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Archives of Disease in Childhood

BMJ

Preprints posted in the last 7 days, ranked by how well they match Archives of Disease in Childhood's content profile, based on 16 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Avoidable childhood respiratory-infection deaths: a frontier analysis of episode-fatality ratios in 204 countries, 1990-2023

Li, D.; Xie, J.; Xue, J.; Chen, H.; Wang, X.; Shen, C.

2026-09-03 pediatrics 10.64898/2026.09.01.26361882 medRxiv
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Background Respiratory infections remain the leading infectious cause of death among children and adolescents, yet the share of these deaths that could be averted with currently feasible care is not routinely quantified. Existing amenable-mortality frameworks rely on cause lists and population-level mortality benchmarks and do not exploit information on how many episodes occur. We propose an episode-fatality-ratio (EFR) frontier approach and apply it to lower respiratory infections (LRI), whooping cough (pertussis) and upper respiratory infections (URI) in 204 countries, 1990-2023. Methods For each cause, country and year we computed EFR = deaths/incident episodes using Global Burden of Disease (GBD) 2023 estimates for ages 0-19 years. The frontier was defined as the 10th-percentile country EFR within each GBD super-region, cause and year; avoidable deaths = max(0, deaths - episodes x frontier EFR). Primary estimates are deterministic; 95% uncertainty intervals (UIs) come from 2,000 Monte Carlo draws. Sensitivity analyses varied the frontier percentile, applied an aspirational global frontier, constructed pertussis counterfactuals, and recomputed all estimates within the single under-5 age band. Results In 2023, 333,803 childhood deaths from lower respiratory infections (95% UI 289,123-417,460; 46.9% of LRI deaths) were avoidable. Summing the three causes deterministically gives 391,034 avoidable deaths (46.5% of 840,444); the combined figure is a deterministic sum, and a UI is available for the LRI component only. The pertussis (43,958; 39.0%) and URI (13,273; 81.0%) estimates are secondary: their deterministic point values fall below their own Monte Carlo intervals and the underlying death estimates carry very wide uncertainty (global pertussis UI 12,545-321,874). Avoidable deaths fell from 1,050,468 (44.9%) in 1990, but between 2019 and 2023 the avoidable share for LRI+URI barely moved (48.7% to 47.7%) while absolute avoidable deaths fell 14.5%, a pattern consistent with stalled convergence to the frontier. Sub-Saharan Africa plus South Asia held 73.1% of avoidable deaths in 2023 versus 41.8% in 1990; ten countries accounted for 59.1%. Conclusion Nearly half of childhood respiratory-infection deaths remain avoidable relative to within-region best practice, and the residual burden is increasingly concentrated in low-income settings. In the pertussis counterfactual, most countries kept pace with their regional frontier, so further gains require advancing the frontier itself through quality-of-care improvements.

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Towards Electronic Health Records-Based Paediatric Growth References: Results from the SwissPedGrowth Project

Leuenberger, L. M.; Shoman, Y.; Romero, F.; Sasaki, M.; Deligianni, X.; Goebel, N.; Mozun, R.; Bielicki, J. A.; Burckhardt, M.-A.; Saner, C.; Schwitzgebel, V.; Hauschild, M.; Righini Grunder, F.; Mueller, P.; Schlapbach, L. J.; Jenni, O.; Spycher, B. D.; Kuehni, C. E.; Belle, F. N.; SwissPedHealth consotrium,

2026-09-02 pediatrics 10.64898/2026.08.28.26361619 medRxiv
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BACKGROUND: We used anthropometric data from electronic health records (EHRs) of Swiss childrens hospitals to evaluate growth references and estimate centile curves. METHODS: We received EHRs extracted from seven Swiss childrens hospitals and analysed two samples: all children with a height, weight, body mass index (BMI), or head circumference recording, and a subsample restricted to children without diseases potentially affecting growth, weighted to represent the general population. We calculated mean z-scores based on the World Health Organization growth references adopted for Switzerland in 2011 (CH-WHO 2011) and current Swiss growth references (Swiss 2026). We estimated sex-specific centile curves in the subsample using generalised additive models for location, scale, and shape. RESULTS: We included 213,868 children with height, 448,002 with weight, 209,244 with BMI, and 67,397 with head circumference recordings. Mean z-scores in the all children sample were (CH-WHO 2011; Swiss 2026): height (0.10; -0.19), weight (0.16; -0.09), BMI (0.04; -0.07), head circumference (-0.28, -0.28); and in the subsample: height (0.34; 0.00), weight (0.27; 0.01), BMI (0.18; 0.05), and head circumference (0.04; 0.01). The 50th height, weight, BMI, and head circumference centiles of girls and boys in the subsample closely followed those of Swiss 2026, with slightly wider 3rd and 97th centiles in infancy and adolescence. CONCLUSION: Height, weight, BMI, and head circumference centiles aligned well with the Swiss 2026 growth references in Switzerland, demonstrating that hospital EHRs could contribute to future growth references.

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Exclusive Breastfeeding Among Working Mothers In Ghana: Evidence From The 2022 Ghana Demographic And Health Survey.

Siddiq, A. I.; Saafu, I.; Borkor, E. T.; Vondee, E.; Sampana, F. T.; Okine, B.

2026-08-31 medical education 10.64898/2026.08.26.26361421 medRxiv
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Background: Exclusive breastfeeding may protect infants against common infections and support healthy growth and development. Working mothers may face constraints on exclusive breastfeeding arising from work schedules, separation from their infants, and inadequate breastfeeding support. National evidence on the individual, healthcare-related, and contextual factors associated with exclusive breastfeeding among working Ghanaian mothers appears to remain limited. Design: Cross-sectional secondary analysis. Setting: Nationally representative survey covering urban and rural communities across all 16 administrative regions of Ghana. Participants: The analysis included 620 currently working mothers whose youngest living infants were aged 0-5 completed months and lived with them. The complete-case multivariable analysis included 619 mother-infant pairs. Primary outcome measure: Current exclusive breastfeeding, defined using the standard 24-hour infant-feeding indicator. Infants were classified as exclusively breastfed when they received breast milk without water, formula, animal milk, other liquids, or solid or semi-solid foods during the preceding day or night. Oral rehydration solution, vitamins, minerals and prescribed medicines were permitted. Aim: To estimate the prevalence of exclusive breastfeeding and examine its individual, healthcare-related and contextual correlates among working mothers of infants aged 0-5 months in Ghana. Methods: Birth Recode data from the 2022 Ghana Demographic and Health Survey were analysed. Unweighted frequencies and survey-weighted percentages described the study population. Design-adjusted Wald tests assessed bivariate associations. Survey-weighted binary logistic regression estimated adjusted odds ratios (AORs) and 95% confidence intervals (CIs), accounting for sampling weights, primary sampling units, and strata. Results: The survey-weighted prevalence of exclusive breastfeeding was 54.3% (95% CI: 49.2-59.3). Ethnicity, mode of delivery, region, and community poverty appeared to be statistically significant in the bivariate analyses. In the adjusted model, region was jointly associated with exclusive breastfeeding (p = 0.004). Mothers in the Northern (AOR = 4.93; 95% CI: 1.5-16.17) and Savannah (AOR = 4.22; 95% CI: 1.08-16.41) regions had higher odds than mothers in the Western Region. Mothers in low-education communities had lower odds than those in high-education communities (AOR = 0.54; 95% CI: 0.30-0.98). Although Guan mothers had higher odds than Akan mothers, the overall association with ethnicity was non-significant, and the estimate appeared imprecise. Maternal age, individual education, religion, parity, wealth, infant sex, antenatal care, postnatal care, and residence were not independently associated with exclusive breastfeeding. Conclusion: The prevalence estimate suggests that slightly more than half of working mothers exclusively breastfed their infants. Regional and community differences appeared more pronounced than those associated with most measured individual characteristics. Regionally responsive breastfeeding support and practical community education may contribute to improved coverage. Workplace recommendations require further evidence because employment conditions were not measured directly. Keywords: Exclusive breastfeeding; working mothers; infant feeding; maternal employment; regional inequalities; community education; Ghana; 2022 Ghana Demographic and Health Survey; survey-weighted analysis.

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After the vaccine era: sequencing platform investments as the childhood pneumonia spectrum diversifies

Li, D.; Chen, H.; Xie, J.; Li, J.; Wang, X.; Shen, C.

2026-09-03 pediatrics 10.64898/2026.09.01.26361934 medRxiv
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Background The historic decline in childhood pneumonia mortality was driven substantially by single-pathogen vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Yet the pathogen spectrum underlying child pneumonia deaths is diversifying: the effective number of pathogens rose from 5.57 in 1990 to 9.94 in 2023, and the residual burden is shifting toward opportunistic and hospital-associated pathogens for which no licensed childhood vaccines exist. This paper asks how resources should be sequenced between single-pathogen interventions and platform investments as this transition proceeds. Methods We analyzed Global Burden of Disease Study 2023 deaths from 29 pathogens in ages 0-19 years by super-region, combined with WHO/UNICEF Estimates of National Immunization Coverage (WUENIC) for PCV3 and Hib3. We quantified the spectrum transition under two denominators (26- and 29-pathogen calibers), constructed a share-by-intervenability matrix assigning each pathogen to a dominant intervention channel (vaccine-reachable, mixed, platform-sensitive) under explicit classification rules, compared platform-sensitive deaths with a transparently computed scenario of residual vaccine-preventable deaths, and cross-classified pathogens by age tropism and poverty lock. We anchored platform interventions to verified published evidence. Results The vaccine-preventable group share fell from 54.0% to 40.2% while the opportunistic/hospital group rose from 18.1% to 23.1% (29-pathogen caliber, 1990-2023). Super-region vaccine coverage showed no significant association with pathogen-share change (PCV3 Spearman rho = 0.108, p = 0.818; Hib3 rho = -0.036, p = 0.939), a null result we report as evidence that simple coverage-burden correlations do not hold at the regional level, not as evidence against vaccine value. In 2023, vaccine-reachable pathogens accounted for 441,410 deaths (45.7%, channel including COVID-19), mixed for 126,926 (13.1%), and platform-sensitive pathogens for 396,995 (41.1%). Platform-sensitive deaths were 2.9-5.1 times the scenario estimate of residual vaccine-preventable deaths (52,435-77,512). Nine of 14 classifiable pathogens fell into the poverty-locked, infant-tropic cell (480,922 deaths; Fisher OR = 9.0, p = 0.1758). Conclusions The marginal value of single-pathogen strategies declines as the spectrum diversifies and residual deaths concentrate in platform-sensitive, poverty-locked, infant-tropic pathogens. Vaccine scale-up remains a certain and sizeable opportunity; the next increment of marginal resources should increasingly fund platform capabilities (oxygen systems, antimicrobial access and stewardship, infection prevention and control, referral, and nutrition) delivered as a package to the populations where the residual burden is locked.

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Effects of collaborative clinical visit agenda-setting interventions: A systematic review and meta-analysis

Sierpe, A.; Yen, R. W.; Milliman, A.; Cady, E.; Ahn, B.; Dade, A. E.; Devito, A. M.; Eckert, B. A.; Gopalan, V. V.; Krasinski, S. C.; MacMartin, M. A.; Musacchio, S. G.; Zhang, J.; Saunders, C. H.

2026-09-03 medical education 10.64898/2026.08.30.26361729 medRxiv
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Background Agenda-setting is a fundamental patient-centered communication practice in which a clinician works with a patient to elicit, propose, and organize topics for discussion during a clinical encounter. Various agenda-setting interventions have been developed, including patient-facing tools and clinician training, but their effects have not been systematically evaluated. We aimed to determine the effects of these interventions on encounter, patient, care partner, and clinician outcomes. Methods We searched grey literature and seven databases, including PubMed, from inception through July 2025 for randomized and non-randomized comparative studies of interventions designed to promote or improve clinical visit agenda-setting. Two reviewers independently screened articles and extracted data, with a third reviewer resolving conflicts. We assessed risk of bias using RoB 2 for randomized studies and ROBINS-I for non-randomized studies. We conducted random effects meta-analyses when outcomes were sufficiently comparable, assessed heterogeneity using I2, and rated certainty of evidence using GRADE. Post hoc exploratory subgroup analyses examined study design, adjustment status, and intervention structure. Results Twenty-nine articles describing 22 unique studies met the inclusion criteria, including 13 randomized and nine non-randomized studies. Agenda-setting interventions increased the occurrence of agenda-setting (risk ratio 5.43, 95% confidence interval (CI) 2.06 to 14.28, I2=34.6%) and favored the intervention for concerns addressed when measured as a continuous outcome (standardized mean difference (SMD) 0.37, 95% CI 0.16 to 0.57, I2=65.3%) and overall clinician satisfaction (SMD 0.50, 95% CI 0.23 to 0.78, I2=0.0%). There were no clear differences in the number of concerns raised (mean difference (MD) 0.21, 95% CI -0.19 to 0.61, I2=59.6%), visit duration (MD 0.64 minutes, 95% CI -0.83 to 2.12, I2=51.4%), or overall patient satisfaction (SMD 0.05, 95% CI -0.05 to 0.15, I2=47.0%). Potentially important heterogeneity was present for four of these six outcomes. Post hoc exploratory subgroup analyses did not provide clear evidence that effects varied by study design, adjustment status, or intervention structure. Risk of bias was often high, serious, or critical, and certainty of evidence was low or very low for all pooled outcomes. Conclusions To our knowledge, this is the first comprehensive synthesis of clinical visit agenda-setting interventions. Such interventions may increase the occurrence of agenda-setting and the extent to which patient concerns are addressed without increasing visit length. However, the certainty of evidence was low or very low, and the available evidence does not establish a superior intervention structure.

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Rising rate of non-receipt of vitamin K prophylaxis for newborns, January 2019 - June 2026

Masters, N. B.; Farrar, K. G.; Holler, E.; Lancaster, J. M.

2026-09-02 pediatrics 10.64898/2026.08.31.26361837 medRxiv
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Background: Vitamin K prophylaxis is universally recommended for newborns to prevent life threatening vitamin K deficiency bleeding. Although not on the immunization schedule, vitamin K prophylaxis is often coadministered with hepatitis B birth dose and erythromycin ophthalmic ointment, and rising hesitancy around vaccines/preventive care may spill over into vitamin K administration. Methods: We conducted a retrospective cohort study using Truveta electronic health record data with linked mother-child dyads. Live births to mothers aged 15-49 from January 1, 2019 through June 30, 2026 were included. Vitamin K administration was defined as documentation on the birth date or following day. Logistic regression assessed sociodemographic predictors of non-receipt, and interrupted time series analysis evaluated changes after January 2026. Results: Among 1,026,375 infants, 995,628 (96.97%) had documented vitamin K administration. Non-receipt increased from an average of 2.1% during 2019-2022 to 4.3% in 2025 and 6.1% in 2026, reaching 8.10% in June 2026. Older maternal age, non-Hispanic or Latino ethnicity, Medicaid or unknown insurance, and year of delivery were associated with greater odds of non-receipt. After January 2026, there was no immediate step change, but the odds of vitamin K receipt declined an additional 10% per month (OR: 0.90; 95% CI, 0.88-0.91). Conclusions: Vitamin K non-receipt increased over the study period and accelerated after January 2026. Because vitamin K recommendations were not changed by the January vaccine schedule, this association may reflect broader impacts to confidence in newborn preventive care. Future studies should examine causal mechanisms, parental decision-making, and associated clinical outcomes.

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Young people with obesity and rare disease - genotypes, phenotypes and healthcare use

Chia, C.; Baker, K.

2026-08-31 genetic and genomic medicine 10.64898/2026.08.25.26361359 medRxiv
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Obesity is a significant public health concern. Early-onset obesity in the context of rare disease can reflect genetically-mediated pathology or elevated susceptibility through indirect mechanisms. Mapping the diverse characteristics and needs of young people with obesity in the rare disease population is a first step toward mechanistic and translational research. We carried out a retrospective comparative analysis of demographic, genotypic, phenotypic and health service utilisation data for young people with obesity (cases: n=500) and without obesity (controls: n=11,444) from the UK 100,000 Genomes Project rare disease cohort. Cases and controls were recruited prior to genomic diagnosis, across clinical disorder categories. We observed significant association between socioeconomic deprivation and obesity risk. Young people with obesity had significantly higher utilisations of acute care and mental health services, indicating an overall higher health burden. A curated panel of 519 candidate obesity-associated genes demonstrated aggregate association with obesity, although no single gene reached significance. Phenotypic comparison between cases and controls highlighted increased multi-organ and neurological system involvement, highlighting the overlap between neurodevelopmental and obesity risks. Within the case group, we conducted cluster analysis to identify early-onset obesity groups with different phenotypic profiles, potentially arising from different causal pathways - this identified six obesity subgroups of interest, with differing involvement of neurodevelopmental and other systems. Our study confirms that obesity co-occurs with a wide range of factors within the rare disease population, and is associated with significant physical and mental health needs, requiring holistic lifelong care.

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Diversification without convergence: national childhood respiratory pathogen spectra diverge as they diversify, 1990-2023

Li, D.; Feng, Q.; Zhang, Y.; Chen, H.; Wang, X.; Shen, C.

2026-09-03 pediatrics 10.64898/2026.09.01.26361890 medRxiv
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Background National childhood respiratory pathogen spectra are diversifying nearly everywhere - within-country diversity rose in 203 of 204 countries between 1990 and 2023 - yet whether countries are diversifying toward a common spectrum or along divergent paths is unknown. We quantified between-country compositional distance of national pathogen spectra over the same period. Methods We built national pathogen share vectors from Global Burden of Disease Study 2023 lower respiratory infection etiologic attributions (26 pathogens, 204 countries, ages 0-19 years) at five timepoints spanning 1990-2023. Between-country distance was measured as all pairwise Jensen-Shannon divergences (JSD; primary) and Bray-Curtis dissimilarities, with Baselga and Jaccard decompositions; robustness was assessed across metrics, pathogen panels, low-count thresholds and a balanced panel of 107 countries. Results Mean pairwise JSD rose from 0.0084 in 1990 to 0.0283 in 2023 (+238%; trend p = 0.030), peaking in 2021 (+283%) with a partial 2023 pullback. Bray-Curtis dissimilarity rose +120% and the balanced panel +423%. Divergence was entirely balanced variation (share reallocation), with spectrum richness rising from 18.5 to 21.1 of 26 pathogens. Dispersion rose fastest for influenza (coefficient of variation 0.03 to 0.55) and respiratory syncytial virus (0.08 to 0.48). Within-region distance rose in every computable GBD super-region (five of seven): divergence occurs within regions, not between blocs. Conclusions National spectra are re-sorting along country-specific axes as vaccine-preventable dominance recedes at different speeds. Diversification is universal, but convergence is absent: the transition at the etiologic-spectrum level is asynchronous and path-dependent, with implications for empirical treatment policy and pathogen surveillance.

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Electronic health data exploring cardiorespiratory responses of transfusions in preterm infants: An international multicenter cohort study

Honore, A.; Rech, T.; Scrivens, A.; Binotto, I.; Zandvoort, C. S.; van der Staaij, H.; Peck, M.; Zivanovic, S.; Stanworth, S. J.; Hartley, C.; Dame, C.; Deschmann, E.; the Neonatal Transfusion Network,

2026-09-03 pediatrics 10.64898/2026.09.01.26361418 medRxiv
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Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

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AI Video Analysis of Psychomotor Performance in EMS Education: Agreement With Human Evaluators Across Three Skills

Otte, J. H.; Cartagena, A.

2026-08-31 medical education 10.64898/2026.08.26.26361437 medRxiv
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Background. A primary constraint on the capacity of EMS programs to meet industry demand is psychomotor instruction and verification, requiring direct observation of each student by a qualified evaluator. Whether AI video analysis can relieve it is untested; none has been applied to EMS skill examination or compared with human examiners. Objective. To quantify human EMS evaluator inter-rater reliability and evaluate an AI video-analysis platform against it. Methods. In a prospective, fully crossed study, five certified EMS evaluators and an AI platform independently scored identical video-recorded EMT performances of cervical collar application (n=15), bag-valve-mask (BVM) ventilation (n=14), and medical assessment (n=15) on dichotomous checklists with critical-failure criteria. Agreement was assessed at item, score, and decision levels using Fleiss' kappa, Krippendorff's alpha, Gwet's AC1, and ICC(2,1)/ICC(2,k). Results. Human item agreement was moderate (kappa 0.409 to 0.467), as was single-rater reliability (ICC(2,1) 0.539 to 0.694), against good panel reliability (ICC(2,k) 0.854 to 0.919). Recorded pass/fail agreement was fair (kappa 0.297 to 0.388) and critical-failure agreement near zero for two skills (kappa 0.028, 0.119). AI alignment tracked rubric observability rather than task complexity: r = 0.857 (collar, exceeding every human), -0.173 (BVM), 0.664 (medical), and it was most lenient on two skills. Conclusions. Human evaluators are an imperfect standard, especially on critical failures. The AI was a legitimate additional rater where checklist items were discrete and visually verifiable, but not where credit required judging continuous quantities such as ventilation rate, volume, or suction duration. Defensible uses are formative and archival, not summative. These results reflect an early, non-specialist configuration: a baseline, not a limit.

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Acceptability, feasibility, quality of life and diabetes distress score outcomes: A pragmatic randomised clinical trial on continuous glucose monitoring for people with type 1 diabetes

Marban-Castro, E.; Muhwava, L.; Girdwood, S.; Kemp, T.; Freitas, J.; Kamau, Y.; Otieno, M.; Akach, D.; Morato, A.; Sanz, S.; Fiechter, V.; Erkosar, B.; Watson, M.; Vetter, B.; Haldane, C.; Shilton, S.; Rheeder, P.; Dave, J. A.; Carrihill, M.; Karsas, M.

2026-08-31 endocrinology 10.64898/2026.08.26.26361479 medRxiv
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Introduction: Continuous glucose monitoring (CGM) offers an advancement over traditional self-monitoring of blood glucose (SMBG) for people living with type 1 diabetes (T1D). However, evidence on the acceptability and feasibility of different CGM use cases in African populations remains limited. Methods: This was a pragmatic three-arm, randomised controlled trial on CGM conducted among people living with T1D in three public healthcare clinics in South Africa. Participants were assigned to Arm 1 (continuous CGM), Arm 2 (periodic CGM), or Arm 3 (SMBG). Diabetes education was provided at all study visits. Feasibility was assessed by adherence to CGM use and through the Glucose Monitoring Satisfaction Survey (GMSS). Diabetes distress was measured by the Diabetes Distress Scale (DDS), health-related quality of life (HRQoL) by the EQ-5D scales, and acceptability using the Theoretical Framework of Acceptability (TFA). Surveys were collected on paper and transferred to OpenClinica. Analyses were performed in R. The trial was registered in the Clinical Trials Registry (NCT05944718) on July 13, 2023. Results: A total of 83 participants were included in Arm 1, 85 in Arm 2, and 80 in Arm 3. CGM mean active time was 55% in Arm 1 versus 69% in Arm 2. The proportion of participants meeting the [&ge;]70% active time threshold was higher in Arm 2 (52%) than in Arm 1 (34%). Diabetes' distress declined across arms during the intervention period, with no significant difference between arms; distress increased slightly six months post-intervention but remained below baseline. At 6 months, glucose monitoring satisfaction was significantly higher in both CGM arms than in the SMBG arm, and satisfaction increased over time in CGM arms. Health-related quality of life remained stable across arms during the intervention period with no significant difference between arms. High acceptability was observed in both CGM arms, with higher ratings in the periodic arm. Conclusions: CGM was acceptable to people living with type 1 diabetes and feasible to use in public-sector clinics in South Africa, with high acceptability under continuous and periodic use. Health-related quality of life remained stable across arms, and diabetes-related distress declined, during the intervention period, across arms. Glucose monitoring satisfaction rose significantly in both CGM arms compared to SMBG. Periodic CGM might be a promising and potentially more scalable option than continuous use for public-sector care.

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A Randomized Non-Inferiority Trial of an eHealth Delivery Alternative for Cancer Genetic Testing for Hereditary Cancer (eREACH2)

Lee, K. T.; Egleston, B.; Fetzer, D.; Domchek, S. M.; Fleisher, L.; Wen, K.-Y.; Wagner, L.; Roberts, S.; Howe, S.; Cacioppo, C.; Christiansen, J.; Karpink, K.; Selmani, E.; Mastaglio, E.; Weinberg, M.; Wood, E. M.; Feng, J.; John, S.; Schweickert, K.; Mcleod, B.; Bradbury, A. R.

2026-09-03 genetic and genomic medicine 10.64898/2026.09.01.26361920 medRxiv
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Background: Many at-risk patients lack access to genetic services due to a genetic counselor (GC) workforce shortage. Little is known about how digital alternatives impact patients with and without cancer who meet criteria for genetic testing. Methods: eREACH2 is a randomized 4-arm non-inferiority trial where pre-test (visit 1) and/or return of results (visit 2) GC counseling was replaced with a patient-centered digital intervention. Arms include: A (GC/GC), B (GC/digital), C (digital/GC) and D (digital/digital). Primary outcomes were non-inferiority in uptake of genetic services and change in genetic knowledge and general anxiety from baseline to post-disclosure of results (T0-T2). Secondary cognitive and affective outcomes were assessed using non-inferiority ANOVAs and equivalency chi-squared tests in intention-to-treat and per-protocol analyses. Findings: 773 participants were recruited nationwide; 46.6% from rural areas. Mean age was 51 years (range 20-87), 13% male, 12% non-white, 29% had less than a college education, and 33% had a personal history of cancer. 584 (76%) patients completed testing (14% had a positive result, 16% had a VUS). In the primary ITT analyses, we met the non-inferiority for uptake of genetic services and anxiety, but results were inconclusive for knowledge. Secondary outcomes were heterogeneous across arms. Arm C demonstrated consistently favorable effects, while Arms B and D showed less favorable outcomes in select domains (e.g. satisfaction and MICRA). Patients who received positive or VUS results via digital disclosure had significantly higher MICRA scores - indicating greater negative response to testing. Interpretation: In this large, randomized trial of patients with and without cancer, the eREACH intervention was effective for pre-test counseling, but inconclusive for digital disclosure of results. Exploratory analyses suggest that digital delivery could be a reasonable alternative for individuals receiving negative results, while those receiving positive or VUS results may derive some short-term psychosocial benefit from GC disclosure.

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Community health system vital signs and preventable neonatal mortality in Mashonaland West, Zimbabwe: a cluster-randomised controlled trial

Gabida, M.; Kazonga, E.; Bowa, K.

2026-08-31 public and global health 10.64898/2026.08.26.26361392 medRxiv
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Abstract Preventable neonatal deaths remain a major public health problem in Zimbabwe, where near-universal antenatal and facility-delivery coverage coexist with a rising neonatal mortality rate. This study evaluated whether institutionalising three core "vital signs" of the community health system (a trained village health worker (VHW) workforce, functional community governance structures, and modified women's and men's participatory learning and action groups) reduces preventable neonatal deaths in Mashonaland West Province. An embedded QUAN (qual) mixed-methods design was used, with a two-arm, parallel-group cluster-randomised controlled trial as the dominant strand. Fifty-two ward-level clusters were randomised 1:1 to the institutionalised community health system package or to standard Ministry of Health and Child Care community services, and 984 pregnant women were enrolled between 1 September 2020 and 31 October 2021, with each mother-infant pair followed to 28 days after delivery, yielding 973 mother-infant pairs for intention-to-treat analysis. The primary outcome was neonatal death within 28 days of life, expressed per 1,000 live births. The primary analysis used a three-level mixed-effects log-binomial regression model with cluster and community-health-worker random intercepts, adjusted for pre-specified covariates. Supervised machine-learning classifiers with leave-one-cluster-out cross-validation, Cox proportional-hazards regression, and multilevel logistic models were fitted as supplementary analyses. An embedded longitudinal process evaluation used key informant interviews and focus group discussions, which were analysed thematically and integrated with the quantitative findings. The neonatal mortality rate was 44.8 per 1,000 live births in the intervention arm versus 110.1 per 1,000 in the control arm. The adjusted risk ratio for neonatal death was 0.43 (95% CI 0.26-0.70; p < 0.001), a 57% relative reduction, with a number needed to treat of 16 mother-infant pairs (95% CI 11-29). Low birthweight (<2,500 g), birth interval under two years, and low community women's literacy were the strongest risk factors, while trained VHWs, functional community governance, early antenatal care, and sustained participatory group attendance were independently protective. The women's and men's groups were protective in a dose-dependent manner, becoming significant at four or more cycles (about 14 meetings) (adjusted odds ratio 0.71; 95% CI 0.60-0.85; p = 0.001). A random forest classifier discriminated against neonatal deaths with a cross-validated area under the curve of 0.842 and a sensitivity of 0.912. Qualitative findings converged with the trial results, identifying male engagement, earlier care-seeking, danger-sign literacy, social-network activation, and community death audits as the behavioural and structural mechanisms of change. Institutionalising the community health system package (trained VHWs, functional governance, early antenatal engagement, and sustained participatory groups) was associated with a substantial reduction in preventable neonatal deaths. The findings suggest that in high-coverage, high-mortality settings, the binding constraint is structural rather than clinical, and that scaling functional community governance and workforce infrastructure in the most disadvantaged communities may accelerate progress toward neonatal survival targets. The principal limitations are a one-year follow-up period, the rarity of neonatal death, and concurrent national programming that only partially reached the control clusters. Trial registration: Pan African Clinical Trials Registry, PACTR202607591142118 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=PACTR202607591142118); registered retrospectively on 7 July 2026.

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Usability, acceptability and feasibility of continuous glucose monitoring among children and adolescents with type 1 diabetes in Kenya

Amolo, P.; Mungai, L.; Karume, A. K.; Kibugi, J.; Mwende, W.; Botella, N.; Haldane, C.; Kamau, Y.; Marban-Castro, E.

2026-09-01 endocrinology 10.64898/2026.08.27.26361447 medRxiv
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Introduction Continuous Glucose Monitoring (CGM) is considered standard care in high-income countries. There is, however, limited published evidence on CGM use in low- and middle-income countries. The purpose of this study was to assess the usability, acceptability, and feasibility of CGM use among people living with type 1 diabetes (T1D) and caregivers in a low-resource setting. Research Design and Methods This prospective study conducted at the Kenyatta National Hospital purposively enrolled persons aged 4-25 years who had been on management for T1D for at least six months, and caregivers of those under 18 years. Fourty youth living with T1D used CGM for three months in place of self monitoring of blood glucose (SMBG). The System Usability Scale (SUS), a Theoretical Framework of Acceptability-based questionnaire, the Diabetes Distress Scale (DDS), the Glucose Monitoring Satisfaction Survey (GMSS), and a feasibility survey were administered. Outcomes were summarized descriptively, including means, medians, and frequencies using R statistical software. Results The median SUS score was 98.8 (IQR 92.5-100.0). Acceptability was high, and the median total GMSS score improved from 3.73 to 4.73. Among adolescents and adults, the median overall DDS score reduced from 1.54 to 1.36, with reductions in scores in all domains, except for hypoglycemia distress which increased, and physician distress which remained low. Among caregivers, the median overall DDS score declined from 2.05 (moderate distress) to 1.90 (low distress), with modest reductions in teen management and parent-teen relationship distress and a slight increase in personal distress. Median CGM active wear time was 89%. Conclusion This study comprehensively evaluated CGM across usability, acceptability, and feasibility outcomes, with the findings supporting the integration of CGM into routine diabetes management in low-resource settings. The short follow-up period, however, may not capture changing perceptions or long-term adherence.

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ClinSeg: Robust Brain Segmentation for Clinically Acquired Pediatric MRI

Levitis, E.; Tregidgo, H. F. J.; Zimmerman, D.; Jung, B.; Karandikar, S.; Gardner, M.; Mattisson, P.; Kafadar, E.; Zapaishchykova, A.; Kann, B. H.; Sotardi, S. T.; Vossough, A.; Huang, H.; Billot, B.; Iglesias Gonzales, J. E.; Alexander, D. C.; Alexander-Bloch, A. F.; Seidlitz, J.

2026-09-02 pediatrics 10.64898/2026.08.28.26361643 medRxiv
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Clinical brain MRIs from pediatric health systems represent a viable resource for modeling early neurodevelopmental trajectories and studying neurodevelopmental risk in real-world populations. However, a limitation to date has been the performance of existing segmentation tools for measuring various brain phenotypes in clinical scans. In particular, many tools underperform in infant scans due to morphological and physical changes such as rapid myelination. Here, we introduce ClinSeg: a robust segmentation approach tailored to early-life clinical MRIs with variable orientation, resolution, and contrast. We leverage existing registration and synthetic data generation tools to construct a training corpus for a 3d U-Net spanning anatomical and contrast diversity, including scans with morphological abnormalities from a pediatric hospital. Validated against manual segmentations, ClinSeg outperforms existing models in infancy while matching them in childhood and adolescence. Finally, ClinSeg enables the construction of reference brain growth trajectories in 11,699 individuals from 0-21 years of age, leading to the detection of more nuanced age-related findings in clinical groups.

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People living with multiple long-term conditions have different pathways of unscheduled care in hospital: findings from an analysis of routinely-collected clinical data

Witham, M.; Evison, F.; Bellass, S.; Cooper, R.; Gallier, S.; Pretorius, S.; Sapey, E.; Suklan, J.; Sayer, A. A.

2026-09-01 health informatics 10.64898/2026.08.28.26361696 medRxiv
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Study Objective Little is known about where in hospital care for multiple long-term conditions (MLTC) is delivered. We aimed to describe pathways of care (ward transfers) and outcomes for people admitted to hospital for unscheduled care by MLTC status and other key sociodemographic characteristics. Design and setting Analysis of routinely-collected electronic health records from a large acute UK hospital. Participants Adult unscheduled care admissions from 1st July 2018 to 30th June 2019. The presence of two or more of 59 long-term conditions was ascertained using ICD-10 codes from previous hospital discharges. Main outcome measures Markov state transition probabilities were derived for ward moves and compared for MLTC vs no MLTC, age, sex, ethnicity and neighbourhood deprivation. Outcomes (length of stay, death, readmission, move from definitive ward) and time spent in emergency and assessment departments were compared between subgroups. Results A total of 33,252 adults, mean age 56.0 (SD 21.9) years were analysed; 14,834 (42.4%) had MLTC. People with MLTC were more likely to die in hospital (4.2 vs 1.9%, p<0.001), transfer to internal medicine wards or older peoples medicine wards, were less likely to transfer to surgical wards, had longer median length of stay (1.83 vs 0.69 days, p<0.001), stayed longer in acute medical units (15.5 vs 9.6 hours, p<0.001), and were more likely to move from their definitive ward (18.2 vs 16.4%, p=0.002). Conclusion Unscheduled hospital care pathways are complex and differ for people with MLTC, who have worse outcomes and may be less likely to receive optimal care.

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The effectiveness of a complex intervention, aimed at reducing hospital occupancy, to improve Emergency Department patient flow: a retrospective controlled interrupted time series

McHenry, R. D.; Caesar, D.; Clarke, B.; Mackay, D.; Pell, J.

2026-09-03 health systems and quality improvement 10.64898/2026.08.31.26361802 medRxiv
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Objectives Emergency department (ED) crowding is recognised as an important public health concern internationally, and is driven principally by exit block, the shortage of inpatient beds for patients requiring admission. This study aimed to evaluate whether a complex intervention targeting hospital occupancy improved ED patient flow, and quantified the change in attendances. Methods A controlled interrupted time series using weekly, publicly reported Public Health Scotland data from 1 January 2022 to 1 February 2026. The multi-component intervention focused on reducing hospital occupancy and included additional adult social care funding; engagement with regional social care providers; accelerated implementation of the Discharge without Delay programme; re-evaluation of whole-hospital escalation thresholds and response; resource and data supporting inpatient department reductions in length of stay; and additional investment in remote clinical assessment. The intervention commenced at a large tertiary ED on 01 February 2025. Primary outcomes were the proportions of attendances spending [&ge;]4, [&ge;]8 and [&ge;]12 hours in the ED. The secondary outcome was attendance volume. Segmented regression was fitted with a contemporaneous control series, seasonal terms and autoregressive moving average errors. Long waits were additionally illustrated as potentially avoided deaths. Results The analysis covered 161 pre-intervention and 52 post-intervention weeks. Relative to pre-intervention levels, the proportion of attendances waiting over 4 hours fell by 10.4% (95% CI 1.6 to 19.2%), by 16.4% (95%CI 1.3 to 31.5%) over 8 hours and by 24.3% (95%CI 2.6 to 46.1%) over 12 hours. Using established associations between long ED waits and excess mortality, by one-year the intervention was potentially associated with 54 fewer excess deaths (95%CI 19 to 93). Attendances rose by 3.8% (95%CI 1.3 to 6.4%) against the counterfactual. Conclusions A complex intervention targeting hospital occupancy was associated with a reduction in long ED waits despite rising attendances. Interventions addressing hospital occupancy can meaningfully improve ED crowding.

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GLP-1/GIP Uptake, Indication, and Access Pathways Among US Adults in the Understanding America Study

Chaturvedi, R. R.; Gracner, T.; Perez-Arce, F.; Suen, S.-c.; Jin, J.; Orriens, B.; Pacula, R. L.; Sexton Ward, A.; Haile, R.; Kapteyn, A.

2026-09-02 endocrinology 10.64898/2026.08.28.26361368 medRxiv
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Importance: Evidence on GLP-1/GIP therapies is largely derived from trials enrolling selected populations or medical records that miss utilization outside healthcare channels. No nationally representative cohort has characterized real-world uptake, indications, and access. Objective: To characterize GLP-1/GIP prevalence, indication, clinical profile, and access. Design: Prospective cohort study with three GLP-1/GIP surveillance waves (March 2024, December 2024, October 2025). Setting: The Understanding America Study, an address-based, nationally representative panel of approximately 15,000 US adults aged 18+ years initiated in 2014. Participants: UAS participants responding to at least one surveillance wave (n=9150). Exposures: GLP-1/GIP use status (never vs any use, comprising current and former use), self-reported primary indication (diabetes, weight loss, or other), and access pathway (traditional vs non-traditional). Main Outcomes and Measures: Survey-weighted prevalence of GLP-1/GIP use, overall and by indication and access pathway; sociodemographic, cardiometabolic, treatment, and access characteristics; and smartwatch-derived resting heart rate, heart rate variability, maximum activity heart rate, step count, and sleep duration and variability. Results: Among n=9150 adults (1274 with any use; 60.9% female; median age 53 years), weighted prevalence increased 46%, from 8.2% (March 2024) to 12.0% (October 2025) representing 32 million. Weight-loss indications grew, reaching nearly half of use (4.1% to 5.6%); diabetes-indicated use was stable (5.3% to 5.4%). Users carried high cardiometabolic burden (obesity, 68.2%; diabetes, 53.6%) but diverged by indication: diabetes-indicated users were older (median, 59 vs 49 years), whereas weight-loss-indicated users were more often female (69.9% vs 51.3%) and healthier. One in three users (~9 million) had non-traditional access, especially in weight-loss-indicated users, of whom 33% had no conventional prescription; 41% used compounding, online, or foreign pharmacies; and, 43% lacked coverage. Non-traditional users were five times as likely to report an unlisted, likely compounded formulation (19.8% vs 4.1%). All p<0.05. Conclusions and Relevance: Real-world GLP-1/GIP use has grown rapidly and diversified substantially in indication, access, and population profile. One in 3 users obtained treatment through nontraditional channels largely invisible to claims data, raising long-term safety, efficacy, and coverage questions. GLIMMER provides a public, nationally representative longitudinal evidence base for future payer and provider decisions.

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Household hunger trajectories and mental health symptoms of adolescent girls and young women in rural South Africa: an HPTN-068 longitudinal study

Chakraborty, R.; Rosenberg, M.; Weigel, M. M.; Pettifor, A.; Kahn, K.; Gomez-Olive, F. X.

2026-09-03 public and global health 10.64898/2026.09.01.26361988 medRxiv
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Purpose Despite the high documented prevalence of hunger and poor mental health in adolescent girls and young women (AGYW) in South Africa, this relationship remains understudied, with existing studies limited by their cross-sectional designs. This longitudinal study aimed to identify the association of hunger trajectories with anxiety and depressive symptoms, and hope in AGYW. Methods We used secondary data from the HIV Prevention Trials Network (HPTN) -068 conducted in rural Agincourt, South Africa. Complete data from 1779 AGYW collected at baseline (2011/12) and three annual follow-up visits were used. Hunger trajectories, measured using the Household Hunger Scale, were estimated via Group-Based Trajectory Modelling. Self-reported incident anxiety and depressive symptoms and hope were assessed based on AGYWs last two follow-up visits. Covariate adjusted modified Poisson regression models estimated the association between hunger trajectories and incident anxiety symptoms, incident depressive symptoms, and hope. Results Moderate-severe hunger was prevalent in 11.0%, 10.8%, and 6.0% of the households at baseline, follow-up 1, and 2, respectively. Incident anxiety symptoms were reported by 4.5%, incident depressive symptoms by 20.0% and hopelessness by 52.8% of the AGYW. Two hunger trajectories were identified- no hunger (82%) and marginal hunger (18%). Hunger trajectories were not associated with incident anxiety symptoms [RR:1.09, 95% CI: 0.55, 2.18], incident depressive symptoms [RR: 0.97; 95% CI: 0.72, 1.33] nor hope [RR: 1.00; 95% CI: 0.81, 1.23] in AGYW. Conclusion Better understanding of the factors that promote resiliency and mental health of AGYW in this setting is warranted to inform the design of interventions.

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Nurture Early for Optimal Nutrition (NEON): A pilot cluster randomised controlled trial of community-facilitator-led participatory learning and action womens groups to improve infant feeding & care among South Asian families in East London

Manikam, L.; Fatima, A.; Patil, P.; Mayadewi, C. A.; El Khatib, T.; Drazdzewska, J.; Oyebode, O.; Llewellyn, C. H.; Webb-Martin, K.; Irish, C.; Archibong, M.; Gilmour, J.; Kalungi, P.; Batura, N.; Shringarpure, K.; Lakhanpaul, M.; Heys, M.; NEON Steering Team,

2026-08-31 public and global health 10.64898/2026.08.28.26361604 medRxiv
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South Asian communities in the UK experience disproportionate maternal and child health inequalities linked to non-recommended infant feeding practices, limited health literacy, and socioeconomic constraints. Participatory learning and action (PLA) is effective in low- and middle-income countries, but high-income evidence is scarce. This pilot assessed the feasibility of a community facilitator-led PLA intervention to improve infant feeding among South Asian families in East London. A three-arm pilot feasibility cluster randomised controlled trial (ISRCTN10234623) was conducted in Tower Hamlets and Newham, East London (May-September 2022), with 12 wards randomised 1:1:1 to face-to-face PLA, online PLA, or usual care. Multilingual community facilitators delivered eight biweekly sessions over 14 weeks. Feasibility outcomes were assessed against prespecified Go/Stop criteria; exploratory outcomes included child feeding behaviours (Children's Eating Behaviour Questionnaire, CEBQ), parental feeding style (Parental Feeding Style Questionnaire, PFSQ), and child BMI Z-scores. Of 263 enrolled participants, 261 had a recorded trial arm allocation; consent to the pilot feasibility study was 70.7% (186/263; 95% CI 65.0-75.9%) meeting the [&ge;]50% Go criterion. Attendance was 37% (Tower Hamlets 59%, Newham 29%), below the [&ge;]80% Go threshold. Six-month retention was 54.8% (Tower Hamlets 78%, Newham 48.5%; 95% CI 41.8-55.3%), triggering the Definite Stop criterion. Significant baseline imbalances included BMI Z-score (p = 0.005), ethnicity, borough, and education; no between-arm BMI differences were observed at follow-up (p = 0.249). CEBQ and PFSQ baseline completion was 24.5% and 23.0%, with no usable follow-up data. PLA Phases 3 and 4 were not completed by any group; all participants providing feedback reported it acceptable. Recruitment was feasible and the intervention acceptable, but a Definite Stop criterion was triggered in Newham, no group completed the full PLA cycle, and outcome data were insufficient for evaluation. A definitive trial requires stratified randomisation, digitised multilingual data collection, participant reimbursement, and explicit PLA phase-completion criteria.