Update on Alcohol, Other Drugs, and Health

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Update on Alcohol, Other

Drugs, and Health

May–June 2013

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Studies on Interventions &

Assessments

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Alcohol Screening and Brief Intervention Not Effective

in Clinical Practice

Kaner E, et al. BMJ 2013;346:e8501.Summary by Richard Saitz, MD, MPH

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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.

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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.

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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.

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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.

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Systematic Screening Is More Effective than Targeted

Screening at Engaging Primary Care Patients in

Discussions about Alcohol, Especially Those with Lower

Risk UseReinholdz H, et al. Alcohol Alcohol. 2013;48(2):172–

179.Summary by Nicolas Bertholet, MD, MSc

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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.

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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.


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.


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).


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.


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.


Studies on Health Outcomes


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


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.


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.


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.


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.


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.


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


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).

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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.

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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.


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.


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


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.



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.

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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.

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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.


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.


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

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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

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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.

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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.

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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.


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


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.



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.


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.


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).


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.


Studies on HIV and HCV


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

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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.

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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).

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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-.


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.


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).


Risky Alcohol Use Associated with Elevated Serum Aminotransferase

Levels in HIV/HCV Coinfected Patients

Tsui JI, et al. J Stud Alcohol and Drugs. 2013;74(2):266–270.

Summary by Jeanette M. Tetrault, MD

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Objectives/Methods

Using data from the prospective observational cohort HIV-Longitudinal Interrelationships of Viruses and Ethanol (HIV-LIVE) study, the authors assessed the association between National Institute on Alcohol Abuse and Alcoholism (NIAAA)-defined risky alcohol consumption* and serum aminotransferase levels in HIV-infected patients with and without HCV infection.

Regression models that can account for repeated measures were used to assess the association between risky alcohol use and AST and ALT levels over time.

* >14 standard drinks per week or >4 drinks per day for men, or >7 drinks per week or >3 drinks per day for women.

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Results

Of 397 HIV-infected subjects in the HIV-LIVE study with HCV serologic testing, 200 (50.4%) had detectable HCV viral load and were considered HIV/HCV coinfected.

Among coinfected subjects, risky alcohol use was associated with higher mean AST (adjusted means 62.2 versus 51.4 U/L; adjusted ratio of means 1.2) and ALT (adjusted means 51.3 versus 41.6 U/L.; adjusted ratio of means 1.2), compared with those without risky alcohol use.

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Results (cont’d)

Among HIV monoinfected subjects, the authors found no differences in AST or ALT among patients with or without risky alcohol use.


Comments

Among HIV/HCV coinfected subjects, mean AST and ALT levels were approximately 20% higher in those with risky alcohol use compared with those without risky alcohol use, while no such association was noted in HIV monoinfected subjects.

These data suggest that alcohol use may be particularly concerning in HIV/HCV coinfected patients and that physicians should consider tailoring counseling messages regarding the harmful effects of alcohol to this population.


Adding Enhanced Counseling to Standard Medical

Management Does Not Improve Outcomes for HIV-

Positive Individuals with Opioid Dependence Who are Prescribed Buprenorphine

Tetrault JM, et al. J Subst Abuse Treat. 2012;43(4):433–439.Summary by Darius A. Rastegar, MD


Objectives/Methods The provision of buprenorphine with medical

management in an office-based setting has been shown to be an effective treatment for opioid dependence. The addition of further counseling, however, has not been shown to improve outcomes.

For HIV-positive individuals, providing buprenorphine treatment may improve their care, but the impact of further counseling has not been studied in this population.



The 47 HIV-positive opioid-dependent subjects in this 12-week study were all prescribed buprenorphine and received standard bi-weekly physician visits; 22 were randomly assigned to receive additional enhanced counseling (drug counseling and medication adherence management), delivered by a trained nurse.


Results

There was no significant difference in the percentage of opioid-negative urine drug tests between the standard and enhanced treatment arms (64% versus 69%, respectively).

There was no significant difference in the mean number of continuous weeks of opioid abstinence (4.9 weeks for standard treatment versus 5.2 weeks for enhanced).


Results (cont’d)

There was likewise no significant difference in the following secondary endpoints: percent cocaine-negative urine-drug tests study completion rate buprenorphine adherence antiretroviral adherence HIV clinical outcomes


Comments This study supports the findings of previous

studies and extends them to individuals with opioid dependence who are HIV-positive. The results of these studies have been consistent and indicate that for patients who are prescribed buprenorphine, routinely adding counseling beyond that which is delivered by physicians in 15-minute visits does not offer additional benefit.

This study was small and somewhat underpowered and could not exclude a modest benefit; moreover, there may always be select individuals who benefit from additional counseling.


Concurrent Addiction and HCV Treatment Improves

HCV Treatment Completion

Dimova RB, et al. Clin Infect Dis. 2013;56(6):806–816. Summary by Jeanette M. Tetrault, MD


Objectives/Methods

The purpose of this meta-analysis was to determine the impact of support services on HCV treatment completion and success rates among HCV-infected people with drug use, measured by sustained virologic response (SVR), which is defined as undetectable viral load at the end of treatment and 24 weeks subsequent.

The meta-analysis included 36 studies—published between 2004 and 2011—that collectively reported data from 2866 patients.


Results The HCV treatment completion rate was 83.4%

(95% confidence interval [CI]: 77.1–88.9%). Among 25 studies including patients

undergoing concurrent addiction treatment, the higher the proportion of addiction-treated patients, the greater the likelihood of treatment completion.

After removing outliers, the pooled SVR rate was 55.5% (95% CI: 50.6–60.3%). Genotype 1 and 4 infection and HIV coinfection were associated with a decreased SVR rate; after adjusting for these factors, SVR was associated with treatment performed by a multidisciplinary team.


Comments

Despite some heterogeneity of studies, the results of this meta-analysis suggest that overall treatment completion SVR rates among HCV-infected drug users undergoing treatment with pegylated interferon and ribavirin are comparable to previous trials that excluded people with drug use, particularly when patients are concurrently treated for addiction.


Self-reported Unhealthy Alcohol Use Predicts

Virological Rebound in HIV/HCV Coinfected

PatientsMarcellin F, et al. Addiction. February 20, 2013 [Epub

ahead of print]. doi: 10.1111/add.12149 Summary by David Fuster, MD, PhD & Alexander Y. Walley,

MD, MSc


Objectives/Methods

Unhealthy alcohol use is common in HIV-infected patients and is believed to have a negative impact on the course of HIV infection, in part because it is associated with poor adherence to antiretroviral therapy (ART).

Unhealthy use is even more harmful in people coinfected with HCV because of the increased risk of progression to end-stage liver disease.

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Investigators in France performed a prospective study to evaluate the impact of heavy alcohol use,* measured either by physician’s perceptions or patient self-administered interview, on time to detectable viral load.

The sample included 512 patients coinfected with HIV/HCV who had achieved viral suppression** through ART.

Median follow-up was 21 months.

*Defined as consuming ≥4 drinks (11-14 g alcohol) per day for men or ≥3 drinks per day for women “on a regular basis” in the past 6 months.

**HIV RNA below the limit of detection.



Results At study enrollment, 9% of participants self-

reported heavy alcohol use, and 15% were considered to have heavy alcohol use by their physicians.

Physician report agreed with self-report in 90% of patients not reporting heavy alcohol use and in 77% of those who did, but 61% of those classified by physicians as having heavy alcohol use did not report heavy alcohol use, and 2% of those classified as abstainers or low-risk drinkers reported heavy alcohol use.


Results (cont’d)

During follow-up, 101 participants (20%) had a detectable viral load. Self-reported heavy alcohol use was independently associated with detectable viral load (adjusted hazard ratio 2), while physician-reported heavy alcohol use was not.


Comments

This study found that heavy alcohol use is associated with detectable HIV viral load, probably through its effect on ART adherence. Furthermore, the results stress the importance of patient self-report (in contrast to physician’s impressions).

These results add to mounting evidence that heavy alcohol use should be avoided in HIV/HCV co-infected patients.

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Update on Alcohol, Other Drugs, and Health