Sleep features in alcohol use disorder: A systematic review and meta-analysis of polysomnographic findings in case-control studies

Background and objectives Alcohol use disorder (AUD) is often linked to sleep problems, but previous studies on sleep abnormalities in AUD have produced inconsistent results. This study aims to provide a comprehensive analysis of objectively measured sleep abnormalities in AUD and determine the impact of related and demographic factors on sleep disturbance. Methods We conducted a comprehensive search of several databases from 1968 to 2023 to identify relevant studies. A total of 12 studies, consisting of 13 datasets, were included in the analysis. We extracted information on sleep microarchitecture, as well as demographic and clinical features, from each study. The GRADE approach was used to assess the reliability and strength of the evidence. Results Patients with AUD exhibited several sleep abnormalities, including longer sleep onset latency, lower sleep efficiency, increased stage 1 sleep, decreased stage 2 sleep, reduced slow wave sleep, and elevated rapid eye movement (REM) sleep density and first REM minute. The sleep patterns in individuals with AUD were also influenced by factors such as ethnicity, age, gender, and abstinence period. Conclusions This study is the largest quantitative assessment of impaired sleep as a diagnostic marker in patients with AUD. Understanding the sleep patterns of individuals with AUD can assist clinicians in developing effective treatment plans for managing sleep-related symptoms associated with AUD. (AU)

Hepatology consultation is associated with decreased early return to alcohol use after discharge from an inpatient alcohol use disorder treatment program.

BACKGROUND: Alcohol cessation is the only intervention that both prevents and halts the progressions of alcohol-associated liver disease. The aim of this study was to assess the relationship between a return to alcohol use and consultation with hepatology in treatment-seeking patients with alcohol use disorder (AUD). METHODS: Two hundred forty-two patients with AUD were enrolled in an inpatient treatment program, with hepatology consultation provided for 143 (59%) patients at the request of the primary team. Patients not seen by hepatology served as controls. The primary outcome was any alcohol use after discharge assessed using AUDIT-C at 26 weeks after discharge. RESULTS: For the primary endpoint, AUDIT at week 26, 61% of the hepatology group and 28% of the controls completed the questionnaire (p=0.07). For the secondary endpoint at week 52, these numbers were 22% and 11% (p = 0.6). At week 26, 39 (45%) patients in the hepatology group versus 31 (70%) controls (p = 0.006) returned to alcohol use. Patients evaluated by hepatology had decreased rates of hazardous alcohol use compared to controls, with 36 (41%) versus 29 (66%) (p = 0.008) of the patients, respectively, reporting hazardous use. There were no significant differences in baseline characteristics between groups and no difference in rates of prescribing AUD therapy. There was no difference in outcomes at 52 weeks. CONCLUSIONS: Patients evaluated by hepatology had significantly lower rates of return to alcohol use and lower rates of hazardous drinking at 26 weeks but not at 52 weeks. These findings suggest that hepatology evaluation during inpatient treatment of AUD may lead to decreased rates of early return to alcohol use.

Positive allosteric modulators of the GABAB receptor: a new class of ligands with therapeutic potential for alcohol use disorder.

BACKGROUND: Positive allosteric modulators (PAMs) of the GABAB receptor constitute a new class of GABAB-receptor ligands. GABAB PAMs reproduce several pharmacological effects of the orthosteric GABAB receptor agonist, baclofen, although displaying a better safety profile. AIMS: This paper reviews the reducing or, frequently, even suppressing effects of all GABAB PAMs tested to date on multiple alcohol-related behaviours in laboratory rodents exposed to validated experimental models of human alcohol use disorder. RESULTS: Acute or repeated treatment with CGP7930, GS39783, BHF177, rac-BHFF, ADX71441, CMPPE, COR659, ASP8062, KK-92A, and ORM-27669 reduced excessive alcohol drinking, relapse- and binge-like drinking, operant alcohol self-administration, reinstatement of alcohol seeking, and alcohol-induced conditioned place preference in rats and mice. CONCLUSIONS: These effects closely mirrored those of baclofen; notably, they were associated to remarkably lower levels of tolerance and toxicity. The recent transition of ASP8062 to clinical testing will soon prove whether these highly consistent preclinical data translate to AUD patients.

Keeping you connected or keeping you addicted? Weekly use of social media platforms is associated with hazardous alcohol use and problem gambling among adults.

AIMS: A wide variety of social media platforms exist, each offering tailored solutions to attract specific target audiences based on their social media needs and interests. This diversity may pose a risk factor for the development or perpetuation of harmful behaviors. Research has established a connection between social media use and increased health risk behaviors. This six-wave exploratory longitudinal study investigated the associations between active social media use, hazardous alcohol use, and problem gambling among adult social media users. METHODS: Data were collected via surveys in 6-month intervals, starting in March-April 2021 (T1: N = 1530; Mage = 46.67; SD = 16.42; 50.33% male). Of the T1 respondents, 58.10% participated in T6 (n = 889). Measures included the frequency of use of different social media platforms, the 3-item Alcohol Use Disorders Identification Test (AUDIT-C), and the Problem Gambling Severity Index (PGSI). Hybrid multilevel regression models were used for analyses. RESULTS: We found positive within-person effects of weekly Facebook use and between-person effects of weekly use of Facebook, TikTok, and gambling-related online communities on drinking. These results suggest an increase in hazardous alcohol consumption over time among the platforms' active users. Weekly Instagram use had a negative between-person effect on hazardous alcohol use. Individuals using TikTok or gambling communities weekly were more prone to problem gambling compared to non-weekly users. CONCLUSIONS: There are risks involved in the active use of some social media services among adult users. Prevention work, including digital health interventions, should be targeted according to the appropriate user group.

The burden of anxiety, depression, and stress, along with the prevalence of symptoms of PTSD, and perceptions of the drivers of psychological harms, as perceived by doctors and nurses working in ICUs in Nepal during the COVID-19 pandemic; a mixed method evaluation.

BACKGROUND: The COVID-19 pandemic resulted in significant physical and psychological impacts for survivors, and for the healthcare professionals caring for patients. Nurses and doctors in critical care faced longer working hours, increased burden of patients, and limited resources, all in the context of personal social isolation and uncertainties regarding cross-infection. We evaluated the burden of anxiety, depression, stress, post-traumatic stress disorder (PTSD), and alcohol dependence among doctors and nurses working in intensive care units (ICUs) in Nepal and explored the individual and social drivers for these impacts. METHODS: We conducted a mixed-methods study in Nepal, using an online survey to assess psychological well-being and semi-structured interviews to explore perceptions as to the drivers of anxiety, stress, and depression. Participants were recruited from existing national critical care professional organisations in Nepal and using a snowball technique. The online survey comprised of validated assessment tools for anxiety, depression, stress, PTSD, and alcohol dependence; all tools were analysed using published guidelines. Interviews were analysed using rapid appraisal techniques, and themes regarding the drivers for psychological distress were explored. RESULTS: 134 respondents (113 nurses, 21 doctors) completed the online survey. Twenty-eight (21%) participants experienced moderate to severe symptoms of depression; 67 (50%) experienced moderate or severe symptoms of anxiety; 114 (85%) had scores indicative of moderate to high levels of stress; 46 out of 100 reported symptoms of PTSD. Compared to doctors, nurses experienced more severe symptoms of depression, anxiety, and PTSD, whereas doctors experienced higher levels of stress than nurses. Most (95%) participants had scores indicative of low risk of alcohol dependence. Twenty participants were followed up in interviews. Social stigmatism, physical and emotional safety, enforced role change and the absence of organisational support were perceived drivers for poor psychological well-being. CONCLUSION: Nurses and doctors working in ICU during the COVID-19 pandemic sustained psychological impacts, manifesting as stress, anxiety, and for some, symptoms of PTSD. Nurses were more vulnerable. Individual characteristics and professional inequalities in healthcare may be potential modifiable factors for policy makers seeking to mitigate risks for healthcare providers.

The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action.

Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic-assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4-12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5-MeO-DMT. Primarily, 5-MeO-DMT is able to induce mystical experiences and ego-dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood-related comorbidities consistent with the negative reinforcement and self-medication paradigms. In addition, preliminary evidence indicates that 5-MeO-DMT modulates neural oscillations that might subserve ego-dissolution (increases in gamma), psychological flexibility and mindfulness (increases in theta), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5-MeO-DMT is characterized by neuroplasticity, anti-inflammation, 5-HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood-related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action.

Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

AIMS: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems. METHODS: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346). The Timeline Follow-back was used to assess WHO risk drinking level reductions and the Pittsburgh Sleep Quality Index was used to assess sleep quality over the prior month at baseline and the end of treatment. RESULTS: Sleep problem scores in the active medication and placebo groups improved equally. Fewer sleep problems were noted among individuals who achieved at least a 1-level reduction (B = -0.99, 95% confidence interval (CI) [-1.77, -0.20], P = .014) or at least a 2-level reduction (B = -0.80, 95% CI [-1.47, -0.14], P = .018) in WHO risk drinking levels at the end of treatment. Reductions in drinking, with abstainers excluded from the analysis, also predicted fewer sleep problems at the end of treatment (1-level: B = -1.01, 95% CI [-1.83, -0.20], P = .015; 2-level: B = -0.90, 95% CI [-1.59, -0.22], P = .010). CONCLUSIONS: Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted.

Effectiveness of a Web-Based Individual Coping and Alcohol Intervention Program for Children of Parents With Alcohol Use Problems: Randomized Controlled Trial.

BACKGROUND: Children whose parents have alcohol use problems are at an increased risk of several negative consequences, such as poor school performance, an earlier onset of substance use, and poor mental health. Many would benefit from support programs, but the figures reveal that only a small proportion is reached by existing support. Digital interventions can provide readily accessible support and potentially reach a large number of children. Research on digital interventions aimed at this target group is scarce. We have developed a novel digital therapist-assisted self-management intervention targeting adolescents whose parents had alcohol use problems. This program aims to strengthen coping behaviors, improve mental health, and decrease alcohol consumption in adolescents. OBJECTIVE: This study aims to examine the effectiveness of a novel web-based therapist-assisted self-management intervention for adolescents whose parents have alcohol use problems. METHODS: Participants were recruited on the internet from social media and websites containing health-related information about adolescents. Possible participants were screened using the short version of the Children of Alcoholics Screening Test-6. Eligible participants were randomly allocated to either the intervention group (n=101) or the waitlist control group (n=103), and they were unblinded to the condition. The assessments, all self-assessed, consisted of a baseline and 2 follow-ups after 2 and 6 months. The primary outcome was the Coping With Parents Abuse Questionnaire (CPAQ), and secondary outcomes were the Center for Epidemiological Studies Depression Scale, Alcohol Use Disorders Identification Test (AUDIT-C), and Ladder of Life (LoL). RESULTS: For the primary outcome, CPAQ, a small but inconclusive treatment effect was observed (Cohen d=-0.05 at both follow-up time points). The intervention group scored 38% and 46% lower than the control group on the continuous part of the AUDIT-C at the 2- and 6-month follow-up, respectively. All other between-group comparisons were inconclusive at either follow-up time point. Adherence was low, as only 24% (24/101) of the participants in the intervention group completed the intervention. CONCLUSIONS: The findings were inconclusive for the primary outcome but demonstrate that a digital therapist-assisted self-management intervention may contribute to a reduction in alcohol consumption. These results highlight the potential for digital interventions to reach a vulnerable, hard-to-reach group of adolescents but underscore the need to develop more engaging support interventions to increase adherence. TRIAL REGISTRATION: ISRCTN Registry ISRCTN41545712; https://www.isrctn.com/ISRCTN41545712?q=ISRCTN41545712. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1471-2458-12-35.

Neuron enriched extracellular vesicles' MicroRNA expression profiles as a marker of early life alcohol consumption.

Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched extracellular vesicles' (EVs') microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biology. Neuron-enriched EVs' miRNA expression was measured from plasma samples collected from young people using a commercially available microarray platform while alcohol consumption was measured using the Alcohol Use Disorders Identification Test. Linear regression and network analyses were used to identify significantly differentially expressed miRNAs and to characterize the implicated biological pathways, respectively. Compared to alcohol naïve controls, young people reporting high alcohol consumption exhibited significantly higher expression of three neuron-enriched EVs' miRNAs including miR-30a-5p, miR-194-5p, and miR-339-3p, although only miR-30a-5p and miR-194-5p survived multiple test correction. The miRNA-miRNA interaction network inferred by a network inference algorithm did not detect any differentially expressed miRNAs with a high cutoff on edge scores. However, when the cutoff of the algorithm was reduced, five miRNAs were identified as interacting with miR-194-5p and miR-30a-5p. These seven miRNAs were associated with 25 biological functions; miR-194-5p was the most highly connected node and was highly correlated with the other miRNAs in this cluster. Our observed association between neuron-enriched EVs' miRNAs and alcohol consumption concurs with results from experimental animal models of alcohol use and suggests that high rates of alcohol consumption during the adolescent/young adult years may impact brain functioning and development by modulating miRNA expression.

Prevalence of common risk factors of major noncommunicable diseases among sexual and gender minorities in Kathmandu valley, Nepal.

Four noncommunicable diseases (NCDs): cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes, account for 71% of global deaths. However, little is known about the NCDs risk profile of sexual and gender minorities (SGMs). This study aimed to determine the prevalence of NCDs risk factors among the SGMs of Kathmandu valley, Nepal. A cross-sectional study was conducted among SGMs in the Kathmandu valley, Nepal. We recruited 140 participants using the snowball sampling method. A face-to-face interview was done using a structured questionnaire adapted from World Health Organization Step Wise Approach to Surveillance (STEPS instruments V2.2 2019) along with blood pressure and anthropometric measurements. Data were analyzed using Statistical Package for Social Science (SPSS.v20). More than two-thirds of the participants, 96 (68.6%), had co-occurrence of NCDs risk factors. The prevalence of insufficient fruits and vegetables consumption, current smoking, harmful alcohol consumption, overweight/obesity, and hypertension were 95.7%, 40.0%, 32.9%, 28.5%, and 28.6%, respectively. There was a significant association between hypertension, harmful alcohol consumption, and overweight/obesity with the participants' age, employment status, and marital status, respectively. Study findings indicated a higher prevalence of NCDs risk factors among SGMs. National-level NCDs surveillance, policy planning, prevention, and targeted health interventions should prioritize the SGMs.

Measuring refugees' capabilities: translation, adaptation, and valuation of the OxCAP-MH into Juba Arabic for use among South Sudanese male refugees in Uganda.

BACKGROUND: Forcibly displaced populations are highly vulnerable to psychosocial distress and mental disorders, including alcohol misuse. In an ongoing trial that seeks to develop a transdiagnostic intervention addressing psychological distress and alcohol use disorders among conflict-affected populations, we will carry out a cost-effectiveness evaluation using a capability-based Oxford Capabilities Mental Health (OxCAP-MH) measure. The OxCAP-MH is a 16-item questionnaire developed from the Capability Approach, that covers multiple domains of functioning and welfare. The aim of the current paper is to present the results of the translation, cultural adaptation and valuation of the OxCAP-MH into Juba Arabic for South Sudanese refugees living in Uganda. We adhered to the official Translation and Linguistic Validation process of the OxCAP-MH. To carry out the translation, the Concept Elaboration document, official English version of the OxCAP-MH, and the Back-Translation Review Template were used. Four independent translators were used for forward and back translations. The reconciled translated version was then piloted in two focus group discussions (N = 16) in Rhino refugee settlement. A most important to least important valuation of the sixteen capability domains covered in the OxCAP-MH was also done. RESULTS: The Juba Arabic version of the OxCAP-MH was finalized following a systematic iterative process. The content of the Juba Arabic version remained unchanged, but key concepts were adapted to ensure cultural acceptability, feasibility, and comprehension of the measure in the local context of Rhino refugee settlement. Most participants had low levels of literacy and required support with filling in the tool. Participants suggested an additional capability that is currently not reflected in the OxCAP-MH, namely access to food. Furthermore, discussions around the valuation exercise of the sixteen domains led to two separate importance scales, which showed relevant differences. CONCLUSIONS: In this context, the OxCAP-MH was considered culturally acceptable. The valuation exercise proved cognitively demanding. Participants voiced confusion over how to answer the questions on the OxCAP-MH instrument due to low levels of literacy. These concerns invite consideration for future research to consider how measures such as the OxCAP-MH can be made more accessible to individuals with low literacy rates in resource poor settings.

Male sex and hazardous alcohol use following military sexual assault increase suicide risk among US service members and veterans.

Background: Higher alcohol use and military sexual assault (MSA) are associated with increased risk of death by suicide. Risk for death by suicide is rapidly increasing among females, who report higher rates of MSA, yet actual death by suicide and alcohol use are higher among males. It is not well understood whether higher alcohol use confers greater suicide risk in male or female service members and veterans who have experienced MSA.Objective: To determine whether the association between alcohol misuse and suicide risk was moderated by biological sex in a sample of male and female service members (N = 400, 50% female) who reported MSA.Method: Participants completed surveys of alcohol use and suicide risk as well as a demographic inventory. Linear regression with an interaction term was used to determine if suicide risk differed by sex and alcohol use severity after accounting for discharge status, sexual orientation, and age.Results: Average scores on the suicide risk measure were consistent with an inpatient psychiatric sample and scores on the AUDIT-C were indicative of a probable positive screen for alcohol misuse. Suicide risk was most pronounced among males who reported higher levels of hazardous alcohol use. A sensitivity analysis examining suicide risk by sex and screening results for alcohol misuse (positive/negative) showed that men with a probable positive screen had higher suicide risk.Discussion: The current study provides novel findings on suicide risk among survivors of military sexual violence by including both male and female survivors. Interventions to decrease suicide risk following MSA may consider alcohol reduction strategies, and optimizing these interventions in males. Engaging military culture at both the US Departments of Defense and Veterans Affairs to encourage more healthy alcohol consumption may mitigate this public health concern. Future research may consider how country of origin relates to these associations.

Average scores for the suicide risk measure and alcohol use were high among a sample of male and female survivors of military sexual assault.Suicide risk was most pronounced among males who reported higher levels of hazardous alcohol use.A sensitivity analysis examining suicide risk by sex and screening results for alcohol misuse (positive/negative) showed that men with a probable positive screen had higher suicide risk.

Prevention of alcohol exposed pregnancies in Europe: the FAR SEAS guidelines.

INTRODUCTION: Drinking during pregnancy is the leading cause of birth defects and child developmental disorders in Europe. The adverse effects of drinking during pregnancy may include physical, behavioural and cognitive problems, known collectively as fetal alcohol spectrum disorders (FASD). Evidence-based comprehensive recommendations at the European level on how to implement preventive and treatment policies to reduce alcohol-exposed pregnancies are needed. FAR SEAS, a tendered service contract (number 20,187,106) awarded by the European Commission, aimed at developing guidelines to respond to this knowledge gap. METHODS: FAR SEAS recommendations were built on (1) a two-phase review of interventions, (2) an international expert consultation, and (3) a pilot study on prevention of FASD conducted in the Mazovia region of Poland. The review of interventions included nineteen electronic open access databases, several repositories of grey literature and a key informant consultation covering most European Union (EU) countries and an additional guidelines search. After triangulating sources, 94 records were collected. Experts contributed in the design of the research questions, addressing the gaps in the literature and reviewing the recommendations formulated. The Polish pilot added nuances from real world practice to the formulated recommendations, resulting in the final set of guidelines for dissemination. RESULTS: The FAR SEAS Guidelines comprise 23 recommendations grouped into different topics areas of policies, communication strategies, screening, brief intervention and referral to treatment, treatment and social services. The recommendations highlight the need to respect women's autonomy and avoid discrimination and stigmatization; using universal screening for women of childbearing age, including detection of other psychosocial risks (such as domestic violence); and individualized, comprehensive and multidisciplinary supportive interventions for those who require it, such as those with alcohol use disorders, including women's partners. Policies to prevent FASD should be multicomponent, and public health communication should combine information about the risks together with self-efficacy messages to promote changes. CONCLUSIONS: The FAR SEAS guidelines are a tool to support policy-makers and service managers in implementing effective programmes to reduce prenatal alcohol exposure among general and at-risk population groups. FASD prevention has to involve comprehensive and multi-level evidence-based policies and practice, with services and activities tailored to the needs of women at differing levels of risk, and with due attention to reducing stigma.

Study on the risk factors of postoperative wound complications in patients with ankle fracture.

Wound complications after surgery for ankle fractures can lead to catastrophic consequences. The purpose of this study was to evaluate the risk factors of postoperative wound complications in patients with ankle fracture and to determine their effects on prognosis. 200 patients with ankle fracture treated in our hospital from October 2021 to December 2023 were analysed retrospectively. The total incidence of postoperative wound complications was 19% (38/200). Type of complications: wound edge necrosis 15 cases (39.47%), dehiscence (reopening of wound) 13 cases (34.21%), delayed healing (>30 days) 10 cases (26.32%); Univariate analysis showed that patients' age, body mass index (BMI), current smoking, alcoholism, diabetes mellitus, injury mechanism, open fracture, wound classification, higher American Society of Anesthesiologists (ASA) score and operation time were all associated with postoperative wound complications. Multivariate Logistic regression model shows: age ≥60 years old OR3.671 (1.875-5.937), BMI OR1.198 (1.143-1.324), current smoking OR2.727 (1.251-5.602), alcoholism OR1.143 (1.034-1.267), complicated with diabetes OR2.763 (1.236-4.852), injury mechanism (high vs. low and medium energy) OR2.437 (1.238-4.786), open fracture OR1.943 (1.8262.139), wound classification (II vs. I) OR4.423 (1.73511.674), ASA score (III-IV vs. I-II) OR1.307 (1.113-2.194) was an independent risk factor for postoperative wound complications in patients with ankle fracture. Further, ROC curves showed that these nine independent influences had high accuracy and validity in predicting postoperative wound complications in patients with ankle fractures. In conclusion, independent risk factors for postoperative complications of ankle fracture were age >60 years, BMI, injury mechanism, open fracture, wound classification (II vs. I), ASA score, current smoking, and alcoholism. The wound classification (II vs. I) has the highest diagnostic value.

Comorbid physical health burden of serious mental health disorders in 32 European countries.

BACKGROUND: Mental health disorders (MHDs) are associated with physical health disparities, but underlying excess risk and health burden have not yet been comprehensively assessed. OBJECTIVE: To assess the burden of comorbid physical health conditions (PHCs) across serious MHDs in Europe. METHODS: We estimated the relative prevalence risk of PHCs associated with alcohol use disorders (AUD), bipolar disorder (BD), depressive disorders (DD) and schizophrenia (SZ) across working-age populations of 32 European countries in 2019 based on a targeted literature review. Excess physical health burden was modelled using population-attributable fractions and country-level prevalence data. FINDINGS: We screened 10 960 studies, of which 41 were deemed eligible, with a total sample size of over 18 million persons. Relative prevalence of PHCs was reported in 54%, 20%, 15%, 5% and 7% of studies, respectively, for SZ, DD, BD, AUD or mixed. Significant relative risk estimates ranged from 1.44 to 3.66 for BD, from 1.43 to 2.21 for DD, from 0.81 to 1.97 for SZ and 3.31 for AUD. Excess physical health burden ranged between 27% and 67% of the total, corresponding to 84 million (AUD), 67 million (BD), 66 million (DD) and 5 million (SZ) PHC diagnoses in Europe. A 1% reduction in excess risk assuming causal inference could result in two million fewer PHCs across investigated MHDs. CONCLUSIONS: This is the first comprehensive study of the physical health burden of serious MHDs in Europe. The methods allow for updates, refinement and extension to other MHDs or geographical areas. CLINICAL IMPLICATIONS: The results indicate potential population health benefits achievable through more integrated mental and physical healthcare and prevention approaches.

Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage.

BACKGROUND: Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. RESULTS: Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1ß and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. CONCLUSION: Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.

Inhibition of the Sodium-Calcium Exchanger Reverse Mode Activity Reduces Alcohol Consumption in Rats.

Excessive and uncontrolled consumption of alcohol can cause alcohol use disorder (AUD), but its pharmacological mechanisms are not fully understood. Inhibiting the reverse mode activity of the sodium-calcium exchanger (NCX) can reduce the risk of alcohol withdrawal seizures, suggesting that NCX could play a role in controlling alcohol consumption. Here, we investigated how two potent inhibitors of NCX reverse mode activity, SN-6 (NCX1) and KB-R7943 (NCX3), affect voluntary alcohol consumption in adult male and female rats using the intermittent alcohol access two-bottle choice paradigm. Initially, animals were trained to drink 7.5% ethanol and water for four weeks before administering SN-6 and KB-R7934. Afterward, their alcohol intake, preference, and water intake were recorded 2 and 24 h after exposure to water and 7.5% ethanol. SN-6 significantly reduced alcohol consumption by 48% in male and 36% in female rats without affecting their water intake. Additionally, SN-6 significantly reduced alcohol preference in females by 27%. However, KB-R7943 reduced alcohol consumption by 42% in female rats and did not affect alcohol preference or water intake. These findings suggest that alcohol exposure increased NCX reverse activity, and targeting NCX1 could be an effective strategy for reducing alcohol consumption in subjects susceptible to withdrawal seizures.

Does This Patient Have Alcohol Use Disorder?: The Rational Clinical Examination Systematic Review.

Importance: The accuracy of screening tests for alcohol use disorder (defined as a problematic pattern of alcohol use leading to clinically significant impairment or distress) requires reassessment to align with the latest definition in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). Objective: To assess the diagnostic accuracy of screening tools in identifying individuals with alcohol use disorder as defined in the DSM-5. Data Sources and Study Selection: The databases of MEDLINE and Embase were searched (January 2013-February 2023) for original studies on the diagnostic accuracy of brief screening tools to identify alcohol use disorder according to the DSM-5 definition. Because diagnosis of alcohol use disorder does not include excessive alcohol use as a criterion, studies of screening tools that identify excessive or high-risk drinking among younger (aged 9-18 years), older (aged ≥65 years), and pregnant persons also were retained. Data Extraction and Synthesis: Sensitivity, specificity, and likelihood ratios (LRs) were calculated. When appropriate, a meta-analysis was performed to calculate a summary LR. Results: Of 4303 identified studies, 35 were retained (N = 79 633). There were 11 691 individuals with alcohol use disorder or a history of excessive drinking. Across all age categories, a score of 8 or greater on the Alcohol Use Disorders Identification Test (AUDIT) increased the likelihood of alcohol use disorder (LR, 6.5 [95% CI, 3.9-11]). A positive screening result using AUDIT identified alcohol use disorder better among females (LR, 6.9 [95% CI, 3.9-12]) than among males (LR, 3.8 [95% CI, 2.6-5.5]) (P = .003). An AUDIT score of less than 8 reduced the likelihood of alcohol use disorder similarly for both males and females (LR, 0.33 [95% CI, 0.20-0.52]). The abbreviated AUDIT-Consumption (AUDIT-C) has sex-specific cutoff scores of 4 or greater for males and 3 or greater for females, but was less useful for identifying alcohol use disorder (males: LR, 1.8 [95% CI, 1.5-2.2]; females: LR, 2.0 [95% CI, 1.8-2.3]). The AUDIT-C appeared useful for identifying measures of excessive alcohol use in younger people (aged 9-18 years) and in those older than 60 years of age. For those younger than 18 years of age, the National Institute on Alcohol Abuse and Alcoholism age-specific drinking thresholds were helpful for assessing the likelihood of alcohol use disorder at the lowest risk threshold (LR, 0.15 [95% CI, 0.11-0.21]), at the moderate risk threshold (LR, 3.4 [95% CI, 2.8-4.1]), and at the highest risk threshold (LR, 15 [95% CI, 12-19]). Among persons who were pregnant and screened within 48 hours after delivery, an AUDIT score of 4 or greater identified those more likely to have alcohol use disorder (LR, 6.4 [95% CI, 5.1-8.0]), whereas scores of less than 2 for the Tolerance, Worried, Eye-Opener, Amnesia and Cut-Down screening tool and the Tolerance, Annoyed, Cut-Down and Eye-Opener screening tool identified alcohol use disorder similarly (LR, 0.05 [95% CI, 0.01-0.20]). Conclusions and Relevance: The AUDIT screening tool is useful to identify alcohol use disorder in adults and in individuals within 48 hours postpartum. The National Institute on Alcohol Abuse and Alcoholism youth screening tool is helpful to identify children and adolescents with alcohol use disorder. The AUDIT-C appears useful for identifying various measures of excessive alcohol use in young people and in older adults.

Unmet need for alcohol use disorder treatment in reproductive-age females, with emphasis on pregnant and parenting populations in the United States: Findings from NSDUH 2015-2021.

The negative effects of alcohol use can transmit intergenerational harm if alcohol use disorder (AUD) occurs during pregnancy and/or while parenting a child. Prenatal alcohol exposure is the leading preventable cause of congenital anomalies in the USA, and heavy drinking in women has been on the rise, further accelerated by the COVID-19 pandemic. This study describes the most recent patterns in the past year AUD prevalence and treatment among reproductive-aged women, with a specific focus on pregnant and parenting women, and barriers to treatment among those affected. We analyzed data on reproductive-age women from the National Survey on Drug Use and Health (2015-2021). We used generalized linear models to estimate prevalence ratios (PR) for past 12-month AUD and its treatment based on DSM-V criteria. We considered sociodemographic characteristics, including age, race/ethnicity, income, health insurance type, and arrest history. Pregnant and parenting women displayed lower risk for AUD (PR = 0.48, 95% CI:0.41-0.57; PR = 0.5 95% CI:0.48-0.54, respectively) relative to non-pregnant/non-parenting women. Excess risk for AUD was associated with education (some college vs. college graduates, PR = 1.07, 95% CI:1.01-1.13) and history of arrests (PR = 2.93, 95% CI:2.67-3.21). There were no clear differences in AUD treatment use based on parenting or pregnancy status. Among those with AUD, the prevalence of treatment was higher among individuals aged 35-49 years compared to those 18-25 years (PR = 1.6, 95% CI: 1.19-2.14) and in those enrolled in Medicaid vs. private insurance (PR = 2.62, 95%CI:1.97-3.47). Financial barriers and treatment not being a priority were the most frequently reported barriers to treatment. To promote well-being among parents and their children, healthcare providers should prioritize reproductive-age women at higher AUD risk. Decreasing the stigma attached to AUD and intensifying efforts to educate women about the dangers of AUD may improve treatment use among pregnant and parenting women.