Evidence Summary
Alcohol Misuse: Screening and Behavioral Counseling Interventions in Primary Care
September 25, 2012
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
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Behavioral Counseling After Screening for Alcohol Misuse in Primary Care
A Systematic Review and Meta-Analysis for the U.S. Preventive Services Task Force
Release Date: September 25, 2012
By Daniel E. Jonas, MD, MPH; James C. Garbutt, MD; Halle R. Amick, MSPH; Janice M. Brown, PhD; Kimberly A. Brownley, PhD; Carol L. Council, MSPH; Anthony J. Viera, MD, MPH; Tania M. Wilkins, MS; Cody J. Schwartz, MPH; Emily M. Richmond, MPH; John Yeatts, MPH; Tammeka Swinson Evans, MOP; Sally D. Wood, BA; and Russell P. Harris, MD, MPH
The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.
This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
This article was first published in Annals of Internal Medicine on September 25, 2012 (Ann Intern Med; http://www.annals.org).
Background: Alcohol misuse, which includes the full spectrum from risky drinking to alcohol dependence, is a leading cause of preventable death in the United States.
Purpose: To evaluate the benefits and harms of behavioral counseling interventions for adolescents and adults who misuse alcohol.
Data Sources: MEDLINE, EMBASE, the Cochrane Library, CINAHL, PsycINFO, and reference lists of published literature (January 1985 through January 2012, limited to English-language articles).
Study Selection: Controlled trials at least 6 months in duration that enrolled persons with alcohol misuse identified by screening in primary care settings and evaluated behavioral counseling interventions.
Data Extraction: One reviewer extracted data and a second checked accuracy. Two independent reviewers assigned quality ratings and graded the strength of the evidence.
Data Synthesis: The 23 included trials generally excluded persons with alcohol dependence. The best evidence was for brief (10- to 15-minute) multicontact interventions. Among adults receiving behavioral interventions, consumption decreased by 3.6 drinks per week from baseline (weighted mean difference, 3.6 drinks/wk [95% CI, 2.4 to 4.8 drinks/wk]; 10 trials; 4332 participants), 12% fewer adults reported heavy drinking episodes (risk difference, 0.12 [CI, 0.07 to 0.16]; 7 trials; 2737 participants), and 11% more adults reported drinking less than the recommended limits (risk difference, 0.11 [CI, 0.08 to 0.13]; 9 trials; 5973 participants) over 12 months compared with control participants (moderate strength of evidence). Evidence was insufficient to draw conclusions about accidents, injuries, or alcohol-related liver problems. Trials enrolling young adults or college students showed reduced consumption and fewer heavy drinking episodes (moderate strength of evidence). Little or no evidence of harms was found.
Limitations: Results may be biased to the null because the behavior of control participants could have been affected by alcohol misuse assessments. In addition, evidence is probably inapplicable to persons with alcohol dependence and selective reporting may have occurred.
Conclusions: Behavioral counseling interventions improve behavioral outcomes for adults with risky drinking.
Primary Funding Source: Agency for Healthcare Research and Quality.
Alcohol misuse, which includes the full spectrum from risky or hazardous drinking to alcohol dependence1-3, is associated with numerous health and social problems and more than 85,000 deaths per year in the United States4, 5. Alcohol misuse is the third leading cause of preventable death in the United States, after tobacco use and being overweight6. It contributes to hypertension, cirrhosis, gastritis, gastric ulcers, pancreatitis, breast cancer, neuropathy, cardiomyopathy, anemia, osteoporosis, cognitive impairment, depression, insomnia, anxiety, suicide, injury, and violence7-9. The definitions of the spectrum of alcohol misuse (that is, unhealthy alcohol use1 continue to evolve. For this review, we use the definitions in Table 110-12.
About 30% of the U.S. population misuse alcohol, with most engaging in what is considered risky drinking1. Recent U.S.-based data13 revealed that 21.3% of primary care patients reported risky drinking.
Cross-sectional and cohort studies have consistently related high average alcohol consumption and heavy per-occasion use to short- or long-term health consequences14,15. A meta-analysis examining the association between all-cause mortality and average alcohol consumption16 found that men who drank an average of at least 4 drinks per day and women who drank an average of at least 2 drinks per day had increased mortality relative to nondrinkers. The National Institute on Alcohol Abuse and Alcoholism has proposed guidelines17 to limit the risks for drinking-related consequences. The maximum recommended consumption is 3 or fewer standard drinks per day (≤7/wk) for adult women and anyone older than 65 years, and 4 or fewer standard drinks per day (≤14/week) for men15,17,18. These guidelines do not apply to persons for whom alcohol intake is contraindicated, such as pregnant women, persons with alcohol dependence or medical conditions that can be worsened by drinking, or those receiving medications that interact with alcohol.
Behavioral counseling interventions include the range of personal counseling and related behavior-change interventions that are used to help patients change health-related behaviors19. “Counseling” here denotes a cooperative method of work that demands active participation from both patient and clinician and aims to facilitate the patient's independent initiative19. The goal of behavioral interventions for alcohol misuse is to eliminate risky drinking practices (for example, by encouraging fewer drinks per occasion or not drinking before driving) rather than to achieve abstinence.
For the Effective Health Care Program of the Agency for Healthcare Research and Quality (AHRQ) and to assist the U.S. Preventive Services Task Force (USPSTF) in updating its 2004 recommendation statemen20, we conducted a systematic review and meta-analysis of the effectiveness of screening followed by behavioral counseling, with or without referral, for alcohol misuse in primary care settings21. The full report21 addressed 7 questions Appendix Figure 1.
We developed and followed a standard protocol. A technical report that details methods and includes search strategies and additional evidence tables is available at www.effectivehealthcare.ahrq.gov/reports/final.cfm.
Key Questions and Analytic Framework
The USPSTF and AHRQ determined the focus of this review. Investigators developed key questions and created an analytic framework that incorporated the key questions and outlined patient populations, interventions, comparators, outcomes (including adverse effects), and settings Appendix Figure 1. This report focuses on the key questions related to benefits and harms of behavioral interventions.
Data Sources and Searches
We searched MEDLINE, EMBASE, the Cochrane Library, CINAHL, PsycINFO, and the International Pharmaceutical Abstracts from 1 January 1985 to 31 January 2012, limited to English-language articles. The start date was selected on the basis of the earliest publication date found in previous reviews and expert opinion. We used Medical Subject Headings as search terms when available and key words when appropriate, focusing on terms to describe relevant populations, screening, and behavioral interventions.
Study Selection
We developed inclusion and exclusion criteria with respect to populations, interventions, comparators, outcomes, timing, settings, and study designs22,23. For the question related to behavioral interventions, we included randomized, controlled trials at least 6 months in duration, that enrolled adults or adolescents with alcohol misuse identified by screening in primary care settings, and that evaluated whether a counseling intervention improved behavioral or health outcomes.
Two investigators independently reviewed titles and abstracts, and then another 2 investigators independently reviewed the full text of all articles marked for possible inclusion during the initial review to determine final inclusion or exclusion. Disagreements were resolved with an experienced team member.
Data Extraction and Quality Assessment
We designed and used structured forms to extract pertinent information from each article, including information about the methods and populations, interventions, comparators, outcomes, timing, settings, and study designs. All data extractions were reviewed for completeness and accuracy by a second team member.
We assessed the quality (internal validity) of studies using predefined criteria based on those developed by the USPSTF (ratings of good, fair, or poor)24 and the University of York Centre for Reviews and Dissemination25. These included assessment of the adequacy of randomization, allocation concealment, similarity of groups at baseline, masking, attrition, and whether intention-to-treat analysis was used. Two independent reviewers assigned quality ratings for each study. Disagreements were resolved by an experienced member of the team.
Data Synthesis and Analysis
We stratified evidence by population (adults, older adults, young adults or college students, and pregnant women). Quantitative analyses were conducted of outcomes reported by a sufficient number of studies that were homogeneous enough to justify combining their results. We used random-effects models. For the outcome of alcohol consumption, the effect measure was mean difference between the intervention and control groups for change from baseline in drinks per week. The percentages of patients who had episodes of heavy drinking and those who achieved recommended drinking limits were compared (between intervention and control groups) with a risk difference. Because follow-up periods varied, the analysis for all-cause mortality was based on deaths per person-year and the comparison between intervention and control groups was calculated as a risk ratio. Analyses were conducted by using Comprehensive Meta Analysis, version 2.2.055 (BioStat, Englewood, New Jersey).
We used subgroup analyses to explore whether results differed by intensity, sex, country, deliverer of the intervention, or setting. The chi-square and I2 statistics were calculated to assess heterogeneity in effects between studies26,27. When quantitative analyses were not appropriate (for example, because of heterogeneity, insufficient number of similar studies, or insufficient or varied outcome reporting), we synthesized the data qualitatively.
To assess the differential effects of using more or less time and single or multiple contacts, we grouped interventions by intensity of counseling, as measured by the duration and number of contacts: very brief (≤5 minutes, single-contact), brief (6 to 15 minutes, single-contact), extended (>15 minutes, single-contact), brief multicontact (each contact ≤15 minutes), or extended multicontact (some contacts >15 minutes).
We then graded the strength of evidence (SOE) as high, moderate, low, or insufficient on the basis of the guidance established for the Evidence-based Practice Center Program Appendix Table 228. Two reviewers assessed each domain for each key outcome, and differences were resolved by consensus.
Role of the Funding Source
This review was funded by AHRQ. Staff of AHRQ and members of the USPSTF participated in developing the scope of the work and reviewed draft manuscripts. Approval from AHRQ for copyright assertion was required before the manuscript could be submitted for publication, but the authors are solely responsible for the content and the decision to submit it for publication.
We included 38 articles reporting on 23 randomized, controlled trials Appendix Figure 2. Sample sizes ranged from 72 to 1559, and study durations ranged from 6 to 48 months Appendix Table 3. Eleven studies were done solely in the United States, 2 focused on older adults, 5 focused on young adults or college students, and 1 enrolled pregnant women. We identified no studies of adolescents.
Fourteen of the interventions29-50 were delivered by a primary care physician alone or with a health educator or nurse. Three51-54 were delivered by a nurse or physician assistant, 1 by a psychologist55-57, 2 by a researcher58-62, and 1 by unspecified interventionists63. Two interventions in college students64-66 were conducted via a computer. Most trials tested brief multicontact interventions31-34,42,46,50,51,53,64,65 or brief interventions29,49,52,58,60,62-66; fewer tested very brief45,63, extended30, or extended multicontact interventions38,45,48,55,60. Interventions were heterogeneous and included various counseling approaches, such as brief advice, feedback, or motivational interviews, and cognitive behavioral strategies, such as self-completed action plans, written health education or self-help materials, drinking diaries, or problem-solving exercises to complete at home Appendix Table 4. Most comparator groups received screening or assessment followed by usual care or by provision of a general health pamphlet. A few studies included additional components in comparator groups that could have biased results toward the null, such as recording screening or assessment results on the chart 45 or forwarding them to physicians 60, advice from nurses on reducing drinking and a leaflet with benchmark alcohol guides52, a pamphlet on the health effects of alcohol consumption64-66, or a booklet about preventing alcohol problems48. We summarize the main findings by population and outcome and report the SOE for each.
Screening
We found no studies meeting inclusion criteria that randomly assigned participants, practices, or providers to screening and a comparator (no studies addressing questions 1 or 3) Appendix Table 1. We found adequate evidence that several screening instruments can detect alcohol misuse in adults with acceptable sensitivity and specificity21. The full technical report includes additional details about the accuracy of screening tests.
Effectiveness for Improving Intermediate Outcomes
Table 2 summarizes the results of meta-analyses for consumption, heavy drinking, and recommended drinking limits, by population. The Figure shows the forest plots for 12-month outcomes from our meta-analyses for adults. Overall, evidence supports the effectiveness of behavioral interventions for improving several intermediate outcomes for adults, older adults, and young adults or college students. For pregnant women, the included study (250 participants)30 did not provide evidence of effectiveness for improving intermediate outcomes over 6 months or longer (low or insufficient SOE, depending on the outcome). Subgroup analyses identified no significant differences between men and women. Brief multicontact interventions had the best evidence of effectiveness across populations and outcomes and had follow-up data spanning several years. Meta-analyses of studies in adults found very brief and brief single-contact interventions to be ineffective for some outcomes and less effective than brief multicontact interventions for others.
Effectiveness for Reducing Morbidity, Reducing Mortality, or Changing Other Outcomes
Table 3 summarizes results, by population. Our meta-analyses found no statistically significant reduction in all-cause mortality for adults (rate ratio, 0.64 [95% CI, 0.24 to 1.7]; 4 trials) or for all age groups combined (rate ratio, 0.52 [CI, 0.22 to 1.2]; 6 trials). Point estimates tended toward favoring interventions, but few studies reported mortality and few long-term data were available. No studies that enrolled pregnant women and reported these outcomes were found (insufficient SOE).
Potential Adverse Effects
We found no evidence of direct harms, aside from opportunity costs associated with interventions, which ranged from 5 minutes to 2 hours dispersed over several in-person or telephone visits (moderate SOE). We searched for evidence of potential adverse effects, such as illegal substance use, increased smoking, anxiety, stigma, labeling, discrimination, or interference with the physician–patient relationship. We found no evidence for most of these potential harms and very limited evidence reporting no difference between groups for smoking rates and anxiety (low SOE). Other than the results for opportunity costs, our results are limited by the few trials that reported any information; 5 of 23 reported smoking29,33,34,39,41,49,50, and 2 reported anxiety29,49.
Health Care System Influences
Where the study was conducted (United States vs. non–United States) had no impact on the effectiveness of interventions for consumption outcomes. Data showed a tendency toward greater reduction in consumption for interventions delivered in academic- or research-oriented settings than for those delivered in community-based settings (weighted mean difference, −5.0 drinks/wk [CI, −7.6 to −2.5 drinks/wk] vs. −3.2 drinks/wk [CI, −4.3 to −2.2 drinks/wk]; 3 vs. 7 trials). Interventions delivered mostly by primary care providers showed a tendency toward greater reduction in consumption than did those delivered primarily by research personnel (weighted mean difference, −4.0 drinks/wk [CI, −5.4 to −2.6 drinks/wk] vs. −3.0 drinks/wk [CI, −5.0 to −1.0 drinks/wk]; 7 vs. 2 trials). Our consumption meta-analysis included only 1 intervention delivered by a nurse52, and the reduction was not statistically significant in that study (weighted mean difference, −0.2 drinks/wk [CI, −8.9 to 8.6 drinks/wk]). Two other studies, each of which provided insufficient data for our consumption meta-analysis, reported benefits of interventions delivered primarily by nurses51 or by nurses and physician assistants53 for some consumption outcomes. In addition, 2 interventions conducted by computer reported some evidence of effectiveness for reduced consumption in college students64-66.
We found no studies that directly addressed our overarching question (Key Question 1)—no studies randomly assigned patients, practices, or providers to screening and comparator groups and subsequently provided interventions for those with positive screening results. All of the included studies randomly assigned patients after they had received positive screening results.
We found that behavioral counseling interventions improved drinking behavior outcomes (moderate SOE) and reduced hospital days (low SOE) for adults with risky drinking. For most health outcomes, available evidence either found no difference between intervention and control groups, such as for mortality (low SOE), or was insufficient to draw conclusions, such as for alcohol-related liver problems (insufficient SOE). Long-term outcomes from 2 studies33,35-37,39, 42,43 revealed that participants in the intervention groups maintained reductions in consumption or continued to reduce consumption, but differences between intervention and control groups were no longer statistically significant by 48 months. Studies identified delayed reduction in consumption in control groups that could reflect the natural history of alcohol consumption, the cumulative effect of follow-up with the health care system, differential attrition (if more participants lost to follow-up in the control group were risky drinkers), or (late) regression to the mean.
The evidence for effectiveness in adults is strongest for brief multicontact interventions. The effect sizes for these interventions were greater than those for other intensities (although CIs often overlapped). In addition, the best studies show that the effect of brief multicontact interventions remains for several years35,36,43 and also show improvement for some utilization outcomes, such as fewer hospital days35,36 and costs (benefit–cost ratio of 39:1 over 48 months [CI, 5.4 to 72.5])36.
The brief multicontact interventions generally lasted 10 to 15 minutes per contact. All of the brief multicontact interventions in our meta-analyses of behavioral outcomes at 12 months were delivered by primary care providers, sometimes with additional intervention from a nurse or health educator. For example, the intervention in Project TrEAT (Trial for Early Alcohol Treatment)33 included two 15-minute visits with a primary care provider 1 month apart and two 5-minute follow-up phone calls from a nurse 2 weeks after each visit. The intervention also included feedback about health behaviors, a review of problem drinking prevalence, a list of the adverse effects of alcohol, a worksheet on drinking cues, a drinking agreement or prescription, and drinking diary cards. Of note, 2 studies of brief multicontact interventions in adults, both of which provided insufficient data for our meta-analyses, reported benefits of interventions delivered primarily by nurses51 or by nurses and physician assistants53 for some consumption outcomes.
Evidence suggests that very brief interventions (up to 5 minutes, single-contact) and brief interventions (up to 15 minutes, single-contact) are less effective or ineffective, depending on the outcome. Although extended multicontact interventions seem to be effective for improving intermediate outcomes, we found no evidence that they are more effective than brief multicontact interventions.
The only included study that enrolled pregnant women (250 participants)30 found no difference in reduced consumption between groups but did find higher rates of continued abstinence among women who were abstinent before the assessment in the intervention group than among those in the control group. Our searches identified other studies focusing on pregnant women that did not meet our inclusion criteria67-84. Several took place in such settings as jails or specialized drug and alcohol treatment centers75, and others lacked a control group or followed participants for fewer than 6 months73,84. Several of these studies reported benefits of interventions, including reduced consumption73,84, reduced risk for an alcohol-exposed pregnancy75, higher rates of abstinence79, and better fetal and newborn outcomes (higher birth weights and lengths and reduced fetal mortality rates79).
We have described several categories of alcohol misuse (such as risky or hazardous use and alcohol dependence). These categories are not all discrete (an individual may meet the definition of more than one). Included trials generally enrolled participants with risky or hazardous drinking, but the trials used varying terminology to describe the populations and often enrolled heterogeneous samples. Nevertheless, most investigators excluded participants with alcohol dependence or constructed their inclusion and exclusion criteria to substantially limit the number of such participants. Our best assessment is that our overall findings apply to risky or hazardous drinkers but not to persons with alcohol dependence. It is uncertain whether our findings apply to harmful drinkers or persons with alcohol abuse.
All interventions required support systems to provide screening; screening-related assessment; and in some cases, provider prompting. Screening assessments were often multistep processes that included interviews with research personnel that lasted up to 30 minutes. Less time would be required for screening and screening-related assessments in primary care practice. We estimate that 5 to 10 minutes would be required for persons who had positive screening results, with most of the time used to assess whether such persons have alcohol abuse or dependence (and should probably be referred for specialized treatment) as opposed to risky or hazardous drinking (for which behavioral counseling interventions in primary care may be effective). Nevertheless, support systems are probably required for effective screening and intervention. In addition, most interventions required training providers or staff.
It is unclear whether our findings apply to persons with certain comorbid conditions, and some researchers have suggested that brief behavioral interventions may be ineffective or less effective in people with comorbid psychiatric conditions. A subgroup analysis from a German study56 found that brief interventions did not reduce drinking among 88 participants with comorbid anxiety or depression. Although most trials in our review did not exclude persons with depression, anxiety, or chronic pain, it is unclear how many participants with these conditions were included in most trials.
A previous systematic review85 found no evidence of efficacy for brief behavioral interventions in patients with alcohol dependence in primary care settings. Our review also found no such evidence. Included studies that enrolled more than 10% of participants with alcohol dependence reported interventions to be less effective or ineffective than studies that did not enroll alcohol-dependent participants.
Screening for alcohol misuse will inevitably identify some alcohol-dependent individuals; thus, providers and those making recommendations need information about whether effective interventions are available for alcohol dependence. If complete abstinence is used as an outcome, 15% to 35% of patients have been reported to achieve 1 year of sobriety after such treatment approaches86 as pharmacotherapy, motivational enhancement therapy, cognitive behavioral therapy, 12-step facilitation, and therapy at alcoholism-treatment centers. Similar sobriety outcomes at 3 to 5 years or longer have been reported9.
Our review has limitations. First, the scope of our review was limited to primary care settings. Second, most evidence involved self-report of alcohol use. Investigators in some trials verified self-reported use with other persons (such as family members). Self-report of alcohol use has been found to be accurate if collected carefully87,88. Third, the assessments conducted in the included trials could have concealed benefits of interventions (and biased results toward the null) by causing behavior changes. Control participants generally reduced alcohol consumption. Possible explanations include increased awareness of drinking, discussions with their provider about drinking that were prompted by the screening questions, receipt of some minimal intervention (control groups in the included studies often received some printed educational materials), or regression to the mean. A recent systematic review89 concluded that answering questions on drinking in brief intervention trials seems to alter subsequent self-reported behavior, potentially generating bias by exposing nonintervention control groups to an integral component of the intervention. Finally, publication bias and selective reporting may be present.
In conclusion, behavioral counseling interventions improve intermediate outcomes, such as alcohol consumption, heavy drinking episodes, and drinking above recommended amounts (moderate SOE) and may reduce hospital days (low SOE) for adults with risky or hazardous drinking. For most health outcomes, available evidence found no difference between intervention and control groups, such as for mortality (low SOE), or was insufficient to draw conclusions about the effectiveness of behavioral interventions, such as for alcohol-related accidents or quality of life (insufficient SOE). Brief multicontact interventions (about 10 to 15 minutes per contact) have the best evidence of effectiveness for adults.
Source: This article was first published in Annals of Internal Medicine (Ann Intern Med 2012).
Grant Support: By AHRQ, contract 290-2007-10056-I.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-1085.
Requests for Single Reprints: Daniel E. Jonas, MD, MPH, University of North Carolina at Chapel Hill, Department of Medicine, 5034 Old
Clinic Building, CB 7110, Chapel Hill, NC 27599; e-mail, daniel_jonas@med.unc.edu.
Current author addresses and author contributions are available at http://www.annals.org.
AHRQ Publication No. 12-05171-EF-3
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Text Description
The figure displays three forest plots of studies reporting the following 12-month outcomes in adults: change in alcohol consumption from baseline, number of heavy drinking episodes, and achieving recommended drinking limits. Next to each forest plot is its corresponding data, with a row for the results of each study and a pooled result from meta-analysis of all relevant trials. In addition, the analysis is stratified by the intensity of the intervention (very brief, brief, brief multicontact, and extended multicontact). The data displayed are the difference in means of: 1) drinks per week consumed, 2) number of adults who achieved recommended drinking limits, and 3) number of adults with no heavy drinking episodes in behavioral counseling intervention groups versus control groups. Adults who received counseling interventions drank less, complied more with recommended drinking limits, and had less heavy drinking episodes at 12-month followup compared with those who were in the control groups.
Term | Definition |
---|---|
Risky or hazardous use5 | Consumption of alcohol above recommended daily, weekly, or per occasion amounts. Consumption levels that increase the risk for health consequences. |
Harmful use10,11 | A pattern of drinking that is already causing damage to health. The damage may be either physical (e.g., liver damage from chronic drinking) or mental (e.g., depressive episodes secondary to drinking). |
Alcohol abuse12 | A maladaptive pattern of alcohol use leading to clinically significant impairment or distress, as manifested by ≥1 of the following within a 12-mo period:
|
Alcohol dependence (alcoholism, alcohol addiction)12 | A maladaptive pattern of alcohol use leading to clinically significant impairment or distress, as manifested by ≥3 of the following at any time in the same 12-mo period:
|
Population | Mean Consumption† | Heavy Drinking Episodes‡ | Recommended Drinking Limits | |||
---|---|---|---|---|---|---|
Results | Strength of Evidence | Results | Strength of Evidence | Results | Strength of Evidence | |
Adults | 3.6 fewer drinks/wk (95% CI, 2.4–4.8 drinks/wk); 10 trials; 4332 participants | Moderate | 12% fewer participants reported heavy drinking episodes (CI, 7%–16%); 7 trials; 2737 participants | Moderate | Achieved by 11% more participants (CI, 8%–13%); 9 trials; 5973 participants | Moderate |
Older adults | 1.7 fewer drinks/wk (CI, 0.6–2.8 drinks/wk); 2 trials; 776 participants | Moderate | - | Insufficient | Achieved by 9% more participants (CI, 2%–16%); 2 trials, 776 participants | Low |
Young adults/college students | 1.7 fewer drinks/wk (CI, 0.7–2.6 drinks/wk); 3 trials; 1421 participants§ | Moderate | 0.9 fewer heavy drinking days per month (CI, 0.3–1.5 fewer); 3 trials; 1448 participants§a | Moderate | - | Insufficient |
Pregnant women | Data from 1 study found no difference | Low | - | Insufficient | - | Insufficient |
Adolescents | - | Insufficient | - | Insufficient | - | Insufficien |
* All outcomes are 12-mo unless indicated. All percentages are absolute risk differences from our meta-analyses.
† Baseline consumption, adults: mean, about 23 drinks/wk; median, about 19 drinks/wk; range, 8–62 drinks/wk (data from 16 trials). Baseline consumption, older adults: 15.2–16.6 drinks/wk (data from 2 trials). Baseline consumption, young adults/college students: mean, about 15 drinks/wk; median, about 17 drinks/wk; range, 8–18 drinks/wk (2 of the 5 trials did not report).
‡ Generally defined as consumption of ≥5 standard drinks for men and ≥4 for women.
§ These data are 6-mo outcomes. For consumption for young adults, we could not calculate pooled point estimates for 12-mo data but the range of reduction was 1.2– 4.1 drinks/wk at 12 mo (moderate strength); for heavy drinking days for young adults, differences were not statistically significant at 12 mo (low strength).
a Baseline heavy drinking days for young adults/college students, about 6–7 heavy drinking days over the past month.
Outcomes | Adults | Older Adults | Young Adults/College Students | |||
---|---|---|---|---|---|---|
Results | Strength of Evidence | Strength of Evidence | Results | Strength of Evidence | ||
Health outcomes | ||||||
Mortality | Rate ratio, 0.64 (95% CI, 0.24 to 1.7); 4 trials; 2006 participants† | Low | Insufficient | 1 death reported in a control group | Insufficient | |
Alcohol-related accidents‡ | Insufficient | Insufficient | Fewer motor vehicle crashes with nonfatal injuries (9 vs. 20 crashes; P < 0.05) and fewer total motor vehicle events (114 vs. 149 events; P < 0.05) after 48 mo§ | Low | ||
Alcohol-related liver problems | Insufficient | Insufficient | Insufficient | |||
Utilization outcomes | ||||||
Hospitalization | Fewer hospital days in the past 6 mo at 6, 12, and 48 mo: 35 vs. 180 d, 91 vs. 146 d, and 420 vs. 664 d, respectively; all P < 0.05§ | Low | Insufficient | Fewer hospital days but no statistically significant difference (131 vs. 150 d; P = NS)§ | Low | |
Emergency visits | No statistically significant differencea | Low | Insufficient | Fewer emergency department visits (103 vs. 177 visits; P < 0.01)§ | Low | |
Primary care visits | No significant difference (weighted mean difference, −0.14 visits [CI, −0.5 to 0.2 visits]; 4 trials; 946 participants) | Low | Insufficient | Insufficient | ||
Other outcomes | ||||||
Academic problems | - | - | - | Fewer consequences related to academic role expectations: rate ratio between 0.70 and 0.80¶ | Moderate | |
Legal problems** | No significant difference over 48 mo for most legal problems but fewer controlled substance/liquor violations (2 vs. 11 violations; P < 0.05)§ | Low | Insufficient | No significant difference for most legal problems but fewer controlled substance/liquor violations (0 vs. 8 violations; P < 0.01)§ | Low | |
Quality of life | No difference found in 3 trials (353 participants) | Low | Insufficient | Insufficient |
* Data are reported for 12-mo outcomes unless otherwise noted.
† A meta-analysis that combined all age groups (adults, older adults, and young adults/college students) also found no statistically significant reduction in mortality (rate ratio, 0.52 [CI, 0.22 to 1.2]; 6 trials; 2255 participants), although point estimates trended toward favoring behavioral interventions. Few trials reported mortality, additional studies would be needed to increase precision, and few long-term data are available.
‡ “Accidents” indicates motor vehicle events and injuries.
§These data are from Project TrEAT (Trial for Early Alcohol Treatment)35,35,36, the best available evidence. The data for young adults are from Project TrEAT subgroup analyses (226 participants).
a Results trended in favor of the intervention group at 6, 12, and 48 mo: 47 vs. 70 visits (P < 0.10), 60 vs. 62 visits (P > 0.10), and 302 vs. 376 visits (P < 0.10), respectively33,35,36.
¶ Evidence from 2 trials (576 and 104 participants) conducted in New Zealand.
** Includes assault, battery, or child abuse; resisting or obstructing an officer or disorderly conduct; criminal or property damage; theft or robbery; and other arrests.
1. What is the direct evidence that screening for alcohol misuse followed by a behavioral counseling intervention, with or without referral, leads to reduced morbidity (e.g., alcohol-related morbidity or alcohol-related accidents and injuries), reduced mortality, or changes in other long-term (≥6 mo) outcomes (e.g., health care utilization, sick days, costs, legal issues, or employment stability)?
2. How do specific screening modalities compare with one another for detecting alcohol misuse?
3. What adverse effects are associated with screening for alcohol misuse and screening-related assessment?
4a. How do behavioral counseling interventions, with or without referral, compare with usual care for improving intermediate outcomes (e.g., change in mean number of drinks per drinking day or heavy drinking episodes) for people with alcohol misuse as identified by screening?
4b. How do specific behavioral counseling approaches, with or without referral, compare with one another for improving intermediate outcomes for people with alcohol misuse as identified by screening?
5. What adverse effects are associated with behavioral counseling interventions, with or without referral, for people with alcohol misuse as identified by screening?
6. How do behavioral counseling interventions, with or without referral, compare with one another and with usual care for reducing morbidity (e.g., alcohol-related morbidity or alcohol-related accidents and injuries), reducing mortality, or changing other long-term (≥6 mo) outcomes (e.g., health care utilization, sick days, costs, legal issues, or employment stability) for people with alcohol misuse as identified by screening?
7. To what extent do health care system influences promote or hinder effective screening and interventions for alcohol misuse?
Definitions of the Grades of Overall Strength of Evidence28
Grade | Definition |
---|---|
High | High confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence in the estimate of effect. |
Moderate | Moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of the effect and may change the estimate. |
Low | Low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the estimate of the effect and is likely to change the estimate. |
Insufficient | Evidence either is unavailable or does not permit estimation of an effect. |
Study | Participants (Alcohol-Dependent), n (%) | Duration, mo | Country or State | Setting | Mean Age, y* | Women, %* | Nonwhite, %* | Baseline Alcohol Consumption, drinks/wk* | Quality |
---|---|---|---|---|---|---|---|---|---|
Adults | |||||||||
Anderson and Scott, 199229 | 154 (NR) | 12 | United Kingdom | 8 PC group practices | 43-45.1 | 0 | NR | 37.9-38.8 | Fair |
WHO Brief Intervention Study Group, 199663 | 1559 (0) | 9 | 8, including United States | Outpatient medical settings | 35.9-36.9 | 19.2 | NR | NR | Fair |
Bischof et al, 200855; Grothues et al, 200856; and Reinhardt et al, 200857 | 408 (30.4) | 12 | Germany | 85 general practices | 35.9-36.8 | 31.9 | NR | 21-25.2 | Fair |
Curry et al, 200331 | 307 (NR) | 12 | Washington | 23 PCPs in an HMO and an urban clinic | 47 | 35 | 20 | 14.2 | Fair |
Fleming et al, 199733; Fleming et al, 200035; Fleming et al, 200236; Grossberg et al, 200437; and Manwell et al, 200039 | 774 (NR)† | 48 | Wisconsin | 17 community PC practices | NR‡ | 38 | 5.6-11.9 | 18.9-19.1 | Good |
Fleming et al, 200851, and Wilton et al, 200954 | 235 (NR) | 6 | Wisconsin | 34 obstetric practices | Median, 28 | 100 | 18.3 | 8-8.5 | Good |
Lock et al, 200652 | 127 (0) | 12 | United Kingdom | General practices | 44.1 | 50 | NR | 23-26.48 | Fair |
Maisto et al, 200160,61 and Gordon et al, 200359 | 301 (NR) | 12 | Pennsylvania | 12 PC clinics | 45.6 | 30.2 | 23.3 | 15.5-18.6 | Fair |
Noknoy et al, 201053 | 117 (13.8-15.3)§ | 6 | Thailand | Rural PC units | 37 | 8.5 | 100 (Thai) | 15.15 | Fair |
Ockene et al, 199942; Ockene et al, 200943; and Reiff-Hekking et al, 200544 | 530 (2) | 48 | Massachusetts | 4 PC sites (93 clinicians) | 43.5-44.2 | 32.1-38.7 | 4.3-6.6 | 16.6-18.9 | Fair |
Richmond et al, 199545 | 378 (35)|| | 12 | Australia | 40 PC practices | 37.7 | 43 | NR | 38.5 | Fair |
Rubio et al, 201046 | 752 (0) | 12 | Spain | 20 PC centers in Madrid | NR; >70% were 31-40 | 34.7 | NR | 26.90-27.40 | Fair |
Saitz et al, 200347 | 312 (NR) | 6 | Massachusetts | Urban academic PC practice | 42.2-43.7 | 29-43 | 80-82 | Mean, 5.5-5.6 drinks/drinking day | Fair |
Scott and Anderson, 199149 | 72 (NR) | 12 | United Kingdom | 8 PC group practices | 44.4-47.2 | 100 | NR | 25.8-26.7 | Fair |
Freeborn et al, 200058, and Senft et al, 199762 | 516 (0) | 24 | Oregon | 3 PC clinics in an HMO | 41.9-43 | 28.1-31.1 | 17.4-18.7 | 16.5 | Fair |
Wallace et al, 198850 | 909 (NR) | 12 | United Kingdom | 47 group practices | 41.7-44.6 | 29.1-29.8 | NR | 35.1 (women) and 62.2 (men) | Fair |
Older adults | |||||||||
Fleming et al, 199934, and Mundt et al, 200541 | 158 (0) | 24 | Wisconsin | 24 PC practices | NR; >92% were 65-75 | 33.5 | NR | 15.5-16.6 | Fair |
Lin et al, 201038, and Moore et al, 201140 | 631 (NR) | 12 | California | PC practices (145 PCPs) | 68.4 | 29 | 13 | 15.2 | Fair |
Young adults/college students | |||||||||
Fleming et al, 201032 | 986 (0) | 12 | United States and Canada | 5 college health clinics | 21 | 50.5-51.3 | 8.1-10.5 | 17.3-17.8 | Good |
Grossberg et al, 200437 | 226 (NR)¶ | 48 | Wisconsin | 17 community PC practices | NR** | 51 | 14 | 16.2-18.3 | Good |
Kypri et al, 200764, and Kypri et al, 200865 | 576 (NR) | 12 | New Zealand | University primary health care service | 20.1-20.3 | 52 | NR | NR | Good |
Kypri et al, 200466 | 104 (NR) | 6 | New Zealand | University student health service | 19.99-20.4 | 50 | NR | NR | Fair |
Schaus et al, 200948 | 363 (0) | 12 | Florida | College student health center | 20.6 | 52 | 22 | 8.4-9.6 | Fair |
Pregnant women | |||||||||
Chang et al, 199930 | 250 (0 current)†† | About 6 | Massachusetts | Obstetric practices | 30.7 | 100 | 22 | Mean, 0.6-0.9 drinks per drinking day‡‡ | Fair |
NR = not reported/unclear; PC = primary care; PCP = primary care physician; TrEAT = Trial for Early Alcohol Treatment; WHO = World Health Organization.
* When data were not reported for the total sample but were presented for each study group, the range of the means for the various study groups are reported.
† According to a medical record audit, 6 participants received formal alcohol treatment during the 1-y follow-up period; those 6 may ultimately have received a diagnosis of alcohol dependence.
‡ Group 1, men: age 18-30 y, 20.2%; 31-40 y, 27.2%; 41-50 y, 23.9%; 51-65 y, 28.8%. Group 1, women: age 18-30 y, 43.5%; 31-40 y, 25.9%; 41-50 y, 15.6%; 51-65 y, 15.0%. Group 2, men: age 18-30 y, 26.0%; 31-40 y, 25.1%; 41-50 y, 21.3%; 51-65 y, 27.7%. Group 2, women: age 18-30 y, 35.7%; 31-40 y, 35.7%; 41-50 y, 18.2%; 51-65 y, 10.5%.
§ Based on an Alcohol Use Disorders Identification Test score >25.
|| Percentage with moderate physical dependence based on the physical dependence score from the Comprehensive Drinker Profile. The study excluded participants with evidence of severe alcohol dependence (physical dependence score >10) or those with severe levels of alcohol-related problems (Michigan Alcohol Screening Test score >20).
¶ In this subgroup analysis of TrEAT33, 226 of 774 enrolled participants were young adults (aged 18 to 30 y).
** Age 18-21 y, 21%; 22-25 y, 37%; and 26-30 y, 47%.
†† None of the 250 participants satisfied Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria for current alcohol abuse or dependence at enrollment; however, 40% satisfied criteria for lifetime alcohol abuse or dependence (not reported separately) and 3 participants had been treated for an alcohol problem.
‡‡ While pregnant, including abstainers. The reported mean excluding abstainers was 1.5-2.1 drinks/drinking day while pregnant.
Population and Type of Intervention | Study, Year (Reference) | Intervention | Delivery By | Delivery Method | Contacts, n | Length of Each Contact |
---|---|---|---|---|---|---|
Adults | ||||||
Very brief | Richmond et al, 199545 | Group 2: Physician advice and a self-help manual (after assessment) | PCP | In person | 1 | 5 min |
WHO Brief Intervention Study Group, 199663 | Group 1: Advice and an illustrated pamphlet | Various clinic staff | In person | 1 | 5 min | |
Brief | Anderson and Scott, 199229 | Brief advice, feedback about own consumption and norms, and a self-help booklet | PCP | In person | 1 | 10 min |
Lock et al, 200652 | Brief advice (drink-less protocol) on standard drink units, recommended consumption levels, benefits of cutting down, tips on reducing consumption, advice on goal-setting, action plan, and self-help booklet/diary | Nurse or PA | In person | 1 | 5-10 min | |
Maisto et al, 200160,61, and Gordon et al, 200359 | Brief advice that emphasized feedback from baseline results and implications for drinking, coupled with advice about a goal to reduce or stop alcohol consumption | Research staff | In person | 1 | 10-15 min | |
Scott and Anderson, 199149 | Brief advice, feedback about own consumption and norms, and a self-help booklet | PCP | In person | 1 | 10 min | |
Freeborn et al, 200058, and Senft et al, 199762 | 30-s message from PCP and 15-min session with health counselor immediately after PCP visit | PCP and study health counselor | In person | 1 | About 15 min | |
WHO Brief Intervention Study Group, 199663 | Group 2: Brief intervention and 30-page, illustrated problem-solving manual | Various clinic staff | In person | 1 | 15 min | |
Brief multicontact | Curry et al, 200331 | Brief motivational message from PCP during regularly scheduled visit, self-help manual, written personalized feedback, and ≤3 outreach phone counseling calls from health educator | PCP and research health educator | In person and phone | Up to 4 | 1-5 min PCP; mean for phone calls, 14 min |
Fleming et al, 199733; Fleming et al, 200035; Fleming et al, 200236; Grossberg et al, 200437; and Manwell et al, 200039 | Two visits with PCP, 1 mo apart, and a follow-up phone call from the clinic nurse 2 wk after each visit; workbook containing feedback about current health behaviors, review of prevalence of problem drinking, list of adverse effects of alcohol, worksheet on drinking cues, drinking agreement or prescription, and drinking diary cards | PCP and nurse | In person and phone | 4 | 15 min for PCP contacts; NR for phone calls | |
Fleming et al, 200851, and Wilton et al, 200954 | Two visits, each with phone follow-up, and a workbook containing scripted messages with feedback about current health behaviors, prevalence of problem drinking, list of adverse effects of alcohol focused on women and pregnancy, worksheet on drinking cues, drinking agreement in the form of a prescription, and drinking diary cards | Nurse (90%) or obstetrician | In person and phone | 4 | 15 min for in-person contacts; NR for phone calls | |
Noknoy et al, 201053 | Motivational enhancement protocol: Brief counseling sessions that used a patient-centered interviewing style and considered stages of change | Nurse or PA | In person | 3 | 15 min | |
Ockene et al, 199942; Ockene et al, 200943; and Reiff-Hekking et al, 200544 | Tailored consultation with a clinician plus follow-up visit, counseling (entailed talking about number of drinks/wk, heavy drinking episodes, or both), patient alcohol consumption info and education materials attached to the patient's chart by research assistants at regular office visit, and receipt of a health booklet at enrollment | PCP | In person | 2 | 5-10 min | |
Rubio et al, 201046 | Brief advice given by using an intervention workbook containing a review of alcohol-related health effects, a pie chart displaying frequency of types of at-risk drinkers, list of methods for cutting down, a treatment contract, and cognitive behavioral exercises; phone reinforcement by a nurse; and a general health booklet | PCP | In person | 2 | 10-15 min | |
Wallace et al, 198850 | Brief advice, an information booklet ("That's the Limit"), sex-based recommendations for limiting drinking, a drinking diary, and follow-up sessions | PCP | In person | 1 to 5* | NR† | |
Extended multicontact | Bischof et al, 200855 | Group 1 (full care) comprised immediate computerized postassessment feedback and multiple sessions of counseling by a psychologist
Group 2 (stepped care) comprised immediate computerized postassessment feedback and a maximum of 3 counseling sessions with a psychologist; sessions were discontinued if patients indicated consumption below study criteria and high self-efficacy to maintain desired behavior |
Trained psychologists from research team
|
Phone
|
4
Up to 4 |
Scheduled for 30 min each; mean received, 80.3 min
|
Richmond et al, 199545 | Group 1 (the Alcoholscreen program) comprised 5 short consultations (introduction, patient education, 3 follow-ups) designed to reduce drinking to recommended limits and included a self-help manual, daily alcohol diary, and personalized patient education and counseling | PCP | In person | 5 | 15-20 min (initial); 5-25 min (follow-ups) | |
Maisto et al, 20016061, and Gordon et al, 200359 | Motivational enhancement: longer, main initial session; 2 shorter booster sessions; use of empathy and other techniques to enhance motivation; focus on feedback of assessment data and setting alcohol-use goals | Research staff | In person | 3 | 30-45 min (main); 15-20 min (boosters) | |
Not reported or unknown | Saitz et al, 200347 | Providing physicians with positive alcohol screening results and specific recommendations for their patients at a visit | PCP | In person | NR/unknown‡ | NR/unknown‡ |
Older adults | ||||||
Brief multicontact | Fleming et al, 199934, and Mundt et al, 200541 | General health booklet plus drinking behavior feedback (workbook), review of problem-drinking prevalence, reasons for drinking, adverse effects of alcohol, drinking cues, a "prescribed" drinking agreement, and drinking diary cards | PCP and nurse | In person and phone | 4 | 10-15 min for PCP contacts; NR for phone calls |
Extended multicontact |
Lin et al, 201038, and Moore et al, 201140 | Personalized risk report and diary for tracking alcohol use; PCP gave oral and written advice in prescription style via an alcohol education booklet, followed by additional feedback and counseling with motivational interviewing from a health educator at weeks 2, 4, and 8 | PCP and health educator | In person and phone | 4 | 15-20 min |
Young adults/college students | ||||||
Brief | Kypri et al, 200764, and Kypri et al, 200865 | Web-based assessment and personalized feedback on drinking | Self | Computer | 1 | 10-15 min |
Kypri et al, 200466 | Web-based assessment and personalized feedback on drinking | Self | Computer | 1 | 10-15 min | |
Brief multicontact | Fleming et al, 201032 | Two visits 1 month apart with PCP and a follow-up phone call or e-mail from the PCP after each visit, feedback about current behaviors, review of prevalence of high-risk drinking among college students, list of alcohol's adverse consequences relevant to college students, lists of personal likes and dislikes of drinking, worksheets on drinking cues, BAC level calculator, life goals and alcohol effects, prescription agreement, and drinking diary cards | PCP | In person | 4 | 15 min |
Grossberg et al, 200437 | Subgroup analysis of young adults enrolled in Project TrEAT (Fleming et al, 199733 | PCP and nurse | In person | 4 | 15 min | |
Kypri et al, 200764, and Kypri et al, 200466 | Web-based assessment and personalized feedback on drinking | Self | Computer | 3 | 10-15 min | |
Extended multicontact |
Schaus et al, 200948 | Motivational intervention sessions that combined patient-centered motivational interviewing and cognitive-behavioral skills training plus a booklet on alcohol prevention | PCP | In person | 2 | 20 min |
Pregnant women | ||||||
Extended | Chang et al, 199930 | Review of lifestyle changes made since pregnancy, articulation of drinking goals, identification of circumstances in which participant might be tempted to drink, alternatives to drinking in such situations, take-home manual with tailored notes, and U.S. Surgeon General recommendation | PCP and researcher | In person | 1 | 2-h assessment, 45-min intervention |
BAC = blood alcohol content; NR = not reported; PA = physician assistant; PCP = primary care physician; TrEAT = Trial for Early Alcohol Treatment; WHO = World Health Organization.
* All participants received an invitation to a 1-mo follow-up; other follow-up was offered at 4, 7, and 10 mo at the discretion of the practitioner.
† Not reported in the article. Physicians were trained to do "up to 15 minutes," and the author believes sessions were generally 10-15 min (Wallace P, personal communication).
‡ No particular behavioral intervention was required; the intervention was to provide physicians with positive screening results. On the basis of assessment immediately after the visit, some discussion about drinking was reported for 51% (residents) to 74% (faculty) of visits in the intervention group and 70% (residents) and 51% (faculty) in the control group.
Text Description
Appendix Figure 1 is titled “Analytic Framework for Screening, Behavioral Counseling, and Referral in Primary Care to Reduce Alcohol Misuse.” The framework begins on the left with the patient population of interest: adolescents and adults. The following subgroups of interest are specified: college students, older adults (age 65 or older), veterans, pregnant women, racial or ethnic minorities, those with co-occurring mental health or chronic medical conditions, and those with varying severity of alcohol problems. An arrow with the word “screening” goes from the population on the left to a box containing the words “alcohol misuse.” “KQ 2” is also above this arrow, to indicate that the second key question focuses on screening instruments for alcohol misuse. A curvy arrow labeled “KQ 3” descends from the “screening” arrow to an elliptical shape with the words “adverse effects of screening” to illustrate the focus of KQ 3. Another arrow goes from the “alcohol misuse” box to the right to an “intermediate outcomes” box, with the words “intervention” and “KQ 4.” A curvy arrow labeled “KQ 5” descends from this “intervention” arrow to an elliptical shape with the words “adverse effects of intervention” to illustrate the focus of KQ 5. A dashed line to the right connects the “intermediate outcomes” box to a “long-term outcomes” box. The intermediate outcomes include measures of lower-risk alcohol use. The long-term outcomes include all-cause and alcohol-related mortality, alcohol-related morbidity, alcohol-related accidents and injuries, quality of life, health care utilization, sick days, costs, legal issues, and employment stability. KQ 1 is depicted by an overarching arrow that goes all the way from the “screening” arrow on the left to the “long-term outcomes” box. The focus of KQ 6 is depicted by an overarching arrow that goes from the “intervention” arrow to the “long-term outcomes.” A diamond-shaped kite containing the words “health care system influences” is located near the top of the figure and is connected to the screening and intervention arrows with dashed lines to illustrate the focus of KQ 7.
Text Description
Appendix Figure 2 is titled “Summary of Evidence Search and Selection.” The figure is a flow chart that summarizes the search and selection of articles. There were 8,993 citations of randomized trials identified by searching MEDLINE, Embase, the Cochrane Library, CINAHL, PsycINFO, and the International Pharmaceutical Abstracts databases. In addition, 227 references were identified by searching reference lists of selected articles, and 216 articles were identified by a search of the clinicaltrials.gov database. After removal of duplicate citations, titles and abstracts of 6,277 records were screened for potential inclusion. Of these, 718 were deemed appropriate for full-text review to determine eligibility. After full-text review, 680 were excluded: 9 were in a language other than English; 201 were the wrong type of publication; 454 failed to meet eligibility criteria; 10 were deemed poor quality; and 6 were systematic reviews older than 5 years. Thirty-eight articles representing 23 trials were included in this report’s qualitative synthesis and 19 trials were included in quantitative analyses.