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Browsing by Author "Goings, Michael J."
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Item Acute Kidney Injury Interacts With Coma, Acidosis, and Impaired Perfusion to Significantly Increase Risk of Death in Children With Severe Malaria(Oxford University Press, 2022) Namazzi, Ruth; Opoka, Robert; Datta, Dibyadyuti; Bangirana, Paul; Batte, Anthony; Berrens, Zachary; Goings, Michael J.; Schwaderer, Andrew L.; Conroy, Andrea L.; John, Chandy C.; Pediatrics, School of MedicineBackground: 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.Item Hydroxyurea reduces infections in children with sickle cell anemia in Uganda(American Society of Hematology, 2024) Namazzi, Ruth; Bond, Caitlin; Conroy, Andrea L.; Datta, Dibyadyuti; Tagoola, Abner; Goings, Michael J.; Jang, Jeong Hoon; Ware, Russell E.; Opoka, Robert; John, Chandy C.; Pediatrics, School of MedicineAfter 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 ).Item Severe falciparum malaria in young children is associated with an increased risk of post-discharge hospitalization: a prospective cohort study(Springer Nature, 2024-12-04) Opoka, Robert O.; Namazzi, Ruth; Datta, Dibyadyuti; Bangirana, Paul; Conroy, Andrea L.; Goings, Michael J.; Mellencamp, Kagan A.; John, Chandy C.; Pediatrics, School of MedicineBackground: Few studies have described post-discharge morbidity of children with specific manifestations of severe malaria (SM) beyond severe malarial anaemia or cerebral malaria. Methods: Children 6 months to 4 years of age admitted at Jinja and Mulago hospitals in Uganda, with one or more of the five most common forms of SM, cerebral malaria (n = 53), respiratory distress syndrome (n = 108), malaria with complicated seizures (n = 160), severe malarial anaemia (n = 155) or prostration (n = 75), were followed for 12 months after discharge, alongside asymptomatic community children (CC) (n = 120) of similar ages recruited from the households or neighbourhoods of the children with SM. Incidence and risk of hospitalizations, death or outpatient clinic visits were compared between children with SM and CC. Results: 312/551 (56.6%) of children with SM had one or more post-discharge hospitalization over 12 months, compared to 37/120 (30.8%) of CC. Frequency of hospitalization was similar across all forms of SM. Compared to CC, children with SM had a significantly higher risk of all-cause hospitalization (adjusted hazard ratio (aHR) 1.91, 95% confidence interval (CI) 1.39-2.63, p < 0.001) and hospitalization for severe malaria (aHR 1.94, CI 1.36-2.78, p < 0.001), but a similar risk of outpatient clinic visits for malaria (aHR 1.24, 95% CI 0.89-1.73, p = 0.20). 82% of hospitalizations in children with SM (575/700) and CC (50/61) were due to malaria. Conclusions: In this malaria endemic region, children with the five most common forms of SM had higher rates of post-discharge hospitalization than asymptomatic community children, and > 80% of hospitalizations were due to severe malaria. Studies of post-discharge malaria chemoprevention are urgently needed for children with SM, to determine if this treatment can reduce post-discharge morbidity.Item Zinc for infection prevention in children with sickle cell anemia: a randomized double-blind placebo-controlled trial(American Society of Hematology, 2023) Namazzi, Ruth; Opoka, Robert; Conroy, Andrea L.; Datta, Dibyadyuti; Tagoola, Abner; Bond, Caitlin; Goings, Michael J.; Ryu, Moon-Suhn; Cusick, Sarah E.; Krebs, Nancy F.; Jang, Jeong Hoon; Tu, Wanzhu; Ware, Russell E.; John, Chandy C.; Biostatistics and Health Data Science, School of MedicineData 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.