Update on Alcohol, Other Drugs, and Health

Update on Alcohol, Other Drugs, and Health May–June 2013 www.aodhealth.org

Studies on Interventions & Assessments www.aodhealth.org 2

Alcohol Screening and Brief Intervention Not Effective in Clinical Practice Kaner E, et al. BMJ 2013;346:e8501. Summary by Richard Saitz, MD, MPH www.aodhealth.org 3

Objectives/Methods Randomized controlled-efficacy trials consistently find modest favorable effects of brief intervention (BI) for nondependent unhealthy alcohol use identified by screening in primary care settings. Investigators randomly assigned 24 primary care practices to implement screening for unhealthy alcohol use and then either a patient information brochure, 5 minutes of brief advice, or 20 minutes of health behavior change counseling. www.aodhealth.org 4

Results Practices were paid approximately $4500 plus additional compensation for each screening and each intervention. Five practices did not recruit the requisite 31 patients and were replaced; 5 practices were reassigned to one of the more intensive interventions after completing initial recruitment targets. Due to slow recruitment, research staff accomplished the screening and BI in 10 of the practices. www.aodhealth.org 5

Results (cont’d) • Of 756 patients enrolled, 81% had 6-month outcome data; only 57% of those assigned to counseling received it. • The odds of having an Alcohol Use Disorders Identification Test score of <8 (i.e., no unhealthy use) were lower, though not significantly different for advice (odds ratio [OR], 0.85) and counseling (OR, 0.78), versus information only. Intention-to-treat and per-protocol analyses yielded similar results. www.aodhealth.org

Comments Screening and BI were both challenging to implement and ineffective in primary care practices. These findings should be carefully considered by those involved in major implementation efforts worldwide and serve as a reality check for clinicians working to implement alcohol screening and BI in their practices. www.aodhealth.org 7

Systematic Screening Is More Effective than Targeted Screening at Engaging Primary Care Patients in Discussions about Alcohol, Especially Those with Lower Risk Use Reinholdz H, et al.Alcohol Alcohol. 2013;48(2):172–179. Summary by Nicolas Bertholet, MD, MSc www.aodhealth.org 8

Objectives/Methods Implementing systematic screening for risky drinking can be a burden for primary care practices (PCPs). An alternative is the use of a targeted approach. Both methods were compared in a randomized trial of 16 PCPs in Sweden (N=3609 patients) to assess their impact on alcohol discussions. www.aodhealth.org 9

Objectives/Methods (cont’d) • In the systematic group, patients were asked to complete the AUDIT-C* and give it to their primary care physician before the consultation. • In the consultation-based early identification group, clinicians were encouraged to be alert for signs of alcohol-related issues during the consultation but did not receive AUDIT-C screening results; patients completed the AUDIT-C after the consultation. *Alcohol Use Disorders Identification Test—Consumption. www.aodhealth.org

Results Among patients who screened positive for risky drinking* the mean age was 44 years for men and 42 years for women. Among patients with whom the issue of alcohol was brought up, the mean age was 54 years for men and 44 years for women. In the systematic group, 62.5% of patients with risky drinking and 64.2% of patients with lower-risk drinking had the issue of alcohol brought up. In the identification group, the proportions were 29.7% and 30.1%, respectively. *Defined as AUDIT-C scores of ≥5 for men and ≥4 for women. www.aodhealth.org 11

Results (cont’d) • Looking at patients with risky drinking only, a higher proportion in the systematic group had the issue brought up compared with the identification group. This association was significant for men, women, and both genders combined. • Among patients with risky drinking who had the issue of alcohol brought up, the mean AUDIT-C score was significantly higher in the identification group (5.8) compared with the systematic group (5.2). www.aodhealth.org

Comments The method used by PCPs to identify at-risk drinking dramatically impacts the proportion of patients who discuss alcohol with their primary care physicians. Although systematic screening did not lead to systematic conversations about alcohol in this study, it did allow for a much higher proportion of patients with risky alcohol use to engage in such conversations. www.aodhealth.org 13

Comments (cont’d) A targeted approach allows patients with more severe risky use to be identified, but systematic screening helps identify patients with lower-risk alcohol use (potentially even more than it helps identify patients with more severe problems) who may benefit from a single brief intervention. www.aodhealth.org 14

Studies on Health Outcomes www.aodhealth.org 15

Update on the Association between Alcohol Consumption, Cognitive Functioning, and Dementia Panza F, et al. Int J Geriatr Psychiatry. 2012;27(12):1218–1238. Summary by R. Curtis Ellison, MD www.aodhealth.org 16

Objectives/Methods Scientists in Italy conducted an extensive review of the research published between 1987–2011 that examined the relationship between alcohol consumption, cognitive function, and dementia. For cognitive impairment, the authors reviewed 14 cross-sectional studies; for cognitive decline, they reviewed 21 longitudinal studies; and for dementia or predementia, they reviewed 26 longitudinal and 7 other studies. www.aodhealth.org 17

Results Current data support an association between low-risk drinking* and lower risk of dementia. Protective effects of low-risk alcohol consumption against cognitive decline are suggested to be more likely in the absence of the apolipoprotein E (APOE) e4 allele associated with Alzheimer Disease and where wine is the beverage. *There was significant variability across studies in defining low-risk drinking in both men and women. www.aodhealth.org 18

Results (cont’d) • Suggested mechanisms by which low-risk alcohol intake may be neuroprotective include reduction in vascular risk factors; fewer brain infarcts and a U-shaped relationship with white matter lesions; stimulation of the release of hippocampal acetylcholine (in animal models); and antioxidant effects of polyphenols, especially from wine. www.aodhealth.org 19

Comments There are always problems in having to develop guidelines for alcohol consumption based only on observational data, with no large clinical trials to judge effect. While results in prospective studies are quite consistent, many studies included in this review lacked data on beverage type and pattern of drinking, which may be important determinants of health outcomes. www.aodhealth.org 20

Comments (cont’d) • Despite the recognized limitations, current observational data support that consuming low-risk amounts of alcohol, especially of wine, is associated with less cognitive decline and dementia. www.aodhealth.org 21

Distributing Naloxone to People Who Use Heroin for Lay Treatment of Overdose is Cost-Effective Coffin PO, et al. Ann Intern Med. 2013;158(1):1–9. Summary by Kevin L. Kraemer, MD, MSc www.aodhealth.org 22

Objectives/Methods Researchers used a decision analytic computer model to estimate the cost-effectiveness (CE) of distributing naloxone to people with heroin use to reverse overdoses. The model compared a strategy of distributing naloxone to 20% of people who use heroin with a strategy of no distribution and was designed to bias against the naloxone strategy. Values and ranges for the model parameters (proportions, transition rates, costs, utilities) were extracted from published literature. The model outputs were costs, quality-adjusted life-years (QALYs), and incremental CE ratios (costs per QALY). www.aodhealth.org 23

Results In the base case analysis, the naloxone distribution strategy: prevented 6% of overdose deaths. required the distribution of 227 naloxone kits to prevent 1 overdose death. had an incremental CE ratio of $438 per QALY gained. 24 www.aodhealth.org

Results (cont’d) In sensitivity analyses, the naloxone distribution strategy remained cost-effective (most incremental CE ratios less than $1000 per QALY gained) over a wide range of scenarios and parameter values. Even the worst-case scenario (overdoses rarely witnessed and naloxone more expensive, less efficacious, and rarely carried) had an incremental CE ratio of $14,000 per QALY. www.aodhealth.org 25

Comments This well-done analysis suggests that naloxone distribution is highly cost-effective when compared with no distribution. The incremental CE ratios are far lower than those for many common healthcare practices and well within thresholds considered cost-effective by policymakers. Although controlled data were not available for some parameters of the model, it appears robust and lends support to the distribution of naloxone to people who abuse heroin and prescription opioids. www.aodhealth.org 26

Walley AY, et al. BMJ 2013;346:f174.Summary by Darius A. Rastegar, MD Overdose Education and Nasal Naloxone Distribution are Associated with a Reduction in Overdose Fatalities www.aodhealth.org 27

Objectives/Methods To determine whether providing opioid overdose education with naloxone distribution (OEND) is an effective strategy for reducing overdose fatality, the researchers evaluated the impact of an OEND program in Massachusetts. The program provided education to people at risk for overdose and bystanders on minimizing the risk of overdose and recognizing and responding to overdose by providing rescue breathing, administering nasal naloxone, and staying with the person until medical personnel arrived. 28 www.aodhealth.org

Objectives/Methods (cont’d) • Enrollees received a rescue kit with two doses of naloxone. • The program included 19 communities that accounted for 30% of the state population and used interrupted times series analysis to compare community-year strata that have high and low rates of OEND implementation with those with no implementation. www.aodhealth.org 29

Results • Over a 3-year period in the 19 communities studied, 2912 individuals were enrolled in OEND and 327 rescue attempts were reported. • Compared with no implementation, both low and high implementation of OEND were associated with lower rates of opioid overdose deaths, with an adjusted rate ratio of 0.73 in low-implementer community-year strata and 0.54 in the high-implementer community-year strata. • There was no significant difference in opioid overdose-related acute care hospital utilization. www.aodhealth.org 30

Comments Opioid overdose education and naloxone distribution are two tools to help reduce unintentional opioid overdose deaths. Other measures that have been shown to reduce overdose fatalities are opioid agonist treatment and supervised injection facilities. While acute care hospital utilization was not reduced, the authors point out that this could be due to the fact that the training encouraged bystanders to engage the emergency medical system. www.aodhealth.org 31

Comments (cont’d) • This program targeted people who use illicit drugs; another population at risk that may benefit from OEND is individuals who are prescribed opioids for chronic pain. www.aodhealth.org 32 32

Controlled Trials Support the Use of Benzodiazepines for Prevention and Treatment of Alcohol Withdrawal Syndrome in the Intensive Care Unit Unger LA, et al. Alcohol Clin Exp Res. 2013;37(4):675–686. Summary by Kevin L. Kraemer, MD, MSc www.aodhealth.org 33

Objectives/Methods Two independent working groups conducted a systematic review of controlled trials published 1971–2011 on prevention and treatment of alcohol withdrawal syndrome (AWS) in the intensive care unit (ICU). Six prevention trials (4 randomized, 2 nonrandomized) and 8 treatment trials (4 randomized, 4 nonrandomized) were identified. Reasons for ICU admission were a mix of surgery, trauma, medical illness, and severe AWS. Definition and scoring of AWS and study outcome were highly heterogeneous across trials. www.aodhealth.org

Objectives/Methods (cont’d) Drugs assessed for AWS prevention were ethanol infusion, clonidine, flunitrazepam, clomethiazol + haloperidol, flunitrazepam + haloperidol, and midazolam. Drugs assessed for AWS treatment included those listed above as well as gamma-hydroxybutyric acid, phenobarbital, lorazepam, and flunitrazepam + clonidine. www.aodhealth.org

Results All AWS prevention and treatment regimens were effective compared with control. Benzodiazepines were effective and safe for AWS prevention and treatment, whereas ethanol infusion was effective and safe for AWS prevention. www.aodhealth.org 36

Comments The trials in this systematic review tended to be small and not high-quality, and heterogeneity prevented pooling of results. Nonetheless, benzodiazepines can be regarded as the strategy with the most evidence-based support for AWS prevention and treatment in the ICU. Although ethanol infusion was effective for AWS prevention, it not should supplant benzodiazepines because the level of evidence is weaker, it is difficult to titrate, and has no apparent benefit over benzodiazepines. www.aodhealth.org 37

Haddad MS, et al. Drug Alcohol Depend. January 6, 2013 [Epub ahead of print]. doi: 10.1016/j.drugalcdep.2012.12.008.Summary by Alexander Y. Walley, MD, MSc Office-based Buprenorphine Treatment is Feasible in Federally Qualified Health Centers www.aodhealth.org 38

Objectives/Methods Buprenorphine/naloxone treatment for opioid dependence has been demonstrated to be feasible in multiple primary care settings, including academic medical centers, private practices, and HIV clinics. Researchers conducted a retrospective review of electronic medical records in 2 federally qualified health centers (FQHCs) in Connecticut to identify clinical factors associated with retention in buprenorphine (BUP) treatment and opioid abstinence. www.aodhealth.org 39

Objectives/Methods (cont’d) • Records were reviewed for 266 patients who received at least 1 BUP prescription from 1 of 4 prescribers between July 1, 2007, and December 1, 2008, and who were observed for 6 to 21.5 months. www.aodhealth.org 40

Results • The mean age of patients was 40 years; 70% were male, 70% were prescribed BUP by family practitioners, 30% were treated by a psychiatrist, 72% were diagnosed with a mood or anxiety disorder, 65% were treated for a mood or anxiety disorder, and 80% initiated care at the FQHC to receive BUP. The mean stabilization dose was 17.8 mg. • Retention in treatment at 6 months was 57%. Patients with cocaine use at treatment initiation (adjusted hazard ratio [AHR], 2.18) were more likely to drop out of BUP treatment, whereas patients who were older (AHR, 0.96), female (AHR, 0.59), receiving psychiatric medication (AHR, 0.69), HCV-infected (AHR, 0.56), or receiving on-site substance abuse counseling (AHR, 0.54) were less likely to drop out. www.aodhealth.org 41

Results (cont’d) • Urine toxicology results were opioid-abstinent for 30% of the patients at every test and 72% of patients at their last observed test. Patients with cocaine use at treatment initiation were less likely to have an opioid-abstinent last urine test (adjusted odds ratio [AOR], 0.43), whereas patients prescribed psychiatric medications were more likely to have an opioid-abstinent last urine test (AOR, 1.66). www.aodhealth.org 42

Comments Whereas comorbid psychiatric illness typically is associated with worse addiction treatment outcomes, this study found that patients with psychiatric comorbidity treated with medication had improved retention and were more likely to be abstinent from opioids. The prospect of integrated care models that deliver high-quality medical, psychiatric, and addiction treatment that produces improved outcomes warrants prospective implementation studies. www.aodhealth.org 43

Studies on HIV and HCV www.aodhealth.org 44

Drug-related Causes the Primary Reasons for Death among People with Injection Drug Use who are Seropositive for HCV Kielland KB, et al. J Hepatol. 2013;58(1):31–37. Summary by Judith Tsui, MD, MPH www.aodhealth.org 45

Objectives/Methods To determine whether hepatitis C virus (HCV) is a major cause of mortality among people who use injection drugs, this observational cohort study included 523 HCV seropositive patients admitted to residential substance use treatment in Norway followed using the national mortality register. www.aodhealth.org

Results Of the 523 HCV seropositive people with injection drug use, 63% were HCV RNA+ (i.e., had chronic infection). At the end of follow-up (mean 33 years), 42% died. The mortality rate for HCV RNA+ people was 1.75 per 100 person-years, versus 2.05 in HCV- people (i.e., presumed to have spontaneous clearance)(P=0.25). www.aodhealth.org 47

Results (cont’d) • Opioid overdose was the most frequent cause of death, followed by violent death and suicide. • Twelve patients (7.5%) died of liver disease; 10 were HCV RNA+ and the remaining 2 had chronic hepatitis B. • Restricting analyses to those ≥50 years of age, the liver-related mortality rate was 0.94 per 100 person-years among HCV RNA+ people, and was 0 (no deaths) among those who were HCV RNA-. www.aodhealth.org 48 48

Comments This study confirms high mortality rates for people who use injection drugs and reinforces that drug-related causes remain the primary risks for death in this population. Thus, some patients with HCV may not benefit from HCV treatment because of competing causes of death. However, among people with injection drug use who survive beyond age 50, liver-related mortality emerges as a cause of premature death, confirming prior modeling studies. www.aodhealth.org 49

Comments (cont’d) • The study’s main finding should be cautiously interpreted given that there was some potential for misclassification bias (cases of unidentified reinfection or clearance through treatment). www.aodhealth.org 50 50 50

Update on Alcohol, Other Drugs, and Health