The Lancet Regional Health - Europe

Background Despite the significant impact of longstanding paediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial and is primarily driven by nonPCV13 serotypes. Higher valent vaccines such as the 20 valent PCV (PCV20) may provide additional public health and economic benefits, yet their value in the contemporary UK setting has not been fully assessed using recent data. Methods We updated an age structured dynamic transmission model using post COVID 19 UK epidemiology (2001 to 2023) to compare pediatric PCV20 with PCV13 and PCV15. Over a 10 year horizon, we assessed cost effectiveness and number needed to vaccinate (NNV), capturing invasive and non invasive disease cases, deaths, costs, quality adjusted life years, and incremental cost effectiveness ratios. PCV20 was evaluated under 1+1 and 2+1 schedules; PCV13 and PCV15 were assessed under 1+1. Scenario analyses examined key uncertainties. Results PCV20 was estimated to avert more cases and deaths than PCV13 or PCV15, driven by broader serotype coverage and indirect effects. Both PCV20 schedules were dominant or cost saving versus lower valent comparators, with lower NNVs. PCV20s higher vaccination costs were offset by reductions in downstream healthcare expenditures. Conclusion Paediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency, supporting timely adoption.

Lower cognitive ability measured in childhood or late adolescence has been consistently associated with higher mortality risk across adulthood. However, this evidence largely relies on single assessments, leaving it unclear to what extent mortality risk reflects cognitive differences established early in life versus developmental divergence during adolescence - a period of substantial neurocognitive plasticity. Using two nationally representative Swedish cohorts comprising 9,412 males born in 1948 and 1953, we linked cognitive ability assessed in primary school at age 13 years and military conscription at age 18 years to all-cause and cause-specific mortality recorded in nationwide registers through 2025. We decomposed late-adolescent cognitive ability into childhood cognitive level and adolescent cognitive change and evaluated their independent associations with mortality. Childhood cognitive level (HR = 0.81; 95% CI, 0.78-0.85) and adolescent cognitive change (HR = 0.84; 95% CI, 0.79-0.89) independently predicted lower mortality risk, also after adjustment for parental education. Childhood cognitive level and adolescent cognitive change showed partially distinct cause-specific patterns. Childhood cognitive level was most strongly associated with mortality from intrinsic causes, whereas adolescent cognitive change showed relatively stronger associations with external causes, particularly accidental deaths. Although adolescent cognitive change was associated with psychosocial factors including education and psychiatric diagnosis at conscription, its association with mortality persisted after adjustment for these factors. These findings suggest that cognitive development during adolescence carries independent prognostic information regarding long-term survival beyond cognitive level established by late childhood, highlighting adolescence as a consequential period for lifelong health.

BackgroundBrain disorders are leading contributors to increasing disability and spending worldwide. In 2022 the Swiss Brain Health Plan (SBHP) was launched to promote brain health and prevent brain disorders. To guide the implementation of the SBHP, we performed a detailed analysis of the health and economic burden of brain disorders in Switzerland. MethodsWe analyzed Global Burden of Disease 2023 disability-adjusted life years (DALYs) and Institute for Health Metrics and Evaluation (IHME) cause-specific health-care spending estimates for Switzerland. DALYs were quantified for 1990 - 2023. Spending was analyzed for 2000 - 2019 across six types of care. We examined age and sex patterns, spending distribution, and international comparisons with six other countries (Germany, France, Denmark, Norway, Italy, Singapore). To assess short- and longer-term association between burden and spending estimates, we fitted panel regression models with disorder and year fixed effects under one-year and five-year lag specifications. FindingsBoth disease burden and spending were highly concentrated in a small number of conditions in Switzerland. In 2023, ten brain disorders accounted for 82{middle dot}9% of Switzerlands total DALY burden. In 2019, ten brain disorders accounted for 86{middle dot}0% of all direct brain-health spending, with dementia alone comprising 29{middle dot}5% of total expenditures. Among seven analyzed comparator countries, Switzerland had the highest per-capita brain-health spending and the highest spending per DALY. In fixed-effects panel models that accounted for spending persistence, lagged DALYs were not statistically associated with subsequent spending. Suicide prevention and addiction showed significant lower-than-expected health-sector spending (self-harm: {beta} = -0{middle dot}23; drug use disorders: {beta} = -0{middle dot}08 to -0{middle dot}18 across lag models). InterpretationBrain disorders generate a large burden in Switzerland. Within the IHME estimates, the burden-spending relationship over time appears limited. The implementation of the SBHP will refer to the current data and call for a burden-informed financing to guide strategic cross-sectorial allocation and prevention investments. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe drew on evidence from the Global Burden of Disease (GBD) 2023 estimates on neurological and mental health conditions, and on cause-specific health-care spending data from the Institute for Health Metrics and Evaluation for Switzerland and selected high-income countries. These sources show that brain disorders are major contributors to disability and premature mortality, and that Switzerland is among the worlds highest spenders per capita on health care. Prior work has described the costs of individual brain disorders and drivers of health expenditure growth; however, it has often treated burden and spending as partly separate domains, leaving the country-level link between cause-specific disability-adjusted life-years (DALYs) and cause-specific spending, over time and in either direction, poorly characterized. Added value of this studyTo our knowledge, this is the first study in a single country to systematically link cause-specific DALYs and cause-specific direct health-care spending for brain disorders and to examine their longitudinal and bi-directional associations. Using harmonized GBD 2023 estimates and IHME 2019 cause-specific health spending data, we quantify the health and economic burden of 23 brain disorders in Switzerland across age, sex, care setting, and time, and benchmark patterns against six other high-income countries. By applying panel regression models with disorder and year fixed effects, we assess whether modeled spending shows any association with prior modeled burden once spending persistence is accounted for, and identify conditions with higher or lower spending relative to burden. Implications of all the available evidenceSwitzerland bears a major burden of brain disorders and devotes substantial resources to their care, yet within the modeled estimates, spending does not consistently correspond to burden over time. Disorders with long-standing multisectoral programs tended to show lower spending-to-burden ratios, suggesting that coordinated action beyond the health sector may reduce downstream health-sector demand. For Switzerland and similar health systems, these findings support national brain-health strategies that strengthen life-course prevention and early intervention, and that integrate financing with burden data to inform priority setting and periodic reassessment of resource allocation.

Population ageing increases the importance of cognitive capacity for making decisions about retirement and living independently beyond it. We tested whether post-war educational expansion and working-life social mobility eliminate the association between social class of origin and cognition in early old age using the 1958 National Child Development Study. Two outcomes were analysed at age 62: standard episodic memory (immediate + delayed word recall) and long-term episodic memory, capturing accurate half-century recall of childhood household facts (rooms and people at age 11 validated against mothers responses). Social mobility trajectories derived in prior work were classified into predominantly manual versus non-manual class trajectories. Models were estimated separately for women and men across three specifications: (i) social origin and controls, (ii) adding social mobility, and (iii) adding weighting to address healthy survivor bias. Education was consistently associated with both outcomes. For long-term episodic memory, social origin gradients were clearer than for short-term episodic memory, with men from service/professional origins showing a 13 percentage-point higher probability of accurate half-century recall than men from manual origins. These findings indicate that education expansion and working-life social mobility failed to release the grip of social origin on long-term episodic memory.

BackgroundGiven emerging evidence on the waning of immunity from typhoid conjugate vaccines (TCV), the World Health Organization (WHO) commissioned a multi-model comparison to determine the optimal schedule in terms of health and economic impact to inform updated recommendations for TCV use across different settings. Methods and findingsTo identify optimal vaccination strategies across different incidence settings and vaccine waning assumptions, we compared two agent-based and two compartmental dynamic models of typhoid transmission. All models were fitted to harmonized age-specific incidence data from medium, high, and very high incidence settings. We assessed different TCV schedules under slow- and fast-waning scenarios to evaluate the best age for routine vaccination and the potential need for booster doses and catch-up campaigns. We evaluated the public health and economic impact predicted for each model and scenario using the net-monetary-benefit framework to determine cost-effectiveness under two representative scenarios for the health outcomes and costs of vaccination and treatment. Over a 10-year time horizon, routine vaccination at 9 months with a catch-up campaign to 15 years and a booster dose at 5 years was predicted to have the greatest impact, reducing cases by a median of 48-64% across the incidence settings. Across all four models, TCV introduction with a catch-up campaign was cost-effective at willingness-to-pay (WTP) thresholds >$1,250 per disability-adjusted life-year (DALY) averted in medium incidence settings when costs and case-fatality risk (CFR) are high and in high incidence settings when costs and CFR are low. The optimal strategy was to delay vaccination to 2 or 5 years of age if waning is fast, depending on the age of peak incidence. In very high incidence settings, TCV introduction at 9 months or 2 years of age was cost-saving, and adding a booster dose at 5 years was cost-effective at most WTP values across all scenarios. ConclusionsModel predictions for the impact and cost-effectiveness of different TCV schedules were fairly robust to uncertainty in parameter values and model structure, but the optimal strategy depends on the typhoid incidence rate, CFR, and waning rate of vaccine protection.

Background Hospital admissions for mental health (MH) and stress related presentations (SRP; symptoms without a clear medical cause which may be psychosomatic in nature) among children and young people (CYP) have risen over time. Rehospitalisation contributes to service costs, may indicate gaps in community based care, and can also disrupt education and social development. Methods This retrospective cohort study used NHS Hospital Episode Statistics to identify all CYP aged 10 to 25 with >1 MH/SRP related hospital admissions in England between 1 April 2014 and 31 March 2018, with follow up until 31 March 2019. Admissions were classified from ICD10 codes into internalising, externalising, personality, and eating disorders, psychosis, self-harm, substance use, postpartum, or potentially psychosomatic diagnostic groups. Outcomes included 30 day all cause readmission, 1 year all cause readmission, and 1 year MH/SRP-specific rehospitalisation. Time to rehospitalisation, and number of MH/SRP readmissions were also evaluated. Clinical and sociodemographic characteristics associated with rehospitalisation were assessed using regression models, time to rehospitalisation using Kaplan Meier analyses, and diagnostic transitions were visualised using Sankey diagrams. Results Of 492,061 CYP with hospital admission for MH/SRP, approximately one third were rehospitalised within one year. Females, older CYP and those from more deprived areas had higher odds of all cause readmission. The odds of MH/SRP rehospitalisation were highest among those aged 14 to 15 years. Co occurring chronic physical health conditions, personality and eating disorders were associated with higher odds, and shorter time, to readmission. Conclusions Rehospitalisation following MH/SRP admissions is common and socioeconomically patterned among CYP. Targeted discharge planning and continuity of care interventions are needed, particularly for high risk CYP admitted with eating and personality disorders.

BackgroundSurgery is a widely used treatment option but the impact of surgery on long-term disease across socioeconomic groups is unknown. MethodsLongitudinal population study using linked primary and secondary care data describing adults ([≥]18 years) in England recorded in the Clinical Practice Research Datalink (CPRD) between 1st January 2012 and 31st December 2021. Socioeconomic deprivation was defined using the Index of Multiple Deprivation (IMD). The exposure was surgery and primary outcome was long-term disease. Data are presented as n (%), median (IQR), and adjusted hazards ratios (HR) with 95% confidence intervals. FindingsOf 18,329,659 people, 8,951,145 (48{middle dot}8%) underwent surgery. 78{middle dot}6% of index surgeries were elective (n=7,032,475), 21{middle dot}4% were emergency (n=1,918,670). Amongst surgical patients, 4,741,188 (52{middle dot}0%) were women, 3,540,136 (39{middle dot}6%) from the most deprived deciles (IMD 1-4) and 994,595 (11{middle dot}1%) from a minority ethnic group. Age-standardised rates of surgery were higher in deprived individuals (comparative rate ratio IMD 1 vs. IMD 10 elective: 1{middle dot}11 (95% CI 1{middle dot}11-1{middle dot}11), emergency: 1{middle dot}54 (1{middle dot}54-1{middle dot}54)). Age at first surgery was 42 (27-60) years for elective and 42 (25-65) years for emergency surgery overall, but lower for people from IMD 1-4 (elective: 39 (26-57) years, emergency: 38 (24-60) years). Rates of long-term disease increased following both elective (baseline 19{middle dot}6%, three years 24{middle dot}5%) and emergency surgery (baseline 10{middle dot}3%, three years 12{middle dot}3%). Risk of new long-term disease following surgery increased with increasing levels of deprivation (IMD 1 vs. IMD 10 elective: HR 1{middle dot}46 (1{middle dot}45-1{middle dot}48), emergency: HR 1{middle dot}46 (1{middle dot}44-1{middle dot}48)). InterpretationSurgical treatment is strongly associated with the onset of long-term disease and factors which limit healthy life expectancy. Surgery occurs at a younger age among socioeconomically deprived groups and may be linked to health inequalities. Similar but more complex patterns of inequality were seen in minority ethnic groups. FundingBarts Charity and UK Academy of Medical Sciences. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSThe impact of surgery on long-term health outcomes beyond mortality and surgical complications such as persistent pain is unknown. People from deprived socioeconomic and minority ethnic groups experience increased risks of postoperative complications, readmissions, and death. We searched PubMed, for English language publications in adults aged over 19 years, over the last 10 years to 10th February 2026 using the following search terms: (surg* OR operat*) AND (long-term outcome OR chronic disease OR comorbidit* OR co-morbidit* OR multimorbidit* OR multi-morbidity*) AND (ethnic* OR race OR racial OR socio* OR depriv* OR ineq* OR disparit*). We identified 7,979 reports. To our knowledge, no previous studies have examined the development of long-term disease following surgery or differences in long-term outcomes following surgery between different socioeconomic and ethnic groups. Added value of this studyThis large national cohort study is to our knowledge the first to examine the relationship between surgery and onset of long-term disease. We included over 18{middle dot}3 million individuals, of whom 48{middle dot}8% underwent a surgical procedure during the study period. 5% of elective surgical patients and 2% of emergency surgical patients developed new long-term disease within three years of surgery. Accounting for differences in age, people from the most deprived decile experienced 11% higher rates of elective and 54% higher rates of emergency surgery compared to the least deprived. People in the most deprived decile underwent their first surgery nearly ten years earlier than those in the least deprived decile with a 46% higher risk of developing new long-term disease within three years of surgery. Although age standardised rates of surgery were lower, people from minority ethnic backgrounds underwent surgery for the first time up to sixteen years earlier that those from white backgrounds and had similarly had higher risk of developing new long-term disease at three years. Implications of all the available evidenceSurgical treatments are associated with onset of long-term disease. This unexpected consequence should be considered when managing patients expectations when planning surgery with them. There are important inequalities in rates of both elective and emergency surgery, and the age this first occurs, between different socioeconomic and ethnic groups. Those from socioeconomically deprived backgrounds and minority ethnic groups undergo surgery at a younger age and are also at greater risk of developing long-term disease and hence reduced healthy life expectancy. One explanation for this may be differences in lifestyle and disease prevention behaviour. Surgery is therefore an important marker for inequalities in healthy life expectancy. The perioperative period is a key opportunity to better manage long-term health to reduce further inequalities. The patterns of these relationships are complex, and a more detailed understanding is needed to ensure that surgery can be better utilised as an opportunity to improve societal health.

BackgroundReceiving fewer COVID-19 vaccine doses than recommended ("undervaccination") may increase risks of death, severe COVID-19, and post-COVID condition. However, population-scale evidence from Italy remains limited. We aimed to characterise determinants of undervaccination in Lombardy and to quantify its association with mortality, severe COVID-19, and long COVID outcomes. MethodsWe conducted a population-based study including all residents of Lombardy aged [&ge;]30 years who were alive on June 1, 2022 (n=6,836,566), and followed them until Dec 31, 2024. Vaccine deficit was defined as the difference between age-specific recommended doses (three for <60 years; four for [&ge;]60 years) and doses received, and was modelled as a time-varying exposure. Outcomes were all-cause mortality, severe COVID-19 (hospitalisation or COVID-19-related death), and long COVID defined using symptom-based ICD codes recorded [&ge;]1 month after infection. Determinants of undervaccination were assessed using multivariable logistic regression. Age-stratified Cox models estimated adjusted hazard ratios (HRs). Counterfactual vaccination scenarios were simulated using fitted survival models. ResultsOn June 1, 2022, 1,668,014 individuals (24{middle dot}4%) were not up to date with recommended vaccination. Undervaccination was more frequent in younger adults, women, individuals born outside Europe, rural residents, and those with high comorbidity burden. During follow-up, 265,383 deaths, 52,121 severe COVID-19 events, and 23,780 long COVID events occurred. In adults aged [&ge;]60 years, increasing vaccine deficit was associated with progressively higher risks of mortality (HR up to 1{middle dot}63) and severe COVID-19 (HR up to 2{middle dot}16). Associations were weaker in younger adults. For long COVID, effect estimates were modest and sensitive to outcome definition. Simulated universal booster coverage in adults [&ge;]60 years was associated with substantial reductions in expected deaths and severe COVID-19 events. ConclusionAbout one in four adults in Lombardy was undervaccinated by mid-2022. An increasing vaccine deficit was associated with a higher risk of severe COVID-19 and mortality, particularly in older adults. Sustaining booster uptake in high-risk groups remains central to mitigating the COVID-19 burden.

Background: Mortality rates have declined across most high-income countries for decades, but recent evidence suggests a slowdown in improvements or a shift to increasing mortality, particularly among working-age populations. The international distribution and drivers of these trends remain incompletely understood. Methods: Mortality trends during 2012-2019 were analysed using all-cause and cause-specific data from 30 countries. Trends were estimated via linear regression. K-means clustering with Dynamic Time Warping identified countries and ICD-10 chapters with similar temporal trajectories. Results: Trends varied substantially by nation. While Japan, Switzerland, and the Republic of Korea maintained consistent declines in all-cause mortality rates, increases were concentrated in the United States, Canada, and the United Kingdom, most prominently in persons aged 30-59 years. However, cause-specific analysis showed that rising mortality was not confined to these countries: most countries exhibited increases in at least one ICD-10 chapter, with several European countries showing increases across multiple chapters. Across countries, a small set of causes recurred among increasing trends, including external causes (self-harm, drug poisoning) at younger ages and chronic conditions (cardiovascular and liver diseases, specific cancers) in mid-life. Notably, ill-defined causes of death consistently appeared among the increasing causes across countries and age groups. Conclusions: Mortality increases in the 2010s were geographically more widespread than previously recognized. The recurrent rise in mortality from ill-defined causes suggests that an important component of mortality change remains poorly characterized. These findings indicate that stalled health progress is a systemic challenge across many high-income societies.

Background The COVID-19 pandemic exacerbated health disparities globally, with certain populations experiencing disproportionate disease burdens. In Australia, COVID-19 deaths occurred disproportionately among first-generation migrants. This study examined risk factors for COVID-19 infection in a Victorian cohort recruited from priority populations, including healthcare workers, people with chronic health conditions, and culturally and linguistically diverse (CALD) communities. Methods We conducted a cross-sectional analysis of participants from the Optimise longitudinal cohort study (September 2020-December 2023). The primary outcome was the self-reported count of confirmed COVID-19 infections (PCR or rapid antigen test positive) from December 2019 to December 2023. We used Poisson regression to examine associations between baseline sociodemographic characteristics and infection count, calculating unadjusted and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Results Of 433 participants (median age 51 years, 75% female), 25% reported no infections, 48% reported one infection, and 27% reported two or more infections. In univariate analysis, CALD status (IRR=1.24,95%CI:1.02-1.50) and larger household size (2-5 people, IRR=1.71,95%CI:1.14-2.50) were associated with higher infection rates, while chronic health conditions (IRR=0.73, 95%CI:0.61-0.88) and older age (IRR=0.54, 95%CI:0.43-0.67) were associated with lower infection rates. In adjusted analysis, younger age (18-34 years vs [&ge;]55 years: aIRR=0.63,95%CI:0.48-0.82) and medium household size (living alone vs 2-5 person household: aIRR=1.42, 95%CI:1.11-1.83) remained significant predictors. CALD status and socioeconomic status showed no independent association with infection risk after adjustment for household size and age. Conclusion COVID-19 infection risk in this Victorian cohort was driven by younger age and larger household size rather than CALD status or socioeconomic status, suggesting that housing density and age, rather than cultural or socioeconomic characteristics, determined infection patterns. Future pandemic preparedness should prioritise policies enabling safe quarantine and isolation for individuals in larger households and workplace protections and economic security for younger essential workers.

BackgroundEthnic minorities and socioeconomically disadvantaged populations in the UK are at increased risk of obesity. We modelled longitudinal body mass index (BMI) trajectories through infancy, childhood, and adolescence to identify at-risk groups and modifiable risk factors. MethodsThis cohort sampled 10,350 White and South Asian children born in Leicestershire, 1985-1997. We included 5,571 participants with [&ge;]3 BMI measurements between 0-18 years collected from healthcare records, questionnaires, and study visits. We used Group-Based Trajectory Modelling of BMI, separately by sex and ethnicity, and combined. We identified at-risk groups and modifiable risk factors using multinomial logistic regression, with inverse probability weighting to reduce selection bias. ResultsWe identified similar five BMI trajectories across sex and ethnicity: stable normal BMI (47%); persistent low BMI (30%); early overweight resolving (8%); childhood onset obesity (4%); and adolescent onset overweight (11%). Childhood onset obesity deviated from stable normal BMI at 2-4 years of age, adolescent onset overweight at 4-6 years. South Asians were at higher risk of childhood onset obesity (aOR: 1.66 [95%CI 1.08-2.53]) and adolescent onset overweight (1.29 [0.98-1.71]) than Whites. Children from deprived backgrounds (1.66 [0.92-2.82], most vs least deprived quintile) and those with less educated parents (1.67 [1.08-2.63], compulsory vs higher education) were at increased risk of childhood onset obesity. Smoking during pregnancy (1.50 [0.88-2.54]) and absence of breastfeeding (1.56 [1.07-2.29]) increased risk of childhood onset obesity. Physical activity decreased risk of childhood onset obesity (0.64 [0.44-0.93], [&ge;]4 vs 0-3 hours/week) and adolescent onset overweight (0.75 [0.59-0.94]). ConclusionBMI trajectories diverge as early as age 2 years, revealing ethnic and social inequalities. Obesity strategies in the UK should intervene during critical windows in early life and prioritise South Asian children and those from socioeconomically deprived backgrounds.

HighlightsO_LIHealth inequalities have widened over 15 years, favouring high-income groups C_LIO_LIInequality in physical activity & mental health widened the most pre-intervention C_LIO_LIPost-intervention, inequalities persisted but stayed relatively unchanged. C_LIO_LILong-term illness and unemployment were key drivers of inequality C_LIO_LIThe greenway may have slowed down the inequality widening but the impact is limited C_LI BackgroundEvidence concerning health inequalities following urban green and blue space UGBS) interventions is limited. This study examined the changes in health inequalities after a major urban regeneration project, the Connswater Community Greenway (CCG), in Belfast, UK. MethodCross-sectional household surveys were conducted in 2010/11 (baseline), 2017/18 (immediately after completion), and 2023/24 (long-term follow-up) with a sample of approximately 1,000 adults each wave. Using concentration indices (CI), income-related health inequalities for three outcomes (physical activity, mental wellbeing and quality of life) were measured. A regression-based decomposition of concentration index examined the contribution of sociodemographic factors to the observed inequalities underpinning each outcome over time. ResultsAcross three waves, there was widening of inequalities over the 15-year period across all three health outcomes, with those from high-income groups reported higher levels of physical activity (CI=0.33, SE=0.026), better mental wellbeing (CI=0.03, SE=0.003), and better quality of life (CI=0.09, SE=0.008). The widening inequalities mainly occurred during the construction phase of CCG (2010-2017) and remained stable post-intervention (2017-2023). Decomposition analysis revealed that the pro-poor concentration of long-term illness and unemployment was the key driver that together explained approximately 51%-76% of the inequalities. ConclusionThe CCG was limited in reducing health inequalities which were mainly driven by long-term illness and unemployment - factors beyond the direct scope of the UGBS intervention - resulting in low-income groups likely to fall further behind the wealthier groups. The widening of inequality is consistent with findings from other public interventions that did not have a primary equity focus.

Background: The two-child benefit cap, implemented in April 2017, restricted Universal Credit and Child Tax Credit to the first two children in households with three or more children. We evaluate the impact of the two-child benefit cap on parental mental, general, and financial health, as well as investigate how this may differ in particular sociodemographic and economic subgroups based on sex, ethnicity and income. Methods: Data was obtained from parents (youngest child aged 5 or under) in the UK Household Longitudinal Survey from 2009 to 2023. Outcomes included parental mental health (psychological distress and life satisfaction), general health (health-related quality of life (HRQoL), self-rated health and health satisfaction), and financial health (current financial situation and financial outlook). We used complementary policy evaluation methods with different strengths and assumptions to triangulate evidence and strengthen inference: interrupted time series (ITS), difference-in-differences (DiD) and controlled time series analysis (CITS). Subgroup analyses were stratified by sex, ethnicity, and income. Findings: Across methods, findings consistently indicate that the policy worsened life satisfaction, self-rated health, health satisfaction, and financial health for parents of 3+ children. Findings were less consistent across methods for psychological distress and HRQoL. For instance, for psychological distress ITS and CITS indicate adverse impacts of the policy; however, one DiD model did not support this conclusion due to greater average worsening in the control group between the pre- and post-periods. Subgroup analyses indicate greater mental health and general health impacts in lower income, male and ethnic minority parents; while financial health was negatively impacted in all subgroups examined. Conclusions: Using repeated cross-sectional panel data and triangulating across causal inference methods, we conclude that the two-child benefit cap in the UK had a measurable adverse impact on most health outcomes examined, with worse outcomes for male, lower income and ethnic minority parents.

BackgroundInternalizing disorders and cardiometabolic disease are common conditions that frequently co-occur in later life and may be attributed to shared genetic influences. While phenotypic effects of polygenic liability of adult disorders may emerge early in life, studies have not investigated this in the context of multimorbidity. This study set out to investigate early manifestations of polygenic liability to adult internalizing-cardiometabolic multimorbidity (ICM-MM) in a UK population birth cohort. MethodsWe used data from 5,821 individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC). We modelled trajectories of 12 mental and cardiometabolic health outcomes using mixed effects models, and investigated effects of adult ICM-MM polygenic liability on these trajectories. We also investigated associations of adult ICM-MM polygenic liability with circulating inflammatory proteins (Olink Target 96 Inflammation panel) at ages 9 and 24. ResultsAdult ICM-MM polygenic liability is associated with cardiometabolic traits and inflammation, and with changes in depressive symptoms and cardiometabolic traits over time in childhood through to early adulthood. A notable early life biological footprint is inflammation. We found that higher ICM-MM polygenic liability is consistently associated with higher interleukin-6 (IL6), tumor necrosis family superfamily member 14 (TNFSF14) and hepatocyte growth factor (HGF) levels in both childhood and early adulthood. ConclusionsAdult ICM-MM polygenic liability manifests early in life through changes in mental and cardiometabolic health and blood biomarkers, especially in increases of circulating inflammatory proteins related to obesity, immune cell chemotaxis and migration that may contribute to disease pathogenesis by seeding inflammation in relevant tissues.

Background Heatwaves increasingly threaten public health in the Mediterranean region, and Greece is among the hardest hit countries. Yet evidence on long-term adaptation, spatial vulnerability, and the contribution of human-induced climate change to heatwave-related mortality in Greece remains limited. Methods We analysed 2,144,957 all cause deaths in Greece during 2000 and 2019 using a time stratified case crossover design. We derived population weighted daily maximum temperatures at NUTS3 level from ERA5 reanalysis and WorldPop. We applied six heatwave definitions (HD1-HD6) varying by duration (2 or 3 consecutive days or more) and thresholds (90th, 95th, 99th percentiles). We fitted Bayesian hierarchical Poisson models to estimate heatwave-mortality associations varying by space and time. We additionally adjusted for relative humidity and national. We then combined these estimates with probabilistic climate attribution methods to quantify the number and proportion of heatwave-related deaths attributable to human induced climate change. Results Heatwaves raised mortality consistently, with relative risks from 1.08 (95% CrI (Credible Interval): 1.07- 1.09; HD1) to 1.15 (1.11- 1.20; HD6). Risks increased with heatwave intensity and duration and peaked among females and adults aged 85 years and older. We did not detect a consistent temporal decline in risk or marked spatial heterogeneity. Human induced climate accounted for 51-94% of heatwave related deaths across definitions. The proportion attributable to climate change rose over time. Conclusions Heatwaves already impose a major mortality burden in Greece, with more than half driven by anthropogenic climate change and little evidence of population level adaptation. These findings call for rapid emissions reductions and targeted adaptation, including stronger heat health warning systems and protection of vulnerable groups.

Objective To examine ethnic differences in the incidence and age-related trajectories of childhood health conditions from birth to adolescence within a UK birth cohort. Design Longitudinal population-based birth cohort with linkage to primary care electronic health records. Setting Born in Bradford (BiB), a multi-ethnic birth cohort in Bradford, UK. Participants 13,282 children (36% White British, 44% Pakistani British, 20% other ethnicity) born 2007 to 2011 with linked primary care records and over 1 year follow-up. Main outcome measures Incident diagnoses of atopic conditions (asthma, eczema, allergic rhinoconjunctivitis), overweight/obesity, common mental health disorders (anxiety, depression), and neurodevelopmental disorders (including ADHD and autism). Incidence rates, Kaplan-Meier cumulative incidence, and Cox regression hazards ratios (HRs) were estimated. Results Atopic conditions emerged early (median onset 5 to 6 years) and were more common among Pakistani British children, with higher hazards of eczema (HR 2.29, 95% CI 2.01 to 2.61), allergic rhinoconjunctivitis (HR 2.27, 2.00 to 2.58), and asthma (HR 1.35, 1.22 to 1.50). Overweight/ obesity developed later (median 9 to 10 years) and were also more frequent in Pakistani British children (HR 1.25, 1.16 to 1.35). In contrast, common mental health disorders emerged predominantly in early adolescence (median around 13 years), and both mental health and neurodevelopmental diagnoses were more frequently recorded among White British children; Pakistani British children had lower hazards of neurodevelopmental diagnoses (HR 0.28, 0.23 to 0.35) and mental health disorders (HR 0.53, 0.41 to 0.70). Conclusions Ethnic differences in childhood health are condition-specific and vary by age of onset, emerging at distinct stages. These findings inform the timing of prevention, service planning, and research into underlying mechanism.

Background Education outcomes predict life chances. However, poverty, ill-health and disability are barriers to achievement. We examined determinants of academic attainment of children with and without major congenital anomalies in state-funded mainstream schools at ages 11 and 16 (key stages [KS] 2 and 4). Methods and Findings Routinely collected electronic records for children born in Wales 01/01/1998-31/12/2007 until 31/12/2019 were linked in the Secure Anonymised Information Linkage (SAIL) Databank. Education outcomes were explored using logistic regression, adjusting for: anomalies, maternal and child deprivation, prescribing, hospitalisation, gestation length, childs sex, and special education needs (SEN) provision. Children with anomalies were less likely to achieve academic standards: however, attainment was more closely associated with affluence. At age 11, 81.87% (7167/8754) with and 93.80% (232,450/247,814) without anomalies passed (odds ratio [OR] 0.30, 95% confidence intervals [CI] 0.28-0.32). At age 16, 46.76% (2070/4427) with and 56.10% (69,732/124,300) without anomalies achieved 5 General Certificates of Secondary Education (GCSEs) at grades C-A* including English/Welsh, Maths and Science (EWMS) (OR 0.69, 0.65-0.73). Discrepancies narrowed in adjusted analyses, particularly when SEN provision was accounted: aOR 0.72 (0.66-0.78) at KS2, and aOR 0.93, (0.87-1.00) for 5 GCSEs C-A* with EWMS. These GCSEs were achieved by 29.65% (307/1034) children with anomalies and 38.42% (10,875/28,305) of unaffected children in the most deprived quintile{dagger}: in the most affluent quintile, figures were 67.57% (547/810) and 74.98% (16,978/22,644). Children with anomalies, receiving maximum SEN support, eligible for Free School Meals (FSM) were the least successful: 5/192 (2.6%) passed 5 GCSEs C-A* with EWMS, as did 37/354 (10.4%) ineligible for FSM. The strongest associations with these GCSEs were SEN statements (aOR 0.07, 0.06-0.07), FSM eligibility (aOR 0.39, 0.37-0.41), and epilepsy (aOR 0.60, 0.45-0.80). However, data were unavailable for 15-18% of children, mainly those educated outside mainstream schools, and some co-morbidities. Generalisation of findings to other countries rests with readers. Conclusions Many children with anomalies from affluent households succeeded. The children left behind lived with poverty and ill-health from congenital anomalies and/or epilepsy. SEN provision mitigated the impact of disadvantage, but poor children with anomalies were unlikely to succeed. {dagger}taking maternal Welsh Index of Multiple Deprivation (WIMD) 2014 at birth.

ObjectiveTo evaluate the impact of equity-focused community-engagement initiatives on the uptake of five routine childhood vaccinations. DesignQuasi-experimental study within a synthetic control analysis framework. SettingPrimary care in England between April 2019 and March 2025. Childhood vaccination data were obtained from the Cover of Vaccination Evaluated Rapidly (COVER) programme. InterventionThe Health Equity Liverpool Project (HELP) is a community-engagement vaccination initiative implemented between October 2023 and June 2024 across nine sites in central and north Liverpool. Activities were co-developed with local partners and delivered in neighbourhoods with persistently low childhood vaccine coverage. Intervention practices were defined as those located within 1 km of HELP delivery sites (n=19). A weighted combination of non-intervention practices across England (n=5826) was used to construct a synthetic control group. Main outcomesQuarterly counts of vaccinated children following intervention implementation for first doses of the measles, mumps and rubella vaccine (MMR1 at 24 months and at 5 years), second dose of MMR (MMR2 at 5 years), pneumococcal conjugate vaccine (PCV at 24 months), the 6-in-1 vaccine, covering diphtheria, tetanus, pertussis, polio, haemophilus influenzae type b, and hepatitis B (at 12 months), and the rotavirus vaccine (at 12 months). ResultsFollowing HELP, rotavirus vaccine uptake increased by 10.03% (95% CI 0.37% to 24.63%), corresponding to 120 (95% CI 4 to 295) additional infants vaccinated in the intervention group compared to the synthetic control. Similarly, 6-in-1 vaccine uptake rose by 11.56% (95% CI 2.37% to 25.56% [~]143 95% CI 29 to 317 additional children vaccinated. No statistically significant changes were observed for MMR1, MMR2, or PCV. Improvements were short-lived, with uptakes returning to pre-intervention levels after approximately nine months. ConclusionsCommunity-engagement vaccination interventions may produce a modest short-term improvement in uptake of selected early life vaccines but show limited evidence of benefit for MMR uptake. Our findings suggest that such approaches are unlikely to have a sustained impact without long-term investment, integration into existing immunisation systems and addressing the wider social determinants of health. What is already known on this topic?O_LIChildhood vaccination rates in England have declined over the last decade and inequalities in uptake are persistent andwidening. C_LIO_LIChildren in socioeconomically deprived areas are less likely to receive routine vaccinations, reflecting both structural barriers and vaccine hesitancy driven by misinformation and lack of trust. C_LIO_LIInnovative community engagement interventions are recommended to address these inequalities, yet evidence of their effectiveness remains limited. C_LI What this study adds?O_LIOur study shows that hyperlocal community engagement interventions can increase uptake of early-life infant vaccines (rotavirus and 6-in-1) by around 10-12% but provides limited evidence of similar improvements for the MMR vaccine. C_LIO_LIThe observed improvements in infant vaccines were transient, returning to baseline levels after approximately nine months, suggesting that one-off initiatives may not produce sustained public health gains without tackling wider social determinants of health. C_LI

Abstract textO_ST_ABSBackgroundC_ST_ABSAs hepatitis A (HA) incidence declines in Europe and infections occur later in life, clinical presentations may worsen, particularly during outbreaks involving adults. AimWe analysed temporal trends and factors associated with severe disease and mortality among patients hospitalised for HA in France between 2013 and 2024. MethodsICD-10 codes B150 or B159 as primary discharge diagnosis were used to identify HA cases from the National Discharge Data Set. Severity (hepatic and/or extrahepatic organ failure within 12 weeks post-admission) and mortality were analysed using adjusted odds ratios in original and propensity-matched samples. Trends were assessed across five periods covering the 2017 epidemic and COVID-19, with 2013-2016 as reference. ResultsAmong 7,928 cases (60.6% male; median age 30) 29.1% developed severe HA, and 1.43% died. Risk of severe HA increased with age (+17% of risk per decade, p < 0.001), male sex (+39%, p < 0.001), smoking (+25%, p=0.024), liver risk factors (+32%, p=0.026), and cirrhosis (+48%, p = 0.024). Risk of death increased with cirrhosis (3.55-fold, p < 0.001) and high Charlson Comorbidity Index (CCI) (9.95-fold, p < 0.001), but not with advanced age. Compared with 2013-2016, severe HA increased by 60% (p<0.001) and case fatality increased 2.22-fold (p=0.003) in 2021-2024. ConclusionsHA severity and mortality have increased in France over the last decade, with advanced age and male sex increasing severity but not mortality, and high CCI limiting access to organ support, thereby increasing mortality in frail patients. Our findings highlight the need for targeted prevention and optimized care strategies for high-risk groups.

Previous research links Adverse Childhood Experiences (ACEs) with problem gambling, but most studies rely on retrospective reporting and focus narrowly on maltreatment, overlooking adversities such as parental mental health issues. Using data on 3794 young adults in the Avon Longitudinal Study of Parents and Children, we examined longitudinal associations between 10 prospectively measured ACEs (individually and cumulatively), and moderate-risk/problem gambling (Problem Gambling Severity Index >=3) at ages 17, 20 and 24, adjusted for socioeconomic and other background factors. Population attributable fractions (PAFs) estimated proportions of cases potentially attributable to ACEs. Most ACEs were associated with higher odds of moderate-risk/problem gambling across ages (24/30 estimates) after adjustment, though effect sizes were generally small (median adjusted odds ratio [aOR] 1.31, interquartile range 1.24-1.59), and confidence intervals (CIs) wide. Sexual abuse showed the strongest association (aORs 2.4-4.2, CIs 0.5-10.5), while bullying and parental conviction were associated at ages 17 and 20 only, parental separation age 24 only. Evidence for a dose-response relationship was weak. PAFs suggested ACEs accounted for up to 12% of moderate-risk/problem gambling cases. These findings highlight potential impacts of ACEs on later gambling behaviour, but imprecise estimates suggest findings should be interpreted cautiously and strengthened through larger datasets and meta-analyses.