Drug and alcohol reviewJie Yang, Louisa Picco, Paul Dietze, Peter Higgs, Suzanne Nielsen
INTRODUCTION: Pain is highly prevalent among people with opioid use disorder (OUD), yet it is often undertreated. Whether opioid agonist treatment (OAT) improves pain outcomes is unknown among this target population. This research aimed to explore associations between pain severity and current OAT status in a longitudinal cohort of people who inject drugs. METHODS: Data were drawn from the Melbourne Injecting Drug User Cohort Study (SuperMIX), comprising individuals with a drug injection history recruited from areas across Greater Melbourne and Geelong, Australia, between 2008 and 2024. Eligible participants were adults who reported ever being in OAT for at least one time point. Participants were classified into four groups based on their self-reported pain level (from none to severe). Multilevel ordinal logistic regression with a participant-level random intercept examined the association between pain severity and current OAT status, comparing current OAT (methadone or buprenorphine) with no current OAT as the reference category. Current OAT status was treated as a time-varying exposure, with methadone and buprenorphine examined separately in sensitivity analyses. Models were adjusted for demographic and clinical characteristics and substance use history. RESULTS: A total of 1328 participants were eligible for inclusion. At baseline, most were male (67.7%), on government income support (81.9%), and had pain at any level in the past 4 weeks (66.0%), with a mean age of 36.7 (SD 10.6) years. No association between pain severity and current OAT status was observed, while several other factors associated with higher pain severity were identified, such as older age, poorer overall health and the use of other opioids. DISCUSSION AND CONCLUSIONS: While OAT status was not associated with pain severity in this study, several other factors associated with higher pain severity were identified. These findings highlight the multifactorial nature of pain in this population and the importance of considering broader physical and emotional health when managing pain.
Pakistan journal of pharmaceutical sciencesYong Ni, Zhiqiang Tang, Ting Huang, Jian Gong
BACKGROUND: Acute alcohol intoxication (AAI) is a common emergency with no specific antidote. Metadoxine has shown potential but lacks sufficient real-world evidence, particularly in Chinese populations. OBJECTIVES: To evaluate the clinical efficacy and safety of metadoxine in patients with acute alcohol intoxication. METHODS: This single-center retrospective cohort study included 124 patients with AAI admitted to an emergency department between January and December 2024. Patients were divided into metadoxine plus conventional treatment (n=62) or conventional treatment alone (n=62) after propensity score matching. Primary outcomes were time to consciousness recovery (Glasgow Coma Scale ≥14) and treatment effectiveness rate (symptom improvement within 6 hours without treatment escalation). Secondary outcomes included time to symptom relief, emergency stay, time to vital sign stabilization, blood ethanol decline rate, adverse reactions, and liver function changes. RESULTS: Metadoxine significantly shortened consciousness recovery time (3.05±1.45 vs. 5.65±1.58 hours, mean difference -2.60 hours, 95% CI: -3.14 to -2.06, p < 0.001) and improved treatment effectiveness rate (93.5% vs. 77.4%, OR=4.04, 95% CI: 1.30-12.56, p = 0.011). All secondary outcomes were significantly better in the metadoxine group (p < 0.001 for time-related outcomes and blood ethanol decline). No significant differences were observed in adverse reactions (9.68% vs. 6.45%, p = 0.510) or post-treatment liver enzyme abnormalities (12.90% vs. 16.13%, p = 0.610). Subgroup analysis showed a significant interaction by initial Glasgow Coma Scale (p = 0.037), indicating greater efficacy in patients with moderate-to-severe impairment. CONCLUSION: Metadoxine, when added to conventional supportive therapy, significantly accelerates consciousness recovery and improves clinical outcomes in acute alcohol intoxication without increasing short-term adverse events. The benefit appears more pronounced in patients with lower Glasgow Coma Scale scores.
Drug and alcohol reviewJasmin Jiuying Han, Michael R Desjardins, Julia McQuoid, Janardan Devkota, Joseph J C Waring, Kekoa Lopez-Paguyo, Nhung Nguyen, Pamela M Ling, Johannes Thrul
INTRODUCTION: Ecological momentary assessment (EMA) allows researchers to capture substance use as it occurs in daily life, but participants may not report every use event. Little is known about whether the environments where people spend time affect the completeness of these reports. METHODS: We examined how consistently young adults reported cigarette and cannabis use through event-based EMA and whether reporting differed by the social vulnerability of places they visited. We analysed 30 days of GPS-enabled EMA and daily diary data from 34 young adults in California (730 participant days). We compared daily cigarette and cannabis use events reported through EMA with those reported in the following day's diary and classified EMA reports as lower than, matching, or higher than the diary. Using GPS data and the Social Vulnerability Index, we measured the social vulnerability of participants' daily activity spaces relative to home. RESULTS: Bayesian multilevel multinomial logistic regression showed that higher social vulnerability in daily activity spaces relative to home was associated with greater odds of reporting fewer use events through EMA than in the daily diary for cigarettes (aOR 1.55, 95% CrI 1.25-1.93) and cannabis (aOR 1.28, 95% CrI 1.06-1.55). The association for cigarettes was also observed in a larger independent dataset. DISCUSSION AND CONCLUSIONS: These findings suggest that the completeness of real-time substance use reporting may depend partly on where participants spend their time. Researchers using event-based EMA should consider environmental context when interpreting incomplete reports and designing studies to improve data completeness.
Drug and alcohol reviewLouise MacGregor, Timothy Weaver, John Strang, Stephen Pilling, Nicola Metrebian, Kimberley Goldsmith
INTRODUCTION: Contingency Management (CM) involves the systematic application of positive reinforcement (financial incentives) to promote behaviour change, to improve treatment outcomes for individuals with opioid use disorder (OUD). To better understand patient heterogeneity, this study sought to identify meaningful subgroups/classes underlying the population based on characteristic groupings, followed by determining whether CM effectiveness varied between these subgroups. METHODS: Baseline characteristics (evidenced/theorised to impact CM effectiveness) of participants with OUD from the PRAISe trial (N = 552) were empirically examined using latent class analysis. Model selection was based on fit statistics and interpretability. Class was then evaluated as a potential moderator of CM effectiveness on abstinence from heroin using a mixed effects model (consistent with the PRAISe trial analysis). RESULTS: A four-class solution best described the population: (1) Less clinically complex/low alcohol dependence/high motivation to quit heroin (N = 115); (2) More clinically complex/low alcohol/high motivation (N = 287); (3) More clinically complex/high alcohol/high motivation (N = 73); and (4) More clinically complex/moderate alcohol/low motivation (N = 77). CM for Attendance, previously shown to increase heroin abstinence in the overall study sample, was more effective than no CM for participants in class (1) and (2) exclusively (OR = 5.21; 95% CI 1.25, 21.78 and OR = 1.87; 95% CI 1.03, 3.40, respectively). CM targeted at abstinence, previously shown to not be effective compared to no CM overall, was not effective in any class. DISCUSSION AND CONCLUSIONS: CM targeted at attendance is more effective for two subgroups of the OUD population characterised by either less complex clinical presentation and/or low dependence on alcohol. Individual differences may therefore inform a targeted CM treatment approach.
Liver international : official journal of the International Association for the Study of the LiverMassimo Puoti, Alessandro Tavelli, Giuseppina Brancaccio, Maria Giovanna Quaranta, Maria Elena Tosti, Giovanni Battista Gaeta, Loreta A Kondili, Antonella d'Ar…
BACKGROUND AND AIMS: Hepatitis D virus (HDV) infection has historically been more prevalent among people with HIV (PWH) due to shared transmission routes. Whether HIV status still identifies a subgroup at higher risk of HDV in contemporary settings remains unclear. METHODS: We performed two cross-sectional analyses assessing anti-HDV prevalence among HBsAg-positive PWH enrolled in the ICONA cohort in 2009-2012 and 2019-2023, compared with HIV-negative individuals from the MASTER and PITER cohorts. RESULTS: Anti-HDV prevalence among PWH declined from 19.1% to 12.5%, converging with that observed in HIV-negative individuals (12.7%). Injection drug use markedly decreased over time among PWH and remained the strongest determinant of HDV infection. In multivariable analyses, HDV seropositivity was associated with age, injection drug use, and birth outside Italy, but not with HIV infection in the contemporary period. CONCLUSION: These findings indicate that HIV infection is no longer independently associated with HDV infection in this setting and support universal HDV screening strategies.
Bioscience reportsAfolabi Akanbi, Kim Bridle, Darrell H G Crawford
Steatotic liver disease (SLD) encompasses a broad spectrum of disorders influenced by metabolic dysfunction, alcohol use, and other cofactors. The updated classification of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD), along with the recognition of the overlapping entity MetALD, allows for better identification of patients at increased risk of progressive liver injury. While iron dysregulation is known to worsen both MASLD and ALD, its role within MetALD remains poorly defined. Understanding how iron contributes to this combined phenotype may provide new insight into why these patients experience more severe disease outcomes. This review synthesises current evidence linking iron to MASLD, ALD, and their intersection in MetALD. It introduces the concept of Fe-MetALD, a "triple-hit" phenotype where metabolic dysfunction, alcohol, and iron overload act together to accelerate liver injury. Mechanistically, these insults share common pathways involving oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, and hepatic stellate cell activation, collectively promoting fibrosis progression and potentially increasing the risk of cirrhosis and hepatocellular carcinoma. Experimental studies suggest that the combination of these insults produces more severe liver injury than any individual factor alone. Emerging therapies that target iron pathways, including hepcidin mimetics, ferroportin inhibitors, and iron-reduction strategies like venesection or chelation, may offer therapeutic potential, although current evidence remains largely preclinical. Recognising Fe-MetALD as a high-risk phenotype supports incorporating iron markers into diagnosis and developing therapies targeting metabolic, alcohol-related, and iron-mediated injury. Understanding this triple-hit interaction may improve risk stratification and guide future therapies for SLD.
PloS onePeiyuan Liu, Tania de Jesús Espinosa, Elham Samami, Bernard Mensah, Hermine Poghosyan
BACKGROUND: Economic instability may shape substance use (i.e., cigarette use and cannabis use) among the adult population. However, their relationship remains poorly understood. This study estimated the prevalence of economic instability indicators (i.e., employment instability, received food stamps, food insecurity, housing insecurity, and threatened utility shutoffs), exclusive cigarette use (TU), exclusive cannabis use (CU), and cigarette-cannabis co-use (TCU), and investigated the associations between economic instability indicators and these distinct substance use patterns among adults aged ≥18 years. METHODS: This study used cross-sectional population-based data from the 2023 Behavioral Risk Factor Surveillance System (BRFSS) Marijuana Use and Social Determinants and Health Equity modules, administered in 10 US states. The 2023 BRFSS achieved a response rate of 44.7%. The sample included (unweighted n = 50,481; weighted N = 24,896,969) adults ≥18 years. The outcome variables were TU, CU, and TCU. Indicators of economic instability included employment instability, receipt of food stamps, food insecurity, housing insecurity, and threats of utility shutoffs. Weighted descriptive statistics and multivariable multinomial logistic regression analyses were conducted. RESULTS: Overall, 48.6% of the participants were aged ≤50 years, 52.6% were women, and 64.4% self-identified as non-Hispanic White. The prevalences of TU, CU, and TCU were 8.1%, 11.1%, and 3.6%, respectively. Participants experiencing employment instability, housing insecurity, or threats of utility shutoffs were more likely to engage in CU compared to TU or TCU (P ≤ 0.01). All economic instability indicators were significantly associated with TCU, with the strongest association observed for those who received food stamps (aRRR = 2.27, 95% CI: 1.75-2.94), which was also significantly associated with TU (aRRR = 1.55, 95% CI: 1.24-1.93). Threats of utility shutoffs (aRRR = 1.37, 95% CI: 1.10-1.70) and housing insecurity (aRRR = 1.27, 95% CI: 1.04-1.55) were significantly associated with CU. CONCLUSIONS: Economic instability indicators are significantly associated with cigarette and cannabis use, as well as their co-use patterns among US adults residing in the 10 participating states. Effective, targeted public health interventions to mitigate substance use risk in economically precarious populations are needed. Healthcare providers should routinely screen for economic instability to identify individuals at high risk for substance use and provide them with social services and behavioral health interventions.
European respiratory review : an official journal of the European Respiratory SocietyChristina Lildharrie, Faith N Veenker, Kylee B Miller, Michele-Vera Yonga, Sarah Abey, Gene-Jack Wang, Sung Won Kim, Sukru B Demiral, Nora D Volkow
Drug overdose remains an urgent public health concern as it is a leading cause of fatal injury in the United States, with approximately 90% being attributed to opioid-induced respiratory depression from synthetic opioids. This statistic is primarily driven by the rise in the use of fentanyl, a potent synthetic opioid and its increased use in combination with stimulant drugs. The rise in the combined use of opioids and stimulants raises questions about pharmacological and physiological interactions, and its implication for the treatment of their addictive consequences and of overdoses. Though opioid-related fatalities are due to respiratory depression and stimulant fatalities predominantly from cardiac disruption, co-use creates interactions that remain under studied. Similarly, how medications designed to treat opioid use disorder impact respiration has been mostly neglected. Here, we review preclinical and clinical studies on the effects of opioids and stimulants on respiration, focusing on brainstem respiratory nuclei, and explore implications for advancing prevention and treatment strategies for drug-related overdose.
Journal of medical Internet researchMarianthi Markatou, Raktim Mukhopadhyay, Jeff Good, Yihao Tan, Arpan Dharia, Lawrence S Brown, Andrew H Talal
Large language model (LLM)-based systems have tremendous potential to improve patient-centered health care, especially for medically underserved populations. However, realizing this potential requires careful consideration of the socio-technical contexts in which LLMs are used. The design of such systems should consider the vulnerabilities of any medically underserved group that the system intends to support, and provide trustworthy evidence for its use. This viewpoint reports the lessons learned from our experience and research with the CREATE (Culture, Respect, Education, Advancement, Trust, and Expertise) framework for engaging multiple stakeholders to guide the integration of LLM-based systems for improved health care delivery. We propose an extension of the traditional hierarchy of evidence model and identify key junction points in clinical workflows at which LLM-based systems can potentially be used to improve patient care. The key messages can be summarized as follows: (1) users of AI technologies, such as LLM-based tools, must be aware of the strengths, limitations, and impact of these technologies on health care delivery workflows and on the quality of generated evidence on which health care recommendations are based; (2) users must also be aware of the impact of data quality on AI outputs and on the evidence generated from the use of these systems; (3) the evidence pyramid provides a framework that facilitates the evaluation of the output generated by AI systems; (4) the CREATE framework facilitates the engagement of a variety of stakeholders. We propose concrete approaches for its validation and implementation; (5) any system designed to support people with opioid use disorder (OUD) needs to consider the overall lack of trust and stigmatizing experiences of this population with the health care system, and we discuss various aspects of the evaluation process necessary to build trust; (6) to discuss research directions that need to be addressed before LLM-based systems can be integrated usefully in patient health care.
Medical science monitor : international medical journal of experimental and clinical researchIzabela Staszewska, Alicja Mastej, Dominika Mech, Mikołaj Tomasz Marynowski, Ewelina A Soroka
Adverse childhood experiences (ACEs) are a significant determinant of health across the life course and exhibit a dose-dependent relationship with the risk of mental and physical disorders in adulthood. One common yet under-recognized ACE is growing up in a family with an alcohol problem. The objective of this study was to review current data on the neurobiological mechanisms and clinical consequences of early exposure to parental alcohol use disorder, considered an ACE, along with implications for medical practice. A review was conducted of the literature on ACEs, with a particular focus on exposure to parental alcohol use disorder, the co-occurrence of other developmental adversities, and health outcomes in adulthood. Data on ACE screening and the trauma-informed care approach were also included. Parental alcohol use disorder often co-occurs with violence, neglect, and mental health disorders among caregivers, increasing overall stress exposure. Chronic developmental stress is associated with hypothalamic-pituitary-adrenal axis dysregulation and persistent inflammation, as well as an increased risk of depression, anxiety disorders, posttraumatic stress disorder, and substance use disorders. Somatic consequences are also described, including a higher risk of type 2 diabetes and cardiovascular disease, as well as a poorer response to treatment in individuals with ACE exposure. The term adult children of alcoholics is descriptive in nature and does not constitute a diagnostic entity. Early exposure to a parent's alcohol use disorder as an ACE is associated with multidimensional health consequences in adulthood. Further research is needed on the efficacy and safety of ACE screening and the implementation of trauma-informed care.
INTRODUCTION: Persons with substance use disorders (SUDs) have markedly increased risk for lifestyle-related diseases and reduced life expectancy. Initial findings suggest that high-intensity physical training (HIT) represents an efficient and effective training modality for improving physical and functional capacity for persons with SUDs. However, acheiving such improvements depends not only on the availability of such training modalities but also on adherence, which remains insufficiently understood in this population. Thus, to extend the benefits of HIT to additional persons within this population, there is a need for a broader, deeper, and more patient-centred understanding of their experiences with HIT integrated into specialised treatment, including facilitators and barriers to adherence. METHODS AND ANALYSIS: This protocol article presents an ongoing qualitative collaborative health service study where inpatients with SUDs are interviewed in-depth about their experiences of and adherence to HIT by semi-structured interview guides. Approximately 20 inpatients with SUDs will be purposively recruited based on relevant background variables and inclusion criteria to ensure breadth in experiences: 10 who have adhered to supervised HIT as part of specialised SUD treatment and 10 who have not. Depth will be supported through in-depth interviewing, reflexive field notes, and collaborative thematic analysis with persons with lived experiences. ETHICS AND DISSEMINATION: The study has received ethical approval from Regional Committees for Medical and Health Research Ethics (Reference ID: 2019/501). By strengthening the knowledge base on factors influencing adherence and non-adherence in HIT as part of clinical practice, the findings may support patient's adherence to HIT integrated in SUD treatment in a more person-centred way, ultimately benefiting the physical and functional capacity for additional persons with SUDs. Findings will be disseminated together with persons with lived experiences via conferences, peer-reviewed publications, as well as popular-scientific communication and media. Finally, the findings may generate theoretically informative insights into patients' experiences and mechanisms influencing adherence to HIT, as well as novel concepts and insights needed for new research directions within an increasingly prioritised field in specialised SUD treatment.
Psychological medicineAvery Chan Eun, Kevin H Yang, Joseph J Palamar
BACKGROUND: Psilocybin use has increased in the US alongside promising therapeutic potential for depression, raising concerns that individuals may forgo conventional mental health treatment for unsupervised psilocybin use. However, no nationally representative studies have examined whether psilocybin use is associated with differential treatment utilization or perceived unmet need for mental health care among individuals with depression. METHODS: We analyzed data from 6,793 individuals aged ≥ 12 years with a past-year major depressive episode (MDE) from the 2024 National Survey on Drug Use and Health, a nationally representative survey of the noninstitutionalized US population. Sociodemographic and substance use characteristics were first compared by past-year psilocybin use. We then examined associations between past-year psilocybin use and eight past-year mental health treatment outcomes using Poisson regression, adjusting for sociodemographic characteristics, other past-year substance use, psychotherapeutic prescription misuse, and alcohol use disorder. RESULTS: Among individuals with past-year MDE, an estimated 7.3% (95% CI: 6.4-8.3) used psilocybin in the past year. In multivariable models, psilocybin use was not associated with any mental health treatment utilization, including outpatient, inpatient, or telehealth treatment; prescription medication use for mental health; seeing a doctor for depressive feelings; or prescription medication use for depressive feelings. However, psilocybin use was associated with greater perceived unmet treatment need (52.0% vs. 33.9%; aPR = 1.44; 95% CI: 1.04-2.01). CONCLUSIONS: Findings suggest that psilocybin use among individuals with depression co-occurs with perceived unmet need for conventional mental health care but is not associated with lower utilization of any conventional mental health treatments.
PloS oneFaisal Adi Irawan, Ferry Efendi, Praba Diyan Rachmawati
BACKGROUND: Glue-sniffing among street-connected children and adolescents is a neglected public health and social issue with acute toxicity, entrenched stigma, and long-term life-course harms. In Merauke (South Papua), everyday practices, peer dynamics, and social labeling remain under-described. OBJECTIVE: To explore lived experiences of street-connected children and adolescents who use inhalants in Merauke, focusing on initiation, accessibility, peer processes, harms, return to glue use, and perceived stigma. METHODS: We conducted an inductive descriptive qualitative study with children and adolescents aged 12-18 years who reported glue use in the prior three months. Participants were recruited via gatekeeper-facilitated snowball sampling until information power indicated sufficiency. Data comprised semi-structured in-depth interviews (audio-recorded) and field notes; brief member checking closed each session and after the analysis. Transcripts were analyzed using inductive content analysis in NVivo 15. RESULTS: Twenty-two participants (19 male, 3 female) shared narratives; among the nine who recalled their age at initiation, first glue use occurred between 5 and 12 years. Participants reported inhaling commercially available adhesive products. Five categories emerged: (1) Early Exposure, Easy Access, and Peer Influence (Early Initiation, Easy Availability, and coercive invitations); (2) Everyday Glue Use and Its consequences (earmarking daily income for glue, polysubstance patterns, concealment, somatic/perceptual disturbances); (3) Social dynamics and peer support (in group solidarity, ambivalent community/enforcement responses, painful labeling); (4) Returning to the cycle (peer-triggered return, difficulty quitting, and strong attachment to glue); and (5) Hopes and multilevel strategies (age-gated sales and basic-needs support). CONCLUSIONS: Glue-sniffing in Merauke is sustained by permissive retail environments and peer-mediated cues set against structural deprivation. Effective prevention requires integrated policy, peer, service, and social-protection responses tailored to local contexts.
BACKGROUND: Alcohol use disorder (AUD) involves an impaired ability to stop or control alcohol use despite adverse consequences and represents a major public health problem. While AUD is most prevalent among college students, integrated evidence-based treatments for this population are lacking. OBJECTIVE: The objectives of our study were to test the feasibility and acceptability of a newly developed behavioral intervention, problem-solving therapy and Apple Watch (PST-APPLE), and to preliminarily investigate the effectiveness of PST-APPLE among college students with symptoms of AUD. METHODS: Participants were recruited through online advertising and on campus at universities in the Chicago area between May and September 2024. They were randomized in a 1:1 ratio using block randomization to the intervention group (PST-APPLE: n=12 individuals) or the control group (education-only: n=14 individuals), with the data analyst blinded to treatment assignment. Participants in the intervention group completed 12 weeks of the PST-APPLE intervention, delivered remotely via Zoom videoconferencing and interactions with the Apple Watch. Participants in the control group were asked to watch a 20-minute abstinence-motivation video and then participate in a 30-minute group discussion via Zoom. All participants completed follow-up assessments at 3 months. Outcomes included alcohol-related problems (Alcohol Use Disorders Identification Test [AUDIT] and Rutgers Alcohol Problem Index [RAPI]) and drinking motivation (Drinking Motives Questionnaire Revised [DMQR]). RESULTS: We enrolled 26 participants aged 18-25 years. The mean age was 22.5 (SD 2.20) years. We found reduced scores between preintervention and postintervention measures in the intervention group using 2-tailed paired t tests and baseline-adjusted analysis of covariance, including reduced alcohol misuse and problems (AUDIT and RAPI scores) and reduced DMQR social and coping motivation scores. Baseline-adjusted mean differences comparing the intervention with the control group showed reductions in alcohol use (AUDIT; mean difference -4.70, 95% CI -8.69 to -0.70) and in DMQR social motivation (mean difference -0.85, 95% CI -1.51 to -0.18) and enhancement motivation scores (mean difference -0.75, 95% CI -1.47 to -0.04). CONCLUSIONS: Our study findings indicate that the PST-APPLE intervention is feasible, acceptable, and hypothesis generating among college students with AUD. While findings are promising, this pilot study was not powered for definitive efficacy testing. A fully powered randomized controlled trial is needed to confirm these effects. Future studies could adapt PST-APPLE to other wrist-worn electronic devices/watches that capture physiological data (eg, Fitbit, Samsung Galaxy Watch) to increase reach and scalability, particularly among younger adults and digitally literate populations.
Translational psychiatrySimon Jangard, Joana B Vieira, Maria Å Garke, Olivia Ojala, Kristoffer N T Månsson, Maria Hedman-Lagerlöf, Karolina Sörman, Samir El Alaoui, Alexander Rozental…
Prosocial behavior, the tendency to act for others' benefit, is essential for mental health. Although social contexts strongly shape prosocial behavior in healthy individuals, its relevance across psychiatric disorders remains unclear. We examined whether context-dependent prosocial behaviors were associated with baseline psychiatric symptoms and longitudinal symptom trajectories. In a one-year longitudinal cohort study, Swedish adults (n = 4484) with at least one self-reported psychiatric disorder completed standardized questionnaires of six prosocial behavior subtypes at baseline, followed by monthly reports of alcohol use, substance use, anxiety, and depressive symptoms. Latent class linear mixed models identified longitudinal symptom trajectories, and logistic regression models investigated their associations with baseline prosocial behavior subtypes. All models adjusted for demographic covariates and shared variance across psychiatric symptom domains. Three prosocial behavior subtypes showed longitudinal associations with stable psychiatric symptom trajectory classes. Higher anonymous prosociality was associated with lower odds of belonging to the stable high alcohol use trajectory (OR = 0.89, p = 0.013). Higher public prosociality was associated with higher odds of belonging to the stable high substance use trajectory (OR = 1.15, p = 0.036). Higher emotional prosociality was associated with higher odds of belonging to the stable high anxiety trajectory (OR = 1.25, p < 0.001). No prosocial subtype was associated with depressive symptom trajectories. Overall, context-dependent prosocial behaviors were associated with persistent levels of alcohol use, substance use, and anxiety symptoms. These findings suggest that specific prosocial behaviors may refine transdiagnostic models of social dysfunction by indexing stable patterns of psychiatric symptom burden.
Myxoedema coma is a rare but life-threatening manifestation of hypothyroidism with high associated mortality. We present the case of a man in his sixties with known hypothyroidism and alcohol dependence who collapsed at home with profound hypothermia, refractory hypoglycaemia, hypoxia and reduced consciousness. Initial findings were easily attributable to excess alcohol; however, clinical features including periorbital oedema and bedside echocardiogram revealed moderate pericardial effusion, which prompted further investigation. Thyroid function tests confirmed severe hypothyroidism with elevated thyroid-stimulating hormone and suppressed free T3 and free T4 levels. Imaging revealed a substantial pericardial effusion and left basal pneumonia. The patient was treated with intravenous glucose, active warming, hydrocortisone and intravenous thyroxine along with antibiotics and supportive care. The patient achieved steady clinical and biochemical improvements following critical care admission. This case highlights the diagnostic challenge of recognising myxoedema coma and emphasises the importance of maintaining a high index of suspicion for endocrine emergencies.
Substance abuse treatment, prevention, and policyMohamed Baklola, Mohamed Terra, Mohammed Al-Azab, Ghada Elkhawaga, Najim Alshahrani
BACKGROUND: Substance use disorders (SUDs) represent a growing public health challenge in Saudi Arabia despite strict legal and social controls. Addiction management is primarily delivered through centralized inpatient and residential rehabilitation programs; however, the available evidence remains fragmented, and opportunities for healthcare technology integration have not been comprehensively synthesized. METHODS: A scoping review was conducted in accordance with the PRISMA-ScR guidelines to map addiction management and rehabilitation programs in Saudi Arabia and identify opportunities for healthcare technology integration. Comprehensive searches were performed across PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and supplementary sources from database inception to October 2025. Original empirical studies evaluating addiction treatment, rehabilitation, or aftercare services in Saudi Arabia were included. Data were systematically charted and synthesized using a descriptive thematic narrative approach. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Nine studies published between 1995 and 2024 met the inclusion criteria. The evidence demonstrated a progressive evolution from predominantly detoxification-focused services toward multidisciplinary rehabilitation models incorporating therapeutic communities and structured aftercare. Despite these advances, long-term retention remained limited, relapse and hospital readmission were common, and community-based rehabilitation was underrepresented. Social determinants, particularly unemployment, family conflict, and limited social support, consistently influenced rehabilitation outcomes. Healthcare technology integration was minimal, with electronic health records primarily used for retrospective analyses and no studies evaluating telehealth, mobile health applications, remote monitoring, or artificial intelligence-supported addiction care. Methodological quality was predominantly moderate, with three studies rated as high quality, five as moderate quality, and one as low quality. CONCLUSION: Although addiction rehabilitation services in Saudi Arabia have evolved toward more comprehensive multidisciplinary models of care, important gaps remain in long-term recovery support, community-based rehabilitation, standardized outcome monitoring, and digital health integration. Strengthening aftercare and adopting healthcare technologies may improve continuity of care, enhance recovery outcomes, and support the ongoing transformation of addiction services under Saudi Vision 2030.
Southern medical journalBrooke Benton, Thomas Snead, Shreya Visvanathan, Holeh Heydari, David Alexander Condra, Lori Moore, Nicole Lewis, Aleksandr Fuks, Martin Olsen
OBJECTIVE: The objective of this study was to evaluate the effect of intrauterine buprenorphine exposure during pregnancy on fetal head circumference. METHODS: This retrospective cohort study reviewed fetal ultrasound reports. Fetal anatomic surveys were typically performed at approximately 20 weeks' gestation. Patients administered medication-assisted treatment (MAT) for opioid use disorder commonly had follow-up estimated fetal weight scans at approximately 32 weeks' gestation due to risks of intrauterine growth restriction. A retrospective review of ultrasound reports for three groups of patients was performed. The very-low-dose (VLD) group (127 patients) was taking ≤2 mg buprenorphine in their third trimester; the traditional dose (TD) group (103 patients) received higher-dose MAT that was consistent with current recommendations. The control group, no buprenorphine use, included 212 patients. One-way analysis of variance and Tukey's multiple comparison tests were used for statistical analysis. The effect size was measured using ω2 [Formula: see text]. RESULTS: At the initial anatomy scan, no significant differences between groups were observed for head circumferences. By the third trimester growth scan, TD fetuses had significantly smaller head circumference percentiles compared with controls (P = 0.045). The estimated fetal weight percentile was lower in both buprenorphine groups compared with controls (VLD group vs controls, P = 0.021; TD group vs controls, P = 0.006), with TD fetuses showing the largest difference. Although TD head circumference percentiles were different from the controls, no significant differences were observed between the VLD group and either the TD group or controls for head circumference percentiles. CONCLUSIONS: Previous studies have shown decreased head circumference in newborns in association with maternal MAT. This is the first study to provide ultrasound confirmation of decreased head circumference in fetuses exposed to buprenorphine. VLD buprenorphine may be associated with more favorable fetal growth measures compared with a TD. Interventions during pregnancy, including lowest effective dose treatment, may preserve fetal brain growth and improve long-term neurodevelopmental outcomes.
Langenbeck's archives of surgerySolonas Symeou, Kevin Lee Boon Chun, Emmanouil Sinakos, Georgios Tsoulfas, Austin D Schenk
BACKGROUND: A 6-month abstinence period before listing patients with alcohol-related liver disease (ALD) for liver transplantation (LT) is the current standard practice at many transplant centers worldwide. Its prognostic validity is, however, debated because it has not been prospectively validated, and because many ALD patients do not survive long enough to make it onto the waitlist. METHODS: A meta-analysis was conducted in accordance with the guidelines put forth by Cochrane and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Three databases (PubMed/Medline, Scopus and Cochrane Library) were searched to identify studies comparing early (eLT) and standard LT (sLT). RESULTS: Twelve studies comparing eLT and sLT for ALD were included, encompassing 2323 patients with ALD. Mortality [Risk ratio (RR) = 0.94, 95% Confidence Interval (CI): 0.73-1.22] and patient survival [Hazard Ratio (HR) = 1.10, 95% CI: 0.83-1.45] did not differ significantly between eLT and sLT. Any alcohol relapse was more frequent following eLT but did not reach significance in the primary analysis (RR = 1.37, 95%CI: 0.95-2.00). This association became statistically significant on leave-one-out and subgroup analyses. Early LT patients had a higher risk of acute graft rejection (RR = 1.22, 95% CI: 0.98-1.52) but comparable graft loss (RR = 0.97, 95% CI: 0.74-1.27). Post-operative risk of infection did not differ significantly (RR = 1.19, 95% CI: 0.80-1.77), but eLT was associated with longer hospitalization [Mean Difference (MD) = 5.24 days, 95% CI: 0.15-10.33]. CONCLUSIONS: Early LT offers survival similar to sLT and is a reasonable option when medical therapy fails. However, the equivocal evidence of higher morbidity and alcohol relapse, and the longer hospitalization, support careful multidisciplinary selection and close post-transplant surveillance, particularly among recipients with alcohol-related hepatitis.
Archives of women's mental healthAna Vitória Corrêa Lima, Jéssica Lima De Oliveira Pinheiro Gaia, Divane De Vargas
BACKGROUND: Despite the increase in alcohol use among women worldwide, evidence on scalable, gender-responsive interventions remains limited, particularly in primary-care settings. This study evaluated the effectiveness of a nurse-delivered, telephonic brief intervention (BI) for reducing risky and harmful alcohol use among women. METHODS: This randomized controlled trial included 151 women recruited from four primary-care facilities in São Paulo, Brazil, who scored 8-19 on the Alcohol Use Disorders Identification Test (AUDIT). Participants were randomly assigned to an intervention group (IG), which received a nurse-delivered telephone BI, or a control group (CG), which received feedback only. The primary outcome was the change in AUDIT scores assessed longitudinally from baseline through 24 months of follow-up. RESULTS: In women receiving the telephonic BI, AUDIT scores significantly reduced during the first 6 months postintervention. Although this benefit was attenuated over longer-term follow-up, AUDIT scores in the control group followed an increasing trajectory over time. Race and household income were significantly associated with AUDIT scores; this suggests that socioeconomic factors may influence patterns of alcohol-related risk and intervention outcomes. CONCLUSIONS: A nurse-delivered telephonic BI produced meaningful short- to medium-term reductions in risky and harmful alcohol use among women in the primary-care setting. The attenuation of effects beyond 6 months suggests that a single brief intervention may be insufficient to sustain behavioral change over the long term and supports the evaluation of booster sessions or other low-intensity follow-up strategies. As a low-cost and scalable approach that can be integrated into routine primary care, telephonic BI may expand access to alcohol-related preventive care for women, particularly in resource-constrained settings. CLINICAL TRIAL NUMBER: RBR-6msv2kv.
JAMA health forumJessica Williams, Mia Kouveliotes, Nev Jones, Morgan C Shields
IMPORTANCE: While there is much research on stigma toward marginalized populations, public perceptions regarding deservingness of basic human and civil rights of these groups have not been examined in a nationwide sample of US adults. OBJECTIVE: To understand the US public's perceptions regarding deservingness of basic human and contested civil rights for people with severe physical disabilities (SPDs), severe mental illness (SMI), and substance use disorders (SUDs). DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was a nationwide US internet-based quota panel survey of US adults (aged ≥18 years) who completed the survey. Responses were collected from January 17 to February 12, 2025. MAIN OUTCOMES AND MEASURES: Participants rated their support for 5 human rights (adequate standard of living, high standards of health, legal capacity, freedom from torture, living independently) and 3 civil rights (being a parent, running for political office, owning a gun) for people with SPDs, SMI, and SUDs using a 5-point Likert scale, with marginalized subgroups presented to participants in randomized order. McNemar test for paired binary data was used to examine differences in mean support across subgroups, and linear probability regression models were used to identify demographic variables associated with support. RESULTS: In this survey of 1442 US adult participants (849 female [58.9%]; 588 male [40.8%]; 3 nonbinary [0.2%]; and 2 preferred not to say [0.1%]), the SPD subgroup received significantly higher support across all 5 human rights and 3 civil rights compared with SMI and SUD subgroups. For example, 79.0% (95% CI, 76.9%-81.2%) of participants supported the right to live independently for people with SPDs, while 67.0% supported this right for those with SMI (95% CI, 64.6%-69.5%) and 68.4% supported this right for those with SUDs (95% CI, 66.0%-70.9%). Civil rights received lower support across all 3 subgroups; for example, 40.1% (95% CI, 37.5%-42.6%) supported the right to run for political office for those with SMI and 41.4% (95% CI, 38.8%-44.0%) for those with SUDs compared with 62.7% (95% CI, 60.1%-65.2%) for those with SPDs. Democratic affiliation and lived experience with behavioral health care were associated with higher support for human rights (eg, among those with SUDs, up to 17.1 and 14.2 percentage points higher support, respectively). Male sex and younger age (18-24 years) were associated with greater support for civil rights (eg, male sex with 17.9 percentage points higher support for gun ownership among those with SPDs and age 18-24 years with a 27.1 percentage-point difference among those with SMI). CONCLUSIONS AND RELEVANCE: These findings contribute important evidence to the existing literature on stigma, highlighting discrepancies in public support for basic human and contested civil rights across marginalized subgroups, which can inform interventions to address public attitudes toward people with behavioral health conditions.
International journal of mental health nursingJofen Kihlström, Martin Salzmann-Erikson, Irene Hylander, Maria Lindberg
Adolescent substance use frequently co-occurs with mental-health difficulties and social adversity. Existing research highlights heterogeneous risk profiles and a paucity of integrated service models that bridge health- and social-care sectors. A qualitative case study was undertaken at the newly established MiniMaria treatment centre in Sweden. Data were gathered through participant observation of 18 steering-, project- and operative-group meetings, four workplace meetings, and semi-structured interviews with five staff members. Reflexive thematic analysis was applied iteratively, guided by a conceptual framework of collaborative advantage (power, trust, organizational culture, leadership, goal management). This study adheres to the Standards for Reporting Qualitative Research (SRQR) checklist. Four overarching themes emerged: (1) divergent organizational cultures and power; (2) fragmented goal management; (3) fluctuating trust and leadership; and (4) operational-level impact on staff. Middle-management pragmatism compensated for strategic indecision, sustaining service delivery despite resource constraints (for instance absence of a dedicated physician). The MiniMaria project demonstrates that clear, enforceable governance structures are vital for integrated youth services. When senior-level alignment falters, empowered front-line managers can preserve continuity of care, but the sustainability of such models hinges on explicit memoranda, shared information systems and ongoing cultural monitoring.
European journal of sport scienceP Sampedro-Piquero, A Cordellat-Marzal, M Dragotti, L Mandolesi, O Gigliotta, R D Moreno-Fernández
Alcohol craving is a key process in alcohol abuse, especially during young adulthood, a period of heightened vulnerability and continued brain development. Although acute physical exercise has been proposed as a potential strategy to reduce craving and modulate affective and cognitive processes, current evidence remains limited regarding its effectiveness and underlying mechanisms. This systematic review examined the effects of brief exercise interventions on alcohol craving in young adults with problematic alcohol use or alcohol use disorder (AUD) and explored available evidence on associated neurobiological responses. Four electronic databases were searched for studies published between 2016 and 2026 following PRISMA guidelines. The review protocol was registered in PROSPERO (CRD420261371036). Eligible studies included participants aged 18-29 years and assessed alcohol craving following a single bout of exercise. Random-effects meta-analyses using Hedges' g were conducted when sufficient data were available, while additional outcomes were synthesized narratively. Six studies met the inclusion criteria. Meta-analysis showed a moderate and statistically significant reduction in alcohol craving following acute exercise compared with baseline or control conditions (g ≈ 0.55), with moderate between-study heterogeneity. Narrative findings indicated that acute exercise was often accompanied by reductions in anxiety and negative affective state, modulation of stress-related physiological markers, improvements in executive functioning, and changes in indices of brain and autonomic activity, although findings varied across studies. Overall, available evidence suggests that a single session of physical exercise may be associated with short-term reductions in alcohol craving in young adults, highlighting the need for further clinically focused and methodologically robust research.
American journal of public healthAvijit Mitra, Richeek Pradhan, Kirsha S Gordon, Haijuan Yan, Robert D Kerns, William C Becker, Hong Yu
Objectives. To examine associations between opioid overdose (OOD) deaths among veterans and natural language processing (NLP)‒enriched social determinants of health (SDOH). Methods. We conducted a nested case‒control study using a cohort (n = 6 854 031) from the US Veterans Health Administration database with any record of service between October 2017 and September 2021. Participants were followed for up to 2 years from cohort entry, ending in September 2021. An NLP system extracted 8 SDOHs from unstructured notes, while structured data captured 6, yielding 9 distinct SDOHs with 5 common to both. Results. A total of 5411 veterans experienced fatal OOD over 21 397 462 person-years of follow-up and were matched with 21 623 controls. NLP-extracted SDOHs captured 90.08% of structured and 97.28% of all SDOHs. All measured SDOHs were significantly associated with increased risk of fatal OOD. The strongest association was for housing instability (adjusted odds ratio [AOR] = 3.36; 95% confidence interval [CI] = 2.96, 3.81), followed by legal problems (AOR = 3.07; 95% CI = 2.55, 3.70) and financial problems (AOR = 2.63; 95% CI = 2.32, 2.98). Conclusions. NLP-extracted SDOHs were significantly associated with fatal OOD risks among veterans and exhibited comparable direction and magnitude of association to structured SDOHs. (Am J Public Health. 2026;116(10):1575-1585. https://doi.org/10.2105/AJPH.2026.308697).
Pharmacoepidemiology and drug safetyChristopher T Rentsch, Vanessa A Palzes, Mingjian Shi, Michael R Setzer, Samantha G Malone, Andrea H Kline-Simon, Emma L Winterlind, Lorenzo Leggio, Vincent Lo…
PURPOSE: Alcohol use disorder (AUD) remains a major public health problem, with few effective treatments. L-type calcium channel blockers (LTCCBs) have genetic and preclinical support as potential treatments for AUD. METHODS: We evaluated whether brain penetrant (BP)-LTCCBs are associated with reduced alcohol consumption in two preregistered observational cohort studies using electronic health records from the US Department of Veterans Affairs (VA) and Kaiser Permanente Northern California (KPNC). New users of BP-LTCCBs (nifedipine or felodipine) were compared with new users of a non-BP-LTCCB (amlodipine) and with unexposed patients from the same clinics, requiring a 180-day washout and ≥ 60 days' supply. Propensity score matching was performed across all exposure contrasts. The primary outcome was change in drinks per week from pre-index to end of follow-up using difference-in-differences (DiD) models, with prespecified subgroup analyses by AUD diagnosis, drinking level, and sex. RESULTS: Across both health systems, BP-LTCCB initiation was not associated with greater reductions in drinks per week than either comparator, with broadly consistent findings across all subgroups; though some subgroups were small and imprecise. In the VA, the DiD comparing BP-LTCCB with non-BP-LTCCB was 0.14 drinks/week (95% CI -0.06, 0.34), and versus unexposed was 0.00 (95% CI -0.18, 0.19). Similar results were observed in KPNC (BP-LTCCB vs. non-BP-LTCCB: 0.31, 95% CI -0.48, 1.11; BP-LTCCB vs. unexposed: 0.16, 95% CI -0.67, 0.99). CONCLUSIONS: In two large, preregistered EHR-based cohorts, we found no evidence that BP-LTCCBs were associated with reduced drinking relative to comparators. Despite compelling genetic and preclinical evidence, these findings do not support repurposing BP-LTCCBs for AUD and instead prioritize alternative pharmacologic targets.
Health affairs (Project Hope)Anna C Holdiman, Dale S Mantey, Tim Mercer, Alexander Testa, Shreya Jain, John Embers-Weems, Kasey Claborn, Justin Benzer
Timely access to substance use disorder (SUD) treatment is critical to improving health outcomes, yet treatment delays remain a barrier. Using national Treatment Episode Data Set-Admissions data from the period 2017-22, we conducted the first national study to examine the association of referral pathways and housing status with treatment delays among 962,702 first-time SUD admissions. Compared with individual referrals, criminal legal referrals were associated with more than twice the odds of delayed admission. This association differed by housing status and was strongest among people experiencing homelessness. These findings suggest that homelessness may intensify barriers to timely SUD treatment for people referred via criminal legal referral pathways. Our results are concerning in light of the 2025 executive order, "Ending Crime and Disorder on America's Streets," which emphasizes the use of civil commitment and institutionalization for people experiencing homelessness and people with SUD. To improve treatment retention and reduce substance use, policy efforts should prioritize removing administrative and legal barriers to SUD treatment. Low-threshold treatment models and treatment with low barriers to participation should be expanded.
Alcohol, clinical & experimental researchShannon D Glenn, Michael A Russell, Robert J Turrisi, Veronica L Richards
BACKGROUND: Alcohol use is necessary-but not sufficient-for understanding why individuals experience an alcohol-induced blackout (AIB). Drinking motives are one of the most proximal risk factors for alcohol use. This study conducts a comprehensive within-person examination of AIBs predicted by prospective daily reports of drinking motives and alcohol use measured using a transdermal alcohol concentration (TAC) biosensor. METHODS: Participants were young adults who engaged in risky drinking and experienced at least 1 AIB in the past 3-months (N = 169, Mage = 20.8, 53% female, 87% White, 10% Hispanic). They wore TAC biosensors and completed twice daily surveys about drinking motives and AIBs over six social weekends (i.e., Thursday-Sunday). TAC drinking features (peak, rise rate, and rise duration) were extracted from TAC data for each day. Two-level multilevel structural equation models were conducted to examine the associations between drinking motives, latent intoxication estimated from TAC features, and AIBs. Aim 1 examined separate models for each motive (enhancement, social, coping, conformity). Aim 2 examined a single model with each motive adjusting for the others. RESULTS: In Aim 1, on days when participants reported higher enhancement, social, coping, and conformity motives, the associated increase in TAC intoxication was associated with increased odds of experiencing an AIB. In Aim 2, when all motives were entered into a single model, only social motives resulted in increased TAC, which subsequently increased the odds of an AIB occurring. CONCLUSIONS: Findings demonstrate that days when an individual reports above average drinking motives relative to their own average, they are at increased risk of engaging in riskier drinking, which may result in subsequent AIBs. These findings suggest that daily changes in drinking motives may be an important intervention pathway for preventing risky drinking and subsequent AIBs.
Health promotion journal of Australia : official journal of Australian Association of Health Promotion ProfessionalsElizabeth Paton, Jennifer Peprah, Dara Sampson, Jaelea Skehan
ISSUE ADDRESSED: How people communicate about suicide, mental health concerns and alcohol and other drug (AOD) concerns matters. The words and images used can reinforce or reduce shame and stigma, or impact help-seeking and help-offering behaviours. In some cases, how people communicate may increase or decrease suicidal behaviour in Australia communities. METHODS: This paper outlines findings from an Australian Delphi survey to find consensus on what constitutes best practice advice for communicating about mental health concerns, suicide, and AOD concerns. Three panels, including a panel of people with lived experience, were used by the researchers to achieve consensus amongst those considered experts where evidence and consistency was lacking. RESULTS: Consensus ratings and qualitative feedback were received from 40 experts across two Delphi survey rounds. In total, 70 of 106 statements were endorsed for inclusion in guidelines for image or language use relating to mental health, mental health concerns, suicide and AOD concerns. CONCLUSIONS: Consensus ratings and qualitative feedback provided clear, broad-level guidance that formed the foundation for two new sets of guidelines. This builds on existing language focused guidelines to deliver updated and evidence-informed guidelines for use in the media as well as other sites of communication where people may be exposed to harmful or helpful words and images. SO WHAT?: These new guidelines are designed to help Australian communities to communicate safely and sensitively, and with a more coherent voice, about suicide, mental health concerns and AOD concerns. In turn, they contribute to broader efforts to reduce stigma and distress across Australian communities.
Individuals with fetal alcohol spectrum disorders exhibit impaired auditory processing and atypical auditory behaviors across the disorder's spectrum. Although low to moderate prenatal alcohol exposure (PAE) is a prevalent type of exposure, the developmental trajectory of auditory processing deficits resulting from this level of exposure remains unknown. To examine the effects of PAE in the auditory system, we utilized the maternal voluntary alcohol consumption paradigm to model chronic low to moderate PAE throughout gestation. We measured auditory brainstem responses (ABRs) in juvenile mice (postnatal day 16-19) and longitudinally across early adolescence (4-5 weeks), late adolescence (7-8 weeks), and young adulthood (12-14 weeks). ABR abnormalities were first observed in juvenile PAE mice. The effects of PAE on brainstem auditory processing were most prominent in early adolescence, largely dissipated in late adolescence, and showed a reemergence in early adulthood. PAE mice showed elevated ABR thresholds, prolonged wave latencies, and reduced wave amplitudes. Ratios of ABR peak 3 relative to the first ABR peak indicated that the auditory brainstem pathways were hyperactive in PAE mice. The amplitude ratio was found to be elevated from early adolescence to early adulthood, suggesting that PAE has a persistent effect on auditory processing. We found a significant correlation between the amplitude ratios in early adolescent PAE mice and dam ethanol consumption, which point toward dose-dependent brainstem gain dysregulation. Our study shows multilevel auditory alterations highlighting the vulnerability of central auditory pathways to PAE and fills an important gap in understanding auditory processing deficits in a clinically relevant exposure model.
Liver international : official journal of the International Association for the Study of the LiverNiharika Jakhar, Tobias Seibel, Maria Mironova, Corinna Meeßen, Jan Clusmann, Yazhou Chen, Thriveni B Raju, Paul-Henry Koop, Juliette E Pearce, Ivan G Costa, T…
BACKGROUND AND AIMS: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most prevalent liver disease, yet accurate early detection remains challenging. A particular diagnostic obstacle is distinguishing MASLD from metabolic dysfunction and alcohol-related liver disease (MetALD), currently defined using clinically informed moderate alcohol consumption thresholds without biological validation. This study aimed to identify and externally validate plasma proteomic signatures associated with MASLD and assess whether proteomic profiles support a molecular distinction between MASLD and MetALD as currently defined. METHODS: We analysed plasma proteomic profiles using OLINK data from UK Biobank (UKB) participants with liver MRI. MASLD was defined as MRI-PDFF ≥ 5% and metabolic dysfunction (n = 165), MetALD (n = 46) as MASLD with additional moderate alcohol intake and controls as PDFF < 5% (n = 741). RESULTS: Compared to controls, participants with MASLD showed 17 upregulated and 3 downregulated proteins after Bonferroni correction (adjusted p < 0.05). Among upregulated proteins, leptin (LEP), fatty acid-binding protein, liver (FABP1) and aminoacylase1 (ACY1) and among downregulated, insulin-like growth factor-binding protein 1 (IGFBP1) were externally validated in an independent cohort (clinicaltrials.gov NCT02520609, n = 47). Individuals with MetALD showed no significant proteomic distinction from MASLD. Although the small MetALD sample size may have limited detection of differences, direct differential expression analysis did not identify statistically significant differences between MASLD and MetALD under the current clinical thresholds. CONCLUSIONS: MASLD was associated with a reproducible plasma proteomic signature enriched for proteins involved in lipid metabolism, inflammation and hormonal regulation. We did not identify a clear proteomic distinction between MASLD and MetALD under the current alcohol thresholds. However, this finding should be interpreted considering limited power and potential alcohol-exposure misclassification.
JAMA network openAhra Kim, Andrew D Wiese, Sarah Osmundson, Chad You, Carlos G Grijalva, Margaret A Adgent, Alexandra C Sundermann, Andrew J Spieker, Amelie Pham, Stephen W Pat…
IMPORTANCE: Overdose is the leading cause of maternal mortality in the US, yet evidence on how medications for opioid use disorder (MOUD) affect postpartum overdose and mortality risk is limited. It is unclear whether cumulative MOUD exposure during this period reduces overdose or death beyond 90 days post partum. OBJECTIVE: To examine whether longer duration of MOUD dispensed during pregnancy and early post partum is associated with reduced overdose or death through 365 days post partum. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective cohort study of individuals delivering between 2007 and 2020, assessed through 1 year post partum or until the first outcome, through 2021. The study used Tennessee Medicaid (TennCare) data linked to vital records (birth and death certificates) and Tennessee Hospital Discharge Data. Participants were individuals aged 15 to 44 years with at least 1 day of dispensed MOUD during the exposure window (90 days before to 41 days after delivery), a delivery at least 20 weeks' gestation, and continuous TennCare enrollment during the exposure period. Data were analyzed from July 2024 to July 2026. EXPOSURE: Total unique, nonoverlapping days of dispensed MOUD (buprenorphine and/or naltrexone) from 90 days before delivery through 41 days after delivery, with overlapping fills deduplicated so each calendar day was counted only once. MAIN OUTCOMES AND MEASURES: The primary outcome was the first occurrence of all-cause death or overdose (opioid or nonopioid) from inpatient, outpatient, and emergency department claims 42 to 365 days post partum. Multivariable Cox proportional hazards models were used to estimate the association between MOUD days' supply and risk of death or overdose, adjusting for maternal and clinical characteristics. RESULTS: The cohort included 9360 pregnancies among 7776 individuals (median [IQR] age at delivery, 27 [24-31] years). The 1-year postpartum risk of death or overdose was 1.58% (148 individuals), with a median (IQR) time to event of 186.5 (92.5-258.8) days. The median (IQR) MOUD duration during the 132-day exposure period was 88 (43-111) days. Longer MOUD duration was associated with lower risk of death or overdose, with the lowest hazard at 132 days' supply (adjusted hazard ratio for 132 vs 1 day, 0.52; 95% CI, 0.31-0.88). CONCLUSIONS AND RELEVANCE: Longer duration of MOUD receipt during pregnancy and early post partum was associated with lower risk of overdose or death in the first year post partum, underscoring the importance of supporting continuous MOUD treatment during this period.
Journal of neuroendocrinologyViolet M Kimble, Mary Zanda, Hayde Sanchez, Clare Flannery, Jane R Taylor, Anjali Rajadhyaksha, Nii A Addy
Social withdrawal during cocaine abstinence is a significant predictor of relapse, yet the neuroendocrine mechanisms underlying this vulnerability remain poorly understood, particularly in females. Estradiol, a potent neuromodulator of mesocorticolimbic circuitry, regulates dopamine-dependent processes that encode social motivation. L-type calcium channels (LTCCs) similarly regulate neuronal excitability and plasticity in corticolimbic regions implicated in addiction and affective regulation, and estradiol interacts with LTCC signaling through both membrane-initiated and transcriptional mechanisms. However, whether estradiol and LTCCs functionally converge to regulate social behavior during cocaine abstinence is unknown. Here, we used a preclinical behavioral pharmacology approach to examine this interaction in female Sprague-Dawley rats. Ovariectomized (OVX) rats with or without 17β-estradiol replacement underwent jugular catheterization and self-administered cocaine (0.5 mg/kg/inf, FR1) or saline for 10 days, followed by 17 days of forced abstinence. Social preference was assessed using a three-chamber social interaction test, with systemic isradipine (1.2 mg/kg, i.p.) administered 15 min prior to testing. Cocaine abstinence significantly reduced social preference in intact females. LTCC blockade with isradipine restored social preference, but this effect was dependent on ovarian hormone status: isradipine normalized social behavior in sham-operated and OVX + E2 rats but not in OVX rats lacking estradiol. Multiple linear regression confirmed that ovarian hormone status and isradipine treatment, but not total cocaine intake, significantly predicted social preference, with a robust hormone × isradipine interaction explaining 44.6% of behavioral variance. These findings demonstrate that estradiol does not simply protect against abstinence-related social deficits but rather biases neural signaling such that social behavior becomes sensitive to LTCC-dependent mechanisms. This work identifies a functional estradiol-LTCC interaction regulating social motivation during cocaine abstinence and highlights the importance of hormonal state in shaping sex-specific addiction vulnerability.
Journal of the American Board of Family Medicine : JABFMOmolola E Adepoju
Telemedicine for opioid use disorder (teleOUD) represents a critical opportunity to expand access to evidence-based treatment while reducing stigma and structural barriers that have long impeded recovery. Yet, gaps persist in awareness, education, and trust among both clinicians and patients. Family medicine, grounded in continuity, collaboration, and community-centered care, is uniquely positioned to close these gaps. By embedding teleOUD education into training programs, normalizing its use in primary care, and fostering interprofessional partnerships, family physicians can transform how OUD is treated and perceived. As teleOUD becomes an integral part of care delivery, the challenge ahead is not only technological adoption, but rebuilding trust, reshaping clinical culture, and ensuring that every patient can access treatment without fear or stigma.
American journal of public healthKarli R Hochstatter, Talia Nadel, Raavi Gupta, Anubhav Jangra, Nicole D'Anna, Jan Gryczynski, Yuxin Li, Jason Graham, Hannah Johnson, Nabila El-Bassel, Ziqing …
Objectives. To develop and evaluate human-centered artificial intelligence (AI) models that identify suspected overdose deaths using narrative reports from medicolegal death investigations and describe ethical considerations for using AI in overdose surveillance. Methods. We trained AI models using 2022-2023 data from the New York City Office of Chief Medical Examiner (OCME). Narrative death investigation reports (n = 9263) were analyzed using a 2-step pipeline that first extracted textual evidence for 18 expert-defined indicators of overdose and then predicted overdose using 2 large language model families: LLaMA-8B-Instruct and ClinicalModernBERT. Domain experts provided feedback throughout model development, and safeguards were implemented to protect confidentiality and evaluate algorithmic bias. Results. The LLaMA-8B-Instruct model achieved 88% positive predictive value (PPV), 92% sensitivity, 84% negative predictive value (NPV), 76% specificity, and 85% macro-F1. The ClinicalModernBERT model achieved 83% PPV, 92% sensitivity, 82% NPV, 67% specificity, and 81% macro-F1. Both AI models outperformed OCME's existing surveillance tool and conventional logistic regression approaches. Conclusions. Human-centered AI may support timely and accurate overdose surveillance, but responsible implementation requires expert oversight, a privacy-compliant infrastructure, and ongoing evaluation of potential bias. (Am J Public Health. 2026;116(10):1565-1574. https://doi.org/10.2105/AJPH.2026.308698).
Liver international : official journal of the International Association for the Study of the LiverClara Juul Stenderup, Margarita Dudina, Kirstine Kobberøe Søgaard, Morten Daniel Jensen, Peter Jepsen
BACKGROUND & AIMS: Liver cirrhosis is associated with an increased risk of bacterial infections, but there is a lack of reliable population-based data to quantify this risk. We examined the incidence and predictors of community-acquired serious systemic infections. METHODS: This was a population-based study that included all patients in the Central Denmark Region diagnosed with alcohol-related cirrhosis (ALD cirrhosis) in 2013-2022. We computed the cumulative incidence of community-acquired serious systemic infections, encompassing sepsis and bacteraemia. We used Fine & Gray regression to investigate predictors of infection within the first year. RESULTS: We included 2511 patients with ALD cirrhosis (69.3% males, median age 61 years, median MELD-NA score 13). Their cumulative risk of a first-time community-acquired serious systemic infection was 3.8% (95% CI: 3.1-4.6) after 1 year and 5.9% (95% CI: 5.0-6.9) after 3 years. The most frequent causative pathogens were Enterobacterales (38%), Staphylococci (25%) and Streptococci (22%). Increasing MELD-Na score at cirrhosis diagnosis was associated with an increased risk of serious systemic infection within the first year after diagnosis (subdistribution hazard ratio = 1.05, 95% CI: 1.02-1.08, per 1 point increase). The 30-day all-cause mortality was 30% (95% CI: 23-37) following hospitalization with a serious systemic infection. CONCLUSIONS: This population-based study determined the risk and mortality of serious systemic infections in ALD cirrhosis. Our findings will be important for future studies of interventions to prevent infections.
Australian health review : a publication of the Australian Hospital AssociationChampika Pattullo, William Dace, Anita Pelecanos, Gerben Keijzers, Peter Donovan
OBJECTIVE: Chronic opioid use can develop in previously opioid-naïve patients following an emergency department (ED) or hospital admission; however, most evidence is from North America. This study aims to assess the prevalence of persistent opioid use after an ED presentation in an Australian setting. METHODS: This was a population-based, retrospective cohort study using state-based linked data. Persistent opioid use was defined as continued use after 12 months, among previously opioid-naïve patients who filled an opioid prescription following discharge from any Queensland public hospital ED between 1 January 2011 and 31 December 2017. Descriptive statistics were used to summarise demographic characteristics of the study population and to outline primary outcome measures. RESULTS: There were 3,082,681 ED presentations during the study period, and 11,281,039 opioid prescriptions within 12 months of the ED presentations included in the study. A total of 186,545 opioid-naïve patients had an opioid prescription associated with their ED presentation, with more prescriptions in 2017 (34,273) compared with 2011 (14,896), driven predominantly by oxycodone prescription increases. However, of the total cohort, only 3539 (1.9%) were classified as persistent opioid users, with similar annual proportions seen throughout the study period. CONCLUSION: The proportion of patients progressing to persistent opioid use after ED presentation was low and remained relatively stable, despite a substantial increase in the number of patients receiving at least one opioid prescription after an ED presentation. These results highlight the need for continued focus on appropriate prescribing and patient safety.
Basic & clinical pharmacology & toxicologyJanina Salmelainen, Miia Tiihonen, Heidi Taipale, Johannes Lieslehto, Antti Tanskanen, Jari Tiihonen, Aleksi Hamina
Pharmacotherapy may reduce overall suicide risk in bipolar disorder, but prescribed medicines can also be causative agents in suicidal and accidental poisonings. This nationwide, nested case-control study utilized data from several national registers in Finland in 1996-2018. In a cohort of 60 045 individuals aged 15-65 with bipolar disorder, cases with fatal poisoning due to medicines or illicit substances were matched by age and sex to four controls each. The association between fatal poisoning and medicine use in the prior 2 weeks was examined using conditional logistic regression. The 777 (1.3%) cases who died of poisoning due to medicines or illicit substances during the study period were matched to 3108 controls. Of cases, 56.5% (n = 439) died of a suicidal poisoning and 38.4% (n = 298) of an accidental poisoning. After adjusting for sociodemographic characters, comorbidities and other medicine use, tricyclic antidepressants (aOR 3.07, 95% CI 2.09-4.50), gabapentinoids (3.05, 2.08-4.47), opioids (2.65, 1.88-3.75), benzodiazepines (2.13, 1.71-2.64), Z-drugs (2.19, 1.66-2.88) and antipsychotics (1.94, 1.56-2.40) were associated with fatal poisonings. While the associations may reflect clinical severity of the disorder among users of these medicines, increased caution is warranted when prescribing them to individuals at elevated risk of poisoning.
Addiction biologySabine Hoffmann, Iris Reinhard, Christiane Mühle, Patrick Bach, Leonard Wenger, Dominic Reichert, Rafat Boroumand-Jazi, Sibel Nayman, Christine Kuehner, Matthi…
Alcohol use disorder (AUD) causes a high burden worldwide. The menstrual cycle and the progesterone-to-estradiol ratio are related to alcohol consumption in females and males with AUD. However, the underlying mechanisms triggering problem drinking in everyday life remain to be determined. This longitudinal multicentre study analysed associations of menstrual cycle phases (1316 of 70 naturally cycling females with AUD) and progesterone-to-estradiol ratios (quantified in 567 blood samples of 256 males with AUD) with real-world 12-month data on loss of control over alcohol consumption and craving measured via 17296 and 10482 smartphone entries using general linear mixed models. Females with severe AUD stated less frequent loss of control in the midluteal and late luteal phases characterized by high progesterone-to-estradiol ratios compared to the follicular phase. In the total female sample, craving was lower during the late luteal and menstrual phases compared to the follicular phase. Similarly, males with moderate and severe AUD reported less frequent loss of control in phases of a high progesterone-to-estradiol ratio. The identified biobehavioural interplay suggests that increasing progesterone relative to estradiol may assist individuals with AUD in re-establishing control over alcohol consumption and reducing craving. When employed in conjunction with customized just-in-time adaptive digital interventions, this approach has the potential to evolve into a novel precision medicine strategy for AUD. The findings also underscore the necessity for the development of treatments tailored to the phases of the menstrual cycle, thereby addressing the critical underrepresentation of females in AUD research.
CNS neuroscience & therapeuticsCheng Zhang, Hu Li, Ming-Fen Ho
AIMS: Opioid use disorder remains a major public health crisis in the United States, driven largely by rising overdose deaths from synthetic opioids, such as fentanyl. Emerging population-level evidence suggests that GLP-1 receptor agonists (GLP-1RAs) may reduce overdose risk. However, their underlying molecular mechanisms are not well understood. We investigated the transcriptional effects of fentanyl and GLP-1RAs using human induced pluripotent stem cell (iPSC)-derived forebrain organoids and neurons. METHODS: Organoids were treated with fentanyl, liraglutide, or exenatide, followed by RNA sequencing. We extended these analyses to iPSC-derived neurons exposed to additional therapeutic candidates, including the anticonvulsants topiramate and gabapentin, and the metabolic modulator β-hydroxybutyrate. All compounds were tested at clinically relevant concentrations, and transcriptomic and functional genomic assays were performed. RESULTS: Across models and drug classes, we identified modulation of endoplasmic reticulum (ER) stress signaling as a shared molecular mechanism. Fentanyl and GLP-1RAs consistently downregulated ER stress-related genes, with TRIB3 as the most strongly suppressed target. We further identified CEBPB as a key upstream regulator and confirmed reduced CEBPB DNA-binding activity in ER stress-related genes. CONCLUSION: These findings highlight ER stress modulation as a convergent pathway with potential therapeutic relevance for substance use disorders.
JAMA network openScott E Hadland, Ijeoma Opara, Vicki Fung, Dandi Dong, Sitara Weerakoon, Jonathan Rodean, Marie-Abèle C Bind, Bonnie T Zima, Meredith Glass, Margarita Alegría,…
IMPORTANCE: One in 100 adolescents and young adults (hereafter "youths") in the US has an opioid use disorder (OUD), yet little is known about the extent to which they receive care aligned with national quality measures. OBJECTIVE: To evaluate progression through the OUD cascade of care (COC) among Medicaid-enrolled youths, with key stages of treatment aligned with national quality measures. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used enrollment and health insurance claims from all US states and Washington, DC, from the 2016-2023 Transformed Medicaid Statistical Information System Analytic Files. Participants had OUD and were aged 13 to 25 years. Data were analyzed from November 3, 2025, to July 24, 2026. EXPOSURES: Diagnosis of OUD and receipt of addiction treatment, including behavioral health services and medications for OUD (MOUD; buprenorphine, methadone, or extended-release naltrexone). MAIN OUTCOMES AND MEASURES: Progression through COC stages aligned with national quality measures: treatment initiation, engagement, MOUD receipt, and 180-day MOUD retention. RESULTS: Among 229 847 youths with OUD enrolled in Medicaid (median age, 22 [IQR, 20-24] years; 117 920 females [51.3%]), 116 458 (50.7%) initiated treatment within 14 days of diagnosis, and 75 614 (32.9%) engaged in care (ie, had 2 or more additional treatment encounters within 34 days of treatment initiation). Among the 75 614 youths who engaged in treatment, 35 011 (46.3%) received MOUD, representing 15.2% of all 229 847 youths with OUD. However, only 554 of 8352 adolescents younger than 18 years who engaged in treatment received MOUD (6.6%), compared with 34 457 of 67 262 young adults 18 years and older (51.2%). Buprenorphine was the most initiated medication (n = 23 990 of 35 011 [68.5%]), followed by methadone (n = 8911 [25.5%]) and extended-release naltrexone (n = 2110 [6.0%]). Overall, only 7070 of 229 847 youths (3.1%) continued medication for 180 days or more. Among youths receiving MOUD, retention was highest for methadone (n = 2334 of 8911 [26.2%]), followed by buprenorphine (n = 4613 of 23 990 [19.2%]) and extended-release naltrexone (n = 123 of 2110 [5.8%]). Median time receiving MOUD varied by medication: methadone, 59 days (IQR, 15-189 days); buprenorphine, 45 days (IQR, 18-128 days); and extended-release naltrexone, 31 days (IQR, 28-82 days) (log-rank test, P < .001). Younger adolescents aged 13 to 15 years and racially minoritized youths had consistently lower progression through the COC. CONCLUSIONS AND RELEVANCE: In this cohort study of Medicaid-enrolled youths with OUD, most did not receive timely, evidence-based treatment, and only 1 in 32 received sustained pharmacotherapy. Gaps and persistent disparities exist across the COC, particularly for youths of color, underscoring the need for policies and care models that expand equitable treatment access.