Developing Recommendations for Evidence-Based Clinical Preventive Services for Diverse Populations: Methods of the U.S. Preventive Services Task Force.

The U.S. Preventive Services Task Force (USPSTF) summarizes the principles and considerations that guide development of its recommendations for diverse U.S. populations. It uses these principles through each step in the evidence-based guideline process: developing the research plan, conducting the evidence review, developing the recommendation, and communicating to guideline users. Three recent recommendations provide examples of how the USPSTF has used these principles: the 2015 recommendation on screening for abnormal blood glucose and type 2 diabetes; the 2016 recommendation on screening for breast cancer; and the recommendation on screening for prostate cancer, which is currently in progress. A more comprehensive list of recommendations that includes considerations for specific populations is also provided.

Lipid Screening in Childhood and Adolescence for Detection of Multifactorial Dyslipidemia: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Multifactorial dyslipidemia, characterized by elevated total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C), is associated with dyslipidemia and markers of atherosclerosis in young adulthood. Screening for dyslipidemia in childhood could delay or reduce cardiovascular events in adulthood. OBJECTIVE: To systematically review the evidence on benefits and harms of screening adolescents and children for multifactorial dyslipidemia for the US Preventive Services Task Force (USPSTF). DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, and PubMed were searched for studies published between January 1, 2005, and June 2, 2015; studies included in a previous USPSTF evidence report and reference lists of relevant studies and ongoing trials were also searched. Surveillance was conducted through April 9, 2016. STUDY SELECTION: Fair- and good-quality studies in English with participants 0 to 20 years of age. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized. MAIN OUTCOMES AND MEASURES: Outcomes included dyslipidemia (TC≥200 mg/dL or LDL-C≥130 mg/dL) and atherosclerosis in childhood; myocardial infarction and ischemic stroke in adulthood; diagnostic yield (number of confirmed cases per children screened); and harms of screening or treatment. Simulated diagnostic yield was calculated as initial screening yield × positive predictive value from a study with confirmatory testing. RESULTS: Screening of children for multifactorial dyslipidemia has not been evaluated in randomized clinical trials. Based on 1 observational study (n = 6500) and nationally representative prevalence estimates, the simulated diagnostic yield of screening for elevated TC varies between 4.8% and 12.3% (higher in obese children [12.3%] and at the ages when TC naturally peaks-7.2% at age 9-11 years and 7.2% at age 16-19 years). One good-quality randomized clinical trial (n = 663) found a modest effect of intensive dietary counseling for a low-fat, low-cholesterol diet on lipid levels at 1 year in children aged 8 to 10 years with mild to moderate dyslipidemia; mean between-group difference in TC change from baseline was -6.1 mg/dL (95% CI, -9.1 to -3.2 mg/dL; P < .001). Between-group differences dissipated by year 5. The intervention did not adversely affect nutritional status, growth, or development over the 18-year study period. One observational study (n = 9245) found that TC concentration at age 12 to 39 years was not associated with death before age 55 years. CONCLUSIONS AND RELEVANCE: The diagnostic yield of lipid screening varies by age and body mass index. No direct evidence was identified for benefits or harms of childhood screening or treatment on outcomes in adulthood. Intensive dietary interventions may be safe, with modest short-term benefit of uncertain clinical significance.

Lipid Screening in Childhood and Adolescence for Detection of Familial Hypercholesterolemia: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Familial hypercholesterolemia (FH) is characterized by elevated cholesterol concentrations early in life. Untreated FH is associated with premature cardiovascular disease in adulthood. OBJECTIVE: To systematically review the evidence on benefits and harms of screening adolescents and children for heterozygous FH for the US Preventive Services Task Force (USPSTF). DATA SOURCES: MEDLINE, the Cochrane Central Register of Controlled Trials, and PubMed were searched for studies published between January 1, 2005, and June 2, 2015; studies included in a previous USPSTF report were also searched. Surveillance was conducted through April 8, 2016. STUDY SELECTION: Fair- and good-quality studies in English with participants 0 to 20 years of age. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized. MAIN OUTCOMES AND MEASURES: Myocardial infarction and ischemic stroke in adulthood; lipid concentrations and atherosclerosis in childhood; diagnostic yield of screening; any harm of screening or treatment. RESULTS: Based on 2 studies (n = 83,241), the diagnostic yield of universal screening for FH in childhood is 1.3 to 4.8 cases per 1000 screened. There was no eligible evidence on the benefits or harms of FH screening in childhood. Eight placebo trials of statin drugs (n = 1071, 6-104 weeks) found low-density lipoprotein cholesterol (LDL-C) decreases of 20% to 40%; 1 trial (n = 214) showed a 2.01% decrease in carotid intima-media thickness with statins, compared with 1.02% with placebo (P = .02). Three placebo trials of bile acid-sequestering agents (n = 332, 8-52 weeks) showed LDL-C reductions of 10% to 20%. In 1 trial (n = 248), ezetimibe with simvastatin resulted in greater LDL-C reductions compared with simvastatin alone at 33 weeks (mean, -54.0% [SD, 1.4%] vs -38.1% [SD, 1.4%]). One trial of ezetimibe monotherapy (n = 138) showed mean LDL-C decreases of 28% (95% CI, -31% to -25%) from baseline and negligible change with placebo at 12 weeks. Eighteen studies found statins generally well tolerated. One observational study found lower, but still normal, dehydroepiandrosterone sulfate concentrations in statin-treated males with FH at 10-year follow-up. Bile acid-sequestering agents were commonly associated with adverse gastrointestinal symptoms and poor palatability. There was no eligible evidence on the effect of FH treatment on myocardial infarction or stroke in adulthood. CONCLUSIONS AND RELEVANCE: Screening can detect FH in children, and lipid-lowering treatment in childhood can reduce lipid concentrations in the short term, with little evidence of harm. There is no evidence for the effect of screening for FH in childhood on lipid concentrations or cardiovascular outcomes in adulthood, or on the long-term benefits or harms of beginning lipid-lowering treatment in childhood.

Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States. OBJECTIVE: To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC. DATA SOURCES: Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2008, through December 31, 2014, with surveillance through February 23, 2016. STUDY SELECTION: English-language studies conducted in asymptomatic populations at general risk of CRC. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted. MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality, test accuracy in detecting CRC or adenomas, and serious adverse events. RESULTS: Four pragmatic randomized clinical trials (RCTs) evaluating 1-time or 2-time flexible sigmoidoscopy (n = 458,002) were associated with decreased CRC-specific mortality compared with no screening (incidence rate ratio, 0.73; 95% CI, 0.66-0.82). Five RCTs with multiple rounds of biennial screening with guaiac-based fecal occult blood testing (n = 419,966) showed reduced CRC-specific mortality (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Seven studies of computed tomographic colonography (CTC) with bowel preparation demonstrated per-person sensitivity and specificity to detect adenomas 6 mm and larger comparable with colonoscopy (sensitivity from 73% [95% CI, 58%-84%] to 98% [95% CI, 91%-100%]; specificity from 89% [95% CI, 84%-93%] to 91% [95% CI, 88%-93%]); variability and imprecision may be due to differences in study designs or CTC protocols. Sensitivity of colonoscopy to detect adenomas 6 mm or larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%). On the basis of a single stool specimen, the most commonly evaluated families of fecal immunochemical tests (FITs) demonstrated good sensitivity (range, 73%-88%) and specificity (range, 90%-96%). One study (n = 9989) found that FIT plus stool DNA test had better sensitivity in detecting CRC than FIT alone (92%) but lower specificity (84%). Serious adverse events from colonoscopy in asymptomatic persons included perforations (4/10,000 procedures, 95% CI, 2-5 in 10,000) and major bleeds (8/10,000 procedures, 95% CI, 5-14 in 10,000). Computed tomographic colonography may have harms resulting from low-dose ionizing radiation exposure or identification of extracolonic findings. CONCLUSIONS AND RELEVANCE: Colonoscopy, flexible sigmoidoscopy, CTC, and stool tests have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed.

Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force.

BACKGROUND: The balance between potential aspirin-related risks and benefits is critical in primary prevention. PURPOSE: To evaluate the risk for serious bleeding with regular aspirin use in cardiovascular disease (CVD) primary prevention. DATA SOURCES: PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (2010 through 6 January 2015), and relevant references from other reviews. STUDY SELECTION: Randomized, controlled trials; cohort studies; and meta-analyses comparing aspirin with placebo or no treatment to prevent CVD or cancer in adults. DATA EXTRACTION: One investigator abstracted data, another checked for accuracy, and 2 assessed study quality. DATA SYNTHESIS: In CVD primary prevention studies, very-low-dose aspirin use (≤100 mg daily or every other day) increased major gastrointestinal (GI) bleeding risk by 58% (odds ratio [OR], 1.58 [95% CI, 1.29 to 1.95]) and hemorrhagic stroke risk by 27% (OR, 1.27 [CI, 0.96 to 1.68]). Projected excess bleeding events with aspirin depend on baseline assumptions. Estimated excess major bleeding events were 1.39 (CI, 0.70 to 2.28) for GI bleeding and 0.32 (CI, -0.05 to 0.82) for hemorrhagic stroke per 1000 person-years of aspirin exposure using baseline bleeding rates from a community-based observational sample. Such events could be greater among older persons, men, and those with CVD risk factors that also increase bleeding risk. LIMITATIONS: Power to detect effects on hemorrhagic stroke was limited. Harms other than serious bleeding were not examined. CONCLUSION: Consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Aspirin for the Prevention of Cancer Incidence and Mortality: Systematic Evidence Reviews for the U.S. Preventive Services Task Force.

BACKGROUND: Cancer is the second leading cause of death in the United States. PURPOSE: To conduct systematic reviews of aspirin and 1) total cancer mortality and incidence in persons eligible for primary prevention of cardiovascular disease (CVD) and 2) colorectal cancer (CRC) mortality and incidence in persons at average CRC risk. DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials through January 2015 and relevant references from other reviews. STUDY SELECTION: Trials comparing oral aspirin versus placebo or no treatment in adults aged 40 years or older were included. Two investigators independently reviewed abstracts and articles against inclusion and quality criteria. DATA EXTRACTION: Data from 20 good- or fair-quality trials were abstracted by one reviewer and checked by another. DATA SYNTHESIS: In CVD primary prevention trials, cancer mortality (relative risk [RR], 0.96 [95% CI, 0.87 to 1.06]) (10 trials; n = 103 787) and incidence (RR, 0.98 [CI, 0.93 to 1.04]) (6 trials; n = 72 926) were similar in aspirin and control groups over 3.6 to 10.1 years. In CVD primary and secondary prevention trials, 20-year CRC mortality was reduced among persons assigned to aspirin therapy (RR, 0.67 [CI, 0.52 to 0.86]) (4 trials; n = 14 033). Aspirin appeared to reduce CRC incidence beginning 10 to 19 years after initiation (RR, 0.60 [CI, 0.47 to 0.76]) (3 trials; n = 47 464). LIMITATIONS: Most data were from clinically and methodologically heterogeneous CVD prevention trials. Outcome assessment and follow-up length varied across studies. Data on non-CRC cancer types and subgroups were limited. CONCLUSION: In CVD primary prevention populations, aspirin's effect on total cancer mortality and incidence was not clearly established. Evidence from CVD primary and secondary prevention studies suggested that aspirin therapy reduces CRC incidence and perhaps mortality approximately 10 years after initiation. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: A Decision Analysis for the U.S. Preventive Services Task Force.

BACKGROUND: Evidence indicates that aspirin is effective for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) but also increases the risk for gastrointestinal (GI) and cerebral hemorrhages. OBJECTIVE: To assess the net balance of benefits and harms from routine aspirin use across clinically relevant age, sex, and CVD risk groups. DESIGN: Decision analysis using a microsimulation model. DATA SOURCES: 3 systematic evidence reviews. TARGET POPULATION: Men and women aged 40 to 79 years with a 10-year CVD risk of 20% or less, and no history of CVD and without elevated risk for GI or cerebral hemorrhages that would contraindicate aspirin use. TIME HORIZON: Lifetime, 20 years, and 10 years. PERSPECTIVE: Clinical. INTERVENTION: Low-dose aspirin (≤100 mg/d). OUTCOME MEASURES: Primary outcomes are length and quality of life measured in net life-years and quality-adjusted life-years. Benefits include reduced nonfatal myocardial infarction, nonfatal ischemic stroke, fatal CVD, CRC incidence, and CRC mortality. Harms include increased fatal and nonfatal GI bleeding and hemorrhagic stroke. RESULTS OF BASE-CASE ANALYSIS: Lifetime net quality-adjusted life-years are positive for most adults initiating aspirin at ages 40 to 69 years, and life expectancy gains are expected for most men and women initiating aspirin at ages 40 to 59 years and 60 to 69 years with higher CVD risk. Harms may exceed benefits for persons starting aspirin in their 70s and for many during the first 10 to 20 years of use. RESULTS OF SENSITIVITY ANALYSIS: Results are most sensitive to the relative risk for hemorrhagic stroke and CVD mortality but are affected by all relative risk estimates, baseline GI bleeding incidence and case-fatality rates, and disutilities associated with aspirin use. LIMITATIONS: Aspirin effects by age are uncertain. Stroke benefits are conservatively estimated. Gastrointestinal bleeding incidence and case-fatality rates account only for age and sex. CONCLUSION: Lifetime aspirin use for primary prevention initiated at younger ages (40 to 69 years) and in persons with higher CVD risk shows the greatest potential for positive net benefit. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Screening for Chronic Obstructive Pulmonary Disease: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. OBJECTIVE: To systematically review literature on the accuracy of screening questionnaires and office-based screening pulmonary function testing and the efficacy and harms of treatment of screen-detected COPD. DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant English-language studies published through January 2015. STUDY SELECTION: Two reviewers independently screened abstracts and studies. The search yielded 13,141 unique citations; 465 full-text articles were reviewed, and 33 studies met the inclusion criteria. DATA EXTRACTION AND SYNTHESIS: Two reviewers rated the quality of each study using USPSTF criteria. MAIN OUTCOMES AND MEASURES: Diagnostic accuracy (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]; treatment efficacy (COPD exacerbations, all-cause mortality, quality of life, and dyspnea); and treatment harms. RESULTS: All screening questionnaires were based on symptoms as well as risk factors such as age and smoking history. The COPD Diagnostic Questionnaire was the most extensively studied (5 studies, n = 3048), with moderate overall performance for COPD detection: area under the receiver operating characteristic curve (AUC), 0.65 to 0.72; sensitivity, 80% to 93%; and specificity, 24% to 49%, at a threshold of greater than 16.5. Positive predictive value and NPV ranged from 17% to 45% and 76% to 98%, respectively. For pulmonary function-based screening tools, FEV1/FEV6 was the best studied (3 studies, n = 1587), with AUC ranging from 0.84 to 0.85. Sensitivity ranged from 51% to 80%. Specificity (range, 90%-95%) and PPV (range, 63%-75%) appeared better than questionnaires. There was not strong evidence to support that screening and supplying smokers with spirometry results improves smoking cessation rates. Treatment trials were unavailable for screen-detected patients. Trials that reported outcomes in patients with mild to moderate COPD included 2 trials of long-acting ß-agonists (LABAs) (n = 3174), 1 RCT of LABAs and inhaled corticosteroids (ICS) (n = 1097), 5 RCTs of the long-acting muscarinic antagonist tiotropium (n = 4592), and 6 RCTs of ICS (n = 3983). They suggested no benefit in all-cause mortality, but a decrease in annual rates of exacerbations with pharmacologic treatments. Few trials reported harms for any individual drug class. Adverse effects were generally mild (eg, dry mouth and cough). CONCLUSIONS AND RELEVANCE: There was no direct evidence available to determine the benefits and harms of screening asymptomatic adults for COPD using questionnaires or office-based screening pulmonary function testing or to determine the benefits of treatment in screen-detected populations. Indirect evidence suggests that the COPD Diagnostic Questionnaire has moderate overall performance for COPD detection. Among patients with mild to moderate COPD, the benefit of pharmacotherapy for reducing exacerbations was modest.

Supplemental Screening for Breast Cancer in Women With Dense Breasts: A Systematic Review for the U.S. Preventive Services Task Force.

BACKGROUND: Screening mammography has lower sensitivity and specificity in women with dense breasts, who experience higher breast cancer risk. PURPOSE: To perform a systematic review of reproducibility of Breast Imaging Reporting and Data System (BI-RADS) density categorization and test performance and clinical outcomes of supplemental screening with breast ultrasonography, magnetic resonance imaging (MRI), and digital breast tomosynthesis (DBT) in women with dense breasts and negative mammography results. DATA SOURCES: MEDLINE, PubMed, EMBASE, and Cochrane database from January 2000 to July 2015. STUDY SELECTION: Studies reporting BI-RADS density reproducibility or supplemental screening results for women with dense breasts. DATA EXTRACTION: Quality assessment and abstraction of 24 studies from 7 countries; 6 studies were good-quality. DATA SYNTHESIS: Three good-quality studies reported reproducibility of BI-RADS density; 13% to 19% of women were recategorized between "dense" and "nondense" at subsequent screening. Two good-quality studies reported that sensitivity of ultrasonography for women with negative mammography results ranged from 80% to 83%; specificity, from 86% to 94%; and positive predictive value (PPV), from 3% to 8%. The sensitivity of MRI ranged from 75% to 100%; specificity, from 78% to 94%; and PPV, from 3% to 33% (3 studies). Rates of additional cancer detection with ultrasonography were 4.4 per 1000 examinations (89% to 93% invasive); recall rates were 14%. Use of MRI detected 3.5 to 28.6 additional cancer cases per 1000 examinations (34% to 86% invasive); recall rates were 12% to 24%. Rates of cancer detection with DBT increased by 1.4 to 2.5 per 1000 examinations compared with mammography alone (3 studies). Recall rates ranged from 7% to 11%, compared with 7% to 17% with mammography alone. No studies examined breast cancer outcomes. LIMITATIONS: Good-quality evidence was sparse. Studies were small and CIs were wide. Definitions of recall were absent or inconsistent. CONCLUSION: Density ratings may be recategorized on serial screening mammography. Supplemental screening of women with dense breasts finds additional breast cancer but increases false-positive results. Use of DBT may reduce recall rates. Effects of supplemental screening on breast cancer outcomes remain unclear. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Behavioral Counseling and Pharmacotherapy Interventions for Tobacco Cessation in Adults, Including Pregnant Women: A Review of Reviews for the U.S. Preventive Services Task Force.

BACKGROUND: Tobacco use is the leading cause of preventable death in the United States. PURPOSE: To review the effectiveness and safety of pharmacotherapy and behavioral interventions for tobacco cessation. DATA SOURCES: 5 databases and 8 organizational Web sites were searched through 1 August 2014 for systematic reviews, and PubMed was searched through 1 March 2015 for trials on electronic nicotine delivery systems. STUDY SELECTION: Two reviewers examined 114 articles to identify English-language reviews that reported health, cessation, or adverse outcomes. DATA EXTRACTION: One reviewer abstracted data from good- and fair-quality reviews, and a second checked for accuracy. DATA SYNTHESIS: 54 reviews were included. Behavioral interventions increased smoking cessation at 6 months or more (physician advice had a pooled risk ratio [RR] of 1.76 [95% CI, 1.58 to 1.96]). Nicotine replacement therapy (RR, 1.60 [CI, 1.53 to 1.68]), bupropion (RR, 1.62 [CI, 1.49 to 1.76]), and varenicline (RR, 2.27 [CI, 2.02 to 2.55]) were also effective for smoking cessation. Combined behavioral and pharmacotherapy interventions increased cessation by 82% compared with minimal intervention or usual care (RR, 1.82 [CI, 1.66 to 2.00]). None of the drugs were associated with major cardiovascular adverse events. Only 2 trials addressed efficacy of electronic cigarettes for smoking cessation and found no benefit. Among pregnant women, behavioral interventions benefited cessation and perinatal health; effects of nicotine replacement therapy were not significant. LIMITATION: Evidence published after each review's last search date was not included. CONCLUSION: Behavioral and pharmacotherapy interventions improve rates of smoking cessation among the general adult population, alone or in combination. Data on the effectiveness and safety of electronic nicotine delivery systems are limited. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Family history and the natural history of colorectal cancer: systematic review.

PURPOSE: Family history of colorectal cancer (CRC) is a known risk factor for CRC and encompasses both genetic and shared environmental risks. METHODS: We conducted a systematic review to estimate the impact of family history on the natural history of CRC and adherence to screening. RESULTS: We found high heterogeneity in family-history definitions, the most common definition being one or more first-degree relatives. The prevalence of family history may be lower than the commonly cited 10%, and confirms evidence for increasing levels of risk associated with increasing family-history burden. There is evidence for higher prevalence of adenomas and of multiple adenomas in people with family history of CRC but no evidence for differential adenoma location or adenoma progression by family history. Limited data regarding the natural history of CRC by family history suggest a differential age or stage at cancer diagnosis and mixed evidence with respect to tumor location. Adherence to recommended colonoscopy screening was higher in people with a family history of CRC. CONCLUSION: Stratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history-based approaches, but for the foreseeable future, family history may remain a valuable clinical tool for identifying individuals at increased risk for CRC.

Diagnostic and predictive accuracy of blood pressure screening methods with consideration of rescreening intervals: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Elevated blood pressure (BP) is the largest contributing risk factor to all-cause and cardiovascular mortality. PURPOSE: To update a systematic review on the benefits and harms of screening for high BP in adults and to summarize evidence on rescreening intervals and diagnostic and predictive accuracy of different BP methods for cardiovascular events. DATA SOURCES: Selected databases searched through 24 February 2014. STUDY SELECTION: Fair- and good-quality trials and diagnostic accuracy and cohort studies conducted in adults and published in English. DATA EXTRACTION: One investigator abstracted data, and a second checked for accuracy. Study quality was dual-reviewed. DATA SYNTHESIS: Ambulatory BP monitoring (ABPM) predicted long-term cardiovascular outcomes independently of office BP (hazard ratio range, 1.28 to 1.40, in 11 studies). Across 27 studies, 35% to 95% of persons with an elevated BP at screening remained hypertensive after nonoffice confirmatory testing. Cardiovascular outcomes in persons who were normotensive after confirmatory testing (isolated clinic hypertension) were similar to outcomes in those who were normotensive at screening. In 40 studies, hypertension incidence after rescreening varied considerably at each yearly interval up to 6 years. Intrastudy comparisons showed at least 2-fold higher incidence in older adults, those with high-normal BP, overweight and obese persons, and African Americans. LIMITATION: Few diagnostic accuracy studies of office BP methods and protocols in untreated adults. CONCLUSION: Evidence supports ABPM as the reference standard for confirming elevated office BP screening results to avoid misdiagnosis and overtreatment of persons with isolated clinic hypertension. Persons with BP in the high-normal range, older persons, those with an above-normal body mass index, and African Americans are at higher risk for hypertension on rescreening within 6 years than are persons without these risk factors. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Ultrasonography screening for abdominal aortic aneurysms: a systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: Long-term follow-up of population-based randomized, controlled trials (RCTs) has demonstrated that screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates in men aged 65 years or older. PURPOSE: To systematically review evidence about the benefits and harms of ultrasonography screening for AAAs in asymptomatic primary care patients. DATA SOURCES: MEDLINE, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials (January 2004 through January 2013), clinical trial registries, reference lists, experts, and a targeted bridge search for population-based screening RCTs through September 2013. STUDY SELECTION: English-language, population-based, fair- to good-quality RCTs and large cohort studies for AAA screening benefits as well as RCTs and cohort and registry studies for harms in adults with AAA. DATA EXTRACTION: Dual quality assessment and abstraction of study details and results. DATA SYNTHESIS: Reviews of 4 RCTs involving 137,214 participants demonstrated that 1-time invitation for AAA screening in men aged 65 years or older reduced AAA rupture and AAA-related mortality rates for up to 10 and 15 years, respectively, but had no statistically significant effect on all-cause mortality rates up to 15 years. Screening was associated with more overall and elective surgeries but fewer emergency operations and lower 30-day operative mortality rates at up to 10- to 15-year follow-up. One RCT involving 9342 women showed that screening had no benefit on AAA-related or all-cause mortality rates. LIMITATIONS: Trials included mostly white men outside of the United States. Information for subgroups and about rescreening was limited. CONCLUSION: One-time invitation for AAA screening in men aged 65 years or older was associated with decreased AAA rupture and AAA-related mortality rates but had little or no effect on all-cause mortality rates. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

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 ß-carotene prevented CVD or cancer, and ß-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.

The ankle-brachial index for peripheral artery disease screening and cardiovascular disease prediction among asymptomatic adults: a systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: Screening for peripheral artery disease (PAD) may reduce morbidity and mortality. PURPOSE: To review the evidence on the ability of the ankle-brachial index (ABI) to predict cardiovascular disease (CVD) morbidity and mortality independent of Framingham Risk Score (FRS) factors in asymptomatic adults and on the benefits and harms of treating screen-detected adults with PAD. DATA SOURCES: MEDLINE and the Cochrane Central Register of Controlled Trials (1996 to September 2012), clinical trial registries, reference lists, and experts. STUDY SELECTION: English-language, population-based prognostic studies evaluating the ABI in addition to the FRS and treatment trials or studies of treatment harms in screen-detected adults with PAD. DATA EXTRACTION: Dual quality assessment and abstraction of relevant study details. DATA SYNTHESIS: One large meta-analysis (n = 43 919) showed that the ABI could reclassify 10-year risk for coronary artery disease (CAD), but it did not report measures of appropriate reclassification (the net reclassification improvement [NRI]). Four heterogeneous risk prediction studies showed that the magnitude of the NRI was probably small when the ABI was added to the FRS to predict CAD or CVD events. Of 2 treatment trials meeting inclusion criteria, 1 large trial (n = 3350) showed that low-dose aspirin did not prevent CVD events in persons with a screen-detected low ABI but may have increased the risk for major bleeding events. LIMITATIONS: Most prognostic studies did not allow for calculation of a bias-corrected NRI. Evidence on treatment benefits and harms was limited to aspirin and was scant. CONCLUSION: Adding the ABI to the FRS probably has limited value for predicting CAD or CVD. Treatment benefits for asymptomatic individuals with screen-detected PAD are not established. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Screening for and treatment of suicide risk relevant to primary care: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: In 2009, suicide accounted for 36 897 deaths in the United States. PURPOSE: To review the accuracy of screening instruments and the efficacy and safety of screening for and treatment of suicide risk in populations and settings relevant to primary care. DATA SOURCES: Citations from MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, and CINAHL (2002 to 17 July 2012); gray literature; and a surveillance search of MEDLINE for additional screening trials (July to December 2012). STUDY SELECTION: Fair- or good-quality English-language studies that assessed the accuracy of screening instruments in primary care or similar populations and trials of suicide prevention interventions in primary or mental health care settings. DATA EXTRACTION: One investigator abstracted data; a second checked the abstraction. Two investigators rated study quality. DATA SYNTHESIS: Evidence was insufficient to determine the benefits of screening in primary care populations; very limited evidence identified no serious harms. Minimal evidence suggested that screening tools can identify some adults at increased risk for suicide in primary care, but accuracy was lower in studies of older adults. Minimal evidence limited to high-risk populations suggested poor performance of screening instruments in adolescents. Trial evidence showed that psychotherapy reduced suicide attempts in high-risk adults but not adolescents. Most trials were insufficiently powered to detect effects on deaths. LIMITATION: Treatment evidence was derived from high-risk rather than screening-detected populations. Evidence relevant to adolescents, older adults, and racial or ethnic minorities was limited. CONCLUSION: Primary care-feasible screening tools might help to identify some adults at increased risk for suicide but have limited ability to detect suicide risk in adolescents. Psychotherapy may reduce suicide attempts in some high-risk adults, but effective interventions for high-risk adolescents are not yet proven. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.