Quality of life depends on the drinking pattern in alcohol-dependent patients.

AIMS: In patients with alcohol dependence, health-related quality of life (QOL) is reduced compared with that of a normal healthy population. The objective of the current analysis was to describe the evolution of health-related QOL in adults with alcohol dependence during a 24-month period after initial assessment for alcohol-related treatment in a routine practice setting, and its relation to drinking pattern which was evaluated across clusters based on the predominant pattern of alcohol use, set against the influence of baseline variables METHODS: The Medical Outcomes Study 36-Item Short-Form Survey (MOS-SF-36) was used to measure QOL at baseline and quarterly for 2 years among participants in CONTROL, a prospective observational study of patients initiating treatment for alcohol dependence. The sample consisted of 160 adults with alcohol dependence (65.6% males) with a mean (SD) age of 45.6 (12.0) years. Alcohol use data were collected using TimeLine Follow-Back. Based on the participant's reported alcohol use, three clusters were identified: 52 (32.5%) mostly abstainers, 64 (40.0%) mostly moderate drinkers and 44 (27.5%) mostly heavy drinkers. Mixed-effect linear regression analysis was used to identify factors that were potentially associated with the mental and physical summary MOS-SF-36 scores at each time point. RESULTS: The mean (SD) MOS-SF-36 mental component summary score (range 0-100, norm 50) was 35.7 (13.6) at baseline [mostly abstainers: 40.4 (14.6); mostly moderate drinkers 35.6 (12.4); mostly heavy drinkers 30.1 (12.1)]. The score improved to 43.1 (13.4) at 3 months [mostly abstainers: 47.4 (12.3); mostly moderate drinkers 44.2 (12.7); mostly heavy drinkers 35.1 (12.9)], to 47.3 (11.4) at 12 months [mostly abstainers: 51.7 (9.7); mostly moderate drinkers 44.8 (11.9); mostly heavy drinkers 44.1 (11.3)], and to 46.6 (11.1) at 24 months [mostly abstainers: 49.2 (11.6); mostly moderate drinkers 45.7 (11.9); mostly heavy drinkers 43.7 (8.8)]. Mixed-effect linear regression multivariate analyses indicated that there was a significant association between a lower 2-year follow-up MOS-SF-36 mental score and being a mostly heavy drinker (-6.97, P < 0.001) or mostly moderate drinker (-3.34 points, P = 0.018) [compared to mostly abstainers], being female (-3.73, P = 0.004), and having a Beck Inventory scale score ≥8 (-6.54, P < 0.001), at baseline. The mean (SD) MOS-SF-36 physical component summary score was 48.8 (10.6) at baseline, remained stable over the follow-up and did not differ across the three clusters. Mixed-effect linear regression univariate analyses found that the average 2-year follow-up MOS-SF-36 physical score was increased (compared with mostly abstainers) in mostly heavy drinkers (+4.44, P = 0.007); no other variables tested influenced the MOS-SF-36 physical score. CONCLUSION: Among individuals with alcohol dependence, a rapid improvement was seen in the mental dimension of QOL following treatment initiation, which was maintained during 24 months. Improvement was associated with the pattern of alcohol use, becoming close to the general population norm in patients classified as mostly abstainers, improving substantially in mostly moderate drinkers and improving only slightly in mostly heavy drinkers. The physical dimension of QOL was generally in the normal range but was not associated with drinking patterns

H+ transport is an integral function of the mitochondrial ADP/ATP carrier.

The mitochondrial ADP/ATP carrier (AAC) is a major transport protein of the inner mitochondrial membrane. It exchanges mitochondrial ATP for cytosolic ADP and controls cellular production of ATP. In addition, it has been proposed that AAC mediates mitochondrial uncoupling, but it has proven difficult to demonstrate this function or to elucidate its mechanisms. Here we record AAC currents directly from inner mitochondrial membranes from various mouse tissues and identify two distinct transport modes: ADP/ATP exchange and H+ transport. The AAC-mediated H+ current requires free fatty acids and resembles the H+ leak via the thermogenic uncoupling protein 1 found in brown fat. The ADP/ATP exchange via AAC negatively regulates the H+ leak, but does not completely inhibit it. This suggests that the H+ leak and mitochondrial uncoupling could be dynamically controlled by cellular ATP demand and the rate of ADP/ATP exchange. By mediating two distinct transport modes, ADP/ATP exchange and H+ leak, AAC connects coupled (ATP production) and uncoupled (thermogenesis) energy conversion in mitochondria

Unique versus shared associations between self-reported behavioral addictions and substance use disorders and mental health problems: A commonality analysis in a large sample of young Swiss men.

Behavioral addictions (BAs) and substance use disorders (SUDs) tend to co-occur; both are associated with mental health problems (MHPs). This study aimed to estimate the proportion of variance in the severity of MHPs explained by BAs and SUDs, individually and shared between addictions. A sample of 5,516 young Swiss men (mean = 25.47 years old; SD = 1.26) completed a self-reporting questionnaire assessing alcohol, cannabis, and tobacco use disorders, illicit drug use other than cannabis, six BAs (Internet, gaming, smartphone, Internet sex, gambling, and work) and four MHPs (major depression, attention-deficit hyperactivity disorder, social anxiety disorder, and borderline personality disorder). Commonality analysis was used to decompose the variance in the severity of MHPs explained (R <sup>2</sup> ) by BAs and SUDs into independent commonality coefficients. These were calculated for unique BA and SUD contributions and for all types of shared contributions. BAs and SUDs explained between a fifth and a quarter of the variance in severity of MHPs, but individual addictions explained only about half of this explained variance uniquely; the other half was shared between addictions. A greater proportion of variance was explained uniquely or shared within BAs compared to SUDs, especially for social anxiety disorder. The interactions of a broad range of addictions should be considered when investigating their associations with MHPs. BAs explain a larger part of the variance in MHPs than do SUDs and therefore play an important role in their interaction with MHPs

Change Talk During Brief Motivational Intervention With Young Adult Males: Strength Matters.

Client change talk (CT) during motivational interviewing (MI) has been described as a predictor of change in alcohol use. We examined the predictive validity of different strength levels of CT within a brief MI session for 174 young men from the general population screened as hazardous drinkers. CT was measured using the MI Skill Code (MISC 2.1) and categorized with positive (toward change) and negative (against change) valence and 3 strength levels (1=low, 2=medium, 3=high). Analyses included linear regression models predicting drinking at 3-month follow-up, while controlling for baseline drinking. Frequency of overall negative CT (i.e., sum of -1, -2, -3) significantly predicted poorer drinking outcomes. In a multivariate model entering frequency of CT utterances at each level of strength (i.e. +1, +2, +3, -1, -2, -3), the directionality of negative strength ratings was consistently in the expected direction, but only CT-2 was statistically significant. In contrast, overall CT positive (i.e., sum of +1, +2, +3) was not a significant predictor of less alcohol use, but the multivariate model showed that the presence of CT+3 significantly predicted less drinking at 3-month follow-up. Averaged strength summary score (i.e. on the scale from -3 to +3) was a significant predictor of better outcome, while percent positive CT was not. Moderation analyses showed that young men with lower baseline readiness to change or lower alcohol problem severity had higher follow-up drinking when they expressed more CT+1 or CT+2, while the opposite pattern was observed with those reporting higher baseline readiness to change or higher alcohol problem severity. Mixed findings for varying levels of positive CT strength might explain previous studies showing poor predictive validity of positive client language in MI. Together with other studies in similar settings, these findings suggest the importance of advanced MI techniques to shape client language to soften negative change talk (also known as sustain talk) and elicit positive CT verbalized with high intensity

Internet-Based Brief Intervention to Prevent Unhealthy Alcohol Use among Young Men: A Randomized Controlled Trial.

INTRODUCTION: Alcohol use is one of the leading modifiable morbidity and mortality risk factors among young adults. STUDY DESIGN: 2 parallel-group randomized controlled trial with follow-up at 1 and 6 months. SETTING/PARTICIPANTS: Internet based study in a general population sample of young men with low-risk drinking, recruited between June 2012 and February 2013. Intervention: Internet-based brief alcohol primary prevention intervention (IBI). The IBI aims at preventing an increase in alcohol use: it consists of normative feedback, feedback on consequences, calorific value alcohol, computed blood alcohol concentration, indication that the reported alcohol use is associated with no or limited risks for health. Intervention group participants received the IBI. Control group (CG) participants completed only an assessment. MAIN OUTCOME MEASURES: Alcohol use (number of drinks per week), binge drinking prevalence. Analyses were conducted in 2014-2015. RESULTS: Of 4365 men invited to participate, 1633 did so; 896 reported low-risk drinking and were randomized (IBI: n = 451; CG: n = 445). At baseline, 1 and 6 months, the mean (SD) number of drinks/week was 2.4(2.2), 2.3(2.6), 2.5(3.0) for IBI, and 2.4(2.3), 2.8(3.7), 2.7(3.9) for CG. Binge drinking, absent at baseline, was reported by 14.4% (IBI) and 19.0% (CG) at 1 month and by 13.3% (IBI) and 13.0% (CG) at 6 months. At 1 month, beneficial intervention effects were observed on the number of drinks/week (p = 0.05). No significant differences were observed at 6 months. CONCLUSION: We found protective short term effects of a primary prevention IBI. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN55991918

Internet-based brief intervention for young men with unhealthy alcohol use: a randomized controlled trial in a general population sample.

To test the efficacy of an internet-based brief intervention (IBI) in decreasing alcohol use among young Swiss men aged 21 years on average. Two parallel-group randomized controlled trial with a 1 : 1 allocation ratio containing follow-up assessments at 1 and 6 months post-randomization Internet-based study in a general population sample. Twenty-one-year-old men from Switzerland with unhealthy alcohol use (> 14 drinks/week or ≥ 6 drinks/occasion at least monthly or Alcohol Use Disorders Identification Test (AUDIT) scores ≥ 8) INTERVENTION: IBI consisting of (1) normative feedback, (2) feedback on consequences of alcohol use, (3) calorific value of reported consumption, (4) computed blood alcohol concentration for reported consumption, (5) indication of risk, (6) information on alcohol and health and (7) recommendations indicating low-risk drinking limits. Control condition: no intervention (assessment only). At 1 and 6 months: quantity/frequency questions on alcohol use (primary outcome: number of drinks/week) and binge drinking prevalence; at 6 months: AUDIT score, consequences of drinking (range = 0-12). Follow-up rates were 92% at 1 month and 91% at 6 months. At 6 months, participants in the intervention group (n = 367) reported greater reductions in the number of drinks/week than participants in the control group (n = 370) [treatment × time interaction, incidence rate ratio (RR) = 0.86, 95% confidence interval (CI) = 0.78; 0.96], but no significant differences were observed on binge drinking prevalence. There was a favourable intervention effect on AUDIT scores (IRR = 0.93, 95% CI = 0.88; 0.98), but not on the number of consequences (IRR = 0.93, 95% CI = 0.84; 1.03). An internet-based brief intervention directed at harmful alcohol use among young men led to a reduction in self-reported alcohol consumption and AUDIT scores compared with a no-intervention control condition (assessment only)

Admissions of patients with alcohol intoxication in the Emergency Department: a growing phenomenon.

QUESTION UNDER STUDY: To investigate the change over time in the number of ED admissions with positive blood alcohol concentration (BAC) and to evaluate predictors of BAC level. METHODS: We conducted a single site retrospective study at the ED of a tertiary referral hospital (western part of Switzerland) and obtained all the BAC performed from 2002 to 2011. We determined the proportion of ED admissions with positive BAC (number of positive BAC/number of admissions). Regression models assessed trends in the proportion of admissions with positive BAC and the predictors of BAC level among patients with positive BAC. RESULTS: A total of 319,489 admissions were recorded and 20,021 BAC tests were performed, of which 14,359 were positive, divided 34.5% female and 65.5% male. The mean (SD) age was 41.7(16.8), and the mean BAC was 2.12(1.04) permille (g of ethanol/liter of blood). An increase in the number of positive BAC was observed, from 756 in 2002 to 1,819 in 2011. The total number of admissions also increased but less: 1.2 versus 2.4 times more admissions with positive BAC. Being male was independently associated with a higher (+0.19 permille) BAC, as was each passing year (+0.03). A significant quadratic association with age indicated a maximum BAC at age 53. CONCLUSION: We observed an increase in the percentage of admissions with positive BAC that was not limited to younger individuals. Given the potential consequences of alcohol intoxication, and the large burden imposed on ED teams, communities should be encouraged to take measures aimed at reducing alcohol intoxication

The psychological impact of the COVID-19 crisis on young Swiss men participating in a cohort study.

The COVID-19 pandemic caused many disturbances to daily life worldwide and may also have significantly affected people's psychological well-being. The present study aimed to describe the psychological impact of the crisis on our sample of young Swiss men and to examine differences due to their linguistic region, experiencing COVID-19 symptoms and living arrangements. Based on an ongoing cohort study, we assessed a general-population sample of young Swiss men (n = 2345; average 29 years old) shortly before (from April 2019) and early on during the COVID-19 crisis (between 13 May and 8 June 2020). This was a unique opportunity to estimate the crisis' psychological impact in the form of depression, perceived stress and sleep quality (assessed before and during COVID-19), and any crisis-induced fears, isolation or psychological trauma. Associations of psychological impact with living arrangements, experiencing COVID-19 symptoms and linguistic region (German-speaking vs French-speaking) were investigated using linear regression models. By the time participants responded to our questionnaire, less than 1% had been tested positive for COVID-19, 2.6% had been tested negative and 14.7% had had some COVID-19 symptoms but had not been tested. About 8.2% of the sample reported at least some symptoms of psychological trauma (≥24 points on the Impact of Event Scale). On average, participants reported higher levels of fear for others (43.6% at least moderate) and economic fear (12.7% at least moderate) than fear for themselves (5.8% at least moderate). Those living alone and those who reported having COVID-19 symptoms themselves, or knowing someone with symptoms, reported higher overall psychological impact in the form of depression, perceived stress, sleep quality, psychological trauma, fear and isolation. Associations with linguistic region varied by outcome, with higher levels of depression and fear in French-speaking regions and higher levels of perceived stress and isolation in German-speaking regions. The crisis had a considerable impact on the psychological well-being of our sample of young Swiss men, and some groups were more affected than others: those living alone and those who had shown COVID-19 symptoms themselves or had known someone with symptoms may have felt a greater psychological impact from the crisis. Supporting those at a higher risk of psychological consequences in such crises, whether through structural measures or via individual support, should be an important aspect of crisis management and could help reduce the overall impact of the current pandemic on Switzerland's population

Effect of a Novel Brief Motivational Intervention for Alcohol-Intoxicated Young Adults in the Emergency Department: A Randomized Clinical Trial.

Heavy drinking among young adults is a major public health concern. Brief motivational interventions in the emergency department have shown promising but inconsistent results. To test whether young adults receiving a newly developed brief motivational intervention reduce their number of heavy drinking days and alcohol-related problems over 1 year compared with participants receiving brief advice. This randomized clinical trial was conducted at an emergency department of a tertiary care university hospital in Lausanne, Switzerland. Recruitment ran from December 2016 to August 2019. Follow-up was conducted after 1, 3, 6, and 12 months. All adults aged 18 to 35 years presenting for any cause and presenting with alcohol intoxication were eligible (N = 2108); 1764 were excluded or refused participation. Follow-up rate was 79% at 12 months and 89% of participants provided follow-up data at least once and were included in the primary analyses. Statistical analysis was performed from September 2020 to January 2021. The novel intervention was based on motivational interviewing and comprised in-person discussion in the emergency department and up to 3 booster telephone calls. The control group received brief advice. Primary outcomes were the number of heavy drinking days (at least 60 g of ethanol) over the previous month and the total score on the Short Inventory of Problems (0-45, higher scores indicating more problems) over the previous 3 months. Hypotheses tested were formulated before data collection. There were 344 young adults included (median [IQR] age: 23 [20-28] years; 84 women [24.4%]). Among the 306 participants providing at least 1 follow-up point, a statistically significant time × group interaction was observed (β = -0.03; 95% CI, -0.05 to 0.00; P = .02), and simple slopes indicated an increase of heavy drinking days over time in the control (β = 0.04; 95% CI, 0.02 to 0.05; P < .001) but not in the intervention group (β = 0.01; 95% CI, -0.01 to 0.03; P = .24). There was no effect on the Short Inventory of Problems score (β = -0.01; 95% CI, -0.03 to 0.02; P = .71). This randomized clinical trial found that a brief motivational intervention implemented in the emergency department provided beneficial effects on heavy drinking, which accounts for a substantial portion of mortality and disease burden among young adults. ISRCTN registry: 13832949

Respiratory motion modelling for MR-guided lung cancer radiotherapy: model development and geometric accuracy evaluation.

Objective.Respiratory motion of lung tumours and adjacent structures is challenging for radiotherapy. Online MR-imaging cannot currently provide real-time volumetric information of the moving patient anatomy, therefore limiting precise dose delivery, delivered dose reconstruction, and downstream adaptation methods.Approach.We tailor a respiratory motion modelling framework towards an MR-Linac workflow to estimate the time-resolved 4D motion from real-time data. We develop a multi-slice acquisition scheme which acquires thick, overlapping 2D motion-slices in different locations and orientations, interleaved with 2D surrogate-slices from a fixed location. The framework fits a motion model directly to the input data without the need for sorting or binning to account for inter- and intra-cycle variation of the breathing motion. The framework alternates between model fitting and motion-compensated super-resolution image reconstruction to recover a high-quality motion-free image and a motion model. The fitted model can then estimate the 4D motion from 2D surrogate-slices. The framework is applied to four simulated anthropomorphic datasets and evaluated against known ground truth anatomy and motion. Clinical applicability is demonstrated by applying our framework to eight datasets acquired on an MR-Linac from four lung cancer patients.Main results.The framework accurately reconstructs high-quality motion-compensated 3D images with 2 mm3isotropic voxels. For the simulated case with the largest target motion, the motion model achieved a mean deformation field error of 1.13 mm. For the patient cases residual error registrations estimate the model error to be 1.07 mm (1.64 mm), 0.91 mm (1.32 mm), and 0.88 mm (1.33 mm) in superior-inferior, anterior-posterior, and left-right directions respectively for the building (application) data.Significance.The motion modelling framework estimates the patient motion with high accuracy and accurately reconstructs the anatomy. The image acquisition scheme can be flexibly integrated into an MR-Linac workflow whilst maintaining the capability of online motion-management strategies based on cine imaging such as target tracking and/or gating