Acute kidney injury (AKI) is prevalent among children with severe malaria, contributing to considerable morbidity and mortality. Oxidative stress has been implicated in the pathophysiology of malaria-induced AKI, and paracetamol, with its antioxidant properties, has been proposed as a solution. This phase I/II randomized trial evaluated paracetamol as a potential renoprotective adjunct in children with severe malaria and acute kidney injury. We conducted a phase I/II open label parallel randomized controlled trial of 40 hospitalized children aged > 6 months to < 12 years with malaria-induced AKI in eastern Uganda. Participants were randomized by a sealed envelope 1:1 to receive either oral paracetamol 20 mg/kg 6 hourly for 48 h or tepid sponging every 30 min until fever subsided. Only the assessors of the primary outcome were masked to the intervention. The primary outcome was renal recovery at 48 h assessed using restricted mean survival time (RMST) in intention to treat population of children according to their randomization groups. Between 19 September 2021 and 25 August 2023, 250 children with hemoglobinuric severe malaria were screened and the 40 enrolled were randomly assigned paracetamol (n = 20) or tepid sponging (n = 20). The mean age was 6.54 (2.61) years. The mean time to renal recovery in the paracetamol group was 0.491 h (95
Randomisation is an essential component of any clinical trial to eliminate selection bias and ensure similar distribution of confounders between the treatment groups. For randomisation to be successfully implemented, there must be adequate allocation concealment. Many low-cost randomisation and allocation concealment methods have the potential to introduce bias by ineffectively concealing the allocation sequence from the researcher and are now rarely used in high-resource settings. In such settings, centralised randomisation services have been developed to prepare the randomisation sequence, conceal the sequence, and provide a secure mechanism to acquire the allocation. Such services are often prohibitively expensive for researchers in low-resource settings or for small/pilot trials. We describe our experience of adopting a low-cost third-party randomisation and allocation concealment process for emergency neonatal research in a low-resource setting. This was a single-site feasibility trial in Eastern Uganda, which randomly assigned neonates in a 1:1 ratio at birth to receive either early continuous positive airways pressure (intervention) or standard of care (control). Centralised third-party randomisation and allocation were used, with two researchers not involved in the trial serving as randomisation coordinators. The lead coordinator prepared a randomisation schedule using http://www.randomization.com/. This was stored securely on a server with exclusive access granted to the randomisation coordinators. Randomly permuted block randomisation was used to ensure balance between the two arms and enhance concealment in group allocation. Block sizes were varied and kept confidential from the investigators and research assistants to prevent prediction of upcoming assignments, and the randomisation sequence was managed by an independent third party. After identifying and obtaining consent, the research assistant requested an allocation from the randomisation coordinators by SMS. Upon receiving the SMS request, the randomisation coordinators sent the allocation to a study tablet device by email. The time from sending the SMS request to the time the allocation email was received was used to evaluate the suitability of this method. One hundred participants were successfully randomised. Group allocation was received for 91/100 (91.0
BACKGROUND:The global burden of multimorbidity-the coexistence of two or more long-term conditions-is increasing. Limited access to primary care in sub-Saharan Africa means acute hospital admission is often the sentinel multimorbidity presentation. This prospective multicentre cohort study aimed to describe the burden, constituent diseases, and outcomes of multimorbidity among patients acutely admitted to hospital in Malawi and Tanzania. METHODS:Adults (ie, those aged ≥18 years) admitted to four hospitals (two tertiary and two district hospitals) with acute medical conditions were consecutively recruited within 24 h of presentation and followed up for 90 days. We estimated the prevalence of HIV infection, diabetes, hypertension, and chronic kidney disease using commercially available point-of-care tests, and captured self-reported and clinical diagnoses (n/N [%]). Health economic data were summarised by median and IQR and modelled using generalised linear models. All-cause 90-day mortality was summarised with Kalplan-Meier plots and analysed using Cox regression models. FINDINGS:1407 adults (657 [46·7%] were female and 750 [53·3%] were male; mean age was 52·3 years [SD 18·4]) were recruited. We examined multimorbidity prevalence in 1007 participants admitted to three hospitals that accept admissions directly from the community. Multimorbidity was found in 473 (47·0%) of 1007 participants and 292 (29·0%) had a single long-term condition. Outcomes at 90 days were determined for 1317 (93·6%) of 1407 participants. Adjusted 90-day mortality was higher in participants with multimorbidity (335 [41·7%] of 804; hazard ratio 1·5 [95% CI 1·1-2·1]) and those with one long-term condition (80 [28·3%] of 283; 1·5 [1·0-2·1]); compared with those with no long-term conditions (31 [13·5%] of 230). Health-related quality of life was lower in participants with multimorbidity compared with those with one long-term condition (median 0·402 [IQR -0·037 to 0·644] vs 0·557 [0·140 to 0·730]; p=0·005) at baseline, and at final observation (0·858 [0·667 to 1·00] vs 1·00 [0·589 to 1·00] respectively; p=0·01). In Tanzania, medical costs incurred by patients were higher in participants with multimorbidity compared with those with one long-term condition (relative effect 5·77 [95% CI 2·99-11·15]; p<0·0001). INTERPRETATION:Multimorbidity is common in patients admitted to hospital in Malawi and Tanzania and associated with worse survival and increased cost. Multimorbidity is an urgent public health threat that requires fundamental health-care delivery reform to address population needs. FUNDING:National Institute for Health and Care Research and Wellcome Trust. TRANSLATIONS:For the Chichewa and Kiswahili translations of the abstract see Supplementary Materials section.
Birth asphyxia (BA) is a significant global health challenge, contributing to an estimated 23
BACKGROUND:In sub-Saharan Africa, malaria remains a public health problem despite some reports of declining incidence in the period 2000-2018. Since 2019, there have been some reports of disease epidemics and resurgences in areas that had registered steep declines and unusual clinical presentations. This study aimed to describe the epidemiology, clinical spectrum, and outcomes of severe malaria in children among malaria-endemic Eastern Uganda, a region that has recently experienced disease epidemics. METHODS:This prospective study was conducted at Mbale Regional Referral Hospital, Uganda, from 08th May 2019 to August 15, 2023, as part of the Malaria Epidemiological, Pathophysiological and Intervention studies in Highly Endemic Eastern Uganda (EDCTP-TMA2016SF-1514-MEPIE Study). Children aged 60 days to 12 years who at admission tested positive for malaria and fulfilled the clinical World Health Organization criteria for surveillance of severe malaria were enrolled into the study following appropriate informed consent. Data were collected using a customized proforma on social demographic characteristics, clinical presentation, treatment, and outcomes. Laboratory analyses included complete blood counts, lactate, glucose, blood gases, electrolytes, metabolites, and coagulation markers. In addition, urinalysis using dipsticks was done. Data were analysed using STATA V15. The study had ethical and regulatory approval before data collection commenced. RESULTS:A total of 1,379 participants were recruited. The median age was 4 years (2 months-12 years). Most children 757/1379 (54.9%) were under 5 years, and 825/1379 (59.8%) were males. The common symptoms were fever 1368 (99.2%), poor appetite 1095 (79.5%), inability to sit upright 1051 (76.2%), vomiting 944 (68.4%) and yellow eyes 833 (60.4%). The common signs included prostration, haemoglobinuria and jaundice. Prolonged hospitalization was found in 284/1339 (21.2%) and was associated with impaired consciousness 116/166 (30.1%), P = 0.003; haemoglobinuria 514/705 (27.1%), P < 0.001 and jaundice 505/690 (26.8%) P < 0.001. The overall mortality was 40/1347 (3.0%). Children who had > 1 severity feature were at a higher risk of mortality. CONCLUSION:In this prospective study of children with severe malaria in Eastern Uganda, the overall mortality was 3.0% and the more the disease clinical syndromes the higher the risk of death.
