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Health conditions in adults with atrial fibrillation compared with the general population: a population-based cross-sectional analysis.

BACKGROUND: Atrial fibrillation (AF) prevalence is rising due to population ageing and comorbidity is an increasing problem. The aim of this study was to examine the prevalence and association of coexisting health conditions among adults with AF in the general population. METHODS: Cross-sectional analysis of Clinical Practice Research Datalink (CPRD) primary care electronic medical records in England linked to hospital admissions as of 30 November 2015. CPRD is broadly representative of the UK general population in terms of age, sex and ethnicity. We estimated prevalence and used logistic regression examining risk factors of age, sex and socioeconomic status (SES) to compare prevalence of 252 physical and mental health conditions and 23 higher level health condition groups in adults with AF compared with adults without AF. RESULTS: 34 338 adults with AF (57% male; 83% ≥65 years) and 907 739 without AF (49% male; 23% ≥65 years) were identified. Adjusted for age and sex, adults with AF were significantly more likely to have 20/23 (87%) health condition groups than adults without AF. The most prevalent health condition groups in adults with AF were cardiovascular (prevalence of 89% in adults with AF vs 26% in adults without AF, adjusted OR (aOR) 5.82, 95% CI 5.60 to 6.05), gastrointestinal (62% vs 37%, aOR 1.34, 95% CI 1.31 to 1.38) and orthopaedic (58% vs 24%, aOR 1.32, 95% CI 1.29 to 1.35). 151/252 individual conditions were significantly more common in adults with AF including cardiovascular conditions such as cardiomyopathy (4.5% vs 0.3%, aOR 9.58, 95% CI 8.88 to 10.35) and heart failure (18% vs 0.7%, aOR 9.07, 95% CI 8.70 to 9.46), and non-cardiovascular conditions such as pleural effusion (16% vs 1.8%, aOR 3.55, 95% CI 3.42 to 3.67) and oesophageal malignancy (0.3% vs 0.0%, aOR 2.14, 95% CI 1.69 to 2.70). Associations were similar after SES adjustment. CONCLUSIONS: While cardiovascular conditions are highly prevalent and strongly associated with AF, a wide spectrum of non-cardiovascular conditions were also strongly associated, requiring a greater understanding of managing comorbid conditions with management principles contradictory to AF.

Humans

Epigenetic signature of very low birth weight in young adult life.

BACKGROUND: Globally, one in ten babies is born preterm (<37 weeks), and 1-2% preterm at very low birth weight (VLBW, <1500&#x2009;g). As adults, they are at increased risk for a plethora of health conditions, e.g., cardiometabolic disease, which may partly be mediated by epigenetic regulation. We compared blood DNA methylation between young adults born at VLBW and controls. METHODS: 157 subjects born at VLBW and 161 controls born at term, from the Helsinki Study of Very Low Birth Weight Adults, were assessed for peripheral venous blood DNA methylation levels at mean age of 22 years. Significant CpG-sites (5'-C-phosphate-G-3') were meta-analyzed against continuous birth weight in four independent cohorts (pooled n&#x2009;=&#x2009;2235) with cohort mean ages varying from 0 to 31 years. RESULTS: In the discovery cohort, 66 CpG-sites were differentially methylated between VLBW adults and controls. Top hits were located in HIF3A, EBF4, and an intergenic region nearest to GLI2 (distance 57,533&#x2009;bp). Five CpG-sites, all in proximity to GLI2, were hypermethylated in VLBW and associated with lower birth weight in the meta-analysis. CONCLUSION: We identified differentially methylated CpG-sites suggesting an epigenetic signature of preterm birth at VLBW present in adult life. IMPACT: Being born preterm at very low birth weight has major implications for later health and chronic disease risk factors. The mechanism linking preterm birth to later outcomes remains unknown. Our cohort study of 157 very low birth weight adults and 161 controls found 66 differentially methylated sites at mean age of 22 years. Our findings suggest an epigenetic mark of preterm birth present in adulthood, which opens up opportunities for mechanistic studies.

Humans

Substance use and co-occurring mental health conditions among adolescents and young adults in North America: a systematic review.

BACKGROUND: Substance use and co-occurring mental health conditions are common among adolescents and young adults and represent an important clinical and public health concern in North America. Trauma exposure, psychiatric symptoms, and social adversity frequently co-occur with substance-related problems in this population. This systematic review aimed to synthesize evidence on prevalence patterns, associated clinical and psychosocial factors, and care-related implications described in the literature on adolescents and young adults with substance use and co-occurring mental health conditions. METHODS: This systematic review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024581685). A systematic search was conducted in MEDLINE (Ovid), Embase, PsycINFO, and Google Scholar. Eligible studies examined adolescents and young adults (&#x2264;&#x2009;25 years) in North America. A combination of subject headings, keywords, and synonyms for the concepts "adolescents," "young adults," "substance use disorders," and "co-occurring mental health conditions" was used. Of 1,882 records identified, 29 studies met the inclusion criteria. Given the heterogeneity of the literature, findings were synthesized narratively. RESULTS: The included studies showed heterogeneity in population, setting, denominator, and ascertainment method. Across the literature, depressive, anxiety-related, trauma-related, and externalizing mental health presentations were frequently reported alongside substance-related problems in adolescents and young adults. Trauma exposure, adverse childhood experiences, and broader social adversity were also commonly reported in association with substance-related problems across studies. Care-related implications were more limited and were largely derived as future directions mentioned across studies rather than direct evaluations of youth-specific service models. CONCLUSION: Co-occurring mental health and substance-related problems were frequently reported among adolescents and young adults in high-risk and service-engaged populations in North America. Trauma and social adversity were prominent across the reviewed literature, while direct evidence for evaluated, integrated, youth-specific care models remains limited. These findings support the relevance of developmentally appropriate, integrated, and trauma-informed approaches to care and highlight the need for further research directly evaluating improved service delivery models for this population. CLINICAL TRIAL NUMBER: Not applicable.

Humans

Epidemiology, diagnosis, and surgical management of urolithiasis in older adults: overview from EAU endourology.

PURPOSE OF REVIEW: Population ageing is changing everyday urological practice. The number of older adults is increasing, and urology already treats a patient population that is, on average, older than the general population. Consequently, older adults with urolithiasis represent a core part of contemporary endourological practice. Given this, a focused review of the available evidence is valuable to inform clinical practice. RECENT FINDINGS: A peak in stone disease can occur in older adults who may also be less likely to present with the classical features of renal colic. As such, delayed or missed diagnosis may carry greater clinical consequences. Although the literature remains relatively limited, ureteroscopy, shock wave lithotripsy, and percutaneous nephrolithotomy remain feasible options in appropriately selected older adults. In this group in particular, broader health associations merit consideration, as the presence of urolithiasis in older adults may reflect overall health status in later life. SUMMARY: The burden of urolithiasis in older adults is increasing and now represents a routine component of everyday clinical practice. Clinical presentation may differ from that seen in younger "index" patients, and complications may have a greater impact on recovery and function. Management should therefore be individualized, taking into account comorbidity, frailty, functional status, and the patient's own priorities.

Humans

Older adults with resectable gastric cancer undergoing perioperative chemotherapy or preoperative chemoradiotherapy plus perioperative chemotherapy: A secondary analysis of the AGITG TOPGEAR phase III trial.

PURPOSE: To evaluate treatment adherence, adverse events, and survival in older (&#x2265;70 years) adults undergoing perioperative treatment for gastric cancer. METHODS: Patients with resectable gastric/gastro-esophageal junction adenocarcinoma (ECOG 0-1) enrolled in the phase III TOPGEAR trial were randomized to perioperative chemotherapy (ECF/ECX or FLOT) alone or perioperative chemotherapy plus preoperative chemoradiotherapy (45&#x202f;Gy in 25 fractions with concurrent fluoropyrimidine). In this exploratory analysis, treatment completion, grade &#x2265;&#x202f;3 adverse events (CTCAE v3.0), surgical outcomes, overall survival (OS) and progression-free survival (PFS) were compared between older and younger adults. RESULTS: Of the 574 patients enrolled, 135 (24%) were &#x2265;&#x202f;70 years. Older adults more frequently required preoperative chemotherapy dose reductions, omissions, or delays (chemoradiotherapy: 55% vs 35%, p&#x202f;=&#x202f;0.004; chemotherapy: 60% vs 48%, p&#x202f;=&#x202f;0.087). Rates of grade &#x2265;&#x202f;3 adverse events were comparable between older and younger patients (chemoradiotherapy: 66% vs 67%, p&#x202f;=&#x202f;0.874; chemotherapy: 68% vs 59%, p&#x202f;=&#x202f;0.220), but older adults more often had hematologic toxicity and grade &#x2265;&#x202f;3 diarrhea in the chemotherapy group (56% vs 37%, p&#x202f;=&#x202f;0.006; 21% vs 6%, p&#x202f;<&#x202f;0.001). Resection rates, grade 3/4 surgical complications, number of removed lymph nodes, and 30-/90-day mortality were similar by age. OS and PFS were comparable across age groups, with numerically favorable outcomes for older adults (OS: HR 0.86, 95% CI 0.58-1.26 [chemoradiotherapy]; HR 0.75, 95% CI 0.51-1.11 [chemotherapy]; PFS: HR 0.78, 95% CI 0.53-1.15 [chemoradiotherapy]; HR 0.70, 95% CI 0.47-1.03 [chemotherapy]). CONCLUSIONS: Older adults with gastric cancer achieved comparable oncologic outcomes to younger patients, despite more frequent treatment modifications and higher hematologic toxicity.

Humans

Multi-omics analysis reveals stage-associated differences in gut immunity and microbiota between juvenile and adult common carp (Cyprinus carpio).

In vertebrates, the development of intestinal immunity is closely associated with dynamic changes in the gut microbiota. However, stage-associated differences in intestinal immunity and gut microbial communities remain poorly characterized in teleost fish. In this study, transcriptomic analysis combined with 16S rRNA gene sequencing was employed to characterize intestinal immunity and gut microbial communities in juvenile and adult common carp (Cyprinus carpio). Transcriptomic profiling revealed marked developmental differences in intestinal immune function. Juvenile carp exhibited a predominantly innate immune phenotype, characterized by elevated expression of pro-inflammatory cytokines, antimicrobial peptides, and lysozyme-related genes. This immune profile was accompanied by enhanced mucosal barrier function and a relatively pro-inflammatory intestinal environment. In contrast, adult carp displayed increased expression of genes associated with adaptive immunity, suggesting that adult common carp exhibit relatively stronger adaptive immune characteristics than juvenile fish. Gut microbiota analysis demonstrated significant stage-dependent differences in microbial diversity and community composition. Juvenile fish were enriched with bacterial taxa potentially associated with innate immune activation, whereas adult fish harbored distinct microbial communities linked to intestinal homeostasis and barrier maintenance. Furthermore, correlation analyses identified significant associations between specific microbial taxa and innate immune-related gene expression, suggesting a close association between gut microbiota composition and intestinal immune characteristics in juvenile and adult common carp. Collectively, these findings reveal stage-associated differences in intestinal immunity and gut microbial communities between juvenile and adult common carp, thereby providing insights into intestinal immune characteristics at different developmental stages in teleost fish.

Animals

Effectiveness of digital health technologies for post-discharge follow-up and management in older adults: a systematic review.

Older adults (&#x2265;65 years) are a rapidly growing population that are experiencing a higher number of hospitalisation admissions, longer hospital stays, and greater hospitalisation-related costs than younger adults. There is an important gap in post-discharge care for older adults, and digital technologies, such as video visits, mobile health apps, and remote patient monitoring, may support follow-up and management after hospital discharge. This systematic review examined the effectiveness, feasibility, acceptability, and impact (ie, effects on rehospitalisation, quality of life, mental health, adherence, and patient satisfaction) of technology-based interventions used for the follow-up and management of older adults after hospital discharge. MEDLINE (via PubMed), Scopus, and Web of Science were searched from database inception to January, 2026. The search identified 1972 records, of which 46 studies met the inclusion criteria: older adult populations (aged &#x2265;65 years), a technology-based intervention, post-discharge follow-up or management, and empirical data. Overall, digital post-discharge interventions were reported to be feasible, with good engagement, adherence, compliance, and retention; low dropout rates; and positive patient satisfaction. However, mixed findings were reported regarding rehospitalisation rates and mental health outcomes for virtual care compared with those for traditional care. Digital health technologies might represent a promising step towards improving post-discharge health care and continuity of care for older adults.

Journal Article

Medication safety in older adults in India: an integrative PhD synthesis of direct evidence and contextual implementation evidence.

BACKGROUND: Unsafe medication practices among older adults are an important global health concern, particularly in low- and middle-income countries where multimorbidity, fragmented care, self-medication, and informal healthcare provision intersect. OBJECTIVE(S): To synthesize direct evidence on medication safety among older adults in India and contextual evidence on deprescribing and community-level provider interventions relevant to safer medication use. METHODS: This PhD synthesis integrates four studies: a record-based cross-sectional study on polypharmacy and cardiovascular autonomic function in Kolkata; a six-city community study of 600 Indian older adults; a systematic review and meta-analysis on deprescribing preventive medications in frail or end-of-life older adults; and a systematic review of informal healthcare provider interventions in low- and middle-income countries. Studies I-II provided direct Indian older-adult evidence, while Studies III-IV provided indirect contextual evidence for their optimization and implementation. RESULTS: Polypharmacy was associated with higher anticholinergic burden and numerically higher cardiac autonomic neuropathy although residual confounding limits causal interpretation. In the multicity study, one-third had polypharmacy, while potentially inappropriate medications, prescribing omissions, and self-medication were common. Risks were higher with multimorbidity, recent hospitalization, care transitions, or living alone. Deprescribing showed no statistically significant increase in mortality, hospitalization, or major cardiovascular events, but heterogeneity was high and certainty low to very low. Informal-provider interventions showed the potential to improve knowledge, referral, case management, and medication-related practices. CONCLUSIONS: Medication safety among older adults in India requires an integrated continuum approach, but direct evidence supports only some components and implementation strategies that need prospective evaluation.

Humans

Association of Socioeconomic Factors With Oral Health in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Oral diseases remain disproportionately prevalent among older adults. However, evidence on oral health inequalities among older adults remains dispersed across studies that have used different socioeconomic indicators and oral health measures and has not been synthesised. OBJECTIVE: To synthesise the evidence on the association between socioeconomic factors and oral health among older adults aged 75&#x2009;years and older. METHODS: A systematic review and meta-analysis was conducted following PRISMA guidelines. The Medline, Embase, and CENTRAL databases were searched. Studies reporting socioeconomic factors (education, income, occupation, area-level deprivation, and multi-aspect socioeconomic position) and oral health (dentition status, dental caries, periodontal disease, dry mouth, oral function, oral health behaviours, and oral health-related quality of life (OHRQoL)) among older adults were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Sixty-eight studies were included. Meta-analyses showed that socioeconomic disadvantage in older adults was associated with: (1) poor dentition status: fewer natural teeth, higher prevalence of edentulism, and lacking a functional dentition; (2) more teeth with decay; (3) irregular dental attendance; and (4) poorer OHRQoL. Similar patterns were generally observed for periodontal disease, dry mouth, and oral function, although no meta-analysis could be performed due to limited evidence and heterogeneous oral health measures. CONCLUSION: Socioeconomic disadvantage was consistently associated with poor oral health in older adults. Associations were more pronounced for dentition status, reflecting the cumulative socioeconomic disadvantage over the life course. Socioeconomic factors should be considered to inform prevention, clinical decision-making and oral healthcare planning for the ageing population. TRIAL REGISTRATION: PROSPERO Registration CRD420251231319.

Aged

Stratifying the risk of transition to adult-onset psychiatric disorders in adolescents with anxiety.

BACKGROUND: Escalating mental health service demands have created a need to better identify young people most likely to require continued support from mental health services at the transition between childhood and adulthood. Anxiety is the most common adolescent mental health condition, yet its clinical significance and prognosis are not well understood. We aimed to examine the risk of young adult-onset psychiatric disorders in individuals with an adolescent anxiety disorder, and identify stratifiers of risk of subsequent psychiatric disorders in this group. METHODS: Individuals from the Norwegian Mother, Father, and Child Cohort Study (MoBa) with linked health records and aged 18 or over as of the 31st December 2023 were included. Those diagnosed with any ICD-10 anxiety disorder when aged 10-17 years were defined as having an adolescent anxiety disorder (n=2107, controls n=47,582). Polygenic scores (PGS) for psychiatric and neurodevelopmental conditions were calculated using LDpred2. Anxiety, comorbidities, and parental psychiatric history were defined through linked ICD-10 diagnoses. Sex was defined through linked records. Individuals were defined as having a young adult-onset psychiatric disorder if they first received any new psychiatric diagnosis aged 18-24. RESULTS: Adolescent anxiety diagnosis was associated with increased risk of all adult-onset psychiatric disorders (HR= 2.33-8.65). Post-traumatic stress disorder PGS, parental history of severe mental illness, and female sex were associated with increased risk of transition to a young adult-onset psychiatric disorder in people with an adolescent anxiety disorder. CONCLUSIONS: Adolescent anxiety greatly increases the risk of a psychiatric disorder during the transition to adult life. Clinicians should consider female sex and parental psychiatric history when prioritising young people with anxiety for adult mental health service support. Future research needs to further consider whether polygenic scores would aid risk stratification in clinical practice.

Norwegian Mother Father and Child Cohort Study

Targeted Nrf2 activation improves vascular endothelial function with aging and prevents vascular dysfunction following disuse in younger and older adults.

Aging and physical inactivity/disuse contribute to cardiovascular disease, which is attributable, in part, to vascular endothelial dysfunction associated with impaired nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling. However, the ability to augment Nrf2 activation and its effects on age- and disuse-related vascular dysfunction in humans remains limited. In a double-blind, randomized, placebo-controlled study design 20 younger adults (8M/12F, age 27&#x202f;&#xb1;&#x202f;7&#x202f;y) and 24 older adults (12M/12F, age 67&#x202f;&#xb1;&#x202f;8&#x202f;y) were randomized to receive either placebo or PB125 (200&#x202f;mg/day, Nrf2 activator) across three visits: baseline, 2 weeks of supplementation, and following either 5 days of bed rest (old) or 2 weeks of limb immobilization (young). Brachial and popliteal artery flow-mediated dilation (FMD), passive leg movement-induced (PLM) leg blood flow (LBF) and vascular conductance (LVC) and serum antioxidant status (superoxide dismutase, SOD) were assessed at each timepoint. Compared to placebo, 2 weeks of PB125 increased brachial (PB125: 2.8&#x202f;&#xb1;&#x202f;1.5 to 3.8&#x202f;&#xb1;&#x202f;1.3%, p&#x202f;<&#x202f;0.0001) and popliteal FMD (PB125: 1.5&#x202f;&#xb1;&#x202f;1.5 to 2.3&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.033) in older, but not younger adults (both, p&#x202f;>&#x202f;0.27). During bed rest, PB125 preserved brachial (3.8&#x202f;&#xb1;&#x202f;1.3 to 3.6&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.543) and popliteal FMD (2.3&#x202f;&#xb1;&#x202f;1.4 to 2.7&#x202f;&#xb1;&#x202f;1.4%, p&#x202f;=&#x202f;0.269), LVC (1.1&#x202f;&#xb1;&#x202f;0.8 to 1.1&#x202f;&#xb1;&#x202f;1.5 AUC, p&#x202f;=&#x202f;0.530) and circulating SOD concentrations (28.3&#x202f;&#xb1;&#x202f;7.2 to 28.6&#x202f;&#xb1;&#x202f;8.6 U/mL, p&#x202f;=&#x202f;0.888) in older adults compared to placebo (all, p&#x202f;<&#x202f;0.05). Following limb immobilization, PB125 preserved popliteal FMD (4.4&#x202f;&#xb1;&#x202f;2.8 to 3.4&#x202f;&#xb1;&#x202f;1.8%, p&#x202f;=&#x202f;0.302) in younger adults compared to placebo (p&#x202f;<&#x202f;0.05). These findings demonstrate targeted Nrf2 activation with PB125 improves age-related vascular endothelial dysfunction while preserving vascular function and antioxidant capacity following periods of disuse.

Humans

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS&#x202f;&#xd7;&#x202f;RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans

Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.

BACKGROUND AND AIMS: To elucidate the genetic architecture of blood pressure (BP) and heart rate (HR) during early life and assess their potential relevance to adult health outcomes. METHODS: The largest genome-wide association study (GWAS) meta-analyses to date of childhood systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (n = 28 425) and HR (n = 22 565) were conducted in children of European ancestry aged 4-17 years. Follow-up analyses included comparisons with adult GWAS results, polygenic risk score (PRS) analyses in independent cohorts of diverse ancestries, and a phenome-wide association study in the UK Biobank. RESULTS: Eight genome-wide significant loci were identified for childhood BP (KIAA2013, CACNB2, PLCE1, PAX2, COL4A2, RP11-236L14.1, CFDP1, TPX2) and three loci for childhood HR (CCDC141, ACHE, MYH6); all novel in children but previously reported in adults. Childhood PRSs explained up to 1.6% of BP variance and 5.2% of HR variance among children of European ancestry. Genetic correlations between childhood and adulthood BP traits were moderate (rg = 0.4-0.7), suggesting age-specific genetic effects on BP. In the UK Biobank, higher childhood BP PRS levels were significantly associated with a broad range of adult health outcomes, particularly cardiometabolic outcomes such as hypertension, angina, myocardial infarction, and cardiovascular disease-related mortality. CONCLUSIONS: These findings advance the understanding of the genetic architecture of childhood BP and HR and provide compelling genetic evidence linking childhood BP to a broad spectrum of adult health outcomes-particularly cardiometabolic conditions-which may inform targeted prevention strategies from a young age.

Humans

Prospective Longitudinal Associations Between Adverse Childhood Experiences and Adult Mental Health Outcomes: Systematic Review and Meta-Analysis.

Research suggests a strong, dose-response relationship between adverse childhood experiences (ACEs) and poor adult mental health outcomes. This systematic review and meta-analysis aimed to systematically investigate the existence and strength of prospective associations between ACEs and adult mental health outcomes: anxiety, depression, psychotic-like experiences, post-traumatic stress disorder (PTSD), self-harm, and suicidality. We searched 12 electronic databases for publications after 1990. A narrative synthesis of included studies and random-effects meta-analyses with moderation were completed for all outcomes, excluding self-harm. In total, 62 studies from 15 countries were included. Most studies were from the United States; 95% of publications (N&#x2009;=&#x2009;59) came from high-income countries (HICs) and 5% (N&#x2009;=&#x2009;3) from upper-middle-income countries. Pooled associations between ACEs and adult mental illness were strongest for PTSD (OR&#x2009;=&#x2009;2.26; 95% CI [1.75, 2.77]), followed by anxiety (OR&#x2009;=&#x2009;1.78; 95% CI [1.45, 2.11]), depression (OR&#x2009;=&#x2009;1.61; 95% CI [1.45, 1.76]), psychotic-like experiences (OR&#x2009;=&#x2009;1.34; 95% CI [1.13, 1.54]), and suicidality (OR&#x2009;=&#x2009;1.28; 95% CI [1.13, 1.43]). Moderation analyses suggested ACEs with a violence or maltreatment component were significant risk factors for adult depression compared to household ACEs, and that study location was a significant moderator in the depression, anxiety, and PTSD models. Further moderation effects will be discussed. Findings confirm ACEs are a significant risk factor for mental ill-health in adulthood. Our review highlights the urgent need for research exploring associations between ACEs measured in childhood and adult mental illness outside of HIC settings.

Humans

Adult outcomes of clinically relevant genomic disorders: A systematic review and meta-analysis.

PURPOSE: Genomic disorders comprise a major source of human disease with survival into adulthood for most individuals, but data on adult outcomes are limited. METHODS: We conducted a formal search to identify studies of 14 clinically relevant, molecularly confirmed deletion syndromes with &#x2265;5 adults reporting on prevalence of cardiovascular risk and other outcomes. Outcomes were pooled across deletion syndromes and by syndrome, using random-effects models. RESULTS: Of 1352 studies screened, 53 reported on nonoverlapping samples of 13 deletion syndromes. Estimated pooled prevalences, at age <30-40 for most, included 47% (95% CI 33-57%; n = 2076) for obesity, and for 10 deletion syndromes: diabetes 24% (95% CI 17-33%; n = 1739), hypertension 36% (95% CI 28-33%; n = 1314), and dyslipidemia 29% (95% CI 22-36%; n = 1127). High heterogeneity for each outcome was partly explained by a significant subgroup effect of individual syndrome. The few available mortality studies indicated premature mortality. CONCLUSION: Pooled results suggest that, although there may be elevated prevalence of adult cardiovascular risk conditions, high heterogeneity indicates caution when considering rare deletion syndromes collectively. The paucity of data extending into later adulthood and using age-matched control comparisons supports the need for prospective studies of large, well-phenotyped cohorts to inform adult penetrance of treatable medical diseases in this emerging group of young adults.

Humans

A Systematic Review and Meta-Analysis of the Global Prevalence of Dry Mouth in Older Adults.

OBJECTIVE: The objective of this study is to update prevalence estimates for xerostomia and salivary gland hypofunction (SGH) among older adults through a systematic review and meta-analysis. BACKGROUND: Dry mouth is common among older adults but is inconsistently assessed and reported. Xerostomia and SGH represent distinct conditions with different diagnostic approaches, leading to heterogeneity in prevalence estimates. MATERIALS AND METHODS: A systematic literature search of Medline (PubMed) and Web of Science was conducted from January 2018 to March 2025. This was supplemented by manual backward citation tracking of the foundational review to identify all eligible pre-2018 epidemiological studies. Only studies utilizing population-representative samples of adults aged 50&#x2009;years and older with defined diagnostic criteria were included. Risk of bias was formally assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool for Prevalence Studies. Pooled prevalence estimates were calculated using random-effects meta-analyses. (PROSPERO: CRD420251009592). RESULTS: A total of 37 studies-encompassing over 1.6 million participants-met the inclusion criteria. The pooled global prevalence of xerostomia among older adults was 21% (95% CI: 19%-23%). For SGH, the pooled prevalence measured via UWS was 12% (95% CI: 4%-24%), whereas SWS yielded a prevalence of 13% (95% CI: 3%-28%). High heterogeneity was observed across all analyses. Differences in diagnostic thresholds and saliva collection methods contributed to the observed variability. CONCLUSION: This updated meta-analysis confirms that xerostomia affects around one-fifth of older adults, while SGH is less common, depending on the diagnostic criteria used. Future research should focus on improving diagnostic consistency and sample representativeness to enable more consistent and robust estimates, and thereby better guide prevention and care in geriatric oral health.

Humans

Identification of a novel heterozygous GPD1 missense variant in a Chinese adult patient with recurrent HTG-AP consuming a high-fat diet and heavy smoking.

BACKGROUND: Glycerol-3-phosphate dehydrogenase 1 (GPD1) gene defect can cause hypertriglyceridemia (HTG), which usually occurs in infants. The gene defect has rarely been reported in adult HTG patients. In the present study, we described the clinical and functional analyses of a novel GPD1 missense variant in a Chinese adult patient with recurrent hypertriglyceridemia&#x2011;related acute pancreatitis (HTG-AP), consuming a high-fat diet and smoking heavily. METHODS: Exome sequencing was used to analyze the DNA of the adult patient's blood sample. It was found that there was a new variant of GPD1 gene-p.K327N, which was verified by gold standard-sanger sequencing method. In vitro, the corresponding plasmid was constructed and transfected into human renal HEK-293T cells, and GPD1 protein levels were detected. A biogenic analysis was performed to study the population frequency, conservation, and electric potential diagram of the new variant p.K327N. Finally, the previously reported GPD1 variants were sorted and their phenotypic relationships were compared. RESULTS: A novel heterozygous variant of GPD1, p.K327N (c.981G&#x2009;>&#x2009;C), was found in the proband. Furthermore, the patient's daughter carried this variant, whereas his wife did not carry the variant. The proband with obesity suffered eight episodes of HTG-AP from the age of 36 years, and each onset of AP was correlated to high-fat diet consumption and heavy smoking. In vitro, this variant exerted a relatively mild effect on GPD1 functions, which were associated with its effect upon secretion (~&#x2009;25% of secretion decreased compared with that of the wild-type); thus, eventually impairing protein synthesis. Additionally, 36 patients with GPD1 variants found in previous studies showed significant transient HTG in infancy. The proband carrying the GDP1 variant was the first reported adult with recurrent HTG-AP. CONCLUSION: We identified a novel GPD1 variant, p.K327N, in a Chinese adult male patient with recurrent HTG-AP. The variant probably exerted a mild effect on GPD1 functions. The heterozygosity of this GPD1 variant, in addition to high-fat diet consumption and heavy smoking, probably triggered HTG-AP in the patient.

Adult

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear. We examined five previously identified brain rejuvenation factors in cerebrospinal fluid of adults with autosomal dominant forms of frontotemporal dementia and sporadic Alzheimer's disease. Our frontotemporal dementia cohort included 100 observationally followed adults carrying autosomal dominant frontotemporal dementia mutations (Mage = 49.6; 50% female; 43% C9orf72, 24% GRN, 33% MAPT) and 62 non-carriers (Mage = 52.6; 45% female) with cerebrospinal fluid analysed on Somascan, and longitudinal (Mvisits = 3 years, range 1-7 years) neuropsychological and functional assessments and plasma neurofilament light chain. Our Alzheimer's disease cohort included 35 adults with sporadic Alzheimer's disease (Mage = 69.4; 60% female) and 56 controls (Mage = 68.8, 50% female) who completed the same cerebrospinal fluid and clinical outcome measures cross-sectionally. Levels of C-C motif chemokine ligand 11, C-C motif chemokine ligand 2, beta-2-micorglobulin, bone gamma-carboxyglutamate protein (aka Osteocalcin) and colony stimulating factor 2 in cerebrospinal fluid were linearly combined into a composite score, with higher values reflecting 'pro-youthful' levels. In genetic frontotemporal dementia, higher baseline cerebrospinal fluid rejuvenation proteins predicted slower decline across cognitive, functional, and neurofilament light chain trajectories; estimates were similar across genotypes. In transdiagnostic analyses, higher cerebrospinal fluid rejuvenation proteins associated with better functional, cognitive, and neurofilament light chain outcomes in adults with sporadic Alzheimer's disease. Proteins with pre-clinical evidence for brain rejuvenation show translational clinical relevance in adults with Alzheimer's disease and related dementias and warrant further investigation.

Alzheimer&#x2019;s disease