Medicine and Pharmacology

Abstract: Psychotropic non-adherence affects between two-fifths and three-fifths of patients with schizophrenia-spectrum, major depressive, and bipolar disorders, yet circadian disruption, among the most prevalent features of these illnesses, has rarely been examined as one of its determinants. This narrative review develops the construct of a chronobiological–adherence axis: the bidirectional pathway through which circadian desynchrony erodes, and circadian stabilisation supports, adherence to psychotropic regimens. Integrating molecular-clock biology, chronopharmacology, adherence epidemiology, and intervention research, it identifies five convergent mechanisms: time-of-day-dependent drug handling, rhythmic drug targets, destabilisation of the daily routines that scaffold dose-taking, symptom- and insight-mediated dropout, and treatment-emergent sleep disruption. Poor sleep quality, persistent sleep disturbance, and excessive daytime sleepiness are associated with poorer adherence, while evening chronotype and circadian phase markers predict weaker antidepressant response. Chronotherapeutic strategies, including dosing-time optimisation, bright light, melatonergic agents, wake therapy, interpersonal and social rhythm therapy, and cognitive behavioural therapy for insomnia, improve circadian parameters, but their effects on adherence are seldom measured. Circadian disruption should be treated as a modifiable determinant of non-adherence; adherence assessment should capture circadian status and dose timing; and chronotherapeutic interventions should be tested against objective adherence endpoints.

Abstract: For most of the twentieth century, the official United States definition of rape—"the carnal knowledge of a female forcibly and against her will"—rendered most sexual victimization invisible to law, crime statistics, and epidemiology. This review traces the evolution of legal definitions, measurement technologies, reporting behavior, and epidemiological knowledge of sexual assault in the United States from 1900 through 2026, synthesizing legal history, survey methodology, national and campus prevalence studies, and meta-analytic evidence on consequences. Three revolutions define this history. First, statutory reform between the 1970s and 1990s abolished corroboration and resistance requirements, enacted rape shield protections, and made sexual assault laws gender neutral. Second, the federal statistical definition was revised in 2012-2013 to a gender-neutral, consent-based penetration standard, immediately raising officially recorded counts by more than a third. Third, behaviorally specific measurement—pioneered in the late 1970s and validated in 1987—showed that prevalence estimates from such instruments exceed those from crime-survey questions by four- to eleven-fold. Contemporary surveillance places lifetime attempted or completed rape at 18.3% of United States women and 1.4% of men, concentrated in adolescence and young adulthood and overwhelmingly unreported. Reporting research reveals persistent rape myths and negative institutional reactions as filters that suppress counts and compound harm, while intersectional and life-course analyses show exposure and consequence stratified by race, disability, gender identity, sexual orientation, and cumulative adversity. The history of sexual assault in the United States is largely the history of its definitions and instruments; unresolved issues of harmonization, inclusivity, and standardization define the methodological agenda ahead.

Abstract: Treatment non-adherence is among the most consequential and modifiable determinants of outcome in psychiatric practice, yet prevailing models—built on insight, medication beliefs, side-effect burden, and access—chiefly explain deliberate omission. They leave unexplained a large residue of doses that patients fully intend to take and then miss. This integrative, mechanism-oriented review advances the proposition that micro-cognitive lapses—transient, seconds-to-minutes failures of executive control—constitute an independent and under-recognised determinant of non-adherence in psychiatric outpatients. Evidence is synthesised on executive function, prospective memory, attentional lapses, goal neglect, mind wandering, intraindividual variability, effort-based decision-making, and metacognition across schizophrenia-spectrum, bipolar, depressive, and attention-deficit/hyperactivity disorders, together with the measurement and intervention literatures. Executive dysfunction is transdiagnostic and tracks real-world functioning more closely than symptom severity. Executive and prospective-memory capacity predicts medication-taking most strongly when doses must be self-initiated amid distraction or routine disruption; forgetting, not reasoned refusal, dominates patients’ accounts of missed doses; and retrospective self-report overestimates adherence relative to electronic monitoring. Ambulatory cognitive testing shows that performance fluctuates within persons with distraction, low effort, and being away from home, establishing lapse propensity as state-dependent and measurable in real time. Because brief interruptions rapidly erode therapeutic drug concentrations, individually trivial lapses carry disproportionate clinical cost. Interventions that reduce reliance on moment-to-moment control—habit formation, implementation intentions, environmental cueing, and long-acting formulations—show the most consistent benefit, whereas purely educational approaches show small effects. Reframing adherence as the output of a state-dependent executive system redirects care towards ecological assessment and automaticity-supporting, lapse-tolerant treatment architectures.

Abstract: Virtual Reality (VR) can provide a more convenient and wider accessibility of Cognitive Behavioral Therapy (CBT) by allowing feared situations to be produced and repeated in a virtual reality space. VR-based CBT may be helpful to treat anxiety disorders and psychosis, as well as to address the avoidance and anxiety involved in some cases of Obsessive-Compulsive Disorder (OCD). This focused narrative review aims to summarize evidence available in public sources by 2026, and address the use of VR to treat anxiety disorders, psychosis, and OCD, as well as related conditions. Given the high social and economic burden related to psychosis and the role of avoidance, the preliminary results of a few randomized control trials (RCTs) using VR-based CBT indicate a potential to reduce symptoms and improve quality of life. A key challenge in psychotherapy is translating the practice simulated in a safe environment to the real world. Research is still needed to address this challenge. The goal of this review is to analyze RCTs and summarize the value of VR and psychotherapy integration by including results of qualitative and economic studies.

Abstract: Psychiatric disorders are prevalent in epilepsy, adversely affecting quality of life and clinical outcomes through complex, potentially bidirectional mechanisms. To review the clinical manifestations, pathophysiology, diagnostic challenges, and therapeutic implications of psychiatric comorbidities in epilepsy. This narrative review synthesizes foundational and contemporary literature addressing mood and anxiety disorders, psychoses, dysphoric syndromes, antiseizure medications, biomarkers, and epilepsy surgery. Depression and anxiety are major comorbidities, with evidence supporting bidirectional relationships between depression and epilepsy. Ictal, postictal, and interictal psychiatric manifestations require differentiation from primary psychiatric disorders. Forced normalization and interictal dysphoric disorder remain clinically relevant but incompletely understood. Antiseizure medications may produce beneficial or adverse psychiatric effects. Emerging biomarkers suggest shared neurobiological mechanisms but lack sufficient clinical validation. Psychiatric comorbidities may influence surgical outcomes, while postoperative psychiatric symptoms can occur despite seizure control. Psychiatric assessment should be integrated throughout epilepsy care, including medication selection, presurgical evaluation, and postoperative follow-up. Individualized, multidisciplinary management is essential to improve psychiatric outcomes and quality of life.

Abstract: Cannabidiol (CBD) represents one of the most remarkable examples of the transformation of a natural compound into a modern therapeutic platform. From its chemical characterization by Raphael Mechoulam in the early 1960s, through the discovery of the endocannabinoid system and the later development of cannabinoid-based medicines such as Sativex® and Epidiolex®, scientific understanding of CBD has progressively expanded from phytochemistry to clinical pharmacology.The present article provides an epistemological and historical perspective on this evolution, focusing specifically on the Italian experience that led to the development of NegEnt, a medical device based on micellar water-soluble cannabidiol conceived for the management of psychological distress, particularly anxiety and insomnia. The article reconstructs the scientific, technological, clinical, entrepreneurial and regulatory milestones of the programme, from its theoretical origins in the Entropy of Mind model to the development of micellar cannabidiol, the registration of NegEnt as a medical device, systematic post-marketing clinical observation, and the subsequent evolution toward the Terpenolol platform.Particular attention is devoted to the interaction between theoretical psychiatry, technological innovation, clinical observation and regulatory change. Within this historical trajectory, the emergence of a biophysical interpretation of cannabinoid neuromodulation represents a further conceptual step, shifting attention from uniform pharmacological suppression toward state-dependent processes of functional regulation. The resulting history illustrates how a natural molecule may progressively become incorporated into a broader scientific programme centred on regulation, organization and resilience within complex mental systems.

Abstract: The multi-factorial origin of stress vulnerability remains incompletely understood, hampering the implementation of targeted prevention. As interplays between genes and environment lie at the basis of individual variability, epigenetic mechanisms are considered important mediators of adverse mental health trajectories following stressful experiences. We have previously demonstrated that the X-linked epigenetic factor Methyl-CpG binding protein 2 (MECP2) plays a role in stress susceptibility, with dysfunctional variants in transgenic mice and its downregulation in human populations being associated with a lower ability to cope with adverse events. By leveraging a study of the Italian Twin Registry on mental health during the COVID-19 pandemic, the present study explored whether a genetic component that accounts for individual variability in MECP2 expression may shape risk of developing stress-related mental health deterioration. We report an association between homozygosity for the minor allele of the rs2734647, a single nucleotide polymorphism (SNP) in the MECP2 3’-untranslated region (UTR) that has been linked to allele-specific MECP2 downregulation, and increased symptoms of COVID-19 pandemic-related depression, anxiety and distress in women. Our findings provide additional evidence to the emerging role of MECP2 in stress vulnerability, unveiling the contribution of genetic variation within the MECP2 locus to adverse mental health outcomes in women.

Abstract: The gut microbiome is studied as a modulator of brain function and a contributor to psychiatric pathophysiology, while sleep and circadian disruption are transdiagnostic psychiatric risk factors. Because the gut microbiota oscillates with host circadian clocks, a three-way “microbiome–sleep–psychiatric axis” has been proposed in which circadian disruption mediates microbiome-associated psychiatric risk. This narrative review translates that axis into an explicit counterfactual mediation framework with named paths, stated identification assumptions, and testable predictions, and appraises the evidence against it. We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science to 30 June 2026, report the strategy in full, and tabulate 18 key human studies and each candidate pathway. The mediator–outcome path is well supported in humans, including by Mendelian randomization, but effect sizes are modest (insomnia–depression pooled OR ≈ 2.1–2.8). The exposure–mediator path is demonstrated only in rodents under extreme perturbation, and microbiome–psychiatry associations are small (β-diversity explaining roughly 0.5–2% of variance). Candidate pathways – glucocorticoid rhythmicity, tryptophan–kynurenine metabolism, short-chain fatty acid signalling, vagal transmission, and microglial–neuroimmune crosstalk – each support one limb of the chain and none the whole. Critically, no human study has estimated any mediated effect, and no cohort has measured the microbiome, a validated circadian phenotype, and psychiatric outcomes with temporal ordering. Existing data remain equally compatible with reverse causation and with confounding by shared environmental disruptors. The circadian mediation hypothesis is therefore falsifiable but untested; we specify the cohort, Mendelian randomization, natural-experiment, and interventional designs that would confirm or refute it.

Abstract: Background: Chaihu–Huangqin (CHHQ, Bupleuri Radix–Scutellariae Radix) is the core drug pair of Xiaochaihu Decoction, yet the constituents that reach the brain and the pathways they engage remain largely unknown. Methods: An integrated strategy combining serum pharmacochemistry, brain-region-resolved distribution profiling, network pharmacology, molecular docking, and in vivo validation was developed in a chronic unpredictable mild stress (CUMS) rat model. Results: UPLC-MS/MS-based serum pharmacochemistry identified 97 constituents absorbed into the systemic circulation. In CUMS rats, CHHQ ameliorated depressive-like behaviors, evidenced by increased sucrose preference and reduced immobility in the forced swimming test, without evident hepatic or renal toxicity. Profiling across six depression-related brain regions revealed the largest number of region-specific candidates in the dorsal raphe nucleus (DRN), which was therefore selected as the focus region. Network pharmacology prioritized inflammatory and serotonergic signaling, including the nuclear factor-κB (NF-κB)/NOD-like receptor family pyrin domain-containing 3 (NLRP3)/Caspase-1 axis and the serotonin transporter (SERT), and molecular docking gave GlideScore values of −6.01 to −10.50. In the DRN, CHHQ attenuated microglial activation, decreased TNF-α, IL-1β, and IL-18, and downregulated NF-κB, NLRP3, and Caspase-1, accompanied by restored SERT expression. Conclusion: These findings establish an “absorption into blood—brain-region-resolved detection—DRN candidate prioritization” workflow and provide new insights into the material basis and multi-target mechanism of the CHHQ drug pair.

Abstract: Childhood sexual abuse (CSA) is reliably associated with adult sexual dysfunction, yet the field has historically framed survivors' sexuality in terms of damage rather than recovery. This narrative review asks whether sexual health recovery can occur after childhood abuse, and what trauma-informed care contributes to it. Evidence from meta-analyses, psychophysiological studies, longitudinal cohorts, and randomized treatment trials is synthesized around three questions: the strength of the CSA–dysfunction association, the mechanisms linking them, and the responsiveness of sexual function to intervention. Meta-analytic evidence confirms the association (odds ratio 1.68, 95% CI [1.49, 1.87]), stronger among women than men, although findings are heterogeneous and moderated by comorbidity, abuse characteristics, and family context. Five mechanisms recur: posttraumatic stress with blunted genital arousal and altered cortisol response; dissociation during sexual activity; cognitive-affective processes centered on distraction and avoidance; negative sexual self-schemas and low sexual self-esteem; and relational difficulties including insecure attachment. A reframing of dysfunction as protective — avoiding re-traumatization, regulating closeness, restoring a sense of control — implies that these adaptations must be understood before function is restored. Recovery is nonetheless well documented: roughly one third of sexually abused children show no symptoms and two thirds recover within 12–18 months; latent class analysis of maltreated youth identifies resilient, survival, and improving sexual health trajectories; and mindfulness-based sex therapy and schema-focused expressive writing improve sexual function, with abused women sometimes improving more than non-abused women. Recovery is therefore not automatic but facilitated, and trauma-informed care is the condition under which it occurs.

Abstract: Clozapine remains the only antipsychotic with proven superiority for treatment-resistant schizophrenia, yet its use is constrained by marked interindividual variability in both response and toxicity and by a burdensome adverse-effect profile spanning agranulocytosis, myocarditis, and metabolic syndrome. Three decades of pharmacogenetic research have sought genetic markers capable of predicting, before treatment begins, who will respond and who will suffer harm. This narrative review critically re-examines that record across three domains: pharmacokinetics (metabolism and transport), pharmacodynamics (treatment response), and adverse drug reactions, before evaluating the gap between research findings and clinical implementation. Pharmacokinetic pharmacogenetics has been the field’s most consistent disappointment: CYP1A2 genotype contributes little beyond smoking status, and CYP2C19 and ABCB1 variants exert only modest effects on plasma concentrations. Pharmacodynamic pharmacogenetics has fared no better; candidate genes in the serotonergic and dopaminergic systems, including the celebrated six-single-nucleotide-polymorphism response model, have failed replication in genome-wide and independent cohorts. Only the adverse-reaction domain has yielded durable findings: HLA-DQB1 126Q, HLA-B 158T, and population-specific alleles such as HLA-B*59:01 are biologically coherent and replicated correlates of clozapine-induced agranulocytosis, yet their predictive values remain too low to alter mandatory hematological monitoring. This review identifies five recurring methodological failures underlying this pattern of underdelivery: chronically inadequate sample sizes, phenotype heterogeneity, inadequately handled population stratification, conflation of biological plausibility with clinical evidence, and a translational logic gap between statistical association and actionable prediction. No genetic marker or panel currently meets the evidentiary threshold required to guide clozapine initiation, dosing, or monitoring. Therapeutic drug monitoring informed by smoking status already delivers much of what pharmacogenetics promises, at lower cost and with more direct capture of the dominant determinants of clozapine exposure. Large, adequately powered, trans-ancestral genome-wide studies, evaluated against prospective clinically meaningful outcomes, are needed before genetic testing can be considered ready for clozapine prescribing decisions.

Abstract: Patient satisfaction has become a dominant metric of health care quality, embedded in public reporting, accreditation, and pay-for-performance programs. Its prominence rests on an implicit assumption that satisfied patients have been treated well and have improved. This narrative review synthesizes conceptual and empirical literature to examine whether, how often, and why patients can be highly satisfied despite minimal clinical gain or dissatisfied despite substantial gain. The 2 constructs are related but explain little of each other. In a cohort of 2116 surgical patients, no outcome measure accounted for more than 8% of the variance in satisfaction, which tracked absolute postoperative state rather than change. Complications and readmissions show weak, inconsistent associations with satisfaction, whereas communication and shared decision-making are strongly and independently associated with it. Six mechanisms explain the divergence: expectancy disconfirmation (unmet expectations raised the odds of dissatisfaction after knee arthroplasty more than 10-fold), relational determinants, health-status confounding, placebo and nocebo effects, response shift (detected in 86.7% of longitudinal studies), and measurement artifacts such as ceiling effects and response bias. In low- and middle-income settings, more than half of respondents rated poor-quality care as good or better. Satisfaction should be neither discarded nor used as a surrogate for effectiveness; complementary measurement of care experience, clinical outcome, and expectation fulfillment is the defensible path.

Abstract: Intranasal esketamine has been available for treatment-resistant depression (TRD) since 2019, but the trials that led to its approval answer only some of the questions prescribers face. About 97% of trial participants had failed only one or two antidepressant classes, and patients with bipolar disorder, psychosis, obsessive–compulsive disorder, four personality disorders, moderate-to-severe substance use disorder, or recent suicidal intent were excluded, although such patients are common in practice. This review is meant as a practical guide for prescribers. We discuss the mechanism of action and its clinical implications, ideal and real-world candidates, patients with suicidal ideation, psychiatric comorbidity (including borderline personality disorder), dosing, concomitant medications, prevention and management of adverse effects, comorbid substance use disorder, treatment duration in responders and non-responders, and contraindications. Six tables summarise the drug’s characteristics, receptor pharmacology, patient selection, concomitant medications, adverse-event management and contraindications, including differences between the US and European labels. For each recommendation, we indicate whether it comes from the label, from expert consensus, or from untested practice. The evidence does not show that 84 mg is more effective than 56 mg; comorbidity has seldom predicted non-response in real-world cohorts; the standing benzodiazepine dose should be reviewed before induction; and response is often judged too early.

Abstract: Survivors of sexual violence carry a disproportionate burden of age-related morbidity, including cardiovascular disease, type 2 diabetes and inflammatory conditions, raising the possibility that sexual trauma accelerates the biology of aging rather than acting solely through psychological distress or health behaviors. This narrative review synthesizes translational, epidemiological and biomarker evidence across five mechanistic domains. Epigenetically, posttraumatic stress disorder (PTSD) is associated with accelerated DNA-methylation age, most consistently on the mortality-calibrated GrimAge clock, whereas meta-analytic evidence for cumulative childhood adversity on first- and second-generation clocks is weak. At the cellular level, severe childhood sexual abuse is associated with shorter leukocyte telomeres in several, though not all, studies, and PTSD with telomere attrition, T-cell senescence and oxidative DNA damage. Endocrinologically, childhood sexual abuse produces enduring hypothalamic-pituitary-adrenal axis sensitization and earlier pubertal maturation in girls. Inflammatory evidence is the most robust: childhood maltreatment prospectively predicts adult C-reactive protein, and PTSD is consistently associated with elevated pro-inflammatory cytokines. Metabolically, PTSD is associated with a high prevalence of metabolic syndrome, and childhood sexual abuse with obesity and type 2 diabetes in women. Glucocorticoid-FKBP5-NF-κB signaling and allostatic load emerge as bridges between domains, and we propose an integrated six-step model. Causal inference remains limited by retrospective trauma assessment, confounding by co-occurring adversity and scarce trauma-type-specific analyses. Priorities include prospective, sexual-trauma-specific multi-omic studies and trials testing whether trauma-focused, anti-inflammatory or metabolic interventions can slow the pace of biological aging in survivors.

Abstract: Depression among Black patients is shaped by the interaction of clinical symptoms, cultural meanings, social conditions, and experiences of care. This narrative review examines evidence among African American and other Black populations, including Black–White comparisons and within-Black differences, on symptom presentation, measurement, persistence, disability, comorbidity, and social and cultural correlates, across the United States and selected Canadian, European, and African settings. Targeted searches identified population surveys, clinical studies, psychometric investigations, qualitative research, intervention trials, and relevant reviews. James S. Jackson's research agenda provides a starting point: understanding comparatively favorable findings in the context of historical and continuing adversity. Several United States surveys report lower lifetime prevalence of interview-defined major depression among Black than White adults, while symptom scales often indicate greater depressive burden among Black adults. This Black–White mental health paradox varies by outcome and population; some studies identify greater persistence and disability among Black adults with depression. Studies of hope, positive affect, coping resources, and physical health suggest that the correlates of depression may also differ across groups, although no single mechanism explains the pattern. Evidence on distinctive symptom presentation is mixed. Some studies identify Black–White differences or within-Black variation in bodily symptoms, self-criticism, or interpersonal experiences, whereas others find substantial similarity after accounting for severity and social or medical conditions. Psychiatric and physical comorbidity among Black adults with depression varies across samples, including in comparisons with White adults. Associations of depressive symptoms or MDD with smoking, disease self-management, self-rated health, inflammation, and mortality differ across studies and populations; colorism, trauma, sexuality, gender, and migration further identify within-Black heterogeneity. The review examines associations of discrimination, financial strain, employment conditions, family relationships, and gendered expectations with depressive symptoms, MDD, and treatment use among Black populations. Studies of Black populations also examine political representation and insurance expansion in relation to self-reported mental health, and loneliness, personality, and distinct church-based relationships in relation to depressive symptoms or MDD. Social support, religious involvement, mastery, and socioeconomic resources are associated with depressive symptoms or MDD in several studies, with variation across measures, social positions, and national settings. Studies also identify disparities in medication initiation and selection, communication, continuity, and care quality; stigma, discrimination in care, and medical debt are relevant to treatment access and experience. Cultural assessment and accessible, sustained depression care may improve recognition and engagement. Future research should distinguish symptom burden from diagnosed disorder, assess longitudinal course directly, and avoid treating Black identity as a single cultural or biological category.

Abstract: Major depressive disorder is one of the most prevalent and disabling conditions worldwide, yet fewer than one-third of patients achieve remission with the first antidepressant prescribed. The clinical phenotypes codified across successive editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) — melancholic, atypical, anxious, and psychotic forms of depression — were proposed, in part, because they were thought to predict differential response to specific drug classes. This narrative review evaluates the evidence for phenotype-specific antidepressant efficacy across the full depressive spectrum, including treatment-resistant depression as a longitudinal phenotype and the transdiagnostic reformulations advanced by the Research Domain Criteria initiative. Historical controlled trials demonstrated genuine but circumscribed phenotype–drug interactions, most notably the preferential response of atypical depression to monoamine oxidase inhibitors relative to tricyclic antidepressants. However, contemporary large-scale effectiveness data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trials do not support subtype-based antidepressant selection. Much of the apparent predictive value of melancholic status is confounded by illness severity and placebo responsiveness, while data-driven re-analyses have failed to biologically validate the DSM-defined subtypes. Anxious depression and treatment-resistant depression robustly identify poorer outcomes but do not yet point clinicians toward specific drug classes. Weighing the totality of evidence, categorical depression phenotypes have limited utility in predicting antidepressant response; the most clinically reproducible signal is severity-dependent drug–placebo separation, and the most promising route to precision prescribing lies in transdiagnostic, multimodal biosignatures and machine-learning approaches.

Abstract: The study aimed to examine the effect of a mindful parenting intervention on parents of adolescents exhibiting non-suicidal self-injury (NSSI). Families meeting the specified criteria voluntarily participated, resulting in 23 families in the intervention group and 18 families in the waitlisted treatment group. Both groups were carefully matched in demographic variables. Only the parents in the intervention group received mindfulness parenting intervention, while other participants did not receive any intervention. Prior to and following the intervention, parents and adolescents with NSSI in both groups underwent assessments using a series of scales. Compared to the waitlisted treatment group, adolescents with NSSI in the intervention group exhibited significant reductions in impulsivity, depression, and anxiety scores following the intervention, parents in the intervention group demonstrated a significant reduction in depression and anxiety scores, along with a notable increase in mindful parenting scores after the intervention. Additionally, adolescents with NSSI in the intervention group showed significant improvements in depression and anxiety from pre- to post-intervention. Parents in the intervention group also showed improvements in depression and increases in mindful parenting levels from pre- to post-intervention. The mindful parenting intervention positively impacts both adolescents with NSSI and their parents.

Abstract: Background: Sexually and gender diverse people affected by cancer (SGDc) experience significant disparities and minority stress across the cancer continuum, alongside high levels of unmet psychosocial needs and limited access to affirming support groups. Existing reviews and equity‑focused frameworks have called for SGDc interventions that centre queer and trans experiences, yet few evaluated models exist in psychosocial oncology. Methods: We conducted a pragmatic quality improvement project within the SGDc Program at Princess Margaret Cancer Centre to develop, implement, and evaluate QUEERMUNITY, a queer‑affirming psychotherapy support group for SGDc patients informed by a gender, sex, and relationship diversity (GSRD) framework. A pre‑implementation needs assessment survey of SGDc patients (n = 19) assessed supportive care priorities, including interest in queer‑specific groups. In response, we launched QUEERMUNITY and invited group participants (n = 31) to complete a one‑time cross‑sectional post‑implementation survey assessing perceived impact on safety, relevance, coping, community, and overall satisfaction, supplemented by qualitative feedback and facilitator observations. Results: In the needs assessment, 15 of 19 respondents (52.6-78.9%) rated "patient support groups specifically for 2SLGBTQIA+ patients and caregivers" as important or very important; adolescent/young adult and older‑adult 2SLGBTQIA+ groups were similarly prioritized. Dedicated SGDc‑specific professional supports (psychiatry, psychology, social work, and other healthcare providers) were endorsed as important or very important by 73.7-89.5% of respondents. One year post‑implementation, 25 of 31 QUEERMUNITY participants completed the survey (80.6% response rate). 91.3% reported feeling safe, comfortable, and inclined to continue engagement, with 95.7% recommending the group to others and rating strong satisfaction regarding community, support, queer joy, and pride.. Qualitative feedback highlighted the value of an explicitly queer‑centred space for discussing cancer, identity, and chosen family; relief at not navigating cis‑heteronormative assumptions; and perceived gains in coping, validation, and sense of community. Conclusions: Pre‑implementation data demonstrated strong demand for queer‑specific support groups and SGDc‑tailored professional supports, and post‑implementation findings suggest that QUEERMUNITY is a feasible, acceptable, and highly valued GSRD‑informed queer‑affirming group intervention in psychosocial oncology. This model offers a practical approach to operationalizing minority stress‑informed, intersectional, and GSRD‑theoretical frameworks in cancer care and may contribute to more equitable, affirming services for SGDc populations.

Abstract: We examined factors associated with severe psychosocial maladaptation in adults with epilepsy and described profiles relevant to personalized rehabilitation. This observational study included 480 adults aged 25-45 years assessed in clinical rehabilitation settings during 2018-2026. Neurological, psychiatric, cognitive, and psychosocial characteristics were evaluated. Multivariable logistic regression estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Anxiety symptoms occurred in 59.2%, depressive symptoms in 55.4%, cognitive impairment in 60.8%, and sleep disturbance in 65.0%. Severe maladaptation affected 263 participants (54.8%). Stigma-related distress had the largest adjusted OR (2.67; 95% CI, 1.78-4.01). Depressive symptoms, low adherence, anxiety symptoms, cognitive impairment, sleep disturbance, and drug-resistant epilepsy also retained associations with the outcome. The AUC was 0.82 (95% CI, 0.78-0.86), with a bootstrap-corrected AUC of 0.80. Five predominant rehabilitation profiles were identified. Multidimensional assessment may help identify individual rehabilitation priorities. The observational associations do not establish causality or intervention effectiveness. Calibration and external validation are required before individual clinical use of the model.

Abstract: Background/Objectives: Türkiye is the most populous country reporting to the European drug monitoring system, yet its drug-induced deaths have rarely been studied in the international literature. We describe drug-induced mortality in Türkiye over fifteen years and compare its level and composition with those of European countries. Methods: We assembled all published data of the Council of Forensic Medicine, the national reference institution, on direct drug-induced deaths for 2010–2024, drawing on the national reports and European reporting channels, which proved to carry identical counts. Temporal trends were analysed using segmented Poisson regression. Rates were compared with a fixed panel of ten EU countries with direct age standardisation. Results: A total of 6,129 deaths were recorded. Annual deaths rose seven-fold to 941 in 2017, fell by almost two thirds within two years, reached 246 in 2022 and rose again to 427 in 2024. The net rise in 2024 was entirely attributable to deaths involving synthetic cannabinoids. The wave was concentrated among men aged 15–44. At its height, mortality among young men exceeded the European panel by 1.6 to 2.8 times while the all-ages rate remained below the European level. Women comprised 5.0% of decedents. Opioid involvement fell from 76.5% to 15.5%. Among single-substance deaths, the leading substance changed three times, from heroin to synthetic cannabinoids, MDMA, methamphetamine and back to synthetic cannabinoids. Conclusions: Responses built around opioids reach a minority of deaths. Türkiye needs monitoring that distinguishes changes in mortality from changes in substance attribution, and prevention directed at synthetic cannabinoids, stimulants and young men.