Exploring sources of variability in adherence to guidelines across hospitals in low-income settings: a multi-level analysis of a cross-sectional survey of 22 hospitals.

BACKGROUND: Variability in processes of care and outcomes has been reported widely in high-income settings (at geographic, hospital, physician group and individual physician levels); however, such variability and the factors driving it are rarely examined in low-income settings. METHODS: Using data from a cross-sectional survey undertaken in 22 hospitals (60 case records from each hospital) across Kenya that aimed at evaluating the quality of routine hospital services, we sought to explore variability in four binary inpatient paediatric process indicators. These included three prescribing tasks and use of one diagnostic. To examine for sources of variability, we examined intra-class correlation coefficients (ICC) and their changes using multi-level mixed models with random intercepts for hospital and clinician levels and adjusting for patient and clinician level covariates. RESULTS: Levels of performance varied substantially across indicators and hospitals. The absolute values for ICCs also varied markedly ranging from a maximum of 0.48 to a minimum of 0.09 across the models for HIV testing and prescription of zinc, respectively. More variation was attributable at the hospital level than clinician level after allowing for nesting of clinicians within hospitals for prescription of quinine loading dose for malaria (ICC = 0.30), prescription of zinc for diarrhoea patients (ICC = 0.11) and HIV testing for all children (ICC = 0.43). However, for prescription of correct dose of crystalline penicillin, more of the variability was explained by the clinician level (ICC = 0.21). Adjusting for clinician and patient level covariates only altered, marginally, the ICCs observed in models for the zinc prescription indicator. CONCLUSIONS: Performance varied greatly across place and indicator. The variability that could be explained suggests interventions to improve performance might be best targeted at hospital level factors for three indicators and clinician factors for one. Our data suggest that better understanding of performance and sources of variation might help tailor improvement interventions although further data across a larger set of indicators and sites would help substantiate these findings

Variation in and risk factors for paediatric inpatient all-cause mortality in a low income setting: data from an emerging clinical information network.

BACKGROUND: Hospital mortality data can inform planning for health interventions and may help optimize resource allocation if they are reliable and appropriately interpreted. However such data are often not available in low income countries including Kenya. METHODS: Data from the Clinical Information Network covering 12 county hospitals' paediatric admissions aged 2-59 months for the periods September 2013 to March 2015 were used to describe mortality across differing contexts and to explore whether simple clinical characteristics used to classify severity of illness in common treatment guidelines are consistently associated with inpatient mortality. Regression models accounting for hospital identity and malaria prevalence (low or high) were used. Multiple imputation for missing data was based on a missing at random assumption with sensitivity analyses based on pattern mixture missing not at random assumptions. RESULTS: The overall cluster adjusted crude mortality rate across hospitals was 6 · 2% with an almost 5 fold variation across sites (95% CI 4 · 9 to 7 · 8; range 2 · 1% - 11 · 0%). Hospital identity was significantly associated with mortality. Clinical features included in guidelines for common diseases to assess severity of illness were consistently associated with mortality in multivariable analyses (AROC =0 · 86). CONCLUSION: All-cause mortality is highly variable across hospitals and associated with clinical risk factors identified in disease specific guidelines. A panel of these clinical features may provide a basic common data framework as part of improved health information systems to support evaluations of quality and outcomes of care at scale and inform health system strengthening efforts

A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi

Introduction Moderate to severe acute malnutrition (SAM/MAM) and severe anaemia are important and associated co-morbidities in children aged less than five years. Independently, these two morbidities are responsible for high risk of in-hospital and post-discharge deaths and hospital readmissions. The primary objective of this study is to investigate the risk of death among severely anaemic children with moderate to severe acute malnutrition compared to children with severe anaemia alone. Methods This was a retrospective analysis of data collected from a large prospective study that was investigating severe anaemia in children aged less than 5 years old. The study was conducted at Queen Elizabeth Central Hospital in Blantyre and Chikhwawa district hospital in southern Malawi. Children aged less than five years old; with severe anaemia were screened and enrolled. Each child was followed up for eighteen months at one, three, six, twelve and eighteen months after enrolment. Data were analysed using STATA 15. Results Between July 2002 and July 2004, 382 severely anaemic children were enrolled in the main study. A total of 52 children were excluded due to missing anthropometric data. Out of the 330 included, 53 children were moderately to severely malnourished and 277 were not. At the end of the 18-month follow period, 28.3% of children with MAM/SAM died compared to 13% of children without MAM/SAM (RR 2.1, CI 0.9–4.2, p = 0.03). Similarly, children with moderate to severe malnutrition reported a significantly higher number of malaria infection cases (33.9%) compared to children with severe anaemia alone (27.9%, p = 0.02). However, the number of hospitalizations and recurrence of severe anaemia was similar and not statistically significant between the two groups (RR 0.8 (0.4–1.4), p = 0.6 and RR 1.1 (0.3–2.8), p = 0.8). Conclusion Among children with severe anaemia, those who also had moderate to severe malnutrition had a twofold higher risk of dying compared to those who did not. It is therefore crucial to investigate acute malnutrition among severely anaemic children, as this might be treatable factor associated with high mortality

The clinical use of longitudinal bio-electrical impedance vector analysis in assessing stabilization of children with severe acute malnutrition

Background & aims: Severe Acute Malnutrition (SAM) in children is determined using anthropometry. However, bio-electrical impedance (BI) analysis could improve the estimation of altered body composition linked to edema and/or loss of lean body mass in children with SAM. We aimed to assess: 1) the changes in BI parameters during clinical stabilization and 2) whether BI parameters add prognostic value for clinical outcome beyond the use of anthropometry. Methods: This prospective observational study enrolled children, aged 6–60 months, that were admitted at Queen Elizabeth Central Hospital in Blantyre, Malawi, for complicated SAM (i.e., having either severe wasting or edematous SAM with a complicating illness). Height, weight, mid-upper arm circumference (MUAC), and BI were measured on admission and after clinical stabilization. BI measures were derived from height-adjusted indices of resistance (R/H), reactance (Xc/H), and phase angle (PA) and considered to reflect body fluids and soft tissue in BI vector analysis (BIVA). Results: We studied 183 children with SAM (55% edematous; age 23.0 ± 12.0 months; 54% male) and 42 community participants (age 20.1 ± 12.3 months; male 62%). Compared to community participants, the BIVA of children with edematous SAM were short with low PA and positioned low on the hydration axis which reflects severe fluid retention. In contrast, children with severe wasting had elongated vectors with a PA that was higher than children with edematous SAM but lower than community participants. Their BIVA position fell within the top right quadrant linked to leanness and dehydration. BIVA from severely wasted and edematous SAM patients differed between groups and from community children both at admission and after stabilization (p < 0.001). Vector position shifted during treatment only in children with edematous SAM (p < 0.001) and showed a upward translation suggestive of fluid loss. While PA was lower in children with SAM, PA did not contribute more than anthropometry alone towards explaining mortality, length of stay, or time-to-discharge or time-to-mortality. The variability and heterogeneity in BI measures was high and their overall added predictive value for prognosis of individual children was low. Conclusions: BIVA did not add prognostic value over using anthropometry alone to predict clinical outcome. Several implementation challenges need to be optimized. Thus, in low-resource settings, the routine use of BI in the management of pediatric malnutrition is questionable without improved implementation

Dermatological changes in a prospective cohort of acutely ill, hospitalised Malawian children, stratified according to nutritional status

Rationale: Since the first documentation of skin changes in malnutrition in the early 18th century, various hair and skin changes have been reported in severely malnourished children globally. We aimed to describe the frequency and types of skin conditions in children admitted with acute illness to Queen Elizabeth Central Hospital, Blantyre, Malawi across a spectrum of nutritional status and validate an existing skin assessment tool. Methods: Children between 1 week and 23 months of age with acute illness were enrolled and stratified by anthropometry. Standardised photographs were taken, and three dermatologists assessed skin changes and scored each child according to the SCORDoK tool. Results: Among 103 children, median age of 12 months, 31 (30%) had severe wasting, 11 (11%) kwashiorkor (nutritional oedema), 20 (19%) had moderate wasting, 41 (40%) had no nutritional wasting and 18 (17%) a positive HIV antibody test. Six (5.8%) of the included patients died. 51 (50%) of children presented with at least one skin change. Pigmentary changes were the most common, observed in 35 (34%), with hair loss and bullae, erosions and desquamation the second most prevalent skin condition. Common diagnoses were congenital dermal melanocytosis, diaper dermatitis, eczema and postinflammatory hyperpigmentation. Severe skin changes like flaky paint dermatosis were rarely identified. Inter-rater variability calculations showed only fair agreement (overall Fleiss’ kappa 0.25) while intrarater variability had a fair-moderate agreement (Cohen’s kappa score of 0.47–0.58). Discussion: Skin changes in hospitalised children with an acute illness and stratified according to nutritional status were not as prevalent as historically reported. Dermatological assessment by means of the SKORDoK tool using photographs is less reliable than expected

Dermatological changes in a prospective cohort of acutely ill, hospitalised Malawian children, stratified according to nutritional status

Rationale Since the first documentation of skin changes in malnutrition in the early 18th century, various hair and skin changes have been reported in severely malnourished children globally. We aimed to describe the frequency and types of skin conditions in children admitted with acute illness to Queen Elizabeth Central Hospital, Blantyre, Malawi across a spectrum of nutritional status and validate an existing skin assessment tool. Methods Children between 1 week and 23 months of age with acute illness were enrolled and stratified by anthropometry. Standardised photographs were taken, and three dermatologists assessed skin changes and scored each child according to the SCORDoK tool. Results Among 103 children, median age of 12 months, 31 (30%) had severe wasting, 11 (11%) kwashiorkor (nutritional oedema), 20 (19%) had moderate wasting, 41 (40%) had no nutritional wasting and 18 (17%) a positive HIV antibody test. Six (5.8%) of the included patients died. 51 (50%) of children presented with at least one skin change. Pigmentary changes were the most common, observed in 35 (34%), with hair loss and bullae, erosions and desquamation the second most prevalent skin condition. Common diagnoses were congenital dermal melanocytosis, diaper dermatitis, eczema and postinflammatory hyperpigmentation. Severe skin changes like flaky paint dermatosis were rarely identified. Inter-rater variability calculations showed only fair agreement (overall Fleiss' kappa 0.25) while intrarater variability had a fair-moderate agreement (Cohen's kappa score of 0.47-0.58). Discussion Skin changes in hospitalised children with an acute illness and stratified according to nutritional status were not as prevalent as historically reported. Dermatological assessment by means of the SKORDoK tool using photographs is less reliable than expected.</p

Post-discharge Malaria Chemoprevention in Children Admitted with Severe Anaemia in Malaria-Endemic Settings in Africa: A systematic review and Individual Patient Data meta-analysis of randomised controlled trials

Background: Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital discharge. We conducted an individual patient data (IPD) meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention (PDMC) in children recovering from severe anaemia. Methods: Following PRISMA-IPD guidelines, we searched multiple databases, without time or language restrictions, for randomised controlled trials comparing monthly PDMC with placebo or standard-of-care among children admitted with severe anaemia in malaria-endemic Africa. Trials using daily or weekly malaria prophylaxis were not eligible. Fixed-effects two-stage meta-analysis of risk ratios (RR) was used to generate pooled effect estimates for mortality. Recurrent time-to-event data were analysed using one-stage mixed-effects Prentice-Williams-Peterson Total-Time models to obtain hazard ratios (HRs). This study is registered with PROSPERO-CRD42022308791. Findings: Three double-blind placebo-controlled trials involving 3,663 children with severe anaemia fulfilled the eligibility criteria; 3,507 (95.7%) contributed to the modified intention-to-treat analysis. They received either monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (average 3.1 courses/child) (N=1,085, the Gambia), monthly artemether-lumefantrine given at the end of the 4th and 8th week post-discharge (N=1,373, Malawi), or monthly dihydroartemisinin-piperaquine given at the end of the 2nd, 6th, and 10th week post-discharge (N=1,049, Uganda and Kenya). During the period of chemoprevention, PDMC was associated with a 77% reduction in mortality (RR=0.23 [95% CI 0.08-0.70], p=0.0094, I2=0%) and a 55% reduction in all-cause readmissions (HR=0.45 [0.36-0.56], p<0.0001). The reductions were not sustained after protective drug levels had waned. The small number of trials limited our ability to assess heterogeneity, its sources and publication bias. Interpretation: In malaria-endemic Africa, PDMC reduces mortality and readmissions in recently discharged children recovering from severe anaemia. PDMC can be a valuable strategy for the post-discharge management of this high-risk group. Future research should focus on methods of PDMC delivery, options to prolong the protection duration, other hospitalised special risk groups, and interventions targeting non-malarial causes of post-discharge morbidity

Severe anemia in Malawian children

Background Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. Methods We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling. Results Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD(sup -202/-376) genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B(sub 12) deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age. Conclusions There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considere

Households or hotspots? Defining intervention targets for malaria elimination in Ratanakiri Province, eastern Cambodia

Background. Malaria “hotspots” have been proposed as potential intervention units for targeted malaria elimination. Little is known about hotspot formation and stability in settings outside sub-Saharan Africa. Methods. Clustering of Plasmodium infections at the household and hotspot level was assessed over 2 years in 3 villages in eastern Cambodia. Social and spatial autocorrelation statistics were calculated to assess clustering of malaria risk, and logistic regression was used to assess the effect of living in a malaria hotspot compared to living in a malaria-positive household in the first year of the study on risk of malaria infection in the second year. Results. The crude prevalence of Plasmodium infection was 8.4% in 2016 and 3.6% in 2017. Living in a hotspot in 2016 did not predict Plasmodium risk at the individual or household level in 2017 overall, but living in a Plasmodium-positive household in 2016 strongly predicted living in a Plasmodium-positive household in 2017 (Risk Ratio, 5.00 [95% confidence interval, 2.09–11.96], P < .0001). There was no consistent evidence that malaria risk clustered in groups of socially connected individuals from different households. Conclusions. Malaria risk clustered more clearly in households than in hotspots over 2 years. Household-based strategies should be prioritized in malaria elimination programs in this region

Parasitic, bacterial, viral, immune-mediated, metabolic, and nutritional factors associated with Nodding syndrome

Nodding syndrome is a neglected, disabling and potentially fatal epileptic disorder of unknown aetiology affecting thousands of individuals mostly confined to Eastern sub-Saharan Africa. Previous studies have identified multiple associations – including O. volvulus, antileiomodin-1 antibodies, vitamin B6 deficiency, and measles virus infection – yet none is proven causal. We conducted a case-control study of children with early-stage Nodding syndrome (symptom onset &amp;lt;1 year). Cases and controls were identified through a household survey in the Greater Mundri area in South Sudan. A wide range of parasitic, bacterial, viral, immune-mediated, metabolic, and nutritional risk factors was investigated using conventional and state-of-the-art untargeted assays. Associations were examined by multiple logistic regression analysis and a hypothetical causal model was constructed using structural equation modelling. From 607 children with Nodding syndrome, 72 with early-stage disease were included as cases and matched to 65 household- and 44 community controls. Mansonella perstans infection (odds ratio [OR] 7.04, 95% confidence interval [CI] 2.28-21.7), Necator americanus infection (OR 2.33, 95% CI 1.02-5.3), higher antimalarial seroreactivity (OR 1.75, 95% CI 1.20-2.57), higher vitamin E concentration (OR 1.53 per standard deviation [SD] increase, 95% CI 1.07-2.19) and lower vitamin B12 concentration (OR 0.56 per SD increase, 95% CI 0.36-0.87) were associated with higher odds of NS. In a structural equation model, we hypothesized that M. perstans infection, higher vitamin E concentration and fewer viral exposures increased the risk of Nodding syndrome while lower vitamin B12 concentration, N. americanus and malaria infections resulted from having Nodding syndrome. We found no evidence that O. volvulus, antileiomodin-1 antibodies, vitamin B6 and other factors were associated with Nodding syndrome. Our results argue against several previous causal hypotheses including O. volvulus. Instead, Nodding syndrome may be caused by a complex interplay between multiple pathogens and nutrient levels. Further studies need to confirm these associations and determine the direction of effect