Importance:Equity, diversity, and inclusion (EDI) initiatives are politically polarizing and increasingly adopted in the health care setting. Their broader impact across different health care career types, career stages, and various levels of education remains largely unknown. Objective:To assess EDI programs and their associated outcomes within health care institutions. Data Sources:A Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020-compliant systematic review searching PubMed, Scopus, Web of Science, CINAHL, and PsychINFO databases from January 2010 to December 2023. Study Selection:Two independent reviewers screened studies that assessed EDI programs or policies in health care institutions. Data Extraction and Synthesis:Programs were categorized based on reported outcomes, including participant satisfaction, increased awareness of EDI-related topics, increases in the proportion of underrepresented minority individuals within medical education or the health care workforce, and overall program impact. Odds ratios (ORs) were pooled using a random-effects model. Analyses followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Analysis was conducted June 2025. Main Outcomes and Measures:Outcome measures included the proportion of diversity among the workforce, employee and patient satisfaction, and the proportion of employees recruited and retained after program implementation. Results:In total, 43 studies incorporating more than 15 000 individuals involved in EDI programs were included. Interventions were multifaceted, including 14 career advancement and training programs, 16 diversity representation programs, 11 academia and research support initiatives, and the growth of 2 pipeline programs. Furthermore, interventions demonstrated consistent improvement in EDI initiatives, with perceived benefit in promoting underrepresented minority populations. Findings from the meta-analysis of 2 studies showed that minority representation in competitive medical residencies increased after implementation of 2 EDI interventions (OR, 1.73; 95% CI, 1.21-2.47). Among the 43 studies included in the Joanna Briggs Institute assessment of methodological quality, 7 (16.3%) were rated as high quality, 20 (46.5%) as moderate quality, and 16 (37.2%) as low quality. Conclusions and Relevance:In this systematic review and meta-analysis of EDI initiatives in health care institutions, programs were associated with an increased workforce diversity. These findings support the continued use of EDI initiatives to promote a more inclusive and equitable health care culture.

ObjectiveThe objective of this systematic review is to synthesize and evaluate the evidence involving creatine monohydrate supplementation (CrM) across mental disorders.MethodsMEDLINE, Embase, Cochrane, and PsycINFO were searched up to 09/30/2025 for randomized controlled trials (RCTs) investigating the effect of CrM on psychiatric symptoms and safety in participants with a mental disorder. Risk of bias was assessed.ResultsSix articles from five RCTs were included (CrM: n = 126, placebo: n = 112; mean age=36 ± 14 years; male sex = 26%). Four RCTs reported on major depressive disorder (MDD), one bipolar depression. No other mental disorders were investigated. Two RCTs were low risk of bias and three had some concerns. CrM dosing ranged from 2 to 10 g/day for 4-8 weeks as adjunct treatment. In the treatment of MDD, CrM was tested as combination with escitalopram (k = 1, outperforming selective serotonin reuptake inhibitor (SSRI) + placebo; Cohen's d = 1.13 at 8 weeks), pharmacotherapy augmentation in adults (k = 1) and female adolescents (k = 1, no difference vs placebo), psychotherapy augmentation (k = 1, cognitive behavioural therapy (CBT) + CrM outperforming CBT + placebo) in MDD, and as pharmacotherapy augmentation in bipolar depression (k = 1, no difference vs placebo augmentation). Two trials in MDD found a correlation between CrM brain N-acetylaspartate and phosphocreatine, which was associated with larger improvement. CrM was generally well-tolerated. Two CrM out of 17 participants experienced hypomania/mania.ConclusionCrM shows promise as a combination treatment with SSRIs or for augmenting psychotherapy in MDD in adults. Double-blind, large-scale RCTs investigating the efficacy of CrM, with and without first-line therapies, are needed across mental disorders.

ObjectiveThe aim of this study is to describe the association between electrolyte abnormalities and adverse clinical outcomes, as well as to estimate the prevalence of these abnormalities in individuals with eating disorders.DesignPreferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020-compliant systematic review searching Ovid MEDLINE, EMBASE, and PsycINFO databases from January 2000 to February 2025 was conducted.MethodsWe included studies with any electrolyte abnormality or clinical adverse outcome among individuals with eating disorders. We conducted two meta-analyses to assess (1) the odds of having an electrolyte abnormality among those with an eating disorder diagnosis compared to healthy controls, and (2) the prevalence of electrolyte abnormalities across eating disorder diagnoses.Results20 studies incorporating 25,401 individuals were analysed, with most assessing a young female population. Study designs were predominantly retrospective cohort (n = 11) and cross-sectional (n = 5), with few including general population controls (n = 4). Anorexia nervosa was the most common eating disorder studied, with hypokalemia (n = 13 studies), hyponatremia (n = 11 studies), and hypophosphatemia (n = 7 studies) being the most frequently reported electrolyte abnormalities. The most prevalent adverse outcomes included anemia (n = 5 studies) and skeletal conditions (osteoporosis, osteopenia; n = 5 studies). The results from the meta-analyses showed (1) that individuals with eating disorders had significantly higher odds of experiencing electrolyte abnormalities compared to controls (OR = 3.20, 95% CI:1.48-6.94), and (2) varying pooled prevalences of abnormalities, including hypokalemia (15%), hyponatremia (13%), and hypophosphatemia (17%), across studies.ConclusionElectrolyte abnormalities are common among individuals with eating disorders and are associated with adverse health outcomes.Trial registrationThe study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) - (ID CRD42023477497).

BACKGROUND:Psychiatric comorbidities are common in first-episode psychosis (FEP) and hinder recovery. Problem gambling (PBG), despite potentially serious clinical consequences, remains under-investigated in this population. This study aimed to estimate the incidence of PBG in FEP and identify predictive factors. METHODS:This prospective cohort study was conducted at two FEP programmes in Quebec, Canada. Individuals aged 18-35 years diagnosed with FEP between November-1-2019 and January-31-2023 were screened for PBG using the Problem Gambling Severity Index through May-1-2023. The primary outcome was incident PBG. Time-varying Cox regression models were used to estimate hazard ratios (HRs) for candidate predictors. RESULTS:Among 520 individuals without prior PBG (mean age = 24.6±4.0 years; 28.8% women), 18 developed PBG during a mean follow-up of 478 days, yielding an incidence rate of 2.6 cases/ 100 person-years. In site-adjusted analyses, white ethnicity (HR = 9.7; 95%CI = 1.3-74.8), incomplete high school education (HR = 2.8; 95%CI = 1.1-7.2), stimulant use disorder (HR=2.8; 95%CI = 1.0-7.3), use of D2/D3-5-HT1A partial agonists (HR = 4.6; 95%CI = 1.5-14.1), and prior non-problematic gambling (HR = 3.1; 95%CI = 1.1-8.4) predicted increased risk. Thirteen cases occurred during aripiprazole treatment, which remained associated with increased PBG risk after multivariable adjustment (adjusted HR = 4.7; 95%CI = 1.6-13.9). CONCLUSIONS:Despite the limited number of incident cases, these results suggest that PBG is relatively common PBG and is associated with potential risk factors, including white ethnicity, incomplete high school education, stimulant use disorder, prior non-problematic gambling, and treatment with D2/D3-5-HT1A partial agonists, particularly aripiprazole. These findings underscore the importance of routine screening for PBG and risk-informed antipsychotic prescribing in FEP.

There is growing evidence on the use of pitolisant for the treatment of residual excessive daytime sleepiness (EDS) in adults with obstructive sleep apnea (OSA) treated with continuous positive airway pressure (CPAP). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing pitolisant to a placebo in adults with OSA and residual EDS despite CPAP use. The primary outcome was a change in subjective sleepiness measured on any validated scale. Secondary outcomes included all-cause discontinuation and treatment-emergent adverse events (TEAEs). A random-effects model was used to calculate standardized mean differences (SMDs) and pooled Log risk ratios (Log RRs). Three RCTs (N = 721) were included. Pitolisant significantly reduced Epworth Sleepiness Scale scores (SMD = −0.90, 95% CI = −1.29 to −0.50; low certainty). There were no significant differences between pitolisant and a placebo for all-cause discontinuation (Log RR = −0.27, 95% CI = −1.60 to 1.06; low certainty) or TEAEs (Log RR = 0.04, 95% CI = −0.19 to 0.27; low certainty). The most common adverse events reported while using pitolisant were headache and insomnia. These findings show emerging potential for pitolisant as a therapeutic option in this population. Future studies should include larger sample sizes and objective measures of sleepiness.

Bipolar disorder (BD) typically manifests during adolescence and young adulthood, with unipolar depression (UD) being common initially. Concerns persist that antidepressants may increase the conversion risk from UD to BD. This study employed a target-trial-emulation framework, using an electronic-medical-record database of public-healthcare services in Hong-Kong, to examine BD-conversion risk, defined by two BD-diagnoses or one BD-diagnosis and a mood-stabilizer prescription, over 12-week and 52-week follow-up among individuals aged 6-30 years diagnosed with incident UD between 2002-2022. Participants initiating antidepressants within 90 days of UD were compared to those without antidepressant treatment, applying inverse-probability-weighting to balance baseline characteristics. We further identified factors associated with BD-conversion within both follow-up intervals using weighted-Cox-regression analyses with backward stepwise-selection. Among 10,801 individuals (mean-age=22.1±5.3 years; male=24.9%), 84.7% initiated antidepressants. The outcome occurred in 87 individuals by 12-weeks and in 257 by 52-weeks. Treatment group showed no significantly increased BD-conversion risk at 12-weeks compared to controls (hazard-ratio [HR]=2.94; 95% confidence interval (CI)=0.89-9.69), while a modestly increased risk at 52-weeks (HR=2.14; 95%CI=1.31-3.51). Presence of psychotic features and past psychiatric hospitalization were associated with BD-conversion. Findings were consistent in stratified analyses by age (6-17, 18-30 years) and secondary analyses repeated in a separate cohort of individuals aged >30 years. Our findings indicate no short-term risk of antidepressant-associated BD-conversion in people with UD regardless of age. Although a modest increase in risk was observed at extended 52-week follow-up, this association likely reflects the influence of risk factors rather than antidepressant exposure causally contributing to BD-conversion.

Anxiety disorders are the most prevalent mental health conditions worldwide. While their burden in terms of excess mortality is known to be high, a quantitative systematic evaluation of all-cause and cause-specific mortality and suicide attempt risks in people with anxiety or stress-related disorders is lacking. We performed a systematic review and random effects meta-analysis, in which co-primary outcomes were risk ratios (RRs) for all-cause and suicide-related mortality, and secondary outcomes were natural-cause mortality, other cause-specific mortality, and risk of suicide attempt. Sensitivity and meta-regression analyses were conducted. Overall, 165 studies encompassing 7,395,722 people with any anxiety or stress-related disorder and 135,059,023 controls, from 27 different countries across all continents, were included. Compared with the general population, a higher risk of all-cause mortality was associated with any anxiety or stress-related disorder (n=42, RR=1.54, 95% CI: 1.14-2.08, p=0.005), generalized anxiety disorder (n=9, RR=1.48, 95% CI: 1.23-1.78, p<0.001), and post-traumatic stress disorder (PTSD) and other stress-related disorders (n=21, RR=1.39, 95% CI: 1.15-1.67, p<0.001), but not with panic disorder, phobias, and mixed anxiety or stress-related disorders. Suicide mortality was increased in people with any anxiety or stress-related disorder (n=39, RR=2.88, 95% CI: 2.13-3.89, p<0.001), panic disorder (n=3, RR=3.58, 95% CI: 1.39-9.25, p<0.008), mixed anxiety or stress-related disorders (n=27, RR=2.77, 95% CI: 1.89-4.07, p<0.001), PTSD and other stress-related disorders (n=11, RR=3.13, 95% CI: 1.85-5.28, p<0.001), and generalized anxiety disorder (n=3, RR=1.93, 95% CI: 1.17-3.17, p<0.01). Suicide attempt risk was higher than in the general population in people with all anxiety or stress-related disorders, ranging from RR=6.33 (95% CI: 4.08-9.82, n=5) in panic disorder to RR=2.74 (95% CI: 1.72-4.35, n=5) in phobias. Natural-cause mortality was increased in any anxiety or stress-related disorder (n=19, RR=1.25, 95% CI: 1.09-1.44, p=0.002), generalized anxiety disorder (n=5, RR=1.55, 95% CI: 1.19-2.02, p=0.001), mixed anxiety or stress-related disorders (n=8, RR=1.26, 95% CI: 1.02-1.56, p=0.033), and PTSD and other stress-related disorders (n=9, RR=1.17, 95% CI: 1.03-1.33, p=0.019), but not in panic disorder. Cardiovascular-related deaths were increased in any and mixed anxiety or stress-related disorders and in generalized anxiety disorder, while cancer mortality was increased only in generalized anxiety disorder. When analyzing people with vs. without anxiety disorders with samples being matched by comorbid physical or mental disorders, results remained significant for all-cause mortality in generalized anxiety disorder and panic disorder, but not in any or mixed anxiety or stress-related disorders, and in PTSD and stress-related disorders. When compared with other mental disorders, no difference in co-primary outcomes emerged from more than two studies. Publication bias was present across several analyses, but sensitivity analyses largely confirmed the main findings. In meta-regression analyses, more recent data collection mitigated all-cause mortality, while schizophrenia-spectrum and bipolar disorder comorbidity mitigated suicide mortality risk, possibly driven by underlying treatment. This meta-analysis documents a higher all-cause, suicide and natural-cause mortality, and a higher risk of suicide attempt, in people with anxiety or stress-related disorders compared to the general population. Given the high prevalence and the recognized global treatment gap for these disorders, this finding is of great public health concern, and calls for appropriate prevention, screening and treatment strategies. More studies are needed to fill the publication bias gap and to identify modifiable risk or mitigating factors.

Mental health disorders frequently co-occur with oncological conditions, prompting an umbrella review(UR) to summarize meta-analytic evidence about the outcomes of pharmacological, psychosocial, and brain-stimulation interventions for psychiatric disorders in oncologic populations. We performed an UR of meta-analyses of randomized controlled trials(RCTs) documenting the efficacy of interventions for mental disorders in people with cancer(November 2, 2025). Re-calculated meta-analytic estimates employed the GRADE criteria for credibility. The AMSTAR-Plus Content Score was used to assess the quality of the meta-analyses. Overall, 82 meta-analyses(Number of records=111,331; primary studies=1,659) yielding 113 meta-analytic estimates were included. Five of 113 estimates were assigned a low level of certainty, and 108/113 were assigned a very low GRADE. Major depressive(55/113=48.67%) and any anxiety disorders(43/113=38.05%) emerged as the most frequently studied mental health diseases among the oncologic population. Mindfulness-based-stress-reduction for anxiety disorders in lung cancer was the only intervention significantly outperforming standard treatment(Hedges‘g=-1.46; 95%C.I.=-1.89;-1.04), whereas psychotherapy for women with breast cancer who underwent surgery was inferior to waiting list(in 80% of studies) in the treatment of anxiety due to women’s body image post-mastectomy(G=0.33; 95%C.I.=0.14; 0.52), with relatively higher credibility compared to other outcomes. Meta-regression suggested that psychotherapies might benefit females more than men, and that age might differentially moderate larger and smaller effects of psychotherapies in advanced cancer and any cancer, respectively. While MBSR shows relatively higher-level evidence for anxiety disorders in the oncological population, the level of evidence is low, underscoring the need for further research on alternative treatment modalities. CBT should be part of anxiety management following mastectomy.

BACKGROUND:"Nutraceuticals" and "phytoceuticals" may have antidepressant activity, prompting an in-depth network meta-analysis of randomized clinical trials (RCTs). METHODS:Systematic review and network meta-analysis (PubMed/MEDLINE/EMBASE/Scopus/PsycINFO/CENTRAL/ClinicalTrials.gov (until 01/07/2025) of RCTs vs. placebo or treatment as usual (TAU = antidepressants) testing nutraceuticals/phytoceuticals in major depressive disorder (MDD). Change in depressive symptomatology (standardized-mean-difference = SMD), treatment response, and all-cause discontinuation (acceptability) (risk ratio = RR) were co-primary outcomes. Secondary outcomes were anxiety symptom changes, adverse event-related discontinuation ("tolerability"), and symptom remission. We conducted subgroup, transitivity, and sensitivity analyses to explore/reduce heterogeneity, and assessed global/local inconsistency, publication bias, risk of bias (RoB), and confidence in the evidence (CINeMA/AMSTAR-Plus). RESULTS:Across 163 studies (n = 15,757, distinct compounds' combinations n = 137), several molecules/classes outperformed placebo with very large effect sizes. Restricting analyses to compounds with ≥2RCTs/non-TAU antidepressants/low RoB/non-sponsored trials/non-outliers, higher-than-expected/unrealistic effect sizes emerged vs. placebo for eicosapentaenoic acid (EPA) (k = 20, n = 8483; SMD = -1.67;95%C.I. = -2.38;-0.97), vitamin D3 (k = 3, n = 344; SMD = -1.59;95%C.I. = -2.71;-0.46), and St. John's-wort-extract-ZE117 (k = 3,n = 207;SMD = -1.02;95%C.I = -1.90;-0.15) regarding depressive symptomatology. Substantial heterogeneity (I2 = 85.3%;95%C.I. = 81.9%;88.0%) and global inconsistency (Q-between-designs = 186.91, p < 0.0001) emerged, explained by subgroup and sensitivity analyses, without publication bias. Additionally, a medium effect size emerged vs. placebo for curcumin (k = 2,n = 89;SMD = -0.58;95%C.I. = -0.99;-0.18) regarding anxiety reduction in low RoB analyses. Shugan granules, EPA, EPA+Docosahexaenoic Acid, ZE117, and fluoxetine+EPA response and St. John's wort extract WS5570/ZE117 remission significantly outperformed placebo. Citicoline was associated with significantly more dropouts than placebo. A meta-regression of efficacy effect sizes against adapted AMSTAR-Plus scores showed that larger SMDs were associated with lower AMSTAR scores, indicating lower study quality. Confidence in the evidence was low to very low. CONCLUSIONS:Upon filtering low-quality evidence, only a few nutraceutical/phytoceuticals showed potential for depressive symptoms, warranting more rigorous trials.

QuestionWhat outcomes are associated with equity, diversity, and inclusion (EDI) interventions in health care institutions?FindingsIn this systematic review and meta-analysis of 43 studies involving more than 15 000 individuals, predominantly from the US, a wide range of EDI interventions were successful and perceived as beneficial in increasing diversity in health care. Furthermore, the meta-analysis of 2 studies demonstrated increased minority representation in competitive medical residencies following program implementation.MeaningA broad range of EDI initiatives were associated with increased workforce diversity in health care institutions. This systematic review and meta-analysis assesses equity, diversity, and inclusion initiatives in health care institutions that aimed to promote a more inclusive and equitable health care culture for individuals who beloing to racial and ethnic minority groups. ImportanceEquity, diversity, and inclusion (EDI) initiatives are politically polarizing and increasingly adopted in the health care setting. Their broader impact across different health care career types, career stages, and various levels of education remains largely unknown.ObjectiveTo assess EDI programs and their associated outcomes within health care institutions.Data SourcesA Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020-compliant systematic review searching PubMed, Scopus, Web of Science, CINAHL, and PsychINFO databases from January 2010 to December 2023.Study SelectionTwo independent reviewers screened studies that assessed EDI programs or policies in health care institutions.Data Extraction and SynthesisPrograms were categorized based on reported outcomes, including participant satisfaction, increased awareness of EDI-related topics, increases in the proportion of underrepresented minority individuals within medical education or the health care workforce, and overall program impact. Odds ratios (ORs) were pooled using a random-effects model. Analyses followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Analysis was conducted June 2025.Main Outcomes and MeasuresOutcome measures included the proportion of diversity among the workforce, employee and patient satisfaction, and the proportion of employees recruited and retained after program implementation.ResultsIn total, 43 studies incorporating more than 15 000 individuals involved in EDI programs were included. Interventions were multifaceted, including 14 career advancement and training programs, 16 diversity representation programs, 11 academia and research support initiatives, and the growth of 2 pipeline programs. Furthermore, interventions demonstrated consistent improvement in EDI initiatives, with perceived benefit in promoting underrepresented minority populations. Findings from the meta-analysis of 2 studies showed that minority representation in competitive medical residencies increased after implementation of 2 EDI interventions (OR, 1.73; 95% CI, 1.21-2.47). Among the 43 studies included in the Joanna Briggs Institute assessment of methodological quality, 7 (16.3%) were rated as high quality, 20 (46.5%) as moderate quality, and 16 (37.2%) as low quality.Conclusions and RelevanceIn this systematic review and meta-analysis of EDI initiatives in health care institutions, programs were associated with an increased workforce diversity. These findings support the continued use of EDI initiatives to promote a more inclusive and equitable health care culture.

BACKGROUND:Randomised trials suggest long-acting injectable antipsychotics (LAIs) may outperform oral antipsychotics (OAPs) regarding adherence and relapse prevention in bipolar disorder (BD). We aimed to compare the effectiveness and tolerability of LAIs versus OAPs in observational studies. METHODS:Searching MEDLINE/Embase/PsycINFO until March-25-2025, we conducted a systematic review and random-effects meta-analysis (pre-registered protocol: https://osf.io/gkwrp) of observational studies comparing LAIs versus OAPs in people with BD (primary outcome = study-defined relapse/psychiatric hospitalisation). RESULTS:Seventeen studies (4 = cohort, 13 = mirror-image studies; 6186/3676 participants with BD, respectively, high-quality per Newcastle-Ottawa Scale Score ≥7 = 47.1%) were included. The relative risk (RR) for study-defined relapse/psychiatric hospitalisation was significantly lower with LAIs versus OAPs in cohort (k = 4, RR = 0.63, 95% confidence interval (CI) = 0.44;0.90, P = 0.026) and mirror-image studies (k = 5, RR = 0.46, 95% CI = 0.28;0.77, P = 0.013). LAIs were not significantly superior to OAPs in high-quality cohort studies (k = 3, P = 0.78) but in those adjusted for >5 factors (k = 2, RR = 0.56, 95% CI = 0.37;0.84, P = 0.006) nor in high-quality mirror-image studies (k = 2, P = 0.38), but in each second-generation antipsychotic-LAIs study (aripiprazole-LAI: k = 2, risperidone-LAI: k = 1) (k = 3, RR = 0.40, 95% CI = 0.20;0.80, P = 0.03). In cohort studies, LAIs and OAPs did not differ regarding psychiatric hospitalisations (k = 3, P = 0.078) but data on discontinuation and mortality risk were lacking/not meta-analysable. In mirror-image studies, LAIs were associated with significantly lower psychiatric (k = 4, RR = 0.50, 95% CI = 0.25;0.99, P = 0.048) and depression-related (k = 2, RR = 0.46, 95% CI = 0.24;0.86, P = 0.014), but not mania-related hospitalisation risk (k = 2, P = 0.075). LAIs were associated with fewer psychiatric hospitalisations (k = 7, SMD = -1.73, 95% CI = -2.88;-0.57, P = 0.011), hospitalisation days (k = 9, SMD = -1.35, 95% CI = -2.19;-0.52, P = 0.006), mania-related hospitalisations (k = 3, SMD = -0.87, 95% CI = -1.19;-0.56, P < 0.001) and manic episodes (k = 3, SMD = -1.13, 95% CI = -2.00;-0.26, P = 0.03), but not any mood (k = 4, P = 0.13) or depressive episodes (k = 3, P = 0.14). Tolerability outcomes were missing, and GRADE certainty-of-evidence was "low" to "very low". DISCUSSION:LAIs were superior versus OAPs in preventing relapse/hospitalisation in cohort and mirror-image studies, in the latter particularly for mania-related outcomes. More robust mirror-image and controlled cohort studies are needed to better assess the effectiveness and tolerability of LAI antipsychotics in BD.Plain Language Summary TitleEffectiveness of Long-Acting Injectable Antipsychotics versus Oral Antipsychotics in People with Bipolar Disorder: A Systematic Review and Meta-Analysis of Observational Studies.

Mental disorders have been associated with traditional cardiovascular risk factors that may mediate the risk of acute coronary syndrome (ACS). To estimate the association of ACS among patients with mental disorders, as compared with patients without mental disorders. MEDLINE, Embase, and PubMed were searched for studies between July 1, 2025, and date of database inception. Study screening was performed in duplicates with conflicts resolved upon consensus. Inclusion criteria were as follows: (1) observational or randomized study, (2) measured association with ACS (incident events, risk ratio, odds ratio, hazard ratio [HR]), and (3) investigated any clinical mental disorder (based on DSM and International Classification of Diseases ) before ACS events. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data extraction was performed in duplicate and resolved on consensus. Data were quantitatively synthesized through random-effects meta-analysis. The National Institutes of Health Study Quality Assessment Tools were used to assess the quality of included studies. Studies were analyzed from January 1966 to October 2021. Association and/or risk of ACS. Among 3616 initially identified studies, 25 full-text articles met inclusion criteria with 22 048 504 participants of median (IQR) age 48.0 (34.5-56.1) years, with 13 019 897 males (59.1%). Depressive disorder (HR, 1.40; 95% CI, 1.11-1.78; P = .01; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty = very low), anxiety disorder (HR, 1.63; 95% CI, 1.40-1.89; P < .001; GRADE certainty = low), sleep disorder (HR, 1.60; 95% CI, 1.22-2.10; P < .001; GRADE certainty = low), and posttraumatic stress disorder (PTSD; HR, 2.73; 95% CI, 1.94-3.84; P < .001; GRADE certainty = moderate) were associated with increased risk of ACS. Bipolar (HR, 1.48; 95% CI, 0.47-4.61; P = .28; GRADE certainty = very low) and psychotic (HR, 0.97; 95% CI, 0.01-178.30; P = .06; GRADE certainty = very low) disorders were not significantly associated with increased risk of acute myocardial infarction, although they had similar point estimates to some other mental disorders. Results of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.

Abstract Introduction To systematically review and meta-analyze the efficacy, tolerability, and safety of pitolisant for the treatment of residual excessive daytime sleepiness (EDS) in adults with obstructive sleep apnea (OSA) treated with continuous positive airway pressure (CPAP). Methods Systematic review (MEDLINE/EMBASE/Cochrane/PsycINFO/clinical trial registries, 01/02/2025) of randomized controlled trials (RCTs) comparing pitolisant to placebo in adults with OSA and residual EDS despite CPAP use. The primary outcome was change in subjective sleepiness measured on any validated scale. Secondary outcomes included all-cause discontinuation and treatment-emergent adverse events (TEAEs). A random-effects model was used to calculate standardized mean differences (SMDs) and pooled Log risk ratios (Log RRs) with 95% confidence intervals (CI). Risk of bias was assessed with Cochrane RoB2. Certainty of evidence was assessed with GRADE. Results Three RCTs (N = 721) were included. Pitolisant significantly reduced Epworth Sleepiness Scale scores (SMD = -0.90, 95% CI = -1.29 to -0.50; moderate certainty). There were no significant differences between pitolisant and placebo for all-cause discontinuation (Log RR = 0.76, 95% CI = 0.25 to 2.34; low certainty) or TEAEs (Log RR = 1.04, 95% CI = 0.83 to 1.31; low certainty). The most common adverse events reported while using pitolisant were headache and insomnia. Conclusion Pitolisant is an effective and well-tolerated treatment for reducing subjective EDS in patients with OSA on CPAP therapy. These findings support its potential as a therapeutic option in this population. Future studies should include larger sample sizes and objective measures of sleepiness. Support (if any)

People with psychotic disorders have greater mortality rates following cancer diagnosis, compared to people without psychotic disorders. Prior examinations of the effect of psychotic disorders on survival following cancer diagnosis mediated by stage at diagnosis and treatment disparities did not accommodate for multiple mediators and post-exposure confounding. The present study sought to estimate analogues of the natural indirect effects of having NAPD on mortality following cancer diagnosis, mediated through stage at diagnosis and time to treatment initiation. We identified cases of cancer diagnosed between 1995 and 2019 among people with non-affective psychotic disorders (NAPD) and a comparison group without NAPD, constructed using Ontario health administrative data. Death from any cause was identified using register data. Inverse probability of treatment weighted Cox models were used to estimate the effect of NAPD on mortality following cancer diagnosis mediated by stage at diagnosis and time to treatment initiation, adjusting for relevant confounders. The analytic sample included 3,643 people with NAPD and 15,174 people without NAPD who developed cancer. People with NAPD had a 66

Eating disorders (EDs) substantially impair physical health, psychological well-being, and social functioning. Shorter untreated illness duration has been proposed to be associated with better outcomes, though evidence for this relationship remains mixed. Nonetheless, delays in accessing treatment remain common and contribute to prolonged suffering and risk of lasting harm. This study aimed to estimate the duration of untreated eating disorder (DUED) and examine potential moderators. A PRISMA 2020-compliant systematic review and meta-analysis was conducted. Searches were performed from inception to March 2026 in PubMed, Embase, PsycINFO, and CINAHL. Random-effects models were used to estimate pooled DUED of available studies, with subgroup and meta-regression analyses to explore moderators. Study quality and risk of bias were assessed using National Institutes of Health (NIH) tools. Of 2,776 records identified, 29 studies (n = 17,433) were included. The pooled DUED of available studies was 21.9 months (95

Psychiatric disorders frequently co-occur with endocrine, nutritional, and metabolic disorders, complicating diagnosis, treatment, and prognosis. To date, no umbrella review (UR) has summarized the corresponding evidence. We conducted a UR of meta-analyses of observational studies reporting the prevalence and outcomes of comorbid endocrine, nutritional, metabolic, and psychiatric disorders (DSM/ICD criteria, PubMed/Medline/Scopus/Embase/Web of Science, 13/10/2025). Meta-analytic prevalence and association estimates were recalculated/and graded using quantitative criteria. The methodological quality of the meta-analyses was assessed with AMSTAR-2. Subgroup and meta-regression were conducted. Eighty-one meta-analyses (records=254,154,533, k=1,780) yielded 119 meta-analytic estimates. Among 64 prevalence estimates drafted from the original meta-analyses, 10(6.4%) had strong credibility, namely (among adults unless otherwise specified): obesity in autism spectrum disorder(17.0%, 95%C.I.=13.0-22.0); Vitamin-D deficiency in schizophrenia(65.3%, 95%C.I.=46.4-84.2); major depressive disorder(MDD) in diabetic foot ulcer(47.0%, 95%C.I.=26.0-85.0), in diabetes mellitus(61.8%; 95%C.I.=56.6-66.7%), in metabolic syndrome (30.5%; 95%C.I.=26.3-35.1), and in polycystic ovary syndrome(PCOS)(37.0%; 95%C.I.=29.0-44.0%); anxiety in PCOS(48.0%, 95%C.I.=37.0-59.0), in type-1 diabetes(21.3%, 95%C.I.=17.8-26.7); type-2-diabetes in MDD(8.7%; 95%C.I.=7.3-10.2%); and mild cognitive impairment in type-2-diabetes(45.0%; 95%C.I.=36.0-54.0%). Five of 43(11.7%) outcomes met strong credibility criteria. Comorbid-MDD vs. non-comorbid-MDD posed a higher risk for all-cause mortality (relative risk/RR=1.48, 95%C.I.=1.4-1.6) and dementia (RR=2.1, 95%C.I.=1.7-2.6) among diabetic people. ADHD-comorbidity increased glycate hemoglobin-A1C levels among type-I diabetes children (SMD=0.7, 95%C.I.=0.5-0.9) and type-2 diabetic females (SMD=0.6, 95%CI=0.4-0.7). Diabetes increased the risk of 30-day hospital readmission (RR=1.2, 95%C.I.=1.1-1.3) in people with dementia. This study provides a comprehensive atlas of the prevalence and outcomes associated with multimorbidity across endocrine, nutritional, metabolic, and psychiatric diseases, assessing credibility and prompting integrated, multidisciplinary care.

Serotonergic psychedelics are re-emerging as therapeutic candidates across psychiatry, particularly for treatment-resistant depression. Their rapid and sustained antidepressant effects, alongside evidence for neuroplastic, dopaminergic, and glutamatergic modulation, have prompted interest in whether they could address depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). This narrative review summarizes mechanistic, preclinical, and early clinical findings relevant to psychedelic use in SSDs. Schizophrenia and major depressive disorder share disturbances in dopamine, glutamate, and neuroplasticity, and both involve large-scale network abnormalities. Schizophrenia is associated with widespread dysconnectivity, mesocortical hypodopaminergia, and striatal hyperdopaminergia linked to NMDA receptor hypofunction. Depression is characterized by fronto-limbic and default mode network hyperconnectivity, mesolimbic hypodopaminergia, and reduced cortical glutamatergic tone. Depressive symptoms within SSDs may reflect an intermediate phenotype combining depressive-like hyperconnectivity with schizophrenia-related global dysconnectivity, suggesting that psychedelics' capacity to transiently increase network flexibility and recalibrate maladaptive connectivity may be clinically relevant. Preclinical studies show increased dendritic spine density, enhanced BDNF expression, restored reward sensitivity, and modulation of network dynamics after psychedelic administration. Clinically, uncontrolled exposure appears associated with increased psychosis-related presentations, whereas limited case reports suggest controlled administration may be tolerated in carefully selected, clinically stable individuals with SSDs. To date, only one early-phase trial (MDMA in schizophrenia) is ongoing, and no randomized trials have evaluated psilocybin or LSD in SSDs. Overall, psychedelics are biologically and mechanistically plausible but remain unproven for depressive and negative symptoms in SSDs, which partially overlap. Carefully designed, safety-focused early-phase studies in clinically stable patients are therefore a prerequisite for broader clinical application.