Executive function and attention-deficit/hyperactivity disorder in Ugandan children with perinatal HIV exposure

Background: Attention-deficit/hyperactivity disorder (ADHD) is among the most commonly diagnosed mental disorders in childhood and is associated with substantial deficits in executive functioning and lost academic and occupational attainment. This study evaluates symptoms of ADHD and their association with neurocognitive deficits in a cohort of rural Ugandan children who were born to HIV-infected mothers. Methods: We assessed ADHD symptoms and executive function (including memory and attention) in a non-clinical sample of children born to HIV-infected mothers in rural eastern Uganda. Analyses included assessments of the psychometric properties, factor structure, and convergent and discriminant validity of the ADHD measure (ADHD-Rating Scale-IV); and executive function deficits in children meeting symptom criteria for ADHD. Results: 232 children [54% female; mean age 7.8 years (S.D. 2.0)] were assessed for ADHD and executive function deficits. The ADHD measure showed good internal consistency (α = 0.85.) Confirmatory factor analysis showed an acceptable fit for the diagnostic and statistical manual of mental disorders (DSM-5) two-factor model. Subjects meeting DSM-5 symptom criteria for ADHD had worse parent-rated executive function on six out of seven subscales. Conclusions: Our results demonstrate structural validity of the ADHD measure with this population, strong associations between ADHD symptom severity and poorer executive function, and higher levels of executive function problems in perinatally HIV-exposed Ugandan children with ADHD. These findings suggest that ADHD may be an important neurocognitive disorder associated with executive function problems among children in sub-Saharan African settings where perinatal HIV exposure is common

Voltammetric determination of trace elements (Cu, Pb, Zn) in peloid-based pharmaceuticals

The research on the potential health risk posed to consumers by toxic elements that can be found in peloids is still lacking. Moreover, in Polish law no clinical or pharmacological tests are required to identify healing properties of peloids. The objective of this work was to determine some mineral content in selected peloids used in medical treatment. Anodic stripping voltammetry with differential pulse step was used for zinc, copper and lead determination. Decomposition of organic matrix was conducted by a simple wet digestion procedure using acid digestion vessel. Obtained results showed that proposed methods were suitable for the determination of investigated metallic elements. Lead content varied between 0.18 mg/kg (in MaúÊ Borowinowa) and reached up to 15.5 mg/kg of dry weight for Chokrak peloid. Zinc content ranged from 0.64 to 66.87 mg/kg and copper content was between 0.57 and 7.50 mg/kg. The proposed method was validated, the recovery for peloid samples were 94 ñ 102%; 92 ñ 97%; 96 ñ 106% for copper, zinc and lead, respectively

WCN24-2067 Regional differences in acute kidney injury in Ugandan children hospitalized for Hypoxemia

Introduction: Acute kidney injury (AKI) is associated with increased mortality in hospitalized patients and incidence is highest in resource limited settings. The objective of this study was to assess sub-National regional differences in the incidence of AKI in children \u3c5 years of age hospitalized with an acute febrile illness and hypoxemia. Methods: This was a secondary analysis of a stepped wedge cluster randomized controlled trial, which enrolled children \u3c5 years of age hospitalized with hypoxemia between 2019 and 2021. At least one measure of kidney function was available in 1452 children. A single creatinine was measured at enrolment in a sub-set of 495 children with serum stored and AKI defined using KDIGO criteria where baseline creatinine was estimated using the age-based Pottel equation assuming a normal glomerular filtration rate of 120mL/min per 1.73m2. Markers were divided into structural (uNGAL positive, proteinuria, hematuria) or functional (AKI, saliva urea nitrogen (SUN)) measures of kidney injury. Results: 1452 children were included in this AKI sub-study (Figure 1). The mean age of participants was 1.49 years (standard deviation (SD), 1.21) and 55.7% were male (809/1452). Overall 2.6% of children died (38/1452). The majority of participants enrolled were from the West (31.3%) followed by the East (25.3%), North (24.1%), and Central (19.4%) regions. In general, 48.5% of children had AKI (240/495), the prevalence was highest in Eastern Uganda with 62.4% of children having AKI compared to 25.0% of children in Western Uganda, 44% in Central region and 53% in Northern region (p\u3c0.001). Over a third of children had urine NGAL levels ≥150ng/mL, a marker of structural damage, irrespective of site and rates comparable across sites (p=0.095). Other measures of functional and structural kidney injury varied across sites, proteinuria ranged from 6.3% to 14.0% with rates lower in Central and Eastern Uganda compared to Northern and Western Uganda. Hematuria was over two times more common in Eastern and Northern Uganda compared to Central and Western Uganda. Of all the children 49.0 % were positive for malaria based on rapid diagnostic test (RDT) either as positive pLDH or both pLDH and HRP-2. The presence of a single band positive RDT for HRP-2 alone was associated with increased risk of AKI, severe AKI, elevated BUN, a positive SUN test and urinalysis positive for hematuria or urobilinogen (unadjusted p\u3c0.05). Children with a 3-band positive RDT were more likely to have proteinuria, hematuria, bilirubinuria and urobilinogen by dipstick (unadjusted p\u3c0.05). Regional differences in AKI persisted after adjusting for malaria, age, and sex. Conclusions: As we move towards the ISN 0by25 initiative which aims to eliminate preventable deaths from AKI worldwide by 2025. This study provides key in-country data from a resource limited setting, demonstrating marked regional differences in the incidence of AKI in children hospitalized with hypoxaemia and malaria remains an important predictor of AKI. The substantial within-country heterogeneity of AKI highlights the need for further studies to evaluate regional contributors to local patterns of AKI

Plasmodium falciparum EPCR-binding PfEMP1 expression increases with malaria disease severity and is elevated in retinopathy negative cerebral malaria.

Background Expression of group A and the A-like subset of group B Plasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) is associated with severe malaria (SM). The diversity of var sequences combined with the challenges of distinct classification of patient pathologies has made studying the role of distinct PfEMP1 variants on malaria disease severity challenging. The application of retinopathy in the recent years has provided a further method to clinically evaluate children with cerebral malaria (CM). The question of whether children with clinical CM but no retinopathy represent a completely different disease process or a subgroup within the spectrum of CM remains an important question in malaria. In the current study, we use newly designed primer sets with the best coverage to date in a large cohort of children with SM to determine the role of var genes in malaria disease severity and especially CM as discriminated by retinopathy. Methods We performed qRT-PCR targeting the different subsets of these var genes on samples from Ugandan children with CM (n = 98, of whom 50 had malarial retinopathy [RP] and 47 did not [RN]), severe malarial anemia (SMA, n = 47), and asymptomatic parasitemia (AP, n = 14). The primers used in this study were designed based on var sequences from 226 Illumina whole genome sequenced P. falciparum field isolates. Results Increasing severity of illness was associated with increasing levels of endothelial protein C receptor (EPCR)-binding PfEMP1. EPCR-binding PfEMP1 transcript levels were highest in children with combined CM and SMA and then decreased by level of disease severity: RP CM \u3e RN CM \u3e SMA \u3e AP. Conclusions The study findings indicate that PfEMP1 binding to EPCR is important in the pathogenesis of SM, including RN CM, and suggest that increased expression of EPCR-binding PfEMP1 is associated with progressively more severe disease. Agents that block EPCR-binding of PfEMP1 could provide novel interventions to prevent or decrease disease severity in malaria

Pediatric Malaria with Respiratory Distress: Prognostic Significance of Point-of-Care Lactate

Respiratory distress (RD) in pediatric malaria portends a grave prognosis. Lactic acidosis is a biomarker of severe disease. We investigated whether lactate, measured at admission using a handheld device among children hospitalized with malaria and RD, was predictive of subsequent mortality. We performed a pooled analysis of Ugandan children under five years of age hospitalized with malaria and RD from three past studies. In total, 1324 children with malaria and RD (median age 1.4 years, 46% female) from 21 health facilities were included. Median lactate level at admission was 4.6 mmol/L (IQR 2.6–8.5) and 586 patients (44%) had hyperlactatemia (lactate \u3e 5 mmol/L). The mortality was 84/1324 (6.3%). In a mixed-effects Cox proportional hazard model adjusting for age, sex, clinical severity score (fixed effects), study, and site (random effects), hyperlactatemia was associated with a 3-fold increased hazard of death (aHR 3.0, 95%CI 1.8–5.3, p \u3c 0.0001). Delayed capillary refill time (τ = 0.14, p \u3c 0.0001), hypotension (τ = −0.10, p = 0.00049), anemia (τ = −0.25, p \u3c 0.0001), low tissue oxygen delivery (τ = −0.19, p \u3c 0.0001), high parasite density (τ = 0.10, p \u3c 0.0001), and acute kidney injury (p = 0.00047) were associated with higher lactate levels. In children with malaria and RD, bedside lactate may be a useful triage tool, predictive of mortality

Perceptions of orthopaedic medicine students and their supervisors about practice-based learning: an exploratory qualitative study

Background: Practice-based learning is crucial in forming appropriate strategies for improving learning among the medical students that support the country’s understaffed health sector. Unsatisfactory learning consequently results in poor performance of students and poor quality of health care workforce in the long run. Exploring the perceptions about the current practice-based learning system and how to improve is thus vital. This study set out to explore the perceptions of Orthopaedic medicine students and their supervisors about practice-based learning at a tertiary training hospital. Methods: This was an exploratory phenomenological qualitative study that involved in-depth interviews among 10 Orthopedic students during their rotation in the emergency ward of Mulago hospital and 6 of their supervisors. Interviews were audio-recorded, transcribed, and then imported into Atlas ti 8.3 for analysis. The data were coded and grouped into themes relating to perceptions of practice-based learning, general inductive analysis was used. The general inductive approach involved condensing the raw textual data into a brief and summary format. The summarized format was then analyzed to establish clear links between the perceptions of practice-based learning and the summary findings derived from the raw data. Results: The mean age of the students was 23±1.5 years. Four out of the six supervisors were Orthopaedic officers while the remaining two were principal Orthopaedic officers, four out of the six had a university degree while the other two were diploma holders. The main themes arising were hands-on skills, an unconducive learning environment, the best form of learning, and having an undefined training structure. Particularly, the perceptions included the presence of too many students on the wards during the rotation, frequent stock-outs of supplies for learning, and supervisors being overwhelmed caring for a large number of patients. Conclusion: Barriers to satisfactory practice-based learning were overcrowding on the wards and insufficient training materials. To improve practice-based learning, adequate learning materials are required and the number of students enrolled needs to be appropriate for the student – supervisor ratio

Investigating Differences in Nutritional Parameters in Ugandan Children with Plasmodium falciparum Severe Malaria

Background: The past two decades have witnessed a 60% decline in global malaria mortality. However, two thirds of all malaria deaths continue to occur among children <5 years, with a majority in the WHO African Region. Malnutrition is an important risk factor for malaria. Wasting, Stunting and Underweight are crucial indicators of malnutrition, and are associated with increased mortality in children <5. Annually, 14 million children <5 are classified as wasted and 59 million children are classified as stunted. Objective: The objective of this study is to look at nutritional parameters, weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ), and how they differ over time in children <5 with severe malaria (SM) from the Ugandan cities Mulago and Jinja and the outcomes of mortality and nutritional parameters, underweight, stunting, and wasting. Methods: We defined underweight, stunting, and wasting as 2SD below the WAZ, HAZ, and WHZ means. We evaluated Z-scores and mortality status from children <5 years enrolled in a prospective cohort study (NDI, Neurodevelopmental Impairment in Children with Severe Malaria) at enrollment and 12-month follow-up between two sites. Results: WAZ, HAZ and WHZ at baseline were significantly lower among SM groups than in CC (p<0.01), and the SM group maintained significantly lower WHZ (p<0.01) and HAZ (p<0.001) at 12-month follow-up. Among the children who died, there were no significant differences of nutritional markers in Mulago, but in Jinja there was found to be a significant association between mortality and low WAZ (p<0.05) and underweight (p<0.05). Of children classified as underweight in Jinja, 37.5% of them died compared to 15.9% who survived; additionally, the odds ratio for decreased WAZ and mortality was 0.58 (p<0.05). Conclusion: Underweight, stunting, and wasting may be risk factors for SM, and underweight may exacerbate poor mortality outcomes in rural areas like Jinja. While underweight is worsened among children with SM at 1 month and normalizes by 12 months, stunting remains persistently low at 12 months. Nutritional interventions must be aimed at maintaining linear growth throughout the first year of SM in children <5 to reduce the risk factor of underweight on poor mortality outcomes

A Randomized Controlled Trial to Evaluate if Computerized Cognitive Rehabilitation Improves Neurocognition in Ugandan Children with HIV

Objectives: Clinically stable children with HIV can have neuromotor, attention, memory, visual?spatial, and executive function impairments. We evaluated neuropsychological and behavioral benefits of computerized cognitive rehabilitation training (CCRT) in Ugandan HIV children. Design: One hundred fifty-nine rural Ugandan children with WHO Stage I or II HIV disease (6 to 12 years; 77 boys, 82 girls; M?=?8.9, SD?=?1.86 years) were randomized to one of three treatment arms over a 2-month period. Methods: The CCRT arm received 24 one-hour sessions over 2 months, using Captain's Log (BrainTrain Corporation) programmed for games targeting working memory, attention, and visual?spatial analysis. These games progressed in difficulty as the child's performance improved. The second arm was a ?limited CCRT? with the same games rotated randomly from simple to moderate levels of training. The third arm was a passive control group receiving no training. All children were assessed at enrollment, 2 months (immediately following CCRT), and 3 months after CCRT completion. Results: The CCRT group had significantly greater gains through 3 months of follow-up compared to passive controls on overall Kaufman Assessment Battery for Children?second edition (KABC-II) mental processing index (p?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140132/1/aid.2016.0026.pd

Clinical Comparison of Retinopathy-Positive and Retinopathy-Negative Cerebral Malaria

AbstractCerebral malaria (CM) is a severe and often lethal complication of falciparum malaria. A classic malaria retinopathy is seen in some (retinopathy-positive [RP]) children but not others (retinopathy-negative [RN]), and is associated with increased parasite sequestration. It is unclear whether RN CM is a severe nonmalarial illness with incidental parasitemia or a less severe form of the same malarial illness as RP CM. Understanding the clinical differences between RP and RN CM may help shed light on the pathophysiology of malarial retinopathy. We compared clinical history, physical examination, laboratory findings, and outcomes of RP (N = 167) and RN (N = 87) children admitted to Mulago Hospital, Kampala, Uganda. Compared with RN children, RP children presented with a longer history of illness, as well as physical examination and laboratory findings indicative of more severe disease and organ damage. The hospital course of RP children was complicated by longer coma duration and a greater transfusion burden than RN children. Mortality did not differ significantly between RP and RN children (14.4% versus 8.0%, P = 0.14). Further, severity of retinal hemorrhage correlated with the majority of variables that differed between RP and RN children. The data suggest that RP and RN CM may reflect the spectrum of illness in CM, and that RN CM could be an earlier, less severe form of disease