Heavy Alcohol Use Research Articles

RENAL8: Hypertonic Bicarbonate during Continuous Renal Replacement Therapy in Acute Liver Failure

Introduction: Acute liver failure (ALF) is particularly alarming when presenting with vasodilated shock and multi-organ system failure. Standard manufactured hemofiltration fluid (sodium [Na+] = 140 mEq/L) would result in hyponatremia in vivo. We present a case study of hypertonic NaHCO3 infusion to address simultaneous serum Na+ target and correction of acidemia during continuous therapy. Case Presentation: A 42-year-old female with a history of seizures, and heavy alcohol use presented from outside the hospital for evaluation of stroke-like symptoms and subsequent mechanical fall. Urgent head CT was non-contributory. She was found to be in acute liver failure with total bilirubin 4.7, AST: 15,525 ALT: 5,727, ammonia 267 umol/L [reference range: 18-72], acetaminophen level 29 mcg/mL [reference range 10-30], Na+ 128 mEq/L, lactate >20 mmol/L, PT INR 8.1, PH 7.0 on blood gas and a negative ethanol level/salicylate/urine drug screen. After emergent intubation for encephalopathy and multiorgan system failure, she required multiple vasopressors (epinephrine, vasopressin, and norepinephrine), and received N-acetylcysteine protocol, with intravenous bicarbonate infusion and broad-spectrum antibiotic. High dose continuous veno-venous hemodiafiltration (CVVHDF) was initiated via Baxter PrisMax platform and global effluent dosing of 58mL/kg/hr with post-filter 3% NaCl at a rate of 100 mL/hr to reach goal serum sodium of 140 mEq/dL. [3% NaCl infusion rate calculation: (target infused Na – 140 mEq/L)/ (513 mEq/L – 140 mEq/L) x hemofiltration rate (mL/h)]. She also received Therapeutic Plasma Exchange for ALF for 5 daily sessions using fresh frozen plasma. She continued to have ongoing acidosis with a lactate of 11.7 mmol/L, and serum bicarbonate of 17 mEq/L. On Hospital Day 6, 3% NaCl was changed to hypertonic NaHCO3 drip [4.2% NaHCO3 solution (500 mEq/L in 1L of D5W) at a rate of 100 mL/hr, replacing 3% NaCl on a 1:1 ratio mL/mL]. After 24 hours she had improvement in metabolic acidosis with improvement in serum bicarbonate from 17 to 24 mEq/L, pH of 7.34 to 7.40; pCO2 32 to 42, HCO3 17 to 25 mmHg and serum Na 133 to 140 mEq/L. Unfortunately, on hospital day 8 developed worsening shock requiring vasopressors; a repeat abdominal imaging noted high-grade small bowel obstruction with ischemic bowel and pneumatosis intestinalis and was transitioned to comfort care. Discussion: While CVVHDF can address elevated ammonia in ALF, infused standard therapy fluid (Na+ = 140 mEq/L) would equilibrate serum Na+ to 133 - 135 mEq/L, in the presence of plasma proteins. Post-filter hypertonic saline infusion during CVVHDF would enable simultaneous clamping of serum Na+ to the appropriate target level. Due to heavier molecular size, 4.2% NaHCo3 results in identical Na+ delivery of 3% saline along with the added benefit of improving acidosis. Clinical studies are desirable to define optimal serum Na+ concentrations during CVVDF in various clinical settings.

Burden of high-risk phenotype of heavy alcohol consumption among obese U.S. population: results from National Health and Nutrition Examination Survey, 1999–2020

The phenotype of combined heavy alcohol consumption and obesity has the potential to pose as a considerable health burden in the U.S. No studies using nationally representative data in the U.S. have reported their secular joint prevalence trends. We estimated the prevalence and examined the joint trends of heavy alcohol use and obesity over time among adult U.S. men and women in different age groups and according to race/ethnicity. Using data from 10 cycles of the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020, we examined secular trends in the combined phenotype of heavy drinking and obesity overall and by age-group, sex, and race/ethnicity. The main outcome measures were prevalence of heavy alcohol consumption (>14 drinks/week in men and >7 drinks/week in women) and obesity (BMI ≥30). In 45,292 adults (22,684 men, mean age 49.26 years; and 22,608 women, mean age 49.86), the overall weighted prevalence of combined heavy alcohol drinking and obesity increased from 1.8% (95% CI: 1.2%, 3.1%) in 1999–2000 to 3.1% (95% CI: 2.7%, 3.7%) in 2017–2020 representing an increase of 72% over time. In the joinpoint regression, the combined phenotype of heavy alcohol consumption and obesity increased by 3.25% (95% CI: 1.67%, 4.85%) per year overall from 1999 to 2017. An increasing trend of 9.94% (95% CI: 2.37%, 18.06%) per year was observed among adults aged between 40 and 59 years from 2007 onwards. Prevalence of heavy alcohol consumption in obesity increased at a faster rate among women (APC, 3.96%; 95% CI: 2.14%, 5.82%) than men (APC, 2.47%; 95% CI: 0.63%, 4.35%), and increased among non-Hispanic Whites (APC, 4.12%; 95% CI: 1.50%, 6.82%) and non-Hispanic Blacks (APC, 2.78%; 95% CI: 0.47%, 5.14%), but not Hispanics. The prevalence of combined heavy alcohol consumption and obesity increased overall in the U.S., but the rate of increase differed by age, sex, and race/ethnic groups. Given their independent and potential synergistic effects on premature mortality, public health policies on alcohol consumption need to reflect the background obesity epidemic. Cancer Prevention & Research Institute of Texas (CPRIT) for the Systems Epidemiology of Cancer Training (SECT) Program (RP210037; PI: A. Thrift).

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)

Drinking motives, personality traits and life stressors-identifying pathways to harmful alcohol use in adolescence using a panel network approach.

Models of alcohol use risk suggest that drinking motives represent the most proximal risk factors on which more distal factors converge. However, little is known about how distinct risk factors influence each other and alcohol use on different temporal scales (within a given moment versus over time). We aimed to estimate the dynamic associations of distal (personality and life stressors) and proximal (drinking motives) risk factors, and their relationship to alcohol use in adolescence and early adulthood using a novel graphical vector autoregressive (GVAR) panel network approach. We estimated panel networks on data from the IMAGEN study, a longitudinal European cohort study following adolescents across three waves (aged 16, 19 and 22 years). Our sample consisted of 1829 adolescents (51% females) who reported alcohol use on at least one assessment wave. Risk factors included personality traits (NEO-FFI: neuroticism, extraversion, openness, agreeableness and conscientiousness; SURPS: impulsivity and sensation-seeking), stressful life events (LEQ: sum scores of stressful life events), and drinking motives [drinking motives questionnaire (DMQ): social, enhancement, conformity, coping anxiety and coping depression]. We assessed alcohol use [alcohol use disorders identification test (AUDIT): quantity and frequency] and alcohol-related problems (AUDIT: related problems). Within a given moment, social [partial correlation (pcor) = 0.17] and enhancement motives (pcor = 0.15) co-occurred most strongly with drinking quantity and frequency, while coping depression motives (pcor = 0.13), openness (pcor = 0.05) and impulsivity (pcor = 0.09) were related to alcohol-related problems. The temporal network showed no predictive associations between distal risk factors and drinking motives. Social motives (beta = 0.21), previous alcohol use (beta = 0.11) and openness (beta = 0.10) predicted alcohol-related problems over time (all P < 0.01). Heavy and frequent alcohol use, along with social drinking motives, appear to be key targets for preventing the development of alcohol-related problems throughout late adolescence. We found no evidence for personality traits and life stressors predisposing towards distinct drinking motives over time.

Osteoporosis: Recent Advances

Osteoporosis is characterized by low bone mass, microarchitectural disruption, and skeletal fragility, resulting in decreased bone strength and an increased risk of fracture. Decreased bone strength is related to many factors in addition to bone mineral density (BMD), including rates of bone turnover, bone geometry, and microarchitecture.Osteoporosis has no clinical manifestations until there is a fracture. Complications of fractures include pain, deformity, disability, and loss of height. A clinical diagnosis of osteoporosis may be made in the presence of a fragility fracture, particularly at the spine, hip, wrist, humerus, rib, and pelvis, without measurement of BMD.In the absence of a fragility fracture, BMD assessment by dual-energy x-ray absorptiometry (DXA) is the standard test to diagnose osteoporosis, according to the classification of the World Health Organization. A DXA T-score d”-2.5 is consistent with osteoporosis, whereas a T-score between -1 and -2.5 isosteopenia.All postmenopausal women with osteoporosis should have a history, physical examination, and basic laboratory evaluation. Initial laboratory studies should include a complete blood count (CBC), biochemistry profile, and 25- hydroxyvitamin D (25[OH]D).The need for additional laboratory evaluation depends upon the initial evaluation and Z-score. Women who have abnormalities on initial laboratory testing, suspicious findings on history and physical examination suggesting a secondary cause of osteoporosis, or Zscores d”-2 may require additional evaluation for these secondary causes.Lifestyle measures should be adopted universally to reduce bone loss in postmenopausal women. Lifestyle measures include adequate calcium and vitamin D, exercise, smoking cessation, counseling on fall prevention, and avoidance of heavy alcohol use. In general, 1200 mg of elemental calcium daily, total diet plus supplement, and 800 international units of vitamin D daily are advised. Many patients require vitamin D supplementation as it is difficult to achieve goals with diet alone. Postmenopausal women with established osteoporosis (T-score d”-2.5) or fragility fracture be treated with a pharmacologic agent. For the treatment of high-risk postmenopausal women with T-scores between -1.0 and -2.5, better to start pharmacologic therapy. Most women, for the initial treatmentoral bisphosphonates is good choice.For severe osteoporosis, some experts prefer initial treatment with an anabolic agent, whereas other experts prefer initial treatment with bisphosphonates. Teriparatide and abaloparatide are good anabolic agent. Romosozumab is an alternative. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 194

A patient with dyskeratosis congenita and portal hypertension

AbstractPortal hypertension (PH) refers to a collection of syndromes characterized by an increase in pressure within the portal venous system and/or elevated portal venous blood flow, most commonly caused by cirrhosis. This condition is frequently associated with viral hepatitis and chronic alcohol abuse, and its complications, such as ascites, hepatic encephalopathy, and esophageal varices, have a considerable impact on mortality. Dyskeratosis congenita (DC) is a rare genetic disorder that affects multiple systems, most notably manifesting as dystrophy of the fingernails and toenails, skin pigmentation, and mucosal leukoplakia. While cirrhotic PH is an uncommon complication of DC, we present a case of a young patient who presented with PH and had no history of hepatitis or heavy alcohol use. The patient underwent splenectomy and devascularization to treat hypersplenism and esophagogastric varices caused by PH but developed portal vein thrombosis following the surgery. Given the patient's cutaneous manifestations and cirrhosis that could not be attributed to common causes, we continued to search for the underlying cause of PH until the diagnosis of DC was finally made. The patient was subsequently treated with carvedilol to prevent variceal rebleeding and showed no significant complications or bleeding during follow‐up.

Resting state connectivity in people living with HIV before and after stopping heavy drinking.

Heavy alcohol use in people living with HIV (PLWH) has widespread negative effects on neural functioning. It remains unclear whether experimentally-induced reduction in alcohol use could reverse these effects. We sought to determine the effects of 30-days drinking cessation/reduction on resting state functional connectivity in people with and without HIV. Thirty-five participants (48.6% PLWH) demonstrating heavy alcohol use attempted to stop drinking for 30 days via contingency management (CM). MRI was acquired at baseline and after thirty days, and functional connectivity across five resting-state fMRI (rsfMRI) networks was calculated with the Conn toolbox for Matlab and examined in relation to transdermal alcohol concentration (TAC) recorded by the ankle-worn secure continuous remote alcohol monitor (SCRAM) and self-reported alcohol use (timeline follow-back; TLFB). Associations between alcohol use and reduction, HIV status, functional connectivity, and change in functional connectivity across five major rsfMRI networks were determined relative to the pre- and post-CM timepoints. Baseline resting-state functional connectivity was not significantly associated with average TAC-AUC during the pre-CM period, though higher self-reported alcohol use over the preceding 30 days was significantly associated with higher baseline connectivity within the Dorsal Attention Network (DAN; p-FDR < 0.05). Baseline connectivity within the Salience network was significantly negatively related to objective drinking reduction after intervention (DAN; p-FDR < 0.05), whereas baseline connectivity within the Limbic network was positively associated with self-reported drinking reduction (p-FDR < 0.05). Change in between-networks functional connectivity after intervention was significantly positively associated with biosensor-confirmed drinking reduction such that higher reduction was associated with stronger connectivity between the limbic and fronto-parietal control networks (p-FDR < 0.05). PLWH with lower DAN connectivity at baseline demonstrated poorer alcohol reduction than those with higher DAN connectivity at baseline. Lower resting-state functional connectivity of the Salience network significantly predicted stronger drinking reduction across all participants, suggesting a potential biomarker for reduced susceptibility to the environmental and social cues that often make alcohol use reduction attempts unsuccessful. Increased between-networks connectivity was observed in participants with higher alcohol reduction after CM, suggesting a positive benefit to brain connectivity associated with reduced drinking. PLWH with lower baseline DAN connectivity may not benefit as greatly from CM for alcohol reduction.

Life course differences in heavy episodic drinking behaviors across age, gender, and sexual identity in the United States

•This study examines heavy episodic drinking across age, gender, and sexual identity.•Gay/lesbian and bisexual females experience persistent disparities across age.•Gay and bisexual males experience age specific disparities.•Sexual minority adults in the US report complex patterns of heavy alcohol use.•Heavy drinking disparities do not mirror patterns of alcohol use disorders.

Prevalence of modifiable bleeding risk factors in patient with nonvalvular atrial fibrillation and heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Despite the clear benefit from direct oral anticoagulants (DOAC) in patients with nonvalvular atrial fibrillation (NVAF) and heart failure (HF), major bleeding events may be devastating when they do occur. Identification and correction of potentially modifiable conditions associated with bleeding risk can minimize hemorrhagic complications of DOAC therapy. Data on prevalence of modifiable bleeding risk factors in a cohort of patients treated with DOACs with coexisted NVAF and HF are lacking. The purpose of the study was to assess the rate of high-bleeding risk according to HAS-BLED and prevalence of modifiable HAS-BLED score components in patients with NVAF and HF receiving oral anticoagulants. Methods The study involved consecutive patients with NVAF and HF taking DOACs (rivaroxaban, apixaban, dabigatran) hospitalized with HF decompensation between January 2020 and May 2022. Bleeding risk was stratified by HAS-BLED score. Modifiable and nonmodifiable bleeding risk factors were identified. Numerical data were expressed as median (interquartile range). P&amp;lt;0.05 was considered significant. Results A total of 388 patients (age 73.5 years [66-82], 59.3% males, non-paroxysmal NVAF – 58.8%, CHA2DS2-VASc score 4 [4-5]) were included. Most patients had NYHA class III-IV symptoms (67.9%). Prior myocardial infarction was identified in 37.6%. Median ejection fraction (EF) was 44.5% (34-52). The median HAS-BLED score was 2 (1-3). 26.3% of patients had HAS-BLED score ≥3. The subgroup of patients with NVAF and HF with EF ≤40% had higher bleeding risk compared to those with EF &amp;gt;40% (HAS-BLED ≥3 in 32.1% vs 20.4%, P&amp;lt;0.05). Modifiable and nonmodifiable HAS-BLED score components were identified from study population. Anemia (50.5%), heavy alcohol use or concomitant treatment with antiplatelets, nonsteroidal anti-inflammatory drugs, or paracetamol (21.6%), abnormal renal/liver function (19.6%), uncontrolled hypertension (9.8%) were identified as modifiable bleeding risk factors. Increasing age (78.9%), prior stoke (13.4%) were identified as nonmodifiable bleeding risk factors without significant differences between subgroups of HF. Overall, 10% of patients had nonmodifiable bleeding risk factors only, and 88% had modifiable bleeding risk factors (with or without nonmodifiable risk factors). Abnormal renal/liver function and concomitant treatment/alcohol were more frequent in the subgroup of patients with EF ≤ 40% compared to those with EF &amp;gt; 40% (24.7% vs 10.6%, 28.4% vs 16.8%, respectively; P&amp;lt;0.05). Conclusion Every fourth patient with NVAF and HF has high bleeding risk that can be minimized by modifying risk factors in up to 90% of patients. Anemia was the most frequent modifiable bleeding risk factor.

Re-incarceration and associated social, structural and behavioural factors among people who use drugs in an urban Canadian setting.

People who use drugs (PWUD) are disproportionately incarcerated, however little is known about specific substance use, social and structural factors associated with re-incarceration among PWUD. We aimed to identify the socio-structural and substance use factors associated with re-incarceration among structurally-marginalized PWUD. We used longitudinal data from two prospective cohorts of PWUD in Vancouver, Canada. We included adults reporting at least one incarceration event in the last six months and who completed at least one additional follow-up study visit. We performed multivariable extended Cox regression to explore factors associated with re-incarceration. Among 468 eligible participants, the median age was 40 years (Q1-Q3=34-46 years), 346 (73.9%) were men, 177 (37.8%) identified as Indigenous, and 227 (48.5%) experienced at least one re-incarceration event. Incidence rate of re-incarceration was 157 incarceration events per 1000 person years. In multivariable analyses, homelessness (adjusted hazard ratio [AHR]=2.17; 95% confidence interval [95% CI]: 1.79-2.61), community judicial supervision (AHR=3.89; 95% CI: 3.21-4.71) and re-incarceration during the study period (once: AHR=1.95, 95% CI: 1.55-2.44; two or more events: AHR=1.53, 95% CI: 1.23-1.90) were positively associated with re-incarceration. Among substance use variables that included illicit drugs, only heavy alcohol use remained significantly associated with re-incarceration across analyses after adjustment (AHR=1.32; 95% CI: 1.06-1.65). Engagement in addiction treatment (AHR=0.63; 95% CI: 0.53-0.75), mental illness (AHR=0.70; 95% CI: 0.59-0.84) and age (AHR=0.96; 95% CI: 0.95-0.97) were negatively associated with re-incarceration. Access to housing and substance use services, including treatment for alcohol use disorder, following incarceration may reduce re-incarceration among PWUD. The high rates of re-incarceration of PWUD in our sample underscores how structural factors-such as homelessness and criminalization of substance use-drive re-incarceration among PWUD.

Associations of state and trait empathy with daily alcohol use.

A growing literature documents associations between lower trait empathy and heavier alcohol use and more alcohol problems in adolescent and young adult samples. Prior work linking empathy and alcohol use/problems in these populations has thus far focused on trait rather than state empathy, and researchers often do not differentiate between cognitive and affective empathy. Further, no prior studies have examined associations between daily fluctuations in state empathy and alcohol use. The goal of the current study is to advance knowledge about the associations between state (vs. trait) and cognitive (vs. affective) empathy and alcohol use. Adult alcohol drinkers (n=492; Mage=22.89, SD=5.53; 53.70% female) participated in ecological momentary assessment studies for 7 to 10 days (day n=4683). Multilevel hurdle models were used to investigate associations between day-level state empathy and daily alcohol use at the within-person level, and associations between individual differences in trait empathy and alcohol use across days at the between-person level. Higher day-level state affective empathy was not associated with the likelihood of drinking on a particular day, but it was significantly associated with a greater number of drinks consumed on alcohol-consuming days, with the latter associations remaining after controlling for day-level positive affect (PA) and negative affect (NA). No associations were found for day-level state cognitive empathy, or trait affective or cognitive empathy. On drinking days, when individuals reported more affective empathy than is typical for them, they were more likely to consume a greater number of alcoholic drinks, results that remained when controlling for levels of PA and NA. Daily shifts in affective empathy may be important to consider in efforts to understand alcohol use.

Polygenic risk score for problematic alcohol use predicts heavy drinking and alcohol use disorder symptoms in young adulthood after accounting for adolescent alcohol use and parental alcohol use disorder

BackgroundGenome-wide association studies (GWAS) have identified hundreds of loci associated with alcohol-related traits. GWAS permit the calculation of polygenic risk scores (PRS), which aggregate genetic risk for a trait across the genome. To evaluate the usefulness of a PRS for problematic alcohol use (PAU)—which subsumes alcohol use disorder (AUD) and alcohol-related problems—we tested whether this PRS predicted heavy drinking and alcohol problems after accounting for family history of AUD and prior drinking history, robust and established predictors of PAU. MethodsParticipants (N=665) were European-ancestry members of the Michigan Longitudinal Study, a prospective family study with high rates (65%) of parental AUD. Participants reported their frequency of alcohol use, maximum drinks consumed in a 24-hour period, and alcohol use problems at four assessments in adolescence and young adulthood (11–29 years old). We used polygenic prediction via Bayesian regression and continuous shrinkage priors to create a PAU PRS using summary statistics from a meta-GWAS of PAU. ResultsAfter adjusting for demographic covariates, parental AUD, and drinking and alcohol use problems in early and mid/late adolescence, the PAU PRS was significantly associated with alcohol-related problems in young adulthood (β=.08, p=.047; R2=0.6%). The PAU PRS also had a significant indirect effect on alcohol use problems in young adulthood through earlier drinking and alcohol use problems (β=.02, p=.03). ConclusionsThe PAU PRS predicted alcohol problems in young adulthood after accounting for parental history of AUD and alcohol use in adolescence, providing evidence that genetic data uniquely inform the etiology of alcohol problems.

D47. Predictive Factors for Outcomes in Alloplastic Cranioplasty: A Review of 101 Cases

PURPOSE: To describe factors related to functional and aesthetic outcomes in alloplastic cranioplasty. METHODS: The authors conducted a large-scale retrospective review of patients who underwent alloplastic cranioplasty between 2014 and 2021 at a single institution. Information was collected regarding demographics, wound healing comorbidities, indications for surgery, and outcomes. A multivariable regression analysis was used to determine variables associated with operative complications, implant explantation, and contour defects. RESULTS: One hundred and one patients underwent alloplastic cranioplasty. Fifty-seven percent of patients had at least one wound healing comorbidity. The most frequent indications for surgery were trauma (44%), cerebrovascular accident (18%), and cancer (18%). The operative complication rate was 24%. Thirty-six percent of patients had a postoperative contour deformity, and 16% underwent additional surgeries related to cosmesis. At a median follow-up of 1.5 years, 99% of patients maintained either a primary (84%) or secondarily placed (15%) implant. On multivariable analysis, level four ASA classification (OR 5.9, 95% CI [1.03, 33.1], p = 0.05) and heavy alcohol use (OR 6.2, 95% CI [1.5, 25.5], p = 0.01) were significantly associated with complications. Cerebrovascular accident was associated with contour defects (OR 6.1, 95% CI [1.2, 30.7], p = 0.03). The only factor associated with explantation was heavy alcohol use (p = 0.05). CONCLUSION: This study reviews predictive factors for complications, implant explantation, and poor contour outcomes after alloplastic cranioplasty in a large cohort. Results indicate that alloplastic cranioplasty can have a high success rate with reasonable aesthetic outcomes.

Alcohol, the gut microbiome, and liver disease.

The microorganisms inhabiting our gastrointestinal tract are critical for human health. Chronic heavy alcohol use can modulate the composition and function of the gut microbiota, thereby exacerbating end-organ damage via the gut-brain axis and the gut-liver axis. In this review, we summarize the bacterial, fungal, and viral gut microbial compositional changes associated with alcohol use and alcohol-associated liver disease and discuss the mechanisms of action by which gut dysbiosis reinforces alcohol use behavior and liver inflammation and injury. We also highlight important pre-clinical and clinical trials that target gut microbial-specific mechanisms for the treatment of alcohol use disorder and alcohol-associated liver disease.

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.

Population-attributable risk of modifiable lifestyle factors to hepatocellular carcinoma: The multi-ethnic cohort.

Lifestyle factors are well associated with risk of hepatocellular carcinoma (HCC). However, the impact of reducing adverse lifestyle behaviours on population-level burden of HCC is uncertain. We conducted prospective analysis of the population-based multi-ethnic cohort (MEC) with linkage to cancer registries. The association of lifestyle factors (smoking, alcohol, diet quality assessed by alternate Mediterranean diet score, coffee drinking, physical activity and body mass index) with HCC incidence was examined using Cox regression. Population-attributable risk (PAR, %) for the overall, lean and overweight/obese populations was determined. A total of 753 incident cases of HCC were identified in 181,346 participants over median follow-up of 23.1 years. Lifestyle factors associated with elevated HCC risk included former/current smoking, heavy alcohol use, poor diet quality, lower coffee intake and obesity, but not physical activity. The lifestyle factor with highest PAR was lower coffee intake (21.3%; 95% CI: 8.9%-33.0%), followed by current smoking (15.1%; 11.1%-19.0%), obesity (14.5%; 9.2%-19.8%), heavy alcohol use (7.1%; 3.5%-10.6%) and lower diet quality (4.1%; 0.1%-8.1%). The combined PAR of all high-risk lifestyle factors was 51.9% (95% CI: 30.1%-68.6%). A higher combined PAR was observed among lean (65.2%, 26.8%-85.7%) compared to overweight/obese (37.4%, 11.7%-58.3%) participants. Adjusting for viral hepatitis status in a linked MEC-Medicare dataset resulted in similar PAR results. Modifying lifestyle factors, particularly coffee intake, may have a substantial impact on HCC burden in diverse populations, with greater impact among lean adults. Diet and lifestyle counselling should be incorporated into HCC prevention strategies.

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.

Polygenic influences on the behavioral effects of alcohol withdrawal in a mixed-ancestry population from the collaborative study on the genetics of alcoholism (COGA)

Alcohol withdrawal (AW) is a feature of alcohol use disorder that may occur in up to half of individuals with chronic, heavy alcohol consumption whenever alcohol use is abruptly stopped or significantly reduced. To date, few genes have been robustly associated with AW; this may be partly due to most studies defining AW as a binary construct despite the multiple symptoms and their range in severity from mild to severe. The current study examined the effects of genome-wide loci on a factor score for AW in high risk and community family samples in the Collaborative Study for the Genetics of Alcoholism (COGA). In addition, we tested whether differentially expressed genes associated with alcohol withdrawal in model organisms are enriched in human genome-wide association study (GWAS) effects. Analyses employed roughly equal numbers of males and females (mean age 35, standard deviation = 15; total N = 8009) and included individuals from multiple ancestral backgrounds. Genomic data were imputed to the HRC reference panel and underwent strict quality control procedures using Plink2. Analyses controlled for age, sex, and population stratification effects using ancestral principal components. We found support that AW is a polygenic disease (SNP-heritability = 0.08 [95 % CI = 0.01, 0.15; pedigree-based heritability = 0.12 [0.08,0.16]. We identified five single nucleotide variants that met genomewide significance, some of which have previously been associated with alcohol phenotypes. Gene-level analyses suggest a role for COL19A1 in AW; H-MAGMA analyses implicated 12 genes associated with AW. Cross-species enrichment analyses indicated that variation within genes identified in model organism studies explained <1 % of the phenotypic variability in human AW. Notably, the surrounding regulatory regions of model organism genes explained more variance than expected by chance, indicating that these regulatory regions and gene sets may be important for human AW. Lastly, when comparing the overlap in genes identified from the human GWAS and H-MAGMA analyses with the genes identified from the animal studies, there was modest overlap, indicating some convergence between the methods and organisms.

Covid-19 Stress, Smoking and Heavy Drinking Behaviors in University Students in Singapore

Aims: This study investigates multi-dimensional Covid-19 related stressors and the extent to which these stressors are related to young adult’s smoking and heavy alcohol use among university students in Singapore during the Covid-19 pandemic. Design/Setting/Participants: A total of 2,339 undergraduate students (862 male, 1309 female) in Singapore participated in an online survey. Measures: The Covid-19 Stressors Questionnaire (C19SQ) is a developmentally influenced, Covid-19 related stress scale, used alongside mental health measures (GAD &amp; PHQ) and substance use. Structural equation modeling was used to model the association between four types of Covid-19 related stressors and past month smoking and heavy drinking while accounting for student mental health, family socio-economic status, gender and race/ethnicity. Findings: Stress related to Covid-19 social restrictions was associated with increased likelihood of heavy drinking and smoking behavior, whereas stress related to health concerns was associated with decreased likelihood of smoking and heavy drinking. Covid-19 related stressors related to resource constraints and future uncertainties were not associated with young adult substance use. Conclusions: Our finding that Covid-19 stressors related to Social Restrictions and Health Concerns were particularly salient for university student’s substance use, but in opposite directions, extend prior work by demonstrating that young adult substance use behavior is differentially impacted by specific types of Covid-19 stress and point to areas where public health and clinical intervention efforts can focus in the wake of the Covid-19 pandemic for this vulnerable population.

Contributors to Early Mortality in African Americans, the Jackson Heart Study.

In recent years, premature "deaths of despair" (ie, due to alcohol, drug use, and suicide) among middle-aged White Americans have received increased attention in the popular press, yet there has been less discussion on what explains premature deaths among young African Americans. In this study, we examined factors related to deaths of despair (alcohol use, drug use, smoking) and contextual factors (perceived discrimination, socioeconomic status, neighborhood conditions) as predictors of premature deaths before the age of 65 years among African Americans. The Jackson Heart Study (JHS) is a longitudinal cohort study of African Americans in the Jackson, Mississippi, metropolitan statistical area. We included participants younger than 65 years at baseline (n=4000). Participant enrollment began in 2000 and data for these analyses were collected through 2019. To examine predictors of mortality, we calculated multivariable adjusted hazard ratios (HRs; 95% CI), using Cox proportional hazard models adjusted for age, sex, ideal cardiovascular health metrics, drug use, alcohol intake, functional status, cancer, chronic kidney disease, asthma, waist circumference, depression, income, education, health insurance status, perceived neighborhood safety, and exposure to lifetime discrimination. There were 230 deaths in our cohort, which spanned from 2001-2019. After adjusting for all covariates, males (HR, 1.50; 95% CI, 1.11-2.03), participants who used drugs (HR, 1.53; 95% CI, 1.13-2.08), had a heavy alcohol drinking episode (HR, 1.71; 95% CI, 1.22-2.41), reported 0-1 ideal cardiovascular health metrics (HR, 1.78; 95% CI, 1.06-3.02), had cancer (HR, 2.38; 95% CI, 1.41-4.01), had poor functional status (HR, 1.68; 95% CI, 1.19-2.37), or with annual family income less than $25,000 (HR, 1.63; 95% CI, 1.02-2.62) were more likely to die before 65 years of age. In our large cohort of African American men and women, clinical predictors of premature death included poor cardiovascular health and cancer, and social predictors included low income, drug use, heavy alcohol use, and being a current smoker. Clinical and social interventions are warranted to prevent premature mortality in African Americans.