BMC Medicine

Neighbourhood deprivation is one of the few potential policy-modifiable risk factors for psychiatric and neurological disorders, but the neurobiological pathways underlying these associations remain unclear. We investigated these relationships across three cohorts spanning the life span: the Healthy Brain and Child Development (HBCD) Study (n = 84, aged 0 to 4 weeks postnatal), the Adolescent Brain Cognitive Development (ABCD) Study (n = 4,792, aged 9 to 10 years), and the UK Biobank (UKB; approximately 500,000 adults, aged 44 to 87 years). Neighbourhood deprivation was associated with elevated disease risk, and individual lifestyle factors accounted for only a small fraction of this burden, indicating that the much larger residual effect reflects broader contextual characteristics of deprived environments rather than individual behaviours alone. Across all cohorts, greater deprivation consistently predicted lower cortical and subcortical brain volume, with effects detectable in early development and substantially stronger in adulthood. Across disorders, regional brain volume emerged as a consistent neuroanatomical mediator linking neighbourhood deprivation to neuropsychiatric disease. We further showed that deprivation preferentially affects brain regions intrinsically vulnerable to neuropsychiatric disorders. Spatial decoding analyses implicated dopaminergic and serotonergic neurotransmitter systems together with specific excitatory and inhibitory neuronal classes. Importantly, both the deprivation effects and their neuroanatomical mediation patterns were replicated across independent populations. Our study delivers a translational framework linking neighbourhood deprivation to brain health, which could inform public health policies and preventive interventions.

Objectives: To examine the association between small-area socioeconomic deprivation and risk of early-onset pre-eclampsia (diagnosed <34 weeks gestation) in England, and to assess the relative contributions of individual-level risk factors and variation between maternity care sites to observed inequalities. Design: Retrospective population-based cohort study. Setting: National Health Service (NHS)-funded maternity services in England between 1 January 2021 and 31 March 2025. Participants: 1,027,707 nulliparous pregnant women aged 13-60 years receiving NHS-funded maternity care in England with singleton pregnancies and non-missing deprivation data. Secondary analyses were conducted for 940,505 multiparous pregnant women. Main outcome measures: Early-onset pre-eclampsia, defined as diagnosis before 34 completed weeks of gestation. Results: Increasing socioeconomic deprivation was associated with higher odds of early-onset pre-eclampsia among nulliparous women across all regression models. In the confounder-adjusted model, each one-point increase in the continuous deprivation score (scaled 0-10) was associated with a 3.4% increase in odds of early-onset pre-eclampsia (adjusted odds ratio (aOR) 1.034, 95% confidence interval (CI) 1.027 to 1.041). Adjustment for theorized mediators attenuated the association modestly (aOR 1.023, 95% CI 1.017 to 1.030), while additional adjustment for hospital site further attenuated the association (aOR 1.016, 95% CI 1.009 to 1.023). Elevated BMI, circulatory disease, maternal age over 40 years, Black ethnicity, and endocrine/metabolic disease were among the strongest predictors of early-onset pre-eclampsia. Similar but stronger deprivation associations were observed among multiparous women. Associations between deprivation and late-onset pre-eclampsia were comparatively weak or absent after adjustment. Conclusions: Socioeconomic deprivation was associated with increased risk of early-onset pre-eclampsia in England, particularly among multiparous women. Both individual-level risk factors and variation between maternity care sites appeared to contribute to observed inequalities. These findings support the importance of combining targeted clinical risk reduction with efforts to reduce unwarranted variation in NHS maternity care delivery. Keywords: Maternity care, Pregnancy, Pre-eclampsia, Socioeconomic deprivation, Health equity, National Health Service

Tokyo experienced a measles outbreak (260 cases) in early 2026 despite elimination status. Adults aged 20-39 years were most affected, and 38% of cases were modified measles, increasing with prior vaccination. Although incidence rose until April, the effective reproduction number; R(t) fell below 1, consistent with outbreak control. Multiple clusters were identified, but many cases lacked epidemiological links, suggesting that modified measles is less likely to be considered in differential diagnosis. Intensive contact tracing and surveillance contributed to limiting transmission.

There are no published data on cancer screening by women using medically assisted reproduction (MAR). Such data would aid interpretation of the cancer incidence and risk profiles for this group. Using linked population-based Australian health registries and administrative datasets, we compared organised publicly funded cervical and breast screening episodes for women who received one of three types of MAR and matched women who did not between 1991 and 2016. We modelled the proportion of women screened in the three years before and after first MAR treatment, adjusting for age, remoteness, parity, socio-economic disadvantage, cancer history, and uptake of the other screening program. After adjustment, a greater proportion of women who received MAR than women who did not had cervical screening before MAR (77.3%-84.1% vs 57.5%-62.0%, depending on treatment) and after MAR (77.0%-78.5% vs 68.1%-68.3%). Contrastingly, breast screening estimates were 7.6%-9.6% vs 9.3%-10.5% before MAR and 11.0%-15.0% vs 12.8%-14.9% after MAR.

Background/Objectives We evaluated the impact of the COVID-19 adolescent vaccination in England at two different epidemic points: the autumn (August-November) 2021, in the presence of a large Omicron epidemic wave, and the autumn (August-November) 2022, when the subsequent Omicron epidemic was at an endemic stage. Methods Using the Covasim SARS-CoV-2 model for England, under varying vaccine uptake and onset time, we evaluated the impact of a)vaccinating 18+ only versus additional 12+ vaccination from the autumn 2021; and b)the current immunisation strategy at the time versus additional 12+ vaccination from September 2022, projecting the number of new daily SARS-CoV-2 infections, hospitalisations and deaths. Results In presence of the BA.1 Omicron wave in late 2021, the expanded adolescent vaccination averted ~3,000,000 cases across all-ages, ~1,010,000 SARS-CoV-2 infections in the period 2-6 months from vaccine onset in the vaccinated cohort. During the Omicron waves in 2022, additional adolescents vaccination did not significantly reduce the COVID-19 burden in the entire population, nor within the vaccinated cohort. Conclusions Our findings highlight that adolescent vaccination impact depends on the timing/speed of implementation, other present intervention strategies, and the status of the epidemic at the time and it should not be considered as a stand-alone immunisation strategy.

Background Childhood adversity can affect propensity to risk-taking behaviors. We aim to investigate the relation between childhood adversity and risk-taking behaviors in youth using emergency room (ER) admissions and survey data. Method Using the DANLIFE study, we included 1.2 million Danes. Individuals were assigned into five groups based on childhood adversity exposure from ages 0 to 15 years. We applied survival analyses on repeated outcomes to model ER-admissions due to substances, violence and unintentional injury in the full cohort between ages 16 and 24. We applied logistic regression models to weighted survey data on frequent binge drinking, cannabis use, drug use, and unsafe sex in a nested subsample of 34,064 18 year olds from the Danish National Birth Cohort. Results The high adversity group was at highest risk of ER-admissions due to substances (HR=3.27, 95% CI [3.10, 3.46]), violence (HR=2.67, 95% CI [2.58, 2.76]) and unintentional injuries (HR=1.30, 95% CI [1.28, 1.33]). In the nested subsample, the high adversity was at highest risk of cannabis use (OR=1.59, 95% CI [1.21, 2.09]), drug use (OR=2.44, 95% CI [1.71, 3.49]) and unsafe sex (OR=1.72, 95% CI [1.34, 2.22]), but at lower risk of frequent binge drinking (OR=0.57, 95% CI [0.37, 0.87]). Conclusion These findings highlight how childhood adversity is associated with increased engagement in and harm from risk-taking behaviors. To prevent inequalities in health in youth, there is a need for interventions and policies that promote child welfare, as well as targeted support for youth with harmful behavioral patterns.

Background: Endometriosis affects approximately 10% of reproductive-age women and is associated with substantial diagnostic delay and heterogeneous symptom presentation. Prior machine-learning prediction models have relied on comorbidity data alone or on small candidate-variant genetic scores, with inconsistent or incompletely reported performance. No study has combined a well-powered, multi-ancestry polygenic risk score (PRS) with environmental, reproductive, and symptom data in a single hybrid model. We developed and evaluated hybrid risk-prediction models integrating a genome-wide, multi-ancestry PRS with clinical and symptom data for endometriosis in the US-based All of Us Research Program. Methods: Among 69,376 participants (15,382 endometriosis cases, 53,994 controls) across six genetically inferred ancestry groups, we computed individual-level PRS values using PRS-CS weights derived from an independent, multi-ancestry GWAS. Five nested logistic regression, random forest, and XGBoost models progressively added age, ancestry, and within-ancestry genetic principal components (Model 1), environmental and reproductive factors (Model 2), symptom and comorbidity indicators (Model 3), all covariates combined (Model 4), and PRS x environment interactions (Model 5). Performance was assessed by AUROC in a held-out test set and 5-fold cross-validation, with class-weighted, Youden-optimized thresholds used for sensitivity, specificity, and predictive values; permutation importance identified top contributors. Pairwise AUROC differences were tested with a Holm-corrected DeLong-type test. Results: Discrimination improved from AUROC 0.63 (PRS, age, ancestry, principal components) to 0.72 for the full model, driven mainly by symptom and comorbidity data. XGBoost consistently outperformed logistic regression and random forest. The PRS ranked among the top individual predictors by permutation importance in nearly every model, alongside age, while genetic and demographic information alone gave only modest discrimination, and PRS x environment interactions did not improve on environmental factors alone. Threshold optimization yielded balanced sensitivity and specificity (~0.67/0.65) versus near-zero sensitivity at a default threshold. Conclusions: Combining the PRS with symptom and comorbidity data gave the best discrimination compared to solely a well-powered, multi-ancestry PRS as a predictor of endometriosis. This study clarifies both the promise and current limits of hybrid genetic-clinical prediction for endometriosis and points to symptom-based phenotyping, molecular subtyping, and external validation as priorities.

Background: Curable sexually transmitted infections (STIs) are associated with adverse birth outcomes, yet little cost-effectiveness evidence guides antenatal STI screening policy in high-burden settings. We conducted a cost-effectiveness and cost-utility analysis of the Philani Ndiphile trial in South Africa, comparing One-Time and Two-Time antenatal screening for C. trachomatis, N. gonorrhoeae, and T. vaginalis with standard syndromic management. Methods: A decision-analytic model from the provider perspective simulated costs and outcomes for pregnant women and infants. Costs included diagnostics, treatment, and neonatal hospitalisation for a primary composite outcome of preterm birth and/or low birthweight and its components (secondary trial outcomes). Modelled outcomes included incremental cost (US$) per composite (preterm birth and/or low birthweight) case, per component case and per disability-adjusted life year (DALY) averted. The analysis captured infant outcomes in the first year. Univariate and probabilistic sensitivity analyses were conducted to assess parameter uncertainty and robustness of results. Results: Screening for C. trachomatis, N. gonorrhoeae, and T. vaginalis twice during pregnancy was not cost-effective for preventing the primary composite outcome, nor for preventing low birthweight alone. However, two-time screening was cost-saving for preventing preterm birth alone, averting more DALYs and thereby yielding better health outcomes while reducing healthcare costs compared with syndromic management. One-time screening was not cost-effective for preventing any outcome. Conclusions: Repeat antenatal screening for C. trachomatis, N. gonorrhoeae, and T. vaginalis has the potential to prevent preterm births while reducing healthcare costs in high-burden settings. These findings support further research to confirm the clinical effectiveness of repeat screening and to evaluate longer-term health and economic impacts.

Introduction: Respiratory infections are a leading cause of morbidity. Newly available vaccines to prevent respiratory syncytial virus (RSV) disease and encouraging clinical progress on vaccines for human metapneumovirus (hMPV) and parainfluenza (PIV) could reduce the disease burden beyond existing influenza and SARS-CoV-2 immunisation programs. However, evidence on the contribution of these viruses to respiratory disease burden across the lifespan remains limited. Methods: We reviewed studies from 01/2002-11/2025 reporting age-stratified, medically attended cases of influenza, and at least one of RSV, hMPV, or PIV, in high-income countries, excluding periods substantially overlapping with the COVID-19 pandemic. Using only studies that tested for all four viruses, we estimated the age-specific proportion of cases that were non-influenza (total across RSV, hMPV and PIV) compared to influenza using a mixed-effects logistic regression model. Results: Following exclusions and screening, 61 studies were included in the primary analysis comprising >500,000 detections of the four viruses. We found that a substantial proportion of medically attended respiratory illness in infants and young children was due to PIV, hMPV and RSV, rather than influenza, with a non-influenza virus proportion of 90.2% (95% CI 85.9-93.2%) in young infants aged 0-6 months. The converse was true for school-aged children, with a non-influenza virus proportion of 34.8% (95% CI 26.5-44.2%) in children aged 5-18 years. In adults aged 65+ years, non-influenza causes of medically attended disease were common at 60.2% (95% CI 50.0-69.5%). Restricting to studies reporting hospitalised cases (n=19) produced broadly similar age-specific trends in relative virus burden contributions. Discussion: We highlight the significant burden of medically attended illness due to PIV, hMPV and RSV across ages, particularly in infant and preschool-aged children and older adults, supporting the need for effective vaccines targeting this burden.

Background: Inequalities exist for many health outcomes, but there is limited evidence regarding menstrual symptoms despite their importance for health and wellbeing. We aimed to investigate inequalities in menstrual symptoms according to socioeconomic position and childhood adversity. Methods: In two generations (G0 mothers and G1 offspring) from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK prospective cohort study, we examined associations of multiple indicators of socioeconomic position (SEP) and adverse childhood experiences (ACEs) with menstrual symptoms (pain, abnormal uterine bleeding, and premenstrual syndrome (PMS) measured 3-8-years post-birth in G0 and 17-21-years-old in G1), using multivariable logistic regression. Samples ranged from 4,828 to 9,335 G0 participants and 1,288 to 2,757 G1 participants depending on the exposure-outcome association. Missing data were addressed using multiple imputation and inverse probability weighting. Results: Financial difficulties were associated with greater odds of menstrual pain (G1 OR 1.41; 95% CI 1.07, 1.86: G0 OR 1.55; 95% CI 1.36, 1.76) and irregular cycles (G1 OR 1.60; 95% CI 1.12, 2.29: G0 OR 1.48; 95% CI 1.27, 1.72) in both generations, as well as with short/long cycle lengths in G0 only. Lower education and manual social class were also associated with these three menstrual symptoms in at least one generation. Conversely, higher SEP was associated with PMS in both generations. Higher cumulative ACEs were consistently associated with menstrual pain (4+ compared to none: G1 OR 2.15; 95% CI 1.48, 3.11: G0 OR 1.52; 95% CI 1.29, 1.80) and irregular cycles (G1 OR 1.92; 95% CI 1.20, 3.09: G0 OR 1.54; 95% CI 1.26, 1.87) but not cycle length. Lower parental education, financial difficulties, and cumulative ACEs were associated with heavy bleeding in G1 offspring only, whereas financial difficulties, own manual social class, and cumulative ACEs were associated with prolonged bleeding in G0 mothers only. Higher cumulative ACEs were also associated with PMS in G1 offspring only. Conclusions: We found evidence of inequalities according to socioeconomic disadvantage and childhood adversity for multiple menstrual symptoms, although some associations were only observed in one generation. Findings suggest that menstrual symptoms are disproportionately experienced by socially and socioeconomically disadvantaged women.

Background Annually, nearly 2 million hip, knee, and spinal inpatient surgeries are performed in Canada and the US for osteoarthritis (OA), costing over $37 billion in hospital expenditures. However, 15-30% of patients experience limited or no improvement, resulting in poor value for money. This study evaluated the one-year cost-utility of joint and spine procedures for OA by comparing non-responders to responders, considering various responder definitions. Methods Individual micro-costing data were collected for 1,175 elective hip, knee, and spine patients enrolled in the Longitudinal Evaluation in the Arthritis Program - Osteoarthritis (LEAP-OA) between 2014 and 2018. Quality-adjusted life years (QALYs) were derived using the SF-6D utility index. One-year incremental cost-utility ratios (ICURs) were calculated from the hospital perspective. Results Responder rates varied by definition, ranging from 78%-94% for hip replacements, 64%-90% for knee replacements, 60%-64% for spine fusions, and 50%-68% for spine decompressions. Corresponding ICURs were: $45,956-$51,773/QALY for responders versus $108,593-$485,762/QALY for non-responders for hip replacements; $54,831-$71,151/QALY for responders versus $200,486-$1,203,596/QALY for non-responders for knee replacements; $65,980-$74,422/QALY for responders versus $262,039-$729,686/QALY for non-responders for spine fusions; and $29,947-$42,168/QALY for responders versus $63,195-$662,586/QALY for non-responders for spine decompressions. Conclusions While surgical response rates were highly dependent on the responder definition, ICURs for non-responders were significantly higher than those for responders across all definitions. Beyond the negative impact on patients, there is a compelling economic argument for investment in improved pre-operative identification of patients at risk of surgical non-response. Such efforts could enable more personalized, value-based care pathways and reduce the provision of low-value surgical interventions.

Introduction: The global epidemiology of menopausal symptoms among middle-aged and elderly women remains unclear. Methods: Data on prevalence, comorbidities, incidence and outcomes of menopausal symptoms published up until March 1st 2019 were searched in PubMed, Embase and Cochrane databases. We used a random-effects model to compute point estimates of prevalence for 24 types of menopausal symptoms. We narratively summarized the patterns of the comorbidities, incidence and outcomes of menopausal symptoms due to limited data. Results: A total of 239 studies (n{approx}2.5 million middle-aged and elderly women) from 56 countries and regions were included in the analysis. The global pooled prevalence analysis revealed that hot flashes (48%) and night sweats (30%) were highly prevalent, alongside psychological symptoms like insomnia (47%), irritability (46%), anxiety (39%), and depression (30%). Physical symptoms including joint aches/pain (50%), backache (47%), and tiredness (61%) were also commonly reported. Heat intolerance showed the highest prevalence (76%), while symptoms like urinary incontinence (24%) and poor appetite (8%) were less frequent. These findings highlight the diverse and widespread impact of menopause on women globally, with significant variations across symptom types. Africa showed the highest pooled prevalence across a series of symptoms, compared with other continents. We observed high prevalence in developing countries, especially for psychological and physical symptoms; significant intra-Asian variation in vasomotor symptoms; hypertension and obesity as the most common comorbidities; joint pain, urinary incontinence, and vasomotor symptoms as the most incident complaints; and positive associations with cardiovascular disease in the psychological (depression and insomnia) and physical (joint pain) domains. Conclusion: This study highlights the global burden of menopausal symptoms, with significant differences across continents. The findings call for more inclusive research on underrepresented groups (particularly in Africa) and further investigation into drivers of this marked global heterogeneity in prevalence of menopausal symptoms and their comorbidities, incidence and outcomes.

Importance: Maternal vaccination and long-acting monoclonal antibodies are now available in the U.S. to prevent RSV. Long-acting monoclonal antibody administration in the U.S. commonly occurs after hospital discharge in outpatient settings, leaving some infants unprotected early in life when severe RSV risk is highest. Comparative effectiveness between the two interventions and whether delays affect effectiveness estimates have not been quantified. Objective: To evaluate the effectiveness of infant long-acting monoclonal antibody strategies and a maternal vaccination strategy, each compared to no intervention, and the comparative effectiveness of intervention strategies when accounting for real-world delays in monoclonal antibody receipt. Design: Cohort study using target trial emulation to compare four strategies for prevention of RSV-related outcomes. Setting: The U.S. between 2023 and 2025 using a nationwide database of employer-sponsored commercial insurance claims. Participants: 120,586 commercially insured mother-infants, whose infants were born in the U.S. during the 2023-2024 or 2024-2025 RSV season. Infants who could not be paired with their mother's record, did not enroll in commercial insurance within 75 days from birth, received palivizumab, and had an implausible birth date were excluded. Interventions: Comparison of four RSV prevention strategies: (i) maternal RSVpreF; (ii) long-acting monoclonal antibody given within the first week of life (mAb as intended); (iii) long-acting monoclonal antibody given within a six-month grace period from birth (mAb within grace period); and (iv) a control. Main outcomes and measures: Effectiveness against first RSV-associated hospitalization and medically-attended RSV illness was summarized using adjusted hazard ratios (aHR) and estimated using an inverse propensity weighting approach, with weights accounting for maternal age, maternal comorbidities affecting pregnancy, obstetric and newborn complications, season, region, and birth timing relative to October 1. A weighted Kaplan Meier estimator was used to estimate strategy-specific cumulative incidence of RSV outcomes over time. Results: In the first five weeks of life, the mAb within grace period strategy doubled the hazard of RSV hospitalization (aHR: 2.0 [95% CI: 1.0-4.9]) and increased the hazard of medically-attended RSV (aHR: 1.6 [95% CI: 1.0-2.7]) compared to the maternal RSVpreF strategy. The hazard for RSV hospitalization was similar for the mAb as intended strategy compared to the maternal RSVpreF strategy (aHR = 0.9 [95% CI: 0.3-1.9]). Conclusions and relevance: RSVpreF and monoclonal antibodies were similarly effective when monoclonal antibodies were administered close to birth, but when accounting for real-world delays in monoclonal antibody receipt, the maternal RSVpreF strategy was more effective than the mAb within grace period strategy.

Background: Observational research reports positive associations between type 2 diabetes mellitus (T2DM) and obesity-related cancers (ORCs), but causality remains unclear due to confounding (namely the shared risk factor of obesity, commonly approximated as body mass index, BMI), immortal time bias, and detection-time bias. Here, we aimed to use causal inference methods to minimise the above problems and estimate causal associations between new-onset T2DM and incident cancer. Methods: We performed a cohort study within UK Biobank, comparing new-onset T2DM with unexposed individuals matched 1 to 3 on BMI, age, and sex using a sequential longitudinal approach. The primary outcomes were total incident cancer, divided into ORCs and non-obesity-related cancers (NORCs). The secondary outcomes were site-specific cancers. We developed Cox models to estimate time-split hazard ratios (tsHRs) and 95% confidence intervals (CIs) stratified by sex. Findings: 23,771 participants with new-onset T2DM were matched with 71,170 unexposed participants. During a median follow-up of 5 years, there were 7694 (T2DM: 2432; unexposed: 5262) incident cancers. In men, there was evidence for an effect of T2DM on obesity-related cancer (tsHR 1.39, 95% CI 1.21-1.59), particularly on hepatocellular carcinoma (tsHR 3.97, 95% CI 2.38-6.65), pancreatic (tsHR 1.77, 95% CI 1.15-2.72) and kidney (tsHR 1.62, 95% CI 1.13-2.32) cancers. In women, there was evidence for an effect on obesity-related cancers (tsHR 1.33, 95% CI 1.16-1.52). Importantly, there were no associations with post-menopausal breast and endometrial cancers, two cancer types consistently associated with elevated BMI. There was no effect of new-onset T2DM on incidence of NORCs. There was evidence of detection-time bias, particularly in men. Interpretation: This is the first large-scale study to demonstrate evidence of a BMI-independent associations between new-onset T2DM and incident cancer. In men, this was primarily driven by hepatocellular carcinoma, pancreatic cancer, and kidney cancer. In women, the underlying cancers driving this relationship were less clearly defined. Funding: This study was funded by Cancer Research UK and administered through the Manchester Cancer Research Centre MB-PhD scheme (SEBCATP-2023/100010).

Importance: As new treatments increase quality and length of life in people with multiple sclerosis (MS), effective prevention and management of common comorbidities, including Diabetes Mellitus (DM), is increasingly important. Objective: To compare incidence of DM and its associations with hospitalisation and mortality in adults with MS and matched controls. Design: Using English primary care data from the Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics and national mortality records, we matched adults with MS diagnosed between 2000 and 2023, with up to ten controls without MS by age, sex, and practice. We excluded individuals with preexisting DM, defined using diagnostic and management codes. Outcomes included all-cause hospitalisation (number and duration) and mortality. We used Poisson, negative binomial, linear, and Cox proportional hazards models, adjusting for demographic and socioeconomic factors, adding interaction terms to examine if ethnicity, deprivation, and urbanity were associated with outcomes. Results: We included 9,010 individuals with MS and 78,121 matched controls. Over a mean follow-up of 13.2 years, people with MS had over twice the incidence of DM compared with controls (adjusted incidence rate ratio [aIRR]=2.26, 95% CI: 1.96 to 2.61, p<0.001). Among people with MS, incident DM was associated with higher hospitalisation rates (aIRR=1.82, 95%CI: 1.47 to 2.28, p<0.001), longer hospitalisation duration (median 18 vs 4 days, adjusted beta;=0.53, 95%CI: 0.41 to 0.65, p<0.001), and increased all-cause mortality when incident DM was modelled as a time-varying exposure (adjusted hazard ratio=1.46, 95%CI: 1.17 to 1.82, p<0.001), compared to those who did not develop DM. Similar patterns were observed among controls (hospitalisation rates: aIRR = 2.96, 95% CI 2.63 to 3.23, p<0.001; hospitalisation duration: adjusted {beta} = 0.93, 95% CI: 0.86 to 0.99, p<0.001; mortality [time-varying]: HR = 1.50, 95% CI: 1.27 to 1.77, p<0.001). The relationship between DM and increased hospitalisation was stronger in rural areas among those with MS and stronger in White groups among controls. Conclusions: People with MS are more likely to be diagnosed with DM, resulting in greater all-cause hospitalisation and all-cause mortality. This highlights the importance of equitable screening, prevention, and management of DM in people living with MS, with particular attention to geographical health inequalities.

Background: A maternal vaccine (MV) and a long-lasting monoclonal antibody (la-mAB) have been licensed to protect children against RSV. Given the swift waning of their protection, we evaluated the added benefit of seasonal la-mAB administration for children born to vaccinated mothers shortly after the RSV season in Germany. Methods: We fitted an age- and birth season-structured catalytic model to cross-sectional seroprevalence data of RSV antibodies using a Bayesian framework to estimate the timing of RSV infections in children <5. We then estimated the incidence of severe outcomes in the absence of immunisation in children <1. Finally, we estimated the impact of the MV and of additional la-mAB administration, accounting for the waning of protection. Results: We estimate that children would, on average, be 7 months old (mo) at their first infection, those born in the autumn being the youngest at first infection (4 mo). Together with the children born in the winter, they account for 46% of all RSV hospitalisations and 62% of RSV ICU admissions in unimmunised <1 yo. MV would prevent a total of 776 (473-1,122) hospitalisations per 100,000 vaccinees and 73 (51-94) ICU admissions per 100,000 vaccinees, predominantly among autumn-born children. The summer birth cohort would benefit most from additional la-mAB administration, preventing an additional 46% (10-63) of ICU admissions compared to MV alone, corresponding to an additional 25 (4-45) ICU admissions prevented per 100,000 immunised children. Conclusion: Compared to MV alone, the impact of MV+la-mAB on RSV hospitalisations and ICU admissions would likely be modest.

Background: Few longitudinal studies have examined the long-term health impact of changing malaria prevention and treatment strategies in Africa. This study analyses 35 years of clinical surveillance among paediatric malaria admissions in Kilifi, Kenya. Methods: Children aged 1 month to 14 years who were residents of rural Kilifi Health and Demographic Surveillance System and admitted to Kilifi County Hospital between January 1990 and December 2024 were included. Community malaria exposure was estimated using infection prevalence among children admitted for trauma, elective surgery, bites and neoplasms. Malaria admissions were defined as hospitalisations with a positive blood slide and a primary, secondary, or co-morbid malaria diagnosis. Severe malaria phenotypes including severe anaemia, cerebral malaria, hyper-parasitaemia and in-hospital mortality were also examined. Binomial and Poisson regression models assessed temporal differences, using 1990 to 1996 as the reference period Results: Community malaria prevalence declined from 35% (95% CI: 31, 39) in the 1990s to 2% (95% CI: 1, 4; p<0.001) in 2020 to 2024. Malaria hospitalisations declined from a peak of 25.5 per 1,000 children per annum (p.a.) (95% CI: 24.4, 26.6) in 1999 to 0.65 (95% CI: 0.59, 0.72; p<0.001) between 2020 and 2024. The median age of malaria increased from 19 months (IQR: 12, 39) between 1990 and 1996 to a peak of 48 months (IQR: 28, 78) between 2012 and 2019. Cerebral malaria became proportionally more common than severe anaemia over time. Malaria-specific hospitalised mortality rates declined from 0.43 per 1,000 children p.a. (95% CI: 0.38, 0.49) in the 1990s to 0.03 (95% CI: 0.02, 0.05; p<0.001) during the period 2020-2024. Conclusions: Hospital admission with malaria among children in Kilifi is now uncommon. Sustained reductions in parasite exposure have altered the clinical profile of disease presentation, including both phenotype and age distribution, without resulting in a cumulative increase in disease burden. Expanded and sustained coverage of effective long-lasting insecticidal nets, together with improved access to effective treatment, have likely contributed to this epidemiological transition.

Background: Vaccination with rVSV-ZEBOV is highly effective against Zaire ebolavirus, but protection against Bundibugyo ebolavirus (BDBV) is unknown. We used a stochastic network model of the 2026 Democratic Republic of the Congo BDBV outbreak to evaluate the potential impact of a partially cross-protective vaccine under operationally realistic conditions. Methods: We developed a susceptible-exposed-infectious-recovered model on a two-layer household-community contact network calibrated to public data through July 5, 2026. The model incorporated stochastic detection, isolation, first- and second-degree contact tracing, reactive ring vaccination, and community vaccination. Base-case vaccine efficacy was 45% and included post-exposure protection against disease and mortality, with time to protection modelled as a continuous sigmoidal function. Sensitivity analyses varied vaccine efficacy, timing, case detection, and contact tracing. Findings: Increasing case detection from 30% to 70% and contact tracing from 30% to 80% reduced deaths by 59.8% (IQR 54.6-65.0) compared with base operations without vaccination. Adding reactive ring vaccination reduced deaths by 65.5% (IQR 59.1-71.2) versus base, but by 13.6% (IQR -3.2 to 27.9) versus enhanced operations alone. Community vaccination at 20-80% coverage reduced deaths by 47.1-91.0%. With 50% community coverage, mortality reduction declined from 86% at outbreak declaration to 58% with a 14-day delay. Ring vaccination impact was sensitive to immune-onset timing, with incremental mortality benefit declining from 23% to 10% as the assumed immune-onset midpoint increased from 5 to 14 days. Interpretation: Strengthening case finding and contact tracing is central to mortality reduction in BDBV outbreak response. If rVSV-ZEBOV provides clinically meaningful cross-protection against BDBV, reactive ring vaccination could provide a measurable but modest incremental benefit when operations are already strong. Larger mortality reductions require vaccination that reaches susceptible individuals before exposure, which is more consistent with rapid community vaccination in affected areas.

Childhood obesity is a major global health concern, yet the long-term effects of early-life adiposity on adult fat distribution and underlying biological pathways remain poorly understood. In particular, it is unclear whether childhood BMI differentially influences specific adipose tissue depots and whether circulating proteins mediate these relationships. We conducted a Mendelian randomisation study using genetic instruments for childhood BMI across 12 timepoints from ages 3 to 18 years. Two-sample MR was applied to five MRI-derived adult fat depots (abdominal subcutaneous (ASAT), gluteofemoral (GFAT), visceral (VAT), liver, and pancreatic fat) in UK Biobank. We further implemented a two-step MR framework to assess whether 2,940 circulating plasma proteins (Olink) mediate observed associations, integrating temporal, statistical, and directional evidence across childhood. Genetically predicted higher childhood BMI from approximately age 7 years onwards was associated with increased ASAT and GFAT in adulthood, but showed little evidence of association with visceral, liver, or pancreatic fat, with effects persisting into adolescence. Two-step MR identified 140 proteins influenced by childhood BMI during a developmentally sensitive window, of which seven showed directionally consistent evidence of mediation. These proteins included ACAN, CCL7, and CLIC5 for abdominal subcutaneous fat, and CLIC5, BMP10, CLEC10A, KIT, and IGSF3 for gluteofemoral fat, highlighting partially distinct biological pathways across depots. Childhood BMI exerts depot-specific effects on adult fat distribution, particularly influencing subcutaneous adipose tissue. Circulating proteins provide evidence of potential mediating pathways, supporting the existence of developmentally sensitive biological mechanisms linking early-life adiposity to adult body composition. These findings underscore childhood as a critical period for shaping long-term adipose tissue distribution and highlight potential molecular targets for future intervention strategies.

Each year, over 50 million children receive preventive malaria treatment. However, to date there has been no consensus on the most effective antimalarial drugs to use, especially given geographic differences in drug resistance. Here, we conduct a systematic review comparing the effectiveness of the most commonly used antimalarial chemopreventive regimen, sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ), with other antimalarial drugs in preventing new infections. We searched MEDLINE, Embase, Global Health, PubMed and WWARN clinical trial databases until 06 December 2025 for studies satisfying the inclusion criteria. Studies were included if they were peer-reviewed, randomised-controlled studies in Africa, measuring incidence of infection or clinical episodes of Plasmodium falciparum malaria for at least 28 days post-treatment. We also compiled data on the prevalence of markers of resistance in the parasite dhfr, dhps and mdr1 genes in the study areas. We conducted meta-analyses of incidence rates, with subgroup analyses by drug resistance levels. This review is registered on PROSPERO (CRD42024577149). We identified 27 studies representing 38,252 participants in 32 sites across 13 countries. In pooled analysis, SP+AQ reduced incidence of malaria by 54.6% (95% CI: 33.8-68.8%) compared to SP alone, including significantly outperforming SP even in areas with low SP resistance. These findings suggest that countries currently using SP alone for chemoprevention should consider switching to SP+AQ. Where AQ resistance remains low, available evidence suggests SP+AQ remains efficacious for malaria chemoprevention. SP+AQ was comparable to the artemisinin-based treatment, dihydroartemisinin-piperaquine across all studies (incidence rate ratio 0.93; 95% CI 0.78-1.11). By resistance levels, SP+AQ had slightly higher efficacy in areas with low SP and AQ resistance but had comparable or slightly lower efficacy in areas with higher resistance. Using artemisinin-based treatments for chemoprevention must be balanced against the risk of worsening artemisinin resistance in Eastern and Southern Africa. This study was funded by the UK Royal Society.