Risk factors for symptom exacerbation among treated patients with substance use disorders

Aims The purpose of this study was to develop an index of risk factors to identify patients prospectively with substance use disorders whose substance use symptoms exacerbate during or shortly after treatment, and to identify characteristics of care that may reduce the likelihood of exacerbation. Design, setting, participants On the basis of data obtained from a nation‐wide outcomes monitoring system, a group of 2809 treated patients experienced an exacerbation of their substance use symptoms. These patients were matched on baseline substance abuse problems with 5618 patients who remained stable or improved. Measurements and findings Risk factors for substance use symptom exacerbation included younger age, non‐married status and residential instability; long‐term use of drugs, prior arrests, prior alcohol treatment, alcohol and drug abuse or dependence diagnoses, cocaine abuse or dependence and more severe self‐rated drug problems; and psychiatric problems. High‐risk patients who obtained a longer episode of mental health care were less likely to experience an exacerbation of symptoms. Conclusions Clinicians can identify at treatment entry patients whose substance use symptoms are likely to exacerbate and, by providing these patients a longer duration of care, may reduce the likelihood of symptom exacerbation.     

Paths of entry into alcoholics anonymous: consequences for participation and remission

BACKGROUND: This study compared individuals with alcohol use disorders who, in the first year after initiating help-seeking, entered Alcoholics Anonymous (AA) only, entered professional treatment and AA together, or entered professional treatment only METHODS: A sample of initially untreated individuals (N = 362) was surveyed at baseline and 1 year, 3 years, 8 years, and 16 years later. At each contact point, participants described their participation in AA and treatment and their current alcohol-related functioning. They also described their reasons for entering AA and/or treatment and the perceived benefits of these sources of help RESULTS: Compared with individuals who initially participated only in treatment but later entered AA, those who entered treatment and AA together participated in AA longer and more frequently and were more likely to achieve remission. Among individuals who initially participated only in AA, those who later entered treatment had poorer remission outcomes than those who did not enter treatment. Longer duration of participation in AA was associated with a higher likelihood of remission at all four follow-ups; individuals who dropped out of AA were more likely to relapse or remain nonremitted. CONCLUSIONS: Compared with individuals who participated only in professional treatment in the first year after they initiated help-seeking, individuals who participated in both treatment and AA were more likely to achieve remission. Individuals who entered treatment but delayed participation in AA did not appear to obtain any additional benefit from AA.     

Alcoholics Anonymous attendance, decreases in impulsivity and drinking and psychosocial outcomes over 16 years: moderated-mediation from a developmental perspective

Aims To examine whether decreases in impulsivity account for links between Alcoholics Anonymous (AA) attendance and better drinking and psychosocial outcomes, and whether these mediational ‘effects’ are conditional on age. Design A naturalistic study in which individuals were assessed at baseline, and 1, 8 and 16 years later. Setting Participants initiated help‐seeking through the alcohol intervention system (detoxification programs, information and referral centers). Participants Individuals with alcohol use disorders and no prior history of substance abuse treatment at baseline [n = 628; 47% women; mean age = 34.7 years (standard deviation = 9.4)]. Measurements Self‐reports of impulsivity and drinking pattern at baseline and year 1, duration of AA (number of weeks) in year 1 and drinking (alcohol use problems, self‐efficacy to resist drinking) and psychosocial outcomes (emotional discharge coping, social support) at baseline and follow‐ups. Findings Controlling for changes in drinking pattern, decreases in impulsivity were associated with fewer alcohol use problems, better coping and greater social support and self‐efficacy at year 1, and better coping and greater social support at year 8. Decreases in impulsivity statistically mediated associations between longer AA duration and improvements on all year 1 outcomes and indirect effects were moderated by participant age (significant only for individuals 25 years of age or younger). Conclusions Decreased impulsivity appears to mediate reductions in alcohol‐related problems over 8 years in people attending Alcoholics Anonymous.     

The long-term effectiveness of brief interventions for unsafe alcohol consumption: a 10-year follow-up

Aims To examine the long‐term impact of brief and early interventions for hazardous and harmful alcohol consumption. Design A 9‐month and 10‐year follow‐up of subjects recruited into a randomized controlled trial of a range of alcohol‐related brief interventions. Setting General practices, the outpatient or acute care services of a major city hospital, and a privately run health screening programmeme. Participants The cohort of 554 (non‐dependent) hazardous and harmful drinkers recruited into the Australian arm of the Phase II World Health Organization collaborative project on identification and treatment of persons with harmful alcohol consumption. Intervention The effectiveness of three forms of intervention, ranging from 5 to 60 minutes in duration, were compared with a no‐treatment control condition. Measurements Included drinking behaviour and biological markers of alcohol use. In addition, at 10 years subjects were asked about symptoms of diagnosable alcohol use disorders and their experience of alcohol‐related psychological, social and physical harm. Mortality was also assessed. Findings Results provide further evidence for the short‐term effectiveness of alcohol‐related brief interventions. In comparison to controls, subjects offered intervention: (1) report significantly lower consumption; and (2) less unsafe drinking at 9‐month follow‐up. The intensity of intervention was not related to the amount of change in drinking behaviour. Analysis at 10 years failed to find any differences in outcomes between intervention and control groups in median consumption, mean reduction in consumption from baseline to follow‐up, mortality and ICD‐10 diagnoses of alcohol dependence or harmful alcohol use. Conclusions This study failed to find evidence that brief advice and counselling without regular follow‐up and reinforcement can sustain significant long‐term reductions in drinking behaviour at 10‐year follow‐up.     

Predictors of 16-year mortality among individuals initiating help-seeking for an alcoholic use disorder

BACKGROUND AND METHODS: We examined rates and predictors of mortality in individuals (47% women) who had just initiated help-seeking for their alcohol use disorders (AUDs) at the start of the study (n=628) and were followed for 16 years. RESULTS: For both women and men, the observed-to-expected mortality ratio (1.4) was lower than rates found in samples of treated individuals with AUDs, suggesting that those initiating help-seeking careers have better chances of long-term survival. Of the individuals for whom cause of death was known, 68% died of alcohol-related causes. Men were more likely to die than were women. When gender was controlled, individuals who were older and unmarried and had more alcohol dependence symptoms at baseline were more likely to die over the 16-year period. When these baseline characteristics were controlled, better drinking outcomes at 1 year were associated with a lower likelihood of subsequent death. The combination of a shorter duration of inpatient/residential care and better drinking outcomes at 1 year was related to a lower probability of death, as was the combination of a longer duration of outpatient care or Alcoholics Anonymous attendance and better drinking outcomes at 1 year. CONCLUSIONS: Efforts should be made to help providers identify individuals who are not responding positively to inpatient or residential treatment and intervene to motivate participation in continuing outpatient care and community 12-step self-help groups to reduce the likelihood of a chronic and fatal AUD course.     

How important is treatment? One‐year outcomes of treated and untreated alcohol‐dependent individuals

Aims To compare representative treatment and untreated samples of alcohol‐dependent individuals in rates of abstinence and non‐problematic use at 1‐year follow‐up. Participants and design A total of 482 alcohol‐dependent adults in a northern California county identified through a probability survey of problem drinkers in the general population (n = 111) or a survey of consecutive admissions to public and private substance abuse programs (n = 371) were interviewed in person at baseline and by telephone at 1 year. Measurements Logistic regression models were used to predict 30‐day abstinence and 12‐month non‐problematic alcohol use. Results At follow‐up, alcohol‐dependent individuals in the treatment sample had higher abstinence rates and non‐problematic use outcomes than those in the untreated general population sample. In logistic regression models of the merged samples, being in the treatment sample was related strongly and positively to abstinence and non‐problematic use. Having more drug users and heavy drinkers in one's social network, higher psychiatric comorbidity, and more social consequences were inversely related to abstinence and non‐problematic use in the treatment sample. The number of drug users and heavy drinkers in one's social network was also inversely related to abstinence in both the treatment and untreated general population samples. Results predicting non‐problematic use were similar. Conclusions These results are consistent with other studies that examine treatment effectiveness in the absence of a controlled trial. Although natural recovery also occurs, alcohol‐dependent individuals benefit from treatment. Co‐occurring psychiatric problems continue to be major barriers to treatment effectiveness. An emphasis on changing social networks to be conducive to recovery could heighten both clinical effectiveness and prevention efforts within communities.     

Computer-based psychological treatment for comorbid depression and problematic alcohol and/or cannabis use: a randomized controlled trial of clinical efficacy

Aims To evaluate computer‐ versus therapist‐delivered psychological treatment for people with comorbid depression and alcohol/cannabis use problems. Design Randomized controlled trial. Setting Community‐based participants in the Hunter Region of New South Wales, Australia. Participants Ninety‐seven people with comorbid major depression and alcohol/cannabis misuse. Intervention All participants received a brief intervention (BI) for depressive symptoms and substance misuse, followed by random assignment to: no further treatment (BI alone); or nine sessions of motivational interviewing and cognitive behaviour therapy (intensive MI/CBT). Participants allocated to the intensive MI/CBT condition were selected at random to receive their treatment ‘live’ (i.e. delivered by a psychologist) or via a computer‐based program (with brief weekly input from a psychologist). Measurements Depression, alcohol/cannabis use and hazardous substance use index scores measured at baseline, and 3, 6 and 12 months post‐baseline assessment. Findings (i) Depression responded better to intensive MI/CBT compared to BI alone, with ‘live’ treatment demonstrating a strong short‐term beneficial effect which was matched by computer‐based treatment at 12‐month follow‐up; (ii) problematic alcohol use responded well to BI alone and even better to the intensive MI/CBT intervention; (iii) intensive MI/CBT was significantly better than BI alone in reducing cannabis use and hazardous substance use, with computer‐based therapy showing the largest treatment effect. Conclusions Computer‐based treatment, targeting both depression and substance use simultaneously, results in at least equivalent 12‐month outcomes relative to a ‘live’ intervention. For clinicians treating people with comorbid depression and alcohol problems, BIs addressing both issues appear to be an appropriate and efficacious treatment option. Primary care of those with comorbid depression and cannabis use problems could involve computer‐based integrated interventions for depression and cannabis use, with brief regular contact with the clinician to check on progress.     

Effectiveness of naltrexone in a community treatment program

OBJECTIVE: In several large, well-designed, randomized, double-blind studies, the opiate antagonist naltrexone demonstrated efficacy in the treatment of alcohol dependence. Specifically, when combined with certain psychosocial therapies, naltrexone reduces the number of drinking days, heavy drinking, and time to relapse to alcohol use in alcohol-dependent individuals. Whether this efficacy can be generalized to individuals who have alcohol use disorders and present for treatment at front-line community treatment programs has not been well established. METHODS: A total of 145 patients who presented for treatment at a rural community substance abuse treatment center were randomized to receive naltrexone 50 mg daily plus usual program treatment (n = 54), placebo plus usual treatment (n = 43), or usual treatment alone (n = 48) for 12 week. A total of 133 participants had at least one follow-up visit. Primary outcome measures included percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days (four or more for women and six or more for men), and time to first heavy drinking day. Secondary measures included changes in serum biological markers (alkaline phosphatase, alanine transaminase, aspartate transaminase, and gamma-glutamyltransferase), craving, and psychosocial functioning. RESULTS: In the intention-to-treat analysis, there were no between-group differences for any of the primary drinking outcomes at 12 weeks. In post hoc exploratory analyses, the entire sample of participants was divided into two new groups: (1) people who drank during the 2 weeks before the start of medication (entry drinkers) and (2) people who did not drink during this interval (entry abstainers). Entry abstainers were at an advantage at study entry in that they were significantly more likely to have an inpatient hospitalization immediately before entry into outpatient treatment. Mixed-model analysis of variance revealed a main effect for entry group at the 12-week treatment endpoint on the primary outcome measures of percent days drinking, average drinks per drinking day, average drinks per day, heavy drinking days, and time to first heavy drinking day. Participants in any of the randomized groups who were entry abstainers had significantly better improvement on all of the primary outcome measures. The abstainer groups that were randomized to placebo and usual treatment had significantly better outcomes than the entry drinkers in those perspective groups. However, for the naltrexone-treated group, entry drinkers and entry abstainers had similar improvement in drinking-related outcomes. CONCLUSIONS: These data suggest that naltrexone may offer particular benefit to patients who continue to drink during the early stages of the trial as compared with those who have achieved abstinence before treatment entry.     

Extended telephone-based continuing care for alcohol dependence: 24-month outcomes and subgroup analyses

Aims To determine whether 18 months of telephone continuing care improves 24‐month outcomes for patients with alcohol dependence. Subgroup analyses were performed to identify patients who would benefit most from continuing care. Design Comparative effectiveness trial of continuing care that consisted of monitoring and feedback only (TM) or monitoring and feedback plus counseling (TMC). Patients were randomized to treatment as usual (TAU), TAU plus TM or TAU plus TMC, and followed quarterly for 24 months. Setting Publicly funded intensive out‐patient programs (IOP). Participants A total of 252 alcohol‐dependent patients (49% with current cocaine dependence) who completed 3 weeks of IOP. Measurements Percentage of days drinking, any heavy drinking and a composite good clinical outcome. Findings In the intent‐to‐treat sample, group differences in alcohol outcomes out to 18 months favoring TMC over TAU were no longer present in months 19–24. There was also a non‐significant trend for TMC to perform better than usual care on the good clinical outcome measure (60% vs. 46% good clinical outcome in months 19–24). Overall significant effects favoring TMC and TM over TAU were seen for women; and TMC was also superior to TAU for participants with social support for drinking, low readiness to change and prior alcohol treatments. Most of these effects were obtained on at least two of three outcomes. However, no effects remained significant at 24 months. Conclusions The benefits of an extended telephone‐based continuing care programme to treat alcohol dependence did not persist after the end of the intervention. A post‐hoc analysis suggested that women and individuals with social support for drinking, low readiness to change or prior alcohol treatments may benefit from the intervention.     

Effectiveness of drug and alcohol counselling during methadone treatment: content, frequency, and duration of counselling and association with substance use outcomes

AIMS: The study investigates the relationship between the type and severity of drug and alcohol use problems, and the provision of drug- and alcohol-counselling in methadone programmes. The study also specifically investigates the relationship between content, frequency and duration of counselling provided during the first month of treatment, and heroin, cocaine, and alcohol use outcomes at 6 months. DESIGN, SETTING AND PARTICIPANTS: The sample comprised 276 patients receiving outpatient methadone treatment who were followed-up 6 months after treatment entry. MEASUREMENTS: Data on client characteristics, drug and alcohol problems and on counselling received were collected by structured face-to-face interviews. FINDINGS: Drug-focused counselling was associated with less frequent heroin and cocaine use at follow-up, but was not related to pre-treatment drug use. Alcohol-focused counselling was provided for those with higher levels of drinking at admission but was not significantly associated with drinking outcome at 6 months. CONCLUSIONS: Results indicate that there are complex interactions between presenting substance use problems, provision of counselling and treatment outcomes. These interactions differ by substance type.     

Brief alcohol interventions for mandated college students: comparison of face-to-face counseling and computer-delivered interventions

Aims College students who violate alcohol policies are often mandated to participate in alcohol‐related interventions. This study investigated (i) whether such interventions reduced drinking beyond the sanction alone, (ii) whether a brief motivational intervention (BMI) was more efficacious than two computer‐delivered interventions (CDIs) and (iii) whether intervention response differed by gender. Design Randomized controlled trial with four conditions [brief motivation interventions (BMI), Alcohol 101 Plus?, Alcohol Edu for Sanctions^®, delayed control] and four assessments (baseline, 1, 6 and 12 months). Setting Private residential university in the United States. Participants Students (n = 677; 64% male) who had violated campus alcohol policies and were sanctioned to participate in a risk reduction program. Measurements Consumption (drinks per heaviest and typical week, heavy drinking frequency, peak and typical blood alcohol concentration), alcohol problems and recidivism. Findings Piecewise latent growth models characterized short‐term (1‐month) and longer‐term (1–12 months) change. Female but not male students reduced drinking and problems in the control condition. Males reduced drinking and problems after all interventions relative to control, but did not maintain these gains. Females reduced drinking to a greater extent after a BMI than after either CDI, and maintained reductions relative to baseline across the follow‐up year. No differences in recidivism were found. Conclusions Male and female students responded differently to sanctions for alcohol violations and to risk reduction interventions. BMIs optimized outcomes for both genders. Male students improved after all interventions, but female students improved less after CDIs than after BMI. Intervention effects decayed over time, especially for males.     

Rates and predictors of relapse after natural and treated remission from alcohol use disorders

AIMS: This study examined the rates and predictors of 3-year remission, and subsequent 16-year relapse, among initially untreated individuals with alcohol use disorders who did not obtain help or who participated in treatment and/or Alcoholics Anonymous in the first year after recognizing their need for help. DESIGN AND MEASURES: A sample of individuals (n = 461) who initiated help-seeking was surveyed at baseline and 1 year, 3 years, 8 years and 16 years later. Participants provided information on their life history of drinking, alcohol-related functioning and life context and coping. FINDINGS: Compared to individuals who obtained help, those who did not were less likely to achieve 3-year remission and subsequently were more likely to relapse. Less alcohol consumption and fewer drinking problems, more self-efficacy and less reliance on avoidance coping at baseline predicted 3-year remission; this was especially true of individuals who remitted without help. Among individuals who were remitted at 3 years, those who consumed more alcohol but were less likely to see their drinking as a significant problem, had less self-efficacy, and relied more on avoidance coping, were more likely to relapse by 16 years. These findings held for individuals who initially obtained help and for those who did not. CONCLUSIONS: Natural remission may be followed by a high likelihood of relapse; thus, preventive interventions may be indicated to forestall future alcohol problems among individuals who cut down temporarily on drinking on their own.     

Cohort effects on gender differences in alcohol dependence

Aims The present study investigated the presence of cohort effects on gender differences in the course, severity and symptomatology of DSM‐III‐R alcohol dependence in a community‐based sample. Design A comparison of substance‐related variables among men and women divided into two groups based on the median birth year of the sample was conducted. Participants Participants were 468 men and 132 women with life‐time alcohol dependence, the vast majority of whom were born between 1941 and 1960. Measurements Substance use and DSM‐III‐R substance use disorders were assessed by a structured interview administered in person. Findings Individuals born after 1951 had higher rates of alcohol dependence. Among individuals with alcohol dependence, those born after 1951 had an earlier onset and longer duration of alcohol‐related problems. Significant interactions indicated that these effects were stronger for women than men. Conclusions Risk for alcohol dependence appears to be rising in younger generations, and particularly for younger women, making them an important target group for prevention and treatment programs.     

The impact of depressive symptoms on alcohol and cigarette consumption following treatment for alcohol and nicotine dependence

Background:  Although depression is common among alcohol and tobacco dependent patients, its impact on treatment outcomes is not well established. The purpose of this study was to examine the impact of depressive symptoms on abstinence from tobacco and alcohol after treatment for alcohol dependence and nicotine dependence.
Methods:  The Timing of Alcohol and Smoking Cessation Study (TASC) randomized adults receiving intensive alcohol dependence treatment, who were also smokers, to concurrent or delayed smoking cessation treatment. The sample consisted of 462 adults who completed depression and substance use (alcohol and smoking) assessments at treatment entry and 6, 12, and 18 months posttreatment. Longitudinal regression models were used to examine the relationships between depression and subsequent abstinence from alcohol and tobacco after baseline characteristics, including alcohol and smoking histories, were considered.
Results:  Depressive symptoms were prospectively related to nonabstinence from alcohol. Depressive symptoms at the previous assessment increased the odds of drinking at the subsequent time point by a factor of 1.67 (95% CI 1.14, 2.43), p  < 0.01. Depressive symptoms were not significantly related to subsequent abstinence from cigarettes.
Conclusions:  Depression is an important negative predictor of the ability to maintain abstinence from alcohol within the context of intensive alcoholism and smoking treatment. It may be important to include depression-specific interventions for alcohol and tobacco dependent individuals to facilitate successful drinking treatment outcomes.     

Prevalence of musculoskeletal activity limitation and associated factors among adults in the general population in the 1998 Quebec Health Survey

OBJECTIVE: To estimate the prevalence of short term and longterm musculoskeletal activity limitation among the general adult population of the province of Quebec, and to identify which factors are associated with these limitations. METHODS: We analyzed cross-sectional data from the 1998 Quebec Health Survey. Logarithmic binomial regression models were used to estimate prevalence ratios of (1) short term activity limitation related to musculoskeletal disorders (MSD); and (2) longterm activity limitation related to MSD in relation to demographic and behavioral variables and comorbidity factors. RESULTS: About one-fifth of participants reporting short term activity limitation and one-third of participants reporting longterm activity limitation mentioned MSD as a cause. Multivariate analyses showed that higher age, lower income, being overweight, ill defined nervousness, and the number of traumatic events that occurred before age 18 years were significantly associated with short term and longterm activity limitation related to MSD, whereas being in the minority ethnic group was protective for both outcomes. Female sex, physical inactivity, being a former alcohol drinker, and mental disorders were also associated with longterm activity limitation. CONCLUSION: MSD are a major cause of activity limitation among adults from Quebec. With the aging population and the increasing prevalence of obesity, increasing prevalence of activity limitation related to MSD is to be expected.     

Prevalence and Correlates of Withdrawal‐Related Insomnia among Adults with Alcohol Dependence: Results from a National Survey

Insomnia during acute alcohol withdrawal (AWD) as well as persisting insomnia during postacute withdrawal is associated with relapse. Rates of insomnia in clinical samples of alcohol‐dependent patients range from 36% to 91%, but the prevalence of AWD‐related insomnia in the general population is unknown. The purpose of this study was to describe the prevalence of insomnia as a symptom of acute AWD and its correlates in a general population of alcohol‐dependent individuals. Data were analyzed from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions, which sampled 43,093 adults. The prevalence of AWD‐related insomnia among individuals with a lifetime diagnosis of alcohol dependence was 31.7%, which ranked fourth among the eight listed DSM‐IV withdrawal symptoms. Among individuals who met lifetime criteria for both alcohol dependence and AWD, the prevalence of insomnia was approximately 50%. Lifetime diagnoses of major depression and drug use disorders were significant correlates of AWD‐related insomnia in multivariate analyses. A less than 1‐year duration of the heaviest drinking period as well as the onset of alcohol dependence between ages 18 and 27 were negatively associated with AWD‐related insomnia. AWD‐related insomnia is a common symptom among alcohol‐dependent adults in the general population and is related to lifetime co‐occurring diagnoses, age at onset of alcohol dependence, and duration of heaviest drinking period. Its prevalence in the general population provides a representative base rate against which to compare the widely varying rates reported in clinical populations. Because of its relatively frequent prevalence and association with relapse, assessment and treatment of AWD‐related insomnia should be routinely considered in clinical settings. (Am J Addict 2010;19:238–244)     

Sympathetic Nervous System Activity and Ventricular Tachyarrhythmias: Recent Advances

Sympathetic nervous system activity (SNSA) is believed to participate in the genesis of ventricular tachyarrhythmias (VTA) but understanding has been impeded by the number and complexity of effects and the paucity of data from humans. New information from studies of genetic disorders, animal models, and spontaneous human arrhythmias indicates the importance of the temporal pattern of SNSA in arrhythmia development. The proarrhythmic effects of short‐term elevations of SNSA are exemplified by genetic disorders and include enhancement of early and delayed afterdepolarizations and increased dispersion of repolarization. The role of long‐term elevations of SNSA is suggested by animal models of enhanced SNSA signaling that results in apoptosis, hypertrophy, and fibrosis, and sympathetic nerve sprouting caused by infusion of nerve growth factor. Processes that overlap short‐ and long‐term effects are suggested by changes in R‐R interval variability (RRV) that precede VTA in patients by several hours. SNSA‐mediated alterations in gene expression of ion channels may account for some intermediate‐term effects. The propensity for VTA is highest when short‐, intermediate, and long‐term changes are superimposed. Because the proarrhythmic effects are related to the duration and intensity of SNSA, normal regulatory processes such as parasympathetic activity that inhibits SNSA, and oscillations that continuously vary the intensity of SNSA may provide vital antiarrhythmic protection that is lost in severe heart failure and other disorders. These observations may have therapeutic implications. The recommended use of β‐adrenergic receptor blockers to achieve a constant level of inhibition does not take into account the temporal patterns and regional heterogeneity of SNSA, the proarrhythmic effects of α‐adrenergic receptor stimulation, or the potential proarrhythmic effects of β‐adrenergic receptor blockade. Further research is needed to determine if other approaches to SNSA modulation can enhance the antiarrhythmic effects.     

The efficacy of disulfiram for the treatment of alcohol use disorder

Background: Alcohol use disorders (AUD) involving hazardous, harmful, and addictive misuse of alcohol are widespread in most parts of the world. The aim of this study was to review the effect of disulfiram in the treatment of patients with AUD. The effect of disulfiram was evaluated according to the primary outcome of an intake of alcohol below 30 and 20 g/d for men and women, respectively, as well as secondary outcomes such as days until relapse, alcohol intake, and numbers of drinking days. Methods: A systematic review of the literature was conducted using MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). Results: Eleven randomized controlled trials were included with a total of 1,527 patients. They compared disulfiram treatment with placebo, none or other abstinence‐supportive treatments. Overall, 6 studies reported of a significant better effect on abstinence for patients treated with disulfiram. Six of 9 studies measuring secondary outcomes reported that patients treated with disulfiram had significantly more days until relapse and fewer drinking days, respectively. The quality of the included studies was moderate. Heterogeneity was significant in most of the meta‐analyses, but valid results were found regarding the effect of disulfiram versus placebo over 12 months and unsupervised disulfiram versus other or no treatment. The vast majority of significant studies were of shorter duration, while only 3 studies of 12 months were significant regarding more days until relapse and/or reduction in drinking days. Conclusions: Supervised treatment with disulfiram has some effect on short‐term abstinence and days until relapse as well as number of drinking days when compared with placebo, none, or other treatments for patients with alcohol dependency or abuse. Long‐term effect on abstinence has not been evaluated yet. However, there is a need for more homogeneous and high‐quality studies in the future regarding the efficacy of disulfiram.     

Non‐alcoholic fatty liver disease from pathogenesis to management: an update

Non‐alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the Western world, is tightly associated with obesity and metabolic syndrome. NAFLD entails an increased cardiometabolic and liver‐related risk, the latter regarding almost exclusively non‐alcoholic steatohepatitis (NASH), the progressive form of NAFLD. Pathogenetic models encompass altered hepatic lipid partitioning and adipokine action, increased oxidative stress, free fatty acid lipotoxicity. On this basis, lifestyle‐, drug‐ or surgically induced weight loss, insulin sensitizers, antioxidants, lipid‐lowering drugs have been evaluated in NAFLD/NASH. Most trials are small, of short duration, nonrandomized, without histological end points, thus limiting assessment of long‐term safety and efficacy of proposed treatments. All NAFLD patients should be evaluated for their metabolic, cardiovascular and liver‐related risk. Liver biopsy remains the gold standard for staging NAFLD, but non‐invasive methods are under intense development. Weight loss through lifestyle intervention is the initial approach, because of established efficacy on NAFLD‐associated cardiometabolic abnormalities, and to emerging benefits on necroinflammation and overall disease activity in NASH. Bariatric surgery warrants further evaluation before it can be routinely considered in morbidly obese NASH. Larger‐ and longer‐duration randomized trials assessing safety and benefits of drugs on patient‐oriented outcomes are needed before pharmacological treatment can be routinely recommended for NASH.