Journal Article Annotations
2018, 1st Quarter
Substance Use & Addictive Disorders
Annotations by Thomas Penders, MS, MD, FACLP; S. Alex Sidelnik, MD; and Diana Robinson, MD
- Varenicline for tobacco-dependence treatment in alcohol-dependent smokers: a randomized controlled trial
- Contribution of alcohol use disorders to the burden of dementia in France 2008-13: a nationwide retrospective cohort study
- Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study
PUBLICATION #1 — Substance Use & Addictive Disorders
Varenicline for tobacco-dependence treatment in alcohol-dependent smokers: a randomized controlled trial
Hurt RT, Ebbert JO, Croghan IT, Schroeder DR, Hurt RD, Hays JT
Abstract: Drug Alcohol Depend 2018; 184:12-17
Background: Tobacco use is prevalent among persons with alcohol abuse and dependence. Varenicline has been shown to be the most effective pharmacotherapy for smoking cessation and may decrease alcohol consumption. The purpose of this study was to evaluate the efficacy of 12 weeks of varenicline for increasing smoking abstinence rates in smokers with alcohol abuse or dependence.
Methods: Participants were eligible for enrollment if they were 18 years or older, smoked 10 or more cigarettes per day for at least 6 months, had current alcohol abuse or dependence, and were interested in quitting smoking. Participants were randomly assigned to receive 12 weeks of varenicline 1 mg twice daily or matching placebo. The primary end point was 7-day point prevalence smoking abstinence at week 12.
Results: The 7-day point prevalence smoking abstinence rate at 12 weeks was significantly higher with varenicline (n = 16) than placebo (n = 17) (43.8% vs 5.9%; P = .01). At 24 weeks, the 7-day point prevalence smoking abstinence rate was still significantly higher with varenicline than placebo (31.3% vs 0%; P = .02). At 12 weeks, mean (SD) drinks per drinking day was significantly lower with varenicline than placebo (5.7 [3.9] vs 9.0 [5.3] drinks; treatment effect estimate: −2.8 [90% CI, −6.6 to −1.0]). Adverse events were minor and comparable to varenicline clinical trials.
Conclusions: Varenicline is safe and efficacious for increasing smoking abstinence rates in smokers with alcohol abuse or dependence. Varenicline may decrease alcohol consumption in this population of smokers.
On PubMed: Drug Alcohol Depend 2018; 184:12-17
Annotation (Thomas Penders)
Type of study: Randomized controlled prospective trial
The finding: Among subjects meeting criteria for alcohol use disorders (AUD) who had co-occurring tobacco use disorders (TUD) use of varenicline was associated with both increased abstinence rates for smoking and decreased measures of drinking behaviour in actively drinking individuals with alcohol use disorders when compared to placebo.
Strength and weaknesses: This study adds to evidence for use of varenicline to treat tobacco use disorder is individuals with tobacco use and alcohol use disorder. The treatment effect was of moderate size. Objective measures of smoking cessation were used to verify the tobacco outcomes.
Primary outcomes reached statistical significant though the study was small 33 patients randomized to the treatment (16) and placebo groups (17). Fewer than half of subjects identified as candidates agreed to enter the study limiting generalizability to the entire papulation group of those with AUD and TUD)
Relevance: Rates of smoking are elevated among patients with alcohol use disorders. Smokers with alcohol use disorders are less likely to quit smoking. Among smokers with alcohol use disorders who become abstinent of alcohol, ongoing smoking increases risk of relapse to alcohol use. Both tobacco use and alcohol use are risk factors for a variety of serious medical conditions. Consultation psychiatrists often confront patient in both inpatient and outpatient settings to assist with evaluation and intervention in these two addictive disorders.
PUBLICATION #2 — Substance Use & Addictive Disorders
Contribution of alcohol use disorders to the burden of dementia in France 2008-13: a nationwide retrospective cohort study
Schwarzinger M, Pollock BG, Hasan OSM, Dufouil C, Rehm J; QalyDays Study Group
Abstract: Lancet Public Health 2018; 3(3):e124-e132
Background: Dementia is a prevalent condition, affecting 5-7% of people aged 60 years and older, and a leading cause of disability in people aged 60 years and older globally. We aimed to examine the association between alcohol use disorders and dementia risk, with an emphasis on early-onset dementia (<65 years).
Methods: We analysed a nationwide retrospective cohort of all adult (≥20 years) patients admitted to hospital in metropolitan France between 2008 and 2013. The primary exposure was alcohol use disorders and the main outcome was dementia, both defined by International Classification of Diseases, tenth revision discharge diagnosis codes. Characteristics of early-onset dementia were studied among prevalent cases in 2008-13. Associations of alcohol use disorders and other risk factors with dementia onset were analysed in multivariate Cox models among patients admitted to hospital in 2011-13 with no record of dementia in 2008-10.
Findings: Of 31 624 156 adults discharged from French hospitals between 2008 and 2013, 1 109 343 were diagnosed with dementia and were included in the analyses. Of the 57 353 (5·2%) cases of early-onset dementia, most were either alcohol-related by definition (22 338 [38·9%]) or had an additional diagnosis of alcohol use disorders (10 115 [17·6%]). Alcohol use disorders were the strongest modifiable risk factor for dementia onset, with an adjusted hazard ratio of 3·34 (95% CI 3·28-3·41) for women and 3·36 (3·31-3·41) for men. Alcohol use disorders remained associated with dementia onset for both sexes (adjusted hazard ratios >1·7) in sensitivity analyses on dementia case definition (including Alzheimer’s disease) or older study populations. Also, alcohol use disorders were significantly associated with all other risk factors for dementia onset (all p<0·0001).
Interpretation: Alcohol use disorders were a major risk factor for onset of all types of dementia, and especially early-onset dementia. Thus, screening for heavy drinking should be part of regular medical care, with intervention or treatment being offered when necessary. Additionally, other alcohol policies should be considered to reduce heavy drinking in the general population.
On PubMed: Lancet Public Health 2018; 3(3):e124-e132
Annotation (Alex Sidelnik)
Type of study: Cohort study
The finding: Alcohol use disorders are as a major risk factor for all types of dementia with a significant association in early-onset dementia. Additionally, alcohol use disorders are observed to be the strongest modifiable risk factor for onset of dementia.
Strength and weaknesses: This study is a large retrospective cohort study of patients admitted to French Hospitals from 2008 to 2013 with a primary exposure of alcohol use disorder and main outcome dementia. Association of alcohol use and dementia along with other risk factors for dementia were analysed using a multivariate Cox models. The strengths of the study include a large sample size, significant observed effect (hazard ratio >3.3 for alcohol and all dementia), and robust sensitivity analyses. Limitations of the study include potential for upcoding bias in hospital coding, limitations in properly identifying alcohol use disorders and dementia in hospital discharge coding, and overpowering for statistical differences.
Relevance: The findings from the study suggest that alcohol use disorders may contribute to a substantial burden of risk in the development of dementia. Heavy drinking should be considered a major modifiable risk factor in development of dementia.
PUBLICATION #3 — Substance Use & Addictive Disorders
Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study
Brat GA, Agniel D, Beam A, et al
Abstract: BMJ 2018; 360:j5790
Objective: To quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population.
Design: Retrospective cohort study.
Setting: Surgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016.
Participants: 1 015 116 opioid naive patients undergoing surgery.
Main Outcome Measures: Use of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose.
Results: 568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively.
Conclusions: Each refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact.
On PubMed: BMJ 2018; 360:j5790
Annotation (Diana Robinson)
Type of study: Retrospective cohort study
The finding: This retrospective cohort study queried a large American insurance database (Aetna) to examine the association between opioid prescription refills after surgery and misuse in an opioid naïve population. Interestingly, whereas other studies that focused on chronic opioid users saw high rates of misuse with doses >100 MME/day, this study found a stronger association with misuse in opioid naïve patients receiving longer durations of prescriptions/more refills. The authors found that misuse increased an adjusted 44% for every refill fulfilled and 20% increase every week of prescription. The rate of opioid misuse (0.6% of patients or 183 per 100,000 person years) was consistent with other studies. The authors suggest future research in population based and clinical studies to examine if treating post-operative pain in opioid naïve patients with moderate-high opioid dosages for shorter durations as opposed to lower opioid dosages for longer durations may reduce the risk of misuse
Strength and weaknesses: Strengths include the large sample size (568,613 patients received postoperative opioids) over an 8 year period. The study design included clearly described sensitivity analysis to reduce the risk of unobserved confounding variables. They also included a clear description of determining the morphine milligram equivalent (MME) dosage for each opioid prescription.
Weaknesses included limited generalizability due to the inclusion criteria of commercially insured adults in the United States, so they did not include large populations with Medicaid, Medicare, and veterans. Also, the definition of opioid naïve was those patients that received 7 days or less of opioids in the 60 days prior to surgery which may have missed those receiving prescribed opioids outside of this window or through non-prescription sources which are a frequent source of initial opioid use. Finally, due to the nature of the study relying on the quality of the information in the database, they were unable to exclude those with undocumented pre-surgical misuse or opioid usage.
Relevance: C-L psychiatrists frequently evaluate patients with suspected opioid misuse/use disorders in the inpatient and outpatient settings. On the inpatient service, a clear hospital discharge plan for opioid tapering and discontinuation with attention to the duration and number of refills is essential to reduce opioid misuse. In the outpatient setting, when evaluating postoperative patients it is important to consider additional risk factors for developing an opioid use disorder such as the number of opioid refills and duration of opioid prescription. For both settings it is important to gain additional collateral information through the review of Prescription Monitoring Program databases when possible.