Sickness absence diagnoses among abstainers,low‐risk drinkers and at‐risk drinkers: consideration of the U‐shaped association between alcohol use and sickness absence in four cohort studies

Aims

To estimate differences in the strength and shape of associations between alcohol use and diagnosis‐specific sickness absence.

Design

A multi‐cohort study. Participants (n = 47 520) responded to a survey on alcohol use at two time‐points, and were linked to records of sickness absence. Diagnosis‐specific sickness absence was followed for 4–7 years from the latter survey.

Setting and participants

From Finland, we had population cohort survey data from 1998 and 2003 and employee cohort survey data from 2000–02 and 2004. From France and the United Kingdom, we had employee cohort survey data from 1993 and 1997, and 1985–88 and 1991–94, respectively.

Measurements

We used standard questionnaires to assess alcohol intake categorized into 0, 1–11 and > 11 units per week in women and 0, 1–34 and > 34 units per week in men. We identified groups with stable and changing alcohol use over time. We linked participants to records from sickness absence registers. Diagnoses of sickness absence were coded according to the International Classification of Diseases. Estimates were adjusted for sex, age, socio‐economic status, smoking and body mass index.

Findings

Women who reported drinking 1–11 units and men who reported drinking 1–34 units of alcohol per week in both surveys were the reference group. Compared with them, women and men who reported no alcohol use in either survey had a higher risk of sickness absence due to mental disorders [rate ratio = 1.51, 95% confidence interval (CI) = 1.22–1.88], musculoskeletal disorders (1.22, 95% CI = 1.06–1.41), diseases of the digestive system (1.35, 95% CI = 1.02–1.77) and diseases of the respiratory system (1.49, 95% CI = 1.29–1.72). Women who reported alcohol consumption of > 11 weekly units and men who reported alcohol consumption of > 34 units per week in both surveys were at increased risk of absence due to injury or poisoning (1.44, 95% CI = 1.13–1.83).

Conclusions

In Finland, France and the United Kingdom, people who report not drinking any alcohol on two occasions several years apart appear to have a higher prevalence of sickness absence from work with chronic somatic and mental illness diagnoses than those drinking below a risk threshold of 11 units per week for women and 34 units per week for men. Persistent at‐risk drinking in Finland, France and the United Kingdom appears to be related to increased absence due to injury or poisoning.     

The short‐term impact of the alcohol act on alcohol‐related deaths and hospital admissions in Scotland: a natural experiment

Background and aim

The introduction of the Alcohol Act in Scotland on 1 October 2011, which included a ban on multi‐buy promotions, was probably associated with a fall in off‐trade alcohol sales in the year after its implementation. The aim of this study was to test if the same legislation was associated with reduced levels of alcohol‐related deaths and hospital admissions in the 3‐year period after its introduction.

Design

A natural experiment design using time–series data to assess the impact of the Alcohol Act legislation in Scotland. Comparisons were made with unexposed populations in the rest of Great Britain.

Setting

Scotland with comparable data obtained for geographical control groups in other parts of Great Britain.

Participants

For alcohol‐related deaths, a total of 17 732 in Scotland and 88 001 in England and Wales throughout 169 4‐week periods between January 2001 and December 2013 and for alcohol‐related hospital admissions, a total of 121 314 in Scotland and 696 892 in England throughout 182 4‐week periods between January 2001 and December 2014.

Measurements

Deaths and hospital admissions in Scotland and control groups that were wholly attributable to alcohol for consecutive 4‐week periods between January 2001 and December 2014. Data were obtained by age, sex and area‐based socio‐economic position.

Findings

There was no evidence to suggest that the Alcohol Act was associated with changes in the overall rate of alcohol‐related deaths [incidence rate ratio (IRR) = 0.99, 95% confidence interval (CI) = 0.91–1.07)] or hospital admissions (IRR = 0.98, 95% CI = 0.95–1.02) in Scotland. In control group analyses, the pseudo intervention variable was not associated with a change in alcohol‐related death rates in England/Wales (IRR = 0.99, 95% CI = 0.95–1.02), but was associated with an increase in alcohol‐related hospital admission rates in England (IRR = 1.05, 95% CI = 1.03–1.07). In combined models, the interaction analysis did not provide support for a ‘net effect’ of the legislation on alcohol‐related deaths in Scotland compared with England/Wales (IRR 0.99, 95% CI = 0.95–1.04), but suggested a net reduction in hospital admissions for Scotland compared with England (IRR = 0.93, 95% CI = 0.87–0.98).

Conclusion

The implementation of the Alcohol Act in Scotland has not been associated clearly with a reduction in alcohol‐related deaths or hospital admissions in the 3‐year period after it was implemented in October 2011.     

Excess overdose mortality immediately following transfer of patients and their care as well as after cessation of opioid substitution therapy

Aims

To investigate clustering of all‐cause and overdose deaths after a transfer of patients and their care to alternative treatment provider and after the end of opioid substitution therapy (OST) in opioid‐dependent individuals in specialist addiction treatment.

Design, Setting and Participants

Mortality data were identified within a sample of 5335 patients with opioid use disorder who had received OST treatment between 1 April 2008 and 31 December 2013 from a large mental health‐care provider in the United Kingdom. We investigated the circumstances and distribution of the 332 deaths identified within the observation window with a specific focus on overdose deaths (n = 103) after a planned discharge, dropout and transfer between services.

Measurements

Crude mortality rates for overdose mortality 14 days, 28 days and more than 1 month after the end of treatment/transfer for overdose mortality.

Findings

Of 47 individuals who died from overdose after having been transferred between services, nine died during the first 2 weeks [crude mortality rate (CMR) = 136.4, 95% confidence interval (CI) = 64.3–243.1] and a further five died during the first month post‐transfer (CMR= 79.5, 95% CI = 44.2–129.7). Of the 32 individuals who died from overdose after planned OST cessation, five died during the first 2 weeks (CMR = 151.5, 95% CI = 51.1–319.0) and a further four died during the first month post‐discharge (CMR = 82.6, 95% CI = 38.4–151.0).

Conclusions

In the United Kingdom, opioid‐dependent people who are transferred to an alternative treatment provider for continuation of their opioid substitution therapy experience high overdose mortality rates, with substantially higher rates during the first month (especially during the first 14 days) following transfer.     

The stability of baseline‐defined categories of alcohol consumption during the adult life‐course: a 28‐year prospective cohort study

Background and aims

Studies that report the relationship between alcohol consumption and disease risk have predominantly operationalized drinking according to a single baseline measure. The resulting assumption of longitudinal stability may be simplistic and complicate interpretation of risk estimates. This study aims to describe changes to the volume of consumption during the adult life‐course according to baseline categories of drinking.

Design

A prospective observational study.

Setting

United Kingdom.

Participants

A cohort of British civil servants totalling 6838 men and 3372 women aged 34–55 years at baseline, followed for a mean 19.1 (standard deviation = 9.5) years.

Measurements

The volume of weekly alcohol consumption was estimated from data concerning the frequency and number of drinks consumed. Baseline categories were defined: non‐current drinkers, infrequent drinkers, 0.1–50.0 g/week, 50.1–100.0 g/week, 100.1–150.0 g/week, 150.1–250.0 g/week and >250.0 g/week. For women, the highest category was defined as > 100.0 g/week. Baseline frequency was derived as ‘daily or almost daily’ and ‘not daily or almost daily’. Trajectories were estimated within baseline categories using growth curve models.

Findings

Trajectories differed between men and women, but were relatively stable within light‐to‐moderate categories of baseline consumption. Drinking was least stable within the highest categories of baseline consumption (men: > 250.0 g/week; women: > 100.0 g/week), declining by 47.0 [95% confidence interval (CI) = 40.7, 53.2] and 16.8 g/week (95% CI = 12.6, 21.0), respectively, per 10‐year increase in age. These declines were not a consequence of sudden transitions to complete abstention. Rates of decline appear greatest in older age, with trajectories converging toward moderate volumes.

Conclusion

Among UK civil servants, consumption within baseline drinking categories is generally stable during the life‐course, except among heavier baseline drinkers, for whom intakes decline with increasing age. This shift does not appear to be driven by transitions to non‐drinking. Cohorts of older people may be at particular risk of misclassifying former heavy drinkers as moderate consumers of alcohol.     

Cigarette brand diversity and price changes during the implementation of plain packaging in the United Kingdom

Background and aim

Plain packaging of cigarettes appeared in the United Kingdom in July 2016 and was ubiquitous by May 2017. The change coincided with another legislative change, raising the minimum pack size from 10 to 20 cigarettes. Laws imposing plain packaging on cigarette packs remove another promotional route from tobacco companies, but the effect of such laws on brand diversity, pricing and sales volume is unknown. This study aimed to (1) describe and quantify changes in brand diversity, price segmentation and sales volumes and (2) estimate the association between the introduction of plain cigarette packaging and cigarette pricing in the United Kingdom.

Design

We used a natural experiment design to assess the impact of plain packaging legislation on brand diversity and cigarette prices. The data comprised a sample of 76% of sales of cigarettes in the UK between March 2013 and June 2017.

Setting

United Kingdom.

Measurements

Cigarette prices, number of brands and products and volumes of sales.

Findings

During the period analysed, there was a slight decrease in the number of cigarette brands. There was also an initial increase observed in the number of cigarette products, due mainly to an increase in the number of products in packs of fewer than 20 cigarettes sold before July 2016, which was then followed by a rapid decrease in the number of products that coincided with the implementation of the new legislation. Cigarette sales volumes during this period did not deviate from the preceding secular trend, but prices rose substantially. Regression results showed that price per cigarette, regardless of pack size, was 5.0 [95% confidence interval (CI) = 4.8–5.3] pence higher in plain than in fully branded packs. For packs of 20 cigarettes, price increases were greater in the lower price quintiles, ranging from 2.6 (95% CI = 2.4–2.7) GBP in the lowest to 0.3 (95% CI = 0.3–0.4) GBP per pack in the highest quintile.

Conclusions

The implementation of standardized packaging legislation in the United Kingdom, which included minimum pack sizes of 20, was associated with significant increases overall in the price of manufactured cigarettes, but no clear deviation in the ongoing downward trend in total volume of cigarette sales.     

Motivation to reduce alcohol consumption and subsequent attempts at reduction and changes in consumption in increasing and higher‐risk drinkers in England: a prospective population survey

Aims

To assess how far motivation to reduce alcohol consumption in increasing and higher‐risk drinkers in England predicts self‐reported attempts to reduce alcohol consumption and changes in alcohol intake during the following 6 months.

Methods

This study used self‐reported data from 2928 higher‐risk drinkers in the Alcohol Toolkit Study (ATS): a series of monthly cross‐sectional household surveys of adults aged 16+ years of age in England. Alcohol consumption was measured in an initial survey and in a 6‐month telephone follow‐up interview using the Alcohol Use Disorders Identification Test (AUDIT)‐C questionnaire. Motivation was measured in the initial survey using the Motivation to Reduce Alcohol Consumption (MRAC) scale. Attempts to reduce alcohol consumption during the past 6 months were recorded at follow‐up. Data were analysed using repeated‐measures difference‐in‐differences and logistic regression models.

Results

Participants with higher initial motivation to reduce alcohol consumption were more likely to report that they had made an attempt to reduce consumption at follow‐up [adjusted odds ratio (OR_adj) = 2.39, 95% confidence interval (CI) = 1.75–3.29]. There was an overall reduction in alcohol consumption between initial survey and follow‐up (OR_adj = 0.72, 95% CI = 0.65–0.79), but there was insufficient evidence of an additional effect of motivation to reduce consumption on subsequent changes in alcohol consumption, with the difference‐in‐differences effect instead suggesting an average increase (OR_adj = 1.37, 95% CI = 1.00–1.88).

Conclusions

Increasing and higher‐risk drinkers in England who report greater motivation to reduce their consumption are more likely to report making an attempt to reduce during the next 6 months, but this may not be associated with a reduction in alcohol consumption.     

Impacts of licensed premises trading hour policies on alcohol‐related harms

Background and aim

Evaluations of alcohol policy changes demonstrate that restriction of trading hours of both ‘on’‐ and ‘off’‐licence venues can be an effective means of reducing rates of alcohol‐related harm. Despite this, the effects of different trading hour policy options over time, accounting for different contexts and demographic characteristics, and the common co‐occurrence of other harm reduction strategies in trading hour policy initiatives, are difficult to estimate. The aim of this study was to use dynamic simulation modelling to compare estimated impacts over time of a range of trading hour policy options on various indicators of acute alcohol‐related harm.

Methods

An agent‐based model of alcohol consumption in New South Wales, Australia was developed using existing research evidence, analysis of available data and a structured approach to incorporating expert opinion. Five policy scenarios were simulated, including restrictions to trading hours of on‐licence venues and extensions to trading hours of bottle shops. The impact of the scenarios on four measures of alcohol‐related harm were considered: total acute harms, alcohol‐related violence, emergency department (ED) presentations and hospitalizations.

Results

Simulation of a 3 a.m. (rather than 5 a.m.) closing time resulted in an estimated 12.3 ± 2.4% reduction in total acute alcohol‐related harms, a 7.9 ± 0.8% reduction in violence, an 11.9 ± 2.1% reduction in ED presentations and a 9.5 ± 1.8% reduction in hospitalizations. Further reductions were achieved simulating a 1 a.m. closing time, including a 17.5 ± 1.1% reduction in alcohol‐related violence. Simulated extensions to bottle shop trading hours resulted in increases in rates of all four measures of harm, although most of the effects came from increasing operating hours from 10 p.m. to 11 p.m.

Conclusions

An agent‐based simulation model suggests that restricting trading hours of licensed venues reduces rates of alcohol‐related harm and extending trading hours of bottle shops increases rates of alcohol‐related harm. The model can estimate the effects of a range of policy options.     

Comparison of acute effects of red wine, beer and vodka against hyperoxia-induced oxidative stress and increase in arterial stiffness in healthy humans

Objective

We determined and compared acute effects of different alcoholic beverages on oxygen-induced increase in oxidative stress plasma marker and arterial stiffness in healthy humans.

Methods

Ten males randomly consumed one of four tested beverages: red wine (RW), vodka, beer (0.32 g ethanol/kg body wt) and water as control. Every beverage was consumed once, a week apart, in a cross-over design. The volunteers breathed 100% normobaric O₂ between 60th and 90th min of 3 h study protocol. Plasma lipid peroxides (LOOH) and uric acid (UA) concentration, blood alcohol concentration (BAC) and arterial stiffness (indicated by augmentation index, AIx) were measured before and 30, 60, 90, 120 and 180 min after beverage consumption.

Results

Intake of all alcoholic beverages caused a similar increase of BAC. The oxygen-induced elevation in AIx was similarly reduced in all three groups relative to the control (3.4 ± 1.3%, 5.4 ± 2.2% and 0.2 ± 1.6% vs. 13.7 ± 2.6% for red wine, vodka, beer and control, respectively, 60 min after intake). Exposure to oxygen resulted in increased plasma LOOH in all groups. However, in RW group this increase was lowest (1.1 ± 0.5) in comparison to the vodka (2.1 ± 0.5), beer (1.6 ± 0.3) and control (2.5 ± 0.4 μM/L H₂O₂). 60 min after intake of RW and beer plasma UA significantly increased (34 ± 4 and 15 ± 3) in contrast to vodka and control (−6 ± 2 and −8 ± 2 μmol/L).

Conclusion

All three alcoholic beverages provided similar protection against oxygen-induced increase in arterial stiffness, probably due to central vasodilatatory effect of alcohol itself, but only RW provided protection against oxygen-induced oxidative stress.     

Effects of endovascular cooling on infarct size in ST‐segment elevation myocardial infarction: A patient‐level pooled analysis from randomized trials

Objectives

This study sought to examine the relationship between temperature at reperfusion and infarct size.

Background

Hypothermia consistently reduces infarct size when administered prior to reperfusion in animal studies, however, clinical results have been inconsistent.

Methods

We performed a patient‐level pooled analysis from six randomized control trials of endovascular cooling during primary percutaneous coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI) in 629 patients in which infarct size was assessed within 1 month after randomization by either single‐photon emission computed tomography (SPECT) or cardiac magnetic resonance imaging (cMR).

Results

In anterior infarct patients, after controlling for variability between studies, mean infarct size in controls was 21.3 (95%CI 17.4‐25.3) and in patients with hypothermia <35°C it was 14.8 (95%CI 10.1‐19.6), which was a statistically significant absolute reduction of 6.5%, or a 30% relative reduction in infarct size (P = 0.03). There was no significant difference in infarct size in anterior ≥35°C, or inferior infarct patients. There was no difference in the incidence of death, ventricular arrhythmias, or re‐infarction due to stent thrombosis between hypothermia and control patients.

Conclusions

The present study, drawn from a patient‐level pooled analysis of six randomized trials of endovascular cooling during primary PCI in STEMI, showed a significant reduction in infarct size in patients with anterior STEMI who were cooled to <35°C at the time of reperfusion. The results support the need for trials in patients with anterior STEMI using more powerful cooling devices to optimize the delivery of hypothermia prior to reperfusion.     

Alcohol Quantity and Type on Risk of Recurrent Gout Attacks: An Internet-based Case-crossover Study

Objectives

Although beer and liquor have been associated with risk of incident gout, wine has not. Yet anecdotally, wine is thought to trigger gout attacks. Further, how much alcohol intake is needed to increase the risk of gout attack is not known. We examined the quantity and type of alcohol consumed on risk of recurrent gout attacks.

Methods

We conducted a prospective Internet-based case-crossover study in the US among participants with gout and who had at least one attack during the 1 year of follow-up. We evaluated the association of alcohol intake over the prior 24 hours as well as the type of alcoholic beverage with risk of recurrent gout attack, adjusting for potential time-varying confounders.

Results

This study included 724 participants with gout (78% men, mean age 54 years). There was a significant dose-response relationship between amount of alcohol consumption and risk of recurrent gout attacks (P <.001 for trend). The risk of recurrent gout attack was 1.36 (95% confidence interval [CI], 1.00-1.88) and 1.51 (95% CI, 1.09-2.09) times higher for >1-2 and >2-4 alcoholic beverages, respectively, compared with no alcohol consumption in the prior 24 hours. Consuming wine, beer, or liquor was each associated with an increased risk of gout attack.

Conclusions

Episodic alcohol consumption, regardless of type of alcoholic beverage, was associated with an increased risk of recurrent gout attacks, including potentially with moderate amounts. Individuals with gout should limit alcohol intake of all types to reduce the risk of recurrent gout attacks.     

Development and validation of the Alcoholic Beverage Identification Deep Learning Algorithm version 2 for quantifying alcohol exposure in electronic images

Background

Seeing alcohol in media has been demonstrated to increase alcohol craving, impulsive decision-making, and hazardous drinking. Due to the exponential growth of (social) media use it is important to develop algorithms to quantify alcohol exposure efficiently in electronic images. In this article, we describe the development of an improved version of the Alcoholic Beverage Identification Deep Learning Algorithm (ABIDLA), called ABIDLA2.

Methods

ABIDLA2 was trained on 191,286 images downloaded from Google Image Search results (based on search terms) and Bing Image Search results. In Task-1, ABIDLA2 identified images as containing one of eight beverage categories (beer/cider cup, beer/cider bottle, beer/cider can, wine, champagne, cocktails, whiskey/cognac/brandy, other images). In Task-2, ABIDLA2 made a binary classification between images containing an “alcoholic beverage” or “other”. An ablation study was performed to determine which techniques improved algorithm performance.

Results

ABIDLA2 was most accurate in identifying Whiskey/Cognac/Brandy (88.1%) followed by Beer/Cider Can (80.5%), Beer/Cider Bottle (78.3%), and Wine (77.8%). Its overall accuracy was 77.0% (Task-1) and 87.7% (Task-2). Even the identification of the least accurate beverage category (Champagne, 64.5%) was more than five times higher than random chance (12.5% = 1/8 categories). The implementation of balanced data sampler to address class skewness and the use of self-training to make use of a large, secondary, weakly labeled dataset particularly improved overall algorithm performance.

Conclusion

With extended capabilities and a higher accuracy, ABIDLA2 outperforms its predecessor and enables the screening of any kind of electronic media rapidly to estimate the quantity of alcohol exposure. Quantifying alcohol exposure automatically through algorithms like ABIDLA2 is important because viewing images of alcoholic beverages in media tends to increase alcohol consumption and related harms.     

Needle and syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta‐analysis

Aims

To estimate the effects of needle and syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of hepatitis C virus (HCV) in people who inject drugs (PWID).

Methods

Systematic review and meta‐analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within the last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥ 100% coverage (receiving sufficient or greater number of needles and syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non‐randomized studies tool. Random‐effects models were used in meta‐analysis.

Results

We identified 28 studies (n = 6279) in North America (13), United Kingdom (five), Europe (four), Australia (five) and China (one). Studies were at moderate (two), serious (17) critical (seven) and non‐assessable risk of bias (two). Current OST is associated with 50% [risk ratio (RR) =0.50, 95% confidence interval (CI) = 0.40–0.63] reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I² = 0, P = 0.889). Weaker evidence was found for high NSP coverage (RR = 0.79, 95% CI = 0.39–1.61) with high heterogeneity (I² = 77%, P = 0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR = 0.44, 95% CI = 0.24–0.80) with low heterogeneity (I² = 12.3%, P = 0.337), but not in North America (RR = 1.58, I² = 89.5%, P = < 0.001). Combined OST/NSP is associated with a 74% reduction in HCV acquisition risk (RR = 0.26, 95% CI = 0.07–0.89, I² = 80% P = 0.007). According to Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria, the evidence on OST and combined OST/NSP is low quality, while NSP is very low.

Conclusions

Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle and syringe programmes (NSP). There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence that high coverage is associated with reduced risk in Europe.     

Mecamylamine treatment for alcohol dependence: a randomized controlled trial

Background and aims

The nicotinic acetylcholine receptor antagonist, mecamylamine, is a potential novel pharmacotherapy for alcohol use disorder. The aims were to compare alcohol consumption between mecamylamine and placebo and test if smoking status modified treatment effects.

Design

Out‐patient, randomized, double‐blind clinical trial for 12 weeks of treatment with mecamylamine (10 mg) (n = 65) versus placebo (n = 63).

Setting

Connecticut, USA.

Participants

Individuals had current alcohol dependence (n = 128), had an average age of 48.5 [standard deviation (SD) = 9.4], 110 (85.9%) were men, and included 74 smokers (57.8%) and 54 non‐smokers (42.2%). Participants were randomized to mecamylamine 10 mg per day or placebo. All subjects also received medical management therapy administered by trained research personnel.

Measurements

Primary outcome was percentage of heavy drinking days during the last month of treatment; other outcomes included drinking days, drinks per drinking days, alcohol craving, smoking, symptoms of nicotine withdrawal and side effects.

Findings

There were no significant differences in the percentage of heavy drinking days at 3 months between the mecamylamine (mean = 18.4, SD = 29.0) and placebo treatment groups (mean = 20.4, SD = 29.2) [F_{1, 100} = 1.3, P = 0.25; effect size d = 0.07; mean difference = 2.06, 95% confidence interval (CI) = ?8.96 to 13.08]. There were no significant differences in percentage of drinking days or in drinks per drinking day at month 3 between the mecamylamine and placebo groups; there were no significant interactions.

Conclusions

Mecamylamine 10 mg per day did not reduce alcohol consumption significantly in treatment‐seeking smokers and non‐smokers with alcohol use disorder.     

Major life events and risk of alcohol use disorders: a prospective cohort study

Aims

To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD).

Design

Prospective cohort study with baseline examination in 1991–93 and linkage to national registers to identify AUD at follow‐up.

Setting

Copenhagen, Denmark.

Participants

Individuals (aged 21–93 years) who participated in the Copenhagen City Heart Study in 1991–93 (n = 8758).

Measurements

The primary outcome was first registration with AUD during follow‐up (n = 249). AUD was identified in the Danish National Patient Register, in the Danish Psychiatric Central Register and in an outpatient treatment register. Major life events were assessed by a questionnaire in the Copenhagen City Heart study. Data were analysed by Cox proportional hazards models adjusted for age, sex, educational level, household income, cohabitation status and psychiatric comorbidity.

Findings

Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased risk of AUD. Prospective analyses did not show consistent effects of accumulation of major life events in childhood or adult life, but an additional analysis based on all AUD registrations suggested an association between accumulated childhood events and risk of AUD.

Conclusions

Serious economic problems in adult life are associated strongly with risk of alcohol use disorders, and there may be an influence of accumulated childhood events on risk of alcohol use disorders.     

Rifaximin in non‐alcoholic steatohepatitis: An open‐label pilot study

Aim

Gut microbial dysbiosis is implicated in the pathogenesis of non‐alcoholic steatohepatitis (NASH). We investigated downstream effects of gut microbiota modulation on markers of hepatic inflammation, steatosis, and hepatic and peripheral insulin sensitivity in patients with NASH using rifaximin therapy.

Methods

Patients with biopsy‐proven NASH and elevated aminotransferase values were included in this open‐label pilot study, all receiving 6 weeks rifaximin 400 mg twice daily, followed by a 6‐week observation period. The primary endpoint was change in alanine aminotransferase (ALT) after 6 weeks of rifaximin. Secondary endpoints were change in hepatic lipid content and insulin sensitivity measured with a hyperinsulinemic–euglycemic clamp.

Results

Fifteen patients (13 men and 2 women) with a median (range) age of 46 (32–63) years were included. Seven had diabetes on oral hypoglycemic medications and 8 had no diabetes. After 6 weeks of therapy, no differences were seen in ALT (55 [33–191] vs. 63 [41–218] IU/L, P = 0.41), peripheral glucose uptake (28.9 [19.4–48.3] to 25.5 [17.7–47.9] μmol/kg/min, P = 0.30), hepatic insulin sensitivity (35.2 [15.3–51.7]% vs. 30.0 [10.8–50.5]%, P = 0.47), or hepatic lipid content (21.6 [2.2–46.2]% vs. 24.8 [1.7–59.3]%, P = 0.59) before and after rifaximin treatment. After 12 weeks from baseline, serum ALT increased to 83 (30–217) IU/L, P = 0.02. There was a significant increase in the homeostasis model assessment–estimated insulin resistance index (P = 0.05). The urinary metabolic profile indicated a significant reduction in urinary hippurate with treatment, which reverted to baseline after cessation of rifaximin, although there was no consistent difference in relative abundance of fecal microbiota with treatment.

Conclusion

These data do not indicate a beneficial effect of rifaximin in patients with NASH.     

Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort

Objectives

The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.

Design and setting

An observational study was conducted including 255 patients (mean age 60 years, range 15–93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head‐up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C‐terminal pro‐arginine vasopressin (CT‐proAVP), C‐terminal endothelin‐1 precursor fragment (CT‐proET‐1), midregional fragments of pro‐atrial natriuretic peptide (MR‐proANP) and pro‐adrenomedullin (MR‐proADM).

Results

A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty‐five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR‐proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86–16.74; P < 0.001] and CT‐proET‐1 (OR 7.17, 95% CI 2.43–21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT‐proET‐1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49–30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR‐proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62–26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT‐proET‐1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97–696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT‐proET‐1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15–5.02; P = 0.02), whereas low CT‐proET‐1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25–0.70; P = 0.001).

Conclusions

The levels of MR‐proANP and CT‐proET‐1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.     

The Nature and Extent of Flavored Alcoholic Beverage Consumption among Underage Youth: Results of a National Brand-Specific Survey

Background: Flavored alcoholic beverages are popular among underage drinkers. Existing studies that assessed flavored alcoholic beverage use among youth relied upon respondents to correctly classify the beverages they consume, without defining what alcohol brands belong to this category. Objectives: The aim is to demonstrate a new method for analyzing the consumption of flavored alcoholic beverages among youth on a brand-specific basis, without relying upon youth to correctly classify brands they consume. Methods: Using a prerecruited Internet panel developed by Knowledge Networks, we measured the brands of alcohol consumed by a national sample of youth drinkers, aged 16–20 years, in the United States. The sample consisted of 108 youths who had consumed at least one drink of an alcoholic beverage in the past 30 days. We measured the brand-specific consumption of alcoholic beverages within the past 30 days, ascertaining the consumption of 380 alcohol brands, including 14 brands of flavored alcoholic beverages. Results: Measuring the brand-specific consumption of flavored alcoholic beverages was feasible. Based on a brand-specific identification of flavored alcoholic beverages, nearly half of the youth drinkers in the sample reported having consumed such beverages in the past 30 days. Flavored alcoholic beverage preference was concentrated among the top four brands, which accounted for almost all of the consumption volume reported in our study. Conclusions and scientific significance: These findings underscore the need to assess youth alcohol consumption at the brand level and the potential value of such data in better understanding underage youth drinking behavior and the factors that influence it.