Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data
Authors: Connon Roisin , George Elizabeth C. , Olupot-Olupot Peter , Kiguli Sarah , Chagaluka George , Alaroker Florence , Opoka Robert O. , Mpoya Ayub , Walsh Kevin , Engoru Charles , Nteziyaremye Julius , Mallewa Macpherson , Kennedy Neil , Nakuya Margaret , Namayanja Cate , Nabawanuka Eva , Sennyondo Tonny , Amorut Denis , Williams Musika C. , Bates Imelda , Boele van Hensbroek M. , Evans Jennifer A. , Uyoga Sophie , Williams Thomas N. , Frost Gary , Gibb Diana M. , Maitland Kathryn , Walker A. Sarah ,   on behalf of the TRACT trial group, Kiguli S. , Opoka R. O. , Nabawanuka E. , Kayaga J. , Williams Musika C. , Kadama E. , Mbwali I. , Nuwabaine L. , Nakikwaku R. , Nsubuga J. , Mpande K. , Adoo R. , Ouma O. , Adia N. K. , Olupot-Olupot P. , Nteziyaremye J. , Namanyanga C. , Passi G. , Sennyondo T. , Adong R. , Okalebo C. B. , Atimango E. , Mwamula S. , Kapsindet J. , Muhindo G. Kiluli R. , Thembo G. Masifa N. , Odong G. , Engoru C. , Aloroker F. , Nakuya M. , Amorut D. , Ariima M. , Itipe M. , Atim M. G. , Abeno M. , Amede B. , Olupot M. , Okwi S. , Kulume M. G. , Among G. , Onyas P. , Achipa E. D. , Maitland K. , Mpoya A. , Maitha P. , Uyoga S. , Williams T. N. , Macharia A. , Mallewa M. , Chagaluka G. , Chimalizeni Y. , Kennedy N. , Kumwenda F. , Nkosi E. , Sochera T. , Malenga A. , Gushu B. , Phiri T. , Chisale A. , Mitole N. , Chokani E. , Munthali A. , Maitland K. , Williams T. N. , Frost G. , Walsheto K. , Gibb D. M. , George E. C. , Thomason M. , Baptiste D. , McCabe L. , Walker A. S. , Ali A. , Khamis K. , Madula M. , Abongo G. , Heydermann R. , Bates I. , Urban B. , Boele van Hensbroek M. , Kyomuhendo F. , Nakalanzi S. , Chabuka J. , Mkandawire N. , Evans J. A. , Gibb D. M. , Fitzgerald F. , Molyneux E. , Murphy I. Lubega M. , Kazembe P. , Crawley J. , Peto T. , Musoke P. , Todd J. , Mirembe G. , Tenu F. 
Published: July 2021

Abstract
Background
Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions.

Methods
Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering.

Results
Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48 (95% CI 1.63–3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19–1.74), p < 0.001); history of transfusion (1.48(1.13–1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21–1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features), who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47–0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47–0.76), p < 0.001); younger-age (1.07 (1.03–1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46–0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23–2.44) and 1.46(1.18–1.82) respectively compared to no splenomegaly.
Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severe malaria.

Conclusions
Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important.

Trial registration
ISRCTN ISRCTN84086586.