Psilocybin reduces alcohol self-administration via selective left nucleus accumbens activation in rats.

The use of psilocybin to treat alcohol use disorder is very promising, but the mechanisms of action remain poorly understood. We combined behavioral, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing the effect of intraperitoneal psilocybin or directly within the nucleus accumbens core or the ventral tegmental area. Transcripts from the dopaminergic system were quantified in the nucleus accumbens and prefrontal cortex. Psilocybin significantly reduced (50%) ethanol self-administration when injected 4 hours before the session either intraperitoneally (1mg/kg) or directly within the left nucleus accumbens (0.15µg) but not the right nucleus accumbens or the left ventral tegmental area. The effect of intraperitoneal injection of psilocybin was prevented by intra left nucleus accumbens injection of 0.3µg of the 5-HT2AR antagonist ketanserin. In rats that self-administered ethanol but not in those self-administering saccharin, dopamine D2 receptor mRNA were increased in both the nucleus accumbens and the prefrontal cortex by psilocybin, while D1R mRNA was increased only in the prefrontal cortex. As in humans, psilocybin reduced ethanol self-administration in rats through the 5-HT2AR within the left nucleus accumbens possibly through increased D2R expression. Our results open unexpected perspectives regarding the hemispheric lateralization of psychedelic effects.

A dual-omics approach on the effects of fibroblast growth factor-2 (FGF-2) on ventral tegmental area dopaminergic neurons in response to alcohol consumption in mice.

Harmful alcohol consumption is a major socioeconomic burden to the health system, as it can be the cause of mortality of heavy alcohol drinkers. The dopaminergic (DAergic) system is thought to play an important role in the pathogenesis of alcohol drinking behaviour; however, its exact role remains elusive. Fibroblast growth factor 2 (FGF-2), a neurotrophic factor, associated with both the DAergic system and alcohol consumption, may play an important role in DAergic neuroadaptations during alcohol abuse. Within this study, we aimed to clarify the role of endogenous FGF-2 on the DAergic system and whether there is a possible link to alcohol consumption. We found that lack of FGF-2 reduces the alcohol intake of mice. Transcriptome analysis of DAergic neurons revealed that FGF-2 knockout (FGF-2 KO) shifts the molecular fingerprint of midbrain dopaminergic (mDA) neurons to DA subtypes of the ventral tegmental area (VTA). In line with this, proteomic changes predominantly appear also in the VTA. Interestingly, these changes led to an altered regulation of the FGF-2 signalling cascades and DAergic pathways in a region-specific manner, which was only marginally affected by voluntary alcohol consumption. Thus, lack of FGF-2 not only affects the gene expression but also the proteome of specific brain regions of mDA neurons. Our study provides new insights into the neuroadaptations of the DAergic system during alcohol abuse and, therefore, comprises novel targets for future pharmacological interventions.

The extrastriate symmetry response is robust to alcohol intoxication.

Visual symmetry activates a network of regions in the extrastriate cortex and generates an event-related potential (ERP) called the sustained posterior negativity (SPN). Previous work has found that the SPN is robust to experimental manipulations of task, spatial attention, and memory load. In the current study, we investigated whether the SPN is also robust to alcohol-induced changes in mental state. A pilot experiment (N = 13) found that alcohol unexpectedly increased SPN amplitude. We followed this unexpected result with two new experiments on separate groups, using an alcohol challenge paradigm. One group completed an Oddball discrimination task (N = 26). Another group completed a Regularity discrimination task (N = 26). In both groups, participants consumed a medium dose of alcohol (0.65 g/kg body weight) and a placebo drink, in separate sessions. Alcohol reduced SPN amplitude in the Oddball task (contrary to the pilot results) but had no effect on SPN amplitude in the Regularity task. In contrast, the N1 wave was consistently dampened by alcohol in all experiments. Exploratory analysis indicated that the inconsistent effect of alcohol on SPN amplitude may be partly explained by individual differences in alcohol use. Alcohol reduced the SPN in light drinkers and increased it in heavier drinkers. Despite remaining questions, the results highlight the automaticity of symmetry processing. Symmetry still produces a large SPN response, even when participants are intoxicated, and even when symmetry is not task relevant.

Effect of the COVID-19 pandemic on clinical characteristics and outcomes of adult pneumococcal meningitis patients - a Dutch prospective nationwide cohort study.

PURPOSE: To investigate clinical characteristics and outcomes of patients with pneumococcal meningitis during the COVID-19 pandemic. METHODS: In a Dutch prospective cohort, risk factors and clinical characteristics of pneumococcal meningitis episodes occurring during the COVID-19 pandemic (starting March 2020) were compared with those from baseline and the time afterwards. Outcomes were compared with an age-adjusted logistic regression model. RESULTS: We included 1,699 patients in 2006-2020, 50 patients in 2020-2021, and 182 patients in 2021-2023. After March 2020 relatively more alcoholism was reported (2006-2020, 6.1%; 2020-2021, 18%; 2021-2023, 9.7%; P = 0.002) and otitis-sinusitis was less frequently reported (2006-2020, 45%; 2020-2021, 22%; 2021-2023, 47%; P = 0.006). Other parameters, i.e. age, sex, symptom duration or initial C-reactive protein level, remained unaffected. Compared to baseline, lumbar punctures were more frequently delayed (on admission day, 2006-2020, 89%; 2020-2021, 74%; 2021-2022, 86%; P = 0.002) and outcomes were worse ('good recovery', 2020-2021, OR 0.5, 95% CI 0.3-0.8). CONCLUSION: During the COVID-19 pandemic, we observed worse outcomes in patients with pneumococcal meningitis. This may be explained by differing adherence to restrictions according to risk groups or by reduced health care quality.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

Masculine depression and its problem behaviors: use alcohol and drugs, work hard, and avoid psychiatry!

The gender role influences vulnerability to mental illness. Substance use, even critical in scale, is perceived as masculine, just like hard (over-)work, while not seeking help. With the ongoing separation between gender and sex, masculine norms become more relevant also to females' mental health. The male depression concept highlights the role of male symptoms in affective disorders. However, the empirical evidence is still limited. Here, we use the denomination 'masculine depression' to open the category for female patients and tested substance use patterns, health services' utilization, and working hours as predictors in a case-control study of 163 depressed in-patients (44% women; masculine vs. non-masculine depression according to a median split of the Male Depression Rating Scale-22) and 176 controls (51% women). We assessed higher depression severity in patients with masculine (vs. non-masculine) depression. Masculine depression (vs. non-masculine depression and vs. no depression) was predicted by more frequent and critical use of alcohol (including binge drinking), tobacco, and illicit drugs, and by longer working times. Moreover, fewer health services contacts due to mental complaints during the previous year were associated with masculine (vs. non-masculine) depression. Alarmingly, even critical substance misuse was not significantly associated with more frequent health services contacts; however, the higher the depression severity, the more contacts the patients reported. Here, we provide evidence that patients with masculine depression are highly burdened and undertreated, which applies equally to female and male patients. This study identified promising targets to establish specialized care offers.

Educational inequalities and alcohol-related consequences in Brazil.

AIMS: This study aimed to test whether the alcohol harm paradox (AHP) is observed in Brazil by investigating (i) the association between educational attainment and alcohol-related consequences (ARC) and (ii) the contribution of average alcohol volume consumed (AVC), past-month heavy episodic drinking (HED), smoking, body mass index (BMI), and depression in accounting for the disparities in ARC. METHODS: We analysed data from the 2019 Brazilian National Health Survey, a nationally representative household survey. The composite ARC outcome was considered present when an individual reported a past-year episode of activity failure, amnesia, and concern by others due to alcohol consumption. Adjusted binary logistic regression models were fitted using a hierarchical approach to calculate the odds ratios (OR) and respective 95% confidence intervals (CI), and to assess the contribution of each set of variables in attenuating the educational differences in ARC. RESULTS: Those from the lowest educational strata (incomplete elementary school) exhibited higher odds of ARC than their counterparts (OR: 2.03; 95% CI: 1.73-2.37). Although smoking, BMI, and depression attenuated the educational gradient (i.e. reduced the difference between reference and riskier categories) in ARC by ~13%, the adjustment for AVC and HED amplified inequalities by 0.3% and 5.7%, respectively. CONCLUSION: We found evidence of the AHP in Brazil. Educational inequalities in ARC were scarcely attenuated by behavioural factors, and a suppression effect was noted when adjusting for AVC and HED.

Patterns of publicly funded naltrexone use among patients diagnosed with alcohol use disorder in Ontario.

AIMS: Naltrexone is recommended first-line to manage alcohol use disorder (AUD). With previous studies indicating poor retention on naltrexone, we determined duration of naltrexone use and assessed the association between prescription setting and time to discontinuation in Ontario. METHODS: We conducted a retrospective population-based cohort study among Ontario public drug beneficiaries diagnosed with AUD who initiated publicly funded naltrexone from June 2018 to September 2019. The primary outcome was time to naltrexone discontinuation, with a secondary analysis assessing receipt of at least one prescription refill. We used Cox proportional hazards models and logistic regression to test the association between prescription setting and each medication persistence outcome. RESULTS: Among 2531 new naltrexone patients with AUD, the median duration of naltrexone use was 31 days and 394 (15.6%) continued naltrexone for 6 months or longer. There was no association between setting of initiation and duration of naltrexone use; however, those initiating naltrexone following an acute inpatient hospital stay were more likely to fill a second prescription (aOR 1.43, 95% CI 0.96-2.14), while those initiating after an ED visit were less likely to be dispensed a second prescription (aOR = 0.69, 95% CI 0.52-0.90) compared to those starting in a physician's office. CONCLUSION: Persistence on naltrexone to treat an AUD is low, regardless of the setting of initiation. Further research is needed to elucidate the barriers encountered by patients with AUD that lead to poor treatment persistence in order to develop interventions that facilitate patient-centered access to evidence-based treatment for AUD in the province.

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.

Equivalence of Alcohol Use Disorder Symptom Assessments in Routine Clinical Care When Completed Remotely via Online Patient Portals Versus In Clinic via Paper Questionnaires: Psychometric Evaluation.

BACKGROUND: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommends the paper-based or computerized Alcohol Symptom Checklist to assess alcohol use disorder (AUD) symptoms in routine care when patients report high-risk drinking. However, it is unknown whether Alcohol Symptom Checklist response characteristics differ when it is administered online (eg, remotely via an online electronic health record [EHR] patient portal before an appointment) versus in clinic (eg, on paper after appointment check-in). OBJECTIVE: This study evaluated the psychometric performance of the Alcohol Symptom Checklist when completed online versus in clinic during routine clinical care. METHODS: This cross-sectional, psychometric study obtained EHR data from the Alcohol Symptom Checklist completed by adult patients from an integrated health system in Washington state. The sample included patients who had a primary care visit in 2021 at 1 of 32 primary care practices, were due for annual behavioral health screening, and reported high-risk drinking on the behavioral health screen (Alcohol Use Disorder Identification Test-Consumption score ≥7). After screening, patients with high-risk drinking were typically asked to complete the Alcohol Symptom Checklist-an 11-item questionnaire on which patients self-report whether they had experienced each of the 11 AUD criteria listed in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) over a past-year timeframe. Patients could complete the Alcohol Symptom Checklist online (eg, on a computer, smartphone, or tablet from any location) or in clinic (eg, on paper as part of the rooming process at clinical appointments). We examined sample and measurement characteristics and conducted differential item functioning analyses using item response theory to examine measurement consistency across these 2 assessment modalities. RESULTS: Among 3243 patients meeting eligibility criteria for this secondary analysis (2313/3243, 71% male; 2271/3243, 70% White; and 2014/3243, 62% non-Hispanic), 1640 (51%) completed the Alcohol Symptom Checklist online while 1603 (49%) completed it in clinic. Approximately 46% (752/1640) and 48% (764/1603) reported ≥2 AUD criteria (the threshold for AUD diagnosis) online and in clinic (P=.37), respectively. A small degree of differential item functioning was observed for 4 of 11 items. This differential item functioning produced only minimal impact on total scores used clinically to assess AUD severity, affecting total criteria count by a maximum of 0.13 criteria (on a scale ranging from 0 to 11). CONCLUSIONS: Completing the Alcohol Symptom Checklist online, typically prior to patient check-in, performed similarly to an in-clinic modality typically administered on paper by a medical assistant at the time of the appointment. Findings have implications for using online AUD symptom assessments to streamline workflows, reduce staff burden, reduce stigma, and potentially assess patients who do not receive in-person care. Whether modality of DSM-5 assessment of AUD differentially impacts treatment is unknown.

Chronic alcohol and nicotine consumption as catalyst for systemic inflammatory storm and bone destruction in apical periodontitis.

AIM: To assess the periapical alveolar bone pattern and the serum levels of proinflammatory cytokines, biochemical markers and metabolites in rats subjected to chronic alcohol and nicotine consumption and induced apical periodontitis. METHODOLOGY: Twenty-eight male Wistar rats were divided into four groups: Control, Alcohol, Nicotine and Alcohol+Nicotine. The alcohol groups were exposed to self-administration of a 25% alcohol solution, while the other groups were given only filtered water. The nicotine groups received daily intraperitoneal injections of a nicotine solution (0.19 µL of nicotine/mL), whereas the other groups received saline solution. Periapical lesions were induced by exposing the pulps of the left mandibular first molars for 28 days. After euthanasia, the mandibles were removed and the percentage bone volume, bone mineral density, trabecular thickness, trabecular separation and trabecular number of the periapical bone were measured using micro-computed tomography images. Serum samples were collected for analysis of proinflammatory cytokines (IL-1ß, IL-4, IL-6 and TNF-α), biochemical and metabolomic analysis. Statistical analysis was performed with a significance level of 5%. Nonparametric data were analysed using the Kruskal-Wallis test followed by Dunn's test, while one-way anova followed by Tukey's test was performed for parametric data. RESULTS: The groups exposed to alcohol or nicotine consumption exhibited an altered bone pattern indicating lower bone density and higher levels of IL-1ß, IL-6 and TNF-α compared to the Control group (p < .05). Significant differences were observed among the groups in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, triglycerides, urea, creatinine, albumin, uric acid, bilirubin and calcium. Metabolomic analysis revealed significant differences in glycine, phosphocholine, lysine, lactate, valine, pyruvate and lipids (CH2 CH2 CO), n(CH2 ) and n(CH3 ). Most of these parameters were even more altered in the simultaneous consumption of both substances compared to single consumption. CONCLUSION: Alcohol and nicotine chronic consumption altered several metabolic markers, impaired liver and kidney function, increased the production of systemic proinflammatory mediators and harmed the periapical bone microarchitecture in the presence of apical periodontitis. The simultaneous consumption of alcohol and nicotine intensified these detrimental effects.

Withdrawal interference scale: a novel measure of withdrawal-related life disruption in opioid use disorder and alcohol use disorder.

Background: Hyperkatifeia describes amplified emotional and motivational withdrawal due to addiction-related sensitization of brain-stress-systems. Hyperkatifeia has been proposed as a target for addiction treatment development. However, translation of basic research in this area will require new tools designed to measure hyperkatifeia and related phenomena outside of laboratory settings.Objectives: We define a novel concept, withdrawal interference, and introduce a new tool - the Withdrawal Interference Scale (WIS) - which measures the impact of withdrawal on daily life among individuals with OUD or AUD.Methods: Described are the combined results of three separate cross-sectional studies. The structural validity, convergent validity, construct validity, trans-diagnostic (AUD/OUD) configural, metric, and scalar invariance, internal consistency, and composite reliability of WIS was tested among three independent samples of 1) treatment-seeking adults with OUD (n = 132), 2) treatment-seeking adults with AUD (n = 123), and 3) non-treatment-seeking adults with OUD (n = 140). Males numbered 218 and females were 163.Results: WIS exhibited structural validity (1 factor), convergent validity (average variance extracted .670-.676), construct validity, trans-diagnostic configural (χ2/df = 2.10), metric (Δχ2 = 5.70, p = .681), and scalar invariance (Δχ2 = 12.34, p = .338), internal consistency (α .882-928), and composite reliability (.924-.925).Conclusion: These results suggest WIS is a valid and reliable instrument for measuring withdrawal-related life disruption in AUD and OUD. Further, given our findings of transdiagnostic measurement invariance, WIS scores of individuals with AUD and OUD can be meaningfully compared in future statistical analyses.

Adverse alcohol use and oral health.

OBJECTIVE: To determine whether different alcohol intake dimensions: average alcohol volume consumed (AVC), binge drinking (BD), and alcohol-related consequences (ARC) are associated with self-rated oral health (SROH). METHODS: Secondary cross-sectional analysis of The Brazilian National Health Survey of 2019 data. BD was considered when an individual reported a past-month heavy drinking episode. ARC referred to experiences such as past-year blackouts, concerns from others, or failure in routine activities. Adjusted multivariate Poisson regression models with robust variance were employed to calculate the prevalence ratios (PR) and 95% confidence intervals (CI) of SROH across the entire sample and stratified by sex and age. RESULTS: The sample comprised 88,531 participants aged 18 years or older. Individuals experiencing at least one past-year ARC had an 11% (95% CI: 1.07, 1.15) higher prevalence of poor SROH than their abstainers' counterparts. Associations were more pronounced among men aged less than 50 (PR = 1.09; 95% CI: 1.03, 1.15) and women aged 50 years or more (PR = 1.15; 95% CI: 1.01, 1.30). CONCLUSION: Alcohol-related consequences predicted poor SROH. Oral health inquiries should include the screening for ARC in addition to traditional measurements of AVC or BD, since such exposures may not fully capture the role of alcohol on oral health impairment.

Sodium Bicarbonate Decreases Alcohol Consumption in Mice.

We previously reported that mice with low neuronal pH drink more alcohol, demonstrating the importance of pH for alcohol reward and motivation. In this study, we tested whether systemic pH affects alcohol consumption and if so, whether it occurs by changing the alcohol reward. C57BL/6J mice were given NaHCO3 to raise their blood pH, and the animals' alcohol consumption was measured in the drinking-in-the-dark and two-bottle free choice paradigms. Alcohol consumption was also assessed after suppressing the bitterness of NaHCO3 with sucrose. Alcohol reward was evaluated using a conditioned place preference. In addition, taste sensitivity was assessed by determining quinine and sucrose preference. The results revealed that a pH increase by NaHCO3 caused mice to decrease their alcohol consumption. The decrease in high alcohol contents (20%) was significant and observed at different ages, as well as in both males and females. Alcohol consumption was also decreased after suppressing NaHCO3 bitterness. Oral gavage of NaHCO3 did not alter quinine and sucrose preference. In the conditioned place preference, NaHCO3-treated mice spent less time in the alcohol-injected chamber. Conclusively, the results show that raising systemic pH with NaHCO3 decreases alcohol consumption, as it decreases the alcohol reward value.

A latent state space model for estimating brain dynamics from electroencephalogram (EEG) data.

Modern neuroimaging technologies have substantially advanced the measurement of brain activity. Electroencephalogram (EEG) as a noninvasive neuroimaging technique measures changes in electrical voltage on the scalp induced by brain cortical activity. With its high temporal resolution, EEG has emerged as an increasingly useful tool to study brain connectivity. Challenges with modeling EEG signals of complex brain activity include interactions among unknown sources, low signal-to-noise ratio, and substantial between-subject heterogeneity. In this work, we propose a state space model that jointly analyzes multichannel EEG signals and learns dynamics of different sources corresponding to brain cortical activity. Our model borrows strength from spatially correlated measurements and uses low-dimensional latent states to explain all observed channels. The model can account for patient heterogeneity and quantify the effect of a subject's covariates on the latent space. The EM algorithm, Kalman filtering, and bootstrap resampling are used to fit the state space model and provide comparisons between patient diagnostic groups. We apply the developed approach to a case-control study of alcoholism and reveal significant attenuation of brain activity in response to visual stimuli in alcoholic subjects compared to healthy controls.

Alcohol use and hepatocellular carcinoma risk in patients with alcohol-related cirrhosis.

OBJECTIVES: Insights into risk factors for hepatocellular carcinoma (HCC) among patients with alcohol-related cirrhosis (ALD cirrhosis) are important for decisions about HCC surveillance. We studied the effects of continued hazardous alcohol use in ALD cirrhosis on HCC risk. METHODS: Within a nationwide registry-based cohort of patients with ALD cirrhosis, we compared HCC risk between patients with a continued hazardous alcohol use and matched comparators. We used Fine-Gray regression to compare the risk of HCC and Cox regression to compare all-cause mortality. We also included patients with ALD cirrhosis in a clinical case-control study. Cases had HCC, and controls did not. Alcohol use was quantified using the AUDIT-C-questionnaire. Logistic regression was used to analyze the association between hazardous alcohol use and HCC risk. RESULTS: In the registry-based study, we included 8,616 patients with continued hazardous alcohol use and 8,616 matched comparators. Patients with a continued hazardous alcohol use had a lower HCC risk (subdistribution hazard ratio: 0.64, 95% confidence interval [CI]: 0.57 - 0.72) and higher mortality (hazard ratio: 1.62, 95% CI: 1.56 - 1.67). In the clinical study, we included 146 patients with ALD cirrhosis of whom 53 had newly diagnosed HCC. Hazardous alcohol use was insignificantly associated with a lower HCC risk (odds ratio: 0.61, 95% CI: 0.25 - 1.46). CONCLUSIONS: Hazardous alcohol use in patients with ALD cirrhosis is associated with higher mortality and, consequently, a lower HCC risk. Even if alcohol is carcinogenic, HCC surveillance will therefore likely be more effective in patients with ALD cirrhosis without a hazardous alcohol use.

Alcohol treatment discussions and clinical outcomes among patients with alcohol-related cirrhosis.

BACKGROUND: Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use disorder (AUD) treatment, AUD treatment engagement, and mortality. METHODS: This retrospective cohort study included all patients with ICD-10 diagnosis codes for cirrhosis and AUD who were engaged in hepatology care in a single healthcare system in 2015. Baseline demographic, medical, liver disease, and AUD treatment data were assessed. AUD treatment discussions and initiation, alcohol cessation, and subsequent 5-year mortality were collected. Multivariable models were used to assess the factors associated with subsequent AUD treatment and 5-year mortality. RESULTS: Among 436 patients with cirrhosis due to alcohol, 65 patients (15%) received AUD treatment at baseline, including 48 (11%) receiving behavioral therapy alone, 11 (2%) receiving pharmacotherapy alone, and 6 (1%) receiving both. Over the first year after a baseline hepatology visit, 37 patients engaged in AUD treatment, 51 were retained in treatment, and 14 stopped treatment. Thirty percent of patients had hepatology-documented AUD treatment recommendations and 26% had primary care-documented AUD treatment recommendations. Most hepatology (86%) and primary care (88%) recommendations discussed behavioral therapy alone. Among patients with ongoing alcohol use at baseline, AUD treatment one year later was significantly, independently associated with AUD treatment discussions with hepatology (adjusted odds ratio (aOR): 3.23, 95% confidence interval (CI): 1.58, 6.89) or primary care (aOR: 2.95; 95% CI: 1.44, 6.15) and negatively associated with having Medicaid insurance (aOR: 0.43, 95% CI: 0.18, 0.93). When treatment was discussed in both settings, high rates of treatment ensued (aOR: 10.72, 95% CI: 3.89, 33.52). Over a 5-year follow-up period, 152 (35%) patients died. Ongoing alcohol use, age, hepatic decompensation, and hepatocellular carcinoma were significantly associated with mortality in the final survival model. CONCLUSION: AUD treatment discussions were documented in less than half of hepatology and primary care encounters in patients with alcohol-related cirrhosis, though such discussions were significantly associated with receipt of AUD treatment.

Epidemiology of suicide in the Tri-City metropolitan area in Poland in 2010-2019.

The paper, which is a continuation of our previous epidemiological studies on the phenomenon of suicide in the Tri-City metropolitan area, presents the results of statistical analyses of suicides in the autopsy material of the Department of Forensic Medicine of the Medical University of Gdansk in the years 2010-2019. The purpose of the study was to analyse in detail demographic data of suicides (age, sex, place of death), as well as to assess suicide methods and the impact of alcohol on suicides in the study area. During the 10-year study period, 8495 autopsies were performed, of which 1261 were suicides (14.8%). Statistical analyses were conducted using the statistical data analysis software system STATISTICA, version 13 (StatSoft, Tulsa, Oklahoma, USA). The results of the study indicate a continuing downward trend in the number of suicides since the beginning of the 21th century, with the number of suicides in rural areas increasing over the same period. In the analysed cohort, suicides were committed in particular by middle-aged men and the number of suicides among older people (65 +) increased at the same time. The increase in suicide occurred in late autumn and early spring. The most common method of suicide was hanging. There was a high percentage of inebriated victims (45%), and a comparison of the present studies with previous ones indicates the increasing impact of alcohol on suicide.

Aberrant functional brain network organization is associated with relapse during 1-year follow-up in alcohol-dependent patients.

Alcohol dependence (AD) is a debilitating disease associated with high relapse rates even after long periods of abstinence. Thus, elucidating neurobiological substrates of relapse risk is fundamental for the development of novel targeted interventions that could promote long-lasting abstinence. In the present study, we analysed resting-state functional magnetic resonance imaging (rsfMRI) data from a sample of recently detoxified patients with AD (n = 93) who were followed up for 12 months after rsfMRI assessment. Specifically, we employed graph theoretic analyses to compare functional brain network topology and functional connectivity between future relapsers (REL, n = 59), future abstainers (ABS, n = 28) and age- and gender-matched controls (CON, n = 83). Our results suggest increased whole-brain network segregation, decreased global network integration and overall blunted connectivity strength in REL compared with CON. Conversely, we found evidence for a comparable network architecture in ABS relative to CON. At the nodal level, REL exhibited decreased integration and decoupling between multiple brain systems compared with CON, encompassing regions associated with higher-order executive functions, sensory and reward processing. Among patients with AD, increased coupling between nodes implicated in reward valuation and salience attribution constitutes a particular risk factor for future relapse. Importantly, aberrant network organization in REL was consistently associated with shorter abstinence duration during follow-up, portending to a putative neural signature of relapse risk in AD. Future research should further evaluate the potential diagnostic value of the identified changes in network topology and functional connectivity for relapse prediction at the individual subject level.

Factors associated with alcohol abuse in the Peruvian population: analysis of a national health survey 2019.

AIM: To evaluate the factors associated with alcohol abuse in the Peruvian population. METHODS: A secondary analysis was performed using data from the Demographic and Family Health Survey of Peru, 2019. We included 24 264 Peruvians between 18 and 59 years. For the analysis of association, the Poisson regression model with robust standard errors was used. Adjusted Prevalence Ratios (aPR) with their respective 95% confidence intervals (95% CI) were calculated. RESULTS: The prevalence of alcohol abuse was 5.2%. Having higher education (aPR:1.61; 95%CI:1.04-2.48), being widowed, separated or divorced (aPR:1.73; 95%CI:1.18-2.54), belonging to the third (aPR:1.70; 95%CI:1.12-2.60), fourth (aPR:2.08; 95%CI:1.33-3.23) or fifth socioeconomic quintile (aPR:2.16; 95%CI:1.33-3.50), being from the Sierra (aPR:1.45; 95%CI:1.12-1.87) or Selva (aPR:1.48; 95%CI:1.13-1.94), not having health insurance (aPR:1.25; 95%CI:1.04-1.50), being a current smoker (aPR:2.43; 95%CI:2.02-2.93) and having major depression (aPR:1.77; 95%CI:1.32-2.36) were associated with a higher prevalence of alcohol abuse. On the other hand being a middle-aged adult (aPR:0.73; 95%CI:0.60-0.88), female (aPR:0.16; 95%CI:0.12-0.22) and having started drinking alcohol after the age of 18 years (aPR:0.57; 95%CI:0.47-0.69) were associated with a lower prevalence. CONCLUSIONS: One in 20 Peruvians between 18 and 59 years had alcohol abuse. Age, gender, education level, marital status, socioeconomic level, region, age of first drink, smoking and depression were associated with alcohol abuse.