Diarrhoeal diseases are the second leading cause of morbidity and mortality in children under five, accounting for an estimated 370 000 deaths in 2019 worldwide [1]. Most childhood diarrhoeal cases and the associated morbidity and mortality occur in low- and middle-income countries (LMICs). Children in these nations experience, on average, three diarrhoeal episodes every year [1], […]

Background: Non-communicable diseases represent a major global health challenge. Among these, diabetic ketoacidosis (DKA), an acute complication of type 1 diabetes mellitus in children and adolescents, significantly contributes to worldwide morbidity and mortality. Effective management of DKA relies on adequate insulin therapy, but variability in dosing, administration, and frequency leads to increased risk of complications and delayed DKA resolution. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the insulin dose and route of administration regimens for managing pediatric DKA. Methods: This review followed the PRISMA guidelines and was registered on PROSPERO (CRD42024568747). A comprehensive search of PubMed, CINAHL, Cochrane Library, and Scopus identified studies examining insulin regimens in pediatric DKA. Eligible studies were assessed for risk of bias using the Cochrane’s Risk of Bias (RoB-2) tool, and data were pooled using Review Manager for meta-analysis. Outcomes included morbidity (cerebral injury, hypoglycemia, hypokalemia), mortality, hospital stay, and adverse events. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. This review was commissioned by the WHO for the development of consolidated guidelines on common childhood illnesses. Results: Twelve RCTs, involving 530 participants, were included. A lower insulin dose (0.05 U/kg/h) was associated with a significantly reduced risk of hypoglycemia (RR = 0.39, 95% CI: 0.18–0.88, p = 0.02) and hypokalemia (RR = 0.54, 95% CI: 0.33,0.89, p = 0.01) compared to 0.1 U/kg/h. There were no significant differences in mortality and length of hospital stay between the dosing regimens. Additionally, no significant differences were observed in the incidence of cerebral injury and other adverse events. Conclusions: Findings suggest that lower insulin doses may reduce the risks of hypoglycemia and hypokalemia in children with mild-to-moderate DKA without increasing the risk of mortality, cerebral injury, or length of hospital stay. Further studies are needed to provide an evidence-based core outcome set and refine insulin dosing strategies across the full spectrum of disease severity.

Background: Diabetic ketoacidosis (DKA), a life-threatening complication of type 1 diabetes, requires prompt fluid resuscitation to restore circulatory volume and correct metabolic abnormalities. However, the optimal fluid type, volume, and tonicity remain unclear due to concerns regarding cerebral injury and electrolyte imbalances. Methods: We searched PubMed, CINAHL, Cochrane, Scopus, Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform without date restrictions for randomized controlled trials (RCTs) evaluating fluid regimens in children with DKA. Risk of bias was assessed using the Cochrane RoB-2 tool, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was conducted using RevMan 5.4. Results: The review included 10 RCTs (n = 2291). Children receiving a 20 mL/kg bolus followed by 0.9% saline exclusively for rehydration may have a higher risk of adverse events (AEs) than those receiving 10 mL/kg (risk ratio [RR] = 1.11, 95% CI = 1.01-1.23, low certainty of evidence). However, in children given 0.9% saline exclusively for rehydration, there was a significantly lower risk of hypoglycemia in the 20 mL/kg bolus group compared to the 10 mL/kg group (RR = 0.78, 95% CI = 0.62-0.99, high certainty). For rehydration fluid, compared to 0.45% saline, 0.9% saline (48-72 hours) was associated with a higher risk of hypoglycemia (RR = 1.35, 95% CI = 1.06-1.72, high certainty) and AEs (RR = 1.18, 95% CI = 1.05-1.31, low certainty). Over 36 hours, 0.9% saline may be associated with more AEs (RR = 1.15, 95% CI = 1.03-1.27, low certainty). Conclusion: Smaller bolus volumes may be safer than larger ones, and prolonged use of 0.9% saline may increase the risk of hypoglycemia and AEs, although the certainty of evidence was low.

Background: Diarrhea poses a significant public health challenge, particularly affecting children under five. The link between malnutrition and diarrhea is well established, with diarrhea being a primary cause of malnutrition in young children and malnutrition exacerbating the severity of diarrhea. While the World Health Organization (WHO) recommends a comprehensive approach to both diarrhea and malnutrition management, including oral rehydration, continuous feeding, zinc supplementation, and antibiotics for specific strains, it does not adequately address the complex needs of malnourished children with diarrhea who may benefit from enhanced care in the form of follow-up and monitoring beyond initial treatment. We aimed to assess the effectiveness of enhanced care—defined as hospitalization, close clinical monitoring, or longer follow-up after completion of treatment—compared to WHO-defined standard care in improving clinical outcomes among malnourished children aged 0 to 10 years experiencing acute or persistent diarrhea. Methods: A systematic search across PubMed, CINAHL, Cochrane Library, and Scopus identified 1494 records from 2000 onwards. Observational studies and randomized trials assessing the effectiveness of enhanced care for malnutrition and diarrhea in children in community- or hospital-based settings were considered. This review was commissioned by WHO to revise their guidelines on childhood diarrhea management. Results: Of the 1494 records, 1417 studies were excluded during the title and abstract screening. The remaining 77 studies underwent full-text screening, but all were excluded for not meeting the eligibility criteria. However, three studies assessing alternative care were presented, but none focused on enhanced care. Consequently, no synthesis or risk of bias was conducted. Conclusions: Our review did not identify studies meeting the definition of enhanced care for dehydrating diarrhea in malnourished children, underscoring the need for further research. Future reviews focusing on additional risk factors, including HIV and age, are also essential to establish conclusive evidence regarding the effectiveness of enhanced care in managing children with diarrhea.