The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Recently under the European Society of Cardiology (ESC) EURObservational Research Programme (EORP) PPCM registry the first predictive score was derived. This study sought to test the validity of this predictive score in a cohort of women with PPCM in Uganda. 80 PPCM cases enrolled had a 12-lead electrocardiography, echocardiography at baseline and at 6-months follow-up. Core clinical data included LVEF, LVEDD, duration of symptoms, QRS duration and pre-eclampsia were captured. Recovered participants' scores included one case who scored ≤ 1 and one of 2, six cases had a score of 3, fifteen cases had a score of 4, six cases had a score of 5, two cases had a score of 6 and only five cases had the highest score of 7. The discrimination analysis achieved a c-statistic of 0.67. The ESC EORP PPCM LV predictive recovery score under performed in predicting LV recovery in our Ugandan PPCM cohort.
Poor appetite, often termed anorexia of ageing, may serve as an early marker of adverse health outcomes in old age. This study aimed to evaluate whether poor appetite predicts incident low handgrip strength (HGS), physical disabilities, and reduced quality of life (QoL) in older adults across Europe. Data were drawn from waves 5-9 of the Survey of Health, Ageing and Retirement in Europe (SHARE), including individuals aged 50+. Appetite status was assessed at baseline (2013), and outcomes were tracked longitudinally. Incident low HGS, physical disabilities, and low quality of life were analyzed using logistic regression models adjusting for age, sex, country, comorbidity burden, depressive symptoms (Euro‑D scale), and reduced body mass index. Poor appetite at baseline was a strong predictor of adverse outcomes. In adjusted models, poor appetite was independently associated with higher odds of incident low HGS, physical disabilities, and low QoL, with the strongest effects observed in adults aged 66+; sex‑specific patterns were evident, with women showing greater susceptibility to mobility limitations and men to muscle weakness. The compounded effect of poor appetite, older age, and female gender was particularly pronounced. Incidence rates of all outcomes were nearly doubled in those with poor appetite compared to those with good appetite. Poor appetite is a robust, independent predictor of future muscle weakness, physical disability, and reduced QoL. Routine appetite assessment may help identify at-risk individuals and guide early interventions in ageing populations.
Adolescent obesity is increasing worldwide, and a minority of adolescents are meeting recommended physical activity (PA) and dietary guidelines, particularly among adolescents from low socioeconomic areas. There are limited studies qualitatively investigating the engagement in healthy lifestyle behaviours in this population. Therefore, this study aimed to gain a greater understanding of perceived barriers and facilitators of healthy lifestyle behaviours, specifically PA and dietary behaviours, in this under-represented population. Eight semistructured qualitative focus groups with 35 adolescents aged 13-15 years old were conducted across four European countries (Spain, the Netherlands, Greece, UK) following the Theory of Planned Behaviour framework which states that individual behavioural intentions are grounded on attitudes, subjective norms and perceived behavioural control. Discussions were centred on adolescents' PA and healthy eating behaviours and were thematically analysed. Regarding attitudes, adolescents understood the importance of healthy lifestyle behaviours but often failed to engage in them. Concerning subjective norms, friends and peers were perceived as barriers to PA, except during physical education (PE) classes. Positive relationships between pupils and teachers facilitated PA, and family influence primarily affected dietary behaviours. Regarding perceived behavioural control, the school structures including lack of space and time, as well as limited healthy food options in canteens and the COVID-19 pandemic were barriers to healthy lifestyle behaviours, while mandatory PE classes and school clubs facilitated PA. In conclusion, despite adolescents recognising the significance of healthy lifestyle behaviours they often fail to engage in them. Their healthy lifestyle behaviours were influenced by their friends, families and teachers. The school structure and the COVID-19 pandemic were considered barriers to healthy lifestyle behaviours among adolescents. NCT05002049.
The main aim of the study was to assess the perception of the COVID-19 pandemic by Polish and Slovak medical students. Additional aims were assessment of their satisfaction with the quality of health care services and their attitudes toward vaccination against SARS-CoV-2. A group of 635 (100%) students of nursing and medicine from Poland and Slovakia were surveyed. The results are part of a study conducted as part of international cooperation between the Silesian Medical University in Katowice (Poland) and the Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin (Slovakia). Data were collected using a proprietary questionnaire developed for the purposes of this study. The findings provide exploratory insight into retrospective perceptions related to psychosocial experiences during the COVID-19 pandemic among surveyed medical students from Poland and Slovakia. The lower evaluation of healthcare services during the pandemic and differences observed between Poland and Slovakia may reflect the perceived strain on healthcare systems, although these results should be interpreted with caution. While students expressed confidence in vaccination, differences between declared attitudes and vaccination uptake were observed, which may highlight the possible role of targeted educational and communication strategies. Overall, the findings may suggest the importance of considering psychosocial and systemic factors in shaping health-related attitudes among medical students. However, due to study limitations, the results should be interpreted cautiously and are not fully generalizable and should primarily be understood within the context of the analyzed sample.
Heart failure with preserved ejection fraction (HFpEF) is common in older multimorbid patients and is associated with substantial morbidity and mortality. Pacemaker (PM) patients may be particularly vulnerable given the clustering of conventional HFpEF risk factors and the hemodynamic effects of long-term right ventricular pacing. Nevertheless, HFpEF is rarely systematically assessed in device clinics. To determine the prevalence of HFpEF in a cohort of permanent PM patients using a structured guideline-aligned screening protocol and to characterize their clinical, functional, and pacing-related profiles. PM-HFpEF is a single-center, prospective, cross-sectional study conducted at a tertiary hospital in Portugal. Eligible adults with conventional transvenous pacemakers and right ventricular apical pacing implanted between January 2018 and December 2022 will be invited to attend a one-day screening visit. The protocol includes clinical assessment, N-terminal pro-B-type natriuretic peptide testing, 12-lead electrocardiography, comprehensive transthoracic echocardiography, routine device interrogation, frailty assessment (the Portuguese-validated version of the Edmonton Frail Scale), and health-related quality-of-life evaluation using the 12-item Kansas City Cardiomyopathy Questionnaire. Exercise diastolic stress echocardiography using an upper-limb ergometer will be performed when resting findings are inconclusive. HFpEF will be adjudicated according to the 2021 European Society of Cardiology diagnostic definition. The PM-HFpEF study is designed to provide robust estimates of HFpEF prevalence within a real-world PM population, together with detailed characterization of their clinical and device-related profiles. This information may help inform future clinical assessment and research strategies for this often-overlooked yet clinically significant group of patients.
Chronic obstructive pulmonary disease (COPD) is influenced by environmental exposure and genetic susceptibility. Although large-scale genetic studies have identified loci associated with COPD and lung function, most evidence has come from populations of European ancestry, and data from Asian populations remain limited. This scoping review aimed to summarize KoGES-based studies on genetic and epigenetic associations with COPD and COPD-related lung function phenotypes. PubMed, Scopus, Web of Science, KoreaMed, RISS, KISS, and DBpia were searched from inception to April 27, 2026. Original studies using KoGES data to investigate genetic or epigenetic associations with COPD, airflow limitation, lung function traits, or longitudinal lung function decline were included. The review followed the Arksey and O'Malley framework and PRISMA-ScR guidance. Of 20 unique records identified for final assessment, one conference abstract/preliminary report corresponding to a subsequently published full-length article was removed before screening. The remaining 19 records were screened, and 12 studies met the eligibility criteria. Most KoGES-based studies focused on spirometric traits, including FEV1, FEV1/FVC, and longitudinal lung function decline, rather than clinically defined COPD. Major approaches included genome-wide association studies (GWAS), exome array analysis, gene-environment interaction, polygenic/genetic risk score (PRS/GRS) analysis, epigenome-wide association studies (EWAS), and heritability analysis. Recurrent signals involved FAM13A and the 6p21/AGER region. Recent studies increasingly addressed longitudinal phenotypes, including rapid FEV1 decline and annual lung function decline. KoGES-based studies provide population-specific evidence on genetic and epigenetic associations with COPD-related lung function phenotypes in Koreans. However, evidence for clinically defined COPD, externally validated risk prediction, and integrative multi-omics remains limited. Future studies should distinguish spirometric traits, longitudinal decline, and clinically defined COPD while validating KoGES findings in larger Asian and multi-ethnic populations. COPD develops through a combination of smoking, environmental exposure, and genetic susceptibility. Most large genetic studies on COPD have been conducted in European populations, so less is known about genetic factors in Koreans. We reviewed studies that used data from the Korean Genome and Epidemiology Study (KoGES) to understand what is already known and what research gaps remain. We searched major Korean and international databases for studies that used KoGES data to investigate genetic or epigenetic factors related to COPD or lung function. We then grouped the studies by research type, such as genome-wide association studies, exome-based studies, polygenic risk score studies, interaction studies, and methylation studies. Most KoGES-based studies focused on lung function measurements such as FEV1 and FEV1/FVC rather than clinically diagnosed COPD alone. Repeated evidence was found for several loci, especially FAM13A and the 6p21 region. More recent studies have moved from cross-sectional analyses toward longitudinal outcomes, such as rapid lung function decline and annual change in lung function. Some studies have also begun to evaluate polygenic risk and its interaction with modifiable lifestyle factors. KoGES has helped improve understanding of genetic influences on lung function in Koreans, but important gaps remain. There are still relatively few studies on clinically defined COPD, externally validated genetic risk prediction, and multi-omics integration. More longitudinal and population-specific studies are needed to support future research on early identification, external validation, and prevention-related research questions.
The National Health Service-Galleri randomized trial seeks to determine the extent to which a blood-based multi-cancer screening test can lead to a reduced incidence of a variety of cancers that are at a late stage as of the time of initial diagnosis. In February 2026, the investigators of this trial issued a news release indicating that after several years of follow-up, for a group of 12 pre-specified forms of cancer there was a lower incidence of stage IV cancer among patients in the intervention arm of the trial than in the control arm. The release stated that a group of participants whose stage IV cancer could not have been influenced by the screening - those with stage IV disease already present as of the initial screening exam - had been excluded from this analysis. We argue that while it is appropriate to restrict such an analysis to persons without prevalent stage IV cancer at the start of the trial, a valid result will be obtained only after accounting for the counterparts of these cases that are present in the trial's control arm. We describe how this can be accomplished, and the assumptions needed for such a strategy to succeed.
We aimed to investigate the potential role of polygenic risk in early-onset coronary artery disease (CAD) and recurrence of major adverse coronary events (MACE) in patients with low prevalence of traditional cardiovascular risk factors (CVRFs). This was a prospective study enrolling a cohort of patients with early-onset CAD (<50 years) despite no/few traditional CVRFs. Baseline CAD risk was calculated according to Systematic Coronary Risk Evaluation 2 (SCORE2). The CAD-polygenic risk score (PGS) developed by Khera et al. was computed for the patients and compared with a local control population of unselected individuals. MACE were collected at long term follow-up. We enrolled 42 patients [81% males; median age 44 years, interquartile range (IQR) 40-46] presenting with early-onset CAD from 2014 to 2021. The majority of them (72%) had ≤1 modifiable CVRF with a 3.9% mean risk of developing CV event at 10 years. The control population consisted of 1408 individuals (51% males; median age 39 years, IQR 29-49). We found a significant positive shift in CAD-PGS distribution among early-CAD patients compared with controls (P value < 0.0001). Over a median follow-up of 104 months, 40.5% of patients experienced a new MACE, with an annual incidence rate of 8 (IQR 5-13) per 100 persons/year. In patients with early-onset CAD despite low clinical risk score, we found CAD-PGS values significantly higher than in the general population and a high rate of recurrence of MACE. These findings highlight the potential of PGS in refining CAD risk stratification, properly tailoring prevention strategies.
Host genetic variability, particularly involving inborn errors of immunity (IEI), has emerged as a critical determinant of interindividual differences in COVID-19 severity, yet comprehensive genomic characterization of IEI-related variants in admixed Latin American populations remains scarce. To characterize rare pathogenic variants in IEI-related genes among previously healthy young Brazilian adults with severe COVID-19 and to evaluate their association with clinical outcomes and genetic ancestry. We performed whole-genome sequencing on 161 unrelated Brazilian adults aged 18-60 years, without comorbidities, who required intensive care unit admission for severe COVID-19 across six Brazilian states. A targeted analysis of 504 IEI-related genes, defined by the 2024 International Union of Immunological Societies (IUIS) classification, was conducted using a stringent variant filtering pipeline incorporating predicted functional impact, population rarity (minor allele frequency ≤ 0.01 in gnomAD v4.1 and the 1000 Genomes Project), Combined Annotation-Dependent Depletion (CADD) scores > 15, Gene Damage Index < 13.84, and pathogenicity classification according to American College of Medical Genetics and Genomics (ACMG) guidelines. Ancestry proportions were estimated using ADMIXTURE (K = 3). We identified 49 unique pathogenic or likely pathogenic (P/LP) variants across 37 IEI genes in 45 patients (27.9% of the cohort), comprising 21 pathogenic (42.9%) and 28 likely pathogenic (57.1%) variants. The most frequent molecular consequences were missense variants (n = 21, 42.9%), followed by frameshift (n = 10, 20.4%), stop-gained (n = 9, 18.4%), and splice-site variants (n = 8, 16.3%). Complement deficiencies constituted the largest IEI category (8 variants, 16.3%), followed by phagocyte defects and bone marrow failure (7 variants each, 14.3%). The most frequently affected gene was CFTR (n = 6 variants), and the PMS2 c.2186_2187del frameshift variant was shared among eight unrelated patients, representing the most recurrent variant in the cohort. Seven variants were entirely absent from gnomAD global and Americas databases, including novel variants in FANCA, MVK, TPP2, ELANE, TGFBR1, TCIRG1, and CARD9. Notably, the MVK c.658A > T nonsense variant was identified in two unrelated patients despite its complete absence from reference databases. Ancestry analysis revealed a tri-hybrid profile (European 60.5%, African 26.6%, Amerindian 13.0%), with no significant association between IEI variant carrier status and any ancestry component (all p > 0.6). Strikingly, IEI variant carriers exhibited significantly lower rates of circulatory shock (20.0% vs. 52.6%; OR = 0.23, 95% CI 0.10-0.51, p < 0.001) and acute respiratory distress syndrome (40.0% vs. 61.2%; OR = 0.42, 95% CI 0.21-0.85, p = 0.021) compared to non-carriers, alongside higher absolute lymphocyte counts (median 1,055 vs. 866 cells/mm3, p = 0.024). In-hospital mortality did not differ significantly between groups (11.1% vs. 24.1%; OR = 0.39, 95% CI 0.14-1.09, p = 0.082). These findings demonstrate that rare IEI-related germline variants are present in a substantial proportion of previously healthy young adults with life-threatening COVID-19 and suggest that IEI-associated immune attenuation may modulate disease phenotype by dampening hyperinflammatory responses-potentially protecting against cytokine storm-driven complications while still predisposing to severe illness through impaired viral clearance. This study underscores the relevance of host immunogenetic profiling in admixed populations for understanding the pathophysiology of severe infectious diseases.
Inflammatory rheumatic diseases (IRDs) present substantial risks of infection-related comorbidities during pregnancy. This study evaluates the knowledge, experience, and perceptions of healthcare professionals concerning the prevention of these risks. An international, cross-sectional survey was administered using the SurveyMonkey platform. The survey was disseminated to healthcare professionals specializing in rheumatology, obstetrics, infectious diseases, internal medicine, general practice, and related disciplines through social media channels. Developed in accordance with European Alliance of Associations for Rheumatology (EULAR) recommendations, this survey comprised 30 questions, including multiple-choice, Likert-type, and open-ended formats. A total of 201 healthcare professionals from thirty-six countries participated in the study, with rheumatologists comprising the majority (n = 145, 72.1%). Systemic lupus erythematosus (n = 183), systemic vasculitis (n = 141), and rheumatoid arthritis (n = 86) were identified as the diseases associated with the highest risk of infection-related comorbidities. The most frequently recommended infectious conditions for screening included Hepatitis B (n = 142), urinary tract infections (n = 141), and Hepatitis C (n = 129). The primary risk factors were uncontrolled disease activity (n = 176), high-dose corticosteroid use (n = 164), and high disease severity (n = 162). The most significant systemic barriers were insufficient number of specialists (n = 156), and absence of multidisciplinary teams (n = 155). This study identifies structural and educational deficiencies in the management of infection-related comorbidities among pregnant patients with IRD. The results underscore the need for targeted clinical guidelines, enhanced multidisciplinary care models, and expanded pre-pregnancy counseling.
Exogenous shocks experienced by the population like armed conflicts, natural disasters and economic downturns have all been suggested to correlate with variation in human sex ratio at birth, either through sex-specific embryonic mortality and/or primary sex adjustment. Recently experienced COVID-19 pandemic has also been related to changes in birth sex ratio in some countries but the results have been mixed. In the aftermath of the pandemic, Russia's attack on Ukraine caused further emotional anxiety and economic hardship in Europe. This was also true in Finland, which has had a decade-long close trading history with its neighboring state, Russia. Here, we examined the influence of this "double trouble" on variation in proportion of males born alive as well as male proportion of stillbirths in Finland during 2000-2024, using high-quality monthly census panel data covering the entire Finnish population (a total of 1,355,037 live births and 4,096 stillbirths). The results from Bayesian aggregated binomial time-series regressions showed no evidence for COVID-19-related associations on either the proportion of male live births or stillbirths. We did find an increased proportion of males born alive after 4 months of Russia's offensive but this finding should be considered as exploratory rather than confirmatory. If proportion of male live births or stillbirths can be regarded as a health indicator of the population, our results suggest that Finland as a society showed marked resilience in terms of non-responsive sex ratios when facing these two adverse exogenous shocks.
Chronic obstructive pulmonary disease (COPD) often coexists with sarcopenia, contributing to poorer exercise tolerance, quality of life, and prognosis. Although interest in this topic has increased, a comprehensive bibliometric overview is still lacking. English-language articles and reviews on COPD complicated with sarcopenia published between 2005 and 2025 were retrieved from the Web of Science Core Collection and Scopus. After screening and deduplication, bibliometric and visualisation analyses were conducted using bibliometrix/biblioshiny, VOSviewer, and CiteSpace to evaluate publication trends, major contributors, collaboration networks, co-citation patterns, and keyword evolution. A total of 922 publications from 421 journals were included. Output increased markedly over time, especially after 2018, peaking in 2025. The United States and China were the main contributors and major collaboration hubs, while several European countries showed strong international collaboration and high citation impact. Core journals included International Journal of Chronic Obstructive Pulmonary Disease, Journal of Cachexia, Sarcopenia and Muscle, and Clinical Nutrition. Co-citation analysis showed that the knowledge base was mainly supported by studies on COPD systemic effects and body composition, together with consensus documents on sarcopenia definition and grading. Research hotspots evolved from early work on weight loss, malnutrition, and muscle wasting to functional assessment and clinical outcomes, and more recently to interventions such as nutrition support, resistance training, and pulmonary rehabilitation, alongside emerging mechanistic themes including inflammation, oxidative stress, and metabolic abnormalities. Research on COPD complicated with sarcopenia has shifted from descriptive phenotypes to standardised assessment, functional outcomes, and clinical management. Future studies should strengthen multicentre longitudinal designs and multidisciplinary collaboration to better integrate mechanisms with clinical assessment and intervention.
Management of cryptoglandular anal fistula is characterised by wide variation in diagnostic strategies, surgical techniques and outcome reporting, limiting comparison between studies and hindering evidence-based guideline development. This study aims to implement a standardised core outcome measurement set within a large international observational framework and to evaluate the feasibility of a scalable digitally supported model for global collaborative surgical research. Cryptoglandular anal fistula treatment is a prospective, international, multicentre observational study comprising two components: a short-term audit capturing clinician-reported outcomes at 3 months and a long-term cohort capturing clinician- and patient-reported outcomes over twelve months. Adults undergoing surgery for primary or recurrent cryptoglandular anal fistula are eligible, excluding non-cryptoglandular aetiologies. Data are collected using secure electronic case report forms and digitally administered patient-reported outcome measures, with paper alternatives available where required. Outcomes are defined according to the Anal Fistula Core Outcome Measurement Set and include clinical and radiological healing, recurrence, complications, reintervention, development of additional fistulas, symptoms, psychological impact of treatment, continence, quality of life and additionally work productivity. The study was designed around a predefined nine-step framework, including multidisciplinary coordination, central ethical approval to support local submissions, artificial intelligence-assisted translation of study materials with native review and implementation of secure digital data capture systems. Based on previous European Society of Coloproctology studies and expected centre volumes, the audit arm aims to include approximately 1000 patients and the cohort arm 500 to 750 patients. Central ethical approval has been obtained from the Medical Ethics Review Committee of the Maastricht University Medical Centre+ under METC 2024-0374 (audit arm) and METC 2024-0361 (cohort arm) with local approvals or waivers secured in participating countries according to national regulations. Written informed consent is obtained for cohort participation. Results will be disseminated through peer-reviewed publications and international conferences, with the aim of informing future guideline development and supporting patient-centred care in cryptoglandular anal fistula management.
Sickle cell disease has a profound impact on the physical, mental and social health of affected children. Currently, there is considerable variability among the available patient reported outcomes measures (PROMs) used in children with sickle cell disease, and no consensus has yet been achieved. We aim to assess the psychometric properties of the generic pediatric and proxy Patient-Reported Outcomes Measurement Information System (PROMIS®) measures in children with sickle cell disease living in the Netherlands. Dutch children with sickle cell disease aged 5-17 years old and their caregivers were eligible. The following self-report and proxy-report PROMIS® item banks were evaluated: Anger, Anxiety, Depressive Symptoms, Fatigue, Mobility, Pain Interference, Peer Relationships, Cognitive Functioning, and Global Health. We assessed unidimensionality through confirmatory factory analysis, convergent validity with subscales from the Pediatric Quality of Life Inventory, discriminant validity, reliability, and inter-rater reliability. The study enrolled 102 patients and 102 caregivers, of which 71 were dyads. All item banks displayed sufficient unidimensionality and convergent validity. Discriminant validity was hypothesized and found for "Global Health," "Mobility" (d > 0.3), "Fatigue," and "Pain Interference" (d > 0.3), although some comparisons were non-significant. Reliability was acceptable (a > 0.80, SEM < 0.44) for all PROMIS® measures. Inter-rater reliability was moderately-strong for all item bankss (ICC 0.60-0.78) except for "Peer Relationships" (ICC = 0.47, r = 0.31) and "Global Health" (ICC = 0.26, r = 0.16), which scored lower on correlation.  PROMIS® measures displayed sufficient psychometric properties for use in pediatric sickle cell disease care and research. Proxy-reports seem viable as alternative to self-report forms of PROMIS®. • Sickle cell disease has a profound impact on the physical, mental and social health of affected children and identifying early signs of decline is crucial to intervene before complications arise. • No consensus has yet been achieved among the available patient reported outcomes measures (PROMs) used in children with sickle cell disease living in Europe. • This study provides evidence that PROMIS® measures displayed sufficient psychometric properties for use in European pediatric sickle cell disease care and research. • Proxy-reports seem viable as alternative to self-report forms of PROMIS®.
Multinational clinical trials are increasingly common in the European Economic Area, yet no guideline exists on which EQ-5D value set(s) should be used for health economic evaluations alongside multinational trials. Either a single value set or country-specific value sets can be applied, and previous studies have shown that the choice of value set can impact the estimated utility scores. For the EQ-5D-5L, the impact on European pooled cost-utility analyses has not been established. This study evaluates the impact of EQ-5D-5L value sets on cost-utility outcomes in two multinational trials. Data from two multinational randomized controlled trials were used: (i) supervised exercise compared to usual care for patients with metastatic breast cancer (PREFERABLE-EFFECT), (ii) hemodiafiltration compared to hemodialysis for patients with kidney failure (CONVINCE). EQ-5D-5L was assessed at baseline and during follow-up. Utility scores and quality-adjusted life years (QALYs) were calculated with the country-specific value set for each participant, and with the value set of each included country. The probability of cost-effectiveness was estimated using bootstrapping. Mean assigned utility scores per year alive ranged between 0.762 and 0.889 for PREFERABLE-EFFECT, and 0.673 and 0.806 for CONVINCE. The difference in utility scores is largest when participants report low quality of life. Estimated QALY gains ranged between 0.013 and 0.020 for PREFERABLE-EFFECT and 0.045 and 0.058 for CONVINCE. The maximum difference in probability of cost-effectiveness between the value sets was Δ8.3% at €80,000/QALY in PREFERABLE-EFFECT, and Δ11.1% at €40,000/QALY for CONVINCE. Choice of value set led to substantial variation in absolute utility scores and QALYs, which may influence cost-utility outcomes. This impact could be greater when an intervention prevents or aids recovery of health conditions associated with low quality of life, or results in large mortality differences. Scenario analyses using multiple value sets should be conducted for multinational trials.
Early detection is critical in pancreatic ductal adenocarcinoma (PDAC)-one of the most lethal malignancies due to its typically late diagnosis. In this study, we aimed to validate an epidemiological risk score (ERS) designed to identify individuals at increased risk of developing PDAC prior to the use of imaging or other diagnostic procedures. The ERS was constructed through a meta-analysis of 24 well-established epidemiological risk factors. We applied this score to a prospective cohort of 178 high-risk individuals with a family history of PDAC within the IMAGene project (ClinicalTrials.gov registration code: NCT06334458). To evaluate the predictive value of the ERS, all participants underwent whole-body or abdominal magnetic resonance imaging (MRI) and the findings were classified according to the Oncologically Relevant Findings Reporting and Data System criteria to identify and categorize lesions based on their malignant potential. External validation was conducted by using a subset of the UK Biobank (UKB) cohort (≈300 000 individuals), among whom 1648 were diagnosed with PDAC. Higher ERS values were associated with the presence of potentially malignant lesions on MRI. Both pancreatic and extra-pancreatic malignant lesions were more frequent among individuals with higher ERS scores (P = .01 and P = .02 respectively) compared with controls. External validation in PDAC cases within the UKB cohort confirmed these associations. Our findings support the integration of the ERS as a feasible, low-cost tool for PDAC risk stratification, with the potential to facilitate earlier detection and improve clinical outcomes.
Chronic subdural hematoma (cSDH) frequently affects elderly patients receiving low-dose aspirin, yet the optimal perioperative management of aspirin before burr-hole drainage remains uncertain. We assessed whether the timing of aspirin discontinuation influences early postoperative hemorrhagic and thromboembolic events, functional outcome, recurrence, and length of stay (LOS). Multicenter retrospective cohort of consecutive aspirin-treated adults undergoing burr-hole craniotomy plus subdural drain for cSDH at four European centers, stratified into continuation, short-pause (≤5 d), and long-pause (>5 d) prior to surgery groups. The primary endpoints were postoperative hemorrhagic events within 48 h and thromboembolic events reported within 1 month. Secondary endpoints included Glasgow Outcome scale (GOS) at discharge/1 month, modified Rankin Scale (mRS) at 6 months, length of stay (LOS), 3-month recurrence, reoperation, and 1-month mortality. One hundred forty patients were analyzed (continuation n = 24; short pause n = 47; long pause n = 69). Baseline characteristics were balanced except for higher perioperative desmopressin in the continuation group (54.2% vs 8.5% vs 1.5%; p < 0.001). Among 104 patients with 1-month data, 6 acute (≤48 h) hemorrhagic events (5.8%) occurred: 4/19 (21.1%) with continuation versus 0/40 (0%) and 2/45 (4.4%) with short and long pause (three-group p = 0.005). Pooled, continuation versus any discontinuation gave 4/19 (21.1%) vs 2/85 (2.4%) (Fisher p = 0.010; unadjusted OR 9.70, 95% CI 1.88-49.91; adjusted OR 11.58, 95% CI 1.40-95.39, p = 0.023, after controlling for age, Charlson Comorbidity Index [CCI], baseline mRS, desmopressin, and prophylactic indication). The sensitivity analysis excluding desmopressin recipients (n = 88) showed a consistent direction of effect (continuation 2/9, 22.2% vs discontinuation 2/79, 2.5%; Fisher p = 0.05). Only one thromboembolic event (1.0%) occurred in the continuation group. Functional outcomes favored discontinuation (GOS at 1 month p = 0.004; mRS at 6 months p = 0.004). LOS, 3-month recurrence (8/104, 7.7%; p = 0.88), reoperation, and mortality did not differ significantly. In this real-world multicenter cohort, perioperative continuation of aspirin was associated with a higher rate of 48-hour acute postoperative hemorrhagic events after burr-hole craniotomy for cSDH, while no advantage of pause > 5 days over ≤ 5 days was detected. Thromboembolic events were rare, and no association with aspirin status was found. Prospective studies and meta-analyses are warranted to establish evidence-based guidelines on perioperative aspirin management in cSDH.
Data harmonization is a prerequisite for joint cohort analyses. In this review, we aim to identify and contrast statistical methods for retrospective harmonization of longitudinal data. We performed a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Studies were included if they described statistical methods for retrospectively harmonizing longitudinal data at the participant level. From 35 included papers out of 1,234 hits, we identified three types of statistical methods applicable to tabular data commonly collected in longitudinal epidemiological studies (e.g., questionnaires): (1) distribution-based methods, (2) the proportion score model, and (3) latent variable models. Our results suggest that the suitability of a statistical harmonization method mainly depends on the measurement scales of the original variables as well as on the type of target variable (directly measurable vs. latent). The chosen harmonization method influences how missing subsets of variables are addressed. None of the included studies applied more automated approaches such as machine learning-based procedures for deriving a harmonized dataset. Based on our findings, we present a roadmap that can guide researchers in selecting the most appropriate statistical method for a specific harmonization task and in handling variables collected only in a subset of studies. Data harmonization is still a demanding task that requires the development and application of novel tools for automating the procedures.
With the widespread implementation of antiretroviral therapy (ART), human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has gradually transitioned from a highly fatal infectious disease to a manageable chronic condition. Simultaneously, global population aging has accelerated, making older adults with HIV (≥75 years) an increasingly important group in terms of disease burden. However, the epidemiological characteristics, disease spectrum, and long-term trends of this population-including key metrics such as incidence, mortality, prevalence, and disability-adjusted life years (DALYs)-remain inadequately assessed, particularly regarding epidemiological transitions and inter-country differences in this age group across G7 nations. Data on HIV/AIDS and its subtypes from 1990 to 2021 were obtained from the Global Burden of Disease (GBD) 2021 database for G7 countries (Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States) among individuals aged ≥75 years. Metrics included age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and DALYs. Stratified analyses were performed by age groups (75-79, 80-84, 85-89, 90-94, ≥95 years), sex, and disease subtype. Long-term trends were assessed using Joinpoint regression, calculating the annual percent change (APC) and average annual percent change (AAPC). Between 1990 and 2021, the incidence and mortality of HIV/AIDS in older adults declined continuously in most G7 countries, reflecting the effectiveness of ART and public health interventions. In contrast, prevalence and DALYs increased in some countries, indicating an asymmetric pattern of "decreasing incidence and mortality, but increasing survival and disability." Considerable heterogeneity existed among countries: the United States and several European countries exhibited a high burden among surviving individuals, whereas Japan showed a consistently increasing trend. Sex-specific analysis revealed a higher overall burden in males than females, although the sex gap narrowed in the oldest age groups. The disease spectrum shifted over time, with a declining burden of drug-susceptible tuberculosis and non-communicable chronic diseases (conditions associated with HIV/AIDS) emerging as the primary drivers of DALYs. Older adults should be incorporated into HIV prevention, screening, and health management strategies, with particular attention to chronic disease management, functional maintenance, and multidisciplinary care to address the long-term health challenges posed by aging HIV cohorts.