Review for 10.1186/s12876-016-0434-3 (2016)

Reviewer ’s report  
 
Title: Effect of Coexisting Diabetes Mellitus and Chronic Kidney Disease  on Mortality of 
Cirrhotic Patients with Esophageal Variceal Bleeding  
 
 
Version: 0 Date: 22 Sep 2015  
 
 
Reviewer: Avik  Majumdar  
 
 
Reviewer's report:  
 
This is a second submission of a previously reviewed manuscript, following signifi cant revisions.  
The authors have used a validated Taiwanese population health insurance database to define the 
impact of chronic kidney disease (CKD) and diabetes mellitus (DM) on 42 -day and 1 -year 
mortality in patients with cirrhosis who have had their f irst presentation of esophageal variceal 
bleeding (EVB).  There are once again a number of major revisions that are required before this 
article could be considered as suitable for publication. The quality of written English needs to be 
improved, particula rly in the discussion section.  Furthermore, a number of statements are made 
that are not completely supported by the references given.  Finally, the tables need to be revised, 
as the required statistics have not been adequately presented.  I cannot recomm end the article for 
publication in its current state, particularly given that it is still unsuitable after major revisions.  
 
Major Compulsory Revisions  
The background focuses on the higher risk of DM And CKD on peptic ulcer bleeding.  The 
pathophysiology of EVB is different to that of peptic ulcer bleeding.  Could the authors please 
revise this paragraph to provide appropriate context for their hypothesis  that DM and CKD have 
adverse outcomes in EVB?  
 
In the methods section, could the authors clarify why two subsets of the NHIRD were randomly 
selected?  Why wasn't the entire database used to recruit patients?  A CONSORT -style flow 
diagram may assist in exp laining this process.  
 
The tables presented require revision.  In Table 1, could the authors please provide p values for 
all results presented? (eg. for each of the years of diagnosis of EVB etc.).  Similarly, the p -values 
should be aligned next to the num ber presented rather than the heading.  In Table 2, why is the 
hazard ratio for females, age <50 and urban dwellers 1 and why are confidence intervals and p -
values not provided? The bold -type in the tables should also be removed. In table 3, there are 
once  again hazard ratios of 1 quoted without confidence intervals.  The "reference" group for the 
hazard models should be EVB survivors.  
 
The discussion has a number of statements that are not justified by the references quoted. These 
have been underlined belo w.  These should be corrected before publication can be considered.  
Furthermore, the discussion section should involve more mature interpretation and comparison 
of the existing literature to the authors' data, rather than just listing data from other stud ies.  
Overall, the discussion requires more structure and elaboration on the possible mechanism of the 
increased mortality seen in the co -existence of CKD and DM.  Is it possible to find out the 
causes of death and see if this explains the results seen?  
  
 
Minor Essential Revisions  
 
Line 50 - the term "first diagnosis" of EVB could be misinterpreted.  Please consider 
using "first presentation" or "index presentation"  
 
Line 71 - suggest  "with an annual"  
 
Line 75 - should be "have" instead of "had".  I am no t entirely sure of the relevance of 
stating the higher risk of peptic ulcer bleeding as EVB is a different pathophysiologic 
process.  
 
Line 76 - the word " besides" should be changed here. The reference specifically refers to 
patients with hepatitis B. Plea se reflect this in the text.  
 
Line 79 - this sentence is not grammatically correct.  Once again, the relevance of 
comparing peptic ulcer bleeding is questionable.   
 
Line 83 - Please use the same units for the prevalence of CKD and DM (ie either 
percentage or per 100 000 population)  
 
Line 94 - Taiwan mentioned twice in the same sentence  
 
Line 95 - "purpose" should be "purposes"  
 
Line 106 - "first diagnosis". Same comment as Line 50.  
 
Line 112 -114 - Please revise the grammar used in these sentences.  
 
Line 120 - "ICD -9-CM" is repeated  
 
Line 140 -145 - Please change the term "estimated" and revise the grammar used in these 
sentences eg "a model containing men and women on 42 -day mortality" could be "42 -day 
mortality stratified by gender"  
 
Line 187 - please revise this sentence/reference.  6 -week mortality rates have been 
reported to be 10 -20% in more -recent studies.  
 
Line 191 - this is a misleading statement.  The reference is a study involving 16 patients 
(8 with cirrhosis) and measuring physiologic resp onses to a glucose load. It does not 
imply that diabetes mellitus occurs after the onset of cirrhosis in most cases as suggested 
by the authors.  
 
Line 194 - the referenced study was in a chronic HCV cohort, which should be 
mentioned.  Furthermore, this ref erence contradicts the statement made in Line 191.  The 
patients in the Huang study were patients with HCV, who then developed diabetes and 
subsequently were found to have an increased risk of developing cirrhosis, or 
decompensation in those with establish ed cirrhosis.  
 
Line 196 - Approximately 1% of patients with NAFLD develop cirrhosis, where as in 
non-alcoholic steatohepatitis (NASH), the estimated figure is 15 -20%.  Please amend the 
sentence and references.  
 
Line 197 - Should be "azygos"  
 
Line 198 - suggest replacing with"DM is a bad prognostic factor for the…"  
 
Line 204 - please justify how shorter life expectancy is the reason why diabetes was not 
statistically significant?  
 
Line 209 - The data in table 2 show an improvement in the 42 -day mortality ra te over 
time and ideally should be mentioned  
 
Line 210 -218 - Please revise this paragraph with more interpretation of the literature, 
rather than listing data from other studies  
 
Line 237 - Please use an alternative word to "besides"  
 
Line 257 - Please rev ise the grammar of this sentence  
 
Line 265 -296 - Please revise the grammar of these sentences  
 
Line 270 -272 - The reference quoted did not specifically look at NAFLD prevalence.  
Furthermore, this is somewhat contradicting the statement in Line 248 -249, where the 
prevalence of NAFLD in selected Taiwanese populations is as high as 48.4%, although 
the prevalence of cirrhosis is not mentioned.  
 
Line 273 -276 - Glomerulonephritis  
 
Line 285 - please remove "multiplicatively independent effect"  
 
Line 297 - suggest adding "individually" after CKD.  
 
 
 
Discretionary Revisions  
Nil 
 
Level of Interest  
An article  of limited interest  
 
Quality of Written English  
The overall quality of written English is unsatisfactory for publication without addressing 
the issues above.  
 
Quality of Figures  
Acceptable  
 
Statistical Review  
Yes, and I have assessed the statistics in my  report.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn ade quately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical  review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five y ears received reimbursements, fees, funding, or salary from 
an organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may i n any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial com peting interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
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