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Background: A major challenge to psychological treatment for alcohol use disorder (AUD) is patient non-compliance. A promising new treatment approach that is hypothesized to increase patient compliance is blended treatment, consisting of face-to-face contact with a therapist combined with modules delivered over the internet within the same protocol. While this treatment concept has been developed and proven effective for a variety of mental disorders, it has not yet been examined for AUD., Aims: The study described in this protocol aims to examine and evaluate patient compliance with blended AUD treatment as well as the clinical and cost effectiveness of such treatment compared to face-to-face treatment only., Methods: The study design is a pragmatic, stepped-wedge cluster randomized controlled trial. The included outpatient institutions (planned number of patients: n = 1800) will be randomized in clusters to implement either blended AUD treatment or face-to-face treatment only, i.e. treatment as usual (TAU). Both treatment approaches consist of motivational interviewing and cognitive behavioral therapy. Data on sociodemographics, treatment (e.g. intensity, duration), type of treatment conclusion (compliance vs. dropout), alcohol consumption, addiction severity, consequences of drinking, and quality of life, will be collected at treatment entry, at treatment conclusion, and 6 months after treatment conclusion. The primary outcome is compliance at treatment conclusion, and the secondary outcomes include alcohol consumption and quality of life at six-months follow-up. Data will be analyzed with an Intention-to-treat approach by means of generalized linear mixed models with a random effect for cluster and fixed effect for each step. Also, analyses evaluating cost-effectiveness will be conducted., Discussion: Blended treatment may increase treatment compliance and thus improve treatment outcomes due to increased flexibility of the treatment course. Since this study is conducted within an implementation framework it can easily be scaled up, and when successful, blended treatment has the potential to become an alternative offer in many outpatient clinics nationwide and internationally., Trial Registration: Clinicaltrials.gov .: NCT04535258 , retrospectively registered 01.09.20.

Aims: The objective of this paper was to examine 20-year trends of the socioeconomic status (SES) measures income and employment and their association with current alcohol use behaviors in Danish adults aged 60-70., Methods: Data from The Danish National Health Survey 2013 and the baseline assessment of the Elderly Study (2013-2016) were combined to form four groups from the general population with various drinking patterns, but with no recent treatment for alcohol use disorder (AUD), and one group seeking treatment: Abstinent (n = 691), low- (n = 1978), moderate- (n = 602), and high-risk (HR) drinkers (n = 467), and DSM-5 AUD seeking treatment (n = 262). For all groups, Danish national register data were linked at the individual level obtain find annual information on income and employment during the 20 years prior to interview. Mixed effects models were utilized to model trajectories of income and employment for the five groups., Results: Lower income and employment status was observed from middle-aged adulthood when comparing 12-month abstinence or AUD to individuals with low or moderate alcohol consumption. At the end of the study period, moderate-risk drinkers experienced an increase, and HR drinkers a decrease, in income and rate of employment relative to the low-risk drinkers., Conclusions: Alcohol use behaviors observed in older adults are related to distinct long-term trajectories regarding income and employment status, which are observable already in middle-aged adulthood., (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Objective: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 ( PCSK1 ) may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children., Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C) by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER) causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5' end did not affect PCSK1 promoter activity. In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects., Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children.

Background: The proportion of 60+ years with excessive alcohol intake varies in western countries between 6-16 % among men and 2-7 % among women. Specific events related to aging (e.g. loss of job, physical and mental capacity, or spouse) may contribute to onset or continuation of alcohol use disorders (AUD). We present the rationale and design of a multisite, multinational AUD treatment study for subjects aged 60+ years., Methods/design: 1,000 subjects seeking treatment for AUD according to DSM-5 in outpatient clinics in Denmark, Germany, and New Mexico (USA) are invited to participate in a RCT. Participants are randomly assigned to four sessions of Motivational Enhancement Treatment (MET) or to MET plus an add-on with eight sessions based on the Community Reinforcement Approach (CRA), which include a new module targeting specific problems of older adults. A series of assessment instruments is applied, including the Form-90, Alcohol Dependence Scale, Penn Alcohol Craving Scale, Brief Symptom Inventory and WHO Quality of Life. Enrolment will be completed by April 2016 and data collection by April 2017. The primary outcome is the proportion in each group who are abstinent or have a controlled use of alcohol six months after treatment initiation. Controlled use is defined as maximum blood alcohol content not exceeding 0.05 % during the last month. Total abstinence is a secondary outcome, together with quality of life andcompliance with treatment., Discussion: The study will provide new knowledge about brief treatment of AUD for older subjects. As the treatment is manualized and applied in routine treatment facilities, barriers for implementation in the health care system are relatively low. Finally, as the study is being conducted in three different countries it will also provide significant insight into the possible interaction of service system differences and related patient characteristics in predictionof treatment outcome., Trial Registration: Clinical Trials.gov NCT02084173 , March 7, 2014.

Background: Factors underlying socioeconomic inequalities in mortality are not well understood. This study contributes to our understanding of potential pathways to result in socioeconomic inequalities, by examining alcohol consumption as one potential explanation via comparing socioeconomic inequalities in alcohol-attributable mortality and all-cause mortality., Methods: Web of Science, MEDLINE, PsycINFO and ETOH were searched systematically from their inception to second week of February 2013 for articles reporting alcohol-attributable mortality by socioeconomic status, operationalized by using information on education, occupation, employment status or income. The sex-specific ratios of relative risks (RRRs) of alcohol-attributable mortality to all-cause mortality were pooled for different operationalizations of socioeconomic status using inverse-variance weighted random effects models. These RRRs were then combined to a single estimate., Results: We identified 15 unique papers suitable for a meta-analysis; capturing about 133 million people, 3 741 334 deaths from all causes and 167 652 alcohol-attributable deaths. The overall RRRs amounted to RRR = 1.78 (95% confidence interval (CI) 1.43 to 2.22) and RRR = 1.66 (95% CI 1.20 to 2.31), for women and men, respectively. In other words: lower socioeconomic status leads to 1.5-2-fold higher mortality for alcohol-attributable causes compared with all causes., Conclusions: Alcohol was identified as a factor underlying higher mortality risks in more disadvantaged populations. All alcohol-attributable mortality is in principle avoidable, and future alcohol policies must take into consideration any differential effect on socioeconomic groups., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objectives: Total aortic arch replacement remains a surgical challenge. For the reimplantation of the supra-aortic vessels, either the en bloc (island) or branched graft technique (BGT) is used. The BGT has been proposed to have several advantages over the classical island technique. The purpose of this study was to compare the perioperative and mid-term follow-up results of these two methods., Methods: From March 2006 to December 2010, 103 patients (74.8% male, age 59 ± 12 years) underwent total aortic arch replacement. In 45.6% of the patients (n = 47), branched grafts (Group A, 35 males, 58 ± 13 years) were used, while 54.4% of the patients (n = 56) underwent en bloc technique (Group B, 42 males, 60 ± 12 years). Concomitant procedures were performed as necessary. Twenty-nine (28.2%) patients had an aortic aneurysm [Group A: n = 12 (25.5%), Group B: n = 17 (30.4%)] and 74 (71.8%) patients had an aortic dissection [Group A: n = 35 (74.5%), Group B: n = 39 (69.6%)]. Thirty-one (30.1%) of these patients [Group A: 17 (36.2%), Group B: 14 (25%)] had undergone previous cardiac operations., Results: Cardiopulmonary bypass, cross-clamp and circulatory arrest times were 243 ± 71, 140 ± 55 and 53 ± 28 min in Group A and 249 ± 76, 147 ± 54 and 57 ± 30 min in Group B, respectively (P = n.s.). The overall 30-day mortality was 10.6% in Group A and 16.1% in Group B (P = n.s.). The postoperative stroke rate was 4.3% in Group A and 3.8% in Group B, respectively (P = n.s.). Rethoracotomy due to bleeding was 27.7% in Group A and 23.2% in Group B (P = n.s.). At a mean follow-up of 4.0 years, 61.7% of the patients in Group A were alive and 29.8% had undergone operations on the downstream aorta. In Group B, 60.7% of the patients were alive at a mean follow-up of 4.4 years and 20.0% had undergone operations on the downstream aorta. None of the patients in Group B developed further pathological changes in the 'island' or the proximal supra-aortic vessels., Conclusions: The BGT is not inferior perioperatively or in the mid-term follow-up compared with the classical island technique. Thus, this technique can be used during total arch replacements in most aortic arch pathologies.

Background: The aim of this study was to determine the health care utilization of patients with acute coronary syndrome (ACS) of one German statutory health insurance. The utilization of ambulatory services as well as of inpatient rehabilitation should be regarded. Moreover, the study should reveal the prescription of drugs for secondary prevention. Here, patients showing guideline corresponding prescriptions should be compared with patients without such prescriptions., Methods: A retrospective claims data analysis of one German statutory health insurance was conducted. Health care utilization was considered in the first year after an index hospitalization due to ACS. Beneficiaries for whom an ICD-10 discharge diagnosis of ACS was reported between January 1st 2007 and December 31st 2009 were included. In order to reveal differences in health care utilization depending on the type of ACS (STEMI versus NSTEMI/UA) stratified analyses were performed. Another stratification was done for patients with and without defined drug prescriptions., Results: From 45,188 patients with ACS almost three quarters were assigned to the group of NSTEMI/UA. For 8.9% of all ACS patients (18.74% STEMI, 8.89% NSTEMI/UA), inpatient post-hospital rehabilitation related to ACS was recorded. Ambulatory care related to CHD diagnosis was utilized by 77.6% of patients, more often by STEMI than by NSTEMI/UA patients. For 36.7% and 45.7% of ACS patients, a prescription of aspirin or clopidogrel was recorded, respectively, 79.4% of STEMI patients received at least one prescription for antiplatelet drugs, the corresponding proportion of NSTEMI/UA was 59.8%. A considerable part of patients without prescription dropped out within the first 90 days after the index event., Conclusions: A claims data analysis of one German statutory health insurance fund showed that health care utilization of ACS patients varied depending on the ACS type. It is necessary to distinguish between STEMI and NSTEMI/UA patients when discussing the ambulatory drug utilization.