Wellcome Open Research

BackgroundArtemisinin-based combination therapies (ACTs) are the most widely used treatment for Plasmodium falciparum malaria. Kelch 13 mutations associated with artemisinin partial resistance (ART-R) have emerged in Sub-Saharan Africa (SSA) and are now reported in an increasing number of countries. ACT treatment failure rates are at risk of unprecedented increase. To summarise existing surveillance data and guide future surveillance, we produce modelled estimates of the spatiotemporal distribut...

BackgroundRising kidney discard rates and uncertainty around accepting higher risk donor kidneys highlight the need for decision support tools that integrate donor and recipient factors and communicate risk in ways that are understandable and usable at the time of offer. Conventional indices (e.g., KDPI/KDRI) provide population level signals but do not deliver individualized, cognitively accessible information aligned with real time clinical workflows. ObjectiveTo describe how key transplant st...

UK-based quantitative research on the health and education outcomes of Unaccompanied Asylum-Seeking Children (UASC) remains limited, especially at national level. Linked administrative data provide an unprecedented opportunity to study these outcomes among UASC. This paper lays a foundation for further research, particularly examining the influence of socio-demographic, legal and environmental factors on UASCs health and educational outcomes. We described the UASC population with a first record...

BackgroundPlatelet count and C-reactive protein (CRP) are blood tests commonly used in primary care as part of diagnostic work up for symptomatic patients. Abnormal results of these tests can indicate an undetected cancer; however, it is not known whether the association between an abnormal test result and cancer risk varies by patient ethnicity. MethodsThis cohort study used routinely collected primary and secondary health care records in England with linkage to national cancer registry data. ...

Background Acute malnutrition remains a major public health challenge among children under five in Malawi due to undetected and untreated cases. While several policies and programmes are in place, they face significant resource input and implementation constraints. In this study, we evaluate the potential health impact and cost-effectiveness of three interventions designed to address constraints along the care pathway in childhood acute malnutrition management. These include improving early reco...

BackgroundTwo RSV immunisations products: a maternal vaccine, Abrysvo, and a long-acting monoclonal antibody, nirsevimab, both designed to prevent RSV illness in infants, have recently become available. Modelling evidence is required to inform how to optimally use these products in immunisation programs to reduce the burden of RSV in young children. MethodsWe extend a dynamic transmission model calibrated to RSV-hospitalisation data of children aged < 5 years in temperate Western Australia (WA)...

BackgroundThe 2024 blood culture bottle shortage brought diagnostic resource allocation to the forefront, reflecting persistent, foundational challenges with low-value testing and empiric treatment approaches under clinical uncertainty. ObjectiveTo determine whether a machine learning approach using electronic medical record data can predict bacteremia more effectively than existing systems and practices to guide diagnostic testing and empiric treatment strategies. MethodsIn a retrospective co...

Sepsis caused by drug-resistant pathogens remains a major contributor to under-five mortality in low- and middle-income countries, threatening progress toward Sustainable Development Goal (SDG) 3.2. Blood culture, the gold standard for sepsis diagnosis and antimicrobial stewardship, remains underutilised in routine pediatric care. This study assessed the extent and determinants of blood culture utilisation among hospitalised children under five years with suspected sepsis at four antimicrobial r...

Introduction Glomerular filtration rate (GFR) is invasive to measure. Therefore, in clinical care, estimated GFR is derived from serum levels of endogenous filtration markers such as creatinine and cystatin C. Multiple studies from high income countries showed differences between estimated glomerular filtration rate based on cystatin C (eGFRcys) and creatinine (eGFRcr). This study aimed to assess the agreement between eGFRcys and eGFRcr in Ethiopian children and identify factors influencing high...

Individuals with chronic kidney disease (CKD) have higher rates of hip fracture and post-fracture mortality. Although they may develop age-related osteoporosis similar to those without CKD, they may also exhibit CKD-related metabolic bone disease (MBD), characterized by low, high, or mixed turnover at similar levels of bone mineral density (BMD). Because BMD does not provide information about turnover status, clinical decision-making is challenging. This study evaluated the associations between ...

Background Persistent inequities in immunisation coverage, particularly among zero-dose and under-immunised children, continue to challenge Pakistan's Expanded Programme on Immunization. Weak feedback loop, inconsistent data quality, and limited real-time monitoring impede effective decision-making. This Implementation Research was conducted under the MAINSTREAM Initiative funded by Alliance for Health Policy and Systems Research (AHPSR) and supported by the Aga Khan Community Health Services De...

Background: Schistosoma mansoni is a leading cause of hepatosplenic disease in sub-Saharan Africa. Yet, associations with current Schistosoma mansoni infections and hepatosplenic organometry remain unclear in the context of widespread mass drug administration and co-endemic infections. Methods: From January to February 2024, we conducted a community-based, cross-sectional study nested within the SchistoTrack cohort in three districts of Uganda. Liver and spleen dimensions were assessed via point...

BackgroundThere is disparity between the incidence of malignant hyperthermia (MH) reactions and the prevalence of variants in the RYR1 gene associated with susceptibility to MH (where susceptibility is determined by in vitro contracture tests). Our aims were to use clinical and genetic data from the UK to explain this disparity and to examine if these data are consistent with the clinical risk of MH being inherited as an autosomal dominant trait. MethodsClinical MH and genotyping data were extr...

Students who frequently miss school are at greater risk for academic difficulty. High levels of absenteeism as early as kindergarten have been associated with long-term consequences, such as low reading proficiency in Grade 3 and low academic achievement in Grade 5, both of which have been associated with lower rates of high school graduation and enrollment in post-secondary education. The prevalence of school absenteeism has increased significantly since the COVID-19 pandemic and there have bee...

Background The microbial aetiology of early childhood caries (ECC) in sub-Saharan African populations remains poorly characterised, with most studies focusing on conventional cariogenic pathogens like Streptococcus mutans. This study aimed to characterise the salivary microbial profile of children with ECC in urban Kano, northern Nigeria. Methods In this cross-sectional study of 162 children aged 3-5 years in urban Kano, unstimulated saliva samples were collected and analysed using standard bact...

BackgroundDelivering timely, high-quality feedback on resident scholarly projects is labour-intensive, especially in large programmes. We developed an AI-assisted evaluation system, powered by the open-weight LLaMA-3.1 large-language model (LLM), to generate formative feedback on Family Medicine residents scholarly projects and compared its performance with expert human evaluators. MethodsWe evaluated whether the AI-generated feedback achieves comparable quality to expert feedback. The tool ing...

Background and aimsPopulation screening for liver disease in high-risk groups is recommended. Community diagnosis of liver disease is a challenge due to the asymptomatic nature of disease until very advanced stages. Moreover, regional variation in testing availability can result in people with clinically significant liver disease being missed. Machine learning (ML) has been proposed as a method to reduce diagnostic error and automate screening. We present a novel machine learning derived algorit...

BackgroundPacked lunches are a common feature of early childhood food provision, yet evidence describing their nutritional composition in early years settings remains limited. Understanding the foods provided during this developmental period is important, given the potential influence of early dietary exposures on later health. AimTo characterise the composition, nutritional quality, cost, and dietary patterns of packed lunches brought from home in Early Childhood Education and Care settings, a...

RationaleAutonomic dysfunction is a hallmark of sepsis pathophysiology, yet its quantification remains challenging. Multiscale entropy (MSE) derived from heart rate variability (HRV) offers a dynamic measure of physiological complexity and may serve as a biomarker of early deterioration associated with subsequent organ failure, vasopressor escalation, or mortality. ObjectiveTo determine whether MSE computed across multiple temporal scales during the first 24 hours of Intensive Care Unit (ICU) a...

BackgroundNewborns requiring inpatient care, particularly small and sick newborns (SSNBs), face high risk of mortality. Newborns referred from other facilities may experience worse outcomes than those born and managed within the same hospital (inborn newborns). Understanding factors contributing to this disparity in outcomes could support efforts to scale-up care and accelerate progress towards achieving Sustainable Development Goals target 3.2. MethodsData on 130,773 newborns admitted to 13 ho...