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Update on Alcohol, Other Drugs, and Health November–December 2013 www.aodhealth.org 1 Studies on Interventions & Assessments www.aodhealth.org 2 Chronic Care Management in Primary Care for Patients with Substance Dependence Yields Little Benefit Saitz R, et al. JAMA. 2013;310(11):1156–1167. Summary by Darius A. Rastegar, MD www.aodhealth.org 3 Objectives/Methods Providing multidisciplinary patient-centered proactive care in the form of chronic care management (CCM) may be one way to reduce the adverse health consequences and high rates of health care utilization that are associated with substance use. www.aodhealth.org 4 Objectives/Methods (cont’d) This randomized controlled trial included 563 participants with alcohol, stimulant, or opioid dependence. Subjects assigned to CCM received care from a team that included a nurse, a social worker, internists, and a psychiatrist with addiction expertise; the CCM visits were separate from primary care visits. The control group received primary care at the same center, without additional services. www.aodhealth.org 5 Results There was no significant difference in the primary outcome measure of 30-day abstinence from stimulants, opioids, or heavy alcohol use at 12-month follow-up between the CCM (44%) and control (42%) groups. There was likewise no significant difference in Addiction Severity Index scores, quality of life measures, and hospital or emergency department utilization. Those assigned to CCM were significantly more likely to receive addiction pharmacotherapy (21% versus 15% in the control arm). www.aodhealth.org 6 Comments It is disappointing that this model of care failed to show a significant benefit. This study does not suggest that primary care practitioners cannot help patients with substance dependence; the control group received primary care services and likely benefited from them. As the authors point out, a likely explanation for these results is that their study achieved a “small increase in use of addiction treatments that are modestly efficacious for only some subsets of people with addictions.” More clinical trials are needed to test other approaches. www.aodhealth.org 7 Counseling Adds No Detectable Benefit to Patients Receiving Buprenorphine Treatment and Medical Management for Opioid Dependence Ling W, et al. Addiction. 2013:108(10);1788–1798. Amato L, et al. Cochrane Database Syst Rev. 2011;(10):CD004147. Summary by Peter D. Friedmann, MD, MPH www.aodhealth.org 8 Objectives The Drug Abuse Treatment Act of 2000 requires that physicians prescribing buprenorphine in the US be able to refer patients for ancillary counseling, but several studies have been unable to detect benefit from psychosocial treatments in addition to buprenorphine and physician-provided medical management. www.aodhealth.org 9 Objectives/Methods (cont’d) This study randomized 202 outpatients with opioid dependence receiving buprenorphine and medical management to 16 weeks of treatment within one of four groups: Cognitive behavioral therapy (CBT) Contingency management (CM) Both CBT and CM; or Buprenorphine treatment and medical management alone (control) www.aodhealth.org 10 Results There was no difference across groups during the 16week active treatment phase or over the 52-week followup in the percentage of participants with opioid-negative urine test results; 71% of the buprenorphine and medical management control group had three or more consecutive opioid-negative urine test results compared with 66% of the CBT group, 74% of the CM group, and 76% of those who received both CBT and CM. There were no differences between the groups’ treatment retention rates, withdrawal symptoms, craving, other drug use, or adverse events. www.aodhealth.org 11 Comments This study confirms a recent meta-analysis (Amato et al., 2011), which found that psychosocial counseling delivers no detected benefit when combined with opioid agonist treatment and physician-provided medical management for people with opioid dependence. The possibility remains that additional counseling may prove to be beneficial to select subgroups or in maintaining long-term recovery after the first year; however, a provider’s inability to arrange for additional behavioral counseling should not be a barrier to the provision of effective opioid agonist treatment. www.aodhealth.org 12 Varenicline a Potential Treatment Option for Alcohol Use Disorders in Smokers and Nonsmokers Litten RZ, et al. J Addict Med. 2013;7(4):277–286. Summary by Jeanette M. Tetrault, MD www.aodhealth.org 13 Objectives/Methods Varenicline is a partial α4β2 nicotinic acetylcholine agonist approved for smoking cessation. Preclinical studies have suggested reduced alcohol intake in the setting of varenicline; a human laboratory study suggested reduced drinking, alcohol craving, and reinforcing effects of alcohol intake in individuals with heavy smoking and drinking behaviors; and a small preliminary study of smokers with heavy drinking given varenicline for 3 weeks suggested a greater reduction in alcohol craving and fewer heavy drinking days over placebo. www.aodhealth.org 14 Objectives/Methods (cont’d) This is the first reported multi-site clinical trial of varenicline in smokers and nonsmokers with alcohol dependence. Two hundred patients with alcohol dependence were randomized to receive double-blind varenicline or placebo plus a computerized behavioral intervention for 13 weeks. www.aodhealth.org 15 Results Patients in the varenicline group reported a lower weekly percentage of heavy drinking days over those in the placebo group (38% versus 48%, respectively). Smoking status did not alter the primary outcome. The varenicline group had fewer drinks per drinking day (6 versus 7) and a lower percentage of very heavy drinking days over placebo (18% versus 26%). www.aodhealth.org 16 Results (cont’d) Abstinence did not differ between the two groups. Adverse events were those expected and varenicline was well tolerated between the two groups. www.aodhealth.org 17 Comments In this study, varenicline reduced alcohol consumption among smokers and nonsmokers compared with placebo. Larger, longer-duration studies are needed to replicate the data presented in this proof-of-concept trial. www.aodhealth.org 18 Screening and Assessment for Unhealthy Alcohol Use Can Determine Hospital Inpatients’ Risk for Alcohol Withdrawal Pecoraro A, et al. J Gen Intern Med. 2013 [Epub ahead of print]. PMID: 23959745. Summary by Peter D. Friedmann, MD, MPH www.aodhealth.org 19 Objectives/Methods Screening is intended to identify unhealthy alcohol use for interventions, but this study examined whether alcohol screening tools can also stratify hospitalized patients for their risk of alcohol withdrawal syndrome (AWS). In a case-control study of all adult medical or surgical inpatients from a single hospital, investigators identified 223 patients who developed AWS after admission and 466 randomly-selected controls without AWS. All patients had been screened at admission with the Alcohol Use Disorders Identification Test-(Piccinelli) Consumption (AUDIT-PC), which includes five of the ten items from the full AUDIT. www.aodhealth.org 20 Results An AUDIT-PC score of ≥4 proved to be the best cut point between true and false positives for AWS; 9% of cases would be missed. For every 17 patients whose screening resulted in a false positive, one was correctly identified as having AWS. Among patients who scored ≥4 on the AUDIT-PC, the post-test probability of AWS was 5.8%. www.aodhealth.org 21 Comments This study suggests that a screening questionnaire, the AUDIT-PC, might risk-stratify hospitalized patients for AWS. However, prospective validation with an independent sample is necessary before this tool can be recommended for this purpose. An implication is that even a rudimentary assessment of the alcohol history among inpatients who screen positive for unhealthy drinking can have important clinical and prognostic implications. www.aodhealth.org 22 Patients Who Initially Screen Negative for Unhealthy Alcohol Use May Need to be Screened Again Lapham GT, et al. Alcohol Clin Exp Res. 2013 [Epub ahead of print]. doi: 10.1111/acer.12260. Summary by Kevin L. Kraemer, MD, MSc www.aodhealth.org 23 Objectives/Methods To determine whether some patients who screen negative for unhealthy alcohol use have a risk of converting to a positive screen in the future, researchers retrospectively examined Alcohol Use Disorder Identification Test– Consumption (AUDIT-C) data collected from 462,126 outpatients screened on 2 occasions (one year apart). The main outcome was conversion from a negative AUDIT-C score (0–2 in women and 0– 3 in men) to a positive score (≥3 in women and ≥4 in men). www.aodhealth.org 24 Results Initially, 75% of the patients screened had a negative AUDIT-C score; 18% had a positive score; and 8% had addiction treatment or an alcohol use disorder diagnosis in the year before initial screening or between the initial and subsequent screens. Overall, 5% of women and 6% of men with initial negative screens converted to a positive screen the following year. In adjusted analyses, younger men with initial scores of 3 were most likely to convert to positive screens. In contrast, older patients, women, and those with initial scores of 0 were least likely to convert. In no patient subgroup was the probability of converting to a positive screen below 2% or greater than 39%. www.aodhealth.org 25 Comments This study suggests that the probability of converting from a negative to a positive screen for unhealthy alcohol use is high enough to justify repeating the screen for all patients after one year. It does not address whether patients with more than 2 consecutive negative screens should be eligible for cessation of screening. www.aodhealth.org 26 Emergency Department Brief Intervention May Decrease Some Risky Driving and Drinking Behaviors in Young Adults Sommers MS, et al. Alcohol Clin Exp Res. 2013;37(10):1753–1762. Summary by Kevin L. Kraemer, MD, MSc and Richard Saitz, MD, MPH www.aodhealth.org 27 Objectives/Methods The results of alcohol brief intervention trials in emergency departments (EDs) have been mixed and in trauma centers largely disappointing (i.e., no effect of intervention). www.aodhealth.org 28 Objectives/Methods (cont’d) In this study, researchers targeted a subpopulation with two risks, randomizing 476 ED patients with risky driving and drinking,* aged 18 to 44 years, to: An assessment followed by two brief interventions addressing both issues An assessment-only control; or A no-contact control (no assessment, no intervention) *Defined by the authors as: within the past month, ≥2 risky driving behaviors (partial or non-use of a seatbelt; ≥2 occasions of driving 20 mph over the speed limit; ≥2 occasions of driving through a yellow light as it turns to red), AND ≥2 risky drinking behaviors (≥11 standard drinks in a week for women and ≥14 for men; ≥4 drinks on a typical drinking day; ≥5 drinks on one occasion for women and ≥6 for men). www.aodhealth.org 29 Results 31% of participants were lost to follow-up, more in the brief intervention group than in the other groups. At 3, 6, and 9 months, participants in the brief intervention group were less likely than those in the assessment-only group to report “not always wearing a seat belt” (39–45% versus 50–55%), but no less likely to report exceeding the speed limit by 20 mph. At 3 and 6 months, participants in the brief intervention group reported fewer maximum drinks per occasion (median 6 versus 8) and reports of ≥5 drinks in a day (27–30% versus 40–43%) than did the assessment-only group. www.aodhealth.org 30 Results (cont’d) The intervention had no effect on 4 secondary drinking outcomes or 6 measures of traffic offenses and crashes, although it was associated with fewer reports of 4 other risky driving behaviors (e.g., fewer times driving through yellow light as it turns to red). The brief intervention group did not differ with either control group on any risky driving and drinking outcomes at 12 months. Outcomes for the assessment-only group were not substantially different from the no-contact control group. www.aodhealth.org 31 Comments The mixed findings on self-report outcomes and differential loss to follow-up raise concerns about the validity of the findings, particularly in the context of prior studies. Interestingly, assessments—often thought to explain the many negative studies of brief intervention—had no effects on outcomes. www.aodhealth.org 32 Comments (cont’d) Nonetheless, this study suggests that 2 brief counseling sessions for a select group of ED patients with two risky behaviors (risky driving and drinking) may modestly reduce some aspects of both in the short term. But it also suggests that better interventions are needed for more robust and longer-term success (e.g., booster interventions using electronic methods and/or in primary care settings). www.aodhealth.org 33 Studies on Health Outcomes www.aodhealth.org 34 Race and Socioeconomic Status Affect Emergency Department Opioid Prescribing for Pain Joynt M, et al. J Gen Intern Med. 2013 [Epub ahead of print]. PMID: 23797920. Summary by Richard Saitz, MD, MPH www.aodhealth.org 35 Objectives/Methods Prior research suggests that factors besides pain— such as patient race and ethnicity—affect opioid prescribing for pain, but those studies have often not adjusted for socioeconomic status (SES). In this study, investigators examined the association between race, ethnicity, and neighborhood SES on prescription of an opioid during an emergency department (ED) visit for moderate or severe pain in the National Hospital Ambulatory Care Survey. During 4 years there were over 183 million visits and opioids were prescribed during 50,264 of them. www.aodhealth.org 36 Results Compared with patients living in areas with the highest SES, patients living in areas with the lowest SES were less likely to receive opioids (39% versus 49% when neighborhood poverty was >20%; 41% versus 47% when median income was <$33,000; and 43% versus 46% when <13% held a bachelor’s degree). Black (39% versus 46% for white) and Hispanic (40% versus 45% for non-Hispanic) patients were less likely to receive opioids. All differences were significant in analyses adjusted for race, ethnicity, SES, sex, pain severity, injury, hospital type, past ED visits, and geography. www.aodhealth.org 37 Comments This study adjusted for neighborhood rather than individual SES. Nonetheless, it does provide support for the hypothesis that race, ethnicity, and SES impact opioid receipt for pain. Clinicians should be aware that this may happen, and researchers should attend to discovering why, with an eye toward eliminating any inappropriate disparities. www.aodhealth.org 38 General Population Preferences Regarding Treatment for Alcohol Use Disorders Suggest Pervasive Stigma Andréasson S, et al. Alcohol Alcohol. 2013;48(6):694–699. Summary by Nicolas Bertholet, MD, MSc www.aodhealth.org 39 Objectives/Methods To investigate treatment preferences for alcohol use disorders, researchers conducted a random, crosssectional survey of the Swedish general population aged 16–80. A total of 9005 individuals completed the survey (62% response rate). Participants were asked which type and source of treatment they would recommend to a friend or relative with unhealthy alcohol use. www.aodhealth.org 40 Objectives/Methods (cont’d) Treatment types were: Treatment via internet Alcoholics Anonymous or other support groups Psychotherapy Pharmacotherapy; and Residential treatment www.aodhealth.org 41 Objectives/Methods (cont’d) Treatment sources were: Social services Psychiatry or other addiction specialist treatment Primary health care; and Occupational health care www.aodhealth.org 42 Results Individuals with lower* alcohol use tended to recommend support groups as their preferred form of treatment, whereas individuals with higher consumption** favored psychotherapy. Treatment via the internet was the least preferred option among the respondents. More than 50% of participants reported psychiatry or other addiction specialist treatment as their preferred source of treatment. Around 10% cited primary health care as their preferred source of treatment and 20% occupational health services. * Defined by the authors as 0–28 drinks in a week for men, or 0–18 drinks in a week for women (one drink containing 12 g of alcohol). ** Defined as >28 drinks in a week for men, or >18 drinks in a week for women. www.aodhealth.org 43 Comments Treatment for alcohol use disorders remains stigmatized; this study suggests that newer forms of treatment (pharmacotherapy, internet) are less commonly recognized as options by the general population. The dissemination of information on alcohol use disorders and available treatments, especially new medications, seems to be key to disseminating effective treatments. Adapting the delivery of treatment for alcohol use disorders to the reported preferences may reduce some of the stigma. www.aodhealth.org 44 Moderate Alcohol Intake May Lower the Risk of Rheumatoid Arthritis Jin Z, et al. Ann Rheum Dis. July 29, 2013 [Epub ahead of print]. doi: 10.1136/annrheumdis-2013-203323. Summary by R. Curtis Ellison, MD www.aodhealth.org 45 Objectives/Methods Few prospective cohort studies have included an adequate number of cases to test the association of alcohol consumption with the development of rheumatoid arthritis (RA). This large meta-analysis evaluated the relationship between alcohol consumption and the diagnosis of RA in 1878 subjects, based on prospective data from 5 cohort studies and 3 nested case-control studies. www.aodhealth.org 46 Results Overall, subjects reporting low-to-moderate alcohol consumption (<15 g in a day) had a lower risk of RA (relative risk [RR], 0.86) than abstainers. Compared with no alcohol consumption, the adjusted RR was 0.93 for 3 g of alcohol in a day; 0.86 for 9 g in a day; 0.88 for 12 g in a day; 0.91 for 15 g in a day; and 1.28 for 30 g in a day, with stronger effects among women. Subgroup analysis indicated that consistent low-tomoderate alcohol consumption for a period of at least 10 years was found to have a 17% reduction in RA risk for both men and women. www.aodhealth.org 47 Comments This study concludes that moderate alcohol consumption is inversely associated with the development of RA. It suggests a “J-shaped” curve, with a lowered risk for an average intake of up to 15 g in a day in comparison with abstainers, and an increased risk with heavier drinking. Down-regulation of the immune response and a decrease in pro-inflammatory cytokines is the probable mechanism of alcohol’s protective effect on the risk of RA, though the increased risk at higher levels remains unexplained. www.aodhealth.org 48 Prenatal Cocaine Exposure Impacts Adolescent Development, but Clinical Relevance is Unclear Buckingham-Howes S, et al. Pediatrics. 2013;131(6):e1917–1936. Summary by Sarah Bagley, MD† and Judith Tsui, MD, MPH †Contributing Editorial Intern and Addiction Medicine Fellow, Clinical Addiction Research and Education (CARE) Unit, Section of General Internal Medicine, Boston University School of Medicine, Boston, MA. www.aodhealth.org 49 Objectives/Methods During the crack cocaine epidemic there was concern that prenatal cocaine exposure (PCE) would have long-term adverse effects on development. This systematic review examined the impact of PCE on adolescent outcomes. www.aodhealth.org 50 Objectives/Methods (cont’d) Twenty-seven studies representing nine cohorts were identified and four outcomes of interest were reported: Behavior Cognition/school performance Brain structure/function; and Physiologic response www.aodhealth.org 51 Results Eleven studies reported behavioral outcomes such as drug use, victimization, and attention problems. Seven of those studies had statistically significant findings consistent with adverse effects. Eight studies reported cognition/school performance. Six had statistically significant findings consistent with adverse effects. Eight studies reported results about brain morphology and functioning using neuroimaging. Four studies had statistically significant findings consistent with adverse effects. www.aodhealth.org 52 Results (cont’d) Three studies reported physiologic response variability using cortisol levels. The results were inconsistent but all studies showed alterations in the cortisol response to stress in the PCE groups. Most of the differences between those exposed and unexposed to cocaine were small to moderate. www.aodhealth.org 53 Comments This systematic review represents the first effort to synthesize information on studies of PCE effects in adolescence. 70% of the studies had significant findings; however, the authors point out that the clinical relevance of those findings is unclear. These mixed results are consistent with prior reviews of PCE and early (pre-adolescent) development. www.aodhealth.org 54 Studies on HIV and HCV www.aodhealth.org 55 Illicit Substance Use is Associated with HIV Medication Non-Adherence and Risky Behaviors Mimiaga MJ, et al. Am J Pub Health. 2013;103(8):1457–1467. Summary by Darius A. Rastegar, MD www.aodhealth.org 56 Objectives/Methods Investigators used data from a cohort of 3413 HIV-infected patients to examine illicit substance use and its association with HIV medication adherence, psychological distress, and HIV risk behaviors. Self-reported substance use within the past 3 months was broken into 6 categories: Crack-cocaine Amphetamines Opiates Marijuana Injection drug use (IDU); and Polydrug use (a combination of crack-cocaine, amphetamines, opiates, or marijuana) www.aodhealth.org 57 Results Overall, 24% of subjects reported marijuana use, 9% amphetamine use, 8.5% crack-cocaine use, 2% opiate use, and 3% IDU; 10% of participants reported polydrug use. In multivariable models, non-adherence to HIV medications in the previous three months was associated with each of the substance use categories, except for marijuana. Having a detectable viral load was associated with crackcocaine use, IDU, and polydrug use. www.aodhealth.org 58 Results (cont’d) Engaging in unprotected anal sex was associated with marijuana, amphetamine, opiate, polydrug use, and IDU; the association was strongest for amphetamine and IDU. Vaginal sex risk behaviors were associated only with polydrug and crackcocaine use. www.aodhealth.org 59 Comments This study supports previous observations of an association between illicit substance use and HIV medication non-adherence and risky behaviors. While substance use may simply be a marker for risktaking behavior, it makes sense to screen patients with HIV for substance use and provide counseling. For those who have a substance use disorder, providing targeted treatment may offer additional benefits. Counseling alone is probably not sufficient and further investigation is needed on how to improve adherence and reduce risky behaviors among this population. www.aodhealth.org 60 Perceptions of Hepatitis C Screening and Treatment among People with Illicit Drug Use Jordan AE, et al. Harm Reduct J. 2013;10:10. Summary by Jeanette M. Tetrault, MD www.aodhealth.org 61 Objectives/Methods Despite the existence of effective treatment options, people with illicit drug use are less likely to be screened and treated for hepatitis C virus (HCV) than those without drug use. This disparity is especially pronounced among racial and ethnic minorities. www.aodhealth.org 62 Objectives/Methods (cont’d) The purpose of this qualitative study was to explore attitudes, perceptions, and experiences regarding HCV testing, referral, and treatment among racial and ethnic minorities with drug use. Ninety-five participants recruited from HIV primary care clinics, methadone maintenance programs, and syringe exchange programs in New York and San Francisco were included in 14 focus groups. www.aodhealth.org 63 Results Many participants reported that they underwent testing at their treatment facility but were unaware of other voluntary testing sites. Participants reported that receipt of a positive test was often accompanied by an unclear message about next steps. www.aodhealth.org 64 Results (cont’d) Many participants perceived a lack of need for treatment due to asymptomatic state, health care messages minimizing the severity of the disease, and inadequate recommendations for treatment by health care professionals. Social networks and interactions with peers were a common source of HCV-related information. www.aodhealth.org 65 Comments Although people with illicit drug use have a high prevalence of HCV, testing and treatment are not always offered to this population. Perceived inconsistent health care messages regarding the natural history of the disease contribute to a lack of understanding among patients. www.aodhealth.org 66 Comments (cont’d) Standardization of public health messages—including those delivered via social networking, peer support groups, and post-test counseling—may improve the general understanding of the natural history and treatment of HCV among people with drug use. www.aodhealth.org 67 Directly Observed Treatment for Hepatitis C Virus Infection among People with Active Drug Use Hilsden RJ, et al. Clin Infect Dis. 2013;57 Suppl 2:S90–96. Summary by Judith Tsui, MD, MPH www.aodhealth.org 68 Objectives/Methods This study appears to be the first randomized controlled trial (RCT) of treatment for HCV with directly observed interferon (peg-IFN) alpha-2a plus selfadministered ribavirin (RBV) conducted exclusively among adults with active* injection drug or crack cocaine use. * Defined as use at least once in a month and within 3 months of the date of randomization. www.aodhealth.org 69 Objectives/Methods (cont’d) Subjects were randomized to either immediate treatment with peg-IFN/RBV or delayed treatment (after 24–48 weeks). The original primary outcome was loss to follow-up and adverse events. The authors here report on sustained virologic response (SVR)—defined as undetectable HCV RNA— 24 weeks after completion of treatment. www.aodhealth.org 70 Results 377 participants were screened and only 66 (18%) were enrolled. The leading reasons for exclusion were cessation of drug use (82), loss to follow-up (72), and HCV RNA-negative status (61). The study was terminated early as the desired sample size (100) could not be achieved. In intention-to-treat analysis, SVR was 65% in the immediate group and 39% in the delayed group. Recent drug use in the past month did not impact treatment completion or SVR. www.aodhealth.org 71 Comments The results of this study suggest a benefit for immediate treatment over delayed treatment, although the authors encourage readers to interpret the findings with caution as they are observed in a small number of patents and the study was not originally designed to answer a question regarding efficacy via SVR. www.aodhealth.org 72 Comments (cont’d) The inability of the investigators to recruit their targeted sample size informs translation into real-world settings. As newer therapies for HCV with fewer side effects and shorter duration of treatment become available, it may become easier to treat people with illicit drug use and HCV. www.aodhealth.org 73