Evelyn P. Whitlock

Screening for Colorectal Cancer: A Targeted, Updated Systematic Review for the U.S. Preventive Services Task Force

Colorectal cancer ranks third in incidence and second in cause of cancer death for both men and women (1). Most cases of colorectal cancer occur in average-risk individuals (those without a family or predisposing medical history), and increasing age, male sex, and black race are associated with increased incidence (2). Black persons have the highest incidence of and mortality rates from colorectal cancer among all racial and ethnic subgroups (37) and nearly double the colorectal cancerrelated mortality rate compared with other ethnic minorities (8). Colorectal cancer screening has been recommended by the U.S. Preventive Services Task Force (USPSTF) and many other organizations for more than 10 years (9). On the basis of evidence from multiple randomized, controlled trials (RCTs), a screening program with repeated annual or biennial guaiac fecal occult blood tests (FOBTs) and endoscopic follow-up of positive test results reduces colorectal cancer mortality; according to a recent update, colorectal cancer mortality was reduced 16% (CI, 10% to 22%) after 12 to 18 years (10). Extrapolating from trial evidence, clinical studies of test accuracy, and other supporting evidence, the USPSTF recognized flexible sigmoidoscopy (with or without FOBTs), colonoscopy, and double-contrast barium enema as other colorectal cancer screening options in 2002 (11, 12). However, because colorectal cancer screening tests have potential harms, limited accessibility, or imperfect acceptability to patients, and no tests could be identified as superior in cost-effectiveness analysis (13), the USPSTF also recommended that choice among recommended methods for colorectal cancer screening to be individualized to patients or practice settings (14). Despite strong recommendations from the USPSTF and many others, serial national surveys document inadequate, slowly improving rates of colorectal cancer screening in the United States (1520). In 2006, 60.8% of adults 50 years of age or older reported recent colorectal screening (20). Disparities in colorectal cancer screening exist, with lower rates of colorectal cancer screening in nonwhite and Hispanic populations (16, 21, 22) and in areas with higher poverty rates (23). To increase the uptake of and benefits from recommended colorectal cancer screening, researchers have sought to improve the accuracy, acceptability, or accessibility of screening by introducing new tests or enhancing existing tests. However, the availability of additional options for colorectal cancer screeningincluding highly sensitive guaiac FOBT; fecal immunochemical testing; fecal DNA testing; and virtual colonoscopy approaches, such as computed tomographic (CT) colonographyhas created uncertainty about what methods should be used for colorectal cancer screening in the general population. To assist the USPSTF in updating its 2002 recommendation for colorectal cancer screening in average-risk adults age 50 years or older, we conducted a targeted systematic review primarily focused on evidence gaps or new evidence since the previous review. This approach updated what the USPSTF judged was the most important evidence for newer colorectal cancer screening tests and community-performed endoscopies, and it was supplemented by a companion decision analysis examining screening program performance and life-years gained by using different colorectal cancer screening tests, test intervals, and starting and stopping ages (24). Methods Under guidance from the USPSTF, this targeted review addressed only the first 3 questions of the full evidence chain in the analytic framework (Figure 1). From our larger report (25), we report here the accuracy (one-time test performance characteristics) and potential harms of newer colorectal cancer screening tests (high-sensitivity FOBTs, fecal immunochemical tests, fecal DNA testing, and CT colonography) in screening populations (key questions 2b and 3b) and the accuracy and harms of screening colonoscopy and flexible sigmoidoscopy in the community setting (key questions 2a and 3a). In the full report, we discuss lack of new data on the mortality benefits of colorectal cancer screening beyond FOBT programs (key question 1); race-, sex-, and age-related issues in colorectal cancer screening; considerations of targeted screening recommendations; and suggested future research. Detailed methods are provided in the Appendix and Appendix Tables 1, 2, and 3 and in the full report (25). Figure 1. Analytic framework and key questions ( KQs ). KQ1: What is the effectiveness of the following screening methods (alone or in combination) in reducing mortality from colorectal cancer? a. Flexible sigmoidoscopy, b. Colonoscopy, c. Computed tomographic (CT) colonography, d. Fecal screening tests: i. High-sensitivity guaiac fecal occult blood test (FOBTs); ii. Fecal immunochemical test; iii. Fecal DNA test. KQ2a: What are the sensitivity and specificity of 1) colonoscopy and 2) flexible sigmoidoscopy when used to screen for colorectal cancer in the community practice setting? KQ2b: What are the test performance characteristics of 1) CT colonography and 2) fecal screening tests (as listed in KQ1d) for colorectal cancer screening, as compared to an acceptable reference standard? KQ3a: What are age-specific rates of harm from colonoscopy and flexible sigmoidoscopy in the community practice setting? KQ3b: What are the adverse effects of newer tests, including 1) CT colonography and 2) fecal screening tests (as listed in KQ1d)? Appendix Table 1. Eligibility Criteria for Studies, by Key Question Appendix Table 2. U.S. Preventive Services Task Force Design-Specific Quality Rating Criteria Appendix Table 3. SAS Code for the Meta-Analysis of Serious Complications Searches and Selection Process In brief, we searched PubMed; Database of Abstracts of Reviews of Effects; Cochrane Database of Systematic Reviews; and the Institute of Medicine, National Institute for Health and Clinical Effectiveness, and Health Technology Assessment databases for recent systematic reviews (19992006) to support our review of all key questions (26). We found 11 existing systematic reviews for newer colorectal cancer screening tests (key question 2b). Using methods detailed in the Appendix, we selected 3 good-quality reviews of CT colonography (27, 28) or fecal DNA testing (29) to locate relevant primary studies; we supplemented these with additional MEDLINE and Cochrane Library searches from January 2006 through January 2008 to locate additional studies published after the end date of the searches. Because there were no good-quality relevant systematic reviews for reports on fecal immunochemical tests (key questions 2b and 3b), we searched MEDLINE and the Cochrane Library (19902008) and from 2000 to 2008 to locate studies of the harms of screening tests (key questions 3a and 3b) since the 2002 report. Abstracts and articles were dual-reviewed against inclusion criteria (Appendix) and required agreement of 2 reviewers. Eligible studies reported on the sensitivity and specificity of colorectal cancer screening tests or on health outcomes. We excluded studies that did not address average-risk populations for colorectal cancer screening, unless an average-risk subgroup was reported. We excluded casecontrol studies of screening accuracy because these may overestimate sensitivity as a design-related source of bias (30), as recently demonstrated for FOBTs (31). To avoid biases related to reference standards, we excluded studies of test accuracy that incompletely applied a valid reference standard or used an inadequate reference standard (32). For CT colonography, we considered only technologies that were compared with colonoscopy in average-risk populations, used a multidetector scanner (27), and reported per-patient sensitivity and specificity. In all, we evaluated 3948 abstracts and 490 full-text articles (Figure 2). Figure 2. Study selection. KQ= key question; SER= standardized evidence review. For list of key questions, see legend for Figure 1. Quality Assessment and Data Abstraction Two investigators critically appraised and quality-rated all eligible studies by using design-specific USPSTF criteria (33) supplemented by other criteria (Appendix). Poor-quality studies were excluded. One investigator abstracted key elements of included studies into standardized evidence tables. A second reviewer verified these data. We resolved disagreements about data abstraction or quality appraisal by consensus. Evidence tables and tables of excluded studies for each key question are available in the full report (25). Data Synthesis and Analysis We report qualitative synthesis of the results for most key questions because of study heterogeneity. The performance of screening tests is preferentially described per person (sensitivity and specificity), supplemented by per-polyp analyses (miss rates). Sensitivity for large adenomas from 2 similar studies of CT colonography screening was combined by using the inverse variance fixed-effects model because no heterogeneity was detected on the basis of the Cochran Q test and the I 2 statistic (34). Because of the stringency of our inclusion criteria for studies to estimate rates of endoscopy harms in the community practice setting (key question 3a), included studies were clinically homogeneous enough to pool. A random-effects logistic model was used to evaluate statistical heterogeneity, estimate pooled rates, and explore potential sources of variation for complications from study-level characteristics (35, 36). Model details and SAS PROC NLMIXED code are provided in the Appendix. Total serious adverse events required hospital admission (for example, perforation, major bleeding, severe abdominal symptoms, and cardiovascular events) or resulted in death. Results of exploratory analyses for potential sources of variation for pooled estimates are discussed in the full report, along with pooled estimates for individual complications, su

Behavioral Counseling Interventions in Primary Care To Reduce Risky/Harmful Alcohol Use by Adults: A Summary of the Evidence for the U.S. Preventive Services Task Force

Alcohol misuse, including risky and harmful drinking, alcohol abuse, and dependence, is associated with numerous health and social problems and with more than 100 000 deaths per year (1). Risky drinkers consume alcohol above recommended daily, weekly, or per-occasion amounts. Harmful drinkers experience harm associated with their alcohol use but do not meet criteria for alcohol abuse or dependence (2). Persons who misuse alcohol have elevated risks for a host of health problems (3-6), including violence-related trauma and injury (4). Most individuals who consume alcohol do so in moderation and without adverse consequences, however, and observational research suggests light or moderate use may be beneficial for some people (7-20). The assumption underlying brief behavioral counseling interventions in primary care is that, for identified risky or harmful drinkers, reducing overall alcohol consumption or adopting safer drinking patterns (that is, fewer drinks per occasion and not drinking before driving) will reduce the risk for medical, social, and psychological problems (21). Little experimental evidence supports this assumption, and most epidemiologic evidence relates health outcomes to existing drinking behaviors rather than to changes in drinking behaviors. Cross-sectional and cohort studies have consistently related high average alcohol consumption to short- or long-term health consequences (4, 22). A meta-analysis of studies examining the association between all-cause mortality and average alcohol consumption found that men averaging at least 4 drinks per day and women averaging 2 or more drinks per day experienced significantly increased mortality relative to nondrinkers (23). Studies also relate heavy per-occasion alcohol use (binge drinking) to acute injury risks and alcohol-related life problems (4, 22). Injury rates are higher for binge drinkers who consume 5 or more drinks on one occasion as infrequently as 3 to 6 times per year, even when average intake is not excessive (24). In the United States, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has proposed epidemiologically based alcohol use guidelines to limit risks for short- and long-term drinking-related consequences by establishing age- and sex-specific recommended consumption thresholds (25). Maximum recommended consumption is 1 or less standard drink per day for adult women and for anyone older than 65 years of age and 2 or fewer standard drinks per day for adult men. These guidelines do not apply to persons (such as adolescents, pregnant women, and persons with alcohol dependence or medical conditions or medication use) for whom alcohol intake is contraindicated, or to circumstances (driving) in which no consumption is considered safe. Primary care clinicians commonly see patients with a range of alcohol-related risks and problems. In Wisconsin, about 20% of primary care patients were found to exceed NIAAA guidelines and to qualify as risky drinkers (26). Across multiple primary care populations, 4% to 29% are risky drinkers, 0.3% to 10% are harmful drinkers, and 2% to 9% exhibit alcohol dependence (27). Prevalence of these forms of alcohol misuse generally is higher in males and younger persons of all races and ethnicities (28). The NIAAA and others encourage physicians to identify patients with alcohol-related risks or problems and to provide office-based brief interventions or referrals as needed (25, 29, 30). In everyday practice, screening and screening-related assessment procedures are necessary to identify the range of alcohol users in order to offer appropriate treatment (31, 32). Even so, few primary care clinicians use recommended screening protocols or offer treatment (33). To assist the U.S. Preventive Services Task Force (USPSTF) in updating its 1996 recommendation (34), the Oregon Evidence-based Practice Center systematically reviewed the evidence on primary carebased behavioral counseling interventions for risky/harmful alcohol use; systematic evidence reviews and meta-analyses since the last USPSTF report (35-39) did not adequately address the key questions posed by the USPSTF. This review was exempted by the Institutional Review Board at Kaiser Permanente Northwest (FWA 00002344-IRB 00000405). Our review addressed the following questions: Do behavioral counseling interventions in primary care reduce risky or harmful alcohol use? What are elements of effective interventions? Do such interventions improve health outcomes? What methods were used to identify risky/harmful drinkers for behavioral counseling interventions in primary care? What adverse effects are associated with interventions addressing risky/harmful drinkers in primary care? What health care system influences are present in effective interventions for risky and harmful drinkers in primary care? Methods We concentrated our review on the program elements of brief primary care interventions for risky and harmful drinkers and their effects on alcohol use, health outcomes, and intermediate alcohol-related outcomes. Appendix Figure 1 shows the analytic framework and key questions guiding the entire systematic evidence review. Methods not described in this section appear in the Appendix, Appendix Figures 2 and 3, and Appendix Table 1. Appendix Figure 1. Analytic framework and key questions ( KQs ). Appendix Figure 2. Literature search and retrieval results. Appendix Figure 3. Risky/harmful alcohol use: quality recheck instrument. Definitions No consistent definitions for the drinking patterns that should be the focus of primary care interventions are available from existing guidelines or research; however, it is commonly held that less severe alcohol problems are appropriate for brief interventions in primary care, whereas more severe problems need specialty addiction treatment (41). We adapted the following definitions from a recent systematic review of primary care screening for alcohol problems (2). Risky or hazardous drinkers are at risk from consumption that exceeds daily, weekly, or per-occasion thresholds (other terms further distinguish risky/harmful users who exceed longer-term thresholdshigh-average or heavy usersfrom heavy occasional or binge drinkers, who exceed per-occasion thresholds). Harmful drinkers experience physical, social, or psychological harm from their above-threshold alcohol use without meeting criteria for dependence. Alcohol-abusing/dependent drinkers continue to use alcohol despite significant negative physical, psychological, and social consequences (42); generally meet criteria for abuse or dependence as outlined in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (43); and are candidates for specialty addiction treatment. Our review focuses on studies oriented toward the risky/hazardous/harmful category, which we refer to as risky/harmful drinkers. Fiellin and colleagues (2) similarly divide the literature on screening instruments for alcohol problems into studies that focus primarily on risky, heavy, or harmful drinking and studies that focus on detecting alcohol abuse or dependence. Among the brief intervention studies targeting risky/harmful drinkers selected for this review, we classified intervention groups into 1 of 3 levels of intensity: 1) very brief interventions had 1 session, up to 5 minutes long; 2) brief interventions had 1 session, up to 15 minutes long; and 3) brief multicontact interventions had an initial session up to 15 minutes long, plus follow-up contacts. We used the definition of primary care recommended by the Institute of Medicine (44) (see Inclusion and Exclusion Criteria in the Appendix) to identify relevant medical settings for our review. Inclusion and Exclusion Criteria We included English-language reports of randomized or nonrandomized, controlled clinical trials of nondependent drinkers 12 years of age or older who received a primary care behavioral counseling intervention primarily to reduce alcohol intake. We excluded studies based in hospitals or emergency departments, specialty addiction treatment settings, behavioral health departments, and schools or community agencies without health clinics. We also excluded studies among comorbid patient populations because of limited generalizability to primary care. We excluded studies rated as having poor quality, as described below. Search Strategy We identified 5 recent systematic reviews addressing primary care brief interventions to reduce risky/harmful alcohol use (35-39) and 3 addressing screening (2, 45, 46) from the Cochrane Database of Systematic Reviews and Database of Research Effectiveness (DARE). Relevant trials were identified from searches of MEDLINE, Cochrane Controlled Clinical Trials, PsycINFO, HealthSTAR, and CINAHL databases (1994 to April 2002), reference lists of systematic reviews, the USPSTF 1996 recommendation (34), and experts. We conducted separate searches in MEDLINE and PsycINFO from 1994 through April 2002 to identify any literature on harms related to alcohol screening, screening-related assessment, or intervention. None was found. The Appendix contains further search strategy details, along with information on our abstract and article review processes. We used USPSTF internal validity criteria (40) (Table 1), supplemented by specific quality criteria addressing study randomization, attrition, and intention-to-treat analyses from the Cochrane Drug and Alcohol Group (CDAG) (47) (Appendix Figure 3), to grade the quality of trials that met inclusion and exclusion criteria. We assigned each studys final quality rating according to investigator team consensus. Minimal to no attrition, nondifferential attrition, and replacement of missing values in the outcome analyses were key features of trials rated good quality. Studies receiving a consensus rating of poor quality (n = 27) were excluded from the review (Appendix Table 2). Major quality problems included nonrandom assignment, noncomparable bas

Screening and interventions for childhood overweight: a summary of evidence for the US Preventive Services Task Force.

Background. Childhood and adolescent overweight and obesity are related to health risks, medical conditions, and increased risk of adult obesity, with its attendant effects on morbidity and mortality rates. The prevalence of childhood overweight and obesity has more than doubled in the past 25 years. Purpose. This evidence synthesis examines the evidence for the benefits and harms of screening and early treatment of overweight among children and adolescents in clinical settings. Methods. We developed an analytic framework and 7 key questions representing the logical evidence connecting screening and weight control interventions with changes in overweight and behavioral, physiologic, and health outcomes in childhood or adulthood. We searched the Cochrane Library from 1996 to April 2004. We searched Medline, PsycINFO, DARE, and CINAHL from 1966 to April 2004. One reviewer abstracted relevant information from each included article into standardized evidence tables, and a second reviewer checked key elements. Two reviewers quality-graded each article with US Preventive Services Task Force criteria. Results. Although BMI is a measure of relative weight rather than adiposity, it is recommended widely for use among children and adolescents to determine overweight and is the currently preferred measure. The risk of adult overweight from childhood overweight provides the best available evidence to judge the clinical validity of BMI as an overweight criterion for children and adolescents. BMI measures in childhood track to adulthood moderately or very well, with stronger tracking seen for children with ≥1 obese parent and children who are more overweight or older. The probability of adult obesity (BMI of >30 kg/m2) is ≥50% among children >13 years of age whose BMI percentiles meet or exceed the 95th percentile for age and gender. BMI-based overweight categorization for individuals, particularly for racial/ethnic minorities with differences in body composition, may have limited validity because BMI measures cannot differentiate between increased weight for height attributable to relatively greater fat-free mass (muscle, bone, and fluids) and that attributable to greater fat. No trials of screening programs to identify and to treat childhood overweight have been reported. Limited research is available on effective, generalizable interventions for overweight children and adolescents that can be conducted in primary care settings or through primary care referrals. Conclusions. BMI measurements of overweight among older adolescents identify those at increased risk of developing adult obesity. Interventions to treat overweight adolescents in clinical settings have not been shown to have clinically significant benefits, and they are not widely available. Screening to categorize overweight among children under age 12 or 13 who are not clearly overweight may not provide reliable risk categorization for adult obesity. Screening in this age group is compromised by the fact that there is little generalizable evidence for primary care interventions. Because existing trials report modest short- to medium-term improvements (∼10–20% decrease in percentage of overweight or a few units of change in BMI), however, overweight improvements among children and adolescents seem possible.

Effectiveness of Weight Management Interventions in Children: A Targeted Systematic Review for the USPSTF

CONTEXT: Targeted systematic review to support the updated US Preventive Services Task Force (USPSTF) recommendation on screening for obesity in children and adolescents. OBJECTIVES: To examine the benefits and harms of behavioral and pharmacologic weight-management interventions for overweight and obese children and adolescents. METHODS: Our data sources were Ovid Medline, PsycINFO, the Education Resources Information Center, the Database of Abstracts of Reviews of Effects, the Cochrane databases, reference lists of other reviews and trials, and expert recommendations. After 2 investigators reviewed 2786 abstracts and 369 articles against inclusion/exclusion criteria, we included 15 fair- to good-quality trials in which the effects of treatment on weight, weight-related comorbidities, and harms were evaluated. Studies were quality rated by 2 investigators using established criteria. Investigators abstracted data into standard evidence tables. RESULTS: In the available research, obese (or overweight) children and adolescents aged 4 to 18 years were enrolled, and no studies targeted those younger than 4 years. Comprehensive behavioral interventions of medium-to-high intensity were the most effective behavioral approach with 1.9 to 3.3 kg/m2 difference favoring intervention groups at 12 months. More limited evidence suggests that these improvements can be maintained over the 12 months after the end of treatments and that there are few harms with behavioral interventions. Two medications combined with behavioral interventions resulted in small (0.85 kg/m2 for orlistat) or moderate (2.6 kg/m2 for sibutramine) BMI reduction in obese adolescents on active medication; however, no studies followed weight changes after medication use ended. Potential adverse effects were greater than for behavioral interventions alone and varied in severity. Only 1 medication (orlistat) has been approved by the US Food and Drug Administration for prescription use in those aged ≥12 years. CONCLUSIONS: Over the past several years, research into weight management in obese children and adolescents has improved in quality and quantity. Despite important gaps, available research supports at least short-term benefits of comprehensive medium- to high-intensity behavioral interventions in obese children and adolescents.

Screening for abdominal aortic aneurysm: A best-evidence systematic review for the U.S. Preventive Services Task Force

An abdominal aortic aneurysm (AAA) occurs when the aorta below the renal arteries expands to a maximal diameter of 3.0 cm or greater. Abdominal aortic aneurysms are found in 4% to 8% of older men and 0.5% to 1.5% of older women (1-5). Age, smoking, sex, and family history are the most significant AAA risk factors (1). Aortic aneurysms account for about 15000 deaths in the United States annually; of these, 9000 are AAA-related and the remainder are due to thoracic aortic aneurysms (6, 7). Most AAA deaths occur in men 65 years of age and older (8, 9). Although AAAs may be asymptomatic for years, as many as 1 in 3 eventually rupture if left untreated (10). The prognosis for ruptured AAAs is grim. Since most patients with ruptured AAAs die out of the hospital or before surgery (11), and since the operative mortality rate for emergent AAA repair is high (12), only 10% to 25% of individuals with ruptured AAAs survive until hospital discharge. Ultrasonography of the abdomen is accurate (13, 14) and reliable (15) in detecting AAAs. Survival after elective surgical repair approaches that of the general population (16). Elective AAA repair, however, may result in significant harms, such as operative mortality, myocardial infarction, respiratory and renal failure, and changes in functional status (17, 18). In its 1996 recommendation, the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against routine AAA screening of asymptomatic adults. The Task Force cited the need for data from population-based screening trials to determine whether the potential benefit from preventing ruptured AAAs justified the potential risks from increased surgery (19). Since 1996, results from 4 population-based randomized, controlled trials of AAA screening have been published (5, 9, 20-24). On the basis of this new evidence, the USPSTF sought to update its 1996 recommendation by reassessing the benefits and harms of population-based AAA screening. This systematic review was performed by investigators from the Oregon Evidence-based Practice Center, Portland, Oregon, in collaboration with the USPSTF and the Agency for Healthcare Research and Quality, Rockville, Maryland. Descriptions of the analytic framework, key questions, literature search, inclusion criteria, data extraction methods, quality rating, and trial flow diagram are provided in the Appendix, Appendix Figures 1 and 2, and the Appendix Table. The evidence review focused on the following key questions: 1a) Does AAA screening, in an asymptomatic average-risk or high-risk population, reduce AAA-related adverse health outcomes? 1b) For individuals who do not have AAAs on initial screening, does periodic repeated screening reduce AAA-related adverse health outcomes? 2) What are the harms associated with AAA screening? 3) For AAAs 3.0 to 5.4 cm detected through screening, does immediate repair or surveillance reduce AAA-related adverse health outcomes? 4) What are the harms associated with repair of AAAs 5.5 cm or greater? 5) What are the harms associated with immediate repair or surveillance of AAAs 3.0 to 5.4 cm? This article focuses only on key questions 1a, 1b, 2, and 4, which are most relevant to determining the net benefit (benefit minus harms) of population-based screening for AAA. Key questions 3 and 5 address management strategies for AAAs 3.0 to 5.4 cm, which are at much lower risk for rupture than larger AAAs (25, 26). Key questions 3 and 5 are reviewed in our full systematic evidence synthesis (available at www.preventiveservices.ahrq.gov). Methods We performed this review on the basis of methods previously established by the USPSTF (27). We initially developed an analytic framework and key questions, in conjunction with USPSTF liaisons, to define the strategy used to perform this systematic review. Since direct evidence regarding population-based screening from randomized, controlled trials was available, we did not explicitly review the accuracy and reliability of ultrasonography in population-based AAA screening. The sensitivity of ultrasound scanning for an AAA is 95%, and the specificity approaches 100%; the examination is safe and reliable (14, 15, 28, 29). Limited ultrasonography for AAA screening can be performed in less than 10 minutes (30). To identify relevant studies, we searched MEDLINE (January 1994 through July 2004), the Cochrane Database of Systematic Reviews (2004, Issue 1), and the Cochrane Controlled Trials Register (January 1994 through May 2004). Literature search strategies are summarized in the Appendix. We identified additional studies from the reference lists of retrieved articles, periodic hand searches of relevant journals, and suggestions from experts. To evaluate the effectiveness of AAA screening (key question 1a), we searched for randomized, controlled trials of population-based screening for AAA. To evaluate the benefit of periodic repeated screening after a normal scan (key question 1b), we identified cohort or follow-up studies of patients without AAAs identified in population screening studies. To evaluate the potential harms associated with AAA screening and treatment (key questions 2 and 4), we examined data from the trials of population screening and searched for other relevant retrospective or prospective cohort studies. Two authors reviewed 271 abstracts and 26 articles using defined inclusion criteria and abstracted relevant information about the population, setting, interventions, and outcomes of each included trial of screening and harms (see the Appendix and Appendix Figure 2 for inclusion criteria and the trial flow diagram). Predefined criteria from the USPSTF were used to assess the internal validity of each population-based screening trial and to assign quality ratings of good, fair, or poor (27). We did not assign quality ratings for studies of repeated screening or harms of screening and treatment. We used published data from the trials of population-based AAA screening to calculate estimates of unadjusted odds ratios (ORs) and 95% CIs for AAA-related mortality and all-cause mortality. We performed meta-analyses to calculate summary estimates for AAA-related mortality and all-cause mortality using the DerSimonian and Laird random-effects model (31). When no heterogeneity is present, the DerSimonian and Laird random-effects estimate is identical to the fixed-effects estimate. We deemed the random-effects model to be more appropriate than a fixed-effects model because the included studies differed in characteristics such as population, starting and stopping ages for screening, outcomes ascertainment, and duration of follow-up (32). We used graphs of trial outcomes and the MantelHaenszel chi-square test to assess heterogeneity. We used RevMan software (Reviewer Manager Version 4.2.2, 2003, The Cochrane Collaboration, Oxford, United Kingdom) to perform all statistical analyses. We modeled the impact of screening on AAA-related mortality over 5 years for 100000 U.S. men age 65 to 74 years. We also examined how the modeled impact of screening would differ in those with a history of smoking and those who had never smoked within this same sample. This article is based on a full evidence synthesis, which is available at www.preventiveservices.ahrq.gov. Role of the Funding Source This research was funded by the Agency for Healthcare Research and Quality under a contract to support the work of the U.S. Preventive Services Task Force. Agency staff and Task Force members participated in the initial design of the study and reviewed interim analyses and the final manuscript. The full evidence report was distributed for review to content experts and was revised accordingly. Agency approval was required before this manuscript could be submitted for publication, but the authors are solely responsible for its content and the decision to submit it. Data Synthesis Trial Characteristics We identified 4 randomized, controlled trials that evaluated population-based screening for AAA: the Multicentre Aneurysm Screening Study (MASS) from the United Kingdom (22); the Chichester, United Kingdom, screening study (5, 9, 20); the Viborg County, Denmark, screening study (21); and the Western Australia screening study (23, 33, 34). Table 1 shows the characteristics of the 4 screening trials. All trials identified potential participants age 65 years or older at average risk for AAA through population registries or regional health directories. The 4 trials included more than 125000 total participants. Different stopping ages were used for each trial and ranged from 73 years to 83 years. No data were provided on race or ethnicity. Only the Chichester trial included women. Table 1. Characteristics of Screening Trials for Abdominal Aortic Aneurysm In MASS and in the Chichester and Western Australia trials, participants were excluded before randomization if they resided in nursing homes. In MASS and in the Chichester trial, participants were also excluded before, and without knowledge of, randomization if their primary physician deemed them unfit for elective AAA repair. Participants were then randomly assigned to an intervention group that received an invitation to attend screening or to a control group that received usual care. All control group participants were followed passively and without contact. Across the 4 trials, 63% to 80% of invited participants attended ultrasound scanning. On an intention-to-treat basis, those who were invited to screening but did not attend were also included in the analysis. In MASS and in the Chichester and Viborg County trials, patients with AAAs exceeding a threshold size of 5.0 to 6.0 cm on initial measurement were referred to a vascular surgeon. Patients with smaller AAAs periodically underwent repeated scanning and were referred to a vascular surgeon for AAAs that had expanded to or above the threshold size. In MASS and in the Chichester trial, patients were also referred if the AA

Evidence-based behavioral medicine: What is it and how do we achieve it?

The goal of evidence-based medicine is ultimately to improve patient outcomes and quality of care. Systematic reviews of the available published evidence are required to identify interventions that lead to improvements in behavior, health, and well-being. Authoritative literature reviews depend on the quality of published research and research reports. The Consolidated Standards for Reporting Trials (CONSORT) Statement (www.consort-statement.org) was developed to improve the design and reporting of interventions involving randomized clinical trials (RCTs) in medical journals. We describe the 22 CONSORT guidelines and explain their application to behavioral medicine research and to evidence-based practice. Additional behavioral medicine-specific guidelines (e.g., treatment adherence) are also presented. Use of these guidelines by clinicians, educators, policymakers, and researchers who design, report, and evaluate or review RCTs will strengthen the research itself and accelerate efforts to apply behavioral medicine research to improve the processes and outcomes of behavioral medicine practice.

Effectiveness of Primary Care-Relevant Treatments for Obesity in Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force

BACKGROUND Overweight and obesity in adults are common and adversely affect health. PURPOSE To summarize effectiveness and harms of primary care-relevant weight-loss interventions for overweight and obese adults. DATA SOURCES MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2005 to September 2010; systematic reviews for identifying trials before 2005. STUDY SELECTION Two investigators appraised 6498 abstracts and 648 articles. Clinical trials were included if control groups received minimal interventions. Articles were rated as good, fair, or poor by using design-specific criteria. DATA EXTRACTION One investigator abstracted study characteristics and findings for good- and fair-quality studies; a second checked them. DATA SYNTHESIS Behaviorally based treatment resulted in 3-kg (6.6-lb) greater weight loss in intervention than control participants after 12 to 18 months, with more treatment sessions associated with greater loss. Limited data suggest weight-loss maintenance for 1 year or more. Orlistat plus behavioral intervention resulted in 3-kg (6.6-lb) more weight loss than did placebo after 12 months. Metformin resulted in less weight loss. Data on effects of weight-loss treatment on long-term health outcomes (for example, death and cardiovascular disease) were insufficient. Weight-loss treatment reduced diabetes incidence in participants with prediabetes. Effects on intermediate outcomes (for example, lipids and blood pressure) were mixed and small. Data on serious medication harms were insufficient. Medications commonly caused withdrawals due to gastrointestinal symptoms. LIMITATIONS Few studies reported health outcomes. Behaviorally based treatments were heterogeneous and specific elements were not well-described. Many studies could not be pooled because of insufficient reporting of variance data. Medication trials had high attrition, lacked postdiscontinuation data, and were inadequately powered for rare adverse effects. CONCLUSION Behaviorally based treatments are safe and effective for weight loss and maintenance. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Primary Care-Relevant Interventions to Prevent Falling in Older Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force

BACKGROUND Falls among older adults are both prevalent and preventable. PURPOSE To describe the benefits and harms of interventions that could be used by primary care practitioners to prevent falling among community-dwelling older adults. DATA SOURCES The reviewers evaluated trials from a good-quality systematic review published in 2003 and searched MEDLINE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL from the end of that reviews search date to February 2010 to identify additional English-language trials. STUDY SELECTION Two reviewers independently screened 3423 abstracts and 638 articles to identify randomized, controlled trials (RCTs) of primary care-relevant interventions among community-dwelling older adults that reported falls or fallers as an outcome. Trials were independently critically appraised to include only good- or fair-quality trials; discrepancies were resolved by a third reviewer. DATA EXTRACTION One reviewer abstracted data from 61 articles into standardized evidence tables that were verified by a second reviewer. DATA SYNTHESIS Overall, the included evidence was of fair quality. In 16 RCTs evaluating exercise or physical therapy, interventions reduced falling (risk ratio, 0.87 [95% CI, 0.81 to 0.94]). In 9 RCTs of vitamin D supplementation, interventions reduced falling (risk ratio, 0.83 [CI, 0.77 to 0.89]). In 19 trials involving multifactorial assessment and management, interventions with comprehensive management seemed to reduce falling, although overall pooled estimates were not statistically significant (risk ratio, 0.94 [CI, 0.87 to 1.02]). Limited evidence suggested that serious clinical harms were no more common for older adults in intervention groups than for those in control groups. LIMITATIONS Interventions and methods of fall ascertainment were heterogeneous. Data on potential harms of interventions were scant and often not reported. CONCLUSION Primary care-relevant interventions exist that can reduce falling among community-dwelling older adults. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Screening for Depression in Adult Patients in Primary Care Settings: A Systematic Evidence Review

Major depressive disorder (MDD) is common, with an estimated lifetime prevalence of 13.2%. In primary care settings, prevalence estimates of MDD range from 5% to 13% in all adults (1, 2), with lower estimates in those older than 55 years (6% to 9%) (3, 4). Primary care practitioners manage approximately one third to one half of nonelderly adults (5, 6) and almost two thirds of older adults (7) who received treatment for MDD. The severity of depressive symptoms in patients who receive treatment in primary care is equivalent to that of patients treated in psychiatric settings (8). For example, approximately 43% of such primary care patients report some degree of suicidal ideation within the previous week (8, 9). In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended screening adults for depression in clinical practices that have systems to ensure accurate diagnosis, effective treatment, and follow-up. Subsequent reviewers have concluded that screening does not improve health outcomes (10), but care management systems for depressed patients improve depression remission rates (11). Commentators on these divergent reviews have been divided (12, 13). We conducted this systematic review to aid the USPSTF in updating its 2002 recommendation for adult depression screening in primary care. We sought to 1) identify evidence published since the previous review on the benefits of screening for depression in primary care and integrate it with the previously identified evidence and 2) review the evidence in several areas in which evidence was insufficient at the time of the previous review or not was examined by the previous review (14). This includes the benefits of depression treatment in older adults, the harms of depression screening, and the harms of depression treatment with antidepressant medications. Methods Scope of the Review We developed an analytic framework (Appendix Figure 1) and 5 key questions that focused on the evidence that the USPSTF required to update its recommendation by using the USPSTFs methods (15). Appendix Figure 1. Analytic framework and key questions. SSRI = selective serotonin reuptake inhibitor. 1. Is there direct evidence that screening for depression among adults and elderly patients in primary care reduces morbidity and/or mortality? 1a. What is the effect of clinician feedback of screening test results (with or without additional care management support) on depression response and remission in screening-detected depressed patients receiving usual care? 2. What are the adverse effects of screening for depressive disorders in adults and elderly patients in primary care? 3. Is antidepressant and/or psychotherapy treatment of elderly depressed patients effective in improving health outcomes? 4. What are the adverse effects of antidepressant treatment (particularly selective serotonin reuptake inhibitors [SSRIs] and other second-generation drugs) for depression in adults and elderly patients? This article discusses methods and results for key questions 1, 1a, and 4. Detailed methods and results for the remaining key questions are in the full report (16). Data Sources and Searches We used the Database of Abstracts of Reviews of Effects, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE, and PsycINFO to search for relevant systematic reviews, meta-analyses, and primary studies published in English from January 1998 to December 2007. The full report provides the search strategies (16). Study Selection Two investigators reviewed 4088 abstracts published in English and 412 full-text articles (Appendix Figure 2) against key questionspecific inclusion and exclusion criteria (Appendix Table 1). Articles for key questions 1 and 1a were limited to randomized and controlled clinical trials that were conducted in primary care or similar settings. Key question 1 trials compared outcomes in screened and unscreened patients. Trials for key question 1a were required to have used the screening results for care decisions for intervention recipients and not for the control participants. Outcomes for these 2 questions were focused on depression response and remission. Appendix Figure 2. Search results and article flow, by key question. KQ = key question. * Numbers differ slightly from the full report (16) because only articles relevant to the more limited body of literature discussed in this publication are included in this figure. Appendix Table 1. Inclusion and Exclusion Criteria for KQs Discussed We focused our review of harms of treatment (key question 4) on already-synthesized evidence, supplemented by large observational studies. Methods for incorporating systematic reviews and meta-analyses are detailed elsewhere (Appendix Table 2). We examined serious adverse effects associated with antidepressant treatment, including suicide-related events (completed suicide, serious self-harm or attempted suicide, suicidal ideation, or suicidal behavior [usually defined to include suicide attempts, preparatory acts, or nonfatal serious self-harm]), and serious psychiatric events, including hospitalization. For older adults, we also considered evidence of serious medical events (for example, upper gastrointestinal bleeding) that were associated with SSRI and other second-generation antidepressant use. We examined rates of early discontinuation as a proxy for less serious adverse effects, particularly discontinuation due to adverse effects as a measure of tolerability. We focused on second-generation antidepressants (SSRIs in particular) because of their preponderance of use in the United States (17, 18). Appendix Table 2. Use of Existing Systematic Reviews Updated Searching and Study Examination Because of the delay between completion of the systematic review and publication, we repeated our search strategy through February 2009. We reviewed 800 abstracts against inclusion and exclusion criteria, and 21 seemed to meet criteria for this systematic review. After examining results of each of these new studies (as described in the abstracts), we determined that they would be unlikely to change our conclusions. Appendix Table 3 lists these studies. Appendix Table 3. Studies Found in Bridge Search With Possible Inclusion or Exclusion Criteria Data Extraction and Quality Assessment Two investigators rated articles for quality by using design-specific quality criteria on the basis of the USPSTF methods (15). The National Institute for Health and Clinical Excellence (19) criteria (for all study designs) and the Oxman criteria (20) (for systematic reviews) supplemented these methods. One investigator abstracted data from included studies into evidence tables and another verified it. The full review shows complete quality criteria (16). Regulatory reviews provided unique challenges and could not be evaluated by using typical quality criteria. For example, their search approach was different because they can mandate that manufacturers supply requested data. Because of the large number of trials (often in the hundreds) and proprietary information involved, however, they did not provide detailed information about individual trials. Data Synthesis and Analysis Data synthesis was primarily qualitative because of clinical heterogeneity. For cohort studies included for key question 4, we calculated absolute event rates and CIs for suicide-related events on the basis of reported data if this information was not provided. The 95% CIs were calculated on the basis of a Poisson distribution by using the GENMOD procedure (SAS software, version 8.2, SAS Institute, Cary, North Carolina) with the RISK option. Similarly, for the meta-analyses of antidepressant trials included for key question 4, we calculated missing CIs by using the FREQ procedure. Role of Funding Source The Agency for Healthcare Research and Quality funded this work, provided project oversight, and assisted in external review of the draft report but had no role in the design, conduct, or reporting of the review. The authors worked with 4 USPSTF members at key points throughout the review process to develop the analytic framework and key questions and resolve issues about scope and approach. The draft systematic review was reviewed by 6 experts and was revised on the basis of their feedback. Results Key Question 1 Is there direct evidence that screening for depression among adults and elderly patients in primary care reduces morbidity and/or mortality? One fair-quality randomized, controlled trial (RCT) of primary care patients reported mixed results when screened participants were compared with an unscreened usual care group (21) (Table). Concerns about the follow-up sample, however, limit our confidence in the results. At 3-month follow-up, the proportion of people who met criteria for depression, according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, was similar in the screened (37%) and usual care groups (46%) (P= 0.19), although power to detect a population-level effect was inadequate (n= 218). After the investigators controlled for baseline severity of depression (which differed between the screened and usual care groups in the full randomized sample), the mean reduction in symptom counts derived from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, was similar for the 2 groups (1.6 in screened patients vs. 1.5 in unscreened patients; P= 0.21). However, among the subset of patients who were depressed at baseline, screened patients were more likely than unscreened patients to be in complete remission at follow-up (1 symptom of depression in 48% of those screened vs. 27% of those not screened; P< 0.05). Only patients from 1 of the 2 study sites were included in the follow-up sample. At this site, only those with a diagnosis of depression at baseline and a random sample of the remaining participants (oversampling those with depressive sympt

Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force

BACKGROUND Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION Dual quality assessments and data abstraction. DATA SYNTHESIS Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers. LIMITATIONS The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.