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Purpose The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. Methods The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO.sub.2 3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. Results The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO.sub.2 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO.sub.2 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO.sub.2 < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h mortality in liberal vs permissive comparison was 1.16 (0.49-2.74; p = 0.73); HFNT vs LFO comparison was 0.60 (0.33-1.06; p = 0.08). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare. Conclusions Respiratory support with HFNT showing potential benefit should prompt further trials., Author(s): K. Maitland [sup.1] [sup.4], S. Kiguli [sup.2], P. Olupot-Olupot [sup.3], M. Hamaluba [sup.4], K. Thomas [sup.5], F. Alaroker [sup.6], R. O. Opoka [sup.2] [sup.7], A. Tagoola [sup.7], V. Bandika [...]

Background. Mentorship is useful in enhancing student learning experiences. The provision of feedback by faculty mentors is a central activity within a fruitful mentorship relationship. Therefore, effective feedback delivery by mentors is key to the development of successful mentorship relationships. Mentorship is a social interactive relationship between mentors and mentees. Therefore, activity theory, a sociocultural theory, has been applied in this study to develop a framework for feedback delivery within the mentorship educational alliance between mentors and mentees. Objective. The purpose of the study was to explore experiences of students and faculty mentors regarding feedback in a mentorship relationship, and to develop a feedback delivery framework in a mentorship relationship underpinned by activity theory. Methods. This was a mixed-method sequential study conducted at Makerere University College of Health Sciences using both quantitative and qualitative data collection methods. The study involved undergraduate medical students and faculty mentors. Data were collected through self-administered questionnaires, focus group discussions and interviews. Descriptive statistics were used for quantitative data, while thematic analysis was used for qualitative data. Results. Most students reported negative experiences with feedback received during the mentorship process. Of the total of 150, a significant number of students (n=60) reported receiving no feedback at all from their mentors. One hundred students reported that feedback received from mentors focused on only weaknesses, and 80 reported that the feedback was not timely. A total of 130 students reported that the feedback sessions were a one-way process, with limited involvement of mentees. The feedback also tended to focus on academics, with limited emphasis on psychosocial contextual aspects that may potentially influence student learning. The focus group discussions with students confirmed most of the quantitative findings. The interviews with faculty mentors led to the emergence of two key themes, namely: (i) limited understanding of feedback delivery during mentorship; and (ii) need for feedback guidelines for faculty mentors. Based on the findings of the mixed-method study as well as the theory guiding the study, a feedback framework for mentorship interactions has been suggested. Conclusion. While students generally reported low satisfaction with feedback received from mentors, faculty suggested the need to have feedback guidelines for mentors to frame their feedback during mentorship interactions. A feedback framework to guide mentorship interactions has therefore been suggested as a result of this study, guided by principles of activity theory. [ABSTRACT FROM AUTHOR]

Prior studies indicate a substantial link between maternal depression and early child health but give limited consideration to the direction of this relationship or the context in which it occurs. We sought to create a contextually informed conceptual framework of this relationship through semi-structured interviews with women that had lived experience of caring for an HIV-infected child while coping with depression and anxiety symptoms. Caregivers explained their role in raising healthy children as complex and complicated by poverty, stigma, and isolation. Caregivers discussed the effects of their own mental health on child well-being as primarily emotional and behavioral, and explained how looking after a child could bring distress, particularly when unable to provide desired care for sick children. Our findings suggest the need for investigation of the reciprocal effects of child sickness on caregiver wellness and for integrated programs that holistically address the needs of HIV-affected families. [ABSTRACT FROM AUTHOR]

A clarification to the article "Dilemmas in undertaking research in paediatric intensive care" that was published in 2014 issue is presented.

Objective To describe chest radiograph findings among children hospitalized with clinically diagnosed severe pneumonia and hypoxaemia at three tertiary facilities in Uganda. Methods The study involved clinical and radiograph data on a random sample of 375 children aged 28 days to 12 years enrolled in the Children's Oxygen Administration Strategies Trial in 2017. Children were hospitalized with a history of respiratory illness and respiratory distress complicated by hypoxaemia, defined as a peripheral oxygen saturation (SpO2) < 92%. Radiologists blinded to clinical findings interpreted chest radiographs using standardized World Health Organization method for paediatric chest radiograph reporting. We report clinical and chest radiograph findings using descriptive statistics. Findings Overall, 45.9% (172/375) of children had radiological pneumonia, 36.3% (136/375) had a normal chest radiograph and 32.8% (123/375) had other radiograph abnormalities, with or without pneumonia. In addition, 28.3% (106/375) had a cardiovascular abnormality, including 14.9% (56/375) with both pneumonia and another abnormality. There was no significant difference in the prevalence of radiological pneumonia or of cardiovascular abnormalities or in 28-day mortality between children with severe hypoxaemia (SpO2: < 80%) and those with mild hypoxaemia (SpO2: 80 to < 92%). Conclusion Cardiovascular abnormalities were relatively common among children hospitalized with severe pneumonia in Uganda. The standard clinical criteria used to identify pneumonia among children in resource-poor settings were sensitive but lacked specificity. Chest radiographs should be performed routinely for all children with clinical signs of severe pneumonia because it provides useful information on both cardiovascular and respiratory systems. [ABSTRACT FROM AUTHOR]

Background: Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period.Methods: We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether-lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin-piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice-Williams-Peterson total-time approach.Results: From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P<0.001). The lower incidence of readmission or death in the chemoprevention group than in the placebo group was restricted to the intervention period (week 3 through week 14) (hazard ratio, 0.30; 95% CI, 0.22 to 0.42) and was not sustained after that time (week 15 through week 26) (hazard ratio, 1.13; 95% CI, 0.87 to 1.47). No serious adverse events were attributed to dihydroartemisinin-piperaquine.Conclusions: In areas with intense malaria transmission, 3 months of postdischarge malaria chemoprevention with monthly dihydroartemisinin-piperaquine in children who had recently received treatment for severe anemia prevented more deaths or readmissions for any reason after discharge than placebo. (Funded by the Research Council of Norway and the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT02671175.). [ABSTRACT FROM AUTHOR]

Background: Severe anemia (hemoglobin level, <6 g per deciliter) is a leading cause of hospital admission and death in children in sub-Saharan Africa. The World Health Organization recommends transfusion of 20 ml of whole-blood equivalent per kilogram of body weight for anemia, regardless of hemoglobin level.Methods: In this factorial, open-label trial, we randomly assigned Ugandan and Malawian children 2 months to 12 years of age with a hemoglobin level of less than 6 g per deciliter and severity features (e.g., respiratory distress or reduced consciousness) to receive immediate blood transfusion with 20 ml per kilogram or 30 ml per kilogram. Three other randomized analyses investigated immediate as compared with no immediate transfusion, the administration of postdischarge micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole. The primary outcome was 28-day mortality.Results: A total of 3196 eligible children (median age, 37 months; 2050 [64.1%] with malaria) were assigned to receive a transfusion of 30 ml per kilogram (1598 children) or 20 ml per kilogram (1598 children) and were followed for 180 days. A total of 1592 children (99.6%) in the higher-volume group and 1596 (99.9%) in the lower-volume group started transfusion (median, 1.2 hours after randomization). The mean (±SD) volume of total blood transfused per child was 475±385 ml and 353±348 ml, respectively; 197 children (12.3%) and 300 children (18.8%) in the respective groups received additional transfusions. Overall, 55 children (3.4%) in the higher-volume group and 72 (4.5%) in the lower-volume group died before 28 days (hazard ratio, 0.76; 95% confidence interval [CI], 0.54 to 1.08; P = 0.12 by log-rank test). This finding masked significant heterogeneity in 28-day mortality according to the presence or absence of fever (>37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days.Conclusions: Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586.). [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends not performing transfusions in African children hospitalized for uncomplicated severe anemia (hemoglobin level of 4 to 6 g per deciliter and no signs of clinical severity). However, high mortality and readmission rates suggest that less restrictive transfusion strategies might improve outcomes.Methods: In this factorial, open-label, randomized, controlled trial, we assigned Ugandan and Malawian children 2 months to 12 years of age with uncomplicated severe anemia to immediate transfusion with 20 ml or 30 ml of whole-blood equivalent per kilogram of body weight, as determined in a second simultaneous randomization, or no immediate transfusion (control group), in which transfusion with 20 ml of whole-blood equivalent per kilogram was triggered by new signs of clinical severity or a drop in hemoglobin to below 4 g per deciliter. The primary outcome was 28-day mortality. Three other randomizations investigated transfusion volume, postdischarge supplementation with micronutrients, and postdischarge prophylaxis with trimethoprim-sulfamethoxazole.Results: A total of 1565 children (median age, 26 months) underwent randomization, with 778 assigned to the immediate-transfusion group and 787 to the control group; 984 children (62.9%) had malaria. The children were followed for 180 days, and 71 (4.5%) were lost to follow-up. During the primary hospitalization, transfusion was performed in all the children in the immediate-transfusion group and in 386 (49.0%) in the control group (median time to transfusion, 1.3 hours vs. 24.9 hours after randomization). The mean (±SD) total blood volume transfused per child was 314±228 ml in the immediate-transfusion group and 142±224 ml in the control group. Death had occurred by 28 days in 7 children (0.9%) in the immediate-transfusion group and in 13 (1.7%) in the control group (hazard ratio, 0.54; 95% confidence interval [CI], 0.22 to 1.36; P = 0.19) and by 180 days in 35 (4.5%) and 47 (6.0%), respectively (hazard ratio, 0.75; 95% CI, 0.48 to 1.15), without evidence of interaction with other randomizations (P>0.20) or evidence of between-group differences in readmissions, serious adverse events, or hemoglobin recovery at 180 days. The mean length of hospital stay was 0.9 days longer in the control group.Conclusions: There was no evidence of differences in clinical outcomes over 6 months between the children who received immediate transfusion and those who did not. The triggered-transfusion strategy in the control group resulted in lower blood use; however, the length of hospital stay was longer, and this strategy required clinical and hemoglobin monitoring. (Funded by the Medical Research Council and Department for International Development; TRACT Current Controlled Trials number, ISRCTN84086586.). [ABSTRACT FROM AUTHOR]

Introduction Women living in HIV-affected communities in sub-Sahara Africa are at increased risk for anxiety and depression. Objective We aimed to assess the effect of a year-long parenting program in rural Eastern Uganda on caregiver's depression and anxiety symptoms and assess their functioning. Methods One hundred and twenty-two caregivers and their HIV-infected preschool children (2-5 years) were randomly assigned to biweekly Mediational Intervention for Sensitizing Caregivers (MISC) training or a health and nutrition curriculum (treatment as usual-TAU). Dyads were assessed at baseline, 6-, 12- and 24-months. Primary outcomes were caregiver's depression and anxiety symptoms (Hopkins Symptom Checklist) and functional impairment. Treatment arms were compared using mixed effects models adjusting for outcome values at baseline, age, sex, and ARV status. Results Fifty-eight child-caregiver dyads received the intervention and 60 received TAU. Most (75%) caregivers were the biological mothers of children and had a mean age of 37 years. At baseline, 63% of women had clinically relevant symptoms of depression or anxiety. Compared to TAU, caregivers in the treatment arm had a reduction in depressive symptoms at 24-months (HSCL-25 score = 0.75 vs. 0.92, P = 0.06), and functionality significantly increased at 6-months (0.32 vs 0.49; P = 0.02) and was sustained at 12-months (0.24 vs 0.39; P = 0.04). Discussion Findings show that caregiver mental health and functioning was significantly better in those who received the parenting training, compared to those who received TAU. Conclusions Parenting training interventions can be useful to promote both maternal mental health and child development in low-income countries. [ABSTRACT FROM AUTHOR]

Background: Pneumonia remains the leading cause of mortality among children under 5 years. Poor nutritional status increases pneumonia mortality. Nutritional status assessed by anthropometry alone does not provide information on which body composition element predicts survival. Body composition proxy measures including arm-fat-area (AFA), arm-muscle-area (AMA), and arm-muscle-circumference (AMC) could be useful predictors., Objective: To compare the ability of fat and muscle mass indices to predict 6-month survival among children with severe pneumonia., Methods: This prospective cohort study was nested in the COAST-Nutrition trial (ISRCTN10829073, 06/06/2018) conducted between June 2020 and October 2022 in Uganda and Kenya. We included children aged 6-59 months hospitalized for severe pneumonia with hypoxemia. Children with severe malnutrition, known chronic lung or cardiac diseases were excluded. Anthropometry and clinical status were assessed at enrolment and at follow-up to day 180. We examined Receiver Operator Characteristic (ROC) curves of fat and muscle mass indices with 6-month survival as the outcome, and compared the areas under the curve (AUCs) using chi-square tests. Cox survival analysis models assessed time-to-mortality., Results: We included 369 participants. The median age was 15-months (IQR 9, 26), and 59.4% (219/369) of participants were male. The baseline measurements were: median MUAC 15.0 cm (IQR 14.0,16.0); arm-fat-area 5.6cm 2 (IQR 4.7, 6.8); arm-muscle-area 11.4cm 2 (IQR 10.0, 12.7); and arm-muscle-circumference 12.2 cm (IQR 11.5, 12.9). Sixteen (4.3%) participants died and 4 (1.1%) were lost-to-follow-up. The AUC for Arm-Fat-Area was not significantly higher than that for Arm-Muscle-Area and Arm-Muscle-Circumference [AUC 0.77 (95%CI 0.64-0.90) vs. 0.61 (95%CI 0.48-0.74), p = 0.09 and 0.63 (95%CI 0.51-0.75), p = 0.16 respectively], but was not statistically different from MUAC (AUC 0.73 (95%CI 0.62-0.85), p = 0.47). Increase in Arm-Fat-Area and Arm-Muscle-Circumference significantly improved survival [aHR 0.40 (95%CI 0.24-0.64), p = < 0.01 and 0.59 (95%CI 0.36-1.06), p = 0.03 respectively]. Survival prediction using Arm-Fat-Area was not statistically different from that of MUAC (p = 0.54)., Conclusions: Muscle mass did not predict 6-month survival better than fat mass in children with severe pneumonia. Fat mass appears to be a better predictor. Effects of fat and muscle could be considered for prognosis and targeted interventions., (© 2024. The Author(s).)

Background: Sub-Saharan Africa bears the highest burden of sickle cell disease (SCD) globally with Nigeria, Democratic Republic of Congo, Tanzania, Uganda being the most affected countries. Uganda reports approximately 20,000 SCD births annually, constituting 6.67% of reported global SCD births. Despite this, there is a paucity of comprehensive data on SCD from the African continent. SCD registries offer a promising avenue for conducting prospective studies, elucidating disease severity patterns, and evaluating the intricate interplay of social, environmental, and genetic factors. This paper describes the establishment of the Sickle Pan Africa Research Consortium (SPARCo) Uganda registry, encompassing its design, development, data collection, and key insights learned, aligning with collaborative efforts in Nigeria, Tanzania, and Ghana SPARCo registries., Methods: The registry was created using pre-existing case report forms harmonized from the SPARCo data dictionary and ontology to fit Uganda clinical needs. The case report forms were developed with SCD data elements of interest including demographics, consent, baseline, clinical, laboratory and others. That data was then parsed into a customized REDCap database, configured to suit the optimized ontologies and support retrieval aggregations and analyses. Patients were enrolled from one national referral and three regional referral hospitals in Uganda., Results: A nationwide electronic patient-consented registry for SCD was established from four regional hospitals. A total of 5,655 patients were enrolled from Mulago National Referral Hospital (58%), Jinja Regional Referral (14.4%), Mbale Regional Referral (16.9%), and Lira Regional Referral (10.7%) hospitals between June 2022 and October 2023., Conclusion: Uganda has been able to develop a SCD registry consistent with data from Tanzania, Nigeria and Ghana. Our findings demonstrate that it's feasible to develop longitudinal SCD registries in sub-Saharan Africa. These registries will be crucial for facilitating a range of studies, including the analysis of SCD clinical phenotypes and patient outcomes, newborn screening, and evaluation of hydroxyurea use, among others. This initiative underscores the potential for developing comprehensive disease registries in resource-limited settings, fostering collaborative, data-driven research efforts aimed at addressing the multifaceted challenges of SCD in Africa., (© 2024. The Author(s).)

Abstract: After starting hydroxyurea treatment, Ugandan children with sickle cell anemia had 60% fewer severe or invasive infections, including malaria, bacteremia, respiratory tract infections, and gastroenteritis, than before starting hydroxyurea treatment (incidence rate ratio, 0.40 [95% confidence interval, 0.29-0.54]; P < .001)., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital discharge. We conducted a systematic review and individual patient data meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention in children recovering from severe anaemia., Methods: This analysis was conducted according to PRISMA-IPD guidelines. We searched multiple databases on Aug 28, 2023, without date or language restrictions, for randomised controlled trials comparing monthly post-discharge malaria chemoprevention with placebo or standard of care among children (aged <15 years) admitted with severe anaemia in malaria-endemic Africa. Trials using daily or weekly malaria prophylaxis were not eligible. The investigators from all eligible trials shared pseudonymised datasets, which were standardised and merged for analysis. The primary outcome was all-cause mortality during the intervention period. Analyses were performed in the modified intention-to-treat population, including all randomly assigned participants who contributed to the endpoint. Fixed-effects two-stage meta-analysis of risk ratios (RRs) was used to generate pooled effect estimates for mortality. Recurrent time-to-event data (readmissions or clinic visits) were analysed using one-stage mixed-effects Prentice-Williams-Peterson total-time models to obtain hazard ratios (HRs). This study is registered with PROSPERO, CRD42022308791., Findings: Our search identified 91 articles, of which 78 were excluded by title and abstract, and a further ten did not meet eligibility criteria. Three double-blind, placebo-controlled trials, including 3663 children with severe anaemia, were included in the systematic review and meta-analysis; 3507 (95·7%) contributed to the modified intention-to-treat analysis. Participants received monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (mean 3·1 courses per child [range 1-6]; n=1085; The Gambia), monthly artemether-lumefantrine given at the end of weeks 4 and 8 post discharge (n=1373; Malawi), or monthly dihydroartemisinin-piperaquine given at the end of weeks 2, 6, and 10 post discharge (n=1049; Uganda and Kenya). During the intervention period, post-discharge malaria chemoprevention was associated with a 77% reduction in mortality (RR 0·23 [95% CI 0·08-0·70], p=0·0094, I 2 =0%) and a 55% reduction in all-cause readmissions (HR 0·45 [95% CI 0·36-0·56], p<0·0001) compared with placebo. The protective effect was restricted to the intervention period and was not sustained after the direct pharmacodynamic effect of the drugs had waned. The small number of trials limited our ability to assess heterogeneity, its sources, and publication bias., Interpretation: In malaria-endemic Africa, post-discharge malaria chemoprevention reduces mortality and readmissions in recently discharged children recovering from severe anaemia. Post-discharge malaria chemoprevention could be a valuable strategy for the management of this group at high risk. Future research should focus on methods of delivery, options to prolong the protection duration, other hospitalised groups at high risk, and interventions targeting non-malarial causes of post-discharge morbidity., Funding: The Research-Council of Norway and the Bill-&-Melinda-Gates-Foundation through the Worldwide-Antimalarial-Research-Network., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Cerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI-MRA) in sub-Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood-based brain biomarkers of cerebral infarcts have been identified in non-SCA adults. Using plasma samples from a well-characterized cross-sectional sample of Ugandan children with SCA, we explored relationships between biomarker levels and MRI-detected cerebral infarcts and transcranial Doppler (TCD) arterial velocity. Testing was performed using a 4-plex panel of brain injury biomarkers, including neurofilament light chain (NfL), a central nervous system neuron-specific protein. Mean biomarker levels from the SCA group (n = 81) were similar to those from non-SCA sibling controls (n = 54). Within the SCA group, NfL levels were significantly higher in those with MRI-detected infarcts compared to no infarcts, and higher with elevated TCD velocity versus normal velocity. Elevated NfL remained strongly associated with MRI-detected infarcts after adjusting for sex and age. All non-SCA controls and SCA participants lacking MRI-detected infarcts had low NfL levels. These data suggest potential utility of plasma-based NfL levels to identify children with SCA cerebrovascular injury. Replication and prospective studies are needed to confirm these novel findings and the clinical utility of NfL versus MRI imaging., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Data from small clinical trials in the United States and India suggest zinc supplementation reduces infection in adolescents and adults with sickle cell anemia (SCA), but no studies of zinc supplementation for infection prevention have been conducted in children with SCA living in Africa. We conducted a randomized double-blind placebo-controlled trial to assess zinc supplementation for prevention of severe or invasive infections in Ugandan children 1.00-4.99 years with SCA. Of 252 enrolled participants, 124 were assigned zinc (10 mg) and 126 assigned placebo once daily for 12 months. The primary outcome was incidence of protocol-defined severe or invasive infections. Infection incidence did not differ between treatment arms (282 vs. 270 severe or invasive infections per 100 person-years, respectively, incidence rate ratio of 1.04 [95% confidence interval (CI), 0.81, 1.32, p=0.78]), adjusting for hydroxyurea treatment. There was also no difference between treatment arms in incidence of serious adverse events or SCA-related events. Children receiving zinc had increased serum levels after 12-months, but at study exit, 41% remained zinc deficient (<65 μg/dL). In post-hoc analysis, occurrence of stroke or death was lower in the zinc treatment arm (adjusted hazard ratio (95% CI), 0.22 (0.05, 1.00); p=0.05). Daily 10 mg zinc supplementation for 12 months did not prevent severe or invasive infections in Ugandan children with SCA, but many supplemented children remained zinc deficient. Optimal zinc dosing and the role of zinc in preventing stroke or death in SCA warrant further investigation. This trial was registered at clinicaltrials.gov as #NCT03528434., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: An estimated 300,000 babies are born with sickle cell anaemia (SCA) annually. Affected children have chronic ill health and suffer premature death. Febrile illnesses such as malaria commonly precipitate acute crises in children with SCA. Thus, chemoprophylaxis for malaria is an important preventive strategy, but current regimes are either sub-optimally effective (e.g. monthly sulphadoxine-pyrimethamine, SP) or difficult to adhere to (e.g. daily proguanil). We propose dihydroartemisinin-piperaquine (DP) as the agent with the most potential to be used across Africa., Methods: This will be a randomised, double-blind, parallel-group superiority trial of weekly single-day courses of DP compared to monthly single-day courses of SP in children with SCA. The study will be conducted in eastern (Uganda) and southern (Malawi) Africa using randomisation stratified by body weight and study centre. Participants will be randomised using an allocation of 1:1 to DP or SP. We will investigate the efficacy, safety, acceptability and uptake and cost-effectiveness of malaria chemoprevention with weekly courses of DP vs monthly SP in 548 to 824 children with SCA followed up for 12-18 months. We will also assess toxicity from cumulative DP dosing and the development of resistance. Participant recruitment commenced on 30 April 2021; follow-up is ongoing., Discussion: At the end of this study, findings will be used to inform regional health policy. This manuscript is prepared from protocol version 2.1 dated 1 January 2022., Trial Registration: The trial was registered at ClinicalTrials.gov, NCT04844099 . Registered on 08 April 2021., (© 2023. The Author(s).)

Children recovering from severe malarial anaemia (SMA) remain at high risk of readmission and death after discharge from hospital. However, a recent trial found that post-discharge malaria chemoprevention (PDMC) with dihydroartemisinin-piperaquine reduces this risk. We developed a mathematical model describing the daily incidence of uncomplicated and severe malaria requiring readmission among 0-5-year old children after hospitalised SMA. We fitted the model to a multicentre clinical PDMC trial using Bayesian methods and modelled the potential impact of PDMC across malaria-endemic African countries. In the 20 highest-burden countries, we estimate that only 2-5 children need to be given PDMC to prevent one hospitalised malaria episode, and less than 100 to prevent one death. If all hospitalised SMA cases access PDMC in moderate-to-high transmission areas, 38,600 (range 16,900-88,400) malaria-associated readmissions could be prevented annually, depending on access to hospital care. We estimate that recurrent SMA post-discharge constitutes 19% of all SMA episodes in moderate-to-high transmission settings., (© 2023. The Author(s).)

Background: Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized., Methods: Between 2014 and 2017, 600 children aged 6-48 months to 4 years hospitalized with severe malaria were enrolled in a prospective clinical cohort study evaluating clinical predictors of mortality in children with severe malaria., Results: The mean age of children in this cohort was 2.1 years (standard deviation, 0.9 years) and 338 children (56.3%) were male. Mortality was 7.3%, and 52.3% of deaths occurred within 12 hours of admission. Coma, acidosis, impaired perfusion, AKI, elevated blood urea nitrogen (BUN), and hyperkalemia were associated with increased mortality (all P < .001). AKI interacted with each risk factor to increase mortality (P < .001 for interaction). Children with clinical indications for dialysis (14.4% of all children) had an increased risk of death compared with those with no indications for dialysis (odds ratio, 6.56; 95% confidence interval, 3.41-12.59)., Conclusions: AKI interacts with coma, acidosis, or impaired perfusion to significantly increase the risk of death in severe malaria. Among children with AKI, those who have hyperkalemia or elevated BUN have a higher risk of death. A better understanding of the causes of these complications of severe malaria, and development and implementation of measures to prevent and treat them, such as dialysis, are needed to reduce mortality in severe malaria., Competing Interests: Potential conflicts of interest. A. L. C. reports being a member of the XXV pediatric Acute Dialysis Quality Initiative on Setting the Landscape and Designing the Future of Pediatric Critical Care Nephrology. C. C. J. reports participation on FEVER DSMB (Birbeck, principal investigator) and Treating Brain Welling in Cerebral Malaria (Taylor, principal investigator). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Medical schools in Sub-Saharan Africa have adopted competency based medical education (CBME) to improve the quality of graduates trained. In 2015, Makerere University College of Health Sciences (MaKCHS) implemented CBME for the Bachelor of Medicine and Bachelor of Surgery (MBChB) programme in order to produce doctors with the required attributes to address community health needs. However, no formal evaluation of the curriculum has been conducted to determine whether all established competencies are being assessed., Objective: To evaluate whether assessment methods within the MBChB curriculum address the stated competencies., Methods: The evaluation adopted a cross-sectional study design in which the MBChB curriculum was evaluated using an Essential Course Evidence Form (ECEF) that was developed to collect information about each assessment used for each course. Information was collected on: (1) Assessment title, (2) Description, (3) Competency domain (4) Sub-competency addressed, (5) Student instructions, and (6) Grading method/details. Data were entered into a structured Access data base. In addition, face-to-face interviews were conducted with faculty course coordinators., Results: The MBChB curriculum consisted of 62 courses over 5 years, focusing on preclinical skills in years 1-2 and clinical skills in years 3-5. Fifty-nine competencies were identified and aggregated into 9 domains. Fifty-eight competencies were assessed at least one time in the curriculum. Faculty cited limited training in assessment as well as large student numbers as hindrances to designing robust assessments for the competencies., Conclusion: CBME was successfully implemented evidenced by all but one of the 59 competencies within the nine domains established being assessed within the MBChB curriculum at MaKCHS. Faculty interviewed were largely aware of it, however indicated the need for more training in competency-based assessment to improve the implementation of CBME., (© 2022. The Author(s).)

Background: Children hospitalised with severe anaemia in malaria-endemic areas are at a high risk of dying or being readmitted within six months of discharge. A trial in Kenya and Uganda showed that three months of postdischarge malaria chemoprevention (PDMC) with monthly dihydroartemisinin-piperaquine (DP) substantially reduced this risk. The World Health Organization recently included PDMC in its malaria chemoprevention guidelines. We conducted a cost-effectiveness analysis of community-based PDMC delivery (supplying all three PDMC-DP courses to caregivers at discharge to administer at home), facility-based PDMC delivery (monthly dispensing of PDMC-DP at the hospital), and the standard of care (no PDMC)., Methods: We combined data from two recently completed trials; one placebo-controlled trial in Kenya and Uganda collecting efficacy data (May 6, 2016 until November 15, 2018; n=1049), and one delivery mechanism trial from Malawi collecting adherence data (March 24, 2016 until October 3, 2018; n=375). Cost data were collected alongside both trials. Three Markov decision models, one each for Malawi, Kenya, and Uganda, were used to compute incremental cost-effectiveness ratios expressed as costs per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were performed to account for uncertainty., Findings: Both PDMC strategies were cost-saving in each country, meaning less costly and more effective in increasing health-adjusted life expectancy than the standard of care. The estimated incremental cost savings for community-based PDMC compared to the standard of care were US$ 22·10 (Malawi), 38·52 (Kenya), and 26·23 (Uganda) per child treated. The incremental effectiveness gain using either PDMC strategy varied between 0·3 and 0·4 QALYs. Community-based PDMC was less costly and more effective than facility-based PDMC. These results remained robust in sensitivity analyses., Interpretation: PDMC under implementation conditions is cost-saving. Caregivers receiving PDMC at discharge is a cost-effective delivery strategy for implementation in malaria-endemic southeastern African settings., Funding: Research Council of Norway., Competing Interests: There are no conflicts of interest to declare., (© 2022 The Authors.)

Objective: Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injury. We performed brain magnetic resonance imaging and angiography (MRI-MRA) in Ugandan children with SCA to identify structural cerebrovascular abnormalities and examine their relationship to standardized clinical assessments., Methods: A sub-sample (n=81) was selected from a cross-sectional study of children attending SCA clinic, including 52 (64.2%) with and 29 (35.8%) without clinically detected abnormalities. Clinical evaluation included assessment for prior stroke, cognitive testing and cerebral arterial transcranial doppler (TCD) flow velocity. MRI-MRA scans were interpreted by at least two neuroradiologists., Results: Mean age was 6.5±2.7 years, with 39 (48.1%) female. Mean haemoglobin was 7.3±0.9 g/dl. Overall, 13 (16.0%) were malnourished. Infarcts and/or stenoses were detected in 55 (67.9%) participants, with stenoses primarily in the anterior circulation. Infarcts were seen in those with normal 17/29 (58.6%) or abnormal 34/52 (65.4%) clinical testing (p=0.181). Neither abnormal MRI nor MRA was associated with age, sex, haemoglobin, or malnutrition. Abnormal MRA was highly associated with infarcts (p<0.0001). Participants with abnormal imaging had two-fold higher proportion of stroke on exam and/or impaired cognition. Stroke on exam was strongly associated with an imaging abnormality after adjusting for age, sex, malnutrition, and haemoglobin (OR 11.8, 95%CI 1.87-74.2)., Conclusion: Over half of these SCA children had cerebrovascular infarcts and/or arterial stenoses. Cerebrovascular disease was frequently undetectable by clinical assessments. While rarely available in under-resourced settings, MRI-MRA brain imaging is an important tool for defining SCA cerebrovascular disease and for assessing impact of clinical intervention trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The funding agency had no role in study design, the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the paper for publication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pediatric critical care has continued to advance since our last article, " Pediatric Critical Care in Resource-Limited Settings-Overview and Lessons Learned" was written just 3 years ago. In that article, we reviewed the history, current state, and gaps in level of care between low- and middle-income countries (LMICs) and high-income countries (HICs). In this article, we have highlighted recent advancements in pediatric critical care in LMICs in the areas of research, training and education, and technology. We acknowledge how the COVID-19 pandemic has contributed to increasing the speed of some developments. We discuss the advancements, some lessons learned, as well as the ongoing gaps that need to be addressed in the coming decade. Continued understanding of the importance of equitable sustainable partnerships in the bidirectional exchange of knowledge and collaboration in all advancement efforts (research, technology, etc.) remains essential to guide all of us to new frontiers in pediatric critical care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bjorklund, Slusher, Day, Yola, Sleeth, Kiragu, Shirk, Krohn and Opoka.)