Prolonged Alcohol Use Research Articles

Dexmedetomidine as Adjunctive Therapy for the Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis.

Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases where benzodiazepines are not adequate in controlling persistent autonomic hyperactivity or anxiety, dexmedetomidine could be utilized. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the ICUs, with the potential reduction in healthcare costs. The purpose of this systematic review and meta-analysis (PROSPERO CRD42018084370) is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care for the treatment of AWS. We retrieved literature from PubMed, EMBASE, and CENTRAL until 10 January 2024. Eligible studies were both randomized trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was tracheal intubation; secondary outcomes were (i) bradycardia and (ii) hypotension. A total of 3585 papers were retrieved: 2635 from EMBASE, 930 from Medline, and 20 from CENTRAL. After eliminating duplicates, 2960 papers were screened by title and abstract; 75 out of the 2960 papers were read in full text. The qualitative synthesis included nine of all manuscripts read in full text. The quantitative synthesis included eight studies for the primary outcome (tracheal intubation), seven for the secondary outcome bradycardia, and six for the secondary outcome hypotension. The meta-analysis showed that Dexmedetomidine, as adjunctive therapy, is not more effective than standard therapy in reducing the risk of tracheal intubation in AWS [RR: 0.57, 95% CI: 0.25-1.3, p = 0.15]. It also appears to be less safe than sedative therapy as it significantly increases the risk of bradycardia [RR: 2.68, 95% CI: 1.79-4.16, p = 0.0016]. Hypotension was not significantly different in patients who received dexmedetomidine [RR: 1.5, 95% CI: 0.69-3.49, p = 0.21].

Could Alcohol-Related Cognitive Decline Be the Result of Iron-Induced Neuroinflammation?

Excessive and prolonged alcohol use can have long-term severe neurological consequences. The mechanisms involved may be complicated; however, new evidence seems to indicate the involvement of iron accumulation and neuroinflammation. Prolonged alcohol consumption has been linked to the accumulation of iron in specific regions of the brain. Evidence suggests that excess iron in the brain can trigger microglia activation in response. This activation leads to the release of pro-inflammatory cytokines and reactive oxygen species, which can cause damage to neurons and surrounding brain tissue. Additionally, iron-induced oxidative stress and inflammation can disrupt the blood-brain barrier, allowing immune cells from the periphery to infiltrate the brain. This infiltration can lead to further neuroinflammatory responses. Inflammation in the brain subsequently disrupts neuronal networks, impairs synaptic plasticity, and accelerates neuronal cell death. Consequently, cognitive functions such as memory, attention, and decision-making are compromised. Additionally, chronic neuroinflammation can hasten the development and progression of neurodegenerative diseases, further exacerbating cognitive impairment. Therefore, alcohol could act as a trigger for iron-induced neuroinflammation and cognitive decline. Overall, the mechanisms at play here seem to strongly link alcohol with cognitive decline, with neuroinflammation resulting from alcohol-induced iron accumulation playing a pivotal role.

Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis.

Neurologists have a difficult time identifying sporadic cerebellar ataxia. Multiple system atrophy of the cerebellar type (MSA-C), spontaneous late cortical cerebellar atrophy, and prolonged alcohol use are a few possible causes. In a group of people with sporadic cerebellar ataxia that was not MSA-C, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was recently discovered. Chinese single-hospital cohort will be used in this study to genetic screen for SCA-related genes. One hundred forty individuals with CA were monitored over 8 years. Thirty-one individuals had familial CA, 109 patients had sporadic CA, 73 had MSA-C, and 36 had non-MSA-C sporadic CA. In 28 of the 31 non-MSA-C sporadic patients who requested the test, we carried out gene analysis, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, SCA31, and dentatorubro-pallidoluysian atrophy (DRPLA). The control group consisted of family members of the patients. In 57% of the instances with spontaneous CA that were not MSA-C, gene abnormalities were discovered. The most frequent exception among individuals with sporadic CA was SCA6 (36%), followed by monsters in SCA1, 2, 3, 8, and DRPLA. In contrast, 75% of the patients with familial CA had gene abnormalities, the most frequent of which was SCA6 abnormality. The age of 69 vs 59 was higher, and the CAG repeat length was a minor age of 23 vs 25 in the former instances compared to the last one among individuals with SCA6 anomalies that were sporadic as opposed to familial cases. In sporadic CA, autosomal-dominant mutations in SCA genes, notably in SCA6, are common. Although the cause of the increased incidence of SCA6 mutations is unknown, it may be related to a greater age of onset and varied penetrance of SCA6 mutations.

Alcohol related dementia and Brain Imaging

IntroductionAlcohol is considered a social evil worldwide owing to its vast array of associated problems and complications, which may manifest in medical, legal or social domains. Excessive and prolonged alcohol use may lead to permanent structural and functional damage to the brain. The evidence from neuroimaging, neuropathological reports and autopsy evaluations suggest some degree of brain pathology in individuals diagnosed with an alcohol related disorder.ObjectivesThe aim of this study is to characterize the structural imaging findings on computed tomography (CT) and magnetic resonance (MR) imaging of our sample and provide an overview of the literature on the subject.MethodsRetrospective observational study with inpatients of Coimbra Hospital and University Centre (CHUC), who had alcohol use disorder diagnosis associated with dementia or cognition deficit. Patients were admitted from 2017 to 2021 and submitted to neuroimaging: CT and MR. Data was collected in May 2021 at informatic system.ResultsAmong 38 participants, the median age was 64 years; 86,8% were male. 35 realize CT, 34 with alterations: 23 with microvascular lesions, 17 with cortical atrophy, 8 with white matter hypodensities and 7 with subcortical atrophy. From all patients, only 14 realize MR, 13 with alterations, the most common vascular leukoencephalopathy and cortical atrophy.ConclusionsOur results support the hypothesis of neuroimaging changes resulting from alcohol consumption. The severity of alcohol dependence also correlates with neuropathophysiological and neuroimaging changes. Volume shrinkage, altered glucose metabolism and perfusion along with evidence of markedly decreased neuron density are commonly reported. The evidence of neuro-circuit disturbances is seen in form of significant loss of white matter (most prominent in the prefrontal cortex, cerebellum and corpus callosum) on functional imaging. Greater cognitive impairment has been associated with multiple and repeated withdrawal due to greater neuronal damage, and can limit the psychotherapeutic intervention, the adherence to pharmacological therapy and abstinence maintenance. The sheer presence of alcohol use disorder should encourage a neuroimaging evaluation.Disclosure of InterestNone Declared

Clinical Practice Guidelines for Assessment and Management of Patients with Substance Intoxication Presenting to the Emergency Department.

Clinical Practice Guidelines for Assessment and Management of Patients with Substance Intoxication Presenting to the Emergency Department.

Effectiveness of Psychosocial Intervention in the Management of Alcohol Dependence Syndrome with Poor Marital Adjustment: A Case Report

Aim: Globally, it has been found that the mean lifetime prevalence of alcohol use is 80% and for alcohol use disorder (AUD) is 8.6%, and AUD has an adverse impact on an individual as well as on the person’s family. In view of the same, we choose a case of alcohol dependence syndrome (ADS) to investigate the effect of long-term alcohol use on family dynamics, marital adjustment, interpersonal relationship, and motivational level of the individual with ADS, as well as the effectiveness of pre- and post- brief psychosocial intervention in the treatment outcome of the individual with ADS by involving his family and strengthening his interpersonal relationships.
 Presentation of the Case: The client had a history of alcohol use for 22 years. Gradually, his alcohol intake was increased from 100 ml/day to 2-5 litres/day in the last few years. Due to his worsening condition, he was admitted to hospital in 2016 and diagnosed with ADS. He remained abstinent for the next 5–6 months after discharge, but had poor treatment compliance. For the past 2.5 years (2016– 2019), the client again started drinking and the symptoms recurred. He was admitted there again on May 30, 2019. It was found that the prolonged alcohol use of the client had an adverse impact on his spouse’s wellbeing and also on his interpersonal relationships with his parents and siblings. Further, it was found that the client had a lower level of motivation, poor adaptive patterns, inadequate social support, and poor marital adjustment.
 Discussion: This study discovered a significant difference between pre- and post-psychosocial intervention in the management of ADS. After our intervention, the client has been doing well. His marital adjustment has increased with his improvement in quality of life, family dynamics, and adaptive patterns.
 Conclusion: It was found that psychosocial intervention with the person with alcohol dependence as well as his family is effective and plays a very crucial role in treatment and wellbeing.

Alcohol-related brain damage: A mixed-method evaluation of an online awareness-raising programme for frontline care and support practitioners.

Alcohol-related brain damage (ARBD) is an umbrella term referring to the neurocognitive impairments caused by excessive and prolonged alcohol use and the associated nutritional deficiencies. This study evaluated the outcomes of an online research-informed training program for ARBD which aimed to improve client outcomes by promoting support staff's awareness and confidence in working with clients who may have (or who are at risk of developing) the condition. Staff working within a large non-governmental non-profit housing organisation (n=883) enrolled in the training program. Questionnaires were used pre- and post-training to collect self-reported awareness of ARBD and confidence in supporting individuals with the condition. Semi-structured interviews were conducted with 27 staff members approximately 10 weeks post-completion of the program. Interviews were audio-recorded, transcribed verbatim and analysed by employing qualitative content analysis. Findings from the questionnaires indicated a significant increase in all measures after completing the training program. Three main themes were developed based on the interview data: changes to awareness and understanding; professional practice; and training-specific characteristics. Participants reported changes in their ability to identify potential service users with ARBD and confidence in doing so. Our findings demonstrate that online training programs can be effective in improving support staff's ability to identify ARBD, potentially leading an increase in signposting service users to relevant services. The research-informed nature of the training demonstrates that translating research findings directly to frontline workers can have a substantial impact and may improve outcomes for this client group.

61-Year-Old Man With Nausea and Vomiting

61-Year-Old Man With Nausea and Vomiting

AYURVEDIC MANAGEMENT OF CHRONIC LIVER DISEASE (CLD) –AN ANALYTICAL REVIEW

Liver controls our whole body activities. Liver cirrhosis is a most common medical problem today. One and the chief cause of it is chronic alcoholic consumption. Excessive and prolonged use of alcohol affects every organ of the body. Although liver, heart and kidney are most affected due to heavy consumption, alcohol induced liver cirrhosis is a life threatening condition in maximum cases. More than 50% people of in India rely on Ayurveda and herbal medicine for liver diseases. More than three hundred herbo-mineral preparations are available in Ayurvedic system of medicine for the treatment of jaundice and chronic liver diseases. Ayurveda plays a master role in the fast and safe recovery of damaged liver. Liver cirrhosis can be correlated to Kumbhakamala in Ayurveda w.s.r. etiology, symptoms, complications and line of treatment. Ayurvedic drugs helps in rejuvenating the liver and minimizing the complications of cirrhosis such a liver cancer, fulminant hepatitis and prevents the chronicity of the disease. In the present article, analytical review of liver disorders and its management in Ayurveda has been evaluated.

Alterations in connectivity of the bed nucleus of the stria terminalis during early abstinence in individuals with alcohol use disorder.

For individuals with Alcohol Use Disorder (AUD), long-term recovery is difficult in part due to symptoms of anxiety that occur during early abstinence and can trigger relapse. Research in rodent models of AUD has identified the bed nucleus of the stria terminalis (BNST), a small, sexually dimorphic, subcortical region, as critical for regulating anxiety-like behaviors during abstinence, particularly in female mice. Furthermore, prolonged alcohol use and subsequent abstinence alter BNST afferent and efferent connections to other brain regions. To our knowledge, however, no studies of early abstinence have investigated BNST structural connectivity in humans during abstinence; this study addresses that gap. Nineteen participants with AUD currently in early abstinence and 20 healthy controls completed a diffusion tensor imaging (DTI) scan. BNST structural connectivity was evaluated using probabilistic tractography. A linear mixed model was used to test between-groups differences in BNST network connectivity. Exploratory analyses were conducted to test for correlations between BNST connectivity and alcohol use severity and anxiety within the abstinence group. Sex was included as a factor for all analyses. The BNST showed stronger structural connectivity with the BNST network in early abstinence women than in control women, which was not seen in men. Women also showed region-specific differences, with stronger BNST-hypothalamus structural connectivity but weaker vmPFC-BNST structural connectivity than men. Exploratory analyses also demonstrated a relationship between alcohol use severity and vmPFC-BNST structural connectivity that was moderated by sex. This study is the first to demonstrate BNST structural connectivity differences in early abstinence and revealed key sex differences. The sex-specific differences in BNST structural connectivity during early abstinence could underlie known sex differences in abstinence symptoms and relapse risk and help to inform potential sex-specific treatments.

Evaluation of the Erythrocyte Membrane in Head and Neck Cancer Patients.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous and complex disease, both from a clinical and molecular point of view. The prolonged use of alcohol and tobacco, along with the release of tumor secretions can modulate blood cells, such as erythrocytes. Here, this study was conducted with 24 patients diagnosed with HNSCC and an equal number of healthy individuals are matched by age and gender. The levels of lipid peroxidation were measured using the individual plasma, while for lipid concentrations, identification and quantification Na, K-ATPase activity and osmotic fragility, the red blood cell concentrate were used. The release of TBARS was significantly higher in patients with HNSCC. The lipid profile assays demonstrated a rearrangement of the erythrocyte membrane due to a decrease in total phospholipids and phosphatidylethanolamine followed by an increase in total cholesterol and phosphatidylcholine. Na, K-ATPase activity also increased. Erythrocytes were more fragile in patients with HNSCC than in health individuals. Therefore, the membrane of erythrocytes were rearranged and Na, K-ATPase function altered in the HNSCC patients. Our findings suggests that the alcohol, tobacco and tumor secretion modulate in a specific manner that the erythrocytes membranes of these patients making this system a potential tool for HNSCC biomarker of tumor progression.

Nonsurgical treatment of oral cavity leukoplakia

Treatment of the oral cavity leukoplakia, a potentially malignant lesion, is presently not evidenced based. Leukoplakia is a premalignant lesion of the oral cavity which has increased risk for oral cancer. If the leukoplakia is treated in its incipient stage, the chance of occurrence of the oral cancer can be reduced. Although there are several treatment options for leukoplakia, there is no specific and appropriate one for minimizing the malignant transformation of the leukoplakia. Tobacco and prolonged use of alcohol can cause significant risk factors toward origin of the oral cavity leukoplakia. Surgical excision, cryotherapy, and laser excision are the useful modes of the treatment for oral leukoplakia, but the minimizing the risk of the malignant transformation is still doubtful. However, the medical treatment for oral cavity leukoplakia is often attractive particularly to prevent the transformation of the leukoplakia into malignancy. The medical treatment is based on chemoprevention such as Vitamin A and retinoid, carotenoids, tea extract, bleomycin, and Vitamin C have been used although with inconclusive output. The nonsurgical treatment overweighs because of its non-invasiveness, good cosmetic result, well tolerated by the patient without cumulative toxicity and used when the surgery is avoided or contraindicated. In this review article, we will discuss different nonsurgical treatment options for oral cavity leukoplakia.

Alcoholic-related liver disease: pathogenesis, management and future therapeutic developments.

Alcohol-related liver disease (ALD) is the most frequent cause of advanced chronic liver disease worldwide. Excessive and prolonged alcohol use leads to ALD, which ranges from early forms such as alcoholic fatty liver (AFL) and alcoholic steatohepatitis (ASH), through progressive fibrosis to cirrhosis and the development of hepatocellular cancer (HCC). In addition, patients with underlying ALD and continuous alcohol use can develop alcoholic hepatitis (AH), which presents a rapid progression of liver failure and has a high short-term mortality. Genetic, environmental and epigenetic factors influence the progression of ALD to more severe forms. The pathogenesis of ALD is complex and involves multiple pathways. Recent translational studies have demonstrated a key role of the gut-liver axis and innate immunity in hepatocellular damage and fibrosis. In severe forms, hepatocellular de-differentiation and systemic inflammation contribute to liver failure and multiorgan failure. Alcohol abstinence is the cornerstone of therapy for ALD and the prevention of its complications, but the efficacy and accessibility of psycho-familial-social interventions is still poor and effective public health policies to limit problematic alcohol use need to be implemented. Prednisolone is the only current option for AH, with a transient beneficial effect over placebo. For patients with decompensated ALD-cirrhosis and/or development of HCC, liver transplantation (LT) may be required. In recent years, early LT is being increasingly offered to carefully selected AH patients, with excellent long-term survival. New trials of AH treatments are currently ongoing, and translational studies in human samples are paving the way to new promising targeted therapies.

Evoked K-complexes and altered interaction between the central and autonomic nervous systems during sleep in alcohol use disorder.

There is evidence for impairment in both central nervous system (CNS) and autonomic nervous system (ANS) function with prolonged alcohol use. While these impairments persist into abstinence, partial recovery of function has been demonstrated in both systems during sleep. To investigate potential ANS dysfunction associated with cortical CNS responses (impairment in CNS-ANS coupling), we assessed phasic heart rate (HR) fluctuation associated with tones that did and those that did not elicit a K-complex (KC) during stable N2 non-rapid eye movement (NREM) sleep in a group of 16 recently abstinent alcohol use disorder (AUD) patients (41.6±8.5 years) and a group of 13 sex- and age-matched control participants (46.6±9.3 years). Electroencephalogram (EEG) and electrocardiogram (ECG) data were recorded throughout the night. Alcohol consumption questionnaires were also administered to the AUD patients. AUD patients had elevated HR compared to controls at baseline prior to tone presentation. The HR fluctuation associated with KCs elicited by tone presentation was significantly smaller in amplitude, and tended to be delayed in time, in the AUD group compared with the control group, and the subsequent deceleration was also smaller in AUD patients. In both groups, the increase in HR was larger and occurred earlier when KCs were produced than when they were not, and there was no difference in the magnitude of the KC effect between groups. Phasic HR changes associated with KCs elicited by tones are impaired in AUD participants, reflecting ANS dysfunction possibly caused by an alteration of cardiac vagal trafficking. However, only the timing of the HR response was found to relate to estimated lifetime alcohol consumption in AUD. The clinical meaning and implications of these novel findings need to be determined.

Prevalence of health problems among the regular alcohol users (chronic alcoholics) in urban and rural area of district Amritsar: Punjab: India

Introduction- The menace of alcohol abuse in the Punjab State is not less prevalent than the rest of India. Alcoholism in Punjab is assuming an alarming proportion. Chronic alcohol abuse may lead to mal-absorption of various substances, calcium, vitamin B complex and iron leading to health problems. Objective- To assess the impact of prolonged alcohol use on different systems of the body leading to health problems. Methods-The present cross-sectional study was conducted in rural and urban field practice areas attached to the Department of Community Medicine, Government Medical College, Amritsar. The target population in urban area was 847 and in rural area it was 737. Three sets of proforma i.e. A, B and C were evolved. Results- Majority of the regular alcohol users were suffering from different liver diseases like fatty infiltration 60 (56.08%), alcoholic hepatitis 25 (23.36%), alcoholic cirrhosis 10 (9.35%). In cardiovascular system assessment, 23 (21.50%) were suffering from severe hypertension. Recurrent chest infections were observed in 32 (29.91%). In CNS assessment it was observed that 37 (34.58%) were suffering from loss of recent memory and 51 (47.68%) from insomnia. Delayed ejaculation was observed in 30 (28.04%). Conclusion- There is urgent need for further indepthcommunity based research in a larger sample and for a longer period, should be undertaken jointly by the specialists from the medical profession, social scientists and enforcement agencies to have real picture of alcohol consumption and its effect on health.

Modulation of serotonin and noradrenaline in the BLA by pindolol reduces long-term ethanol intake.

Repeated cycles of binge-like alcohol consumption and abstinence change the activity of several neurotransmitter systems. Some of these changes are consolidated following prolonged alcohol use and are thought to play an important role in the development of dependence. We have previously shown that systemic administration of the dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist pindolol selectively reduces long-term but not short-term binge-like consumption of ethanol and alters excitatory postsynaptic currents in basolateral amygdala (BLA) principal neurons. The aim of this study was to investigate the effects of pindolol microinfusions in the BLA on long-term ethanol intake using the drinking-in-the-dark paradigm in mice. We also microinfused RU24969 (5-HT1A/1B receptor partial agonist) and CGP12177 (β1/2 adrenergic antagonist) following long-term ethanol intake and determined the densities of 5-HT1A/1B receptors and β1/2 adrenergic in the BLA following short-term (4weeks) and long-term ethanol (12weeks) consumption. We show that intra-BLA infusion of pindolol (1000pmol/0.5μl), RU24969 (0.3 and 3pmol/0.5μl) and CGP12177 (500pmol/0.5μl) produce robust decreases in long-term ethanol consumption. Additionally, we identified reduced β1/2 adrenergic receptor expression and no change in 5-HT1A/1B receptor density in the BLA of long-term ethanol-consuming mice. Collectively, our data highlight the effects of pindolol on voluntary, binge-like ethanol consumption behavior following long-term intake.

Training Behavioral Control in Adolescents Using a Serious Game

Risk taking, such as heavy alcohol use, is commonplace among adolescents. Nevertheless, prolonged alcohol use at this age can lead to severe health problems. The goal of this study was to develop and evaluate a serious game training ("The Fling"), aimed at increasing behavioral control in adolescents and thereby helping them to improve control over their alcohol use. The game training was compared to a game placebo and a nongame training version in a randomized controlled trial. A sample of 185 adolescents (mean age 14.9 years) in secondary education participated in the study. They performed four sessions of training, as well as a set of questionnaires and cognitive assessment tasks before and after the training. The basis for the training was the stop-signal paradigm, aimed at increasing behavioral control. The game variants were shown to motivate adolescents beyond the level of the nongame version. Behavioral control improved significantly over time, but this effect was also present in the game placebo, suggesting that the game activities alone may have had a beneficial effect on our measures of behavioral control. As baseline drinking levels were low, no significant training effects on drinking behavior were found. Although the current results are not yet conclusive as to whether "The Fling" is effective as a cognitive training, they do warrant further research in this direction. This study also shows that serious games may be uniquely suitable to bridge the gap between an evidence-based training paradigm and an attractive, motivating training environment.

This paper discusses the relationship between alcohol consumption and suicidal behavior in Belarus

IntroductionSuicide is one of the main causes of premature mortality in Belarus. It is well recognized that drinking is among the major risk factors that are associated with suicidal behavior.AimsThis study was design to extend our understanding the relationship between alcohol and suicidal behavior.MethodsRisk factors for suicidal behavior (completed suicide and parasuicide) among residents of Minsk city and Gomel city were studied.ResultsAmong the residents of Minsk the maximum suicides risk was in the age of 46–60 years, and parasuicide at age 20–39 years. The ratio of men to women - 4:1; they were often BAC-positive (from 38.8% in 2015 to 42% in 2008). Among parasuicides sex ratio of about 1:1; 30% of men aged 20–39 years, were BAC-positive. Studies in the city of Gomel, has shown maximum number of parasuicides in the ages of 18–29 years (39.3% in women and 30.7% men). Among parasuicides the majority of men (57.8%) and a significant proportion of women (34.2%) were BAC-positive. Maximum number of those attempted suicide and dependent on alcohol were among men ages 30–39 years (66.15%) and 50–59 years (65.22%), among women in the age 30–39 years (45.45%).ConclusionsAcute alcohol intoxication is characteristic of young people who commit parasuicide. Chronic alcohol intoxication is a risk factor in middle-aged persons who commit suicide. Prolonged use of alcohol contributes to the development of comorbid mental disorders, during the crisis of middle age is manifested as an increased risk of suicides.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Individual Variation in Alcohol Intake Predicts Reinforcement, Motivation, and Compulsive Alcohol Use in Rats.

Alcohol is one of the most commonly used psychoactive substances. Prolonged alcohol use can result in alcohol use disorder (AUD), characterized by excessive and compulsive alcohol consumption. Importantly, however, the development of AUD only happens in a minority of individuals who consume alcohol. To understand the individual vulnerability for AUD, models that capture both the individual variability in alcohol consumption and the transition from casual to compulsive alcohol use are essential. Individual variability in voluntary alcohol intake and the preference for alcohol were assessed under continuous alcohol access (CAA) and intermittent-every-other-day alcohol access (IAA) schedules in the home cage using outbred Lister Hooded rats. Subsequently, the reinforcing properties of alcohol were tested in an operant setting. In subsequent experiments, we performed a quinine adulteration experiment to assess inflexible alcohol consumption and blood alcohol levels (BALs) were assessed after voluntary alcohol consumption. We found marked individual differences in alcohol consumption and preference under both access schedules, whereby subgroups of high- and low-alcohol-drinking rats (HD and LD) could be identified. HD with IAA increased their alcohol intake over days in the first month, whereas LD did not. Moreover, when alcohol access time was extended from 7 to 24 h/d for rats with IAA, alcohol intake profoundly increased in HD with IAA, whereas LD with IAA maintained low levels of alcohol intake. Furthermore, HD earned more alcohol than LD under both fixed ratio and progressive ratio schedules of reinforcement. We further found that HD continued their intake of a quinine-adulterated alcohol solution to a larger extent than LD and HD showed higher BALs after 30 minutes of alcohol consumption. These profound individual differences in alcohol intake, reinforcement, motivation, and AUD-like behavior provide a promising tool to unravel the neurobehavioral underpinnings of individual vulnerability for AUD.

Prednisolone or Pentoxifylline for Alcoholic Hepatitis

BackgroundAlcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists.MethodsWe conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline.ResultsA total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo–placebo group, 14% (38 of 266 patients) in the prednisolone–placebo group, 19% (50 of 258 patients) in the pentoxifylline–placebo group, and 13% (35 of 260 patients) in the prednisolone–pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002).ConclusionsPentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42, and Current Controlled Trials number, ISRCTN88782125)