Moderate Alcohol Research Articles

Does severity of periodontal disease influence the risk of developing gastrointestinal malignancies?

e15549 Background: In recent years, multiple observational studies have suggested increased risk of developing gastrointestinal (GI) malignancies in patients with prior periodontal disease (PD). Our aim was to determine whether a difference in incidence of GI malignancies exists amongst patients with pre-existing mild-moderate vs. severe PD. Methods: This was a single institution retrospective IRB approved study. We identified a cohort of patients between 2011-21 with PD and concurrent registration in independent dental and medical electronic health record systems at the University of Florida. Patients were stratified into 2 groups based on severity of PD (mild-moderate or severe). Descriptive statistics were used to compare the 2 groups based on demographics and medical history. Cumulative incidence curves were used to compare GI malignancy incidence between the 2 groups. Multivariable logistic regression was used to identify predictors of developing GI malignancies. Results: A total of 2168 patients with PD were identified with a median follow up of 4.7 (IQR 2.6-6.8) yr. Of these, 54% had severe PD and 46% had mild-moderate PD. Severe PD was more common within males (58% vs 50% in females), Black race (62% vs 52% in Caucasians), diabetics (59% vs 52% in non-diabetics), cigarette smokers (60% vs 51% in non-smokers) and excessive alcohol intake (70% vs 61% in moderate alcohol intake). There was no significant difference in cumulative incidence rates of GI malignancies (colon, pancreatic, gastric, hepatic, and esophageal) between the PD groups stratified by severity (12% in severe vs 11% in mild-moderate, p = 0.6 at 5 yr follow up). In univariable logistic regression, severe vs mild-moderate PD OR was 1.12 [95% CI: 0.87,1.46], thus more severe form of PD is not associated with developing a GI malignancy. In multivariable logistic regression, severe vs mild/moderate PD adjusted OR was 1.04 [95% CI: 0.79,1.36], thus also not statistically significant, with other risk factors of developing GI malignancies identified in Table 1. Conclusions: There was no association between the severity of periodontal disease and subsequent development of GI malignancy. [Table: see text]

0480 Psychoactive Substance Use and Sleep Characteristics Among Individuals with Untreated Obstructive Sleep Apnea

Abstract Introduction Obstructive sleep apnea (OSA) is characterized by recurrent airway obstruction causing intermittent hypoxia, arousal from sleep, and autonomic instability, and is associated with a variety of long-term health sequala. The fragmented sleep resulting from these respiratory events leads to disruption in normal sleep architecture and progression to deeper stages of sleep, a potential mediator for some of the functional and neurocognitive impairments seen in this population. Similarly, psychoactive substance use (i.e., nicotine, alcohol, and caffeine) impacts sleep architecture in healthy individuals, but their effects in those with OSA have not been well described. We aimed to describe the association between psychoactive substance use and sleep characteristics and daytime symptoms in individuals with untreated OSA. Methods We performed a secondary, cross-sectional analysis of The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Exposures included current smoking, alcohol, and caffeine use in individuals with untreated OSA. Outcome domains included subjective and objective sleep characteristics, daytime symptoms, and co-morbid conditions. Linear or logistic regression assessed the association between substance use and each domain (e.g., self-reported sleep duration, total polysomnographic sleep time, sleepiness, and anxiety). Results Of the 919 individuals with untreated OSA, 116 (12.6%) were current cigarette smokers, 585 (63.7%) were moderate or heavy alcohol users, and 769 (83.7%) were moderate or heavy caffeine users. Current smokers exhibited lower sleep duration (0.3 hours) and longer sleep latency (5 minutes) compared with non-smokers (all p-values< 0.05). REM sleep increased in those with moderate and heavy alcohol use (2.5 and 5% of total sleep time respectively), and moderate caffeine use (2%, all p-values < 0.05)). The combined smoker plus caffeine group exhibited shorter sleep duration (0.4 hours) and higher risk for chronic pain [Odds Ratio (95%CI) = 4.83 (1.57, 14.9). . Conclusion Both psychoactive substances and untreated OSA impact normal sleep architecture, their cumulative effect may have clinical implications in this subgroup. Stimulating or sedating substances may be used in OSA patients to mitigate daytime and nighttime symptoms respectively. Further investigation into the effects substances have on this population may present opportunities to better understand disease mechanisms and increase the effectiveness of treatment in OSA Support (if any)

0826 Chronotype, unhealthy lifestyle, and diabetes risk in middle-aged US women: A prospective cohort study in Nurses’ Health Study II

Abstract Introduction Chronotype refers to one’s inclination to earlier or later sleeping times. Late chronotype has been linked to increased diabetes risk, which may be mediated through adherence to unhealthy lifestyle. This study aimed to evaluate the interplay among chronotype, lifestyle factors, and diabetes risk. Methods In 2009, 63,594 diabetes-free women (mean age=54 yrs) from the Nurses’ Health Study II self-reported their chronotype using a validated question from the Morningness-Eveningness Questionnaire and were prospectively followed for incident type 2 diabetes (T2DM) until June 2017. Unhealthy lifestyle was defined by having < 4 of the following 6 healthy lifestyle factors: high diet quality (AHEI≥49), physical activity (≥3.5 MET-hours/week), moderate alcohol intake (≥5 and < 15 g/day), normal body mass index (≥18.5 and < 25 kg/m2), non-current smoking, and 7-9 hours of sleep. T2DM was self-reported and confirmed using a validated supplementary questionnaire. We used modified Poisson regression models to estimate the cross-sectional associations between chronotype and unhealthy lifestyle. Cox proportional hazards models were used to estimate the adjusted hazard ratios (aHR) for incident diabetes risk according to chronotype and assess the proportion of the association explained by lifestyle factors (mediation analyses). Results Participants reporting a “definitely-evening” type were 55% (95% CI: 1.51-1.60) more likely to have an unhealthy lifestyle compared with participants reporting a “definitely-morning” type. We documented 1,921 T2DM cases over 468,555 person-years of follow-up. With increasing eveningness, the risk of T2DM became significantly higher (Ptrend< 0.0001). Compared with the “definitely-morning” type, the aHR (95% CI) for T2DM was 1.10 (0.97-1.24) for “more-morning”, 1.01 (0.81-1.27) for “intermediate”, 1.26 (1.11-1.42) for “more-evening”, and 1.65 (1.44-1.90) for “definitely-evening” chronotypes, after adjusting for sociodemographic factors, shift-work, depression and family history of diabetes. Additional adjustment of unhealthy lifestyle explained 56.8% (95% CI: 39.4%-72.6%) of the association [aHR (95% CI) for “definitely-evening” versus “definitely-morning”: 1.27 (1.10-1.46)]. Conclusion Women with a late chronotype are more likely to engage in unhealthy lifestyle behaviors. Late chronotype is prospectively associated with increased diabetes risk, which is partly explained by unhealthy lifestyle behaviors. Our results suggest that lifestyle interventions may potentially reduce the adverse impact of late chronotype on diabetes risk. Support (if any) R01HL155395, K01HL143034, U01CA176726

Association of Healthy Lifestyle Factors and Obesity-Related Diseases in Adults in the UK

ImportanceA healthy lifestyle is associated with a reduced risk of cardiovascular disease in adults with obesity. Little is known about the associations between a healthy lifestyle and the risk of other obesity-attributable diseases in this population.ObjectiveTo examine the association between healthy lifestyle factors and the incidence of major obesity-related diseases in adults with obesity compared with those with normal weight.Design, Setting, and ParticipantsThis cohort study evaluated UK Biobank participants aged 40 to 73 years and free of major obesity-attributable disease at baseline. Participants were enrolled from 2006 to 2010 and prospectively followed up for disease diagnosis.ExposuresA healthy lifestyle score was constructed using information on not smoking, exercising regularly, no or moderate alcohol consumption, and eating a healthy diet. For each lifestyle factor, participants scored 1 if they met the criterion for a healthy lifestyle and 0 otherwise.Main Outcomes and MeasuresThe risk of outcomes according to the healthy lifestyle score in adults with obesity compared with those with normal weight were examined using multivariable Cox proportional hazards models with Bonferroni correction for multiple testing. The data analysis was performed between December 1, 2021, and October 31, 2022.ResultsA total of 438 583 adult participants in the UK Biobank were evaluated (female, 55.1%; male, 44.9%; mean [SD] age, 56.5 [8.1] years), of whom 107 041 (24.4%) had obesity. During a mean (SD) follow-up of 12.8 (1.7) years, 150 454 participants (34.3%) developed at least 1 of the studied diseases. Compared with adults with obesity and 0 healthy lifestyle factors, individuals with obesity who met all 4 healthy lifestyle factors were at lower risk of hypertension (HR, 0.84; 95% CI, 0.78-0.90), ischemic heart disease (HR, 0.72; 95% CI, 0.65-0.80), arrhythmias (HR, 0.71; 95% 0.61-0.81), heart failure (HR, 0.65; 95% CI, 0.53-0.80), arteriosclerosis (HR, 0.19; 95% CI, 0.07-0.56), kidney failure (HR, 0.73; 95% CI, 0.63-0.85), gout (HR, 0.51; 95% CI, 0.38-0.69), sleep disorders (HR, 0.68; 95% CI, 0.56-0.83), and mood disorders (HR, 0.66; 95% CI, 0.56-0.78). The lifestyle profiles associated with the lowest risks included a healthy diet and at least 1 of the 2 healthy behaviors of physical activity and never smoking. Compared with adults with normal weight, those with obesity were at higher risk of several outcomes, irrespective of the lifestyle score (adjusted HRs ranged from 1.41 [95% CI, 1.27-1.56] for arrhythmias to 7.16 [95% CI, 6.36-8.05] for diabetes for adults with obesity and 4 healthy lifestyle factors).Conclusion and RelevanceIn this large cohort study, adherence to a healthy lifestyle was associated with reduced risk of a wide range of obesity-related diseases, but this association was modest in adults with obesity. The findings suggest that although a healthy lifestyle seems to be beneficial, it does not entirely offset the health risks associated with obesity.

Modifiable Risk Factors and Long-term Risk of Type 2 Diabetes Among Individuals With a History of Gestational Diabetes Mellitus: Prospective Cohort Study

(BMJ. 2022;378:e070312) About 8% of US pregnancies are complicated by gestational diabetes mellitus (GDM). Type 2 diabetes is caused by a combination of genetic and lifestyle factors, and undiagnosed diabetes can cause potentially irreversible cardiovascular, renal, or neurological damage. Those affected by GDM are at a heightened risk for type 2 diabetes. This study aimed to evaluate the associations between modifiable risk factors [body mass index (BMI), high-quality diet, regular physical activity, moderate alcohol consumption, and not smoking] and risk of progression to type 2 diabetes in patients who have experienced GDM. A secondary aim was to evaluate whether these associations varied by BMI or genetic susceptibility to type 2 diabetes.

Digital interventions to moderate alcohol consumption in young people: a Cancer Prevention Europe overview of systematic reviews.

Strategies to reduce alcohol consumption would contribute to substantial health benefits in the population, including reducing cancer risk. The increasing accessibility and applicability of digital technologies make these powerful tools suitable to facilitate changes in behaviour in young people which could then translate into both immediate and long-term improvements to public health. We conducted a review of systematic reviews to assess the available evidence on digital interventions aimed at reducing alcohol consumption in sub-populations of young people [school-aged children, college/university students, young adults only (over 18 years) and both adolescent and young adults (<25 years)]. Searches were conducted across relevant databases including KSR Evidence, Cochrane Database of Systematic Reviews (CDSR) and Database of Abstracts of Reviews of Effects (DARE). Records were independently screened by title and abstract and those that met inclusion criteria were obtained for full text screening by two reviewers. Risk of bias (RoB) was assessed with the ROBIS checklist. We employed a narrative analysis. Twenty-seven systematic reviews were included that addressed relevant interventions in one or more of the sub-populations, but those reviews were mostly assessed as low quality. Definitions of "digital intervention" greatly varied across systematic reviews. Available evidence was limited both by sub-population and type of intervention. No reviews reported cancer incidence or influence on cancer related outcomes. In school-aged children eHealth multiple health behaviour change interventions delivered through a variety of digital methods were not effective in preventing or reducing alcohol consumption with no effect on the prevalence of alcohol use [Odds Ratio (OR) = 1.13, 95% CI: 0.95-1.36, review rated low RoB, minimal heterogeneity]. While in adolescents and/or young adults who were identified as risky drinkers, the use of computer or mobile device-based interventions resulted in reduced alcohol consumption when comparing the digital intervention with no/minimal intervention (-13.4 g/week, 95% CI: -19.3 to -7.6, review rated low RoB, moderate to substantial heterogeneity).In University/College students, a range of E-interventions reduced the number of drinks consumed per week compared to assessment only controls although the overall effect was small [standardised mean difference (SMD): -0.15, 95% CI: -0.21 to -0.09]. Web-based personalised feedback interventions demonstrated a small to medium effect on alcohol consumption (SMD: -0.19, 95% CI: -0.27 to -0.11) (review rated high RoB, minimal heterogeneity). In risky drinkers, stand-alone Computerized interventions reduced short (SMD: -0.17, 95% CI: -0.27 to -0.08) and long term (SMD: -0.17, 95% CI: -0.30 to -0.04) alcohol consumption compared to no intervention, while a small effect (SMD: -0.15, 95% CI: -0.25 to -0.06) in favour of computerised assessment and feedback vs. assessment only was observed. No short-term (SMD: -0.10, 95% CI: -0.30 to 0.11) or long-term effect (SMD: -0.11, 95% CI: -0.53 to 0.32) was demonstrated for computerised brief interventions when compared to counsellor based interventions (review rated low RoB, minimal to considerable heterogeneity). In young adults and adolescents, SMS-based interventions did not significantly reduce the quantity of drinks per occasion from baseline (SMD: 0.28, 95% CI: -0.02 to 0.58) or the average number of standard glasses per week (SMD: -0.05, 95% CI: -0.15 to 0.05) but increased the risk of binge drinking episodes (OR = 2.45, 95% CI: 1.32-4.53, review rated high RoB; minimal to substantial heterogeneity). For all results, interpretation has limitations in terms of risk of bias and heterogeneity. Limited evidence suggests some potential for digital interventions, particularly those with feedback, in reducing alcohol consumption in certain sub-populations of younger people. However, this effect is often small, inconsistent or diminishes when only methodologically robust evidence is considered. There is no systematic review evidence that digital interventions reduce cancer incidence through alcohol moderation in young people. To reduce alcohol consumption, a major cancer risk factor, further methodologically robust research is warranted to explore the full potential of digital interventions and to form the basis of evidence based public health initiatives.

Estimates of compliance with Canada's guidelines for low and moderate risk alcohol consumption: the importance of adjustment for underreporting in self-report surveys.

Alcohol is a leading cause of premature mortality; however, awareness of this and of some specific risks is low. Survey-based estimates of drinking at risk levels suffer from substantial underreporting. We show that alcohol use reported in the 2019 Canadian Alcohol and Drug Survey (CADS) accounted for just 38.06% of recorded alcohol consumption. This contributes to alcohol's risks being minimized, by researchers, the public, and policymakers. The new Canada's Guidance on Alcohol and Health (CGAH) defines "moderate risk" as 3 to 6 drinks/week for men and women. Employing published methods to correct for underreporting in the CADS, we estimate that in 2019 the proportion of drinkers at moderate risk of long-term harm to be 50.43% (up from 23.34% without adjustment). We further estimate that, collectively, these drinkers consumed 90.17% of all drinks consumed that year. Similarly, 92.82% of drinks were consumed on days when upper limits for short-term harm (2 drinks/day) were exceeded (up from 65.02% without adjustment). We conclude that adjustments for underreporting of alcohol use in Canada need to be incorporated routinely in public health monitoring. This might help mitigate the widespread underestimation of risky alcohol use as well as the neglect of this public health issue by policymakers.

Impaired cognitive control after moderate prenatal alcohol exposure corresponds to altered EEG power during a rodent touchscreen continuous performance task

Although it is well established that alcohol consumption during pregnancy can lead to lifelong difficulties in offspring, Fetal Alcohol Spectrum Disorders (FASD) remain a common neurodevelopmental syndrome. Translational behavioral tools that target similar brain circuits across species can facilitate understanding of these cognitive consequences. Touchscreen behavioral tasks for rodents enable easy integration of dura recordings of electroencephalographic (EEG) activity in awake behaving animals, with clear translational generalizability. Recently, we showed that Prenatal Alcohol Exposure (PAE) impairs cognitive control on the touchscreen 5-Choice Continuous Performance Task (5C-CPT) which requires animals to touch on target trials (hit) and withhold responding on non-target trials (correct rejection). Here, we extended these findings to determine whether dura EEG recordings would detect task-relevant differences in medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) corresponding with behavioral alterations in PAE animals. Replicating previous findings, PAE mice made more false alarm responses versus controls and had a significantly lower sensitivity index. All mice, regardless of sex or treatment, demonstrated increased frontal theta-band power during correct trials that followed an error (similar to post-error monitoring commonly seen in human participants). All mice showed a significant decrease in parietal beta-band power when performing a correct rejection versus a hit. PAE mice of both sexes showed a significantly larger decrease in parietal beta-band power when successfully rejecting non-target stimuli. These findings suggest that moderate exposure to alcohol during development can have long lasting effects on cognitive control, and task-relevant neural signals may provide a biomarker of impaired function across species.

Leveraging Dynamic Norms to Reduce College Student Alcohol Use: A Test of Four Mediators

ABSTRACT Social norms are common in persuasive messaging. For norms trending in a positive direction, it may be beneficial to emphasize change (i.e. dynamic norm) rather than the status quo (i.e. static norm). To test this proposition, we examined college students’ responses to social norm messages encouraging moderate alcohol use. Undergraduates (N = 842) were randomly assigned to view a dynamic norm (“More college students drinking in moderation”), a static descriptive norm (“Most college students drink in moderation”), or a no message control. Four mechanisms were examined as potential mediators, three of which have been examined in previous work (preconformity, perceived importance, self-efficacy) and one of which was novel (psychological reactance). Results revealed that exposure to either social norm message (dynamic or static descriptive) was associated with more favorable attitude relative to a no message control. Attitude did not differ between the dynamic norm and static descriptive norm conditions. Only psychological reactance mediated the relationship between message condition (dynamic vs. static descriptive norm) and favorable attitude. Implications and future directions are discussed.

Diet as a Risk Factor for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that involves primarily synovial tissuesand typically affects women more than men. An exact cause has yet to be identified, but the disease is thought to manifest due to both genetic and environmental factors. The predominant theory is that RA is an autoimmune disease with environmental triggers. Recently, diet as a risk factor for RA has become of interest. The objective of this narrative review is to determine which dietary factors have an influence on developing RA by examining existing literature on this topic. A PubMed search was built using theMeSH terms: "rheumatoid arthritis," "risk factors," "diet," "nutritional status," "nutrition therapy," "nutrition assessment," "nutrition disorders," "diet, food, and nutrition," and "nutritional requirements." Articles containing a sample size of >10,published in the last 30 years, and written in English were included.Current literature has examined dietary items, such as alcohol, fruit, red meat, and caffeinated beverages, as risk factors for RA. However, the effect of each dietary item has often been variable across studies. The variation in results maybe attributed to the variable categorization of each dietary item across studies, variations in the phrasing of dietary items, differing methods of data collection, and the cohort chosen. This narrative review of the literature showed that moderate alcohol consumption and increasedβ-cryptoxanthin are protective against developing RA. Overall, specific dietary elements and their influence on RA risk is a promising topic, and significant findings may be helpful in preventing the development of RA.

Intention to Engage in Alcohol Use during Pregnancy: The Role of Attitudes and Prototypes

Background: There is no known risk-free level of alcohol use in pregnancy. Despite this, many still believe that occasional drinking is safe. To-date, there is limited evidence of the influences on women’s decisions about low to moderate alcohol use in pregnancy. The aim of this study was to explore alcohol use intentions during pregnancy, using variables from the theory of planned behavior, the prototype/willingness model and personality variables. The study also investigated whether priming participants with exposure to prototypes describing different alcohol use behaviors had an impact on intentions. Methods: Participants, 746 women aged 20 to 45 years, were randomized to be prompted to think of one of two different “types” of behaviors, i.e., small level of alcohol use in pregnancy and ambiguous level of alcohol use in pregnancy. They then completed measures of theoretical variables, impulsivity, venturesomeness, and self-efficacy. Participants then answered whether they intended to use alcohol during a future pregnancy. Results: Over half of the variance in intentions to consume alcohol while pregnant were predicted by the final model (R2 = .527, F (1, 438) = 13.201, p < .001). Positive attitudes toward alcohol use in pregnancy, from the theory of planned behavior, were the most significant predictor of intentions and intentions did not differ between groups according to prototype exposure. Conclusions: Future research should aim to explore the efficacy of interventions to reduce low to moderate alcohol use in pregnancy that utilize both the theory of planned behavior and prototype/willingness model to target determinants of intentions.

Auxins seem promising as a tuning method for balancing sugars with acidity in grape musts from cv. Tempranillo, but not defoliation or application of magnesium to leaves

Global warming boosted by climate change affects grape quality, with increasing total soluble solids (TSS) content and decreasing total acidity (TA). However, current wine preferences increasingly include moderate alcohol content, higher acidity and the preservation of primary aromas reminiscent of grapes. Therefore, we hypothesised that applying phytohormones or mineral nutrients to leaves or carrying out defoliation can improve grape must properties in the face of climate warming and in accordance with current oenological trends. The effects of these three viticultural strategies were assessed independently from one another during three growing seasons in a Vitis vinifera L. cv. Tempranillo vineyard in northern Spain. Specifically, three 1-naphtaleneacetic acid (NAA) treatments, two early defoliations (ED; moderate and severe) and two foliar fertilisations with magnesium (Mg) were applied. Treatment with NAA was the most encouraging strategy for decreasing must TSS while increasing TA: it had slight effects on TSS in general and also slight effects on TA when applied close to veraison. The effects of the Mg treatments and moderate ED had null to slightly adverse effects. Finally, severe ED was clearly counter-productive. This study contributes to understanding the effects of both auxin and early defoliation treatments on grape must TSS, acidity and even yeast assimilable nitrogen (YAN) at harvest time. The favourable effects of NAA application are shown to be consistent though slight. Therefore, according to these results, the application of auxins may be an adequate choice for balancing sugars with acidity in grape musts. However, the results also suggest that more research needs to be undertaken to better characterise the effects of auxin treatments on grape must properties at harvest. In particular, different types of auxins, rates, concentrations and number of applications should be tested in the quest for more marked effects.

Abstract 461: Alcohol Modulates Chemokine- And Hypoxia-induced Endothelial-to-mesenchymal Transition In Vitro And Following Ligation Injury In Vivo

Endothelial-to-mesenchymal transition (EndMT) plays a role in arteriosclerotic cardiovascular disease (CVD). Low-to-moderate alcohol consumption (i.e., 1-3 drinks/d range) protects against endothelial dysfunction and arteriosclerosis, in part by stimulating Notch, but whether it does so by influencing EndMT is unknown. Our aim was to address this question. Human coronary artery endothelial cells (HCAEC) (p5-p14) were treated (7 d) with transforming growth factor β (TGFβ, 10 ng/ml) or exposed to hypoxia (5% O 2 ), in the absence or presence of ‘moderate’ level EtOH (25 mM), or the Notch ligand DLL4 +/- the Notch inhibitor DAPT. EndMT was assessed by determining endothelial marker CD31 and smooth muscle cell marker αSMA expression by immunohistochemistry and qRT-PCR, as well as by cell morphology and extracellular matrix protein Fibronectin production. Both TGFβ and hypoxia induced EndMT of HCAEC as determined by simultaneously decreased CD31 and increased αSMA expression, together with a change in morphology from cobblestone (typical of endothelial cells) to spindle-shaped (typical of mesenchymal cells), and increased fibronectin expression. EtOH inhibited EndMT caused by both TGFβ and hypoxia as indicated by maintenance of CD31 expression and cobblestone morphology, and attenuated αSMA and fibronectin expression in the EtOH treated group vs controls. Similar to EtOH, treatment with DLL4 inhibited TGFβ-induced myogenic αSMA and fibronectin mRNA expression in HCAEC, effects blocked by DAPT. Following carotid ligation in C57Bl/6 mice, ~25% of neointimal and medial cells in the remodeled vessel co-expressed αSMA and CD31 (indicative of myo-endothelial cells), suggesting the involvement of EndMT. In the ‘daily moderate’ alcohol group (2 drinks per day equivalent; peak BAC=15 mM) carotid neointimal hyperplasia was reduced compared to controls concomitant with fewer (&lt;10%) αSMA + /CD31 + myo-endothelial cells suggesting repression of EndMT in that cohort. In conclusion, these data illuminate an inhibitory effect of alcohol on EndMT, potentially mediated via Notch. This effect on endothelial transdifferentiation may underlie, in part, the protective effect of moderate alcohol consumption on CVD.

Metabolic Signature of Healthy Lifestyle and Risk of Rheumatoid Arthritis: Observational and Mendelian Randomization Study

BackgroundAlthough substantial evidence reveals that healthy lifestyle behaviors are associated with a lower risk of rheumatoid arthritis (RA), the underlying metabolic mechanisms remain unclear. ObjectivesThis study aimed to identify the metabolic signature reflecting a healthy lifestyle and investigate its observational and genetic linkage with RA risk. MethodsThis study included 87,258 UK Biobank participants (557 cases with incident RA) aged 37–73 y with complete lifestyle, genotyping, and nuclear magnetic resonance (NMR) metabolomics data. A healthy lifestyle was assessed based on 5 factors: healthy diet, regular exercise, not smoking, moderate alcohol consumption, and normal body mass index. The metabolic signature was developed by summing the selected metabolites’ concentrations weighted by the coefficients using elastic net regression. We used the multivariate Cox model to assess the associations between metabolic signatures and RA risk, and examined the mediating role of the metabolic signature in the impact of a healthy lifestyle on RA. We performed genome-wide association analysis (GWAS) to obtain genetic variants associated with the metabolic signature and then conducted Mendelian randomization (MR) analyses to detect causality. ResultsThe metabolic signature comprised 81 metabolites, robustly correlated with a healthy lifestyle (r = 0.45, P = 4.2 × 10−15). The metabolic signature was inversely associated with RA risk (HR per standard deviation (SD) increment: 0.76; 95% CI: 0.70–0.83), and largely explained the protective effects of healthy lifestyle on RA with 64% (95% CI: 50.4–83.3) mediation proportion. 1- and 2-sample MR analyses also consistently showed the associations of genetically inferred per SD increment in metabolic signature with a reduction in RA risk (HR: 0.84; 95% CI: 0.75–0.94; and P = 0.002 and OR: 0.84; 95% CI: 0.73–0.97; and P = 0.02, respectively). ConclusionsOur findings implicate that the metabolic signature reflecting healthy lifestyle is a potential causal mediator in the development of RA, highlighting the importance of early lifestyle intervention and metabolic status tracking for precise prevention of RA.

Formation of phosphatidylethanol and ethylglucuronide after low to moderate alcohol consumption in volunteers with a previous three-week alcohol abstinence.

Phosphatidylethanol (PEth) is only formed when ethanol is present in blood. This direct alcohol marker has been widely discussed, including the minimum amount of ethanol being necessary to form as much PEth as to exceed the threshold of 20ng/mL in previously PEth negative subjects. In order to corroborate hitherto existing results, a drinking study including 18 participants after a 3-week alcohol abstinence was performed. They consumed a pre-calculated amount of ethanol to reach a blood alcohol concentration (BAC) of at least 0.6g/kg. Blood was drawn before and periodically seven times after alcohol administration on day 1. Blood and urine were also collected the next morning. Dried blood spots (DBS) were prepared immediately from collected venous blood. BAC was determined by head space gas chromatography and the concentrations of both PEth (16:0/18:1, 16:0/18:2 and five additional homologues) and ethyl glucuronide (EtG) were analysed using liquid chromatography-tandem mass spectrometry. Out of 18, 5 participants had concentrations of PEth 16:0/18:1 above the threshold of 20ng/mL, and 11 out of the 18 subjects had concentrations between 10 and 20ng/mL. In addition, four persons had PEth 16:0/18:2 concentrations above 20ng/mL the following morning. All test subjects tested positive for EtG in DBS (≥ 3ng/mL) and urine (≥100ng/mL) upon 20-21h after alcohol administration. By combining both a lower cutoff of 10ng/mL and the homologue PEth 16:0/18:2, the sensitivity to detect a single alcohol intake after a 3-week abstinence increases to 72.2%.

Commentary on Hyland et al.: Digital treatment for alcohol use disorders - challenges and opportunities.

Hyland and colleagues found no significant effects of an internet-delivered cognitive behavioral therapy intervention (iCBT) as addendum to treatment as usual in individuals with moderate alcohol use disorders. While findings can be attributed partially to methodological issues, future studies should focus upon patient preferences and include potential side effects of internet-based interventions. In the field of problematic alcohol consumption, digital interventions have shown promise in non-clinical populations [1]; however, little is known about their efficacy in clinical populations fulfilling criteria for alcohol use disorders (AUDs). Internet-delivered treatment has rapidly evolved as an option for various mental disorders. First meta-analyses show positive effects when compared to non-active controls in disorders such as depression and agoraphobia [2-4], but also for addictive disorders, especially behavioural addictions [5] and tobacco smoking [6]. Given that disorders due to alcohol and/or drugs are highly stigmatized, internet-delivered interventions might be a relevant tool for narrowing the treatment gap in the field. In their excellently conducted randomized controlled trial (RCT), Hyland and colleagues [7] found only weak evidence for an internet-delivered cognitive behavioral therapy (iCBT) intervention as addendum to treatment as usual (TAU) in individuals with AUDs compared to TAU. However, it has to be taken into account that, as comparator in this study, TAU included far more evidence-based components than would usually be expected in most treatment systems world-wide. The high rate of participants willing to take (and receiving) medication is particularly impressive: data from the United States show that only 16.3% of all speciality treatment programmes for alcohol use disorders offered any single medication for AUD treatment [8]. Furthermore, as all participants in the Hyland et al. study were self-selected, the initial motivation to change already might have produced strong effects, especially if we consider the high rates of unassisted recovery that are common in alcohol use disorders [9]. Another encouraging finding is that overall treatment initiation and completion rates are relatively high compared to digital self-help interventions in the field of affective and anxiety disorders [10], where efficacy of these interventions has already been demonstrated. There is no evidence that guided or unguided internet-delivered interventions for AUDs are associated with lower rates of treatment uptake compared to face-to-face delivery. A prior study from the research group of Hyland et al. on a therapist-guided iCBT intervention compared to therapist-delivered CBT showed no differences in uptake numbers between the two conditions, and both interventions did not differ on outcomes [11]. Another RCT on iCBT as a stand-alone intervention for individuals with AUDs [12] even showed that retention rates were better in the iCBT condition compared to therapist-delivered CBT, and that both conditions were superior compared to TAU (which included lower doses of treatment compared to the Hyland et al. study). Given that internet-delivered treatment requires a high level of patient engagement, future studies should take into account the interaction between type of treatment and patient preferences. Internet-delivered interventions might be a good option for some, but certainly not for all, patients suffering from AUDs. A systematic review on effects of matching patient preferences to treatment in the field of substance use disorders suggests that treatment effects might be improved, although findings were inconsistent [13]. Patient preferences have become increasingly important for the development of clinical interventions, and they could play an important role for improving treatment uptake and outcomes by affected individuals [14]. Finally, only recently have studies on the efficacy of treatment assessed potential side effects. A potential risk of digital interventions is that these interventions might incorrectly be viewed as sufficient by some individuals who otherwise would be willing to engage in other evidence-based treatments. The significant difference between the conditions in the Hyland et al. study regarding receipt of medication shows the need for further rigorous, well-conducted studies. For a more detailed understanding on processes of change in newly developed interventions, mixed-methods studies that include the experiences of patients are warranted. GB conceptualized and wrote the manuscript. None.

Alcohol and Cardiovascular Disease: Helpful or Hurtful.

Alcohol has been considered throughout history as both a tonic and a poison. The answer as to which likely depends on one's current health, the amount one consumes, and with what regularity. In examining the relationship of alcohol and cardiovascular health, most, but not all, epidemiological studies suggest that light to moderate alcohol consumption can reduce the incidence of coronary artery disease (CAD), ischemic stroke, and peripheral arterial disease events. Conversely, abuse of alcohol can lead to cardiomyopathy, heart failure, sudden death, and hemorrhagic strokes. In this article, we review the literature studying the effects of alcohol on coronary artery disease and stroke. A recently published study concluded there was no amount of alcohol per day that was heart healthy. Yet more than one hundred previous studies have found that people who drink in moderation have a lower risk of cardiovascular disease events when compared to those who do not drink or drink heavily. Moderate drinking is defined as one to two drinks per day; where one drink is defined as 12 ounces of beer, 5 ounces of wine or 1.5 ounces of hard liquor. In this article we reviewed the data suggesting that consuming alcohol in moderation on a regular basis-as opposed to 7 drinks on Saturday night-could have cardiovascular protective effects.

Nicotine, alcohol, and caffeine use among individuals with untreated obstructive sleep apnea.

Psychoactive substance use (i.e., nicotine, alcohol, and caffeine) has substantial effects on sleep architecture in healthy individuals, but their effects in those with obstructive sleep apnea (OSA) have not been well described. We aimed to describe the association between psychoactive substance use and sleep characteristics and daytime symptoms in individuals with untreated OSA. We performed a secondary, cross-sectional analysis of The Apnea Positive Pressure Long-term Efficacy Study (APPLES). Exposures included current smoking, alcohol and caffeine use in individuals with untreated OSA. Outcome domains included subjective and objective sleep characteristics, daytime symptoms, and comorbid conditions. Linear or logistic regression assessed the association between substance use and each domain (e.g., self-reported sleep duration, total polysomnographic sleep time, sleepiness, and anxiety). Of the 919 individuals with untreated OSA, 116 (12.6%) were current cigarette smokers, 585 (63.7%) were moderate or heavy alcohol users, and 769 (83.7%) were moderate or heavy caffeine users. Participants were on average 52.2±11.9years old, 65.2% were male with a median BMI of 30.6 (IQR: 27.2, 35.9, kg/m2). Current smokers exhibited lower sleep duration (0.3h), longer sleep latency (5min) compared with non-smokers (all p-values < 0.05). People with heavy or moderate alcohol use exhibited more REM sleep (2.5 and 5% of total sleep time respectively), as did those with moderate caffeine use (2%, p-values < 0.05). The combined smoker plus caffeine group exhibited shorter sleep duration (0.4h, p-value < 0.05) and higher risk for chronic pain [Odds Ratio (95%CI) = 4.83 (1.57, 14.9) compared with non-users. Psychoactive substance use is associated with sleep characteristics and clinically relevant correlates in people with untreated OSA. Further investigation into the effects that various substances have on this population may present opportunities to understand disease mechanisms more fullyand increase the effectiveness of treatment in OSA.

Both Moderate and Heavy Alcohol Use Amplify the Adverse Cardiovascular Effects of Smoking in Young Patients with Hypertension.

To evaluate the association of alcohol and smoking combined with cardiovascular and renal events and investigate whether moderate and heavy alcohol consumption have a different impact on this association. The study was conducted in 1208 young-to-middle-age stage 1 hypertensive patients. Subjects were classified into three categories of cigarette smoking and alcohol use, and the risk of adverse outcomes was assessed over a 17.4-year follow-up. In multivariable Cox models, smoking showed a different prognostic impact on alcohol drinkers and abstainers. In the former, an increase in the risk of cardiovascular and renal events was observed compared to nonsmokers (hazard ratio, 2.6, 95% CI, 1.5-4.3, p < 0.001), whereas in the latter, the risk did not achieve the level of statistical significance (p = 0.27) with a significant interaction between smoking and alcohol use (p < 0.001). Among the heavy smokers who also drank alcoholic beverages, the hazard ratio from the fully adjusted model was 4.3 (95% CI, 2.3-8.0, p < 0.0001). In the subjects with moderate alcohol consumption, the risk of smoking and alcohol combined was similar to that found in the whole population (hazard ratio, 2.7; 95% CI, 1.5-3.9, p < 0.001). Among the subjects with heavy alcohol consumption, the hazard ratio was 3.4 (95% CI, 1.3-8.6, p = 0.011). These findings indicate that the detrimental cardiovascular effects of smoking can be worsened by concomitant alcohol use. This synergistic effect occurs not only for heavy alcohol consumption but also for moderate use. Smokers should be aware of the increased risk associated with concomitant alcohol consumption.

Effect of Mobile Health Interventions on Lifestyle and Anthropometric Characteristics of Uncontrolled Hypertensive Participants: Secondary Analyses of a Randomized Controlled Trial.

Our objective was to evaluate the effect of a mobile health (mHealth) intervention on lifestyle adherence and anthropometric characteristics among individuals with uncontrolled hypertension. We performed a randomized controlled trial (ClinicalTrials.gov NCT03005470) where all participants received lifestyle counseling at baseline and were randomly allocated to receive (1) an automatic oscillometric device to measure and register blood pressure (BP) via a mobile application, (2) personalized text messages to stimulate lifestyle changes, (3) both mHealth interventions, or (4) usual clinical treatment (UCT) without technology (control). The outcomes were achieved for at least four of five lifestyle goals (weight loss, not smoking, physical activity, moderate or stopping alcohol consumption, and improving diet quality) and improved anthropometric characteristics at six months. mHealth groups were pooled for the analysis. Among 231 randomized participants (187 in the mHealth group and 45 in the control group), the mean age was 55.4 ± 9.5 years, and 51.9% were men. At six months, achieving at least four of five lifestyle goals was 2.51 times more likely (95% CI: 1.26; 5.00, p = 0.009) to be achieved among participants receiving mHealth interventions. The between-group difference reached clinically relevant, but marginally significant, reduction in body fat (-4.05 kg 95% CI: -8.14; 0.03, p = 0.052), segmental trunk fat (-1.69 kg 95% CI: -3.50; 0.12, p = 0.067), and WC (-4.36 cm 95% CI: -8.81; 0.082, p = 0.054), favoring the intervention group. In conclusion, a six-month lifestyle intervention supported by application-based BP monitoring and text messages significantly improves adherence to lifestyle goals and is likely to reduce some anthropometric characteristics in comparison with the control without technology support.