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Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition

High mortality after discharge from hospital following acute illness has been observed among children with Severe Acute Malnutrition (SAM). However, mechanisms that may be amenable to intervention to reduce risk are unknown. We performed a nested case-control study among HIV-uninfected children aged 2-59 months treated for complicated SAM according to WHO recommendations at four Kenyan hospitals. Blood was drawn from 1778 children when clinically judged stable before discharge from hospital. Cases were children who died within 60 days. Controls were randomly selected children who survived for one year without readmission to hospital. Untargeted proteomics, total protein, cytokines and chemokines, and leptin were assayed in plasma and corresponding biological processes determined. Among 121 cases and 120 controls, increased levels of calprotectin, von Willebrand factor, angiotensinogen, IL8, IL15, IP10, TNFalpha, and decreased levels of leptin, heparin cofactor 2, and serum paraoxonase were associated with mortality after adjusting for possible confounders. Acute phase responses, cellular responses to lipopolysaccharide, neutrophil responses to bacteria, and endothelial responses were enriched among cases. Among apparently clinically stable children with SAM, a sepsis-like profile is associated with subsequent death. This may be due to ongoing bacterial infection, translocated bacterial products or deranged immune response during nutritional recovery.
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Effect of Previous Exposure to Malaria on Blood Pressure in Kilifi, Kenya: A Mendelian Randomization Study

Background Malaria exposure in childhood may contribute to high blood pressure ( BP ) in adults. We used sickle cell trait ( SCT ) and alpha(+)thalassemia, genetic variants conferring partial protection against malaria, as tools to test this hypothesis. Methods and Results Study sites were Kilifi, Kenya, which has malaria transmission, and Nairobi, Kenya, and Jackson, Mississippi, where there is no malaria transmission. The primary outcome was 24-hour systolic BP. Prevalent hypertension, diagnosed using European Society of Hypertension thresholds was a secondary outcome. We performed regression analyses adjusting for age, sex, and estimated glomerular filtration rate. We studied 1127 participants in Kilifi, 516 in Nairobi, and 651 in Jackson. SCT frequency was 21% in Kilifi, 16% in Nairobi, and 9% in Jackson. SCT was associated with -2.4 (95% CI , -4.7 to -0.2) mm Hg lower 24-hour systolic BP in Kilifi but had no effect in Nairobi/Jackson. The effect of SCT in Kilifi was limited to 30- to 59-year-old participants, among whom it was associated with -6.1 mm Hg ( CI , -10.5 to -1.8) lower 24-hour systolic BP. In pooled analysis allowing interaction by site, the effect of SCT on 24-hour systolic BP in Kilifi was -3.5 mm Hg ( CI , -6.9 to -0.1), increasing to -5.2 mm Hg ( CI , -9.5 to -0.9) when replacing estimated glomerular filtration rate with urine albumin to creatinine ratio as a covariate. In Kilifi, the prevalence ratio for hypertension was 0.86 ( CI , 0.76-0.98) for SCT and 0.89 ( CI , 0.80-0.99) for alpha(+)thalassemia. Conclusions Lifelong malaria protection is associated with lower BP in Kilifi. Confirmation of this finding at other sites and elucidating the mechanisms involved may yield new preventive and therapeutic targets.
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Effect of enhancing audit and feedback on uptake of childhood pneumonia treatment policy in hospitals that are part of a clinical network: a cluster randomized trial

BACKGROUND: The World Health Organization (WHO) revised its clinical guidelines for management of childhood pneumonia in 2013. Significant delays have occurred during previous introductions of new guidelines into routine clinical practice in low- and middle-income countries (LMIC). We therefore examined whether providing enhanced audit and feedback as opposed to routine standard feedback might accelerate adoption of the new pneumonia guidelines by clinical teams within hospitals in a low-income setting. METHODS: In this parallel group cluster randomized controlled trial, 12 hospitals were assigned to either enhanced feedback (n = 6 hospitals) or standard feedback (n = 6 hospitals) using restricted randomization. The standard (network) intervention delivered in both trial arms included support to improve collection and quality of patient data, provision of mentorship and team management training for pediatricians, peer-to-peer networking (meetings and social media), and multimodal (print, electronic) bimonthly hospital specific feedback reports on multiple indicators of evidence guideline adherence. In addition to this network intervention, the enhanced feedback group received a monthly hospital-specific feedback sheet targeting pneumonia indicators presented in multiple formats (graphical and text) linked to explicit performance goals and action plans and specific email follow up from a network coordinator. At the start of the trial, all hospitals received a standardized training on the new guidelines and printed booklets containing pneumonia treatment protocols. The primary outcome was the proportion of children admitted with indrawing and/or fast-breathing pneumonia who were correctly classified using new guidelines and received correct antibiotic treatment (oral amoxicillin) in the first 24 h. The secondary outcome was the proportion of correctly classified and treated children for whom clinicians changed treatment from oral amoxicillin to injectable antibiotics. RESULTS: The trial included 2299 childhood pneumonia admissions, 1087 within the hospitals randomized to enhanced feedback intervention, and 1212 to standard feedback. The proportion of children who were correctly classified and treated in the first 24 h during the entire 9-month period was 38.2% (393 out of 1030) and 38.4% (410 out of 1068) in the enhanced feedback and standard feedback groups, respectively (odds ratio 1.11; 95% confidence interval [CI] 0.37-3.34; P = 0.855). However, in exploratory analyses, there was evidence of an interaction between type of feedback and duration (in months) since commencement of intervention, suggesting a difference in adoption of pneumonia policy over time in the enhanced compared to standard feedback arm (OR = 1.25, 95% CI 1.14 to 1.36, P < 0.001). CONCLUSIONS: Enhanced feedback comprising increased frequency, clear messaging aligned with goal setting, and outreach from a coordinator did not lead to a significant overall effect on correct pneumonia classification and treatment during the 9-month trial. There appeared to be a significant effect of time (representing cumulative effect of feedback cycles) on adoption of the new policy in the enhanced feedback compared to standard feedback group. Future studies should plan for longer follow-up periods to confirm these findings. TRIAL REGISTRATION: US National Institutes of Health-ClinicalTrials.gov identifier (NCT number) NCT02817971 . Registered September 28, 2016-retrospectively registered.
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Patient costs of hypertension care in public health care facilities in Kenya

BACKGROUND: Hypertension in low- and middle-income countries, including Kenya, is of economic importance due to its increasing prevalence and its potential to present an economic burden to households. In this study, we examined the patient costs associated with obtaining care for hypertension in public health care facilities in Kenya. METHODS: We conducted a cross-sectional study among adult respondents above 18 years of age, with at least 6 months of treatment in two counties. A total of 212 patients seeking hypertension care at five public facilities were interviewed, and information on care seeking and the associated costs was obtained. We computed both annual direct and indirect costs borne by these patients. RESULTS: Overall, the mean annual direct cost to patients was US$ 304.8 (95% CI, 235.7-374.0). Medicines (mean annual cost, US$ 168.9; 95% CI, 132.5-205.4), transport (mean annual cost, US$ 126.7; 95% CI, 77.6-175.9), and user charges (mean annual cost, US$ 57.7; 95% CI, 43.7-71.6) were the highest direct cost categories. Overall mean annual indirect cost was US$ 171.7 (95% CI, 152.8-190.5). The incidence of catastrophic health care costs was 43.3% (95% CI, 36.8-50.2) and increased to 59.0% (95% CI, 52.2-65.4) when transport costs were included. CONCLUSIONS: Hypertensive patients incur substantial direct and indirect costs. High rates of catastrophic costs illustrate the urgency of improving financial risk protection for these patients and strengthening primary care to ensure affordability of hypertension care.
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Mortality after inpatient treatment for diarrhea in children: a cohort study

BACKGROUND: There is an increasing recognition that children remain at elevated risk of death following discharge from health facilities in resource-poor settings. Diarrhea has previously been highlighted as a risk factor for post-discharge mortality. METHODS: A retrospective cohort study was conducted to estimate the incidence and demographic, clinical, and biochemical features associated with inpatient and 1-year post-discharge mortality amongst children aged 2-59 months admitted with diarrhea from 2007 to 2015 at Kilifi County Hospital and who were residents of Kilifi Health and Demographic Surveillance System (KHDSS). Log-binomial regression was used to identify risk factors for inpatient mortality. Time at risk was from the date of discharge to the date of death, out-migration, or 365 days later. Post-discharge mortality rate was computed per 1000 child-years of observation, and Cox proportion regression used to identify risk factors for mortality. RESULTS: Two thousand six hundred twenty-six child KHDSS residents were admitted with diarrhea, median age 13 (IQR 8-21) months, of which 415 (16%) were severely malnourished and 130 (5.0%) had a positive HIV test. One hundred twenty-one (4.6%) died in the hospital, and of 2505 children discharged alive, 49 (2.1%) died after discharge: 21.4 (95% CI 16.1-28.3) deaths per 1000 child-years. Admission with signs of both diarrhea and severe pneumonia or severe pneumonia alone had a higher risk of both inpatient and post-discharge mortality than admission for diarrhea alone. There was no significant difference in inpatient and post-discharge mortality between children admitted with diarrhea alone and those with other diagnoses excluding severe pneumonia. HIV, low mid-upper arm circumference (MUAC), and bacteremia were associated with both inpatient and post-discharge mortality. Signs of circulatory impairment, sepsis, and abnormal electrolytes were associated with inpatient but not post-discharge mortality. Prior admission and lower chest wall indrawing were associated with post-discharge mortality but not inpatient mortality. Age, stuntedness, and persistent or bloody diarrhea were not associated with mortality before or after discharge. CONCLUSIONS: Our results accentuate the need for research to improve the uptake and outcomes of services for malnutrition and HIV as well as to elucidate causal pathways and test interventions to mitigate these risks.
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