Introduction: Substance use disorders represent a critical global challenge, characterized by multifaceted etiologies often studied in isolation. Epigenetics provides a mechanism linking environmental exposures to biological susceptibility. This review synthesizes the most recent evidence (2023-2025) to analyze substance use disorders complexity through a holistic lens integrating epigenetic, psychological, socio-biological, spiritual, and legal perspectives. Material and Methods: Following PRISMA guidelines, a comprehensive search of databases (PubMed, Scopus, Web of Science, PsycINFO, EMBASE, Cochrane) was conducted. Ninety-four studies meeting inclusion criteria were analyzed. Data were extracted, and random-effects meta-analyses were performed where feasible. Results: Quantitative synthesis revealed significant effect sizes across all domains. Key findings include a strong association between trauma and substance use disorder severity (OR 2.45) and a novel meta-analytic link between trauma and specific epigenetic aberrations (standardized mean differences 0.75). Social support (OR 2.90), religiosity (hazzard ratio 0.65), decriminalization (RR 0.71), and improved access to Medication for opioid use disorder (OR 2.10) emerged as protective factors. Epigenetic studies demonstrated how adversity becomes biologically embedded. Significant cross-domain interactions were identified, with epigenetics acting as a central mediator between environmental experiences and biological outcomes. Conclusion: Evidence supports a holistic, integrated model of substance use disorders where epigenetic processes mediate the biological embedding of risk and resilience. Effective intervention requires breaking down disciplinary silos to simultaneously address psychological trauma, socio-environmental stressors, and their epigenetic influences. Future research must employ longitudinal designs to investigate the reversibility of epigenetic markers and evaluate multilevel interventions incorporating this biological perspective.

Parkinson disease (PD) pathogenesis remains incompletely understood; beyond nigrostriatal loss, nondopaminergic mechanisms including neurovascular unit dysfunction may contribute to disability. Cerebral small vessel disease (CSVD) burden reflects neurovascular dysfunction in the form of white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), and enlarged perivascular spaces (ePVS). In PD cohorts, CSVD burden correlates with worse motor and gait scores. The aim of the study was to explore whether patients with PD exhibit greater CSVD burden than healthy controls (HC). We conducted a PRISMA-conformant systematic review and meta-analysis of studies including adults with idiopathic PD and a HC group that presented data comparing CSVD burden in these 2 groups. Six databases (MEDLINE, Embase, CINAHL Plus, CENTRAL, Scopus, and Web of Science) were searched on May 14 and 15, 2024. Two reviewers independently screened records, extracted data, and assessed risk of bias, with discrepancies resolved by consensus. Continuous outcomes were pooled as standardized mean differences (SMD); dichotomous outcomes as odds ratios (ORs). We evaluated small-study effects for pooled analyses with 10 or more studies using funnel plots and Egger regression test. We examined 13,403 records. Forty-six studies (45 cross-sectional) met inclusion criteria, totaling 3,817 PD and 2,593 HC (mean ages: 66.9 and 66.5, respectively). WMH volume (k = 21) was higher in PD (SMD 0.36, 95% CI 0.11-0.62). Visual ratings also indicated higher WMH in PD: global (k = 14) SMD 0.27 (95% CI 0.08-0.46); periventricular (k = 11) SMD 0.32 (95% CI 0.12-0.51); deep (k = 8) SMD 0.20 (95% CI 0.09-0.31). Differences in CMB (k = 6; OR 1.18, 95% CI 0.57-2.42) and lacunes (k = 4; OR 1.48, 95% CI 0.58-3.78) were not significant. ePVS results were heterogeneous but trended toward greater burden in PD, most notably in the midbrain (k = 3; SMD 1.80, 0.15-3.44). Overall evidence quality was rated as low, reflecting the observational nature of the included studies. Our analysis showed PD to be associated with greater WMH burden and increased midbrain ePVS. Pooled differences in CMB and lacunes were not significant. Substantial heterogeneity and cross-sectional designs limit certainty; standardized imaging and prospective cohorts are needed to define mechanisms and clinical implications.

Effectiveness of AI- and VR-based simulation with traditional teaching in healthcare education: A network meta-analysis.

Efficacy of nonsurgical interventions for the management of adults with cervicogenic headache: a systematic review and meta-analyses.

Comparative Effectiveness of Emotion-Oriented Therapies for Behavioral and Cognitive Outcomes in People With Dementia: A Network Meta-Analysis.

This systematic review and meta-analysis evaluated the effectiveness of mobile app-based psychological interventions in reducing distress (depressive and anxiety symptoms) and improving quality of life among adults in primary care (PC). We included randomized controlled trials (RCTs) involving adults with depression and/or anxiety identified through searches of PsycINFO, PubMed, Embase, and the Cochrane Library from database inception to April 11, 2025. Standardized mean differences (SMDs) and relative risks (RRs) were pooled using fixed- and random-effects models. Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Eleven RCTs (N=2915) met inclusion criteria, contributing 15 comparisons to the meta-analysis (N=2588; intervention vs. treatment as usual). Pooled analyses showed a significant reduction in overall distress (SMD=-0.44; 95% CI -0.68 to -0.21, p<0.001) and a moderate decrease in depressive symptoms (SMD=-0.53, 95% CI -0.81 to -0.24, p<0.001). Limited evidence from four comparisons showed no significant effect on anxiety (SMD=-0.25, 95% CI -0.68 to 0.18, p=0.26). A small but significant improvement in quality of life was found (SMD=0.16, 95% CI 0.06 to 0.25, p=0.001). Participants using apps were more likely to drop out at post-treatment than controls (RR=1.45, 95% CI 1.18 to 1.79, p<0.001). Mobile app-based interventions appear to reduce distress and depressive symptoms and modestly improve quality of life in PC, although no significant effects were observed for anxiety. These findings support the potential role of app-based interventions as accessible tools within primary care. However, the limited and heterogeneous reporting of follow-up assessments restricts conclusions about the durability of these effects over time. Higher dropout rates also highlight the need to improve adherence strategies.

In this meta-analysis, we systematically compared the efficacy of the Allgöwer-Donati suture technique versus the interrupted vertical mattress suture technique in preventing postoperative incision complications following calcaneal fracture surgery. A systematic search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted from their inceptions up to May 2025. This study included randomized-controlled trials (RCTs) involving adults (18-80 years) with closed calcaneal fractures who underwent open reduction and internal fixation (ORIF) via a lateral incision. The primary outcomes were surgical suture time, wound suture time, drainage tube removal time, and the incidence of postoperative complications. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using fixed-effect or random-effects models based on heterogeneity (I2 statistic). Eight RCTs comprising 640 patients were included. The Allgöwer-Donati technique significantly reduced surgical suture time (SMD = 0.81, 95% CI 0.22 to 1.39, p = 0.007; I2 = 47%), drainage tube removal time (SMD = 4.94, 95% CI 4.42-5.47, p < 0.00001; I2 = 65%), and wound suture time (SMD = -3.36, 95% CI -3.90 to -2.81, p < 0.00001; I2 = 34%) compared to the interrupted vertical mattress technique. However, there was no significant difference in the overall rate of postoperative complications between the two techniques (OR = 1.32, 95% CI 0.95-1.82, p = 0.10; I2 = 0%). The Allgöwer-Donati suture technique offers significant advantages in operative efficiency by reducing suture times and drainage duration without increasing the risk of postoperative complications compared to the interrupted vertical mattress technique. It represents a promising suturing option for calcaneal fracture surgery, particularly in settings valuing procedural efficiency.

Ashwagandha (Withania somnifera), as an important herbal medicine, has been increasingly recognized for its role in mental health management, particularly in reducing stress and anxiety, and reflects the growing relevance of complementary and alternative medicine in addressing psychological well-being. The present study aims to investigate its effectiveness by pooling the evidence from existing randomized controlled trials (RCTs). Major medical databases of PubMed, Scopus, and Web of Science Core Collection were searched. Eligible studies were included. Meta-analysis, meta-regression, non-linear dose-response analysis, and subgroup analyses were conducted. Standardized mean differences (SMDs) were calculated. P-values < 0.05 were considered as statistically significant. The study protocol was registered in the PROSPERO database (CRD420251073134). Twenty-two studies met the eligibility criteria and were included. Meta-analysis revealed that supplementation with ashwagandha significantly improves stress (SMD = -5.88; 95 % CI: -8.15 to -3.60), depression (SMD = -5.68; 95 % CI: -8.43 to -2.94), and anxiety (SMD = -6.87; 95 % CI: -8.77 to -4.97). There was significant linear (coefficient = 0.005, P = 0.031) and non-linear (P-nonlinearity = 0.005) association between dosages of administered ashwagandha and stress levels. Current evidence suggests that ashwagandha supplementation holds promising potential in alleviating symptoms of stress, anxiety, and depression. However, to strengthen these findings and translate them into clinical recommendations, well-designed, high-quality trials are still needed to address existing heterogeneity and to establish the most effective dosages and intervention durations.

Autism and the gut metabolome: Evidence for altered short-chain fatty acid profiles from a systematic review and meta-analysis.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic disorders. Howeve, their effects on depressive symptoms and psychological well-being remain uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effects of GLP-1RAs on depressive symptoms and psychological well-being. Random-effects models were used to calculate standardized mean differences (SMDs). Subgroup and meta-regression analyses were performed to explore heterogeneity. The protocol was registered with PROSPERO (CRD42024566217). In total, 25 trials (17,751 participants) evaluated psychological well-being and 11 trials (1961 participants) evaluated depressive symptoms. GLP-1RA treatment was associated with a small but significant improvement in psychological well-being compared with control conditions (SMD=0.374, 95% CI 0.093-0.656), whereas no significant effect was observed for depressive symptoms (SMD=0.079, 95% CI -0.024-0.182). Improvements in psychological well-being were consistently observed in studies using semaglutide, tirzepatide or liraglutide, subcutaneous administration, and in populations with type 2 diabetes mellitus or obesity. GLP-1RA treatment was associated with modest improvements in psychological well-being but not depressive symptoms. These findings should be interpreted cautiously and suggest that any observed psychological benefits are likely indirect, potentially reflecting improvements in metabolic status or general health, rather than direct mood-improving effects.

Virtual reality for pain control during intrauterine device insertion: a systematic review and meta-analysis of randomized controlled trials.

Diagnosis of immune checkpoint inhibitor-related myocarditis (ICI-M) represents a substantial challenge in clinical practice. A range of imaging and laboratory parameters are frequently utilized for diagnosis, but the reliability of these modalities remains controversial. The present meta-analysis evaluates diagnostic and prognostic parameters in ICI-M. After screening PubMed, Cochrane, and Wiley Library, data from 29 trials with 3568 patients were included. In ICI-M, abnormal cardiac magnetic resonance imaging (CMR) was present in 63.4%, including late gadolinium enhancement (LGE) in 65.3% (odds ratio (OR) 5.32, 95% confidence interval (CI) 1.61-17.50; n = 424; p = 0.006) and myo- or pericardial oedema in 16.4% (OR 4.79, 95% CI 0.96-23.92; n = 145; p = 0.06). The most common LGE pattern was mid-myocardial (43%) distribution. Decreased left ventricular ejection fraction (LVEF) was present in 35.9% (OR 5.22, 95% CI 2.02-8.42; n = 1319; p = 0.001) of transthoracic echocardiography (TTE). Cardiac troponins (cTn) (standardized mean difference (SMD) 0.79, 95% CI 0.14-1.44; n = 323; p = 0.02) and brain natriuretic peptides (SMD 0.92, 95% CI 0.30-1.54; n = 201; p = 0.003) were increased in ICI-M. Reduced LVEF (OR 5.11, 95% CI 2.53-7.68; n = 222; p < 0.001) and cTnI elevation (SMD 2.27, 95% CI 0.33-4.22; n = 76; p = 0.02) predicted major adverse cardiovascular events. The study was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD420251087222). Distinct CMR-, TTE-, and laboratory parameters were associated with ICI-M, but did not serve as standalone diagnostic criterium. Aggregate data emphasize the heterogeneity of ICI-M, underscoring the necessity for a multimodal diagnostic approach.

Relationship between gestational age and neurodevelopmental disorders: A nationwide longitudinal retrospective cohort study.

Health-related quality of life in burn survivors from low-and middle-income countries: A systematic review and targeted comparative analysis of rehabilitation interventions.

To determine the efficacy of functional training on cardiorespiratory fitness in individuals with cerebral palsy (CP). Randomized controlled trials involving individuals with CP who had functional training interventions, which also reported cardiorespiratory fitness outcomes, were included in this systematic review. Two independent reviewers searched PubMed, MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL up to February 2025, and selected studies and extracted data. Study quality was assessed using the Cochrane Risk of Bias 2 tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Mean differences and standard mean differences with 95% confidence intervals (CIs) were calculated. From 594 papers, 11 randomized controlled trials (n=387, mean ages 5 years 10 months-20 years 6 months, Gross Motor Function Classification Systems levels I-IV) were included. Functional training had statistically and clinically significant effects on the 6-minute walk test (mean difference=30.91; 95% CI=28.34-33.48; p < 0.001) and Physiological Cost Index (mean difference=-0.16; 95% CI=-0.20 to -0.13; p < 0.001). No effect was found for gait speed or the timed stair test. Functional training has the potential to improve functional exercise capacity in individuals with CP. Given the significant impact of cardiorespiratory problems on the morbidity and mortality of individuals with CP, integrating cardiorespiratory parameters into functional training programmes may contribute to long-term health benefits.

Effects of peer support interventions for family caregivers of persons with dementia: A systematic review and meta-analysis.

Withdrawal of life support following interfacility transfer in older adults with traumatic brain injury.

Does silver diamine fluoride compromise adhesion of restorative materials in dentin of primary teeth? A systematic review and meta-analysis.

Comparative efficacy and safety of Chinese patent medicines in coronary heart disease patients after percutaneous coronary intervention: A systematic review and network meta-analysis.

Vitamin A plays an important role in the development of anemia, providing a new perspective on improving anemia. This study aimed to investigate the dose-response relationship between serum vitamin A and anemia risk, and evaluate its clinical applicability with adjustment for covariates. A 1:3 matched case-control study (202 cases, 606 controls) was conducted, matching for sex and age (±2 y). Assess matching balance using the standardized mean difference. Anemia was defined according to the World Health Organization criteria. Unconditional logistic regression was used to assess the effect of vitamin A after adjusting for confounders. Variable adjustment was informed by a directed acyclic graph, with the primary model adjusting for age, sex, body mass index (BMI), and serum zinc (Zn). A restricted cubic spline (RCS) was applied to analyze the dose-response relationship. Subgroup analysis and interaction tests were used to examine the association across sexes. Model discrimination was evaluated using the receiver operating characteristic curve and its area under the curve (AUC). Model calibration was evaluated using calibration plots, the Hosmer-Lemeshow test, and the Brier score. The case group exhibited significantly lower amounts of BMI, vitamin D, vitamin A, total cholesterol, Zn, and serum ferritin (all P < 0.05). After adjusting for age, sex, BMI, and Zn, each 0.1 μg/mL increase in serum vitamin A was associated with a 27% reduction in anemia risk [odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.62, 0.87, P < 0.001]. RCS analysis confirmed a linear dose-response relationship (P for nonlinearity = 0.922). Sex-stratified analysis using unconditional logistic regression suggested a numerically stronger association in males (OR = 0.55, 95% CI: 0.38, 0.78, P < 0.001) than in females (OR = 0.82, 95% CI: 0.67, 1.00, P = 0.053); "sex × vitamin A" interaction was statistically significant (P = 0.019). The prediction model including vitamin A improved AUC to 0.63 (ΔAUC = 0.11, P < 0.001) and demonstrated good calibration (Brier score = 0.180; Hosmer-Lemeshow P = 0.636). Serum vitamin A demonstrates a significant, independent, and linear inverse association with anemia risk in children and adolescents. This association was more pronounced in males, indicating a potential role for vitamin A in sex-specific anemia prevention strategies.