Social disparity is associated with an increased risk of acute and chronic pancreatitis.

AIM: To study social disparity in acute pancreatitis (AP) and chronic pancreatitis (CP).We also aimed at exploring whether an interaction exists between alcohol intake and socioeconomic factors. METHODS: Prospective cohort study based on data from 271 696 men and women participating in the Danish National Health Surveys 2010, and 2013. Information on alcohol and smoking parameters, body mass index (BMI), diet, and education, were self-reported and information on family income was obtained from administrative registers. Outcome variables (acute and chronic pancreatitis) were obtained from national health registers. RESULTS: The incidence rate ratio (IRR) of developing AP and CP increased with decreasing family income. Compared to participants in the highest income quintile, participants in the lowest income quintile had 43 (95% CI: 14-80%), 99 (95% CI: 26-214%), and 56% (95% CI: 26-94%) higher incidence rates of AP, CP, and all pancreatitis, respectively. The associations persisted after adjustment for alcohol intake, smoking, BMI, and diet.Likewise, participants with only primary school education had an IRR for an AP of 1.30 (95% CI: 1.06-1.59) compared to those with higher education after adjustment for baseline year, age, and sex. We found no interactions between alcohol intake and income or between alcohol intake and education in relation to neither AP, CP, nor all pancreatitis. CONCLUSION: This large prospective population study showed a significant social disparity in incidence rates of pancreatitis by family income, with higher rates among those with the lowest income and education independent of risk factors such as alcohol intake, smoking, BMI, and diet.

Alcohol Drinking Patterns and Risk of Developing Acute and Chronic Pancreatitis.

AIM: The aim was to analyze the effects of drinking pattern and type of alcohol on risk of acute and chronic pancreatitis. METHODS: Prospective cohort study based on data from 316,751 men and women participating in the Danish National Health Surveys 2010 and 2013. Self-reported questionnaire-based alcohol parameters and information on pancreatitis was obtained from national health registers. Cox regression models were used adjusting for baseline year, gender, age, smoking, Body Mass Index, diet and education. RESULTS: Development of acute and chronic pancreatitis increased with alcohol intake with a significant increase among abstainers and those drinking >14 drinks per week compared with individuals drinking 1-7 drinks per week. Frequent binge drinking and frequent drinking (every day) was associated with increased development of acute and chronic pancreatitis compared with those drinking 2-4 days per week. Problematic alcohol use according to the CAGE-C questionnaire was associated with increased development of acute and chronic pancreatitis.Intake of more than 14 drinks of spirits per week was associated with increased development of acute and chronic pancreatitis, and more than 14 drinks of beer per week were associated with increased development of chronic pancreatitis, whereas drinking wine was not associated with development of pancreatitis. CONCLUSION: This large prospective population study showed a J-shaped association between alcohol intake and development of pancreatitis. Drinking every day, frequent binge drinking and problematic alcohol use were associated with increased development of pancreatitis and drinking large amounts of beer and spirits might be more harmful than drinking wine.

Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial.

BackgroundAlcohol use disorder (AUD) is a chronic, relapsing brain disorder that accounts for 5% of deaths annually, and there is an urgent need to develop new targets for therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents and nonhuman primates, but its efficacy in patients with AUD is unknown.MethodsIn a randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking AUD patients were assigned to receive exenatide (2 mg subcutaneously) or placebo once weekly for 26 weeks, in addition to standard cognitive-behavioral therapy. The primary outcome was reduction in number of heavy drinking days. A subgroup also completed functional MRI (fMRI) and single-photon emission CT (SPECT) brain scans.ResultsA total of 127 patients were enrolled. Our data revealed that although exenatide did not significantly reduce the number of heavy drinking days compared with placebo, it significantly attenuated fMRI alcohol cue reactivity in the ventral striatum and septal area, which are crucial brain areas for drug reward and addiction. In addition, dopamine transporter availability was lower in the exenatide group compared with the placebo group. Exploratory analyses revealed that exenatide significantly reduced heavy drinking days and total alcohol intake in a subgroup of obese patients (BMI > 30 kg/m2). Adverse events were mainly gastrointestinal.ConclusionThis randomized controlled trial on the effects of a GLP-1 receptor agonist in AUD patients provides new important knowledge on the effects of GLP-1 receptor agonists as a novel treatment target in addiction.Trial registrationEudraCT: 2016-003343-11. ClinicalTrials.gov (NCT03232112).FundingNovavi Foundation; Research Foundation, Mental Health Services, Capital Region of Denmark; Research Foundation, Capital Region of Denmark; Ivan Nielsen Foundation; A.P. Moeller Foundation; Augustinus Foundation; Woerzner Foundation; Grosserer L.F. Foghts Foundation; Hartmann Foundation; Aase and Ejnar Danielsen Foundation; P.A. Messerschmidt and Wife Foundation; and Lundbeck Foundation.

Bariatric Surgery and Risk of Unemployment and Sickness Absence.

BACKGROUND: Obesity is associated with adverse labor market outcomes. We examine whether undergoing bariatric surgery is associated with better labor market outcomes such as lower risks of unemployment and sickness absence. METHODS: This is a register-based cohort study of 9126 patients undergoing bariatric surgery from 2005 to 2013 and a reference group of 10,328 individuals with obesity. Age: 18-60 years, body mass index (BMI): 32-60 kg/m2. Participants were either working, unemployed, or on sickness absence at baseline. Inverse probability of treatment weighting was used to account for baseline differences between the two groups. Relative risk ratios of labor market participation were estimated at 1 year, 3 years, and 5 years of follow-up. RESULTS: Women who had undergone bariatric surgery had a higher risk of unemployment 1 year (RRR = 1.20 (95% CI: 1.02-1.41)) and 5 years (RRR = 1.23 (95% CI: 1.05-1.44)) after surgery; however, men with bariatric surgery had a lower risk of unemployment after 5 years (RRR = 0.71 (95% CI: 0.55-0.92)). The risk of sickness absence was higher at all follow-up time points for both men and women who had undergone bariatric surgery compared with non-operated references with obesity. CONCLUSIONS: Men undergoing bariatric surgery had a lower risk of unemployment 5 years after surgery compared with non-operated men with obesity; however, women presented a higher risk of unemployment after 5 years. The risk of sickness absence was higher for both men and women up to 5 years after undergoing bariatric surgery.

Risk of somatic disease and mortality in individuals of parents with alcohol use disorder: a register-based cohort study.

AIMS: To estimate the risks of 12 types of somatic disease-alcohol-related, blood, cancer, circulatory, digestive, endocrine and metabolic, genitourinary, infectious, musculoskeletal, nervous, respiratory and skin-in individuals with parental alcohol use disorder (AUD) versus a reference population, and to estimate the risks of all-cause mortality and of death from an alcohol-related cause. DESIGN: Matched cohort study followed-up through nation-wide health registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). SETTING: Denmark. PARTICIPANTS: A total of 14 008 individuals born 1962-2003 of parents with AUD and 139 087 reference offspring randomly selected from the Danish Civil Registration System were followed from their 15th birthday and onward during 1970-2018. Follow-up time ranged between 2 423 955 and 3 208 366 person-years for somatic diseases and was 3 214 411 person-years for all-cause and alcohol-related mortality. MEASUREMENTS: Information on somatic disease was obtained from the Danish National Patient Registry. Causes of death were obtained from the Danish Cause of Death Registry. FINDINGS: Individuals of parents with AUD had a higher risk of alcohol-related diseases (HR = 2.70, 95% CI = 2.24-3.24) compared with the reference individuals. Higher HRs among individuals with parental AUD compared with reference individuals were also observed in all other somatic diseases except for cancer. All-cause mortality (HR = 1.80, 95% CI = 1.63-2.00) and alcohol-related mortality (HR = 3.28, 95% CI = 2.11-5.08) were higher among individuals of parents with AUD compared with the reference individuals. No significant differences were found in relation to the gender of either parents or offspring. CONCLUSIONS: In Denmark, parental alcohol use disorder appears to predict alcohol-related and non-alcohol-related somatic morbidity and mortality in offspring.

An Ethnographic study of unhealthy alcohol use in a Danish Emergency Department.

BACKGROUND: Emergency Departments (EDs) are important arenas for the detection of unhealthy substance use. Screening, Brief Intervention, and Referral to Treatment (SBIRT) for unhealthy alcohol use has been used in some ED settings with funding support from external sources. However, widespread sustained implementation is uncommon, and research aimed at understanding culture as a determinant for implementation is lacking. This study aims to explore cultural practices concerning the handling of patients with unhealthy alcohol use admitted to an ED. METHODS: An ethnographic study was conducted in an ED in the Capital Region of Denmark. The data consists of participant observations of Health Care Professionals (HCPs) and semi-structured interviews with nurses. Data was collected from July 2018 to February 2020. A cultural analysis was performed by using Qualitative Content Analysis as an analytic tool. RESULTS: 150 h of observation and 11 interviews were conducted. Three themes emerged from the analysis: (1) Setting the scene describes how subthemes "flow," "risky environment," and "physical spaces and artefacts" are a part of the contextual environment of an ED, and their implications for patients with unhealthy alcohol use, such as placement in certain rooms; (2) The encounter presents how patients' and HCPs' encounters unfold in everyday practice. Subtheme "Professional differences" showcases how nurses and doctors address patients' alcohol habits differently, and how they do not necessarily act on the information provided, due to several factors. These factors are shown in remaining sub-themes "gut-feeling vs. clinical parameters," "ethical reasoning," and "from compliance to zero-tolerance"; and (3) Collective repertoires shows how language shapes the perception of patients with unhealthy alcohol use, which may cause stigma and stereotyping. Subthemes are "occupiers" and "alcoholic or party animal?". CONCLUSIONS: Unhealthy alcohol use in the ED is entangled in complex cultural networks. Patients with severe and easily recognizable unhealthy alcohol use-characterized by an alcohol diagnosis in the electronic medical record, intoxication, or unwanted behavior-shape the general approach and attitude to unhealthy alcohol use. Consequently, from a prevention perspective, this means that patients with less apparent unhealthy alcohol use tend to be overlooked or neglected, which calls for a systematic screening approach.

Distinct health-related risk profiles among middle-aged and older adults with risky alcohol use from the Danish general population.

BACKGROUND: Knowledge is lacking on distinct health-related risk profiles among the substantial group of middle-aged and older adults with risky alcohol use (AU). Such profiles could inform the planning of interventions and prevention. AIMS: To 1) identify distinct health-related profiles based on different types of health-related functioning limitations and distress and 2) assess associations between these profiles and age, sex, and health-relevant behaviors (e.g., smoking). METHODS: Cross-sectional nation-wide Danish health survey with n = 6630 adults aged 55-64 and n = 7605 aged 65-74 with at least risky AU (>84 g ethanol/week in women, >168 in men). Health-related risk profiles were identified with Latent Class Analysis (LCA). Multinomial regression was applied for the association between risk profiles and auxiliary variables. RESULTS: A six-class LCA solution was found among 55-64 year-olds (classes: 'Normative' [61%], 'Distress' [6%], 'Mental health limitations [5%]', 'Pain-related distress [10%]', 'Broad limitations and pain distress [7%]', 'High overall burden' [11%]) and a five-class solution among 65-74 year-olds. Most classes were comparable across age groups. The 'Distress'-class characterized by pain-distress, tiredness-distress, and sleep-related distress (6%) only showed in the younger group. In both age groups, auxiliary covariates (high-risk AU, possible alcohol use disorder, weekly smoking) were positively associated with problematic profile membership (vs. normative class membership). CONCLUSION: Middle-aged and older adults with risky AU have distinct health-related profiles relevant for the form and content of prevention and interventions. Despite their distinct features, almost all problematic health profiles warrant careful attention regarding high-risk AU and probable alcohol use disorder.

Changes in relationship status following bariatric surgery.

BACKGROUND AND OBJECTIVE: Bariatric surgery is a major event associated with psychological changes such as improvements in self-esteem, increased autonomy, and better self-value. Such changes could affect the patient's interpersonal relationships; however, little is known about the impact of bariatric surgery on changes in relationship status. In this paper, we aim to test the hypothesis that bariatric surgery is associated with changes in interpersonal relationships such as becoming single for those who were in a relationship or entering a relationship among those who were single before surgery. METHODS: This register-based cohort study consisted of 12,493 patients undergoing bariatric surgery (95% gastric bypass) from 2005 to 2013 and a reference group of 15,101 individuals with obesity between the age of 18-63 with a body mass index between 32 and 60 kg/m2. Transitions between married, divorced, widowed, never-married single, and living with a partner without being married were analyzed by Poisson regression. Additionally, the outcome was dichotomized, and transitions between being single and being in a relationship were also analyzed. All analyses were weighted using inverse probability of treatment weighting based on propensity scores. RESULTS: The overall incidence rate ratio (IRR) of changing status from being single to in a relationship was 2.03 (95% CI: 1.18-2.28), and the overall IRR of changing status from being in a relationship to single was 1.66 (95% CI: 1.50-1.83). CONCLUSION: Bariatric surgery is associated with a higher chance of finding a partner among single individuals, and a higher risk of separating from a partner among individuals in a relationship.

[Alcohol-related morbidity and mortality].

Approximately 4,000 deaths are associated with a high alcohol intake in Denmark, most of them among individuals drinking more than the defined safe alcohol limits in Denmark (i.e. 14 drinks (12 g alcohol) per week for women and 21 drinks per week for men). Recent reviews and meta-analyses have generally shown an increasing mortality and morbidity in relation to a number of malignant diseases, while studies on cardiovascular disease often show a J-shaped risk function. Overall analysis of risk across health-related outcomes show that light alcohol intake (1 drink/day) is associated with a very small increase in relative risk. These facts are discussed in this review.

Young adult predictors of alcohol dependence to age 53: a 44-year prospective cohort study of Danish men.

AIMS: To examine if (1) there is a positive association between drinking volume in young men and life-time risk of alcohol dependence (AD) and (2) there are other associations between young adulthood factors and life-time risk of AD. DESIGN: Prospective cohort study of sons of fathers with alcohol use disorder (AUD) and matched low-risk controls without paternal AUD. Setting and participants A total of 204 men, who were assessed at baseline in 1979 at age 19-20 years, were followed through record linkage with Danish registers and consecutive psychiatric interviews at the ages of 33, 43 and 53 years. MEASUREMENTS: AD diagnoses were interview-based according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, or made by treating clinicians according to the International Classification of Diseases (ICD) revision 8 (ICD-8) until 1993 and revision 10 (ICD-10) from 1994.We estimated odds ratios (ORs) with 95% confidence intervals (CI) for the development of AD after adjustment for confounders including smoking, social status and paternal AUD. FINDINGS: The following variables from the examination at age 19-20 independently predicted life-time AD: alcohol consumption > 21 beverages/week versus 0-21 [odds ratio (OR) = 2.46, 95% confidence interval (CI) = 1.22-4.97], police contact (OR = 2.60, 95% CI = 1.28-5.28) and institutionalization related to the individual (OR = 2.90, 95% CI = 1.39-6.02). Compared with < 1 beverages/week, the risk for AD did not increase significantly for drinking volume categories: 1-7, 8-14 or 15-21 beverages/week. CONCLUSION: Independently of other risk factors in young adulthood, young Danish men's risk for life-time alcohol dependence appears to be predicted by a drinking volume at age 19-20 years exceeding 21 beverages per week.

Implementation of AUDIT in the treatment planning process for alcohol use disorder in Greenland.

INTRODUCTION: The aim was to describe the treatment-seeking population with alcohol use disorder by means of data from the AUDIT questionnaire at referral and to evaluate and discuss if this information can be of use in treatment and service planning. METHODS: Data from 2016 to 2018 were extracted from the National Database on Substance Abuse Treatment. The sample included 1281 individual treatment seekers from all over Greenland. RESULTS: Mean age was 38.2 years (SD 12.1 years). Only 60.1% had a total AUDIT score suggesting dependency, and 15.5% had a harmful use. While most only drank 2-4 times a month, about 95% binge drank. Half reported loss of control at least weekly, and one of three had been unable to do what was expected of them, or needed a drink first thing in the morning weekly or more often. In two-third others had been concerned about the drinking. Users of cannabis had a higher AUDIT score, while gambling was unassociated to alcohol use. Substantial gender and regional differences were seen. DISCUSSION: The AUDIT screening was found useful in individual and national treatment planning. Data suggested that particular focus should be given to women in treatment, and the service offered to the East Greenlandic population.

Bariatric surgery and risk of alcohol use disorder: a register-based cohort study.

BACKGROUND: Bariatric surgery has been associated with altered alcohol metabolism. We examined whether patients undergoing bariatric surgery have a higher risk of developing alcohol use disorder (AUD) compared with individuals with obesity who have not received bariatric surgery. METHODS: In this prospective cohort study, we followed 13 430 patients undergoing bariatric surgery (95% gastric bypass) between 2005 and 2013 and a reference group of 21 021 individuals with obesity for a median of 6.9 years (5th-95th percentile: 4.0-9.8). Four different approaches were used to account for baseline differences between the two groups: (i) adjustment; (ii) inverse probability of treatment weighting (IPTW); (iii) 1:1 matching based on propensity scores; and (iv) before-and-after analysis comparing the bariatric surgery group with itself 5 years before and after surgery. Cox proportional hazard modelling was used to estimate hazard ratios of AUD defined from national registers. RESULTS: When applying the IPTW approach, the hazard ratio (HR) of AUD for bariatric surgery patients was 7.29 [95% confidence interval (CI): 5.06-9.48] compared with individuals without surgery. When employing different approaches (adjustment for baseline variables, matching on propensity scores, before-and-after analyses), results were of similar magnitude. Analysis stratified by time after surgery revealed a higher risk of AUD already within the first year following surgery [HR: 2.77 (95% CI: 1.39-5.53)]. CONCLUSIONS: Patients undergoing bariatric surgery have a higher risk of developing AUD compared with individuals without bariatric surgery. The higher risk observed in this group of patients cannot be explained by differences in baseline characteristics such as socioeconomic factors. Despite the higher risk of AUD, only few individuals developed AUD. Individuals with disabling obesity should therefore not rule out surgery based on these results but rather be aware of negative implications.

Time trends in incidence and prevalence of chronic pancreatitis: A 25-year population-based nationwide study.

BACKGROUND: Updated population-based estimates on incidence and prevalence of chronic pancreatitis are scarce. METHODS: We used nationwide healthcare registries to identify all Danish patients diagnosed with chronic pancreatitis and computed crude and standardised incidence rates and prevalence estimates in 1994-2018. Incidence and prevalence were evaluated in relation to patients age and gender, aetiology (alcoholic vs. non-alcoholic) and smoking and alcohol consumption in the general Danish population. RESULTS: The mean incidence rate of chronic pancreatitis during the study period was 12.6 per 100,000 person years for the total population, for women it was 8.6 per 100,000 person years and for men it was 16.7 per 100,000 person years. The standardised incidence rate was stable from 1994 to 2018, remaining at 12.5 per 100,000 person years in the last observation period (2014-2018). The point prevalence of chronic pancreatitis in 2016 was 153.9 per 100,000 persons. A gradual increase in standardised prevalence estimates was observed during the study period from 126.6 in 1996 to 153.9 in 2016. The mean age at chronic pancreatitis diagnosis increased from 52.1 to 60.0 years during the study period. CONCLUSION: The prevalence of chronic pancreatitis is increasing in the Danish population despite a stable incidence level. Improved management strategies and changes in the underlying patient population may explain these observations.

Prevalence of problems with alcohol, marijuana and gambling among patients in a Regional Hospital in Northern Greenland: investigating the potential for brief interventions in a hospital setting.

Problems with alcohol, marijuana and gambling are major public health challenges in Greenland but their prevalence in a hospital setting has not been explored. Healthcare facilities play a significant role in Greenland. One important aspect is their provision of both primary and secondary healthcare services to a small and scattered population while their potential as settings for screening for problems with alcohol, substances and gambling is an unexplored area with large public health potential. This study explored the prevalences of problems with alcohol, marijuana and gambling in a hospital and the potential for the use of a hospital as a setting for screening for alcohol, substance and gambling problems. Patients from the Northern Ilulissat Hospital filled in a self-administered questionnaire regarding their behaviour related to alcohol, marijuana and gambling. Data were weighted and compared to the nationally representative 2018 Health Survey. In the Ilulissat Survey, a large proportion were abstainers but there were still problems related to alcohol, marijuana and gambling indicating a potential for screening in a hospital setting. The results based on data from 2,554 respondents showed that prevalences of problems with alcohol, marijuana and gambling are lower in the Ilulissat Survey compared to the 2018 Health Survey.

Intelligence in young adulthood and alcohol use disorders in a prospective cohort study of Danish men: the role of psychiatric disorders and parental psychiatric history.

OBJECTIVES: The aims were to estimate the association between intelligence measured in young adulthood and risk of alcohol use disorders (AUD) in men and to investigate the potential modification of this association by psychiatric disorders, parental AUD and parental psychiatric disorders. DESIGN: Prospective cohort study based on a linkage of intelligence test scores from draft board examinations and register data on AUD diagnoses during 36 years of follow-up. SETTING: Denmark. PARTICIPANTS: 3287 Danish men from the Copenhagen Perinatal Cohort (born 1959-1961) who appeared before the draft board at a mean age of 18.7 years. PRIMARY OUTCOME MEASURE: First registration with AUD during follow-up was the primary outcome. Information on AUD was based on diagnoses retrieved from national hospital and outpatient treatment registers, defined according to the International Classification of Diseases. RESULTS: 361 (11.0%) men were registered with AUD during follow-up. Low intelligence scores were associated with increased odds of AUD adjusting for parental AUD, parental psychiatric disorders, maternal smoking during pregnancy, birth weight, maternal age at birth, parity and childhood socioeconomic position (OR per SD decrease in intelligence=1.69, 95% CI 1.49 to 1.92). Separate analyses indicated significant interaction (p<0.001) between intelligence and psychiatric disorders. The adjusted OR per SD decrease in intelligence score was 2.04 (95% CI 1.67 to 2.49) in men without other psychiatric disorders whereas the OR was 1.21 (95% CI 1.01 to 1.46) in men with other psychiatric disorders. No interaction was found between intelligence and parental AUD or between intelligence and parental psychiatric disorders. CONCLUSIONS: The association between intelligence in young adulthood and AUD is modified by other psychiatric disorders as low intelligence is primarily a risk factor for men without other psychiatric disorders. Future studies should take other psychiatric disorders into account when investigating associations between intelligence and AUD.

Intelligence Test Scores Before and After Alcohol-Related Disorders-A Longitudinal Study of Danish Male Conscripts.

BACKGROUND: Existing studies on intellectual consequences of alcohol-related disorders are primarily cross-sectional and compare intelligence test scores of individuals with and without alcohol-related disorders, hence mixing the influence of alcohol-related disorders and predisposing factors such as premorbid intelligence. In this large-scale study, the primary aim was to estimate associations of alcohol-related disorders with changes in intelligence test scores from early adulthood to late midlife. METHODS: Data were drawn from a follow-up study on middle-aged men, which included a re-examination of the same intelligence test as completed in young adulthood at military conscription (total analytic sample = 2,499). Alcohol-related hospital diagnoses were obtained from national health registries, whereas treatment for alcohol problems was self-reported at follow-up. The analyses included adjustment for year of birth, retest interval, baseline intelligence quotient (IQ) score, education, smoking, alcohol consumption, and psychiatric and somatic comorbidity. RESULTS: Individuals with alcohol-related hospital diagnoses (8%) had a significantly lower baseline IQ score (95.0 vs. 100.5, p < 0.001) and a larger decline in IQ scores from baseline to follow-up (-8.5 vs. -4.8, p < 0.001) than individuals without such diagnoses. The larger decline in IQ scores with alcohol-related hospital diagnoses remained statistically significant after adjustment for all the covariates. Similar results were revealed when IQ scores before and after self-reported treatment for alcohol problems (10%) were examined. CONCLUSIONS: Individuals with alcohol-related disorders have a lower intelligence test score both in young adulthood and in late midlife, and these disorders, moreover, seem to be associated with more age-related decline in intelligence test scores. Thus, low mean intellectual ability observed in individuals with alcohol-related disorders is probably a result of both lower premorbid intelligence and more intellectual decline.

Natural history of histologically proven alcohol-related liver disease: A systematic review.

BACKGROUND & AIMS: To date, studies into the natural history of alcohol-related liver disease (ALD) have lacked long-term follow-up, large numbers of participants, or both. We performed a systematic review to summarise studies that describe the natural history of histologically proven ALD. METHODS: PubMed and Medline were searched for relevant studies according to pre-specified criteria. Data were extracted to describe the prevalence of ALD, histological progression of disease and mortality. Single-proportion meta-analysis was used to combine data from studies regarding rates of progression or mortality. RESULTS: Thirty-seven studies were included, reporting data from 7,528 participants. Amongst cohorts of hazardous drinkers, on average 15% had normal histological appearance, 27% had hepatic steatosis, 24% had steatohepatitis and 26% had cirrhosis. The annualised rates of progression of pre-cirrhotic disease to cirrhosis were 1% (0-8%) for patients with normal histology, 3% (2-4%) for hepatic steatosis, 10% (6-17%) for steatohepatitis and 8% (3-19%) for fibrosis. Annualised mortality was 6% (4-7%) in patients with steatosis and 8% (5-13%) in cirrhosis. In patients with steatohepatitis on biopsy a marked difference was seen between inpatient cohorts (annual mortality 15%, 8-26%) and mixed cohorts of inpatients and outpatients (annual mortality 5%, 2-10%). Only in steatosis did non-liver-related mortality exceed liver-specific causes of mortality (5% per year vs. 1% per year). CONCLUSIONS: These data confirm the observation that alcohol-related hepatic steatohepatitis requiring admission to hospital is the most dangerous subtype of ALD. Alcohol-related steatosis is not a benign condition as it is associated with significant risk of mortality. LAY SUMMARY: Knowledge of the natural history of a disease allows clinicians and patients to understand the risks that are associated with a medical condition. In this study we systematically gathered all the published data regarding the natural history of alcohol-related liver disease in people who had a liver biopsy. We used this data to define the prevalence of the disease, the annual risk of progression to cirrhosis and the annual risk of death at each stage of the disease.

Adult-Life Alcohol Consumption and Age-Related Cognitive Decline from Early Adulthood to Late Midlife.

AIMS: Alcohol consumption is a modifiable and plausible risk factor for age-related cognitive decline but more longitudinal studies investigating the association are needed. Our aims were to estimate associations of adult-life alcohol consumption and consumption patterns with age-related cognitive decline. METHODS: We investigated the associations of self-reported adult-life weekly alcohol consumption and weekly extreme binge drinking (≥10 units on the same occasion) with changes in test scores on an identical validated test of intelligence completed in early adulthood and late midlife in 2498 Danish men from the Lifestyle and Cognition Follow-up study 2015. Analyses were adjusted for year of birth, retest interval, baseline IQ, education and smoking. RESULTS: Men with adult-life alcohol consumption of more than 28 units/week had a larger decline in IQ scores from early adulthood to late midlife than men consuming 1-14 units/week (B29-35units/week = -3.6; P < 0.001). Likewise, a 1-year increase in weekly extreme binge drinking was associated with a 0.12-point decline in IQ scores (P < 0.001). Weekly extreme binge drinking explained more variance in IQ changes than average weekly consumption. In analyses including mutual adjustment of weekly extreme binge drinking and average weekly alcohol consumption, the estimated IQ decline associated with extreme binge drinking was largely unaffected, whereas the association with weekly alcohol consumption became non-significant. CONCLUSIONS: Adult-life heavy alcohol consumption and extreme binge drinking appear to be associated with larger cognitive decline in men. Moreover, extreme binge drinking may be more important than weekly alcohol consumption in relation to cognitive decline.

Validation and calibration of self-reported height and weight in the Danish Health Examination Survey.

BACKGROUND: Body mass index (BMI) derived from self-reported information is widely used and the validity is therefore crucial. We aim at testing the validity of self-reported height and weight, and to test if the accuracy of self-reported information can be improved by calibration by testing if calibration improved the ability to predict diabetes. METHODS: Data from Danish Health Examination Survey (DANHES) was used. 15 692 participants who had both filled out questionnaire and participated in health examination, and 54 725 participants with questionnaire alone, were included. Data was analyzed using Pearson's R, Cohens Kappa, linear regression and Cox-regression. Self-reported values of height and weight were calibrated using coefficients obtained from linear regression analysis. To evaluate if the calibration improved the ability to predict diabetes, Akaike's information criterion was used. RESULTS: Self-reported height, weight and BMI were highly correlated with measured values (R ≥ 0.92). BMI was under-reported by 0.32 kg m-2 and 0.38 kg m-2 in women and men. The hazard ratio (HR) (95% confidence interval) for diabetes according to measured BMI was 2.09 (1.89-2.27) and for self-reported BMI was 1.60 (1.50-1.70) per 5 kg m-2. Calibrated values of self-reported BMI improved the predictive value of BMI for the risk of diabetes. CONCLUSIONS: Self-reported height and weight correlated highly with physical measurement of height and weight. Measured values of BMI were more strongly associated with diabetes risk as compared to self-reported values. Calibration of the self-reported values improved the accuracy of self-reported height and weight.

Does glucagon-like peptide-1 (GLP-1) receptor agonist stimulation reduce alcohol intake in patients with alcohol dependence: study protocol of a randomised, double-blinded, placebo-controlled clinical trial.

INTRODUCTION: Alcohol dependence is a major public health problem. It is underdiagnosed and undertreated. Even when treated, more than 2/3 of patients in abstinence-oriented treatment will relapse within the first year. Thus, there is an urgent need for efficacious medical treatment of alcohol dependence. Glucagon-like peptide-1 (GLP-1) receptor stimulation has proven to reduce alcohol consumption in preclinical experiments. However, the effect of GLP-1 receptor agonists in humans has to our knowledge, not yet been investigated. METHODS AND ANALYSIS: Design, participants and intervention: The effect of the once-weekly GLP-1-receptor-agonist exenatide will be investigated in a double-blinded, placebo-controlled, randomised clinical trial. 114 outpatients will be recruited and randomised to treatment with either placebo or exenatide once weekly for 26 weeks as a supplement to cognitive-behavioural therapy. The primary endpoint is reduction in number of 'heavy drinking days'. The secondary endpoints include changes in total alcohol consumption, days without consumption, changes in brain activity and function, smoking status, cognition, measures of quality of life and changes in phosphatidylethanol as a biomarker of alcohol consumption from baseline to follow-up at week 26. Status: Currently recruiting patients. ETHICS AND DISSEMINATION: Ethical approval has been obtained. Before screening, all patients will be provided oral and written information about the trial. The study results will be disseminated by peer-review publications and conference presentations and has the potential to reveal a completely new medical treatment of alcohol dependence.