and tear, other factors that \nmay also affect the impedance levels of a cochlear implant \ninclude tissue changes and electrode placement. As \npreviously stated, the environment surrounding the device \nmay contribute to the impedance levels of the electrodes. This \nindicates that any tissue changes (e.g., inflammation, \ninfection, fibrosis) and the location of the electrodes in the \n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 590\n\n\n\n\n\n\n\n\nImpedance changes in cochlear implant electrodes one year after switch on\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                591 \n\n\n\nSample characteristics                                                                                                      n (%) \nSex  \n\n\n\nMale                                                                                                                            61 (49.6) \nFemale                                                                                                                        62 (50.4) \n\n\n\nSide of implantation                                                                                                                \nRight                                                                                                                           79 (64.2) \nLeft                                                                                                                              44 (35.8) \n\n\n\nType of electrode                                                                                                                     \nLateral wall                                                                                                                114 (92.7) \nPerimodiolar                                                                                                                 9 (7.3) \n\n\n\nHearing preservation technique                                                                                              \nYes                                                                                                                              106 (86.2) \nNo                                                                                                                               17 (13.8) \n\n\n\nScala tympani approach                                                                                                           \nRound window                                                                                                           88 (71.5) \nExtended round window                                                                                          18 (14.6) \nCochleostomy                                                                                                             17 (13.8) \n\n\n\nInner ear malformation                                                                                                           \nYes                                                                                                                                 0 (0.0) \nNo                                                                                                                               123 (100) \n\n\n\nScala tympani obliteration                                                                                                       \nYes                                                                                                                                 2 (1.6) \nNo                                                                                                                              121 (98.4)\n\n\n\nTable I: Clinical characteristics of the study population (n = 123)\n\n\n\nElectrode                                           Switch on (k\u03a9)              Follow-up (k\u03a9)                                                Changes \n                                                                                                                                                 MD                      95% CI                 p value \nBasal electrodes              b1                  8.94 \u00b1 3.75                     7.81 \u00b1 3.05                       \u22121.13                \u22121.71, \u22120.54             <0.001 \n                                        b2                          \u00b1                                      \u00b1                               \u22120.60                \u22121.17, \u22120.03              0.041 \nApical electrodes            a1                          \u00b1                                      \u00b1                                0.48                    0.28, 0.99                 0.064 \n                                        a2                  6.41 \u00b1 2.80                     7.09 \u00b1 2.35                        0.67                    0.12, 1.22                 0.017 \n \nUnless otherwise stated, data are expressed as mean \u00b1 standard deviations. p value derived from paired t tests. CI, confidence interval; MD, mean difference. \n \n \n\n\n\nTable II: Impedance levels (k\u03a9) of the measured electrodes at switch on and at 1 year follow-up\n\n\n\nElectrodes                                                  Switch on                                                                                  Follow-up \n                           Approach to           RW                 ERW                   C              Approach to            RW                  ERW                     C \n                          scala tympani                                                                            scala tympani               \nb1 electrode              RW                                          1.74                 2.68                    RW                                             2.17                   2.49 \n                                                                               (p=0.203)         (p=0.019)                                                               (p=0.013)          (p=0.004) \n                                  ERW                 \u22121.74                                       \u22120.94                  ERW                  \u22122.17                                           0.32 \n                                                       (p=0.203)                                 (p>0.999)                                     (p=0.013)                                    (p>0.999) \n                                    C                    \u22122.68               0.94                                              C                    \u22122.49               \u22120.32 \n                                                       (p=0.019)        (p>0.999)                                                             (p=0.004)          (p>0.999)                   \na2 electrode              RW                                          2.17                 2.49                    RW                                            \u22121.95                 \u22121.73 \n                                                                               (p=0.428)         (p>0.999)                                                              (p=0.003)           (p=0.012) \n                                  ERW                 \u22122.17                                        0.32                   ERW                   1.95                                            0.22 \n                                                       (p=0.428)                                 (p=0.253)                                     (p=0.003)                                    (p>0.999) \n                                    C                    \u22122.49              \u22120.32                                             C                      1.73                 \u22120.22  \n                                                       (p>0.999)        (p=0.253)                                                             (p=0.012)          (p>0.999)                   \n \nData expressed as mean difference (p values). p values derived from Tukey\u2019s HSD post hoc ANOVA test. RW, round window; ERW, extended round window; \nC, cochleostomy \n\n\n\nTable III: Comparison of impedance levels of the b1 and a2 cochlear implant electrodes between surgical approaches  \nfor implant insertion\n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 591\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n592                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\ncochlea may affect the electrical current flow and \nsubsequently affect the impedance levels of the electrodes.2,4  \nWith regards to electrode placement, our findings suggest \nthat the surgical approach to implant insertion had an effect \non impedance levels of the electrodes. In this study, we \nrecorded three surgical approaches: round window, extended \nround window, and cochleostomy. In brief, the round window \napproach is a standard method of surgery, performed by \ncreating a small opening in the bone of the round window \nniche, while cochleostomy is a conventional method that \ninvolves drilling a hole in the cochlear bone to insert the \nelectrode array.9 On the other hand, the extended round \nwindow approach is a combination of both round window \nand cochleostomy approaches and is usually performed in \nsituations where the round window is not easily visible \nand/or accessible.10 To date, limited research has been \nconducted to compare the effect of different surgical \napproaches on the impedance levels of cochlear implant \nelectrodes. A previous systematic review by Avasarala et al.11 \n\n\n\nfound that two out of three studies reported that there were \nno substantial differences on impedance levels between \nsurgical approaches, while one study found that round \nwindow approach yielded a lower initial impedance value.11 \n\n\n\nThe study found that significant differences in switch on \nimpedance were observed in the basal-middle electrodes and \nnot in the apical region12, which is consistent with our \nfindings. This may be explained by the fact that traditional \ncochleostomy, which involves drilling a bigger hole in the \ncochlear bone, may induce more extensive tissue damage, \nresulting in higher impedance.13,14 Previous studies foind that \nimpedance level has a correlation to the clinical outcome of \ncochlear implantation. Impedance level might indirectly \nshow the biological changes in the cochlea due to electrode \ninsertion. Changes such as bone formation or the distance \nbetween the electrode and the modiolus will affect the \nimpedance level at mapping. Decreased word score is \ncorrelated with an increased impedance level.15 Nonetheless, \nit should be noted that the outcome of cochlear implantation \n\n\n\nsurgeries is also affected by several factors such as clinical \ncharacteristics of the patients (e.g., age at implantation, \ncomorbidities, duration of implantation, and severity of \nhearing loss) and surgeon's experience and available \nresources. This suggests that further studies are needed to \nconfirm our findings. \n \nThe present study is limited due to its cross-sectional design, \nsuggesting that causalities between variables were unknown. \nFurthermore, other potential confounding factors, such as \nage at intervention and characteristics of patients\u2019 hearing \nloss were not recorded in this study. The fact that there was \nno patient with inner ear anomalies and only two patients \nwith obliterated scala tympani also limited our analysis. \nThese suggest that future studies should also consider these \npotential confounding factors when assessing the impedance \nlevels of cochlear implants over time. \n \n \nCONCLUSION \nThis study adds to the body of evidence supporting the \npremise that the electrical impedance of cochlear implant \nelectrodes may change over time, thereby highlighting the \nimportance of regular impedance assessments for cochlear \nimplant users to ensure the optimal function of the devices. \nIn this cohort, the impedance level of basal electrodes \ndecreased at one year post-implantation, while those of \napical electrodes increased. The present study also suggests \nthat the choice of surgical approach for implant insertion \nmay play a role in the impedance levels of the electrode \narrays. Further research should investigate the potential \ninterplay between surgical approach and other factors that \nmay impact impedance levels to confirm our findings. \n \n \nACKNOWLEDGEMENT \nNot applicable. \n \n\n\n\nFig. 1: Location of the basal (b1, b2) and apical (a1, a2) cochlear implant electrodes in the scala tympani.\n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 592\n\n\n\n\n\n\n\n\nImpedance changes in cochlear implant electrodes one year after switch on\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                593 \n\n\n\nREFERENCES \n1. Leone CA, Mosca F, Grassia R. Variazioni nel tempo \n\n\n\ndell\u2019impedenza degli elettrodi nelle diverse partizioni cocleari in \nadulti con impianto cocleare. Acta Otorhinolaryngologica Italica \n2017; 37(4): 312-9.  \n\n\n\n2. 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Platinum corrosion products from electrode contacts of \nhuman cochlear implants induce cell death in cell culture \nmodels. PLoS One 2018; 13(5): 1-20.  \n\n\n\n7. Hu HC, Chen JKC, Tsai CM, Chen HY, Tung TH, Li LPH. Evolution \nof impedance field telemetry after one day of activation in \ncochlear implant recipients. PLoS One 2017; 12(3): e0173367.  \n\n\n\n8. Wei JJF, Tung TH, Li LPH. Evolution of impedance values in \ncochlear implant patients after early switch-on. PLoS One 2021; \n16(2): e0246545 \n\n\n\n9. Jiam NT, Jiradejvong P, Pearl MS, Limb CJ. The effect of round \nwindow vs cochleostomy surgical approaches on cochlear \nimplant electrode position: a flat-panel computed tomography \nstudy. JAMA Otolaryngol Head Neck Surg 2016; 142(9): 873\u201380.  \n\n\n\n10. Friedland DR, Runge-Samuelson C. Soft cochlear implantation: \nrationale for the surgical approach. Trends Amplif 2009; 13(2): \n124.  \n\n\n\n11. Avasarala VS, Jinka SK, Jeyakumar A. Complications of \ncochleostomy versus round window surgical approaches: a \nsystematic review and meta-analysis. Cureus. 2022; 14(5): \ne25451. \n\n\n\n12. Liu X, Xie L, Wang Y, Yang B. Lower initial electrode impedances \nin minimally invasive cochlear implantation. Acta Otolaryngol \n2019; 139(5): 389-95.  \n\n\n\n13. Jia H, Venail F, Piron JP, Batrel C, Pelliccia P, Artier\u0300es F, et al. \nEffect of surgical technique on electrode impedance after \ncochlear implantation. Ann Otol Rhinol Laryngol 2011; 120(8): \n529-34.  \n\n\n\n14. Burghard A, Lenarz T, Kral A, Paasche G. Insertion site and \nsealing technique affect residual hearing and tissue formation \nafter cochlear implantation. Hear Res 2014; 312: 21-7.  \n\n\n\n15. Caswell-Midwinter B, Doney EM, Arjmandi MK, Jahn KN, \nHerrmann BS, Arenberg JG. The relationship between \nimpedance, programming and word recognition in a large \nclinical dataset of cochlear implant recipients. Trends Hear 2022; \n26: 23312165211060983.\n\n\n\n6-Impedance00108.qxp_3-PRIMARY.qxd  25/09/2023  4:24 PM  Page 593\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                609 \n\n\n\nABSTRACT \nIntroduction: Interleukin (IL)-40 is a recently identified \ncytokine with a novel role in the pathogenesis of \ninflammatory diseases. Since systemic lupus \nerythematosus (SLE) is an autoimmune disease \ncharacterised by a pro-inflammatory response, it is likely \nthat IL-40 contributes to the underlying disease processes \nof this disorder. The aim of the current study was to evaluate \nthe potential of IL-40 to act as a diagnostic biomarker for \nSLE.  \n \nMatrrials and methods: The study included 99 patients with \nSLE who attended the Rheumatology Unit at Baghdad \nTeaching Hospital. These subjects were divided into three \nsubgroups according to disease status: inactive, n = 33; \nactive moderate, n = 33; and active severe, n = 33. \nAdditionally, 33 matched controls were studied. Full medical \nhistories, body mass index, gender and clinical disease \nactivity, the latter evaluated with the SLE disease activity \nindex, were collected. Laboratory parameters measured \nincluded anti-dsDNA antibodies, C3 and C4 levels, \nerythrocyte sedimentation rate and C-reactive protein titres. \nSerum IL-40 levels were quantified using an enzyme-linked \nimmunosorbent assay. \n \nResults: IL-40 levels were significantly higher in patients \n(12.5420 \u00b1 3.00575 ng/L) than in controls (6.1138 \u00b1 0.59452 \nng/L; p < 0.01). Mean serum IL-40 concentration was highest \nin the active severe group (15.2291 \u00b1 2.26540 ng/L) and \ndecreased, in order of disease severity, in the remaining \ncohorts: active moderate, 13.0643 \u00b1 1.23927 ng/L; inactive, \n9.3325 \u00b1 1.62807 ng/L (P < 0.01); controls, 6.1138 \u00b1 0.59452 \nng/L. Serum IL-40 levels showed excellent validity for the \ndiagnosis of SLE with a cut-off value of \u2265 9.3 ng/ml and area \nunder the curve of 0.987. Sensitivity, specificity and \naccuracy were 99%, 90.9% and 96.97%, respectively (P < \n0.001). \n \nConclusions: Serum IL-40 levels were elevated in SLE \npatients. It is therefore proposed that IL-40 is a novel \ncytokine which is associated with SLE and positively linked \nwith disease severity. \n \nKEYWORDS:  \nSystemic lupus erythematosus; SLE; IL-40; autoimmune condition; \ninflammation  \n \n \n \n\n\n\nINTRODUCTION \nSystemic lupus erythematosus (SLE) is a condition that \ndevelops owing to the abnormal immune-mediated \ndestruction of healthy tissues1,2 caused by B and T-cell \nhyperactivity and coincides with reactivity to self-antigens.3 \nIncreased production of antibodies, defective antibody \nclearance and complement and cytokine stimulation are \nsome of the typical characteristics that result in the symptoms \nof SLE. There is up to a 3-fold increase in mortality in patients \nliving with SLE compared to the general population. \nImproved treatment options may reduce mortality rates; \nhowever, superior diagnostic methods which allow for earlier \nor more sensitive detection of the disease are also essential.  \n \nThe earliest signs of SLE reflect constitutional symptoms, \nwhich may be accompanied by mild to moderate joint pain, \nsuggestive of arthritis. However, the presence of an \naccompanying skin rash or skin lesions at various \nanatomical sites supports a diagnosis of SLE.1  \n \nSince SLE is a heterogenous condition, to date, establishing a \ndiagnosis has proved difficult as the presentation often \nreflects the symptoms of alternative conditions, e.g., cancers \nor infectious diseases, such as human immunodeficiency \nvirus and acquired immunodeficiency syndrome.3 Viral \nserological tests and tissue histopathological testing may be \nperformed to exclude other causes. The American College of \nRheumatology (ACR) and the European League Against \nRheumatism (EULAR) have proposed criteria for the \ndiagnosis of SLE. However, as patients with mild diseases are \ncommonly unrecognised by this classification, more rigorous \ntesting is essential.3  \n \nCurrent diagnostic methods for the diagnosis of SLE rely on \nclinical symptom manifestations and are complemented by \nlaboratory tests, such as viral or tissue investigations. The \nlatter includes the anti-nuclear antibody (ANA) test; a \npositive ANA result is supported by an antigen-specific ANA \nfor extractable nuclear antigens, which has a specificity of \napproximately 66% for these complexes. It is recommended \nthat consultants collaborate with a SLE rheumatologist in \norder to attain a more reliable diagnosis. Only a few \nbiomarkers have been recognised as being of value in the \ndiagnosis of SLE, but as none of these can be utilised with \nconfidence in disease management, novel biomarkers are \nurgently required in the field. Elucidation of more precise \nbiomarkers for SLE could greatly improve detection sensitivity \nand reduce the time taken to diagnose patients. However, \nthere has been little success to date. \n\n\n\nSerum interleukin-40: an innovative diagnostic biomarker \nfor patients with systemic lupus erythematosus \n \nAmal Mahdi Al Rubaye, MSc1, Inas K. Sharquie, PhD1, Faiq I. Gorial, FIBMS2 \n\n\n\n     \n1Department of Microbiology and Immunology, College of Medicine, University of Baghdad, Baghdad, Iraq, 2Department of \nMedicine, College of Medicine, University of Baghdad, Baghdad, Iraq  \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 21 July 2023                                                                                                                                                                              \nCorresponding Author: Inas K. Sharquie                                                                                                                                                                             \nEmail:  iksharquie@yahoo.com,  inasksharquie@comed.uobaghdad.edu.iq\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 609\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n610                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nPrevious attempts to elucidate cytokine profiling in SLE have \nincluded the analysis of tumour necrosis factor-\u03b1 (TNF-\u03b1), a \npro-inflammatory cytokine which evidences increased \nexpression in a variety of autoimmune diseases.4 In one \nstudy, no differences between serum TNF-\u03b1 levels in healthy \nand SLE groups were determined, although another study \nsuggested that TNF-\u03b1 was a useful biomarker for SLE. Thus, at \npresent, the role of TNF-\u03b1 in the diagnosis of SLE is unclear.5 \n \nA potentially superior approach is to quantify the levels of \ncytokines secreted by B cells, since SLE is predominantly \nmediated by aberrant B-cell activity, with autoimmune \ndiseases, such as SLE, characterised by the presence of \nautoantibodies. At least one study has demonstrated \naberrant B-cell-associated cytokine profiles in which IL-4 was \nvirtually undetectable in the serum of SLE patients and \ncoincided with a rise in IL-6.6 The recent discovery of the B-\ncell-associated cytokine, IL-40, may also be utilised to \nimprove the diagnosis of SLE, as exemplified in other \ninflammatory conditions.  \n \nIL-40 is a B-cell-associated orphan cytokine encoded by the \ngene, C17orf99, which is secreted via activated B-cells. This \ngene regulates IgG production in order to maintain the \nphysiological function of B-cells.7 Studies have demonstrated \nthat IL-40 accumulates in the synovial joints of patients with \nrheumatoid arthritis (RA); serum IL-40 concentrations in \npatients with RA are substantially increased compared to \nthose detected in healthy controls.8 In RA, IL-40 propagates \npro-inflammatory cytokine release and autoantibody \nproduction; extracellular IL-40 enhances the synthesis of \ntissue-degrading enzymes.9 In one study, the depletion of B-\ncells reduced IL-40 production by 70%, suggesting that B-cell \ntargeted therapies may offer relief from autoimmune \nconditions mediated by IL-40. However, other immune cells \nmay synthesise residual IL-40. IL-40 has also been suggested \nto be a useful biomarker for the detection of type II diabetes \nmellitus and Sj\u00f6gren's syndrome, underscoring its role in the \npathogenesis of inflammatory and autoimmune diseases.10-12  \n \nSince SLE is an autoimmune condition characterised by a \npro-inflammatory response, the detection of IL-40 may be a \nuseful strategy for the identification of individuals with SLE as \naberrant B-cell activity is a hallmark of the disease. However, \nconflicting evidence suggests that IL-40 only regulates local \ninflammation and does not underlie the systemic \ninflammatory response observed in patients with SLE in \nwhom IL-40 levels were comparable to those measured in \ncontrols.10 Before the utility of IL-40 in the diagnosis of SLE \ncan be realised, further studies are required in order to \ninvestigate whether IL-40 plays a role in SLE or whether it is \nsimply a local inflammatory mediator.  \n \nThe principal objective of this present study was to \nthoroughly evaluate and ascertain the potential efficacy of \nIL-40 as a reliable diagnostic biomarker for SLE. \n \n \nMATERIALS AND METHODS \nThis study included 99 patients, aged over 18 years, who were \ndiagnosed with SLE according to the 2019 EULAR/ACR \nclassification criteria.13 They were divided into three \nsubgroups: inactive, n=33; active moderate, n=33; and active \n\n\n\nsevere, n=33. Thirty-three age- and sex-matched healthy \ncontrols were also included. Participants were recruited \nbetween November 2022 and January 2023 from the \nRheumatology Unit at the Baghdad Teaching Hospital. \nExclusion criteria were: concurrent overlapping \ninflammatory arthritis, connective tissue disease or \nseronegative spondyloarthritis; malignancy; pregnancy; \nevidence of infection and patient refusal. Under the direction \nof the rheumatologist, the full patient information page data \nand consent form were completed, and the Committee of \nScientific Ethics from the College of Medicine, University of \nBaghdad approved the study. The ethics committee\u2019s \napproval number was 023.  For each patient, gathered \nbaseline data encompassed blood investigations, full medical \nhistories, body mass index (BMI), gender and clinical disease \nactivity as evaluated with the SLE disease activity index. \nDisease-related laboratory parameters included anti-dsDNA \nantibodies, C3 and C4 levels, erythrocyte sedimentation rate \n(ESR) and C-reactive protein (CRP).  \n \nThe SLE disease activity scoring system consists of 24 \nvariables which cover 9 organ systems and yield a total score \nof 105. A total score \u2264 3 suggests that no flare is present, a \ntotal score > 3 and \u2264 12 is considered to reflect a mild to \nmoderate flare, and a total score > 12 represents a severe \nflare.14 Serum was obtained by centrifuging blood specimens \nfor 10 to 15 minutes at 1000\u20133000 rpm. Serum samples were \nthen frozen at \u221220\u00b0C. The enzyme-linked immunosorbent \nassay technique (Sun Long Biotech Company, China) was \nused to measure serum IL-40 in keeping with the \nmanufacturer\u2019s instructions. A plate reader was used to \ndetermine the absorbance at 450 nm. The immunological \ntesting was done at the International Centre for Research and \nDevelopment. \n \nStatistical Analysis \nStatistical analysis was performed using the Statistical \nPackage for the Social Sciences, version 21 (IBM). Student\u2019s t \ntests, analysis of variance (ANOVA) and the less significant \ndifference (LSD) test were performed for comparisons of \nquantitative variables, i.e. age, BMI and serum IL\u201340 levels, \nbetween studied groups. Normally distributed data are \nexpressed as mean \u00b1 standard deviation. Pearson\u2019s chi-\nsquare test (\u03c72) was used for comparisons of qualitative \nvariables between studied groups, i.e. age groups and BMI. A \nbinomial Z-test was performed for a comparison of gender \nand treatment intake. Pearson\u2019s correlation test was applied \nin order to detect the relationships between serum IL\u201340 \nlevels and age, BMI, duration of SLE disease, ESR and C3 and \nC4 concentrations. The validity of the ELISA test was \nestimated with a ROC curve, cut-off value, area under curve \n(AUC), sensitivity, specificity, positive predictive value (PPV), \nnegative predictive value (NPV) and accuracy. The statistical \nsignificance threshold was deemed to be a P-value < 0.05.  \n \n \nRESULTS \nThe age ranges of the 99 SLE patients and 33 control subjects \nwere 18 to 58 years and 19 to 55 years, respectively. Table I \nillustrate the similarities between the two cohorts with respect \nto the demographic parameters of gender, age group and \nBMI. \n \n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 610\n\n\n\n\n\n\n\n\nSerum interleukin 40: an innovative diagnostic biomarker for patients with systemic lupus erythematosus\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                611 \n\n\n\nFemales were predominant within both studied groups, \ncomprising 93 (93.94%) SLE patients and 30 (90.4%) controls \n(p=0.037).  \n \nThe frequency of subjects was highest within the age range, \n31\u201340 years, in both controls (13, 39.4%) and SLE patients \n(40, 40.4%), followed by the age range 18\u201330 years, i.e. \ncontrols (12, 36.4%) and SLE patients (36, 36.4%) (p=0.991). \nThe mean ages of the two studied groups were similar, i.e. \ncontrols, 35.35 \u00b1 11.783 years, and SLE patients, 34.69 \u00b1 \n9.074 years (p=0.789). \n \nThe frequency of subjects assigned to the BMI classifications \nin the two cohorts was as follows: overweight: controls, 19 \n(57.6%), SLE patients, 40 (40.4%); obese: controls, 8 (24.2%), \nSLE patients, 34 (34.3%); normal weight: controls, 6 (18.2%), \nSLE patients, 25 (25.3%) (p=0.359).  \n \nMean BMI showed a trend towards being greater in the SLE \npatient cohort when compared to the control group, i.e. \n28.1342 \u00b1 5.5956 kg/m2 and 25.8926 \u00b1 3.87481 kg/m2, \nrespectively, but this failed to reach statistical significance \n(p=0.161). \n \nWhen the variables were compared with respect to disease \nactivity using ANOVA, no differences were identified (Table \nII). The mean BMI values of the SLE patients within all three \ngroups of disease activity were similar: active severe, 28.7406 \n\u00b1 6.27527 kg/m2; active moderate, 28.3613 \u00b1 6.04078 kg/m2; \ninactive 27.8319 \u00b1 4.66821 kg/m2 (p=0.101). \n \nLSD test values were also similar between the various levels of \ndisease activity: inactive vs. active moderate, p=0.691; \ninactive vs. active severe, p=0.494; active moderate vs. active \nsevere, p=0.775. \n \nMean disease durations were similar between the different \ndisease activity groups: active moderate, 6.836 \u00b1 5.3956 \nyears; active severe, 5.994 \u00b1 4.2940 years; inactive, 4.306 \u00b1 \n4.7466 years (p=0.185). A within-group comparison of the \nLSD test data demonstrated no differences: inactive vs. active \nmoderate, p=0.072; inactive vs. active severe, p=0.228; active \nmoderate vs. active severe, p=0.546. \n \nMean serum ESR values were higher, the greater the disease \nactivity: active severe disease, 47.18 \u00b1 30.304; active \nmoderate, 40.79 \u00b1 26.415; inactive disease, 21.70 \u00b1 11.509 \n(p<0.001). Similar results were obtained for the LSD test, with \nthe exception of active moderate vs. active severe disease \nstates (p=0.221).  \n \nMean anti-dsDNA levels were modestly elevated in SLE \npatients with active severe disease (92.812 \u00b1 143.821) when \ncompared with those with active moderate disease (30.297 \u00b1 \n24.2616); anti-dsDNA titres were decreased in patients with \ninactive disease (19.233 \u00b1 3.7611, p=0.00). \n \nWithin-group comparisons were shown to be identical by the \nLSD test, with the exception of inactive vs. active moderate \n(p=0.539).  \n \n \n\n\n\nMean C3 levels were lower in SLE patients within the active \nsevere cohort (0.5858 \u00b1 0.37691) compared to those with \nactive moderate disease (0.6973 \u00b1 0.39807) and increased in \nthe inactive group (1.0548 \u00b1 0.49356, p<0.001).  \n \nSignificant differences (P < 0.01) were noted following the LSD \ntest, with the exception of active moderate vs. active severe \n(p=0.253).  \n \nMean C4 levels were diminished in SLE patients with active \nsevere (0.0543 \u00b1 0.05139) compared to those with active \nmoderate (0.2642 \u00b1 0.21645) and inactive disease (0.2812 \u00b1 \n0.08521); these differences were significant (p<0.01) for all \ncomparisons apart from inactive vs. active moderate \n(p=0.528).  \n \nTable III presents the distribution of the CRP data and \ntreatment intake according to the severity of SLE disease. This \nwas non-significant (p=0.164) for DMARDs intake: inactive: \nyes, 31 (93.9%), no, 2 (6.1%); active moderate: yes, 26 \n(78.8%), no, 7 (21.2%); active severe: yes, 25 (75.8%), no, 8 \n(24.2%).   \n \nThe data showed a significant difference (p=0.033) for CRP: \ninactive: positive, 1 (3.03%) negative, 32 (96.97%); active \nmoderate: positive, 2 (6.06%), negative, 31 (93.94%); active \nsevere: positive, 6 (18.18%), negative, 27 (81.82%).  \n \nSignificant differences (p<0.01) were observed for other types \nof treatment intakes: (i) steroid intake: inactive: yes, 12 \n(36.4%), no, 21 (63.6%); active moderate: yes, 25 (75.8%), no, \n8 (24.2%); active severe: yes, 28 (84.85%), no, 5 (15.15%) (P < \n0.001); and (ii) biologics intake: active moderate: yes, 1 (3%), \nno, 32 (97%); active severe, yes, 12 (36.4%), no, 21 (63.6%) \n(p=0.008). \n \nResult indicates that the mean serum IL-40 ng/ml titre in SLE \npatients (n=99) was higher than in controls (n=33), i.e. \n12.5420 \u00b1 3.00575 ng/L vs. 6.1138 \u00b1 0.59452 ng/L (p<0.01). \n \nIt can be clearly observed from the ANOVA and LSD tests \npresented in Table IV that the mean IL-40 levels in the sera of \nSLE patients in the active severe cohort are higher (15.2291 \u00b1 \n2.26540 ng/L) than in those patients in the active moderate \ngroup (13.0643 \u00b1 1.23927 ng/L). The latter values are \nelevated compared to the inactive (9.3325 \u00b1 1.62807 ng/L) \nand control groups (6.1138 \u00b1 0.59452 ng/L) (p<0.01 in all \ncases). \n \nResults also show the mean distributions of IL-40 levels in the \nsera of SLE patients according to the type of treatment intake. \nFor DMARDs intake, mean IL-40 values were lower in those \npatients taking this medication: Yes, 12.2198 \u00b1 2.96423 ng/L; \nNo, 14.0959 \u00b1 2.78502 ng/L (p=0.018). Mean IL-40 levels were \nsimilar amongst patients who were or were not on steroid \ntherapy: Yes, 12.2301 \u00b1 2.72639 ng/L; No, 13.1383 \u00b1 3.44324 \nng/L (p=0.154), and between patients who were or were not \nreceiving biologics: Yes, 14.2086 \u00b1 2.74526 ng/L; No, 14.1315 \n\u00b1 1.96211 ng/L (p=0.907). \n \nA correlation study between IL-40 levels and the other SLE \npatient parameters revealed that there were inverse \n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 611\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n612                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nParameters                                                                                                 Studied groups                                                  p value \n                                                                                                Controls                                   Patients \n                                                                                                  (n=33)                                       (n=99) \n\n\n\nGender                                        Male                                           3 (9.1%)                                   6 (6.06%)                                 0.337 \n                                             Female                                     30 (90.9%)                               93 (93.94%)                                 NS  \n\n\n\nAge-groups                                 18\u201330                                        12 (36.4%)                                36 (36.4%)                               0.991 \n(years)                                         31\u201340                                        13 (39.4%)                                40 (40.4%)                                  NS  \n\n\n\n                                             41\u201350                                         7 (21.2%)                                 21 (21.2%)                                     \n                                             51\u201360                                           1 (3%)                                       2 (2%)                                        \n\n\n\nBMI groups                                 Normal weight                         6 (18.2%)                                 25 (25.3%)                               0.359 \n                                             Overweight                              19 (57.6%)                                40 (40.4%)                                     \n                                             Obese                                        8 (24.2%)                                 34 (34.3%)                                     \n\n\n\nAge (years)                                  Mean                                            35.35                                         34.69                                    0.786 \n                                                                                                                                                                                                    NS \n                                             Std. deviation                              11.783                                        9.074                                         \n                                             Std. error                                      1.915                                         1.074                                         \n\n\n\nBMI (kg/m2)                                 Mean                                          25.8926                                     28.1342                                  0.161 \n                                                                                                                                                                                                    NS \n                                             Std. deviation                             3.87481                                      5.5956                                        \n                                             Std. error                                    0.63942                                      0.5483                                        \n\n\n\n \nNS: non-significant (p>0.05), BMI: body mass index. \n\n\n\nTable I: Demographics and other parameters: distributions within the two studied groups, i.e., SLE patients and controls.\n\n\n\nSLE patient groups                                             Mean                             Std.                          Std.                    LSD test (p value) \n                                                                                                                Deviation                     Error                                     \nBMI                   Inactive                                      27.8319                        4.66821                    0.81263                   A                       0.691 \n                         Active moderate                        28.3613                        6.04078                    1.05156                   B                        0.494 \n                         Active severe                             28.7406                        6.27527                    1.09238                   C                       0.775 \n                                                  ANOVA test  (p value):            p=0.101 \nDuration          Inactive                                        4.306                           4.7466                      0.8263                    A                        0.072 \n(years)              Active moderate                          6.836                           7.3956                      1.2874                    B                        0.228 \n                         Active severe                               5.994                           4.2940                      0.7475                    C                        0.546 \n                                                  ANOVA test (p value):             p=0.185 \nESR                   Inactive                                        21.70                           11.509                       2.004                     A                         0.00 \n                         Active moderate                          40.79                           26.415                       4.598                     B                         0.00 \n                         Active severe                               47.18                           30.304                       5.275                     C                       0.221 \n                                                 ANOVA test (p value):               p<0.001 \nAnti-dsDNA     Inactive                                       19.233                          3.7611                      0.6547                    A                        0.539 \n                         Active moderate                         30.297                         24.2616                     4.2234                    B                         0.00 \n                         Active severe                              92.812                         143.821                    25.0362                   C                        0.001 \n                                                 ANOVA test (p value):               p<0.001 \nC3                     Inactive                                       1.0548                         0.49356                    0.08592                   A                         0.00 \n                         Active moderate                         0.6973                         0.39807                    0.06929                   B                        0.00 \n                         Active severe                              0.5858                         0.37691                    0.06561                   C                        0.253 \n                                                 ANOVA test (p value):                p<0.001 \nC4                     Inactive                                       0.2812                         0.08521                    0.01483                   A                        0.582 \n                         Active moderate                         0.2642                         0.21645                    0.03768                   B                         0.00 \n                         Active severe                              0.0543                         0.05139                    0.00895                   C                         0.00 \n                                                    ANOVA test (p value):         p<0.001 \n \nBMI: body mass index, ESR: erythrocyte sedimentation rate, Anti-ds DNA: Anti-double  \nstranded DNA, C3 and C4: Complement components 3 and 4, LSD: Least Significant \nDifference, A = inactive vs. active moderate, B = inactive vs. active severe,  \nC = active moderate vs. active severe. \n \n \n\n\n\nTable II: Mean distributions of parameters within SLE patient groups\n\n\n\nParameters                                                                                           SLE patient groups                                                          p value \n                                                                          Inactive                   Active moderate                   Active severe \n                                                                           (n=33)                             (n=33)                                  (n=33) \n\n\n\nCRP                                Positive                            1 (3.03%)                       2 (6.06%)                           6 (18.18%)                      **0.033 \n                                Negative                       32 (96.97%)                   31 (93.94%)                        27 (81.82%)                            \n\n\n\nDMARDs intake            Yes                                  31 (93.9%)                     26 (78.8%)                          25 (75.8%)                        0.164 \n                                                                                                                                                                                                       NS \n                                No                                     2 (6.1%)                        7 (21.2%)                            8 (24.2%)                              \n\n\n\nSteroid intake               Yes                                  12 (36.4%)                     25 (75.8%)                         28 (84.85%)                     **<0.01 \n                                No                                   21 (63.6%)                      8 (24.2%)                           5 (15.15%)                             \n\n\n\nBiologics intake            Yes                                                                             1 (3%)                              12 (36.4%)                      **0.008 \n                                No                                                                            32 (97%)                            21 (63.6%)                             \n\n\n\n          \n**p<0.01. NS: non-significant (p>0.05), CRP: C-Reactive Protein, DMARDs: \nDisease- Modifying Anti-Rheumatic Drugs \n\n\n\nTable III: C-reactive protein values and treatment intake distributions within SLE patient groups\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 612\n\n\n\n\n\n\n\n\nSerum interleukin 40: an innovative diagnostic biomarker for patients with systemic lupus erythematosus\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                613 \n\n\n\nrelationships between serum IL-40 titres and C3 (r = \u22120.420, \np<0.01) and C4 levels (r=\u22120.396, p<0.01), and a positive \nrelationship between serum IL-40 levels and ESR values \n(r=0.344, p<0.01). \n \nThe remaining variables demonstrated a weakly positive \ncorrelation which was insignificant (Table V).  \n \nValidity of Tests \nThe results given prove that serum IL-40 levels have excellent \nvalidity for use in the diagnosis or follow-up of SLE patients \nat a cut-off value of 9.3 ng/ml. The performance parameters \nwere: AUC, 0.987; sensitivity, 99%; specificity, 90.9%; PPV, \n97%; NPV, 96.8%; accuracy, 96.97% (p<0.001). \n \n \nDISCUSSION \nIt is well-established that SLE arises from a complicated, \nmultifactorial interaction between various genetic factors. \nMultiple genes contribute towards patient disease \nsusceptibility, which is further refined and controlled by \nenvironmental triggers.15-18 Research has been ongoing for \nseveral decades in order to identify relevant biomarkers for \nSLE,19-22 and although some have shown promising results, no \nsingle biomarker has been able to detect SLE completely and \nreliably in every case. This issue arises as a result of the \nheterogeneous characteristics of SLE, the differing symptom \npresentations observed in practice,23 and the complex \npatterns of hereditability and genetic variation associated \nwith the disease.24   \n\n\n\n \nNonetheless, previous research has indicated that IL-40 plays \na central role in biological disease processes,7-8,10,25 and the \n\n\n\ncytokine has recently been proposed as a contributing factor \nto the development of SLE-associated nephritis.26 In this study, \nmultiple blood markers were evaluated, including IL-40 titres, \nin order to investigate whether or not they played a role in \nthe development and expression of SLE in the selected study \npopulation.  \n \nIt was established that serum IL-40 concentrations differed \nsignificantly between patients with SLE and the controls. A \npositive association between IL-40 levels and lupus severity \nwas identified, in that serum IL-40 titres increased in parallel \nwith the severity and duration of lupus symptoms. Previous \nstudies which have analysed serum IL-40 levels have shown \na similar trend in relation to the identification of RA and \nconcluded that IL-40 is a reliable indicator for the disease 25.  \nIL-40 is a cytokine that plays a central role in the regulation \nand secretion of IgG which, in turn, supports the normal \nfunctioning of B cells and enables the body\u2019s immune system \nto effectively respond to antibodies.7-8,27 IL-40 has not been \nwidely studied, but it appears to be expressed only in \nmammals. It has a unique structure, which makes it \nincomparable to most cytokine families.7,8 The cytokine has \nbeen shown to exert its most potent regulatory influence over \nB cells, acting during foetal development, and within the liver \nand bone marrow.7,28-29 Studies of IL-40 knockout mice \ndemonstrated an effect on B cell development, resulting in \nimpaired and non-functioning cells.8,25 Given that SLE is \nrecognised as an autoimmune disease,6,25 the current results \nsupport the hypothesis that IL-40 could be used to determine \nand diagnose autoimmune dysfunction.    \n \nThe role of IL-40 and its efficacy as a biomarker for detecting \ndisease have now been identified for a range of pathologies \n\n\n\n                                                                                                         IL-40 levels (ng/L) \nSeverity of SLE                                           Mean                                 SD                          Std. error                      LSD test (P value) \nControl                                                        6.1138                            0.59452                        0.07475                      A                     **<0.01 \nInactive                                                        9.3325                            1.62807                        0.28341                       B                      **<0.01 \nActive moderate                                        13.0643                           1.23927                        0.21573                       C                     **<0.01 \nActive severe                                             15.2291                           2.26540                        0.39436                      D                     **<0.01 \nANOVA test (p value);   p=0.00                                                                                                                                E                      **<0.01 \n\n\n\n                                                                                                                                                                             F                      **<0.01 \n \n**(p< 0.01), SD: Standard Deviation, LSD: Least Significant Difference \n\n\n\nTable IV: Mean distributions of IL-40 levels within SLE patient groups and controls\n\n\n\n                                                                              SLE patients (n = 99) \nPearson Correlation                                                                                      IL40 ng/L \nBMI                                                                   r                                                  0.069 \n                                                                   p value                                            0.495  \nAge                                                                  r                                                  0.139 \n                                                                   p value                                            0.171  \nDuration                                                          r                                                  0.181 \n                                                                   p value                                            0.073  \nESR                                                                   r                                                  0.344 \n                                                                   p value                                             0.00  \nAnti-dsDNA                                                     r                                                  0.166 \n                                                                   p value                                            0.101  \nC3                                                                     r                                                 -0.420 \n                                                                   p value                                             0.00  \nC4                                                                     r                                                 -0.396 \n                                                                   p value                                             0.00  \n\n\n\nTable V: Correlation study between IL-40 levels and other SLE patient parameters\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 613\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n614                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nincluding RA8,25 type II diabetes,10 hepatocellular carcinoma30 \nand lupus.11 The present results also imply that IL-40 is an \nimportant biomarker for the detection of SLE, and it is \nsuggested that further work should be targeted towards the \npart played by IL-40 in disease development processes. \nMonitoring serum IL-40 levels could support future clinical \ndiagnosis. Additionally, higher IL-40 titres were associated \nwith SLE symptom severity and so serum IL-40 level \nmonitoring in individuals suspected of having SLE could \nprovide opportunities for early diagnosis and intervention. \n \nIt was determined that the complement indicators, C3 and \nC4, were both negatively correlated with IL-40 levels, \nindicating that a higher titre of IL-40, which is indicative of a \npositive SLE diagnosis, is associated with reduced C3 and C4 \nlevels. This finding supports previous studies which have \nreported diminished blood serum complement factors in \ncases of lupus.9,11  \n \nWhen compared to the cohort of patients with inactive SLE, \nESR values were elevated in the groups with active severe and \nactive moderate disease, which supports existing literature \nshowing that a high ESR indicates active lupus.19 Elevated \nanti-dsDNA antibody levels were also measured in the active \nsevere group as opposed to in SLE patients with active \nmoderate or inactive disease, a finding which supports \nprevious studies that suggest a high level of serum anti-\ndsDNA antibodies are strongly associated with lupus.  \n \nCRP has a complex role in lupus, with modest CRP elevations \noften seen in patients with SLE. In the current study, the \ninactive group exhibited more negative than positive test \noutcomes. Conversely, both types of active SLE patient \ncohorts demonstrated more positive than negative test \noutcomes. The reason for the variation in proportions of \npositive and negative tests across the different SLE types is not \nclear. However, these findings support previous observations, \ni.e. that CRP involvement in lupus appears to be part of a \ncomplex set of processes.19  \n \nA negative association between the use of DMARDs and IL-40 \nlevels was observed, i.e. patients who did not take DMARDs \nhad significantly higher serum IL-40 levels. This suggested \nthat DMARDs may provide a protective effect against rising \nIL-40 levels in cases of SLE. \n \nThis study is the first to demonstrate the positive association \nbetween IL-40 levels and SLE symptom severity, adding \nevidence to suggest that IL-40 plays a role in SLE, and could \nbe used as part of the diagnostic process. A robust sample size \nof 99 SLE and 33 controls was studied. However, it was \nrecognised that when filtering patients by certain variables, \nthe sample size was reduced to a less than ideal number. For \ninstance, the sample size for SLE patients not taking DMARDs \nwas small, i.e. 17 patients, when compared to the sample of \n82 patients who were taking DMARDs. Nonetheless, it is \nconsidered that the results offer robust evidence that \nDMARDs may be protective against the development of SLE \nand support the role of IL-40 in this autoimmune condition. \nSample sizes will always be a challenge in such studies, but it \nis recommended that, where possible, future studies should \ntake all available steps to maximise sample sizes.  \n\n\n\nThe link between IL-40 titres, and SLE symptom severity and \nduration, needs to be confirmed in a larger sample size, and \nin patient populations with greater ethnic diversity. Previous \nstudies have highlighted that Black, Hispanic and Asian \npopulations demonstrate higher rates of SLE,31,32 and it is well-\nestablished that SLE is linked to genetic heritage and \nancestry.24 Furthermore, women are disproportionately \naffected over men.23 A logical next step would therefore be to \nunderstand how the role and function of IL-40 may differ \nbetween different ethnic and geo-spatially distinct \npopulations of individuals with SLE. The majority of studies \nhave been conducted in the Western or developed world,14-\n\n\n\n15,31,32 and a need for further studies to investigate the \nprevalence and presence of SLE in developing nations is \nrecognised. This is especially relevant given that White \npopulations appear to be at a lower risk of the condition.31,32 \n \n \nCONCLUSIONS \nIt was established that serum IL-40 measurements \ndemonstrated strong validity for the identification and \ndiagnosis of SLE, and exhibited greater accuracy than \nrecognised in relation to other disease indications. IL-40 \nlevels were positively correlated with SLE symptom severity \nand duration, indicating that this cytokine could be a \npromising biomarker for SLE, and play a role in early \ndiagnosis and intervention monitoring. This study adds \nfurther evidence to support the observation that IL-40 is \nimportant with respect to the immune response and immune \nsystem regulation. It is hoped that it inspires further studies \nwhich are designed to improve the understanding of the \ncytokine\u2019s potential as a biomarker for SLE and other \nautoimmune diseases.   \n \n \nCONFLICTS OF INTEREST  \nNo conflicts of interest. \n \n \nFUNDING \nThis research article is entirely funded by the authors.  \n \n \nREFERENCES \n1. Kiriakidou M, Ching CL. Systemic lupus erythematosus. Ann \n\n\n\nIntern Med. 2020; 172(11) :ITC81-ITC96. \n2. Justiz Vaillant AA, Goyal A, Varacallo M. Systemic lupus \n\n\n\nerythematosus. In: Stat Pearls. Treasure Island (FL): StatPearls \nPublishing. 2023. \n\n\n\n3. Abdulridha RH, Saud AM, Alosami MH. Evaluation of interferon \nalpha (IFN-\u03b1) in women with systemic lupus erythematosus in \nIraq. Iraqi J Sci 2022; 63(10): 4225\u201333.  \n\n\n\n4. Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, et al. The \nrole of tumor necrosis factor alpha (TNF-\u03b1) in autoimmune \ndisease and current TNF-\u03b1 inhibitors in therapeutics. Int J Mol Sci \n2021; 22(5): 2719. \n\n\n\n5. Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK. High serum \nIFN-alpha activity is a heritable risk factor for systemic lupus \nerythematosus. Genes Immun 2007; 8(6): 492\u2013502. \n\n\n\n6. Abdualkader SN, Wahab Al-Shaikly A, Al-Mousawy KM, Al-Ezzi \nM, Hasso MG, Hassan ZE. Correlation between interleukin-4 and \ninterleukin-6 and auto antibodies in systemic lupus \nerythematosus. J Faculty Med Baghdad 2010; 51(4): 416-8. \n\n\n\n\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 614\n\n\n\n\n\n\n\n\nSerum interleukin 40: an innovative diagnostic biomarker for patients with systemic lupus erythematosus\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                615 \n\n\n\n7. Catalan-Dibene J, Vazquez MI, Luu VP, Nuccio S-P, Karimzadeh \nA, Kastenschmidt JM, et al. Identification of IL-40, a novel B cell-\nassociated cytokine. J Immunol 2017; 199(9): 3326-35. \n\n\n\n8. AG Al Ghuraibawi Z, Sharquie IK, Gorial FI. Diagnostic potential \nof interleukin-40 (IL-40) in rheumatoid arthritis patients. Egypt \nRheumatol 2022; 44(4): 377-80. \n\n\n\n9. Catalan-Dibene J, McIntyre LL, Zlotnik A. Interleukin 30 to \nInterleukin 40. J Interferon Cytokine Res 2018; 38(10): 423-39. \n\n\n\n10. Nussrat SW, Ad'hiah AH. Interleukin-40 is a promising \nbiomarker associated with type 2 diabetes mellitus risk. Immunol \nLett 2023; 254: 1-5. \n\n\n\n11. Rizzo C, La Barbera L, Lo Pizzo M, Mohammadnezhad L, Lentini \nVL, Donzella D, et al. POS0101 Potential involvement of il-40 \nand il-40 producing cells in systemic lupus erythematosus and \nlupus associated nephritis. Annals of the Rheumatic Diseases. \n2022; 81(Suppl 1): 273.  \n\n\n\n12. Zingaretti C, Arig\u00f2 M, Cardaci A, Moro M, Crosti M, Sinisi A, et \nal. Identification of new autoantigens by protein array indicates \na role for IL4 neutralization in autoimmune hepatitis*. \nMolecular & Cellular Proteomics. 2012; 11(12): 1885-97.  \n\n\n\n13. Magallares B, Lobo-Prat D, Castellv\u00ed I, Moya P, Gich I, Martinez-\nMartinez L, et al. Assessment of EULAR/ACR-2019, SLICC-2012 \nand ACR-1997 classification criteria in SLE with longstanding \ndisease. J Clin Med 2021; 10(11): 2377. \n\n\n\n14. Gladman DD, Iba\u00f1ez D, Urowitz MB. Systemic lupus \nerythematosus disease activity index 2000. J Rheumatol 2002; \n29(2): 288-91. \n\n\n\n15. Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The \ngeoepidemiology of systemic lupus erythematosus. Autoimmun \nRev 2010; 9(5): 24. \n\n\n\n16. D\u00f6rner T, Furie R. Novel paradigms in systemic lupus \nerythematosus. Lancet. 2019; 393(10188): 2344-58. \n\n\n\n17. Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, \nBoletis JN, et al. 2019 update of the EULAR recommendations for \nthe management of systemic lupus erythematosus. Ann Rheum \nDis 2019; 78(6): 736-45. \n\n\n\n18. Harvey AM, Shulman LE, Tumulty PA, Conley CL, Schoenrich \nEH. Systemic lupus erythematosus: review of the literature and \nclinical analysis of 138 cases. Medicine 1954; 33(4): 291-437. \n\n\n\n19. Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, et al. \nCytokine IL-6 and IL-10 as biomarkers in systemic lupus \nerythematosus. J Clin Immunol 2007; 27(5): 461-6 \n\n\n\n20. Liu CC, Kao AH, Manzi S, Ahearn JM. Biomarkers in systemic \nlupus erythematosus: challenges and prospects for the future. \nTher Adv Musculoskelet Dis 2013; 5(4): 210-33. \n\n\n\n21. Arriens C, Wren JD, Munroe ME, Mohan C. Systemic lupus \nerythematosus biomarkers: the challenging quest. \nRheumatology 2017; 56(suppl_1): i32\u2013i45. \n\n\n\n22. Ahearn JM, Liu CC, Kao AH, Manzi S. Biomarkers for systemic \nlupus erythematosus. Transl Res 2012; 159(4): 326-42. \n\n\n\n23. Lockshin MD, Barbhaiya M, Izmirly P, Buyon JP, Crow MK. SLE: \nreconciling heterogeneity. Lupus Sci Med 2019; 6(1): e000280. \n\n\n\n24. Owen KA, Grammer AC, Lipsky PE. Deconvoluting the \nheterogeneity of SLE: the contribution of ancestry. J Allergy Clin \nImmunol 2022; 149(1): 12-23. \n\n\n\n25. Navr\u00e1tilov\u00e1 A, Andr\u00e9s Cerezo L, Hulejov\u00e1 H, Be\u010dv\u00e1\u0159 V, Tom\u010d\u00edk \nM, Komarc M, et al. IL-40: A new B cell-associated cytokine up-\nregulated in rheumatoid arthritis decreases following the \nrituximab therapy and correlates with disease activity, \nautoantibodies, and NETosis. Front Immunol. 2021; 12(745523).  \n\n\n\n26. Rizzo C, Barbera LL, Pizzo ML, Mohammadnezhad L, Lentini VL, \nDonzella D, et al. POS0101 Potential involvement of il-40 and il-\n40 producing cells in systemic lupus erythematosus and lupus \nassociated nephritis. Annals of the Rheumatic Diseases. 2022; \n81(Suppl 1): 273.  \n\n\n\n27. Lissoni P, Messina G, Pelizzoni F, Rovelli F, Brivio F, Monzon A, et \nal., editors. The fascination of cytokine immunological science. \n2020. \n\n\n\n28. Lee J, Hever A, Willhite D, Zlotnik A, Hevezi P. Effects of RNA \ndegradation on gene expression analysis of human postmortem \ntissues. Faseb J 2005; 19(10): 1356-8. \n\n\n\n29. Roth RB, Hevezi P, Lee J, Willhite D, Lechner SM, Foster AC, et al. \nGene expression analyses reveal molecular relationships among \n20 regions of the human CNS. Neurogenetics 2006; 7(2): 67\u201380. \n\n\n\n30. Said Nm, Yassin F, Esh AM, Saeed E. Association between serum \nlevel of pentraxin-3 and interleukin-40 with HCC disease in \nEgypt. Biochem Lett 2020; 16(1): 50-62.  \n\n\n\n31. Dall'Era M, Cisternas MG, Snipes K, Herrinton LJ, Gordon C, \nHelmick CG. The incidence and prevalence of systemic lupus \nerythematosus in San Francisco County, California: The \nCalifornia Lupus Surveillance Project. Arthritis Rheumatol. 2017; \n69(10): 1996-2005. \n\n\n\n32. Izmirly PM, Wan I, Sahl S, Buyon JP, Belmont HM, Salmon JE, et \nal. The incidence and prevalence of systemic lupus \nerythematosus in New York County (Manhattan), New York: The \nManhattan Lupus Surveillance Program. Arthritis Rheumatol. \n2017; 69(10): 2006-17 \n\n\n\n\n\n\n\n9-Serum00113.qxp_3-PRIMARY.qxd  25/09/2023  4:25 PM  Page 615\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\n616                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: Gastric cancer (GC) is one of the leading \ncauses of all new cancer cases globally. Although it is no \nlonger reported in the top 10th most common cancer in \nMalaysia, geographical distribution and ethnic influences \nstill obviously exist.  \n \nMaterials and Methods: This is a retrospective analysis of \nhistopathological records in a public tertiary health care \ncentre in Malaysia. The computerised laboratory information \nsystem from the histopathology department of the hospital \nwas retrieved for the period of 2005\u20132018. Descriptive \nanalysis was done using Microsoft Excel.  \n \nResults: There was a total of 233 histologically confirmed \nGC cases. The burden of GC was observed to be an \nincreasing trend from 2016 onwards. Among them, 64% were \nmale and 36% were female. The youngest age of diagnosis \nwas 19, while the oldest one was 93. Malaysian Chinese were \nfound to have the highest incidences (41.63%), followed by \nMalays (32.19%) and Malaysian Indians (23.61%). All cases \nwere of adenocarcinoma cell types and were found to have \npoorly differentiated in majority at the time of diagnosis.  \n \nConclusion: Although this report only represents one \ntertiary health care centre in Malaysia, the Indian Enigma \nwas still observed, as stated in other literatures. Over time, \nthe incidence of GC in Malays has increased. Consideration \nof lifestyle modifications, health education and Helicobacter \npylori eradication in various nations' National Health \nInsurance plans, are encouraged as prevention is always \nbetter than treatment or cure, including the cost load. \n \nKEYWORDS:  \nStomach neoplasms, Malaysia, Ethnic, Geographical, Enigma \n \n \nINTRODUCTION \nGastric cancer (GC) is the fifth leading cause of all newly \ndiagnosed cancer globally and the fourth leading cause of \ncancer-related death in 2020.1 The incidence rate, mortality \nrate and the 5-year prevelance rate of GC were the highest in \nAsia compared to other regions.1 In addition, around 1 in 12 \ncancer-related deaths were attributable to GC in 2018.2 \nAlthough nearly a million new GC cases are diagnosed \nglobally every year, GC is one of the most preventable cancer \ndue to its highly behaviourally influenced nature.2 \n\n\n\nHowever, the incidence, the age-standardized incidence and \nmortality of GC also declined globally.3 Although GC was \nreported as the second-highest incidence and mortality \nworldwide according to the Global Cancer Observatory \n(GLOBOCAN) 1998, GC was reported as the fifth most \ncommon neoplasm of all new cancer cases in GLOBOCAN \n2018.3 New GC cases are still detected, especially in the \nEastern Asian countries and these countries still have a high \nrisk of GC.3 GC was ranked as the 10th most common cancer \nin Malaysia in 2007\u20132011 (Malaysia National Cancer \nRegistry) MNCR report but it was not reported in the top 10 \nlist in the 2012\u20132016 MNCR report.4,5 \n \nIncidence and mortality of GC are highly variable by \ngeography as well as are greatly influenced by diet, \nenvironmental factors, and Helicobacter pylori (H. pylori) \ninfection in the community. GC was common in the United \nStates in previous centuries, but now it is no longer \nprevalent.2 This decreasing trend was most obvious in \ncountries such as Japan and South Korea.2 More than 50% of \nnew incident cases were reported from developing countries.  \nThis downward trend in some regions could be due to the \nearlier detection of GC using screening procedures such as \nupper gastrointestinal endoscopy or radiography and might \nbe due to the reduced H.  pylori infection in some countries.2 \n \nThe age-standardized 5-year net survival rate for GC is still \nbetween 20% and 40%, where 33.1% for the USA and 20.7% \nfor the UK.2 In these countries, although being the well-\ndeveloped countries, GC tends to be diagnosed at an \nadvanced stage.2 In contrast, the age-standardized 5-year net \nsurvival rate for Eastern Asian countries such as South Korea \nand Japan also has higher rates. The 5-year survival rate for \nGC in 2010\u20132014 was reported as 68.9% for South Korea and \n60.3% for Japan. It was strongly believed that the early \ndetection of GC had contributed to these favourable health \noutcomes. However, the median survival rate of GC is less \nthan 12 months in the advanced stage of GC.6 \n \nThe survival rate of GC has improved globally over the \ndecades due to improved case detection, early diagnosis, and \nbetter treatment strategies.2 However, there is still room for \nimprovement to achieve a favourable survival rate \nworldwide.2 Early diagnosis of GC plays an important role in \nachieving a better survival outcome of GC and an \nunderstanding of its epidemiology, variation in ethnicity, \nage, gender and genetic predispositions are crucial. The \n\n\n\nClinicopathological study of gastric cancer in a Malaysian \ntertiary public health care centre \n \nHtet Htet, MMedSc1, Thin Thin Win, MMedSc1, Wong Siew Tung, PhD1, Noor Hasni Bt Shamsudin, MMedSc2, \nKandasami Palayan, FRCS1 \n\n\n\n     \n1School of Medicine, International Medical University, Kuala Lumpur, Malaysia, 2Department of Histopathology, Hospital \nTuanku Ja'afar, Seremban, Ministry of Health, Malaysia \n \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 13 August 2023                                                                                                                                                                         \nCorresponding Author: Htet Htet                                                                                                                                                                                        \nEmail: hhnoel@gmail.com\n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 616\n\n\n\n\n\n\n\n\nClinicopathological study of gastric cancer in a Malaysian tertiary public health care centre\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                617 \n\n\n\nobjective of this study is to investigate the incidence and \ntrend of GC in Malaysia at one of the tertiary health care \ncentres, i.e., Hospital Tuanku Ja'afar (HTJ), Seremban, Negeri \nSembilan state, Malaysia from 2005 to 2018.  \n \n \nMATERIALS AND METHODS \nThis is a retrospective cross-sectional study of the \nhistologically confirmed GC data from 2008 to 2018. All \npatient records of histologically confirmed GC cases during \nthe study period at the Hospital Tuanku Ja\u2019afer (HTJ), \nSeremban, Negeri Sembilan, Malaysia were reviewed. Data \ncollected were clinicopathological parameters which included \nhistopathological diagnosis, age, gender, identification card \nnumber, patient registration number, ethnic group, date of \nbiopsy and histological diagnosis. Inclusion criteria included \nthat the patients must have attended HTJ between 2005 and \n2018 and paraffin-embedded gastric biopsy must be \navailable. The patients diagnosed with GC before 1 January  \n2005 or after 31 December 2018, patients who were \ndiagnosed with oesophageal cancer alone were excluded \nfrom the study. The index date was defined as the date of the \nfirst outpatient or inpatient visit with a diagnosis of GC. \nRecords of the patients who were first diagnosed with GC \nbefore 1st January 2005 were excluded from the study. Data \nwere analysed using Microsoft Excel. Confidentiality of the \ncollected information was maintained by strict measures. The \nnames, ethnic groups and ages of the patients were kept \nprivate and confidential apart from the research team. The \nidentities of patients were not revealed in this report.   \n \n \n \n\n\n\nRESULTS \nThere was a total of 233 cases reported as histologically \nconfirmed GC cases in HTJ, Seremban from 2005 to 2018. The \nnumber of annual reported cases of GC from 2005 to 2018 \nwas found to be varied. The number of reported GC cases in \nHTJ was observed as an increasing trend starting from 2016 \nonwards (Table I). \n \nThe youngest reported case was a 19-year-old Malaysian \nIndian man, and the oldest reported case was a 93-year-old \nMalaysian Chinese woman. The mean age of diagnosis is \n62.24 \u00b1 14.04 years. However, there were 38 cases whose ages \nwere not included in the report, and the estimated age was \ncalculated from the identification card (IC) number of the \npatient (which usually starts with the birth year of the person \nin Malaysia) and the year of the biopsy report. The number \nof reported and confirmed GC cases was found to be highest \namong the age group of 61\u201370, 51\u201360 and 71\u201380, respectively \n(Table II).   \n \nAmong 233 cases, 64% (n = 150) cases were males and 36% \n(n = 83) were females. The youngest age of reported GC cases \nfor females was 23, and the oldest one was 92. The youngest \nage of reported GC case for men was 19 and the oldest was \n93. Malaysian Chinese ethnic group has the highest \nincidence of GC with 41.63% (n = 97), followed by Malays \nwith 32.2% (n = 75) and Malaysian Indians with 23.61% (n \n= 55). There were a few cases reported from ethnic minorities \n1 case each (0.43%) from Orang Asli, Singh and others (Table \nII). \n \nAll reported cases were adenocarcinoma 100% (n = 233). In \nterms of histopathological grading, 45% (n = 104) were \n\n\n\nYear reported       2005         2006       2007       2008      2009        2010      2011     2012       2013       2014       2015     2016     2017    2018 \nNumber of             13             11           13            5           17             23          23         12           12           17           15         22         21        29 \nGC cases                    \n \nNote: GC = gastric cancer  \n\n\n\nTable I: Number of GC cases reported annually at the HTJ, Seremban, Negeri Sembilan, Malaysia from 2005\u20132018\n\n\n\nGender                  Ethnicity                       Number of cases                    Mean age of GC cases a                     Age in years (range) \n                                                                              n (%)                                at the time of diagnosis \n                                                                                                                            Age in years \u00b1 SD                                             \nFemale                    Chinese                              31 (37.35)                                     68.41 \u00b1 12.77                                           45\u201392 \n                                Indian                                26 (31.33)                                     59.38 \u00b1 14.04                                           23\u201380 \n                                 Malay                                24 (28.92)                                     57.76 \u00b1 14.06                                           34\u201383 \n                                others                                 2 (2.41)                                            60 \u00b1 20                                                40\u201380 \n                          Female (Total)                          83 (100)                                       61.99 \u00b1 14.64                                           23\u201392 \nMale                       Chinese                                 66 (44)                                        66.67 \u00b1 10.84                                           42\u201393 \n                                Indian                                29 (19.33)                                     54.63 \u00b1 12.74                                          30\u201383.2 \n                                 Malay                                  51 (34)                                        63.42 \u00b1 13.33                                           28\u201391 \n                                others                                 4 (2.67)                                       43.25 \u00b1 10.96                                           31\u201361 \n                           Male (Total)                           150 (100)                                       62.38 \u00b1 13.7                                            19\u201393 \nTotal                       Chinese                              97 (41.63)                                        67.23 \u00b1 12                                              42\u201393 \n                                Indian                                55 (23.61)                                     55.74 \u00b1 14.29                                          19\u201383.2 \n                                 Malay                                75 (32.19)                                     61.61 \u00b1 13.83                                           28\u201391 \n                                others                                 6 (2.58)                                       48.83 \u00b1 16.61                                           31\u201380 \n                                 Total                                 233 (100)                                      62.24 \u00b1 14.04                                           19\u201393 \n \nNote: SD = standard deviation \n \n\n\n\nTable II. Age, gender, and ethnic incidences of GC cases reported annually at the HTJ, Seremban, Negeri Sembilan, Malaysia from \n2005 to 2018\n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 617\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n618                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\npoorly differentiated type, 21% (n = 21) were moderately \ndifferentiated type, 3% (n = 7) were well-differentiated type, \nwhile there were 1 moderate to poorly differentiated type and \n1 moderate to well-differentiated type, 30% (n = 70) were not \nreported. According to Lauren\u2019s classification, 13% (n = 31) \nwere intestinal type, 15% (n = 34) were diffuse type and 1% \n(n = 2) were mixed type, while 74% (n = 172) did not find a \nreport for pathological subtype. Seven reported cases with \nsignet ring cell types which were considered as diffused type. \n \n \nDISCUSSION \nComparison with Previous Findings   \nThe shifting pattern of ethnic incidence of GC in Malaysia is \nthe most noticeable characteristic of this study. Among the \n233 laboratory-confirmed GC cases from the HTJ, Seremban \nfrom 2005 to 2018, 41.6% of diagnostically confirmed GC \ncases were Malaysian Chinese population, 31.8% were Malay \npopulation and 23.6% were Malaysian Indian population. \nAn earlier study which was done at the HTJ in 2013 showed \n55.0% Malaysian Chinese, 27.8% Malaysian Indian and \n16.6% Malay population.7 The second study which was \ncarried out at the Hospital Ipoh, Perak state, Malaysia also \nshowed 53.6% Malaysian Chinese, 36% Malaysian Indian \nand 26% Malay population. The study represented data from \n1988 to 1998.8 It indicates the increasing incidence of GC in  \nMalay population.  \n \nThe age-standardized rate for GC was 4\u20135 times lower in \nMalay than in the Malaysian Chinese and Malaysian Indian \npopulations. This gap seemed to be narrower due to the \nincreased number of GC cases in the Malay population and \ndecreased the number of cases in the other two populations.9 \nThe findings from this study agrees with the fact of the \nincreased number of GC cases in the Malay population. \nHowever, the incidence rate in the Malaysian Chinese and \nMalaysian Indian populations does not seem to decline \nsignificantly. This partly agrees with the MNCR report (2012\u2013\n2016), which stated as the Malaysian Chinese have the \nhighest incidence rate in both genders.4 According to MNCR \n2012\u20132016, the rate of GC was declined in Malaysia and was \nno longer listed as the 10th most common cancer. However, \nthe incidence of GC in Seremban, Negeri Sembilan state does \nnot seem to be declining until 2018. Globally, the highest \nnumber of cases was observed in Asia, specifically in China.10 \n \nThe mean age of diagnosis for GC was 62.75 \u00b1 13.95 years \nand only 9.8% of them (n = 23) are diagnosed under the age \nof 45 in this study. This agrees with the previous reports 60.8 \n\u00b1 14.744 years (19\u201391) and 65 years (male 65.3 years and \nfemale 63.2 years, p > 0.05).7,8 In our study, 9.8% of the \nreported cases were early-onset GC (45 years or younger) and \nthe remaining 91.2% were conventional GC (older than 45). \nThis finding agrees with the data from Machlowska et al (6), \nwhich stated that GC is not prevalent in younger age groups \nwho are <45 years of age.6 Early-onset GC was rare and not \nmore than 10% of patients underwent disease development.6 \n\n\n\nHowever, the youngest reported case in this study was a 19-\nyear-old Malaysian Indian male patient, and such cases \ncould have a genetic influence as a big role in the \ndevelopment of GC.  \n \n\n\n\nThere were 56.3% male patients in the study by Tata et al (7) \nwhereas our current study indicates that 63% male, \nindicating male predominance in GC.7 Both studies were \ndone in HTJ, Seremban, Negeri Sembilan state, Malaysia. In \nanother study done at the Hospital Ipoh, 68.4% (171 out of \n250 GC patients) were male patients.8 This clearly \ndemonstrates the male predominance in the incidence of GC. \nIn our study, among different populations, men had a higher \nincidence than women (68%, 68% and 52.7%) in all \nMalaysian populations: Malaysian Chinese, Malay and \nMalaysian Indian, respectively. The findings of our study \nagree with the previous reports, that there is a male \npreponderance in all main ethnic groups of Malaysia.4,6 \n\n\n\nGlobally, men have higher incidence than women, and \ndouble the number of cases were reported.9 \n \nAround the 1980s, only 3% of GC patients are diagnosed with \nearly GC but this was increased to 27% as stages 1 and 2 in \nthe twenty-first century, indicating an earlier diagnosis \ntrend.9 The mortality to an incidence rate (MIR) for GC in \nSouth East Asia (SEA) was reported as 0.88 and a similar rate \nwas observed for Malaysia.10 Incidence of GC in Malaysia was \ndeclined by 48% among males and 31% among females in \ntheir last reported period of 13 years.10 \n \nAll 233 cases in our review reported as adenocarcinoma type, \nand this agrees with the previous study.7 Most of the reported \ncases 45% were diagnosed as poorly differentiated, 21% were \nreported as moderately differentiated and only 3% were \nreported as well-differentiated. The site of the tumour was not \nconsistently informed. In the previous study, 45.6% were \ndiagnosed with stage 4B; 36% with stage 4A; and only 3.6% \nwith stage 1.8 This implied the late diagnosis nature of the \ndisease. Survival rate of the studied cases in this report was \nnot traced. The survival rate of GC has improved globally \nover the decades due to improved case detection, early \ndiagnosis, and better treatment strategies.2 However, there is \nstill room for improvement to achieve a favourable survival \nrate worldwide.2 \n \nIn addition, GC can be classified into intestinal type and \ndiffuse type depending on the histopathology.2,4 There was a \ndecline in the sporadic intestinal-type GC, but in contrast, the \nincidence of diffuse-type GC has reportedly increased.6 This \nstudy does not have any prior data to explore further. \n \nGeographic Diversity of GC \nThe incidence of GC displays immense geographical \ndiversity.6,9 This study only represents the data from the \nNegeri Sembilan state, Malaysia. Geographically, Kelantan \nstate, which is northeast of the Peninsular Malaysia, was \nobserved as having the lowest incidence of GC and Kelantan \nMalays were probably having the lowest rates of GC \nglobally.9 Thailand Enigma was reported where the Southern \npart of Thailand, was also observed as a lower incidence of H. \npylori infection compared to North, Northeast and Central \nThailand.11 Geographically, Kelantan state and the Southern \npart of Thailand are neighbouring states and share a \nsignificant pattern of similarity in diet and the abundance of \nsea foods, vegetables and deep-sea water.12 \n \n \n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 618\n\n\n\n\n\n\n\n\nClinicopathological study of gastric cancer in a Malaysian tertiary public health care centre\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                619 \n\n\n\nThe Indian enigma had reported by Misra in 2014.13 The \ngeographical distribution of GC differs widely in the different \nregions of India.13 Southern and Eastern India had shown a \nhigh incidence of GC frequency approximately four times \ncompared to North India.13 Non-vegetarian foods, \nparticularly, spicy and salty meat, fish, pickled food, high rice \nintake, excess chilli consumption, high-temperature foods, \nsmoked dried salted meat, use of soda and consumption of \ndried salted fish were observed as significant risk factors for \nGC compared to North India, where diet is mainly wheat-\nbased, a greater proportion of vegetarians and a higher \nintake of fruits and spices such as turmeric, garlic etc. These \ndietary habits were proposed as one of the explanations for \nthe Indian enigma.13  \n \nGlobally, the age-adjusted incidence rate was observed as a \ndownward trend in Japan which was probably due to \nimproved early diagnosis efforts and improved treatment \noutcomes in Japan.2,10 However, due to the increased number \nof elderly populations, the crude incidence rate of GC \ncontinued to increase, and GC was more frequently detected \nin Japan. After the two peaks in 2030\u20132034 (in men) and \n2025\u20132029 (in women), the decreasing trend of GC could be \nobserved as the younger generation in Japan was more aware \nof health, and they tend to adopt a healthy lifestyle \ncompared to the older generation.2 In February 2013, Japan \nbecame the first country in the world to cover H. pylori \neradication for chronic gastritis under its National Health \nInsurance (NHI) system.10 H. pylori eradication reduces the \nrisk of second GC to approximately one-third that of patients \nwho do not undergo eradication therapy (JAPANGAST study). \nThis indicates the benefit of H. pylori eradication in \npreventing GC.14,15 \n \nRisk Factors of GC \nAs known, H. pylori is classified as a type I carcinogen and is \nreported as a major risk factor for GC, especially for non-\ncardia GC. The reduction of the H. pylori infection rate in the \npopulation has contributed to the decline in the incidence of \nnon-cardia GC. In addition, this trend could be explained by \nthe increased standard of hygiene, better food conservation \nand a high intake of fruits and vegetables.2,4 For cardia GC, it \nis more related to risk factors such as body fat. It was expected \nthat cardia GC might be more frequent in future.2 Most of the \ncases are non-cardia GC in Malaysia, except in Kelantan, \nwhere the main site of involvement is cardia.9 The site of the \ntumour of GC, either cardia or non-cardia did not report \nconsistently and hence, we do not have a precise data \nregarding the cardia and non-cardia types in this study.  \n \nFive-Year Survival Rate of GC \nThe 5-year survival rate for GC in 2010\u20132014 was reported as \n68.9% for South Korea and 60.3% for Japan. However, the 5-\nyear survival rate of GC globally is still around 20%.10 It was \nstrongly believed that the early detection of GC had \ncontributed to these favourable health outcomes. However, \nthe median survival rate of GC is less than 12 months in the \nadvanced stage of GC.6 Due to its high aggressiveness and \nheterogeneous in nature, even with early diagnosis, GC will \nstill constitute as a global health issue.6 \n\n\n\n\n\n\n\nAccessing the trend of GC from one hospital data is not \nsufficient despite the data obtained are more than a decade. \nSome data, such as the age of the patients from certain \nreports, were not included. Confounding factors such as \nfamily history, occupation, comorbidities (e.g., diabetes \nmellitus, history of gastritis), social history (alcohol drinking, \nsmoking etc), dietary history, body mass index (BMI), status \nof H. pylori infection and physical activity were unable to \ninclude in this analysis.  \n \nThe epidemiology of GC in different geographical locations \ncan be sought out in future. The trend and the changes in the \nincidence of GC in previous low-incidence areas such as \nKelantan should also be studied along with the dietary and \nlifestyle changes. The prevalence of H. pylori infections and \nthe incidence of GC in different geographic locations could be \nstudied for Malaysia as well as for Asia and globally. \n \n \nCONCLUSION  \nIn this retrospective study, we studied the clinicopathological \ndata of GC, although the data we reported represented only \none hospital. The incidence of GC cases in Malay population \nwas observed to be increased. Late-onset GC cases were found \nto be more common than early-onset cases, while all reported \ncases were adenocarcinoma types. Globally, it was estimated \nthat there could be 1.8 million new cases and 1.3 million \ndeaths related to GC by 2040.16 And a higher incidence will be \nfound in medium and low HDI (Human Development Index) \ncountries compared to high HDI countries, hence, the SEA \ncountries should be observant on the burden of GC.16 \nAlthough GC showed a downward trend in Malaysia, it could \nagain lead to an increasing trend of GC. Because of the \nnature of high aggressiveness, late diagnosis, association \nwith lifestyle and non-communicable diseases such as \ndiabetes mellitus, the prevalence of H. pylori infection, \nvariation in responsiveness and awareness of the eradication \nregimens, GC could still constitute a local and global health \nissue. Consideration of lifestyle changes, health education, \ndetection and eradication of H. pylori infection and early \ndiagnosis of GC by health check-ups should be encouraged \nby the authorities. Hence, the authorities should consider \nadapting the H. pylori eradication regimen as a part of the \ninsurance scheme; detection of H. pylori as a part of routine \nhealth check-ups; early referral and an exploration of upper \nGI endoscopy of middle-aged people who are above 50 with \ndyspeptic symptoms should be considered. Since certain \ncountries and regions are estimated to have more burden of \nGC, health authorities should plan cancer control initiatives \nwithout delay. \n \n \nDISCLOSURE \nThe authors have no other relevant affiliations or financial \ninvolvement with any organisation or entity with a financial \ninterest in or financial conflict with the subject matter or \nmaterials discussed in the manuscript apart from those \ndisclosed. No writing assistance was utilised in the production \nof this manuscript. \n \n \n \n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 619\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n620                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nACKNOWLEDGEMENTS \nWe would like to thank the Director General of Health \nMalaysia for his permission to publish this article. This study \nis a part of the Fundamental Research Grant Scheme \nFRGS/1/2018/ SKK03/IMU/02/1. The projects and methods \nhad been granted ethical approval by the International \nMedical University, Malaysia with the project ID No: PHMS \n1/2020(04). The authors thank the Head of Department and \nstaff from the Histopathology Department, Hospital Tuanku \nJa'afar, Seremban, Negeri Sembilan State, Malaysia and the \nDirector and staff from the Institute For Research, \nDevelopment & Innovation, International Medical \nUniversity, Kuala Lumpur, Malaysia for their kind permission \nand assistance to retrieve the required data and support of \nthe project.  \n \n \nREFERENCES \n1. Globocan 2020. Cancer Today. Global Cancer Observatory. \n\n\n\nInternational Agency on Research on Cancer. World Health \nOrganization. March 2021. [cited 2023 April 28]. Available from: \nhttps://gco.iarc.fr/today/ \n\n\n\n2. Rawla P, Barsouk A. Epidemiology of gastric cancer: Global \ntrends, risk factors and prevention. Prz Gastroenterol. 2019; \n14(1): 26-38.  \n\n\n\n3. Sekiguchi M, Oda I, Matsuda T, Saito Y. Epidemiological trends \nand future perspectives of gastric cancer in Eastern Asia. \nDigestion 2022; 103(1): 22-8.  \n\n\n\n4. Azizah AM, Hashimah B, Nirmal K, Siti Zubaidah AR, Puteri NA, \nNabihah A et al. Malaysia National Cancer Registry Report \n(MNCR) 2012-2016. National Cancer Registry, National Cancer \nInstitute. Ministry of Health, Malaysia. [cited 2023 April 23] \nAvailable from: https://www.moh.gov.my/moh/resources/ \nPenerbitan/Laporan/Umum/2012-2016%20(MNCRR) \n\n\n\n5. Azizah Ab M, Nor Saleha IT, Noor Hashimah A, Asmah ZA, \nMastulu W. Malaysia National Cancer Registry Report (MNCR) \n2007-2011. National Cancer Registry, National Cancer Institute. \nMinistry of Health, Malaysia. [cited 2023 April 23] Available \nfrom: https://www.crc.gov.my/wp-content/uploads/documents/ \nreport/MNCRRrepor2007-2011.pdf \n\n\n\n6. Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric \ncancer: epidemiology, risk factors, classification, genomic \ncharacteristics and treatment strategies. Int J Mol Sci 2020; \n21(11): 4012.  \n\n\n\n7. Tata MD, Ratnasingam D, Gurunathan R, Palayan K. Delay in \ndiagnosis of upper gastrointestinal cancer: whose fault, is it? Med \nJ Malaysia 2013; 68(3): 275-7.  \n\n\n\n8. Kandasami P, Tan WJ, Norain K. Gastric cancer in Malaysia: the \nneed for early diagnosis. Med J Malaysia. 2003; 58(5): 758-62.  \n\n\n\n9. Lim KG, Palayan K A review of gastric cancer research in \nMalaysia. Asian Pacif J Cancer Prev 2019; 20(1): 5-11.  \n\n\n\n10. Ilic M, Ilic I. Epidemiology of stomach cancer. World J \nGastroenterol 2022; 28(12): 1187-203.  \n\n\n\n11. Pratoomchat B, Tongtawee T. Helicobacter pylori and gastric \ncancer \u201cThailand Enigma\u201d. (Poster presentation) Ann Oncol \n2018; 29 (supplementary 7).  \n\n\n\n12. Takeuchi H, Trang VT, Morimoto N, Nishida Y, Matsumura Y, \nSugiura T. Natural products and food components with anti-\nHelicobacter pylori activities. World J Gastroenterol 2014; 20(27): \n8971-8.  \n\n\n\n13. Misra V, Pandey R, Misra SP, Dwivedi M. Helicobacter pylori and \ngastric cancer: Indian enigma. World J Gastroenterol 2014; 20(6): \n1503-9.  \n\n\n\n14. Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of \nHelicobacter pylori on incidence of metachronous gastric \ncarcinoma after endoscopic resection of early gastric cancer: an \nopen-label, randomised controlled trial. Lancet 2008; 372: 392\u2013\n97.  \n\n\n\n15. Asaka M, Kobayashi M, Kudo T, Akino K, Asaka Y, Fujimori K, \nKikuchi S, Kawai S, Kato M. Gastric cancer deaths by age group \nin Japan: Outlook on preventive measures for elderly adults. \nCancer Sci 2020; 111(10): 3845-53.  \n\n\n\n16. Morgan E, Arnold M, Camargo MC, Gini A, Kunzmann AT, \nMatsuda T, et al. The current and future incidence and mortality \nof gastric cancer in 185 countries, 2020\u201340: a population-based \nmodelling study. eClinicalMedicine 2022; 47: 101404.  \n\n\n\n10-Clinicopathological00130.qxp_3-PRIMARY.qxd  25/09/2023  4:26 PM  Page 620\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\n688                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nAcknowledgement \nSeptember Issue 2023 \n\n\n\n \nThe Editorial Board of The Medical Journal of Malaysia gratefully acknowledge the following \nindividuals for reviewing the papers submitted for publication: \n \n                                                                                                                                                                                                              1. Assoc Prof Dr Abdelkareem A.Ahmed \n\n\n\n2. Dr Aida Abdul Aziz \n3. Prof Dr Anselm Ting Su \n4. Datin Dr Asmah Binti Johar \n5. Dr Azhar Md Zain \n6. Dr Azlan Helmy Abd Samat \n7. Dr Chai Zhen Hoo \n8. Dr Chan Tha A Hing \n9. Dr Chern Phei Ming \n10. Dr Chua Hock Hin \n11. Dr Davinder Singh Bagh \n12. Dr Fauzi Abdul Rani \n13. Dr Gerald Henry \n14. Dr Hana Maizuliana Solehan \n15. Prof Dr Jafri Malin Abdullah \n16. Dr Khadijah Poh \n17. Dr Krishna Kumar G \n18. Dr Kumar Harirajah \n19. Assoc Prof Dr Leelavathi Muthupalaniappen \n20. Dr Mazlin Baseri \n21. Dr Mohd Aizuddin Abd Rahman \n22. Dr Mohd Azmarul A Aziz \n23. Dr Mohd Azmi Bin Suliman \n24. Dr Muhd Siv Azhar Merican Abdullah \n25. Dr Navin Kumar Devaraj \n26. Dr Noor Dina Hashim \n27. Dr Rama Krishna Supramanian \n28. Dr Sanihah Abdul Halim \n29. Dr Sanjiv Rampal \n30. Dr Shaik Farid Abdull Wahab \n31. Dr Suhaila Abd Muid \n32. Dr Sufian Adenan \n33. Prof Dr Thameen Ansari \n34. Dr Thien Thien Lim \n35. Dr Vasu Pillai Letchumanan \n36. Dr Zahir Izuan Azhar \n37. Dr Zainab Abdul Majeed \n\n\n\n \n\n\n\n\n\n\n\n\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023 661 \n\n\n\nABSTRACT \nIntroduction: Burn injuries incur not just significant \nmorbidity but also long-term psychosocial impact. This \nstudy aims to identify the clinico-demographics of children \nhospitalised for burns and factors associated with \nprolonged hospitalisation.  \n\n\n\nMaterials and Methods: Written medical records of burn \npatients admitted to the Sultanah Aminah Hospital \npaediatric surgical ward, from January 2016 to December \n2018, were retrospectively reviewed. Details on the patients\u2019 \nsocio-demographic background, burn injuries, management \nand outcomes were recorded and analysed with logistic \nregression.  \n\n\n\nResults and Conclusion:  Of the 255 children included in the \nstudy, the majority were males (62.7%), children aged \nbetween 1 to 3 years (43.1%), and of the Malay ethnic group \n(83.1%). The commonest injury mechanism was scalds \nburns (81.2%). Staphylococcus aureus remained the \ncommonest organism cultured from paediatric burn \nwounds. Most patients (66.4%) were hospitalised for less \nthan 1 week. A significant number of patients experienced \ncomplications from their injuries. Multivariate analysis \nshowed burns affecting total body surface area > 10% \n(adjusted OR, 13.45 [95% CI 6.25 - 28.96]; p = < 0.001) and \nnon-scald burns (adjusted OR, 2.70 [95% CI 1.12 - 6.50]; p = \n0.027) were the two main factors associated with prolonged \nhospitalisation of more than 1 week. These findings \ndescribing the epidemiology and outcomes of paediatric \nburn cases in a tertiary centre in Malaysia may inform future \npractice. More importantly, the information may contribute \nto the identification of at-risk populations and advise the \ndevelopment of effective prevention strategies to reduce the \nincidence and morbidity associated with paediatric burns in \nthis region. \n\n\n\nKEYWORDS: \nEpidemiology, paediatric,  burns,  Malaysia,  prevention \n\n\n\nINTRODUCTION \nBurns are a significant cause of mortality and morbidity for \npatients and incur high economic burden on healthcare \nsystems.1 Burn injuries in the paediatric population are \npotentially more severe compared to adults as children have \nseveral physiological disadvantages, such as thinner layers of \n\n\n\nskin, less subcutaneous tissue and a larger surface area to \nvolume ratio, which gives rise to increased risk of rapid \npercentage of fluid loss.2 It is clear that paediatric burns are \nlargely preventable injuries, as various primary prevention \ncampaigns have been effective in reducing the incidence of \nburn-related hospitalisation.3,4 However, the ability to \nformulate an effective campaign requires the availability of \nepidemiological data on the various socio-demographic and \nclinical factors surrounding paediatric burns. \n\n\n\nThrough our literature search, only three small studies \nproduced epidemiological data on paediatric burn patients in \nthe Malaysian setting. Two out of the three papers included \nboth adults and children, with the most recent study on \npaediatric burns being published almost 20 years ago in \n2002.5-7 In addition, the total combined number of patients \n(adults and children) from the three studies only amounted to \n379 patients. More recent data is available in the form of a \nposter presentation, which provided some descriptive \nstatistics on 94 paediatric patients who were admitted into \nthe Malacca Hospital from January 2016 to December 2018.8 \nIt is clear that epidemiological data with larger sample sizes \nare needed to inform burns prevention strategies. \n\n\n\nThis study aims to collect the epidemiological data on the \nclinic-demographic factors of hospitalised paediatric burn \npatients from the main tertiary burns referral centre in the \nSouthern part of Peninsula Malaysia in order to identify the \nparameters associated with the patients. In addition, we aim \nto determine factors associated with poorer outcomes by \nusing prolonged hospitalisation, defined as hospital stay \ngreater than 7 days, as the measurement tool. \n\n\n\nMATERIALS AND METHODS \nThis is a retrospective observational study. Ethical approval \nhas been obtained from the Medical Research Ethics \nCommittee (MREC) of the Malaysian Ministry of Health \n(Approval no: NMRR-19-1111-48223) as well as the Monash \nUniversity Human Research Ethics Committee (MUHREC). All \nchildren less than 12 years of age who were admitted to \nHospital Sultanah Aminah Johor Bahru for burn injuries \nfrom January 2016 to December 2018 were included in this \nstudy. This study excluded burn patients treated in the \nemergency department, outpatient setting and patients with \nmissing medical records. Details on the patients\u2019 socio-\ndemographic background, management measures and \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 02 September 2023\nCorresponding Author: Chuen Xian Low\nEmail: kelvinlcx@gmail.com \n\n\n\nThree-year epidemiology of hospitalised paediatric burn \npatients in a Malaysian Tertiary Hospital 2016 \u2013 2018 \n\n\n\nChuen Xian Low1, Ying Quan Kok1, Xuan Song Loo1, Chin Fang Ngim1, Raymond Zhun Ming Lim2, Soong Yuen \nQuah2\n\n\n\n1Jeffrey Cheah School of Medicine Health Sciences, Monash University Malaysia, Malaysia, 2Sultanah Aminah Hospital, Johor \nBahru, Malaysia (HSAJB), Ministry of Health Malaysia, Malaysia \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 661\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n662                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\noutcomes of each individual burn case, such as demographic \nfactors (age, sex, ethnicity), circumstances surrounding the \ninjury (mechanism of burns, location of burns, provision of \nfirst aid), clinical presentation (extent of burns) and \noutcomes (length of hospitalisation, need for surgical \ndebridement, need for blood product transfusion, need for \nICU admission, wound culture results and mortality) were \nrecorded in the case report forms (CRF).  \n \nSultanah Aminah Hospital is the largest referral hospital in \nthe State of Johor and the main paediatric burn referral \ncentre for patients in the Southern region of Peninsula \nMalaysia. All the patients under 12 years of were managed \nby paediatric surgeons in the general paediatric surgical unit. \nAlthough patients were not routinely screened for methicillin \nresistant staphylococcus aureus (MRSA) or extended \u2013 \nspectrum beta lactamase (ESBL) organisms, those with \nknown MRSA or ESBL organisms were placed under contact \nprecautions. Burn patients generally receive management in \nterms of analgesia, dressings and/or fluid resuscitation. The \ntotal burn surface area (TBSA) was estimated using the Lund \nand Browder chart. Patients with TBSA > 10% are \nautomatically given fluid resuscitation using Parkland \nformula with Hartmann\u2019s solution with a goal to maintain \nend organ perfusion. Adequacy of perfusion and fluid \nresuscitation was monitored via urine output, mean arterial \npressure and occasionally blood gas measurements. \nCommon dressings regimes used at the study centre included \nthe following: silver sulfadiazine, carboxymethylcellulose \n(CMC), Bactigras\u2122, Jelonet\u2122 or Intrasite\u2122.  \n \nWound swabs, blood cultures, blood products administration \nand antibiotics administration were not routinely performed \nunless deemed clinically indicated by the treating consultant \npaediatric surgeon. Wound swabs were performed in \ncircumstances where the burn wounds demonstrated signs of \ninfection, such as pus or persistent slough. Blood cultures \nwere generally done in patients who developed signs of \nsepsis. The local practice was for antibiotics to be prescribed \nin suspected burn wound infections, evidenced by occurrence \nof fever 3 days after the date of injury. The first-line antibiotic \nis intravenous cloxacillin, with intravenous ceftazidime \nand/or amikacin as second-line therapies. In addition, blood \ntransfusions were considered in patients with haemoglobin \nlevels less than 8 g/dL, undergoing debridement procedures \nor were septic. Patients with burns affecting joint areas, \nhands or face, severe extensive burns with TBSA > 10% and \nsecond- or third-degree burns were referred to the plastic \nsurgery unit for review and consideration of split skin \ngrafting. Patients with extensive burns with TBSA > 10% were \nalso referred for dietetics input for high protein formula and \ninpatient dietary modifications. \n \nData was analysed using SPSS\u00ae Statistics 26 (IBM \nCorporation, Armonk, NY). Descriptive statistics were used to \npresent the clinico-demographics of patients. Univariate \nanalyses were carried out to identify possible associations \nbetween factors and eventual outcome of burn patients. \nBinary logistic regression was performed on the factors which \nproduced a significant result to assess the impact of those \nindividual factors on the dependent variable (prolonged \nhospitalisation defined as stay greater than seven days). \nStatistical significance was attained when p <0.05. \n \n\n\n\nRESULTS \nPatients\u2019 Description \nAll of the patients in this study were aged 12 and below. \nRecords from the Burns Registry on the paediatrics surgical \nward showed that a total of 327 patients were admitted \nbetween 2016 to 2018. Despite limitations of a paper-based \nrecord, 80% of the patient records (255 out of 327 patients) \nwere included while others were excluded due to missing \ndata. Descriptive statistics were derived from the 255 patient \nrecords that we have identified, after removing the second \nand third admissions for those with numerous admissions. \nFrom the 255 patients, a further five patients were discharged \nagainst medical advice and 14 patients who were transferred \nin/out to/from other hospitals. After excluding these patients, \na total of 236 patients were included in the association \nanalysis to identify factors associated with prolonged \nhospitalisation to enhance the accuracy of results.  \n \nDescriptive Statistics: Clinico-demographic Factors \nData from a total of 255 patients were analysed. Table I \nshows the statistics for the clinic-demographic factors of the \npatients. \n \nGender, Ethnicity, Age Group and Past Medical \nConditions \nThe majority of burn victims were males (n = 160, 62.7%). \nThe breakdown of burn victims by ethnicity are as follows: \nMalay (n = 212, 83.1%), Chinese (n = 21, 8.2%), Indian (n = \n14, 5.5%), others (n = 8, 3.1%). Burn victims were categorised \ninto four different age groups: Infants < 1 years old (n = 62, \n24.3%); toddlers aged 1 to 2.99 years (n = 110, 43.1%); pre-\nschooler aged 3 to 6.99 years (n = 47, 18.4%) and school \ngoing aged 7 to 12 years (n = 36, 14.1%). Only 12 patients \nwere noted to have pre-existing medical condition(s), which \nincluded Tetralogy of Fallot (n = 1), epilepsy (n = 1), G6PD (n \n= 2), bronchial asthma (n = 3), unspecified congenital heart \ndisease (n = 1), neonatal jaundice (n = 1), drug allergies (n = \n3).  \n \nMechanism of Burns, Location of Burns and Extent of \nBurns \nScalds were the commonest cause of injury (n = 207, 81.5%) \nfollowed by direct flame (n = 27, 10.6%) and contact burns (n \n= 12, 4.7%). The most common description leading to the \nscalding episodes describes the behaviour of the child \nreaching out and pulling onto various objects, such as kettle \nwires, tablecloths or containers with scald agents. Direct \nflame burns usually occurred as a result of accidental child \ncontact with burning rubbish or child\u2019s play with lighter \nand/or petrol. Most of the burns occurred indoors (n = 199, \n86.9%), while the rest of the burns occurred outdoors. The \nextent of burns sustained were divided based on their TBSA \ninto the following groups: TBSA 0 to 10% (n = 189, 75.3%); \nTBSA 10 to 20% (n = 57, 22.7%) and TBSA > 20% (n = 5, 2%). \nThe highest TBSA sustained in a child was 36%. \n \nPatterns of Burns Mechanism in Age Groups \nThis is highlighted in Figure 1. In the infant group, scald \nburns represented 95.2% (n = 59) of burn injuries and contact \nburns represented 4.8% of burn injuries (n = 3). The \npercentage of scald burns remained at 92.7% in the toddler \nage group (n = 101), with direct flame burns at 2.8% (n = 3), \ncontact burns are 2.8% (n = 3) and other burns at 1.7% (n = \n2). In the pre-school age group, scald burns decreased to \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 662\n\n\n\n\n\n\n\n\nThree-year epidemiology of hospitalised paediatric burn patients in a Malaysian Tertiary Hospital 2016 \u2013 2018\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                663 \n\n\n\n68.1% (n = 32), direct flame burns increased to 25.6% (n = \n12), contact burns at 4.2% (n = 2) and other burns at 2.1% (n \n= 1). In the school age children, scald burns decreased to \n41.7% (n = 15), direct flame burns increased to 33.3% (n = \n12), contact burns represented 11.1% (n = 4) and other burns \nrepresented 13.9% (n = 5). \n \nProvision of First Aid \nHalf of the patients who sustained burn injuries did not \nreceive any first aid (n = 114, 50.4%). Only one-third of the \npatients had their injuries under running tap water for a \nvariable duration of time (n = 76, 33.6%). Alternative agents \nused by caregivers included toothpaste, aloe vera, traditional \noil, ointments, soy sauce and cream. One caregiver even \nplaced flour onto the child\u2019s wound, while another used egg \nwhite as first aid. \n \nDescriptive Statistics: Outcomes \nTable II shows the statistics for the various outcomes in our \nstudy population. \n \nDuration of hospitalisation \nThis data was synthesised from a total of 236 patients. The \nmedian length of hospitalisation was 4 days (IQR = 8 days). \nUsing 7 days as a cut-off point, one-third of the patients \nexperienced prolonged hospitalisation (n = 80, 33.6%). \n \nWound cultures \nOut of the 255 patients, wound cultures were done on 48 \npatients. Out of the 48 wound swabs, 24 were positive for \norganisms. There were nine patients who had multiple \norganisms cultured from their wounds.  A total of four \npatients cultured drug-resistant organisms (three cases of \nMRSA, one case of ESBL Escherichia coli) The most common \norganism cultured was Staphylococcus aureus (n = 17). Other \norganisms include: Enterococcus sp (n = 6), Pseudomonas sp (n \n= 3), Streptococcus sp (n = 2), E coli (n = 1), Acinetobacter \nbaumannii (n = 1), Enterobacter sp (n = 1).  \n \nBlood culture \nBlood cultures were done on 38 patients, of which only four \npatients had positive results. Two of the patients who were \nadmitted to ICU had consistent organisms cultured from both \ntheir blood and wound samples. The first patient sustained \nTBSA of 36% and had MRSA cultured; whereas the second \npatient sustained TBSA of 18% and had methicillin-sensitive \nStaphylococcus aureus (MSSA) cultured. The other two patients \nhad the following organisms in the blood culture: \nElizabethkingia meningoseptica in one patient and \ncombination of Micrococcus sp. and Enterococcus sp. in the \nother patient. All the four patients sustained burn injuries \nfrom the scalding mechanism. \n \nWound debridement and blood product transfusions \nApproximately one-fifth of the patients required surgical \nwound debridement (n = 45, 17.6%) whereas only a small \nportion of the patients required blood product transfusion (n \n= 19, 7.5%). \n \nICU admissions and mortality \nA total of eight (3.1%) patients required ICU admission for \nthe following reasons: four due to extensive TBSA > 15%, two \n\n\n\ndue to bacteraemia; one due to corneal abrasion; one due to \nshock requiring central venous line insertion and albumin \ninfusion. The patient who sustained a TBSA of 36% and \nMRSA bacteraemia was the only patient who required \nintubation in our study and was intubated for a total period \nof 18 days. There were no mortalities recorded among the \nsubjects within the study period. \n \nFactors Associated with Prolonged Hospitalisation \nThe main parameter utilised as the indicator of poor outcome \nin this study is prolonged hospitalisation. A Chi-squared test \nfor independence (with Yates\u2019 Continuity Correction) \nindicated that the paediatric burn patients with TBSA > 10% \nare 12.4 times more likely to experience prolonged \nhospitalisation (OR, 12.46 [95% CI 5.96 - 26.05]; p = <0.001). \nIn addition, children aged more than 3 years (pre-schooler \nand school going age children) are 2.4 times more likely to \nexperience prolonged hospitalisation compared to infants \nand toddlers (OR, 2.37 [95% CI 1.34 - 4.19]; p = 0.004). \nPatients with non-scald burns are also associated with 2.4 \ntimes increase in odds of experiencing prolonged \nhospitalisation compared to scald burns (OR, 2.46 [95% CI \n1.24 - 4.89]; p = 0.015). \n \nGiven that scalding was the most common mechanism of \ninjury, our team performed further analysis if there were any \nsignificant differences in outcomes from scalding from \ndifferent types of liquid. The scalding mechanism was divided \ninto two categories: plain water scalds and scalds from other \nliquids (curry, oil, etc). There was no significant association \nbetween type of scald fluids and prolonged hospitalisation \n(OR, 1.00 [95% CI 0.53 - 1.90]; p = 1.000). Other factors such \nas gender and ethnicity were also not significantly associated \nwith increase in risk of prolonged hospitalisation. \n \nDirect logistics regression was performed to assess the impact \nof the individual factors on the likelihood that paediatric \nburn patients would experience prolonged hospitalisation. \nThe model contained three independent variables (age \ngreater than 3, TBSA > 10% and non-scald burns). The full \nmodel containing all predictors was statistically significant (p \n<0.001), indicating that the model was able to distinguish \nbetween those who experience prolonged hospitalisation \nversus those who did not experience prolonged \nhospitalisation. The model as a whole explained between \n24.9% (Cox and Snell R square) and 34.5% (Nagelkerke R \nsquared) of variance in hospitalisation duration, and \ncorrectly classified 78.8% of cases. Only two of the three \nindependent variables made a unique statistically significant \ncontribution to the model (TBSA > 10%, non-scald burns). \nThe strongest predictor of prolonged hospitalisation was \nTBSA > 10% where patients were 13 times more likely to \nexperience prolonged hospitalization than those with TBSA \n10% or less, controlling for all other factors in the model \n(Adjusted OR 13.45 [95% CI 6.25 - 28.96]; p = < 0.001). \nPatients with TBSA > 10% are associated with higher \npercentage of antibiotics use (67.7% vs 20.6%), positive \nwound cultures (58.3% vs 41.7%), bacteraemia (13% vs \n6.7%), blood product transfusions (25.8% vs 1.6%), wound \ndebridement (38.7% vs 10.6%) and ICU admission (12.9% vs \n0%) compared to patients with TBSA 10% or less, as outlined \nin Supplementary Table I. Patients who sustained non-scald \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 663\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n664                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nClinico-demographic factors                                                                                                                               n (%) \nSex                                                                 Male                                                                                            160 (62.7%) \n                                                                      Female                                                                                         95 (37.3%) \nEthnicity                                                        Malay                                                                                          212 (83.1%) \n                                                                      Chinese                                                                                         21 (8.2%) \n                                                                      Indian                                                                                           14 (5.5%) \n                                                                      Others                                                                                            8 (3.1%) \nAge group                                                    Infants (< 1 years old)                                                                62 (24.3%) \n                                                                      Toddlers (1\u20132.99 years old)                                                       110 (43.1%) \n                                                                      Pre-schooler (3\u20136.99 years old)                                                  47 (18.4%) \n                                                                      School going (7\u201312 years old)                                                    36 (14.1%) \nMechanism of burns                                    Scald                                                                                           207 (81.5%) \n                                                                      Direct flames                                                                               27 (10.6%) \n                                                                      Contact                                                                                         12 (4.7%) \n                                                                      Others                                                                                            8 (3.2%) \n                                                                      Missing data                                                                                        1 \nType of scald fluids                                      Plain water                                                                                 133 (64.3%) \n                                                                      Others                                                                                          74 (35.2%) \nLocation of burns                                         Indoors                                                                                       199 (86.9%) \n                                                                      Outdoors                                                                                     30 (13.1%) \n                                                                      Missing data                                                                                       26 \nExtent of burns (TBSA)                                0 \u2013 10%                                                                                      189 (75.3%) \n                                                                      10.1 \u2013 20%                                                                                  57 (22.7%) \n                                                                      > 20%                                                                                             5 (2%) \n                                                                      Missing data                                                                                        4 \nProvision of first aid                                    Not given                                                                                   114 (50.4%) \n                                                                      Running water                                                                            76 (33.6%) \n                                                                      Toothpaste                                                                                   15 (6.6%) \n                                                                      Aloe vera                                                                                       3 (1.3%) \n                                                                      Others                                                                                           18 (7.9%) \n                                                                      Missing data                                                                                       29 \n\n\n\nTable I: Patient characteristics\n\n\n\nOutcomes                                                                                                                                                              n (%) \nDuration of hospitalisation                         Prolonged (> 7 days)                                                                  80 (33.6%) \n                                                                      Not prolonged (\u2264 7 days)                                                          156 (66.4%) \nProvision of antibiotics                                Yes                                                                                               82 (32.2%) \n                                                                      No                                                                                               173 (67.8%) \nResults of wound culture                            No growth                                                                                    24 (9.4%) \n                                                                      Positive                                                                                         24 (9.4%) \n                                                                      Not done                                                                                    207 (81.2%) \nResults of blood culture                              No growth                                                                                   34 (13.3%) \n                                                                      Positive                                                                                          4 (1.6%) \n                                                                      Not done                                                                                    217 (85.1%) \nNeed for wound debridement                    Yes                                                                                               45 (17.6%) \n                                                                      No                                                                                               210 (82.4%) \nNeed for blood products                             Yes                                                                                                19 (7.5%) \n                                                                      No                                                                                               236 (92.5%) \nNeed for ICU admission                               Yes                                                                                                 8 (3.1%) \n                                                                      No                                                                                               247 (96.9%) \nMortality                                                       Alive                                                                                            255 (100%) \n                                                                      Deceased                                                                                         0 (0%)\n\n\n\nTable II: Outcomes of paediatric burn patients between 2016 \u2013 2018\n\n\n\nburns were 2.7 times more likely to experience prolonged \nhospitalisation compared to scald burns (adjusted OR, 2.70 \n[95% CI 1.12 - 6.50]; p = 0.027). \n \n \nDISCUSSION \nThere remains a lack of universal definition on the age cut-\noff point for being considered a child. The cut-off points range \nbetween 9 to 20 years of age. Our study provides data for \npatients aged 12 years and below as this was the criteria for \npaediatrics surgical ward admission for our centre. This cut-\n\n\n\noff point is consistent with studies previously performed in \nthe Southeast Asian region.9-11 \n \nMale children accounted for roughly two-thirds of the overall \nadmission, which can be attributed to their risk-taking \nbehaviour.2 It is not surprising that Malay children accounted \nfor the majority of admissions, as Malays are the ethnic \nmajority in the catchment area. The categorisation of \nchildren into various age groups was based on the child\u2019s \nlevel of education, which age ranges consistent with \nclassification from previous studies to allow ease of data \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 664\n\n\n\n\n\n\n\n\nThree-year epidemiology of hospitalised paediatric burn patients in a Malaysian Tertiary Hospital 2016 \u2013 2018\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                665 \n\n\n\nVariables                                 n (%)             Prolonged hospitalisation              Crude OR                  p                Adjusted OR             p \n                                                                              > 7 days                               (95% CI)                                          (95% CI) \n                                                                       Yes                      No \n\n\n\nGender (N = 236)                                                                                                                                                                                                 \nMales                            146 (62.9%)        51 (34.9%)         95 (65.1%)         1.13 (0.65 \u2013 1.97)          0.775                                                 \nFemales                         90 (38.1%)         29 (32.2%)         61 (67.8%)                    Ref                         -                                                     \n\n\n\nEthnicity (N = 236)                                                                                                                                                                                               \nMalay                           198 (83.9%)        68 (34.3%)        130 (65.7%)        1.13 (0.54 \u2013 2.39)          0.887                                                 \nNon-Malay                    38 (16.1%)         12 (31.6%)         26 (68.4%)                    Ref                         -                                                     \n\n\n\nAge (N = 236)                                                                                                                                                                                                      \n> 3                                 76 (32.2%)         36 (47.4%)         40 (52.6%)         2.37 (1.34 \u2013 4.19)          0.004         1.63 (0.79 \u2013 3.40)      0.189 \n\u2264 3                                 160 (67.8%)        44 (27.5%)        116 (72.5%)                   Ref                         -                                                     \n\n\n\nBurns mechanism  \n(N = 235)                                                                                                                                                                                                              \n\n\n\nNon - scalds                   41 (17.4%)         21 (51.2%)         20 (48.8%)        2.462 (1.24 \u2013 4.89)         0.015         2.70 (1.12 \u2013 6.50)      0.027 \nScalds                            194 (82.6%)        58 (29.9%)        136 (70.1%)                   Ref                         -                                                     \n\n\n\nScald injuries  \n(N = 193)                                                                                                                                                                                                              \n\n\n\nPlain water                   123 (63.7%)        37 (30.1%)         86 (69.9%)         1.00 (0.53 \u2013 1.90)          1.000                                                 \nNon-plain water           70 (36.3%)         21 (30.0%)         49 (70.0%)                    Ref                         -                                                     \n\n\n\nDelayed presentation  \n(N = 156)                                                                                                                                                                                                              \n\n\n\n> 2 hours                       52 (33.3%)         16 (30.8%)         36 (69.2%)         0.77 (0.38 \u2013 1.57)          0.592                                                 \n< 2 hours                      104 (66.7%)        38 (36.5%)         66 (63.5%)                    Ref                         -                                                     \n\n\n\nTBSA (N = 232)                                                                                                                                                                                                     \n> 10%                            52 (22.4%)         40 (76.9%)         12 (23.1%)       12.5 (5.96 \u2013 26 .05)       < 0.001     13.45 (6.25 \u2013 28.96)   <0.001 \n10% or less                  180 (77.6%)        38 (21.1%)        142 (78.9%)                   Ref                         -                                                     \n\n\n\n \n*p values presented are extracted from the Yates Continuity Correction as it is a 2 x 2 table \n \n\n\n\nTable III: Factors associated with prolonged length of hospitalisation\n\n\n\nOutcomes                                                                  TBSA 10% or less, n (%)                                             TBSA > 10%, n (%) \nProvision of antibiotics                                                                                                                                                     \n\n\n\nYes                                                                                   39 (20.6%)                                                                42 (67.7%) \nNo                                                                                   150 (79.4%)                                                               20 (32.3%) \n\n\n\nWound culture                                                                                                                                                                  \nNot done                                                                        165 (87.3%)                                                               38 (61.3%) \nDone                                                                                24 (12.7%)                                                                24 (38.7%) \nPositive                                                                            10 (41.7%)                                                                14 (58.3%) \nNo growth                                                                      14 (58.3%)                                                                10 (41.7%) \n\n\n\nBlood culture                                                                                                                                                                    \nNot done                                                                        174 (92.1%)                                                               39 (62.9%) \nDone                                                                                 15 (7.9%)                                                                 23 (37.1%) \nPositive                                                                              1 (6.7%)                                                                   3 (13.0%) \nNo growth                                                                      14 (93.3%)                                                                20 (87.0%) \n\n\n\nBlood transfusion                                                                                                                                                             \nYes                                                                                     3 (1.6%)                                                                  16 (25.8%) \nNo                                                                                   186 (98.4%)                                                               46 (74.2%) \n\n\n\nWound debridement                                                                                                                                                        \nYes                                                                                   20 (10.6%)                                                                24 (38.7%) \nNo                                                                                   169 (89.4%)                                                               38 (61.3%) \n\n\n\nICU admission                                                                                                                                                                    \nYes                                                                                           -                                                                          8 (12.9%) \nNo                                                                                   189 (100%)                                                                54 (87.1%) \n\n\n\n \n*N = 251 \n \n\n\n\nSupplementary Table I: Extent of burns (TBSA) vs outcomes\n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 665\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n666                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\ncomparison.7,11-13 Our study found that toddlers (aged 1\u20132.99 \nyears) were the most vulnerable age group as they \nrepresented the highest number of admissions.  \n \nVarious data uncovered in this study would be crucial in the \ndevelopment of an effective burn prevention campaign. Our \ndata confirms that scalding remains the main mechanism of \nburns injury among young children, with most injuries \noccurring at home.2,14 This is related to the normal \ndevelopmental stages of the children, as most of them start to \nreach for objects and crawl by the age of 6 months followed \nby becoming fully mobile by the age of 18 months.15 This \ntendency for young children to reach out and pull onto \nobjects that cause scalding episodes are crucial intervention \npoints for injury prevention by caregivers. It is also \ninteresting to note that children become more prone to direct \nflame burns as they approach the school age group. This \ntrend was observed in other studies worldwide and was \nattributed to fires from children\u2019s play.15,16 Drawing upon \npaediatric burn prevention measures employed worldwide, \nexamples of prevention strategies to reduce scald and flame \nburns that are relevant to the local population include short \nradio messages on burns prevention, raising height of \ncooking surfaces, safe storage of flammable substances, \nguarding of open fires and home visits with counselling on \nhome hazards.17 The introduction of \u201cChild Safe Home\u201d \nconcept with online information disseminated in the local \nlanguage may be considered. \n \nIt is also evident that there is a lack of awareness on the \nappropriate provision of first aid for burns as only one-third \n\n\n\nof the children had their wounds under running water post-\ninjury. It is unclear if other alternatives, such as toothpaste, \nsoy sauce and egg white, placed on the wound may \npotentially aggravate or contaminate the wound further \nleading to poorer outcomes. However, numerous studies \nbelow have proven the effectiveness of immediate running \nwater lavage for burn injuries. Large scale data from the New \nSouth Wales Agency for Clinical Innovation State-wide Burn \nInjury Service showed initial treatment with running water \nup to 20 minutes was associated with reduction in burn \nwound depth, wound healing time and graft area \nrequirements.18 The seven-year study in Taiwan on over \n12,000 patients demonstrated proper first aid resulted in a \nreduction in length of stay for burns with TBSA less than \n30%.19 A small study in Nigeria observed that burn patients \nwho received water lavage as first aid had a 50% reduction in \nthe development of complications compared to those who did \nnot received it (35.3% vs 18.4%).20 Overall, this highlights the \nutmost importance of emphasising adequate first aid with at \nleast 20 minutes of running water in any burns prevention \ncampaign. Additional first aid strategies include immediate \nremoval of child from burn source and prevention of \nhypothermia by wrapping unaffected areas of child in clean \ndry blankets prior to arrival of the emergency medical \nservices team.21 \n \nThe majority of the paediatric patients (75.3%) who were \nadmitted had TBSA < 10%. This was consistent with various \nlocal and international data.7,11,12,22,23 Comparing our data \nwith the data presented in 1995 by Ibrahim et al based on a \ntertiary burn referral in the capital city of Kuala Lumpur, \n\n\n\nFig. 1: Patterns of burns mechanism in age groups.\n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 666\n\n\n\n\n\n\n\n\nThree-year epidemiology of hospitalised paediatric burn patients in a Malaysian Tertiary Hospital 2016 \u2013 2018\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                667 \n\n\n\nMalaysia, we found that there is a significant reduction in \nproportion of patients requiring hospitalisation greater than \n7days (33.6% in our study vs 49% in Ibrahim et al\u2019s study). \nThis improvement in outcome is thought to be attributed to \nrecent advancements in management of paediatric burns \nand improvements in healthcare infrastructure throughout \nthe years.24  \n \nOur study also provided some preliminary data on the local \nbacteriological profile of burn wounds in children. S. aureus \nremains the predominant organism cultured from wounds of \nour study patients, which was consistent with data from the \nstudy by Ibrahim et. al.7 This is in contrast to studies in \nTurkey and Iran, where coagulase-negative Staphylococcus \nsp. was shown to be the main organism.23,25 In a study \nconducted in India, Acinetobacter baumannii was presented \nas the main organism cultured from paediatric burn \nwounds.26 This variability in reported organisms suggests that \nbacteriological profiles of pathogens vary between region to \nregion. The trend in adult burn patients is more predictable, \nwith S. aureus and Pseudomonas aeruginosa being the two \nmost common pathogens isolated from overall burn wound \nsamples; whereas Acinetobacter baumannii, MRSA and \nPseudomonas aeruginosa were the common organisms \ncultured from wounds of severe burn victims.27 31 It is unclear \nif this bacteriological trend is similar in paediatric burns. \nHence, the data provided by our study may suggest S. aureus \nas the most common organism implicated in local paediatric \nburn wound infections. However, this remains to be proven in \nfuture studies given that only 48 patients in our study had \nwound swabs sent for cultures and the possibility of S. aureus \nbeing a contaminant rather than an infective organism as it \nis a common skin commensal. \n \nGenerally, the mortality rates in paediatric burn patients are \nrather low worldwide. In Malaysia, Ibrahim et al recorded 1% \nmortality rate in 1995, whereas a 3-year study conducted \nbetween 2016 to 2018 at the Malacca Hospital did not record \nany deaths.7,8 Data from Singapore suggested mortality rates \nof 0.28 to 0.4%, and studies in China and Saudi Arabia \nprovided rates of 0.24% and 0.76% respectively.10,11,13,16 In a \nstudy, which analysed 57 years of paediatric burns data from \na single centre in South Australia, it was found that all the \nchildren with TBSA < 40% survived, whereas those with TBSA \n> 40% had a mortality rate of 34%.32 It is worth noting that \nstudies which included older children up to 18 years of age \nrecorded a higher mortality rate.26 This could be due to older \nchildren having higher risk of sustaining severe burns, \nespecially from flame injuries, where flame injuries were \nobserved to be significant predictors of mortality in numerous \nstudies.33,34 We were unable to provide the accurate mortality \nrate for paediatric burns at our centre as none of our patients \ndied during the course of this study. \n \nTBSA > 10% and non-scald burns are the two strongest \npredictors for prolonged hospitalisation based on data from \nour study. This corresponds to data presented in known \nliterature on the influence of these two factors on other \nmeasures of poor outcomes, such as increased risk of \ninfections and mortality.26,33-37 This information would be \nuseful in guiding clinicians to triage paediatric burn patients\u2019 \npresentations, provide rapid care and close monitoring for \n\n\n\nthose with TBSA > 10% and non-scald burns. Burn depth is \nalso important in the initial assessment process given that \ndeeper wounds carry higher risk of complications and may \nrequire surgical intervention. However, there remains \ninaccuracies in burn depth approximation even in large \nexperienced burn centres.21 Hence, it may be more practical \nfor centres to adopt TBSA measurements in favour of burn \ndepth evaluation to guide initial triaging protocols and \nresuscitative efforts with fluid therapy. \n \nDue to the retrospective nature of our study, there were some \nlimitations such as an inadequate account of additional \nsociodemographic variables (e. g., family size and income \ngroup), clinical data such as burn depth and long-term \ncomplications such as scarring and psychological trauma. As \nthis study was based on hospitalised children, the findings \nmay be less applicable to children with milder burns injuries \ntreated in an outpatient setting. This study was conducted on \nsubject prior to COVID-19 pandemic when there were likely \nchanges to the demographics and management approaches \nadopted by healthcare systems.38,39 Nevertheless, as we \nemerged from the COVID-19 pandemic, the study findings \nare likely relevant to the current post-pandemic population.   \n \n \nCONCLUSIONS \nThe findings mentioned above provide a recent update on the \nepidemiology and outcomes of paediatric burn cases based \non a single tertiary centre in Malaysia in the pre-COVID-19 \nera. Data collected on the demography of paediatric burns \npatients would contribute to the identification of at-risk \npopulations, development of effective prevention strategies \nand inform clinical practice and research in the future.   \n \n \nAUTHOR CONTRIBUTIONS \nC.X.L, R.Z.M.L, S.Y.Q and C.F.N performed the relevant \nliterature search, conceived and designed this retrospective \nstudy. Y.Q.K, X.S.L and C.X.L organised rigorous data \ncollection and critical data analysis. C.X.L, Y.Q.K and X.S.L \nperformed the manuscript writing. R.Z.M.L, S.Y.Q, and C.F.N \nprovided conceptualisation, technical support, and \nproofreading. All authors have read and agreed to all the \ninformation and conclusions in the submitted version of the \nmanuscript. \n \n \nFUNDING \nThis research did not receive any specific grant from funding \nagencies in the public, commercial, or not-for-profit sectors. \n \n \nDISCLAIMER \nThe views expressed in the submitted article are based upon \nthe consensus of all authors and do not necessarily represent \nthe official position of the affiliated institutions. \n \n \nACKNOWLEDGEMENTS \nThe authors would like to thank the Director General of \nHealth Malaysia for permission to publish this paper. The \nauthors would also like to express our gratitude towards the \n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 667\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n668                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nMedical Director of Sultanah Aminah Hospital for his \npermission and support to conduct this research. \n \n \nDECLARATION OF INTERESTS \nThe authors declare that there is no conflict of interest. \n \n \nREFERENCES \n1. Pellatt RA, Williams A, Wright H, Young AE. The cost of a major \n\n\n\npaediatric burn. Burns 2010;36(8): 1208-14. \n2. Alnababtah K, Khan S, Ashford R. Socio-demographic factors \n\n\n\nand the prevalence of burns in children: an overview of the \nliterature. Paediatr Int Child Health 2016; 36(1): 45-51. \n\n\n\n3. Edelman LS. 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Burns \n2020; 46(1): 207-12. \n\n\n\n33. Sharma PN, Bang RL, Al-Fadhli AN, Sharma P, Bang S, Ghoneim \nIE. Paediatric burns in Kuwait: incidence, causes and mortality. \nBurns 2006; 32(1): 104-11. \n\n\n\n34. Purcell LN, Banda W, Akinkuotu A, Phillips M, Hayes-Jordan A, \nCharles A. Characteristics and predictors of mortality in-hospital \nmortality following burn injury in infants in a resource-limited \nsetting. Burns 2021; 48(3): 602 \u2013 607. \n\n\n\n35. Saritas A, Cakir ZG, Ak\u00e7ay MN, Kandis H, Ersunan G, Ozt\u00fcrk G, \net al. Predictors of mortality in childhood burns: an 8-year \nreview. J Child Health Care 2014; 18(1): 84-95. \n\n\n\n36. Rodgers GL, Mortensen J, Fisher MC, Lo A, Cresswell A, Long SS. \nPredictors of infectious complications after burn injuries in \nchildren. Pediatr Infect Dis J 2000; 19(10): 990-5. \n\n\n\n37. Fadeyibi IO, Mustapha IA, Ibrahim NA, Faduyile FI, Faboya MO, \nJewo PI, et al. Characteristics of paediatric burns seen at a \ntertiary centre in a low income country: a five year (2004-2008) \nstudy. Burns 2011; 37(3): 528-34. \n\n\n\n38. Ilenghoven D, Hisham A, Ibrahim S, Mohd Yussof SJ. \nRestructuring burns management during the COVID-19 \npandemic: A Malaysian experience. Burns 2020; 46(5): 1236-9. \n\n\n\n39. Tatar R, Enescu DM. The impact of COVID-19 pandemic on the \nactivity of a pediatric burn center in Bucharest, Romania. Burns \n2020; 46(8): 1977-8. \n\n\n\n\n\n\n\n17-Three-year00134.qxp_3-PRIMARY.qxd  27/09/2023  3:10 PM  Page 668\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                639 \n\n\n\nABSTRACT \nIntroduction: There are insufficient data available regarding \nthe outcome of cardiac arrest (CA) resuscitated in the \nemergency department in Malaysia. This study aims to \ndetermine the incidence of CA, the return of spontaneous \ncirculation (ROSC), survival to admission (STA), survival to \ndischarge (STD) and factors influencing the overall outcome \nof CA. \n \nMaterial and Methods: This is a retrospective observational \nstudy done in Hospital Sg Buloh (HSB), a tertiary referral \ncentre in an urban area located north of Kuala Lumpur, \nMalaysia's capital city, from January until December 2018, \ninvolving 289 patients. All cases with CPR and a sustained \nreturn of spontaneous circulation (ROSC) were included in \nthe study and followed up until discharged or died in the \nhospital. \n \nResults: Out of 236 patients recruited, 25.8% achieved \nROSC, 15.7% survived on admission, and 4.2% of patients \nwere discharged alive. Of 74.1% of witnessed OHCA, only \n17.5% received bystander CPR. Factors with favourable \noutcomes include CA in ED (p<0.001), the initial rhythm of \nventricular fibrillation (p=0.003), defibrillation (p=0.024), \nOHCA witnessed by emergency medical services (EMS) \n(p=0.024) and intravenous adrenaline administration \n(p=0.001). When using multivariate regression analysis, \npositive outcomes were associated with the cardiac and \nrespiratory cause of CA (Adjusted Odd Ratio (AOR) 3.66; \n95% Confidence Intervals, 95%CI: 2.52 - 12.61 and AOR 8.76; \n95%CI: 5.76- 15.46, respectively) as well as OHCA witnessed \nby EMS (AOR 10.81; 95%CI: 1.84- 19.52).  \n \nConclusions: Despite being an upper-middle-income \ncountry and having advancements in the healthcare system, \na relatively lower STD rate among survivors of CA in the ED \nwas observed in this study. There was underutilization of the \nEMS among patients with CA. The bystander CPR rate \namong patients with CA in Malaysia is also worryingly low. \nAggressive community participation in cardiac arrest \nawareness programmes is much required. Additionally, in \nachieving better outcomes, implementing standardized \npost-resuscitation care protocols with existing resources \nwill be a challenge for physicians managing cardiac arrest \ncases.  \n \n \n\n\n\nKEYWORDS:  \nCardiac arrest, Cardiopulmonary resuscitation, Emergency \nDepartment, Survival to discharge, In hospital cardiac arrest, Out \nof hospital cardiac arrest, middle-income country \n \n \nINTRODUCTION \nSince the introduction of modern cardiopulmonary \nresuscitation by Peter Safar in the 1950s, the resuscitation \ntechnique has improved with advanced development and \nprotocols.1 Over the years, with a better understanding of the \nbest practice in resuscitation, many countries have advocated \na standardised approach governed by respective societies and \nassociations. \n \nMalaysia has produced its version of cardiac arrest (CA) \nresuscitation protocol through the National Committee on \nResuscitation Training (NCORT) based on the evidence from \nthe International Liason Committee on Resuscitation \n(ILCOR) since 2006.2 Since then, the hospitals in Malaysia \nhave adopted the NCORT recommendation apart from the \nguidelines from American Heart Association. \n \nThe emergency department in Malaysia has developed \nrapidly, from an admission unit for the in-patient ward 20 \nyears ago to advanced acute medical care provided by \nspecialised doctors and equipped with the latest technologies. \nAs a frontline, advanced critical care provider, \ncardiopulmonary resuscitation (CPR) and subsequent \nmanagement are core elements in emergency department \n(ED). However, despite rigorous training among the \nhealthcare staff on standard CPR and resuscitation \ntechniques, there was no official nationwide registry to assess \nthe outcome of post-cardiac arrest management in the \nemergency department. The PAROS database and many \nother studies concentrate on out-of-hospital cardiac arrest \n(OHCA) and their performances without much emphasis on \nthe ED.3,4 \n \nIn a small sample size study on the East Coast of Malaysia, \nthe rate of return of spontaneous circulation (ROSC) post-CPR \nin the ED is 30.2%.5 This is comparable to a study in China \nby Xue et al. (25.8%) and in Pakistan by Moosajee et al. \n(27.4%).6,7 The survival to discharge (STD) ranges between 5.6 \nto 11% in studies outside Malaysia.5-9 Unfortunately, there is \nno data on STD for post-cardiac arrest in the ED or in-hospital \navailable in Malaysia. \n\n\n\nOutcomes of cardiopulmonary resuscitation in the \nemergency department of a tertiary hospital in Malaysia \n \nMohamad Iqhbal Kunji Mohamad, MMedEM, Mohd Amin Mohd Mokhtar, MmedEM, Mohamad Rodi Bin Isa, \nDrPH, Mohd Fazrul Mokhtar, DrEmMed \n\n\n\n     \nFaculty of Medicine, Universiti Teknologi MARA, UITM Sungai Buloh Campus, Jalan Hospital, Sungai Buloh, Selangor, \nMalaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 23 August 2023                                                                                                                                                                         \nCorresponding Author: Mohamad Iqhbal Bin Kunji Mohamad                                                                                                                                           \nEmail: iqhbal9966@uitm.edu.my\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 639\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n640                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nAmongst the factors affecting the outcome is the initial \nrhythm (shockable vs non-shockable), the aetiology (trauma \nvs non-trauma), witnessed arrest and bystander resuscitation, \nthe age, and the interval between collapse and initiation of \nCPR. 5,7 \n \nAs the nation develops as a model of an upper-middle-\nincome country in Asia, there is an urgent need to assess the \noverall outcome of CA and the factors affecting it in the local \nemergency department. This study aimed to examine this, \nconsisting of out-of-hospital and in-department cardiac \narrests. \n \n \nMATERIALS AND METHODS \nThis is a retrospective study done in Hospital Sg Buloh (HSB), \na 620 bedded tertiary referral centre in an urban area located \nnorth of Kuala Lumpur, Malaysia's capital city. The ED \nreceives nearly 13,000 patients in a month. Consultants and \nspecialists were available 24 hours in the emergency \ndepartment, with 36 beds in yellow, red and observation \nzones. The resuscitation equipment is complete and \nconsidered state-of-the-art. It also encompasses a pre-hospital \nand trauma fellowship training centre for emergency \nphysicians and paramedics. \n \nData were retrieved from the hospital information system \n(HIS) electronic record from January until December 2018. A \ntotal of 289 patients that underwent CPR in ED during the \nstudy period were included. The inclusion criteria consisted of \nall cases of CA in the ED, aged 18 and above. This consists of \nthose whose CA developed in the ED while undergoing \ntreatment and those brought into the ED with active CPR \nongoing. Cases with incomplete data, not-for-active-\nresuscitation (NAR) or existing do-not-resuscitate  (DNR) \nadvance directives and aged less than 18-years-old were \nexcluded from this study. Thus, 236 patients fulfilled the \ninclusion criteria and were included in the study. \n \nThe data collected adhered to the Utstein template, which \nconsisted of core elements of patients variables \n(demographic, comorbidities, initial CA rhythm, location of \ncardiac arrest), pre-event variables (presence of witnessed \ncollapse, presence of bystander CPR), CA variables (initial CA \nrhythm, defibrillation, use of resuscitation medications) and \noutcome variables (return of spontaneous circulation [ROSC], \nsurvival to in-patient admission, and survival to discharge).10 \nThe supplemental elements consisted of the aetiology of \ncardiac arrest. All cases with CPR and a sustained ROSC for \nmore than 30 minutes were considered positive outcomes. \nThose with a sustained ROSC of less than 30 minutes were \nconsidered negative results. The positive outcome was further \ndivided into eventual death in the ED while awaiting transfer \nto the critical care unit or ward, death in the critical care unit \nor ward after admission and those who survived and were \ndischarged alive from the hospital. \n \nEmergency department cardiac arrest (EDCA) was defined as \na CA in the ED. In contrast, OHCA were those with CA \noutside the hospital and brought into the ED with ongoing \nCPR or resuscitation by emergency medical system (EMS) \ntransportation provided by the government (Ministry of \nHealth, Ministry of Education, Ministry of Defense) and \n\n\n\ntrained personnel from Red Cross Malaysia and St John \nAmbulance Malaysia or private ambulances from other \nmodes. \n \nThe CA incidence rate was calculated by dividing that year's \ntotal number of cardiac arrests by the estimated total number \nof ED visits, multiplying by 1000. The estimated total number \nof ED visits is 154,00 \n \nStatistical Package for Social Sciences, version 25.0 (SPSS Inc, \nChicago, IL) was used for data analysis. The descriptive \nstatistics were presented using mean and standard deviation \nfor the numerical variable, whereas the categorical variable \nwas presented using frequency and percentage. The \nnormality of the data was tested statistically using \nKolmogorov-Smirnov Test. The Mann-Whitney U and chi-\nsquare tests were used to assess the p-values for continuous \nand categorical data, respectively. \n \nThe dependent variable was the status of ROSC, divided into \nyes and no ROSC. Patients with ROSC were further divided \ninto discharged alive and died in the ward or the ED. The \nfactors affecting the dependent variable of ROSC were \nanalysed with univariable logistic regression analysis. Crude \nodds ratios (c OR) were reported with 95% confidence \nintervals (95% CI). A manual selection of covariates with a \ncut-off p-value of less than 0.25 were included in the \nmultivariable models. Multivariable stepwise backward \nlogistic regression models were created to control for \nconfounding factors. p-value 0.05 (two-tailed) was set for \nstatistical significance.  \n \n \nRESULTS \nThis study included 236 patients who had CA with CPR in the \nED of HSB in 2018. There were 61 ROSC (25.8%) after CPR. \n83.6% of those with ROSC, or 21.6% of patients who received \nCPR, died in ED or the ward. Only 16.4% of those with ROSC, \nor 4.2% of total CPR, survived and were discharged alive from \nthe hospital. These findings are described in detail in Figure \n1. The incidence of CA, calculated based on yearly ED visits, \nis 1.9 for every 1000 visits.  \n \nThe demographics, clinical and other CPR characteristics of \nthe patient population with stratification by ROSC and no \nROSC were described in Table I. There were more males than \nfemales with CA, with the mean age group equally \ndistributed. The most frequent cause of CA was non-trauma, \nwith the majority being cardiac or presumed cardiac causes. \nMost were OHCA cases compared to EDCA (70.3% vs 29.7%). \nDuring resuscitation, 13.6% had an initial shockable rhythm, \nand 19.5% had defibrillation at least once throughout CPR. \nInterestingly, only 87.3% received intravenous adrenaline. \n \nWhen assessing CPR outcomes, those with CA in ED were \nassociated with ROSC (p < 0.001). A similar significant \nassociation was seen in those with a history of defibrillation \n(p = 0.019) and those who received intravenous adrenaline (p \n= 0.007). There was no association between males and \nfemales and ROSC (p = 0.9). There was also no association \nbetween the mean age for those who attained ROSC and \nthose who did not (p = 0.900). \n \n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 640\n\n\n\n\n\n\n\n\nOutcomes of cardiopulmonary resuscitation in the emergency department of a tertiary hospital in Malaysia\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                641 \n\n\n\nAssessing for predictors of ROSC using a multivariate logistic \nregression model, the non-trauma cause, specifically cardiac \n(aOR 3.66; 95%CI: 2.52 12.61), respiratory cause of CA (aOR \n8.76; 95%CI: 5.76 15.46) and OHCA initial arrest witnessed \nby EMS (aOR 10.81; 95%CI: 1.84 19.52) has a better chance \nof survival compared to other factors (Table II). \n \n \nDISCUSSION \nIn this study, the incidence of CA is comparable with the UK \nNational Cardiac Arrest Audit data of 1.6 for every 1000 in-\nhospital patients.11 The percentage of CA patients receiving \nCPR attaining ROSC in the ED is lower than the study by \nChew et al. (30.2%) but almost similar to other studies by Xue \net al. (25.8%) and Moosajee et al. (27.4%). However, only \n4.2% of cases attained STD, lower than other studies in this \nregion, where the STD ranges from 5.6 to 11%, but is similar \nto the cardiac arrest survivor rate in an ED in Brazil.5\u20139,12 \n \nA crucial data that needs further research is the mean age of \npatients with CA in this study, which is 51.3 years, contrasted \nwith other studies of 66 years in the US and Brazil and 73.9 \nyears in the UK.12\u201314 A similar pattern of the high rate of \n\n\n\nnatural deaths at 41-50 years was also reported in an autopsy \nstudy in Kuala Lumpur in 2007, but not much has been \nexplored further ever since.15 This might be linked to the \nyounger age group in Malaysia diagnosed with coronary \nartery disease as reported in the National Cardiovascular \nDisease Database Registry and a study on East Coast.16,17 \n\n\n\nNevertheless there is need for further research on this, as it \nseems in paradox with the national aim of achieving high \nincome nation.18,19 \n \nThe ROSC rate was significantly better in EDCA compared to \nOHCA, with 1 ROSC for every 2 EDCA vs 1 ROSC for every 6 \nOHCA. The ratio for survival to discharge is also markedly \nbetter in EDCA (1:10 vs 1:55). The 10% rate of STD within \nEDCA is similar to studies conducted on in-hospital CA in \nJapan but lower than rates reported in the US and UK.14-16 \n\n\n\nHowever, there is no available local data for comparison. \nFactors such as pre-hospital response time, early \ndefibrillation, witnessed CPR and bystander CPR could have \ncontributed to the better overall EDCA CPR outcome.20  \n \nAs for OHCA, it is essential to examine the factors affecting \nthis cohort since they comprise of the largest group. Only \n\n\n\n                                                                                                                                   Outcome \n                                                   No ROSC                                                                  ROSC                                                      p value \n                                                     (n=175)                  Discharged alive               Died in ward            Died in ED \n                                                                                             (n=10)                              (n=37)                     (n=14) \n\n\n\nRace: \nMalay                                        101 (57.7%)                     6 (60.0%)                       25 (67.6%)               9 (64.3%)                   0.812** \nChinese                                      20 (11.4%)                      2 (20.0%)                        5 (13.5%)                2 (14.3%) \nIndian                                        37 (21.1%)                      2 (20.0%)                        5 (13.5%)                 1 (7.1%) \nOthers                                         17 (9.7%)                        0 (0.0%)                          2 (5.4%)                 2 (14.3%) \n\n\n\nGender: \nMale                                          122 (69.7%)                     6 (60.0%)                       25 (67.6%)               9 (64.3%)                   0.900** \nFemale                                       53 (30.3%)                      4 (40.0%)                       12 (32.4%)               5 (35.7%) \n\n\n\nAge: \nMean (SD)                               51.39 \u00b1 15.86                50.40 \u00b1 13.45                  53.68 \u00b1 15.37          52.21 \u00b1 12.64                 0.858# \nRange                                            18 - 85                           29 - 79                             22 - 80                     21 - 69 \n\n\n\nComorbidities: \nLess than 3                                59 (61.5%)                      4 (57.1%)                       12 (46.2%)               8 (72.7%)                   0.410** \n3 and more                                37 (38.5%)                      3 (42.9%)                       14 (53.8%)               3 (27.3%) \n\n\n\nInitial rhythm during  \ncardiac arrest: \nArrest location \n\n\n\nED                                              36 (20.6%)                      7 (70.0%)                       17 (45.9%)              10 (71.4%)                  <0.001* \nOHCA                                        139 (79.4%)                     3 (30.0%)                       20 (54.1%)               4 (28.6%) \n\n\n\nAny witness (OHCA)?  \n(n = 166) \n\n\n\nYes                                            103 (74.1%)                     2 (66.7%)                       18 (90.0%)              4 (100.0%)                  0.277** \nNo                                              36 (25.9%)                      1 (33.3%)                        2 (10.0%)                 0 (0.0%) \n\n\n\nWho witnesses the arrest?  \n(OHCA)(n = 127) \n\n\n\nFamily                                        74 (71.8%)                     2 (100.0%)                      10 955.6%)              2 (50.0%)                   0.138** \nEMS                                            15 (14.6%)                       0 (0.0%)                         7 (38.9%)                2 (50.0%) \nLayperson                                  14 (13.6%)                       0 (0.0%)                          1 (5.6%)                  0 (0.0%) \n\n\n\nBystander CPR performed  \nfor OHCA? (n = 72) \n\n\n\nEMS                                            44 (61.1%)                       0 (0.0%)                        9 (100.0%)              2 (100.0%)                    0.083 \nNon EMS                                   28 (38.8 %)                    1 (100.0%)                        0 (0.0%)                  0 (0.0%) \n\n\n\n \n*Chi-Square, **Fisher Exact test, #NOVA \nROSC, Return of spontaneous circulation; ED ,Emergency Department ; SD ,Standard Deviation;PEA, Pulseless Electrical Activities ;VF , Ventricular Fibrillation \n; VT, \nVentricular Tachycardia ; OHCA ,Out of hospital cardiac arrest ;CPR ,cardiopulmonary resuscitation;EMS ,Emergency medical services; CA \u2013 Cardiac arrest\n\n\n\nTable I:\u2008Characteristics of patients with cardiac arrest (CA) with or without return of spontaneous circulation (ROSC)\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 641\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n642                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n17.5% of OHCA received bystander CPR by non-EMS, which \nis at the lower end of the range 10.6 - 41.6% in other Pan \nAsian countries and much lower than 47.4% in Europe.3,21 \nThis might be attributed to the low willingness to perform \nCPR, as portrayed by a study on college students in Malaysia \nby Karuthan et al., which stated that respondents were not \nwilling to perform hands-only CPR due to limited knowledge \nof CPR.22 Additionally, there might be concerns about legal \nliability and lack of confidence while performing CPR.23 As \nbystander CPR is the most amenable factor in improving the \noutcome of OHCA, there is an urgent need for public \neducation on the importance and technique of CPR.24 \n \nMost cases were non-shockable as the initial documented \nrhythm was asystole and PEA compared to VF and VT. This is \nnot much different from the studies on non-shockable \nrhythms in the East Coast of Malaysia (84%), the US (76 \u2013 \n81%%) and Taiwan (87.4%).5,13,25,26 \n \n \n\n\n\nThe low adrenaline administration rate is surprising as it is \none of the core drugs and the standard management for all \ncardiac arrests. However, it is comparable to a study done in \nSweden.27 Perhaps a local study needs to be done to analyse \ncompliance with all the standard cardiac arrest management \nand the factors affecting it.  \n \nRegarding the low rate of STD after ROSC, there might be a \nneed for improvisation of care after cardiac arrest. The lack of \nstandard protocolised post-cardiac-arrest management, as \nrecommended by the American Heart Association in the \nchain of survival, mainly due to limited resources, might be \none of the reasons for the low STD. The paramount issue in \nMalaysia\u2019s ED, i.e., the lack of acute beds and ED \nlongboarding, might also hamper the ideal post-resuscitation \ncare protocols.28 \n \nAs this is a small study, we included and analysed the \ntrauma and non-trauma cohorts together, as were the studies \ndone in Sweden, the UK and Japan.11,29,30 Future studies shall \n\n\n\nVariables                                                                                                          ROSC achieved                     \n                                                                                  p value                         OR (95%CI)                  p value              Adj. OR (95%CI) \n\n\n\nRace: \nMalay                                                                          0.374                       1.68 (0.53, 5.31) \nChinese                                                                       0.344                       1.91 (0.50, 7.33) \nIndian                                                                         0.901                       0.92 (0.24, 3.47) \nOthers                                                                          Ref                                   Ref                                                                    \n\n\n\nGender: \nMale                                                                            0.549                       1.21 (0.65, 2.24) \nFemale                                                                          Ref                                   Ref                                                                    \n\n\n\nAge \n52 and above                                                             0.943                       0.98 (0.55, 1.75) \nLess than 52                                                                 Ref                                   Ref                                                                    \n\n\n\nComorbidities (n = 192): \n0                                                                                    Ref                                     1 \n1\u20133                                                                             0.008*                      2.90 (1.32, 6.36) \nMore then 3                                                               0.216                       1.96 (0.68, 5.69)                      \n\n\n\nInitial rhythm during cardiac arrest: \nAsystole                                                                        Ref                                   Ref \nPEA                                                                             0.067                       2.10 (0.95, 4.66) \nVF                                                                               0.003*                      3.86 (1.60, 9.32) \nVT                                                                                0.764                       1.29 (0.25, 6.65)                                                         \n\n\n\nDefibrillation performed: \nYes                                                                             0.024*                      2.20 (1.11, 4.35) \nNo                                                                                 Ref                                   Ref                                                                    \n\n\n\nNon-trauma cause of CA (n = 191): \nCardiac or presume cardiac                                    <0.001*                     4.24 (2.02, 8.92)                 0.003                 3.66(2.52,12.61)  \nRespiratory                                                                0.001*                     5.59 (1.98, 15.79)                0.001                 8.76 (5.76,15.46) \nOthers                                                                          Ref                                   Ref                             Ref                              Ref \n\n\n\nArrest location: \nED                                                                             < 0.001*                    4.86 (2.61, 9.08)                      \nOHCA                                                                           Ref                                   Ref                                                                    \n\n\n\nAny witness? (n = 169) (OHCA) \nYes                                                                              0.109                       2.80 (0.79, 9.84) \nNo                                                                                 Ref                                   Ref                                                                    \n\n\n\nWho witnessed the arrest? (n = 127) (OHCA \nFamily                                                                           Ref                                   Ref                             Ref                              Ref \nEMS                                                                            0.024*                      3.17 (1.16, 8.66)                 0.008                10.81(1.84,19.52) \nLayperson                                                                   0.365                       0.38 (0.05, 3.11)                 0.227                 8.02(0.27,23.24) \n\n\n\n \nMultivariate analysis was done with the backward method, model fits well (Hosmer & Lemeshow test), Cox & Snell R2 = 0.314 \nROSC, Return of spontaneous circulation; ED, Emergency Department ; SD ,Standard Deviation;PEA, Pulseless Electrical Activities ;VF , Ventricular Fibrillation \n; VT, Ventricular Tachycardia ; OHCA ,Out of hospital cardiac arrest ;CPR ,cardiopulmonary resuscitation;EMS ,Emergency  medical  services; CA \u2013 Cardiac \narrest; OR , Odds ratio, Adj OR , Adjusted odds ratio. \n \n\n\n\nTable II: Univariate and multivariate analysis related to the return of spontaneous circulation (ROSC)  \namong cardiac arrest patients in ED\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 642\n\n\n\n\n\n\n\n\nOutcomes of cardiopulmonary resuscitation in the emergency department of a tertiary hospital in Malaysia\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                643 \n\n\n\nfocus on examining each cohort separately with longer study \nperiods and larger sample sizes to gain a better \nunderstanding. The majority of CA is caused by non-\ntraumatic events, with 26.9% ROSC and 4.8% STD, whereas \nfor trauma cases, 17% ROSC and none with STD. In contrast, \nthe STD for post-traumatic CA in the PROPHET and Epistry \nTrauma registries is 6.8%.31 This result is despite the study \nhospital being a trauma centre with the necessary \nsubspecialist care available.  \n \nWith univariable logistic regression analysis, CA in ED, VF as \nfirst rhythm, history of defibrillation, EMS attended CA and \nIV adrenaline administration were associated with a better \nchance of attaining ROSC. These findings are consistent with \nprevious studies in the literature.6,7,32\u201334  \n \nThrough multivariate analysis, independent predictors for \nROSC were cardiac and respiratory causes of CA, and EMS \nattended CA. Due to the small number of STDs, we chose not \nto perform the multivariate analysis as the result might not \nbe accurate. \n\n\n\nLooking at it from a different perspective, during our \nresearch, we discovered that the main challenge we faced in \ngathering the data was the insufficient information recorded. \nWhilst the Utstein template was introduced in 1990 and \nrevised in 2004, it was never widely adopted in Malaysia.10 \nThe variables, consisting of the patient variables, the hospital \nvariables, the CA variables, and the outcome variables would \nbe comprehensive for documentation and data retrieval \npurposes. Unfortunately, from our observation, until this \narticle was written, there was no standard way of \ndocumenting a CA event, even within a single centre. This is \nthe major reason for the variance in term definitions and the \nmissing important data, including the details during the CA \nand the long-term neurological outcomes. Since this study is \nretrospective, we made every effort to maintain the accuracy \nof the data by adhering to the template. Future registry \nimplementation based on this template will produce robust \nresearch comparisons between nations. For that, official \npolicy and continuous administrative support is needed.  \n \n \n\n\n\nFig. 1: Outcome of cardiopulmonary resuscitation of patients with cardiac arrest in the emergency department. \n \n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 643\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n644                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nAlthough the research has reached its primary aims, there \nwere unavoidable limitations. Our study was performed \nretrospectively in a single tertiary centre for a year. The data \ncollected were limited based on the above reasoning. As more \nhospitals in Malaysia are not tertiary, the result should not be \ngeneralised. Hence, our results should be interpreted \ncautiously. We were also unable to ascertain the factors \ninfluencing the survival to discharge after the patients left the \nED resuscitation area; thus, the patient's actual survival and \nneurological status were not captured. \n \nThere is a need to create a cardiac arrest registry in Malaysia. \nThe ROSC and STD rate will directly imply the quality of the \nhealthcare system and the gap to be addressed. The \nAmerican Heart Association\u2019s Get With The Guidelines- \nResuscitation (GWTG-R) registry and the Danish In-Hospital \nCardiac Arrest Registry (DANARREST) can be emulated to be \nimplemented in Malaysia.35 \n\n\n\n \n \nCONCLUSION  \nDespite being an upper-middle-income country and having \nadvancements in the healthcare system, a relatively lower \nSTD rate among survivors of CA in the ED was observed in \nthis study. There was underutilization of the EMS among \npatients with CA. The bystander CPR rate among patients \nwith CA in Malaysia is also worryingly low. Aggressive \ncommunity participation in cardiac arrest awareness \nprogrammes is much required. Additionally, in achieving \nbetter outcomes, implementing standardized post-\nresuscitation care protocols with existing resources will be a \nchallenge for physicians managing cardiac arrest cases.  \n \n \nACKNOWLEDGMENT \nThe authors would like to thank the Director-General of \nHealth Malaysia for his permission to publish this article. \n \n \nDECLARATION \nThis study was approved by the Malaysian Research Ethics \nCommittee (MREC) (NMRR-19-1766-47833) and Universiti \nTeknologi MARA (UiTM) Research Ethics Committee \n(REC/334/19). All methods were performed according to the \nICH Good Clinical Practice Guidelines, Malaysia Good \nClinical Practice Guidelines and the Declaration of Helsinki. \n \n \nREFERENCES \n1. Oransky I. Peter Safar. 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The Danish in-hospital cardiac arrest registry \n(DANARREST). Clin Epidemiol 2019; 11: 397-402.  \n\n\n\n\n\n\n\n14-Outcomes00100.qxp_3-PRIMARY.qxd  25/09/2023  4:27 PM  Page 645\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\n\n\n\n\nABOUT KMI HEALTHCARE                                                                                                      \n\n\n\nKumpulan Medic Iman (KMI Healthcare) is a subsidiary of TDM Berhad business division focusing on healthcare which \nmanages and owns five specialist hospitals in Malaysia since the establishment in 2013. \n\n\n\nEnvisioned to become the \u201cTRUSTED HEALTHCARE PROVIDER OF CHOICE\u201d, we are dedicated towards deeper \nunderstanding the needs of our patients in order to provide quality healthcare services within the living and working \nenvironments of the community. For further details, please visit our website www.kmihealthcare.com . \n\n\n\nKMI Tawau Medical Centre \n\n\n\n\n\n\n\nKMI Tawau Medical Centre, is the first purpose-built boutique private hospital in Tawau owned by Kumpulan Medic \n\n\n\nIman Sdn Bhd. It is situated in the second largest town in Sabah and located in a prominent area that is also the gateway \n\n\n\nfor Indonesians to the east coast of Sabah, the Northern part of Kalimantan. The hospital aims to provide patients with \n\n\n\ncomprehensive outpatient and inpatient healthcare services, supported by a group of dedicated nurses and healthcare \n\n\n\npersonnel.  \n \n\n\n\nAs part of its business expansion, we would like to invite qualified Medical Consultants in the following disciplines : \n\n\n\n\u2022 Obstetrician & Gynaecologist \n\n\n\n\u2022 Internal Medicine Physician \n\n\n\n\u2022 General Surgeon \n\n\n\n\u2022 Orthopaedic Surgeon \n\n\n\n\u2022 Radiologist \n\n\n\n\u2022 Medical Officer \n \n\n\n\nJoin us and build a professional career in the healthcare industry and strive in making people\u2019s life meaningful.  All \napplicants will be treated as private and confidential.  \n\n\n\n \nPotential applicants may email your CV/resume and related documents to hrkmitawau@tdmberhad.com.my \n\n\n\nKindly contact us for details :            \n\n\n\nHuman Resource Department  \n\n\n\nKMI Tawau Medical Centre  \n\n\n\nTB 4551, Jalan Abaca, Bandar Tawau      \n\n\n\n91000 Tawau, Sabah             \n\n\n\nTel : +6089-771873 | Fax : +6089-779785 \n\n\n\n\n\n\n\nOur Hospitals :  \n\n\n\nKMI Kuala Terengganu Medical Centre           KMI Taman Desa Medical Centre   \n\n\n\nKMI Kuantan Medical Centre                           KMI Kelana Jaya Medical Centre \n\n\n\n \n\n\n\n\nhttp://www.kmihealthcare.com/\n\n\n\n\n\n\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\n566                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction: The prevalence of cerebral palsy (CP) in \nMalaysia is estimated at 2.6 per 1000 live births which is \ncomparable to that of Australian and European data with \nranges of 2.3- 4.21,2. Surgical intervention for the \nimprovement of gait function and mobility in CP is a \ncommon practice, however scarce literature of its outcomes \nis available in Southeast Asia. This paper aims to address \nand compare outcomes of surgical interventions in our \ncentre with other countries. \n \nMaterial and Methods: Patients with Spastic CP with Gross \nMotor Function Classification System (GMFCS) I-III that \nunderwent lower limb surgical intervention in our centre \nfrom 2008-2018 were retrospectively reviewed for The Spinal \nAlignment and Range of Motion Measure ROM subscale \n(SAROMM) scores and Functional Mobility Scale (FMS) 18 \nmonths after surgery. Changes in SAROMM, FMS scores and \nminimal clinically important difference (MCID) were \ndetermined.  \n \nResults: 19 patients were included in the study with mean \nage of 12.58. All patients underwent muscle tendon \nprocedures. Box plot analysis of SAROMM showed \nreduction of median scores at 6(26.3%) and 12(47.4%) \nmonths which plateaus at 18 months post-surgery. Repeated \nmeasure ANOVA analysis showed there was a statistically \nsignificant effect of time on SAROMM scores (p <0.001) with \nMCID of 13.4. Improvement of FMS scores was the most at \n50m with 13 children (p < 0.05), one at 5m and five at 500m. \nNone reported worsening of FMS scores at 18 months. There \nwere no changes of GMFCS levels by the end of 18 months. \n \nConclusion:\u2008Surgeries performed on GMFCS I-III patients \nwith the aim of gait improvement translates into improved \nmobility with results comparable to other countries. \n \nKEYWORDS:  \nCerebral palsy, SAROMM, Functional Mobility Scale, Contracture \nrelease \n \n \n\n\n\nINTRODUCTION \nCerebral palsy (CP) is an umbrella term to describe a group \nof disorders characterised my abnormalities of movement \nand posture, causing activity limitation due to a non-\nprogressive brain damage during early development. Even \nthough CP is a static encephalopathy, the musculoskeletal \npathology is progressive leading to secondary deformities of \nbones and joints with loss of function and deterioration of \ntheir walking pattern.  \n \nThere are currently no cure or treatment for the brain \ndamage suffered by CP patients which causes the complex \nmusculoskeletal dysfunctions. Physical therapy, medical and \nneurosurgical interventions serve to reduce and regulate the \nhypertonia while orthopaedic interventions aim to restore \nanatomical structures in an attempt to preserve the walking \nfunction as well as patients\u2019 activity level and therefore their \nquality of life.3 Appropriate holistic care of children with CP \nrequires myriad of disciplines to improve their long-term care \nconsidering their medical and social aspects as well as their \nrehabilitation, education, and assistance.4  \n \nSurgical intervention aims to improve gait, increase mobility \nand treat hip subluxation or dislocations. In a randomised \ncontrol trial of surgery vs conservative treatment of CP \npatients by Thomason et al in 2011, the authors discovered \nthat surgery improved the gait after one year of follow up \nwith good quality of life and functional mobility observed at \n2 years of follow up.5 These findings were further \nsubstantiated by Firth et al., Feger et al., and Chang et al., \nwith outcomes showing surgical intervention to be superior to \nconservative treatment of CP in the long run.6\u20138  \n\n\n\n \n \nMATERIALS AND METHODS \nThis study is a medical record review of 32 children with \nspastic CP that underwent orthopaedic surgical intervention \nbetween 2008-2018 at a tertiary referral university hospital \nfor sub-specialised orthopaedic care. Nineteen patients were \nincluded in the study based on our inclusion criteria which \nincluded a diagnosis of Spastic CP of GMFCS I-III and \ncompleted 18 months of follow up. Patients that are more \n\n\n\nWalking further. How surgery can help the cerebral palsy \nchild \n \nSyed Azhariff (Dr Ortho & Trauma)1, Rashidah Ismail (MRehabMed)2, Manimalar Selvi Naicker \n(MPath,MMedStat)3, Abd Halim Rashid (MS Ortho)4, Brenda Saria Yuliawiratman (MRehabMed)5,6, \nAmaramalar Selvi Naicker (MRehabMed)2 \n\n\n\n     \n1Department of Orthopaedics & Traumatology, Hospital Tuanku Ampuan Najihah, Kuala Pilah Negeri Sembilan, Malaysia, \n2Department of Orthopaedics & Traumatology, Rehabilitation Medicine Unit, Pusat Perubatan Universiti Kebangsaan Malaysia, \nKuala Lumpur Malaysia, 3Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur Malaysia, \n4Department of Orthopaedics & Traumatology, Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur Malaysia, \n5IHT Rehabilitation Centre, Persiaran SILC, Kawasan Perindustrian SILC, lskandar Puteri, Johor, Malaysia, 6VAMED Healthcare \nServices, Menara Tan & Tan, Kuala Lumpur, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 30 June 2023                                                                                                                                                                             \nCorresponding Author: Syed Azhariff                                                                                                                                                                                  \nEmail: syedazhariff@gmail.com\n\n\n\n2-Walking00217.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 566\n\n\n\n\n\n\n\n\nWalking further. How surgery can help the cerebral palsy child\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                567 \n\n\n\nthan 18 years old at time of surgery, history of dorsal \nrhizotomy or intrathecal baclofen surgery were excluded \nfrom the study.  \n \nSurgery was done by three surgeons throughout the 10 years \nwho are experienced in performing these surgeries with \nexperience of 5-20 years between them. The surgical \nindications included gait dysfunction, restricted knee \nextension and flexion, inability to achieve neutral ankle \nposition. 5\u20137,9  \n \nPatients were assessed preoperatively by a multidiscipline \nteam of neuropaediatrician, rehabilitation physician and \npaediatric orthopaedic surgeon prior to decision for surgery \nas well as determination of surgical level and method.  \n \nAdductor release of adductor longus and gracilis were done as \ndescribed by Shore et al.10 Hamstring release involves the \nfractional lengthening of the semitendinosus and \nsemimembranosus. If the increment of popliteal angle \nachieved is <20\u00b0 then biceps femoris is also released.11 \nSurgical correction of equinous deformity includes \ngastrocsoleus recession and triple hemisection of Achilles \ntendon. Both procedures involve the identification of the \nmuscle belly and Achilles tendon with subsequent \nlengthening as described by Firth et al and Takahashi et al.6,12 \nAll patients were kept on casts for two weeks after surgery \nwhich is then continued for 6 weeks total after wound \ninspection. They are then changed to orthoses throughout \ntheir rehabilitation period and follow up.  \n \nOutcome data collected were changes in Gross Motor \nFunction Classification System (GMFCS) levels13 ,  Functional \nMobility Scale (FMS)14 and Spinal Alignment and Range of \nMotion Measure Range of Motion subscale (SAROMM).15 \nStatistical analysis of data collected were analysed using SPSS \nversion 24. Repeated measure ANOVA test was used to \nevaluate the statistical significance of score changes at 18 \nmonths and pre surgical intervention scores.  \n \n \nRESULTS \nNineteen children were included in the study with age \nranging from 5-18 years old (mean=12.58). Nine male and 10 \nfemale children were enrolled. There were five GMFCS I, \nseven GMFCS II, and seven GMFCS III.  Fifteen patients \nunderwent single level surgery, while 4 patients underwent \nsurgery of at least 2 levels. In total 27 lower limbs underwent \nsurgical intervention. All patients underwent muscle tendon \nprocedures (Table I).  \n \nThere were no post-surgical intervention complications such \nas haemorrhage, surgical site infection. Box plot analysis of \nSAROMM showed reduction of median scores at 6 months \nand 12 months which then plateaus at 18 months (Figure 1). \nRepeated measure ANOVA analysis showed there was a \nstatistically significant effect of time on SAROMM scores with \nmean change of 13.4 (p < 0.001, Standard Deviation, SD = \n8.7) at 18 months after surgery.   \n \nThe FMS scores at 18 months post-surgery were compared \nwith their baseline for the distance of 5m, 50m, 500m. \n\n\n\nImprovement of FMS scores was the most at 50m with 13 \nchildren (p < 0.05), one at 5m and five at 500m (Table II). \nNone reported worsening of FMS scores at 18 months. There \nwere no changes of GMFCS levels by the end of 18 months. \n \n \nDISCUSSION \nThe purpose of this study was to assess the impact of \northopaedic surgical intervention on children with cerebral \npalsy. In addition to measuring the range of motion of their \njoints, we also evaluated changes in their mobility, aiming to \ndetermine whether surgical intervention and concurrent \nphysical therapy had a meaningful impact on the quality of \nlife on these children. \n \nThe role of surgical intervention for children with cerebral \npalsy is to improve function and decrease discomfort with the \nassumption that by gait improvement, the general function \nof the patient will improve.16 The SAROMM which has fair to \ngood construct validity was used to detect change in ROM \nfrom baseline and follow up.17 In addition, to determine if \nchange in score is clinically relevant, the minimal clinically \nimportant difference (MCID) is also determined. The results \ngarnered from our study shows that there is a mean change \nin score of 13.4 which is more than the MCID reported by \nChen et al., of 4.07.17 Thus, surgical intervention improves the \nROM of contracted joints within 12 months to be of clinical \nsignificance.  \n \nImprovement in SAROMM scores peaks by 12 months and is \nthe same at 18 months. indicating that after surgical \nintervention, the maximal improvement of ROM is seen by \n12 months and is preserved at 18 months. Apart from this, \nthere were no cases of recurrence detected within the 18 \nmonths period of follow up. However, recurrence of \ncontractures, maintenance of functional levels or functional \ndecline may not be apparent within the short period of follow \nup as it may require at least 5 years of follow up and up to \nearly adulthood to detect recurrence and fully evaluate the \nresults of contracture release.18 \n \nThe mobility and ROM gains observed among CP children \nare not due to surgery alone and is in synchrony with \nphysical therapy. Surgical intervention must be combined \nwith an intensive post-operative rehabilitation programme \nindividually catered and performed under the guidance of \nexperienced physical therapists to maximise functional \nimprovement.5 However, in our setting, the postsurgical \nintervention physical therapy was not strictly controlled and \nthe changes in physical therapy may have been confounded \nsimilar to Chang et al.8 Couple this with inadequacy of \nrecords of therapy sessions, the impact of physical therapy on \nambulatory gains are difficult to assess.  \n \nTo our knowledge, this is the first study in our region to look \nat outcomes of surgical intervention and rehabilitation \nobjectively among CP children. The results achieved are \nsimilar to other studies in improvements of ROM and \nfunctional mobility. The study is limited by its small sample \nsize despite a review of 10 years. This may be due to lack of \nawareness and how misunderstood CP is among Malaysians. \nWe also postulate that parents are reluctant to subject their \n\n\n\n2-Walking00217.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 567\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n568                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nAge                Gender                       GMFCS                   Limb involvement                    Level involvement                         Procedure \n\n\n\n5                     Female                            III                                Bilateral                                        Knee                                           HR \n5                       Male                               I                                     Left                                           Ankle                                          GR \n8                       Male                              II                                     Left                                           Ankle                                     PR + TAL \n9                     Female                            III                                Bilateral                                        Ankle                                          GR \n11                     Male                              III                                Bilateral                                        Knee                                           HR \n11                     Male                               I                                     Left                                           Ankle                                          GR \n12                   Female                            II                                     Left                                            Knee                                           HR \n13                   Female                            III                                Bilateral                                   Hip + Knee                                 HR + TAL \n13                   Female                            II                                     Left                                     Knee + Ankle                               HR + TAL \n14                   Female                            III                                Bilateral                                        Knee                                           HR \n14                   Female                            II                                   Right                                           Knee                                           HR \n14                     Male                              II                                   Right                                    Knee + Ankle                               HR + TAL \n14                   Female                            III                                Bilateral                                        Ankle                                          TAL \n15                     Male                               I                                     Left                                           Ankle                                          GR \n15                   Female                            II                                 Bilateral                                        Ankle                                          TAL \n15                     Male                               I                                    Right                                          Ankle                                          TAL \n16                     Male                               I                                    Right                                    Knee + Ankle                               HR + TAL \n17                     Male                              II                                   Right                                          Ankle                                          GR \n18                   Female                            III                                Bilateral                                        Knee                                           HR \n \n*HR = Hamstring release, GR = Gastrocsoleus recession, PR = Plantar release, TAL = Tendon Achilles lengthening, AR = Adductor release \n\n\n\nTable I: Summary of patients\n\n\n\n                                                          5M                                               50M                                                500M \n                                                     (p value)                                               \nN                                                         1                                                  13                                                     5 \n                                                       (0.351)                                          (0.027)                                             (0.351) \nGMFCS I                                              1                                                   3                                                      2 \nGMFCS II                                             0                                                   4                                                      3                                \nGMFCS III                                            0                                                   6                                                      0 \nMean                                                4.74                                              4.32                                                 3.89 \nSD                                                     1.66                                              1.73                                                 2.13 \n \nGMFCS = Gross Motor Function Classification System \nSD= standard deviation  \n\n\n\nTable II: FMS score improvement at 5m, 50m, 500m at 18 months compared to pre-surgery\n\n\n\nFig. 1: Boxplot analysis of SAROMM showing reduction of median scores at 6 & 12 months which then plateaus at 18 months.\n\n\n\n2-Walking00217.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 568\n\n\n\n\n\n\n\n\nWalking further. How surgery can help the cerebral palsy child\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                569 \n\n\n\nchildren to painful surgery for the sake of gait improvement. \nApart from that, this study is limited to one centre and results \nare not to be generalised to the whole country to reflect the \nlack of access to surgical and rehabilitative facilities \navailable for CP children.  \n \nFurthermore, the lack of a dedicated gait analysis facility at \nour centre hampers our ability of making accurate and \nconcise surgical planning retarding the growth and \ndevelopment of Single Event Multi-Level Surgery (SEMLS) \nwhich is commonly practised in other countries. We were also \nconcerned that the ambulatory function ratings were \nassigned retrospectively using the information available, \nwhich could have impacted their accuracy. \n \n \nCONCLUSION \nWith available data from this research, surgeries performed \non GMFCS I-III patients with the aim of gait improvement \ndoes translate into better mobility outcome which are \ncomparable to present available literature5,6,19. This research \nshould prove to be a steppingstone to expand the research by \nhaving longer follow up of patients thereby increasing the \nsample size thus the strength of the study. Longer follow up \nalso allows us look for recurrences and how surgery has \nimpacted the quality of life and functionality in the \ncommunity.  Furthermore, an addition of gait analysis \nfacilities may enhance the decision-making process and \nallow more accurate surgical prescription for contracture \nrelease among CP children.  \n \n \nREFERENCES \n1. Sellier E, McIntyre S, Smithers-Sheedy H, Platt MJ. European and \n\n\n\nAustralian cerebral palsy surveillance networks working together \nfor collaborative research. Neuropediatrics. 2020;51(02):105-112. \n\n\n\n2. Kamaralzaman S, Ying TC, Mohamed S, Toran H, Satari N, \nAbdullah N. The economic burden of families of children with \ncerebral palsy in Malaysia. Malaysian Journal of Public Health \nMedicine. 2018; 2018(Specialissue1). \n\n\n\n3. Novak I, McIntyre S, Morgan C, Campbell L, Dark L, Morton N, \net al. A systematic review of interventions for children with \ncerebral palsy: state of the evidence. Dev Med Child Neurol. \n2013; 55(10): 885-910. \n\n\n\n4. Bulekbayeva S, Daribayev Z, Ospanova S, Vento S. Cerebral \npalsy: a multidisciplinary, integrated approach is essential. \nLancet Glob Health. 2017; 5(4): e401.  \n\n\n\n5. Thomason P, Baker R, Dodd K, Taylor N, Selber P, Wolfe R, et al. \nSingle-Event Multilevel Surgery in Children with Spastic Diplegia. \nJ Bone Joint Surg. 2011; 93(5): 451-60.  \n\n\n\n6. Firth GB, Passmore E, Sangeux M, Thomason P, Rodda J, Donath \nS, et al. Multilevel surgery for equinus gait in children with \nspastic diplegic cerebral palsy medium-term follow-up with gait \nanalysis. Journal of Bone and Joint Surgery - Series A. 2013; \n95(10): 931-8.  \n\n\n\n7. Feger MA, Lunsford CD, Sauer LD, Novicoff W, Abel MF. \nComparative Effects of Multilevel Muscle Tendon Surgery, \nOsteotomies, and Dorsal Rhizotomy on Functional and Gait \nOutcome Measures for Children With Cerebral Palsy. PM and R. \n2015; 7(5): 485-93.  \n\n\n\n8. Chang CH, Chen YY, Yeh KK, Chen CL. Gross motor function \nchange after multilevel soft tissue release in children with \ncerebral palsy. Biomed J. 2017; 40(3): 163-8.  \n\n\n\n9. Kerr Graham H, Selber P. Musculoskeletal aspects of cerebral \npalsy. J Bone Joint Surg Br. 2003; 85(2): 157-166.  \n\n\n\n10. Shore BJ, Yu X, Desai S, Selber P, Wolfe R, Graham HK. Adductor \nsurgery to prevent hip displacement in children with cerebral \npalsy: the predictive role of the Gross Motor Function \nClassification System. J Bone Joint Surg Am. 2012; 94(4): 326-34.  \n\n\n\n11. Ahmed AAY, Rafalla AAA. Clinical outcome of hamstring \nlengthening to correct flexed knee gait in patients with spastic \ndiplegia. Egypt Orthop J. 2017: 352-8.  \n\n\n\n12. Takahashi S, Shrestha A. The vulpius procedure for correction of \nequinus deformity in patients with hemiplegia. J Bone Joint Surg \nBr. 2002; 84(7): 978-80.  \n\n\n\n13. Palisano R, Rosenbaum P, Bartlett D, Livingston M, Walter S, \nRussell D, et al. Gross Motor Function Classification System \nExpanded and Revised. Reference: Dev Med Child Neurol. 2007; \n39: 214-23.  \n\n\n\n14. Graham HK, Harvey A, Rodda J, Nattrass GR, Pirpiris M. The \nFunctional Mobility Scale (FMS). J Pediatr Orthop 2004; 24(5): \n514-20. \n\n\n\n15. Bartlett DJ. The use of the spinal alignment and range of motion \nmeasure with children and young people with cerebral palsy. \nDev Med Child Neurol. 2013; 55(8): 685-6.  \n\n\n\n16. Davids JR, Ounpuu S, DeLuca PA, Davis RB. Optimization of \nwalking ability of children with cerebral palsy. Instr Course Lect. \n2004; 53(11): 511-22.  \n\n\n\n17. Chen CL, Wu KPH, Liu WY, Cheng HYK, Shen IH, Lin KC. Validity \nand clinimetric properties of the spinal alignment and range of \nmotion measure in children with cerebral palsy. Dev Med Child \nNeurol. 2013; 55(8): 745-750.  \n\n\n\n18. Joo SY, Knowtharapu DN, Rogers KJ, Holmes L, Miller F. \nRecurrence after surgery for equinus foot deformity in children \nwith cerebral palsy: assessment of predisposing factors for \nrecurrence in a long-term follow-up study. J Child Orthop. 2011; \n5(4): 289-96.  \n\n\n\n19. Harvey A, Graham HK, Morris ME, Baker R, Wolfe R. The \nFunctional Mobility Scale: ability to detect change following \nsingle event multilevel surgery. Dev Med Child Neurol. 2007; \n49(8): 603-7.  \n\n\n\n2-Walking00217.qxp_3-PRIMARY.qxd  25/09/2023  4:22 PM  Page 569\n\n\n\n\n\n\n\n\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
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"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\n574                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nABSTRACT \nIntroduction:\u2008Global actions have been implemented \nworldwide to eliminate leprosy. However, under-recognition \nand stigmatisation continue to be the challenges. In Sabah, \nthe grade two disability rate was 0.15/100,000 population in \n2019, implicating a significant delay in diagnosis. This study \naimed to assess the knowledge and attitude towards leprosy \nand the impact of lecture intervention among doctors in \nSabah and Labuan, Malaysia. \n \nMaterials and methods: This study consists of two parts. \nFirst, a cross-sectional study on the knowledge of and \nattitude towards leprosy using an online quesitonnaire was \nconducted among doctors working in the primary care \nclinics and hospitals in Sabah and Labuan. Subsequently, \nthe participants were asked to watched an online pre-\nrecorded video lecture on leprosy and to answered the same \nquestionnaire.   \n \nResults: Of the 310 participants, one fifth (20.6%) had good \nknowledge and 36.5% had positive attitude towards leprosy. \nBeing a specialist (adjusted odds ratio [aOR] 4.55, 95% \nconfidence interval [CI] 2.17\u20139.57, p < 0.001), managed \u2265 5 \nleprosy cases (aOR 3.37, 95% CI 1.52\u20137.47, p = 0.003), and \ninvolved in educational activities related to leprosy within \nlast year (aOR 4.7, 95% CI 1.69\u201313.04, p < 0.001) were the \nsignificant predictors of good knowledge. Working in \ntertiary care was significantly associated with good attitude \ntowards leprosy (OR 2.19, 95% CI 1.22\u20133.94, p = 0.025). There \nwas a significant improvement in participants\u2019 knowledge \npost-intervention (87.0% participants post-lecture vs 20.6% \nparticipants pre-lecture with good knowledge, p < 0.001). \n \nConclusion: The proportion of doctors in Sabah and Labuan \nwith good knowledge and attitude towards leprosy was low. \nKnowledge of leprosy improved significantly post-\nintervention. This highlights the need for educational and \ntraining programmes to improve doctors\u2019 knowledge of \nleprosy.  \n \nKEYWORDS:  \nLeprosy, Hansen\u2019s disease, knowledge, attitude, doctors \n \n \nINTRODUCTION \nLeprosy is an infectious disease caused by Mycobacterium \nleprae that primarily affects the skin and peripheral nerves. \n\n\n\nUntreated disease can lead to mutilating deformities and \nassociated with social stigma. Early diagnosis and treatment \nplay an important role in the prevention of disabilities.1  \n \nGlobally, there were 202,256 new cases detected in 118 \ncountries in 2019. The majority of the new cases (79%) were \nreported in India and Brazil. According to the WHO disability \ngrading, grade 2 disabilities were characterised by visible \ndeformity or visual damage.2 Of the new cases, 10,816 cases \nwere detected with grade 2 disabilities (G2D) with a rate at \n1.4 per million population and 370 (3.4%) cases were \nchildren under the age of 15.3  \n \nMalaysia achieved leprosy elimination in 1994.4 Although \nthe number of new cases has declined over the past years, \nthere were 198 new cases detected in 2019 in Malaysia.5 \nSabah has the highest number of cases in Malaysia with 75 \n(37.9%) new cases. Among which four (5.3%) cases were \nchildren and 6 (8%) cases had grade 2 disabilities with a G2D \nrate of 0.15/100,000.6 Sabah did not achieve the WHO target \nof G2D < 0.02 per 100,000 population and new child cases of \n< 3%. This is an indication of late diagnosis and lack of \ncommunity awareness. \n \nIn Malaysia, the public health sector comprises of three \nlevels: primary, secondary, and tertiary care with a wide \nnetwork of health clinics and hospitals. The primary care \nservice comprises of outpatient clinics at the first point of \nconsultation for patients at the local community. Patients \nmay then be referred to secondary and tertiary care services.7 \nBoth Sabah and Labuan are located on the Northern Borneo \nof Malaysia. In 2019, the incidence rate of leprosy in Sabah \nwas 1.9 per 100,000 population as compared to 0.61 in \nMalaysia.5 Thus, it is important for doctors to have adequate \nknowledge and training in leprosy to recognise and diagnose \nleprosy early. This study aimed to assess the knowledge and \nattitude towards leprosy among medical doctors in Sabah \nand Labuan. \n \n \nMATERIALS AND METHODS \nStudy design and population \nThis was a cross-sectional study with online questionnaire \nconducted among medical doctors working in the primary \ncare clinics, district hospitals (secondary care), emergency \ndepartment and medical department of specialist hospitals \n(tertiary care) in Sabah and Labuan from June 2021 till April \n\n\n\nEvaluating the impact of a pre-recorded online video on \nDoctor's knowledge and attitude towards leprosy in Sabah \nand Labuan - a quasi experimental study \n \nXin Yun Teoh, MRCP1,2, Sook Yee Michelle Voo, AdvMDerm1, Nadirah Sulaiman, BBiomedSc3 \n\n\n\n     \n1Department of Dermatology, Hospital Queen Elizabeth, Sabah, Malaysia, 2Department of Medicine, Dermatology Unit, \nUniversity Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia, 3Clinical Research Centre, Hospital Queen \nElizabeth, Sabah, Malaysia \n\n\n\nORIGINAL ARTICLE \n\n\n\n This article was accepted: 03 July 2023                                                                                                                                                                              \nCorresponding Author: Teoh Xin Yun                                                                                                                                                                                 \nEmail: xinyunteoh@gmail.com\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 574\n\n\n\n\n\n\n\n\nEvaluating the impact of a pre-recorded online video on Doctor's knowledge and attitude towards leprosy\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                575 \n\n\n\n2022. Doctors working in the Dermatology department were \nexcluded.  \n \nThe target participants were recruited by convenience \nsampling. A link to the questionnaire in Google Form was \ndistributed via email to the relevant clinics and departments \nin hospitals. Participants answered an online self-\nadministered questionnaire on leprosy and provided their \nemail at the end of the questionnaire. After completion of the \nquestionnaire, participants later received a link to the pre-\nrecorded 5-minute video lecture and the same set of \nquestionnaire via email. Participants were given a 3-month \ntime frame to watch the video lecture and complete the post-\nvideo questionnaire. After completion of the questionnaire, \nparticipants received their scores and the answers on the \nknowledge section of the questionnaire.  \n \nThis study was approved by the Medical Research and Ethics \nCommittee, Ministry of Health, Malaysia, and was registered \nwith the National Medical Research Registry (NMRR-21-1443-\n60619). \n \nQuestionnaire development and content validation \nThe questionnaire was developed by the investigators of this \nstudy. The content validation of the questionnaire was \nconducted by five senior consultant dermatologists. The \nquestionnaire and the content validation form were sent via \nemail to the consultant dermatologists. The dermatologists \nrated each question on a four-point Likert scale (1- totally \nirrelevant content, 2- irrelevant content, 3- relevant content, \n4- extremely relevant content). The relevance rating for each \nitem was recoded as 1 (relevance scale of 3 or 4) or 0 \n(relevance scale of 1 or 2). Then, the sum of the relevance \nrating of each item was divided by the number of the expert, \ne.g., (1+1+1+1+1)/5 = 1. The average content validity index \n(CVI) across all items was 1, which met the satisfactory level. \nNext, pre-testing of the questionnaire was carried out to ten \npotential participants. The ten responses were included in \nthis study as there were no major changes from the pre-test. \n \nVideo lecture \nThe 5-minute video lecture was prepared and delivered by the \nprincipal investigator. The video lecture explained the cause \nof leprosy, mode of transmission, classifications, clinical \nfeatures, treatment and complications. The content of the \nvideo was approved by three senior consultant \ndermatologists. \n \nQuestionnaire \nInformed consent was obtained from all participants. \nDemographic data and professional characteristics of the \nparticipants were collected in the questionnaire. There was a \ntotal of 24 questions in the questionnaire: 20 questions on \nknowledge and 4 questions on attitude. The questions on \nknowledge comprised of cause of leprosy, mode of \ntransmission, clinical features, treatment and complications. \nEvery correct answer on the knowledge section will be \nawarded 1 mark; no mark will be awarded for wrong or \nunanswered questions. The total marks will be converted to \n100% for interpretation. Categorisation of the score was as \nfollowing:  \u2265 70% good knowledge, 40 - 69% average knowledge \nand < 40% poor knowledge.  \n\n\n\nFor the attitude section of the questionnaire, a five-point \nLikert scale was used. The score was calculated as the \nfollowing: 1- strongly disagree, 2- disagree, 3- neutral, 4- \nagree, 5- strongly agree. Lower total score indicates better \nattitude. Participants who answered disagree or strongly \ndisagree on all questions (with a score of \u2264 8) were regarded \nas having good attitude. A score > 8 was regarded as having \npoor attitude. Categorisation of the knowledge and attitude \nscore were decided by the investigators of this study after \ndiscussion with the three senior consultant dermatologists. \n \nStatistical analysis \nThe data were tabulated and analysed using IBM\u00ae Statistical \nPackage for the Social Sciences (SPSS) Statistics, version 22.0. \nDescriptive analyses were conducted for demographic and \nprofessional characteristics. Continuous variables were \nexpressed as means and standard deviations (SD) and \ncategorical variables as frequencies and percentages. Simple \nlogistic regression analysis was done to analyse factors \nassociated with good knowledge and good attitude. \nMultivariate logistic regression analysis was conducted for \nvariables associated with good knowledge. Forward and \nbackward stepwise variable selection procedures were \napplied. McNemar\u2019s test was done to analyse participants\u2019 \nknowledge and attitude pre and post-intervention. A p-value  \nof < 0.05 was considered statistically significant. \n \n \nRESULTS \nDemographic characteristics of the participants and \nexperience with leprosy patients \nA total of 310 participants were included in this study. The \nmean age of the participants was 31.5 \u00b1 2.91 years. Among \nthe participants working in tertiary hospitals, 129 (95.6%) \nwere from medical department and 6 (4.4%) from emergency \ndepartment.  \n \nThe majority of the participants had limited experience with \nleprosy. More than 80% of them had previously came across, \ndiagnosed, or managed less than five patients with leprosy. \nHigher proportion of primary care (22.5%) and tertiary care \ndoctors (20.7%) came across \u2265 5 leprosy patients compared to \nthe secondary care doctors (11.6%). Overall, more specialists \n(25%) managed \u2265 5 leprosy patients than medical officers \n(9.4%). The majority of the participants (84.8%) did not \nreceive undergraduate teaching on leprosy. Two-thirds \n(67.7%) of the participants last accessed leprosy materials \nmore than a year ago (Table I).  \n \nKnowledge of leprosy \nAs shown in Table I, participants who were specialists, \nworking in primary care or tertiary care, being in service for \n\u2265 5 years, experience with leprosy patients (came across or \ndiagnosed or managed \u2265 5 leprosy cases), previously received \nundergraduate teaching on leprosy and involved in \neducational activities related to leprosy within last year had \nbetter knowledge. \n \nTable II shows the responses to questionnaire pre and post-\nvideo lecture. The majority of the participants were familiar \nwith the causative microorganism (96.5%) and the \ninvestigations of suspected leprosy patients (83.5%). One-\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 575\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n576                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nCharacteristics                                                      Overall                                        Knowledge                                            Attitude \n                                                                           n (%)                   Good               Average               Poor               Good              Poor \n                                                                          n=310                 (\u226570%)              (40-69%)             (<40%)               (\u22648)                 (>8) \n                                                                                                      n = 64                n = 216               n = 30             n = 113           n = 197 \n\n\n\nAge - years, Mean (SD)                                       31.5 (2.91)          32.4 (3.45)          31.3 (2.72)         30.9 (2.58)       31.5 (2.85)      31.5 (2.94) \nGender \n\n\n\nMale                                                               140 (45.2)            28 (20.0)             99 (70.7)             13 (9.3)           57 (40.7)         83 (59.3) \nFemale                                                           170 (54.8)            36 (21.2)            117(68.8)            17(10.0)          56 (32.9)        114 (67.1) \n\n\n\nEthnicity \nBumiputera Sabah                                         59 (19.0)              9 (15.3)              44(74.6)              6 (10.2)           23 (39.0)         36 (61.0) \nMalay                                                              95 (30.6)             22 (23.2)             56 (58.9)            17 (17.9)          33 (34.7)         62 (65.3) \nChinese                                                          115 (37.1)            26 (22.6)             83 (72.2)              6 (5.2)            39 (33.9)         76 (66.1) \nIndian                                                              38 (12.3)              7 (18.4)              30 (78.9)              1 (2.6)            16 (42.1)         22 (57.9) \nOthers                                                               3 (0.9)                      0                     3 (100)                    0                 1 (50.0)           1 (50.0) \n\n\n\nPosition \nMedical officer                                              266 (85.8)            44 (16.5)            193 (72.6)           29 (10.9)          93 (35.0)        173 (65.0) \nSpecialist                                                         44 (14.2)             20 (45.5)             23 (52.3)              1 (2.3)            20 (45.5)         24 (54.5) \n\n\n\nWorkplace \nPrimary care                                                    89 (28.7)             26 (29.2)             55 (61.8)              8 (9.0)            30 (33.7)         59 (66.3) \nSecondary care                                               86 (27.7)               8 (9.3)               61(70.9)             17 (19.8)          23 (26.7)         63 (73.3) \nTertiary care                                                  135 (43.5)            30 (22.2)            100 (74.1)             5 (3.7)            60 (44.4)         75 (55.6) \n\n\n\nYears of service \n< 5                                                                  174 (56.1)            29 (16.7)            124 (71.3)           21 (12.1)          59 (33.9)        115 (66.1) \n\u2265 5                                                                  136 (43.9)            35 (25.7)             92 (67.6)              9 (6.6)            54 (39.7)         82 (60.3) \n\n\n\nNumber of leprosy patients came across  \n< 5                                                                  252 (81.3)            40 (15.9)            184 (73.0)           28 (11.1)          86 (34.1)        166 (65.9) \n\u2265 5                                                                   58 (18.7)             24 (41.4)             32 (55.2)              2 (3.4)            27 (46.6)         31 (53.4) \n\n\n\nNumber of leprosy patients diagnosed                      \n< 5                                                                    301 (97)              59 (19.6)            212 (70.4)           30 (10.0)         108 (35.9)       193 (64.1) \n\u2265 5                                                                       9 (3)                  5 (55.6)               4 (44.4)                    0                 5 (55.6)           4 (44.4) \n\n\n\nNumber of leprosy patients managed                        \n< 5                                                                  274 (88.4)            46 (16.8)            199 (72.6)           29 (10.6)          95 (34.7)        179 (65.3) \n\u2265 5                                                                   36 (11.6)             18 (50.0)             17 (47.2)              1 (2.8)            18 (50.0)         18 (50.0) \n\n\n\nReceived undergraduate teaching on  \nleprosy \n\n\n\nYes                                                                  263 (84.8)            58 (22.1)            178 (67.7)           27 (10.3)          99 (37.6)         33 (70.2) \nNo                                                                    47 (15.2)              6 (12.8)              38 (80.9)              3 (6.4)            14 (29.8)        164 (62.4) \n\n\n\nLast involved in educational  \nactivities related to leprosy \n\n\n\nNever                                                               61 (19.7)              8 (13.1)              43 (70.5)            10 (16.4)          17 (27.9)         44 (72.1) \nWithin last year                                              39 (12.6)             18 (46.2)             21 (53.8)                   0                17 (43.6)         22 (56.4) \nMore than 1 year                                          210 (67.7)            38 (18.1)            152 (72.4)            20 (9.5)           79 (37.6)         44 (72.1) \n\n\n\nEducational source on leprosy accessed \nWebsite                                                          170 (54.8)            36 (21.2)            119 (70.0)            15 (8.8)           67 (39.4)        103 (60.6) \nContinuing Medical Education                    104 (33.5)            27 (26.0)             69 (66.3)              8 (7.7)            48 (46.2)         56 (53.8) \nLeprosy Management Manual                      47 (15.2)             13 (27.7)             33 (70.2)              1 (2.1)            20 (42.6)         27 (57.4) \nTextbook                                                        118 (38.1)            25 (21.1)             82 (69.5)             11 (9.3)           40 (33.9)         78 (66.1) \nJournal articles                                               33 (10.6)              7 (21.2)              25 (75.8)              1 (3.0)            13 (39.4)         20 (66.7) \nCourses                                                              3 (1.0)                2 (66.7)               1 (33.3)                    0                 1 (33.3)           2 (66.7) \nNever access any leprosy related                   30 (9.7)               5 (16.7)              21 (70.0)             4 (13.3)            8 (26.7)          22 (73.3)  \nresources                                                                                                                                                                                                  \n\n\n\n\n\n\n\nTable I: Demographic characteristics of the participants, experience with leprosy patients, knowledge and attitude towards leprosy\n\n\n\nthird (33.5%) of the participants thought that leprosy was \ntransmitted by direct contact. Only 64 (20.6%) participants \nhad good knowledge (score \u2265 70%). Nearly two-thirds of the \nparticipants (69.7%) had average knowledge (score 40 - 69%) \nand the remaining 30 (9.7%) participants had poor \nknowledge (score < 40%).  \n \nTable III shows the univariate and multivariate logistic \nregression analysis of the potential predictors of better \nknowledge score. Position as a specialist (adjusted odds ratio \n[aOR] = 4.55, 95% confidence interval [CI] = 2.17\u20139.57, p < \n0.001), previously managed \u2265 5 leprosy cases (aOR = 3.37, \n95% CI = 1.52\u20137.47, p = 0.003), and last accessed educational \n\n\n\nmaterials related to leprosy within the last year (aOR = 4.7, \n95% CI = 1.69\u201313.04, p < 0.001) were significantly associated \nwith good knowledge.  \n \nAttitude towards leprosy \nMore than one-third (37.8%) of the participants thought \npatients with leprosy need to be isolated from the \ncommunity. Only 113 (36.5%) of the participants had good \nattitude towards leprosy (score \u2264 8). Participants who were \nspecialists, working in tertiary care, with working experience \n\u2265 5 years, experience with leprosy patients, previously \nreceived undergraduate teaching on leprosy and involved in \neducational activities related to leprosy within last year had \n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 576\n\n\n\n\n\n\n\n\nEvaluating the impact of a pre-recorded online video on Doctor's knowledge and attitude towards leprosy\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                577 \n\n\n\nKnowledge and attitude questions                                                     Pre-video lecture, n = 310               Post-video lecture, n = 270 \n                                                                                                                          n (%)                                                    n (%) \n\n\n\nLeprosy is caused by which microorganism? \nMycobacterium leprae*                                                                               299 (96.5)                                            267 (98.9) \nTreponema pallidum                                                                                      10 (3.2)                                                 3 (1.1) \nMadurella mycetomatis                                                                                  1 (0.3)                                                      0 \nMycobacterium ulcerans                                                                                     0                                                          0 \n\n\n\nLeprosy is also known as: \nHansen\u2019s disease*                                                                                         299 (96.5)                                            268 (99.2) \nHumphrey\u2019s disease                                                                                        11 (3.5)                                                 1 (0.4) \nHartmann\u2019s disease                                                                                              0                                                      1 (0.4) \nHarry\u2019s disease                                                                                                     0                                                          0 \n\n\n\nThe mode of transmission for leprosy is: \nDirect contact                                                                                               104 (33.5)                                              12 (4.4) \nDroplet*                                                                                                        180 (58.1)                                            257 (95.2)  \nFaecal oral route                                                                                             17 (5.5)                                                 1 (0.4) \nVector                                                                                                               9 (2.9)                                                      0 \n\n\n\nLeprosy primarily affects:  \nI. Bone, II. Nerve, III. Skin, IV. Eyes \n\n\n\nI, II                                                                                                                     2 (0.6)                                                  1 (0.4) \nII, III *                                                                                                             121 (39.0)                                             99 (36.7) \nII, III, IV                                                                                                          128 (41.3)                                            146 (54.1) \nAll of the above                                                                                             59 (19.0)                                               24 (8.9) \n\n\n\nWhat are the typical cutaneous features of leprosy?  \nI. Hypopigmented patch,  \nII. Loss of sensation,  \nIII. Loss of hair, IV. Loss of sweating \n\n\n\nI, II                                                                                                                  147 (47.4)                                             40 (14.8) \nII, III                                                                                                                   8 (2.6)                                                  1 (0.4) \nII, III, IV                                                                                                            12 (3.9)                                                 3 (1.1) \nAll of the above*                                                                                          143 (46.1)                                            226 (83.7) \n\n\n\nWhat are the cardinal signs of leprosy? \nI. Skin patch with loss of sensation \nII. Enlarged/thickened peripheral nerve with  \ncorresponding loss/impairment of function \nIII. Presence of acid-fast bacilli in slit skin smear \nIV. Loss of corneal reflex \n\n\n\nI, II                                                                                                                   78 (25.2)                                               12 (4.5) \nI, II, III*                                                                                                           125 (40.3)                                            235 (87.0) \nII, III                                                                                                                  14 (4.5)                                                 6 (2.2)  \nAll of the above                                                                                             93 (30.0)                                               17 (6.3) \n\n\n\nWhich nerve is the most frequently affected  \nnerve in leprosy? \n\n\n\nOptic                                                                                                               82 (26.4)                                                9 (3.3) \nPopliteal                                                                                                          21 (6.8)                                                 1 (0.4) \nSciatic                                                                                                               12 (3.9)                                                 1 (0.4) \nUlnar*                                                                                                            195 (62.9)                                            259 (95.9) \n\n\n\nWhich is the most severe form of leprosy? \nBorderline tuberculoid                                                                                    1 (0.3)                                                  1 (0.4) \nLepromatous*                                                                                               269 (86.8)                                            259 (95.9) \nMid borderline                                                                                                 1 (0.3)                                                      0 \nTuberculoid                                                                                                    39 (12.6)                                               10 (3.7) \n\n\n\nWhich of the following patient has leprosy? \n(patients\u2019 photos) \n\n\n\na                                                                                                                        6 (1.9)                                                  3 (1.1) \nb *                                                                                                                   42 (13.6)                                              35 (13.0) \nc                                                                                                                     257 (82.9)                                            229 (84.8) \nd                                                                                                                        5 (1.6)                                                  3 (1.1) \n\n\n\nWhat are the complications of leprosy? \nI. Claw hand, II. Lagophthalmos, III. Scleritis,  \nIV. Neuropathic ulcers \n\n\n\nI, II                                                                                                                   45 (14.5)                                               15 (5.6) \nII, III                                                                                                                   8 (2.6)                                                  6 (2.2) \nII, III, IV                                                                                                           53 (17.1)                                                4 (1.5) \nAll of the above *                                                                                         204 (65.8)                                            245 (90.7) \n\n\n\n\n\n\n\nTable II:\u2008Responses to knowledge and attitude questions\n\n\n\ncont..... pg 578\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 577\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n578                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\nKnowledge item                                                                                    Pre-video lecture, n = 310               Post-video lecture, n = 270 \n                                                                                                                          n (%)                                                    n (%) \n\n\n\nWhat constitutes WHO grade 2 disabilities in leprosy?  \nI. Loss of sensation, II. Blindness, III. Resorption of digits,  \nIV. Loss of corneal reflex \n\n\n\nI, II                                                                                                                   95 (30.6)                                              42 (15.5) \nII, III *                                                                                                              69 (22.3)                                             126 (46.7) \nIII, IV                                                                                                               39 (12.6)                                               20 (7.4) \nAll of the above                                                                                            107 (34.5)                                             82 (30.4) \n\n\n\nWhat are the clinical manifestations of type 2 reaction?  \nI. Painful nodules, II. Fever, III. Lymphadenopathy,  \nIV. Arthralgia \n\n\n\nI, II                                                                                                                   37 (11.9)                                               10 (3.7) \nI, II, III                                                                                                              56 (18.1)                                              36 (13.3) \nII, III                                                                                                                 40 (12.9)                                                4 (1.5)  \nAll of the above*                                                                                          177 (57.1)                                            220 (81.5) \n\n\n\nInvestigations for patients suspected of leprosy include:  \nI. Skin biopsy, II. Slit skin smear, III. Peripheral blood smear,  \nIV. Blood culture \n\n\n\nI, II*                                                                                                                259 (83.5)                                            261 (96.7) \nI, II, IV                                                                                                             42 (13.6)                                                5 (1.8) \nI, IV                                                                                                                   5 (1.6)                                                      0 \nII, III                                                                                                                   4 (1.3)                                                  4 (1.5) \n\n\n\nLeprosy should be notified to the nearest district health  \noffice within: \n\n\n\n1 month                                                                                                            5 (1.6)                                                      0 \n1 week *                                                                                                        139 (44.8)                                            247 (91.5) \n2 weeks                                                                                                            7 (2.3)                                                  2 (0.7) \n24 hours                                                                                                        159 (51.3)                                              21 (7.8) \n\n\n\nThe following drugs are used in leprosy treatment except: \nClofazimine                                                                                                    52 (16.8)                                                1 (0.4) \nDapsone                                                                                                         36 (11.6)                                                1 (0.4) \nIsoniazid *                                                                                                     208 (67.1)                                            263 (97.4) \nRifampicin                                                                                                       14 (4.5)                                                 5 (1.9) \n\n\n\nWhat is the duration of treatment for paucibacillary leprosy? \n3 months                                                                                                         21 (6.8)                                                 3 (1.1) \n6 months*                                                                                                     191 (61.6)                                            259 (95.9)  \n9 months                                                                                                        37 (11.9)                                                5 (1.9) \n12 months                                                                                                      61 (19.7)                                                3 (1.1) \n\n\n\nWhat is the duration of treatment for multibacillary leprosy? \n6 months                                                                                                         23 (7.4)                                                 3 (1.1) \n9 months                                                                                                        31 (10.0)                                                4 (1.5) \n12 months*                                                                                                   179 (57.8)                                            257 (95.2) \n18 months                                                                                                      77 (24.8)                                                6 (2.2) \n\n\n\nWhich of the following drugs is known to cause generalized  \npigmentation of skin? \n\n\n\nRifampicin                                                                                                      35 (11.3)                                               12 (4.5) \nDapsone                                                                                                        125 (40.3)                                             34 (12.6) \nClofazimine*                                                                                                 139 (44.8)                                            222 (82.2) \nIsoniazid                                                                                                         11 (3.6)                                                 2 (0.7) \n\n\n\nCase study 1 \nA 50-year-old man diagnosed with borderline leprosy,  \ntreatment was started 1 month ago. The existing plaques and  \npatches on his trunk and arms became more erythematous  \nand indurated in the last 4 days. How will you manage the  \npatient before referring to a dermatologist? \n\n\n\nStop his leprosy treatment immediately                                                      37 (11.9)                                               20 (7.4) \nEnsure the patient continues his leprosy treatment*                                 88 (28.4)                                             175 (64.8) \nArrange for an urgent slit skin smear                                                          42 (13.6)                                               13 (4.8) \nPerform full blood count, renal profile and liver                                      143 (46.1)                                             62(23.0) \nfunction test                                                                                                                                                                      \n\n\n\n\n\n\n\nTable II:\u2008Responses to knowledge and attitude questions\n\n\n\ncont..... pg 579\n\n\n\ncont from..... pg 577\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 578\n\n\n\n\n\n\n\n\nEvaluating the impact of a pre-recorded online video on Doctor's knowledge and attitude towards leprosy\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                579 \n\n\n\nbetter attitude (Table I). Working in the tertiary care hospitals \nwas an independent predictor of good attitude (OR = 2.19, \n95% CI = 1.22\u20133.94, p = 0.025).  \n \nPre and post-intervention \nThere was a significant increase in proportion of participants \nwith good knowledge post-video lecture (87.0 vs 20.6, p < \n0.001) (Table IV). However, there was no significant change \nof attitude post-intervention.  \n \n \nDISCUSSION \nOnly one-fifth of our study participants had good knowledge \nof leprosy. This finding is consistent with previous studies.8-10 \nIn Ethiopia, 519 (86.3%) healthcare workers had poor \nknowledge of the signs and symptoms of leprosy, leprosy \nreactions and management.8 Similarly, a study in South \nAfrica revealed general lack of basic knowledge of leprosy \namong the primary care doctors.9 Furthermore, poor \nknowledge was reported among 50% of the doctors in \nworking in the dermatology field in China.11  \n \n\n\n\nOur study participants had limited experience with leprosy \npatients (came across, diagnosed or managed < 5 cases of \nleprosy). In Italy, only 11 (10.8%) of the doctors had \ninteraction with a leprosy case, and only 6.9% had diagnosed \nleprosy before and none had managed a leprosy patient.12 In \nSouthern Malawi, 13 (37%) healthcare workers had never \nseen a leprosy patient and 29 (83%) had never diagnosed \nleprosy before.13 Among doctors working in dermatology field \nin China, 20% of them had never seen a leprosy patient and \n41% had never diagnosed leprosy.11 Lack of experience of \ndoctors in leprosy could be due to the lack of exposure to \nleprosy cases in non-endemic areas.  \n \nDiagnosing leprosy is challenging as it can mimic any skin \ncondition.14 In Malaysia, a case series of 27 leprosy patients \nreported that there were missed diagnoses by primary care \ndoctors in 12 patients (44\u00b74%).15 Previous experience with \nleprosy patients was an important predictor of better \nknowledge in our study and previous studies.8,10 Abeje et al \nreported that good knowledge was associated with training \nand exposure to leprosy.8 In Italy, higher knowledge score \nwas reported among doctors who had diagnosed or interacted \n\n\n\nKnowledge item                                                                                    Pre-video lecture, n = 310               Post-video lecture, n = 270 \n                                                                                                                          n (%)                                                    n (%) \n\n\n\nCase study 2 \nA 35-year-old woman with lepromatous leprosy completed  \nher treatment 1 year ago. She complained of painful nodules  \nover arms and legs of 2 weeks duration. Examination showed  \nmultiple, scattered, tender, erythematous subcutaneous  \nnodules. What is your next step in management before  \nreferring to a dermatologist? \n\n\n\nRestart leprosy treatment                                                                              21 (6.8)                                                 6 (2.2) \nPerform a slit skin smear                                                                              139 (44.8)                                             51 (18.9) \nStart prednisolone                                                                                        81 (26.1)                                             104 (38.5) \nSymptomatic treatment *                                                                             69 (22.3)                                             109 (40.4) \n\n\n\nLeprosy patients need to be isolated from community during  \nthe treatment period. \n\n\n\nStrongly disagree                                                                                           41 (13.2)                                              45 (16.7) \nDisagree                                                                                                         88 (28.4)                                              76 (28.1) \nNeutral                                                                                                           64 (20.6)                                              45 (16.7) \nAgree                                                                                                              87 (28.1)                                              78 (28.9) \nStrongly agree                                                                                                30 (9.7)                                                26 (9.6) \n\n\n\nIf someone in your family has leprosy, you would never  \ndisclose it to anyone.  \n\n\n\nStrongly disagree                                                                                           58 (18.7)                                              66 (24.4) \nDisagree                                                                                                         87 (28.1)                                              81 (30.0) \nNeutral                                                                                                          109 (35.2)                                             78 (28.9) \nAgree                                                                                                              46 (14.8)                                              32 (11.9) \nStrongly agree                                                                                                10 (3.2)                                                13 (4.8) \n\n\n\nLeprosy patients should not take part in any social activities. \nStrongly disagree                                                                                           82 (26.4)                                              81 (30.0) \nDisagree                                                                                                        138 (44.5)                                            112 (41.5) \nNeutral                                                                                                           61 (19.7)                                              37 (13.7) \nAgree                                                                                                               25 (8.1)                                               29 (10.7) \nStrongly agree                                                                                                 4 (1.3)                                                 11 (4.1) \n\n\n\nYou will avoid working with a colleague with leprosy. \nStrongly disagree                                                                                           81 (26.1)                                              89 (33.0) \nDisagree                                                                                                        147 (47.4)                                             94 (34.8) \nNeutral                                                                                                           57 (18.4)                                              58 (21.5) \nAgree                                                                                                               19 (6.1)                                                20 (7.4) \nStrongly agree                                                                                                 6 (2.0)                                                  9 (3.3) \n\n\n\n \n*Correct answer(s)  \n\n\n\nTable II:\u2008Responses to knowledge and attitude questions\ncont from..... pg 578\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 579\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n580                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n                                                              Good knowledge (univariate)                                       Good knowledge (multivariate) \n                                                        Crude              95% confidence             p-value a      Adjusted       95% confidence      p-value a \n                                                          odds               interval of OR                                       odds            interval of OR                \n                                                          ratio            Lower            Upper                                   ratio           Lower     Upper  \n                                                          (OR)              value              value                                   (OR)            value       value \n\n\n\nAge group (years) \n< 30                                                    1.00               1.03                4.69               0.043                 \n\u2265 30                                                    2.20                                          \n\n\n\nLevel of care \nPrimary care                                       4.02               1.70                9.50               0.006 \nTertiary                                              2.79               1.21                6.41              0.001 b \nSecondary                                          1.00                                                           0.016 b                                                                         \n\n\n\nPosition                                                                                                                      <0.001                                                                  <0.001 \nMedical officer                                  1.00                                                                                 1.00 \nSpecialist                                            4.21               2.14                8.27                                    4.55              2.17          9.57                 \n\n\n\nYears in service                                                                                                           0.052 \n< 5                                                      1.00 \n\u2265 5                                                      1.73               1.00                3.12                    \n\n\n\nNumber of leprosy cases                                                                                          <0.001                \ncame across \n\n\n\n< 5                                                      1.00 \n\u2265 5                                                      3.74               2.01                6.97                    \n\n\n\nNumber of leprosy cases                                                                                           0.017 \ndiagnosed  \n\n\n\n< 5                                                      1.00 \n\u2265 5                                                      5.13               1.34               19.68 \n\n\n\nNumber of leprosy patients                                                                                     <0.001                                                                   0.003 \nmanaged \n\n\n\n< 5                                                      1.00                                                                                 1.00                                   \n\u2265 5                                                      4.96               2.40               10.25                                   3.37              1.52          7.47 \n\n\n\nReceived teaching on leprosy                                                                                   0.153 \nduring undergraduate \n\n\n\nNo                                                       1.00 \nYes                                                      1.93               0.78                4.78                                                                              \n\n\n\nLast time involved in any                                                                                         <0.001                                                                  <0.001 \neducational activities related  \nto leprosy \n\n\n\nNever                                                  1.00                                                                                 1.00 \nMore than a year                              1.46               0.64                3.33              0.364 b            1.02              0.43          2.42          0.963 b \nWithin last year                                 5.68               2.14               15.04            <0.001 b           4.70              1.69         13.04         0.003 b \n\n\n\n \na Likelihood Ratio (LR) test     b Wald test \nThe model has no interaction terms, no multicollinearity problem and no outliers. \nHosmer-Lemeshow goodness-of-fit test for both models was not significant. \nEighty one percent cases are predicted correctly whether they have good knowledge and AUC of ROC is 72.9% (acceptable discrimination).  \n* No factors associated with good attitude generated from multiple logistic regression \n \n\n\n\nTable III: Factors associated with good knowledge\n\n\n\nKnowledge and attitude                               Pre-intervention,                                   Post-intervention,                                p-value b \n                                                                               n = 310                                                    n = 270 a \n                                                                                 n (%)                                                        n (%)                                                    \nKnowledge                                                                                                                                                                                     <0.001 \n          Good                                                           64 (20.6)                                                  235 (87.0) \n          Average                                                     216 (69.7)                                                  35 (13.0) \n          Poor                                                             30 (9.7)                                                          0                                                       \nAttitude                                                                                                                                                                                           0.044 \n          Good                                                          113 (36.5)                                                 114 (42.2) \n          Poor                                                           197 (63.5)                                                 156 (57.8)                                                \n \na Response rate for post-intervention is 87.1% \nb McNemar\u2019s test (knowledge regroup to two groups - good knowledge vs average to poor) \n            \n\n\n\nTable IV: Pre and post-intervention knowledge and attitude\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 580\n\n\n\n\n\n\n\n\nEvaluating the impact of a pre-recorded online video on Doctor's knowledge and attitude towards leprosy\n\n\n\nMed J Malaysia Vol 78 No 5 September 2023                                                                                                                                                581 \n\n\n\nwith leprosy patients.12 Our participants who were specialists \nand with longer working experience had better knowledge. \nThis is likely due to specialists having more experience \nmanaging leprosy patients (managed \u2265 5 leprosy patients). \nPrimary care doctors with limited experience reported having \nless confidence in diagnosis and management of leprosy.4 \nOur cohort working in primary care clinic or tertiary hospital \nhad better knowledge compared to those working in \nsecondary care (district hospitals). This is likely due to the \nprimary care and tertiary care doctors having more exposure \nto leprosy patients (came across \u2265 5 leprosy patients). The \nmajority of our cohort working in tertiary hospital were from \nthe medical department. It is possible that they were well-\nread on leprosy as a subject in internal medicine.  \n \nThe majority of our cohort did not receive undergraduate \nteaching on leprosy. In India, only 40% of medical students \nwere aware of the cardinal signs of leprosy.16 Furthermore, \nour study found no association between undergraduate \nteaching in leprosy and good knowledge and positive \nattitude. Among medical students in Nigeria, despite having \nlectures on leprosy, only 24.7% of them had good knowledge \nof leprosy.10 A study in India revealed medical interns had \nbetter knowledge and attitude compared to final year \nmedical student.16 A 1-day training program among Indian \nmedical students significantly improved their knowledge and \nattitude towards leprosy.17 This emphasises that over and \nabove teaching medical students about leprosy, exposure to \nleprosy cases and training are imperative to improve \nknowledge and attitude. \n \nRecent access to educational source on leprosy was an \nindependent predictor of good knowledge of leposy. A study \nin Hyderabad revealed that the government doctors had \nbetter knowledge than private practice doctors possibly due to \ncontinuing medical education programmes.18 Private doctors \nin Mumbai were reported to have inadequate knowledge \nlikely due to lack of continuing education on leprosy.19 \n \nOnly 25.8% of healthcare workers in Ethiopia had positive \nattitude towards leprosy patients.8 Negative attitude was also \nreported among doctors working in dermatology field in \nChina.11 In a Sri Lankan study, 34.3% of healthcare providers \nwere scared of leprosy and 22.5% of healthcare providers \nthought that leprosy patients need to be isolated from \nothers.20 Similar to our findings, misconceptions were \nreported among the healthcare workers in Guyana, where \nhalf of them believed leprosy was transmitted through touch \nand half were afraid of this disease.21 Ekeke et al reported that \ngood knowledge of leprosy was associated with positive \nattitude.10 Likewise, a study in Nigeria found that good \nknowledge correlate with favourable attitude towards \nleprosy.22 \n \nThere was a significant improvement in participants' \nknowledge of leprosy post-video lecture intervention. \nConsistent with our findings, interns in Nigeria who attended \nclinical demonstration on leprosy had better knowledge.10 A \nstudy of healthcare providers in Bangladesh demonstrated an \nincrease in knowledge after leprosy training.23 Similarly, there \nwas improvement in knowledge and confidence level among \nfamily medicine physicians in Malaysia after a 3-day lecture \nand hands-on training course.4 Doctors working in \n\n\n\ndermatology field in China demonstrated improvement in \nknowledge and attitude after a lecture and training \nworkshop.11 On the contrary, our study found no significant \nimprovement in doctors\u2019 attitude post-video lecture \nintervention. This may be because attitude change takes \ntime. Annually, the Sabah health department organises a \none-day physical course with lectures on leprosy for the \ndoctors and medical assistants working in government clinics \nand hospitals. Despite that, only a small proportion of the \ndoctors in our study had good knowledge and attitude. This \nis probably because of the nature of physical course that only \nallows limited numbers of participants each time.  \n \nAs our study was conducted during the covid pandemic, \nonline video lecture on leprosy was done as an intervention \nto improve knowledge of leprosy. Post-test questionnaire was \ndone immediately post-video lecture and we were not able to \nassess long term improvement in knowledge and attitude. We \nrecommend regular video lecture training conducted by the \ndermatologists for the medical officers and specialists from all \nlevels of care for exposure and revision to improve knowledge \nof leprosy. Teledermatology consultation is cost effective, \ntime efficient, and will be helpful to increase knowledge \namong the doctors and thus optimise patients\u2019 care. Future \nstudies to assess the impact of hands-on training workshop \ninvolving leprosy patients on knowledge and attitude \ntowards leprosy will be valuable. \n \n \nCONCLUSION \nThe proportion of medical doctors in Sabah and Labuan with \ngood knowledge and good attitude towards leprosy was low. \nPosition as a specialist, experience with leprosy patients and \nrecent education in leprosy were associated with good \nknowledge and attitude. Knowledge of leprosy improved \nsignificantly post-intervention. This highlights the need for \neducational and training programmes to improve doctors\u2019 \nknowledge of leprosy. \n \n \nREFERENCES \n1. Fischer M. Leprosy - an overview of clinical features, diagnosis, \n\n\n\nand treatment. J Dtsch Dermatol Ges 2017; 15(8): 801-27.  \n2. Brandsma JW, Van Brakel WH. WHO disability grading: \n\n\n\noperational definitions. Lepr Rev 2003; 74(4): 366-73. \n3. World Health Organization. Towards Zero Leprosy. Global \n\n\n\nLeprosy (Hansen\u2019s disease) Strategy 2021\u20132030. Geneva: WHO; \n2021, September 14, 2022. [cited  Sept 2022]. Available from: \nhttps://www.who.int/publications/i/item/9789290228509 \n\n\n\n4. Yap FBB, Kiung ST. Knowledge and confidence in the diagnosis \nand management of leprosy among Family Medicine Specialists \nin Malaysia. J Dermatol Dermatol Surg 2016; 46\u201350.  \n\n\n\n5. Ministry of Health Malaysia. Health Indicators 2020. Putrajaya: \nMOH; 2021, September 14, 2022. [cited Sept 2022]. Available \nfrom: https://www.moh.gov.my/moh/resources/Penerbitan/ \nPenerbitan%20Utama/HEALTH%20INDICATOR/01_Petunjuk_K\nesihatan_2020.pdf \n\n\n\n6. Jabatan Negeri Kesihatan Sabah. Laporan Kusta (Januari-\nDisember 2019). Sabah: JKNS. 2020, September 14, 2022. [cited \nSept 2022].  \n\n\n\n7. Sarifah SSR. Public healthcare facility planning in Malaysia: \nusing location allocation models. Healthcare delivery system in \nMalaysia. Malaysia: University of Malaya; 2012. [cited 2022 Sept \n14]. p.37 44. Available from: https://pdfs.semanticscholar.org/ \n964a/1b464f8705306ec827571c23d5d4a1513ab4.pdf \n\n\n\n\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 581\n\n\n\n\n\n\n\n\nOriginal Article \n\n\n\n582                                                                                                                                                Med J Malaysia Vol 78 No 5 September 2023\n\n\n\n8. Abeje T, Negera E, Kebede E, Hailu T, Hassen I, Lema T, et al. \nPerformance of general health workers in leprosy control \nactivities at public health facilities in Amhara and Oromia \nStates, Ethiopia. BMC Health Serv Res 2016; 16: 122.  \n\n\n\n9. Ukpe IS. A study of health workers\u2019 knowledge and practices \nregarding leprosy care and control at primary care clinics in the \nEerstehoek area of Gert Sibande district in Mpumalanga \nProvince, South Africa. SA Fam Pract 2006; 48(5): 16\u201323.  \n\n\n\n10. Ekeke N, Chukwu JN, Nwafor CC, Meka AO, Aguwa E, Uwakwe \nK, et al. Are there knowledge and attitude deficits on leprosy? A \nstudy among medical interns and final year students in \nsoutheast Nigeria. Lepr Rev 2020; 91: 108-18.  \n\n\n\n11. Chen SM, Zhang L, Liu DC, Liu HX. Assessment of knowledge \nand skills in early diagnosis of leprosy and attitudes towards \nleprosy amongst doctors working in dermatological services, \nShandong Province, People's Republic of China. Lepr Rev \n2004;75(4): 348-56.  \n\n\n\n12. Ricc\u00f2 M, Vezzosi L, Ranzieri S, Balzarini F, Mezzoiuso AG, \nVaccaro FG. Understanding leprosy in a nonendemic area: a \npilot study on knowledge, attitudes, beliefs of medical \nprofessionals from North-Western Italy. Acta Biomed 2020; \n91(4): e2020187.   \n\n\n\n13. Mponda K, Anafi G, Laja ET, Chidothe R, et al. Knowledge about \nleprosy among health care workers In Balaka District, Southern \nMalawi. Res Square 2020.  \n\n\n\n14. Kumar B. World Leprosy Day 2015: Renewing commitment for a \nleprosy free world! Indian J Med Res 2015; 141: 1-4.  \n\n\n\n15. Kwan Z, Pailoor J, Tan LL, Robinson S, Wong SM, Ismail R. \nLeprosy--an imported disease. Lepr Rev 2014; 85(3): 170-6.  \n\n\n\n16. Giri PA, Phalke DB, Aarif SM. A study of knowledge, attitude and \npractices regarding leprosy among undergraduates and interns \nof a medical college and hospital from rural India. Indian J Lepr \n2011; 83(2): 75-80.  \n\n\n\n17. Tiwari R, Srivastava DK, Bansal M, Adhikari P, Mishra S. An \nassessment of the impact of one day training programme on \nknowledge and attitude of undergraduate students on leprosy at \nG.R Medical College, Gwalior Madhya Pradesh. Natl J \nCommunity Med 2013; 4(2): 344\u20138.  \n\n\n\n18. Bajaj DR, Matlani BL, Soomro FR, Iqbal MP. Knowledge, attitude \nand practices regarding leprosy among general practitioners at \nHyderabad. J Coll Physicians Surg Pak 2009; 19(4): 215-8.  \n\n\n\n19. Uplekar MW. Private doctors and public health: The case of \nleprosy in Bombay, India. Natl Med J India 1990; 3(4): 162-6.  \n\n\n\n20. Wijeratne MP, \u00d8stbye T. Knowledge, Attitudes and Practices \nrelating to Leprosy among Public Health Care Providers in \nColombo, Sri Lanka. Lepr Rev 2017; 88(1): 75-84.  \n\n\n\n21. Briden A, Maguire E. An assessment of knowledge and attitudes \ntowards amongst leprosy/Hansen's disease workers in Guyana. \nLepr Rev 2003; 74(2): 154-62.  \n\n\n\n22. Ewhrudjakpor C. Health care providers knowledge as correlates \nof their attitudes towards leprosy sufferers in Nigeria. Ethno-Med \n2008; 24(2): 115-20.  \n\n\n\n23. Kabir H, Hossain S. Knowledge on leprosy and its management \namong primary healthcare providers in two districts of \nBangladesh. BMC Health Serv Res 2019; 19(1): 787.  \n\n\n\n\n\n\n\n4-Evaluating00078.qxp_3-PRIMARY.qxd  25/09/2023  4:23 PM  Page 582\n\n\n\n\n\n\n\n\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"
"\n\nNot Found\n\n\nThe requested URL was not found on this server.\n\n\nAdditionally, a 404 Not Found\nerror was encountered while trying to use an ErrorDocument to handle the request.\n\n"