Inflammatory profiles in febrile children with moderate and severe malnutrition presenting at-hospital in Uganda are associated with increased mortality.

BACKGROUND: Children in Africa carry a disproportionate burden of malnutrition and infectious disease. Together, malnutrition and infection are major contributors to global child mortality; however, their collective impact on immune activation are not well described. METHODS: This was a secondary analysis of a prospective cohort study of children hospitalized with acute febrile illness at a single centre in Uganda. We investigated the association between malnutrition (determined using the mid-upper arm circumference, MUAC), immune activation (as measured by inflammatory markers IL-6, IL-8, CXCL10, CHI3L1, sTNFR1, Cystatin C, granzyme B, and sTREM-1), and mortality. FINDINGS: Of the 1850 children eligible for this secondary analysis, 71 (3.8%) and 145 (11.7%) presented with severe acute malnutrition (SAM, MUAC <115 mm) and moderate malnutrition (MUAC 115 to < 125 mm), respectively. SAM was associated with increased concentrations of CHI3L1, sTNFR1, Cystatin C, and sTREM-1, and decreased concentrations of CXCL10 and granzyme B, even after controlling for age, sex, and disease severity at presentation. There were 77 deaths (4.2%). SAM was associated with a 9.2-fold (95% CI 4.8-46), 17-fold (95% CI 3.9-74), and 13-fold (95% CI 3.5-52) increased odds of death in children with pneumonia, malaria, and diarrheal illness, respectively. Mediation analysis implicated sTREM-1 and CHI3L1 in the effect of SAM on mortality, suggesting that enhanced activation of these inflammatory pathways is associated with the increased mortality in undernourished children with pneumonia and malaria. INTERPRETATION: Collectively, these data highlight systemic inflammation as a common pathway associated with malnutrition and infection that could be targeted to mitigate the burden of acute febrile illness in LMICs. FUNDING: This work was supported in part by the Canadian Institutes of Health Research, and by kind donations from The Tesari Foundation and Kim Kertland. The funders had no role in design, analysis, or reporting of these studies.

Biomarkers of Growth Faltering and Neurodevelopmental Delay in Children who are HIV-Exposed but Uninfected: A Systematic Review.

INTRODUCTION: Children who are HIV-exposed but uninfected (CHEU) are at risk of linear growth faltering and neurodevelopmental delay. Circulating biomarkers associated with these adverse outcomes may elucidate pathways of injury. OBJECTIVE: To identify biomarkers associated with growth faltering and neurodevelopmental delay in CHEU. METHODS: We performed a systematic review of electronic databases MEDLINE (1946-April 2021), EMBASE (1974-April 2021), Scopus (2004-April 2021), and PubMed (1985-April 2021), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42021238363). RESULTS: We found seven studies associating biomarker abnormalities and growth outcomes in CHEUs and two studies on biomarker abnormalities and neurodevelopmental delay. Biomarker abnormalities associated with growth restriction were: C-reactive protein (CRP), tumour necrosis factor (TNF), interferon-gamma (IFN-γ), interleukin (IL)-12p70, IFN-γ-induced protein-10 (CXCL10/IP-10), lipopolysaccharide binding protein (LBP), insulin-like growth factor-1 (IGF-1), and IGF-binding protein-1 (IGFBP-1). Biomarkers associated with motor, language, and cognitive delay were CRP, IFN-γ, IL-1ß, -2, -4, -6, -10, -12p70, neutrophil gelatinase-associated lipocalin (NGAL), granulocyte-macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase- 9 (MMP-9). CONCLUSION: Elevated markers of inflammation (acute phase reactants, pro-inflammatory cytokines, chemokines) and intestinal microbial translocation are associated with growth faltering. Elevated markers of inflammation are associated with adverse neurodevelopment.

Cerebrospinal fluid shunt infections in children.

Cerebrospinal fluid (CSF) shunts are commonly used for the long-term management of hydrocephalus in children. Shunt infection remains a common complication, occurring in about 5%-15% of CSF shunts. This narrative review summarises key evidence from recent literature on the epidemiology, pathogenesis, clinical presentation, diagnosis, management, outcomes and prevention of CSF shunt infections in children. The majority of shunt infections occur due to contamination at the time of surgery, with coagulase-negative staphylococci and Staphylococcus aureus being the most common infecting organisms. Clinical presentations of shunt infection can be varied and difficult to recognise. CSF cultures are the primary test used for diagnosis. Other CSF and blood parameters may aid in diagnosis but lack sensitivity and specificity. Core aspects of management of shunt infections include systemic antimicrobial therapy and surgical removal of the shunt. However, many specific treatment recommendations are limited by a lack of robust evidence from large studies or controlled trials. Shunt infections may result in long hospital stays, worsening hydrocephalus, neurological sequelae and other complications, as well as death. Therefore, reducing the incidence of infection and optimising management are high priorities. Antibiotic prophylaxis at the time of shunt placement, improved surgical protocols and antibiotic-impregnated shunts are key strategies to prevent shunt infections. Nevertheless, further work is needed to identify additional strategies to prevent complications and improve outcomes.

Circulating markers of neutrophil activation and lung injury in pediatric pneumonia in low-resource settings.

Diagnostic biomarkers for childhood pneumonia could guide management and improve antibiotic stewardship in low-resource settings where chest x-ray (CXR) is not always available. In this cross-sectional study, we measured chitinase 3-like protein 1 (CHI3L1), surfactant protein D (SP-D), lipocalin-2 (LCN2), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in Ugandan children under the age of five hospitalized with acute lower respiratory tract infection. We determined the association between biomarker levels and primary end-point pneumonia, indicated by CXR consolidation. We included 89 children (median age 11 months, 39% female). Primary endpoint pneumonia was present in 22 (25%). Clinical signs were similar in children with and without CXR consolidation. Broad-spectrum antibiotics (ceftriaxone) were administered in 83 (93%). Levels of CHI3L1, SP-D, LCN2 and TIMP-1 were higher in patients with primary end-point pneumonia compared to patients with normal CXR or other infiltrates. All markers were moderately accurate predictors of primary end-point pneumonia, with area under receiver operator characteristic curves of 0.66-0.70 (p<0.05 for all markers). The probability of CXR consolidation increased monotonically with the number of markers above cut-off. Among 28 patients (31%) in whom all four markers were below the cut-off, the likelihood ratio of CXR consolidation was 0.11 (95%CI 0.015 to 0.73). CHI3L1, SP-D, LCN2 and TIMP-1 were associated with CXR consolidation in children with clinical pneumonia in a low-resource setting. Combinations of quantitative biomarkers may be useful to safely withhold antibiotics in children with a low probability of bacterial infection.

Critical appraisal of a mHealth-assisted community-based cardiovascular disease risk screening program in rural Kenya: an operational research study.

Community health workers (CHWs) can participate in the cascade of hypertension and diabetes management in low and middle-income countries (LMICs). Their services may be enhanced with mobile health (mHealth) tools. In this operational research study, we describe the AFYACHAT mHealth-assisted cardiovascular health screening program in rural Kenya. In this study, A CHW screened a convenience sample of adults ≥ 40 years old in rural Kenya for cardiovascular disease (CVD) risk using the two-way AFYACHAT mHealth instrument. AFYACHAT analyzes a patient's age, sex, smoking, diabetes and systolic blood pressure and provides a four-tiered 10-year CVD risk score. User acceptability was assessed by an end-of-study interview with the CWH. Automated error logs were analyzed. Patient satisfaction was measured with a six-question satisfaction questionnaire. Screened participants with high CVD risk were followed-up via telephone to explore any actions taken following screening. In 24 months, one CHW screened 1650 participants using AFYACHAT. The 10-year risk of CVD was <10% for 1611 (98%) patients, 10 to <20% for 26 (1.6%), 20 to <30% in 12 (0.7%), and ≥30% for 1 (0.1%). The point prevalence of hypertension and diabetes was 27% and 1.9%, respectively. Seventy-five percent of participants with elevated CVD risk sought further medical care. There was high acceptability, a 15% miscode error rate, and high participant satisfaction with the screening program. Our operational research outlines how AFYACHAT mHealth tool can assist CHW perform rapid CVD screening; this provides a model framework for non-communicable disease screening in LMICs.

Anemia and transfusion requirements among Ugandan children with severe malaria treated with intravenous artesunate.

Parenteral artesunate for the treatment of severe malaria in non-immune travelers is associated with late-onset hemolysis. In children in sub-Saharan Africa, the hematologic effects of malaria and artesunate are less well documented. Here we report a prospective case series of 91 children with severe malaria treated with parenteral artesunate, managed at a resource-poor hospital in Africa, with longitudinal data on hemoglobin (Hb), lactate dehydrogenase (LDH), haptoglobin, and erythrocyte morphology. The median (range) age was 2 (1-8) years and 43 (47%) were female. The median (IQR) admission Hb level was 69 (55-78) g/L and 20 patients (22%) had severe malarial anemia (Hb < 50 g/L). During hospitalization, 69 patients (76%) received one or more blood transfusions. Fatal outcome in 8 patients was associated with severe anemia in 6/8 cases. Follow-up Hb measurement was performed on 35 patients (38%) at day 14 after initial hospital admission; the remaining patients had no clinical evidence of anemia at the follow-up visit. The convalescent Hb was median (range) 90 (60-138) g/L, which was significantly higher than the paired admission levels (median increase +28 g/L, p < .001). Evidence of hemolysis (elevated LDH and low haptoglobin) was common at admission and improved by day 14. No patient met the standardized definition of post-artemisinin delayed hemolysis (PADH). In this cohort of young children with severe malaria treated with artesunate, anemia was common at admission, required one or more transfusions in a majority of patients, and markers of hemolysis had normalized by day 14.

Delayed surgery leads to reduced elbow range of motion in children with supracondylar humeral fractures managed at a referral hospital in sub-Saharan Africa.

BACKGROUND: Supracondylar humeral fractures (SHFs) in children are associated with morbidity due to elbow stiffness. Timely operative management and/or physiotherapy are thought to reduce this complication, but pose challenges in settings with limited resources for health. METHODS: This prospective cohort study included 45 pediatric patients with isolated SHF at a large tertiary hospital in Nairobi, Kenya. Patients were managed non-operatively or operatively with varying wait times to surgery, with or without physiotherapy. The measurement of elbow ROM was done up to 12 weeks after removal of Kirshner wires and/or backslab. RESULTS: Elbow ROM increased in the follow-up period, yet residual restricted mobility in the flexion-extension plane was common. Delayed surgical management ≥7 days was associated with reduced elbow ROM in the flexion-extension plane at 12 weeks median IQR 105° 92°-118° vs 120° 108°-124°, p=0.029. Physiotherapy was associated with reduced ROM at 12 weeks p=0.003, possibly due to the use of prolonged immobilization. CONCLUSION: In this study of pediatric SHFs at a resource-limited hospital, elbow flexion was restricted at 12 weeks follow-up and was associated with major delays in operative management. Quality of orthopedic surgical care and physiotherapy services in low-resource settings deserves further attention.

Community-based screening for cardiovascular risk using a novel mHealth tool in rural Kenya.

BACKGROUND: An increasing burden of cardiovascular disease (CVD) in low-resource settings demands innovative public health approaches. OBJECTIVES: To design and test a novel mHealth tool for use by community health workers (CHWs) to identify individuals at high CVD risk who would benefit from education and/or pharmacologic interventions. METHODS: We designed and implemented a novel two-way mobile phone application, "AFYACHAT," to rapidly screen for CVD risk in rural Kenya. AFYACHAT collects and stores SMS text message data entered by a CHW on a subject's age, sex, smoking, diabetes, and systolic blood pressure, and returns as SMS text message the category of 10-year CVD risk: "GREEN" (<10% 10 year risk of cardiovascular event), "YELLOW" (10 to <20%), "orange"(20 to <30%), or "RED" (≥30%). CHWs were equipped and trained to use an automated blood pressure device and the mHealth tool. RESULTS: Five CHWs screened 2,865 subjects in remote rural communities in Kenya over a 22 month period (2015-17). The median age of subjects was 50 (IQR 43 to 60) and 1581 (55%) were female. Point prevalence of hypertension (systolic blood pressure>140mmHg), diabetes, and tobacco use were 23%, 3.2%, and 22%, respectively. Overall, the 10-year risk of CVD among patients was <10% in 2778 (97%) patients, 10 to <20% in 65 (2.3%), 20 to <30% in 12 (0.4%), and ≥30% in 10 (0.2%). CONCLUSION: We have developed a mHealth tool that can be used by CHWs to screen for CVD risk factors, demonstrating proof-of-concept in rural Kenya.

Multiple Administrations of Gadobutrol in the Pediatric Brain: No Change in T1 Signal at MRI.

Purpose To determine whether multiple doses of gadobutrol increase the T1 signal intensity in the brains of children. Materials and Methods This retrospective imaging study evaluated 91 children (median age, 5.4 years; age range, 0-17 years) with brain tumors who underwent five or more MR brain examinations at a single institution. A subgroup of 46 patients received five or more administrations of gadobutrol (0.1 mmol/kg) and underwent follow-up MRI. T1 signal intensity in the globus pallidus and dentate nucleus was measured at the first to sixth unenhanced MR brain examination in these children. Globus pallidus-to-corpus callosum and dentate nucleus-to-corpus callosum signal intensity ratios were analyzed by linear mixed-effect analysis. Subgroup analysis was performed for six children who underwent 14 or more administrations of gadobutrol. Results The globus pallidus-to-corpus callosum ratio increased with patient age (absolute change, 0.0052 per year; 95% confidence interval: 0.0033, 0.0071; P < .0001). There was no change in the dentate nucleus-to-corpus callosum ratio with age (P = .30). Among 46 children who received five or more doses of gadobutrol (median dose, 11 mL; range, 3.9-31 mL), there was no change in signal intensity ratio of the globus pallidus (P = .17) or dentate nucleus (P = .44). Among six children who underwent more than 14 administrations of gadobutrol (median dose, 64 mL; range, 40-91 mL) there was no change in signal intensity ratio of the globus pallidus (P = .15) or dentate nucleus (P = .50). Conclusion No increase in T1-weighted signal intensity ratio was observed in the globus pallidus or dentate nucleus after the administration of at least five doses of gadobutrol. © RSNA, 2018 Online supplemental material is available for this article.

Estradiol Levels Are Altered in Human Immunodeficiency Virus-Infected Pregnant Women Randomized to Efavirenz-Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy.

Background: Combination antiretroviral therapy (cART) use in pregnancy has been associated with hormonal dysregulation. We performed a secondary retrospective analysis of longitudinal progesterone and estradiol levels in pregnancy using specimens from the Protease Inhibitors to Reduce Malaria Morbidity in HIV-infected Pregnant Women study, which randomized Ugandan human immunodeficiency virus (HIV)-infected ART-naive women to initiate either lopinavir/ritonavir (LPV/r)-based or efavirenz (EFV)-based cART. Methods: Three hundred twenty-six women (160 randomized to the EFV arm and 166 women to the LPV/r arm) with at least 1 plasma sample collected during pregnancy were included. Enrollment samples collected prior to cART initiation were used as a cART-naive comparator group. Hormone levels were quantified by enzyme-linked immunosorbent assay. Results: Estradiol levels were differentially affected by the 2 cART regimens. Exposure to LPV/r was associated with an increase in estradiol (P < .0001), whereas exposure to EFV was associated with a decrease in estradiol (P < .0001), relative to the cART-naive gestationally matched comparator group. Lower estradiol levels correlated with small for gestational age (SGA) (P = .0019) and low birth weight (P = .019) in the EFV arm, while higher estradiol levels correlated with SGA in the LPV/r arm (P = .027). Although progesterone levels were similar between treatment arms, we observed an association between SGA and lower progesterone in the LPV/r arm (P = .04). No association was observed between hormone levels and preterm birth in either arm. Levels of progesterone and estradiol were lower in cases of stillbirth, and levels of both hormones declined immediately prior to stillbirth in 5 of 8 cases. Conclusions: Combination ART regimens differentially affect estradiol levels in pregnancy, a hormone critical to the maintenance of a healthy pregnancy. Identifying cART regimens that minimize perinatal HIV transmission without contributing to hormonal dysregulation represents an urgent public health priority. Clinical Trials Registration: NCT00993031.

Repurposing Pharmaceuticals as Neuroprotective Agents for Cerebral Malaria.

BACKGROUND: Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection which may result in death or developmental disability. The pathologic processes leading to CM are not fully elucidated; however, widely accepted mechanisms include parasite sequestration, release of infected red blood cell contents, activation of endothelial cells, increased inflammatory responses, and ultimately dysfunction of the neurovascular unit (NVU). The endothelium plays a central role in these processes as the site of parasitized erythrocyte sequestration and as the regulator of fluid extravasation into the central nervous system. Modulating endothelial barrier function at the NVU may provide new therapeutic approaches to improve outcomes in CM. METHODS: Here we provide a narrative review of the literature of peer-reviewed research relating to adjunctive therapies for CM. We discuss regulatory pathways of the NVU, with a focus on the potential for pharmacologic modulation of the NVU to improve CM outcomes. RESULTS: Recently licensed pharmaceuticals, developed as therapies for cancer or neurologic disease, could be re-purposed for use as host-directed therapies in CM to target pathways involved in endothelial stability and activation. CONCLUSION: The findings of this review highlight recently licensed pharmaceuticals that may be developed as future adjunctive therapies for CM.

Validation of two multiplex platforms to quantify circulating markers of inflammation and endothelial injury in severe infection.

Biomarkers can prognosticate outcome and enable risk-stratification. In severe infection, focusing on multiple markers reflecting pathophysiological mechanisms of organ injury could enhance management and pathway-directed therapeutics. Limited data exist on the performance of multiplex biomarker platforms. Our goal was to compare endothelial and immune activation biomarkers in severe pediatric infections using two multiplex platforms. Frozen plasma from 410 children presenting to the Jinja Regional Hospital in Uganda with suspected infection was used to measure biomarkers of endothelial (Angiopoietin-2, sFlt-1, sVCAM-1, sICAM-1) and immune (IL-6, IP-10, sTNFR-1, CHI3L1) activation. Two multiplex platforms (Luminex®, EllaTM) based on monoclonal antibody sandwich immunoassays using biotin-streptavidin conjugate chemistry were selected with reagents from R&D Systems. The two platforms differed in ease and time of completion, number of samples per assay, and dynamic concentration range. Intra-assay variability assessed using a coefficient of variation (CV%) was 2.2-3.4 for Luminex® and 1.2-2.9 for EllaTM. Correlations for biomarker concentrations within dynamic range of both platforms were best for IL-6 (ρ = 0.96, p<0.0001), IP-10 (ρ = 0.94, p<0.0001) and sFlt-1 (ρ = 0.94, p<0.0001). Agreement between concentrations obtained by both methods assessed by the Bland-Altman test varied, with best agreement for CHI3L1. Our data suggest that biomarkers of endothelial and immune activation can be readily measured with multiplex platforms. Luminex® and EllaTM produced reliable results with excellent CV% values. The EllaTM platform was more automated and completed in 75 minutes, potentially compatible with near-patient use. Trends in concentrations obtained by these methods were highly correlated, although absolute values varied, suggesting caution is required when comparing data from different multiplex platforms.

Radiation Exposure from Diagnostic Imaging in a Cohort of Pediatric Transplant Recipients.

Recipients of solid organ transplants (SOT) have extensive diagnostic imaging (DI). The purpose of this study was to quantify this exposure. Children from northern Alberta with SOTs at Stollery Children's Hospital, Edmonton, Alberta January 1, 2006, to July 31, 2012, were included. Effective doses of radiation were estimated using published norms for DI performed post-transplant up to October 16, 2014. The 54 eligible children had 6215 DI studies (5628 plain films, 293 computerized tomography (CT) scans, 149 positron emission topography (PET) -CT scans, 47 nuclear medicine scans and 98 cardiac catheterizations). Children less than 5 years of age underwent more DI studies than did older children (median (IQR) 140 (66-210) vs 49 (19-105), p = 0.010). Children with post-transplant lymphoproliferative disorder (N = 8) had more CT scans (median (IQR) 13 (5.5-36) vs 1 (0-5), p<0.001) and PET-CT scans (median (IQR) 3.5 (1.5-8) vs 0 (0-0), p<0.001) than did other children. The estimated cumulative effective dose attributed to DI studies post-transplant was median (range) 78 (4.1-400) millisievert (mSv), and 19 of 54 children (35%; 95% confidence interval 24-49%) had a dose >100 mSv. In conclusion, a significant proportion of pediatric transplant recipients have sufficient radiation exposure post-transplant for DI to be at potential risk for radiation-induced malignancies.

Dysregulation of angiopoietin-1 plays a mechanistic role in the pathogenesis of cerebral malaria.

Cerebral malaria is a leading cause of global morbidity and mortality. Interventions targeting the underlying pathophysiology of cerebral malaria may improve outcomes compared to treatment with antimalarials alone. Microvascular leak plays an important role in the pathogenesis of cerebral malaria. The angiopoietin (Ang)-Tie-2 system is a critical regulator of vascular function. We show that Ang-1 expression and soluble Tie-2 expression were associated with disease severity and outcome in a prospective study of Ugandan children with severe malaria and in a preclinical murine model of experimental cerebral malaria. Ang-1 was necessary for maintenance of vascular integrity and survival in a mouse model of cerebral malaria. Therapeutic administration of Ang-1 preserved blood-brain barrier integrity and, in combination with artesunate treatment, improved survival beyond that with artesunate alone. These data define a role for dysregulation of the Ang-Tie-2 axis in the pathogenesis of cerebral malaria and support the evaluation of Ang-Tie-2-based interventions as potential adjunctive therapies for treating severe malaria.

Immunizations in Children Requiring Warfarin Therapy.

Children with conditions requiring chronic warfarin therapy have increased. The importance of receiving immunizations in this population is magnified due to potential weakness in their immune response. There is concern about immunizing on therapeutic anticoagulation due to risk of hematomas and the influence of vaccine on warfarin metabolism. This study evaluated the influence of vaccines on warfarin effect as measured by the International Normalized Ratio and the clinically relevant hematomas or bruising postimmunization. There were no clinically relevant negative outcomes postimmunizations. This study demonstrates that immunizations may be safely administered to children receiving therapeutic warfarin therapy.

Lack of household clustering of malaria in a complex humanitarian emergency: implications for active case detection.

BACKGROUND: Malaria contributes to elevated morbidity and mortality in populations displaced by conflict in tropical zones. In an attempt to reduce malaria transmission in an internally displaced persons (IDP) camp in eastern Democratic Republic of Congo (DRC), we tested a strategy of active case detection of household contacts of malaria cases. METHODS: Prospective community-based survey. RESULTS: From a convenience sample of 100 febrile patients under 5 years of age from the IDP camp presenting to a nearby clinic for management of a fever episode, 19 cases of uncomplicated malaria and 81 controls with non-malarial febrile illness (NFMI) were diagnosed. We engaged community health workers in the IDP camp to screen their household contacts for malaria using rapid diagnostic tests. We detected 29 cases of malaria through this active case-finding procedure. Household contacts of children with uncomplicated malaria were no more likely to have positive Plasmodium falciparum antigenemia than controls with NFMI (OR 0.89, 95% CI 0.33 to 2.4, p = 1.0), suggesting that malaria cases did not cluster at the household level. However, household contacts reporting mild symptoms at the time of community survey (headache, myalgia) had a higher odds of malaria than asymptomatic individuals (OR 14 (95% CI 4.2-48), p ≤ 0.001 and 18 (95% CI 5.9-54), p ≤ 0.001, respectively). CONCLUSION: Screening household contacts of malaria cases was not an efficient case-finding strategy in a Congolese IDP camp. Symptom-based screening may be a simpler and cost-effective method to identify individuals at increased risk of malaria for targeted screening and treatment in an IDP camp.

Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality.

Background. Acute kidney injury (AKI) is a well recognized complication of severe malaria in adults, but the incidence and clinical importance of AKI in pediatric severe malaria (SM) is not well documented. Methods. One hundred eighty children aged 1 to 10 years with SM were enrolled between 2011 and 2013 in Uganda. Kidney function was monitored daily for 4 days using serum creatinine (Cr). Acute kidney injury was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Blood urea nitrogen (BUN) and Cr were assessed using i-STAT, and cystatin C (CysC) was measured by enzyme-linked immunosorbent assay. Results. Eighty-one (45.5%) children had KDIGO-defined AKI in the study: 42 (51.9%) stage 1, 18 (22.2%) stage 2, and 21 (25.9%) stage 3. Acute kidney injury evolved or developed in 50% of children after admission of hospital. There was an increased risk of AKI in children randomized to inhaled nitric oxide (iNO), with 47 (54.0%) of children in the iNO arm developing AKI compared with 34 (37.4%) in the placebo arm (relative risk, 1.36; 95% confidence interval [CI], 1.03-1.80). Duration of hospitalization increased across stages of AKI (P = .002). Acute kidney injury was associated with neurodisability at discharge in the children receiving placebo (25% in children with AKI vs 1.9% in children with no AKI, P = .002). Mortality increased across stages of AKI (P = .006) in the placebo arm, reaching 37.5% in stage 3 AKI. Acute kidney injury was not associated with neurodisability or mortality at discharge in children receiving iNO (P > .05 for both). Levels of kidney biomarkers were predictive of mortality with areas under the curves (AUCs) of 0.80 (95% CI, .65-.95; P = .006) and 0.72 (95% CI, .57-.87; P < .001), respectively. Admission levels of CysC and BUN were elevated in children who died by 6 months (P < .0001 and P = .009, respectively). Conclusions. Acute kidney injury is an underrecognized complication in young children with SM and is associated with increased mortality.

Applying a knowledge-to-action framework for primary prevention of spina bifida in tropical Africa.

Maternal periconceptual folate supplementation reduces the incidence of neural tube defects; however, in settings where population-level food fortification is not available, it is not clear how best to promote this prevention strategy. Guided by a knowledge-to-action methodology, we used mixed quantitative and qualitative methods to define the local disease burden, then designed, implemented and evaluated a culturally tailored educational intervention in eastern Democratic Republic of Congo, where resource limitations and threats to human security contribute to restricted capacity for the prevention and management of congenital malformations. A descriptive case series of 27 patients undergoing surgery for spina bifida demonstrated a short-term mortality of 15% and long-term disability in survivors. A survey of knowledge, attitudes and practices demonstrated a low level of folate awareness (53%) among women of reproductive age. Focus group discussions revealed exotic aetiologic views, significant gender issues and several barriers to folate use. A culturally tailored radio broadcast and an educational video were designed and produced locally based on qualitative and quantitative findings. Evaluation of the video documented high levels of viewer satisfaction and unequivocal knowledge gain (P ≤ 0.001). We conclude that spina bifida poses a significant burden on affected patients and their families in the African context, but folate is underutilized as a prevention strategy. Patient education through video media results in increased awareness and understanding of spina bifida and folate, a first step in empowering women to reduce the risk of spina bifida in their children in the absence of population-wide food fortification.

Validation of supra-pubic ultrasonography for preoperative prostate volume measurement in sub-Saharan Africa.

BACKGROUND: Advances in urological techniques in sub-Saharan Africa need to be supported with practical ancillary diagnostics. This study aimed at determining the accuracy of suprapubic ultrasonography (SPUS) relative to transrectal ultrasonography (TRUS), the current gold standard, in estimating preoperative prostate volume in a sub-Saharan African hospital. METHODS: Cross-sectional study of prospectively enrolled patients with severe lower urinary tract symptoms and histologically confirmed benign prostatic hyperplasia. The volume of the prostate was estimated using two modalities, SPUS and TRUS. Open prostatectomy was performed on all patients, and the mass of the enucleated prostate adenoma was measured directly. RESULTS: Fifty patients were enrolled, with a mean age of 69 years. The mean prostate volume as determined by TRUS, SPUS, and direct measurement of enucleated prostatic tissue was 96.0, 95.9 and 83.5 mL, respectively. Prostate volume determined by SPUS correlated strongly with the TRUS measurement (ρ = 0.98, P < 0.001). The mean difference between the volume estimates by TRUS and SPUS was 0.09 mL [95% CI -2.07 to 1.89, P = 0.93], with upper and lower limits of agreement of -13.8 and +13.6 mL, respectively. Sensitivity, specificity, positive and negative predictive value for SPUS relative to TRUS for classifying patients according to the indication for TURP (prostate volume ≤80 mL) versus open prostatectomy (>80 mL) were 95% or higher. The volume of the enucleated adenoma was less than the volume estimated by ultrasonography by approximately 12.5 mL. CONCLUSION: SPUS is accurate relative to TRUS in assessing preoperative volume of the prostate and can be used in the African context to assign patients to open prostatectomy or TURP.