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Importance: Falls are the most common cause of injury-related morbidity and mortality in older adults., Objective: To systematically review evidence on the effectiveness and harms of fall prevention interventions in community-dwelling older adults., Data Sources: MEDLINE, Cumulative Index for Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Clinical Trials for relevant English-language literature published between January 1, 2016, and May 8, 2023, with ongoing surveillance through March 22, 2024., Study Selection: Randomized clinical trials of interventions to prevent falls in community-dwelling adults 65 years or older., Data Extraction and Synthesis: Critical appraisal and data abstraction by 2 independent reviewers. Random-effects meta-analyses with Knapp-Hartung adjustment., Main Outcomes and Measures: Falls, injurious falls, fall-related fractures, hospitalizations or emergency department visits, people with 1 or more falls, people with injurious falls, people with fall-related fractures, and harms., Results: Eighty-three fair- to good-quality randomized clinical trials (n = 48 839) examined the effectiveness of 6 fall prevention interventions in older adults. This article focuses on the 2 most studied intervention types: multifactorial (28 studies; n = 27 784) and exercise (37 studies; n = 16 117) interventions. Multifactorial interventions were associated with a statistically significant reduction in falls (incidence rate ratio [IRR], 0.84 [95% CI, 0.74-0.95]) but not a statistically significant reduction in individual risk of 1 or more falls (relative risk [RR], 0.96 [95% CI, 0.91-1.02]), injurious falls (IRR, 0.92 [95% CI, 0.84-1.01]), fall-related fractures (IRR, 1.01 [95% CI, 0.81-1.26]), individual risk of injurious falls (RR, 0.92 [95% CI, 0.83-1.02]), or individual risk of fall-related fractures (RR, 0.86 [95% CI, 0.60-1.24]). Exercise interventions were associated with statistically significant reductions in falls (IRR, 0.85 [95% CI, 0.75-0.96]), individual risk of 1 or more falls (RR, 0.92 [95% CI, 0.87-0.98]), and injurious falls (IRR, 0.84 [95% CI, 0.74-0.95]) but not individual risk of injurious falls (RR, 0.90 [95% CI, 0.79-1.02]). Harms associated with multifactorial and exercise interventions were not well reported and were generally rare, minor musculoskeletal symptoms associated with exercise., Conclusions and Relevance: Multifactorial and exercise interventions were associated with reduced falls in multiple good-quality trials. Exercise demonstrated the most consistent statistically significant benefit across multiple fall-related outcomes.

Importance: Lipid screening in childhood and adolescence can lead to early dyslipidemia diagnosis. The long-term benefits of lipid screening and subsequent treatment in this population are uncertain., Objective: To review benefits and harms of screening and treatment of pediatric dyslipidemia due to familial hypercholesterolemia (FH) and multifactorial dyslipidemia., Data Sources: MEDLINE and the Cochrane Central Register of Controlled Trials through May 16, 2022; literature surveillance through March 24, 2023., Study Selection: English-language randomized clinical trials (RCTs) of lipid screening; recent, large US cohort studies reporting diagnostic yield or screen positivity; and RCTs of lipid-lowering interventions., Data Extraction and Synthesis: Single extraction, verified by a second reviewer. Quantitative synthesis using random-effects meta-analysis., Main Outcomes and Measures: Health outcomes, diagnostic yield, intermediate outcomes, behavioral outcomes, and harms., Results: Forty-three studies were included (n = 491 516). No RCTs directly addressed screening effectiveness and harms. Three US studies (n = 395 465) reported prevalence of phenotypically defined FH of 0.2% to 0.4% (1:250 to 1:500). Five studies (n = 142 257) reported multifactorial dyslipidemia prevalence; the prevalence of elevated total cholesterol level (≥200 mg/dL) was 7.1% to 9.4% and of any lipid abnormality was 19.2%. Ten RCTs in children and adolescents with FH (n = 1230) demonstrated that statins were associated with an 81- to 82-mg/dL greater mean reduction in levels of total cholesterol and LDL-C compared with placebo at up to 2 years. Nonstatin-drug trials showed statistically significant lowering of lipid levels in FH populations, but few studies were available for any single drug. Observational studies suggest that statin treatment for FH starting in childhood or adolescence reduces long-term cardiovascular disease risk. Two multifactorial dyslipidemia behavioral counseling trials (n = 934) demonstrated 3- to 6-mg/dL greater reductions in total cholesterol levels compared with the control group, but findings did not persist at longest follow-up. Harms reported in the short-term drug trials were similar in the intervention and control groups., Conclusions and Relevance: No direct evidence on the benefits or harms of pediatric lipid screening was identified. While multifactorial dyslipidemia is common, no evidence was found that treatment is effective for this condition. In contrast, FH is relatively rare; evidence shows that statins reduce lipid levels in children with FH, and observational studies suggest that such treatment has long-term benefit for this condition.

Importance: Low-dose aspirin is used for primary cardiovascular disease prevention and may have benefits for colorectal cancer prevention., Objective: To review the benefits and harms of aspirin in primary cardiovascular disease prevention and colorectal cancer prevention to inform the US Preventive Services Task Force., Data Sources: MEDLINE, PubMed, Embase, and the Cochrane Central Register of Controlled Trials through January 2021; literature surveillance through January 21, 2022., Study Selection: English-language randomized clinical trials (RCTs) of low-dose aspirin (≤100 mg/d) compared with placebo or no intervention in primary prevention populations., Data Extraction and Synthesis: Single extraction, verified by a second reviewer. Quantitative synthesis using Peto fixed-effects meta-analysis., Main Outcomes and Measures: Cardiovascular disease events and mortality, all-cause mortality, colorectal cancer incidence and mortality, major bleeding, and hemorrhagic stroke., Results: Eleven RCTs (N = 134 470) and 1 pilot trial (N = 400) of low-dose aspirin for primary cardiovascular disease prevention were included. Low-dose aspirin was associated with a significant decrease in major cardiovascular disease events (odds ratio [OR], 0.90 [95% CI, 0.85-0.95]; 11 RCTs [n = 134 470]; I2 = 0%; range in absolute effects, -2.5% to 0.1%). Results for individual cardiovascular disease outcomes were significant, with similar magnitude of benefit. Aspirin was not significantly associated with reductions in cardiovascular disease mortality or all-cause mortality. There was limited trial evidence on benefits for colorectal cancer, with the findings highly variable by length of follow-up and statistically significant only when considering long-term observational follow-up beyond randomized trial periods. Low-dose aspirin was associated with significant increases in total major bleeding (OR, 1.44 [95% CI, 1.32-1.57]; 10 RCTs [n = 133 194]; I2 = 4.7%; range in absolute effects, 0.1% to 1.0%) and in site-specific bleeding, with similar magnitude., Conclusions and Relevance: Low-dose aspirin was associated with small absolute risk reductions in major cardiovascular disease events and small absolute increases in major bleeding. Colorectal cancer results were less robust and highly variable.

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2016 recommendation on the use of aspirin for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC)., Objective: To provide updated model-based estimates of the net balance in benefits and harms from routine use of low-dose aspirin for primary prevention., Design, Setting, and Participants: Microsimulation modeling was used to estimate long-term benefits and harms for hypothetical US cohorts of men and women aged 40 to 79 years with up to 20% 10-year risk for an atherosclerotic CVD event and without prior history of CVD or elevated bleeding risks., Exposures: Low-dose (≤100 mg/d) aspirin for lifetime use, unless contraindicated by a bleeding event, and with stopping ages in 5-year intervals from age 65 to 85 years., Main Outcomes and Measures: Primary outcomes were lifetime net benefits measured in quality-adjusted life-years (QALYs) and life-years. Benefits included reduced nonfatal myocardial infarction and ischemic stroke. Harms included increased nonfatal major gastrointestinal bleeding and intracranial hemorrhage. Reduced CRC incidence was considered in sensitivity analysis., Results: Estimated lifetime net QALYs were positive for both men and women at 5% or greater 10-year CVD risk when starting between ages 40 and 59 years and at 10% or greater 10-year CVD risk when starting between ages 60 and 69 years. These estimates ranged from 2.3 (95% CI, -2.7 to 7.4) to 66.2 (95% CI, 58.2 to 74.1) QALYs per 1000 persons. Lifetime net life-years were positive for men at 5% or greater and women at 10% or greater 10-year CVD risk starting aspirin at ages 40 to 49 years and for men at 7.5% or greater and women at 15% or greater 10-year CVD risk at ages 50 to 59 years. These estimates ranged from 0.4 (95% CI, -6.1 to 6.9) to 52.4 (95% CI, 43.9 to 60.9) life-years per 1000 persons. Lifetime net life-years were negative in most cases for persons starting aspirin between ages 60 and 79 years, as were lifetime net QALYs for persons aged 70 to 79 years. Stopping aspirin between ages 65 and 85 years generally showed little advantage compared with lifetime use. Sensitivity analyses showed lifetime net benefits may be higher if aspirin reduced CRC incidence or CVD mortality and lower if aspirin increased fatal major gastrointestinal bleeding or reduced quality of life with routine use., Conclusions and Relevance: This microsimulation study suggested that several population groups may benefit from taking aspirin for the primary prevention of CVD, primarily in persons starting at younger ages with higher 10-year CVD risk.

Importance: Hypertension is a major risk factor for cardiovascular disease and can be modified through lifestyle and pharmacological interventions to reduce cardiovascular events and mortality., Objective: To systematically review the benefits and harms of screening and confirmatory blood pressure measurements in adults, to inform the US Preventive Services Task Force., Data Sources: MEDLINE, PubMed, Cochrane Collaboration Central Registry of Controlled Trials, and CINAHL; surveillance through March 26, 2021., Study Selection: Randomized clinical trials (RCTs) and nonrandomized controlled intervention studies for effectiveness of screening; accuracy studies for screening and confirmatory measurements (ambulatory blood pressure monitoring as the reference standard); RCTs and nonrandomized controlled intervention studies and observational studies for harms of screening and confirmation., Data Extraction and Synthesis: Independent critical appraisal and data abstraction; meta-analyses and qualitative syntheses., Main Outcomes and Measures: Mortality; cardiovascular events; quality of life; sensitivity, specificity, positive and negative predictive values; harms of screening., Results: A total of 52 studies (N = 215 534) were identified in this systematic review. One cluster RCT (n = 140 642) of a multicomponent intervention including hypertension screening reported fewer annual cardiovascular-related hospital admissions for cardiovascular disease in the intervention group compared with the control group (difference, 3.02 per 1000 people; rate ratio, 0.91 [95% CI, 0.86-0.97]). Meta-analysis of 15 studies (n = 11 309) of initial office-based blood pressure screening showed a pooled sensitivity of 0.54 (95% CI, 0.37-0.70) and specificity of 0.90 (95% CI, 0.84-0.95), with considerable clinical and statistical heterogeneity. Eighteen studies (n = 57 128) of various confirmatory blood pressure measurement modalities were heterogeneous. Meta-analysis of 8 office-based confirmation studies (n = 53 183) showed a pooled sensitivity of 0.80 (95% CI, 0.68-0.88) and specificity of 0.55 (95% CI, 0.42-0.66). Meta-analysis of 4 home-based confirmation studies (n = 1001) showed a pooled sensitivity of 0.84 (95% CI, 0.76-0.90) and a specificity of 0.60 (95% CI, 0.48-0.71). Thirteen studies (n = 5150) suggested that screening was associated with no decrement in quality of life or psychological distress; evidence on absenteeism was mixed. Ambulatory blood pressure measurement was associated with temporary sleep disturbance and bruising., Conclusions and Relevance: Screening using office-based blood pressure measurement had major accuracy limitations, including misdiagnosis; however, direct harms of measurement were minimal. Research is needed to determine optimal screening and confirmatory algorithms for clinical practice.

Importance: Ruptured abdominal aortic aneurysms (AAAs) have mortality estimated at 81%., Objective: To systematically review the evidence on benefits and harms of AAA screening and small aneurysm treatment to inform the US Preventive Services Task Force., Data Sources: MEDLINE, PubMed (publisher supplied only), Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials for relevant English-language studies published through September 2018. Surveillance continued through July 2019., Study Selection: Trials of AAA screening benefits and harms; trials and cohort studies of small (3.0-5.4 cm) AAA treatment benefits and harms., Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and extracted data. The Peto method was used to pool odds ratios (ORs) for AAA-related mortality, rupture, and operations; the DerSimonian and Laird random-effects model was used to pool calculated risk ratios for all-cause mortality., Main Outcomes and Measures: AAA and all-cause mortality; AAA rupture; treatment complications., Results: Fifty studies (N = 323 279) met inclusion criteria. Meta-analysis of population-based randomized clinical trials (RCTs) estimated that a screening invitation to men 65 years or older was associated with a reduction in AAA-related mortality over 12 to 15 years (OR, 0.65 [95% CI, 0.57-0.74]; 4 RCTs [n = 124 926]), AAA-related ruptures over 12 to 15 years (OR, 0.62 [95% CI, 0.55-0.70]; 4 RCTs [n = 124 929]), and emergency surgical procedures over 4 to 15 years (OR, 0.57 [95% CI, 0.48-0.68]; 5 RCTS [n = 175 085]). In contrast, no significant association with all-cause mortality benefit was seen at 12- to 15-year follow-up (relative risk, 0.99 [95% CI 0.98-1.00]; 4 RCTs [n = 124 929]). One-time screening was associated with significantly more procedures over 4 to 15 years in the invited group compared with the control group (OR, 1.44 [95% CI, 1.34-1.55]; 5 RCTs [n = 175 085]). Four trials (n = 3314) of small aneurysm surgical treatment demonstrated no significant difference in AAA-related mortality or all-cause mortality compared with surveillance over 1.7 to 12 years. These 4 early surgery trials showed a substantial increase in procedures in the early surgery group. For small aneurysm treatment, registry data (3 studies [n = 14 424]) showed that women had higher surgical complications and postoperative mortality compared with men., Conclusions and Relevance: One-time AAA screening in men 65 years or older was associated with decreased AAA-related mortality and rupture rates but was not associated with all-cause mortality benefit. Higher rates of elective surgery but no long-term differences in quality of life resulted from screening.

Background: Patients with chronic kidney disease (CKD) are at high risk for adverse drug events related to medication dosing errors and prescriptions for relatively contraindicated medications, such as non-steroidal anti-inflammatory drugs (NSAIDs)., Objectives: To examine the scope of and variation in prescribing relatively contraindicated medications and medications above the recommended dose levels among patients with stage III/IV CKD in primary care practice., Methods: This is a cross-sectional descriptive study that used structured electronic health record data. The study participants were patients aged 18 years and older from three primary care clinics in a practice-based research network. Number/proportion of adult patients with stage III/IV CKD; proportion of these patients with at least one NSAID or other relatively contraindicated medication prescribed over 2 years., Results: Of the 7586 eligible adult patients, 4.9% had stage III/IV CKD; 46.6% of these 373 patients with stage III/IV CKD were prescribed at least one relatively contraindicated drug (acarbose, chlorpropamide, glyburide, nitrofurantoin or any NSAID) during the 2-year study period; and 34.0% of patients with stage III/IV CKD were prescribed NSAIDs., Conclusions: Primary care patients with stage III/IV CKD were frequently prescribed or had documented use of relatively contraindicated drugs and thus were at risk of adverse drug events. Given the significant number of individuals with CKD in the USA, research that examines rates of adverse events related to these prescriptions and that tests primary care-based interventions to decrease inappropriate prescribing of relatively contraindicated medications to these patients is needed.

Importance: Peripheral artery disease (PAD) is associated with a high risk for cardiovascular events and poor ambulatory function, even in the absence of symptoms. Screening for PAD with the ankle-brachial index (ABI) may identify patients in need of treatment to improve health outcomes., Objective: To systematically review evidence for the US Preventive Services Task Force on PAD screening with the ABI, the diagnostic accuracy of the test, and the benefits and harms of treatment of screen-detected PAD., Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant English-language studies published between January 2012 and May 2, 2017. Surveillance continued through February 7, 2018., Study Selection: Studies of unselected or generally asymptomatic adults with no known cardiovascular disease., Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers., Main Outcomes and Measures: Cardiovascular morbidity; PAD morbidity; mortality; health-related quality of life; diagnostic accuracy; and serious adverse events., Results: Five studies (N = 5864 participants) were included that examined the indirect evidence for the benefits and harms of screening and treatment of screen-detected PAD. No population-based screening trials evaluated the direct benefits or harms of PAD screening with the ABI alone. A single diagnostic accuracy study of the ABI compared with magnetic resonance angiography gold-standard imaging (n = 306) found low sensitivity (7%-34%) and high specificity (96%-100%) in a screening population. Two adequately powered trials (n = 4626) in asymptomatic populations with and without diabetes with a variably defined low ABI (≤0.95 or ≤0.99) showed no statistically significant effect of aspirin (100 mg daily) for composite CVD outcomes (adjusted hazard ratio [HR], 1.00 [95% CI, 0.81-1.23] and HR, 0.98 [95% CI, 0.76-1.26]). One trial (n = 3350) demonstrated no statistically significant increase in major bleeding events with the use of aspirin (adjusted HR, 1.71 [95% CI, 0.99- 2.97]) and no statistically significant increase in major gastrointestinal bleeding (relative risk, 1.13 [95% CI, 0.44-2.91]). Two exercise trials (n = 932) in screen-relevant populations reported no differences in quality of life, Walking Impairment Questionnaire walking distance, or symptoms at 12 and 52 weeks; no harms were reported., Conclusions and Relevance: There was no direct evidence and limited indirect evidence on the benefits of PAD screening with the ABI in unselected or asymptomatic populations. Available studies suggest low sensitivity and lack of beneficial effect on health outcomes, but these studies have important limitations.

Importance: Falls are the most common cause of injury-related morbidity and mortality among older adults., Objective: To systematically review literature on the effectiveness and harms of fall prevention interventions in community-dwelling older adults to inform the US Preventive Services Task Force., Data Sources: MEDLINE, PubMed, Cumulative Index for Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials for relevant English-language literature published through August 2016, with ongoing surveillance through February 7, 2018., Study Selection: Randomized clinical trials of interventions to prevent falls in community-dwelling adults 65 years and older., Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Random-effects meta-analyses using the method of DerSimonian and Laird., Main Outcomes and Measures: Number of falls (number of unexpected events in which a person comes to rest on the ground, floor, or lower level), people experiencing 1 or more falls, injurious falls, people experiencing injurious falls, fractures, people experiencing fractures, mortality, hospitalizations, institutionalizations, changes in disability, and treatment harms., Results: Sixty-two randomized clinical trials (N = 35 058) examining 7 fall prevention intervention types were identified. This article focused on the 3 most commonly studied intervention types: multifactorial (customized interventions based on initial comprehensive individualized falls risk assessment) (26 trials [n = 15 506]), exercise (21 trials [n = 7297]), and vitamin D supplementation (7 trials [n = 7531]). Multifactorial intervention trials were associated with a reduction in falls (incidence rate ratio [IRR], 0.79 [95% CI, 0.68-0.91]) but were not associated with a reduction in other fall-related morbidity and mortality outcomes. Exercise trials were associated with statistically significant reductions in people experiencing a fall (relative risk, 0.89 [95% 13 CI, 0.81-0.97]) and injurious falls (IRR, 0.81 [95% CI, 0.73-0.90]) and with a statistically nonsignificant reduction in falls (IRR, 0.87 [95% CI, 0.75-1.00]) but showed no association with mortality. Few exercise trials reported fall-related fractures. Seven heterogeneous trials of vitamin D formulations (with or without calcium) showed mixed results. One trial of annual high-dose cholecalciferol (500 000 IU), which has not been replicated, showed an increase in falls, people experiencing a fall, and injuries, while 1 trial of calcitriol showed a reduction in falls and people experiencing a fall; the remaining 5 trials showed no significant difference in falls, people experiencing a fall, or injuries. Harms of multifactorial and exercise trials were rarely reported but generally included minor musculoskeletal injuries., Conclusions and Relevance: Multifactorial and exercise interventions were associated with fall-related benefit, but evidence was most consistent across multiple fall-related outcomes for exercise. Vitamin D supplementation interventions had mixed results, with a high dose being associated with higher rates of fall-related outcomes.

Importance: Recent changes in the periodicity of cervical cancer screening have led to questions about the role of screening pelvic examinations among asymptomatic women., Objective: To systematically review literature on health benefits, accuracy, and harms of the screening pelvic examination for gynecologic conditions for the US Preventive Services Task Force (USPSTF)., Data Sources: MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials for relevant English-language studies published through January 13, 2016, with surveillance through August 3, 2016., Study Selection: Two reviewers independently screened abstracts and studies. The search yielded 8678 unique citations; 316 full-text articles were reviewed, and 9 studies including 27 630 patients met inclusion criteria., Data Extraction and Synthesis: Two reviewers rated study quality using USPSTF criteria., Main Outcomes and Measures: Morbidity; mortality; diagnostic accuracy for any gynecologic cancer or condition except cervical cancer, gonorrhea, and chlamydia, which are covered by other USPSTF screening recommendations; harms (false-positive rates, false-negative rates, surgery rates)., Results: No trials examined the effectiveness of the pelvic examination in reducing all-cause mortality, reducing cancer- and disease-specific morbidity and mortality, or improving quality of life. Eight studies reported accuracy for the screening pelvic examination: ovarian cancer (4 studies; n = 26 432), bacterial vaginosis (2 studies; n = 930), trichomoniasis (1 study; n = 779), and genital herpes (1 study; n = 779). In the 4 ovarian cancer screening studies, low prevalence of ovarian cancer consistently resulted in low positive predictive values (PPVs) and false-positive rates, with a lack of precision in accuracy estimates (sensitivity range, 0%-100%; specificity range, 91%-99%; PPV range, 0%-3.6%; negative predictive value [NPV] range, ≥99%). Each diagnostic accuracy study for bacterial vaginosis, trichomoniasis, and genital herpes was performed in a high-prevalence population with substantial proportions of symptomatic patients and reported accuracy characteristics for individual physical examination findings (bacterial vaginosis, homogeneous discharge: sensitivity range, 69%-79%; specificity range, 54%-97%; PPV range, 52%-95%; NPV range, 79%-80%; herpes simplex virus, vulvar ulcerations: sensitivity, 20%; specificity, 98%; PPV, 88%; NPV, 57%; trichomoniasis, colpitis macularis: sensitivity, 2%; specificity, 100%; PPV, 100%; NPV, 85%). Surgery rates resulting from an abnormal screening pelvic examination for ovarian cancer ranged from 5% to 36% at 1 year, with the largest study reporting an 11% surgery rate and 1% complication rate within 1 year of a screening pelvic examination with abnormal findings., Conclusions and Relevance: No direct evidence was identified for overall benefits and harms of the pelvic examination as a 1-time or periodic screening test. Limited evidence was identified regarding the diagnostic accuracy and harms of routine screening pelvic examinations in asymptomatic primary care populations.

Background: Cardiovascular disease (CVD) is the leading cause of death in the United States., Purpose: To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in adults aged 40 years or older and to evaluate effect modification in subpopulations., Data Sources: MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews., Study Selection: Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events., Data Extraction: Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second., Data Synthesis: Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk [RR], 0.78 [95% CI, 0.71 to 0.87]) but not nonfatal stroke; aspirin showed little or no benefit for all-cause or cardiovascular mortality. Benefits began within the first 5 years. Older adults achieved greater relative MI reduction, but no other effect modifications were found in analyzed subpopulations. In trials with aspirin doses of 100 mg or less per day, the reduction in nonfatal MI benefit persisted (absolute risk reduction, 0.15 to 1.43 events per 1000 person-years) and a 14% reduction in nonfatal stroke benefit was noted, but no benefit was found for all-cause mortality (RR, 0.95 [CI, 0.89 to 1.01]) or cardiovascular mortality (RR, 0.97 [CI, 0.85 to 1.10])., Limitation: Evidence for aspirin in primary prevention is heterogeneous and limited by rare events and few credible subgroup analyses., Conclusion: The beneficial effect of aspirin for the primary prevention of CVD is modest and occurs at doses of 100 mg or less per day. Older adults seem to achieve a greater relative MI benefit., Primary Funding Source: Agency for Healthcare Research and Quality.

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.

Background: Adverse drug events (ADEs) are a leading cause of death in the United States. Patients with stage 3 and 4 chronic kidney disease (CKD) are at particular risk because many medications are cleared by the kidneys. Alerts in the electronic health record (EHR) about drug appropriateness and dosing at the time of prescription have been shown to reduce ADEs for patients with stage 3 and 4 CKD in inpatient settings, but more research is needed about the implementation and effectiveness of such alerts in outpatient settings., Objective: To explore factors that might inform the implementation of an electronic drug-disease alert for patients with CKD in primary care clinics, using Rogers' diffusion of innovations theory as an analytic framework., Methods: Interviews were conducted with key informants in four diverse clinics using various EHR systems. Interviews were audio recorded and transcribed. results Although all clinics had a current method for calculating glomerular filtration rate (GFR), clinics were heterogeneous with regard to current electronic decision support practices, quality improvement resources, and organizational culture and structure., Conclusion: Understanding variation in organizational culture and infrastructure across primary care clinics is important in planning implementation of an intervention to reduce ADEs among patients with CKD.

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 β-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.

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.

Background and Objectives: Efficient and accurate medication refill authorization is an integral service provided by family physicians and an essential skill to teach family medicine residents. The goal of this study was to examine the variation in medication refill protocols, procedures, and resources in family medicine residency practices across a five-state region as a background for development of best practices., Methods: Structured telephone interviews with a key informant at each of 11 clinical practices in a five-state (Washington, Wyoming, Alaska, Montana, and Idaho) family medicine residency network focused on refill protocols and procedures, which personnel have authorization authority, and other factors related to refill protocols and medication prescribing curriculum. Key themes were abstracted from interview notes., Results: There was marked variation in refill protocols and procedures across the clinical sites. While all practices were able to identify their refill procedure, no two practices' procedures were the same, and only 36.4% had a formal written protocol that could be identified by the key informant. All of the practices with formal protocols routinely reviewed medical records before authorizing refills (100%, four/four) compared to less than half of those without formal protocols (42.9%, three/seven). Practices with formal protocols (75.0%) also transferred refill requests between staff prior to authorization more than those without formal protocols (57.1%)., Conclusions: Refill protocols and procedures were highly variable across these family medicine residency program practices. Surprisingly, formal written refill protocols were uncommon. Further research to identify best practices in medication refill procedures associated with safety outcomes is warranted.

Background: Increasing diabetes, hypertension, and hypercholesterolemia rates expose some young women to medications with potential adverse fetal effects, such as angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and statins. This study examined whether quality improvement (QI) interventions promote informed consent and contraception to minimize risks with use of ACE-I/ARB/statins., Methods: This longitudinal cohort study at 7 clinics abstracted medical records of 328 women aged 18 to 44 with ≥1 prescription for ACE-I/ARB/statins and ≥1 visit for hypertension, diabetes, or hypercholesterolemia during the previous year. We measured informed consent documentation and contraceptive methods before and after QI interventions in which providers contacted their patients to discuss medication risks and benefits., Results: Of 179 women who were not surgically sterilized, only 11.7% had documented informed consent related to the risks of ACE-I/ARB/statin use. One hundred fifty-eight women were eligible for the QI intervention (not surgically sterilized, no documented informed consent); only 76 (48.1%) received the intervention. Before the intervention, 23.7% of these 76 were "at risk" of an adverse fetal effect. After the intervention, only 7.9% (P ≤ .001) were "at risk" because some women started contraception, discontinued ACE-I/ARB/statins, or changed drug class., Conclusions: Women prescribed ACE-I/ARB/statins were not consistently using contraception or were not consistently informed of the risks. Provider-implemented QI interventions improved care but were difficult to accomplish, suggesting that new interventions are needed.

Improving patient outcomes in community-based settings is the goal of both the Clinical Translational Science Award program and practice-based quality improvement (QI) programs. Given this common goal, integrating QI and outcomes research is a promising strategy for developing, implementing, and evaluating clinical interventions. This article describes the challenges and strengths illuminated by the conduct of a combined research/QI study in a nascent practice-based research network. Challenges include research's exclusion of clinic patients who might benefit from the intervention; QI programs' less uniform approach to intervention implementation; and the need for both academic and clinically relevant products and publications. A major strength is the increased likelihood of both engaging clinical practices in research and developing successful clinical interventions. Required elements for success include identification of enthusiastic clinical research "champions," involvement of researchers with clinical experience, and adequate funding to support both research and clinical resources and dissemination. Combined Ql/research projects in the practice-based research environment have the potential to improve and shorten the cycle from good idea to improved clinical outcomes in real-world settings., (© 2012 Wiley Periodicals, Inc.)

Background: Cerebrovascular disease is the third leading cause of death in the United States. The proportion of all strokes attributable to previously asymptomatic carotid artery stenosis (CAS) is low. In 1996, the U.S. Preventive Services Task Force concluded that evidence was insufficient to recommend for or against screening of asymptomatic persons for CAS by using physical examination or carotid ultrasonography., Purpose: To examine the evidence of benefits and harms of screening asymptomatic patients with duplex ultrasonography and treatment with carotid endarterectomy for CAS., Data Sources: MEDLINE and Cochrane Library (search dates January 1994 to April 2007), recent systematic reviews, reference lists of retrieved articles, and suggestions from experts., Study Selection: English-language randomized, controlled trials (RCTs) of screening for CAS; RCTs of carotid endarterectomy versus medical treatment; systematic reviews of screening tests; and observational studies of harms from carotid endarterectomy were selected to answer the following questions: Is there direct evidence that screening with ultrasonography for asymptomatic CAS reduces strokes? What is the accuracy of ultrasonography to detect CAS? Does intervention with carotid endarterectomy reduce morbidity or mortality? Does screening or carotid endarterectomy result in harm?, Data Extraction: All studies were reviewed, abstracted, and rated for quality by using predefined Task Force criteria., Data Synthesis: No RCTs of screening for CAS have been done. According to systematic reviews, the sensitivity of ultrasonography is approximately 94% and the specificity is approximately 92%. Treatment of CAS in selected patients by selected surgeons could lead to an approximately 5-percentage point absolute reduction in strokes over 5 years. Thirty-day stroke and death rates from carotid endarterectomy vary from 2.7% to 4.7% in RCTs; higher rates have been reported in observational studies (up to 6.7%)., Limitations: Evidence is inadequate to stratify people into categories of risk for clinically important CAS. The RCTs of carotid endarterectomy versus medical treatment were conducted in selected populations with selected surgeons., Conclusion: The actual stroke reduction from screening asymptomatic patients and treatment with carotid endarterectomy is unknown; the benefit is limited by a low overall prevalence of treatable disease in the general asymptomatic population and harms from treatment.

The major goal of the U.S. Preventive Services Task Force (USPSTF) is to provide a reliable and accurate source of evidence-based recommendations on a wide range of preventive services. In this article, the USPSTF updates and reviews the process by which it evaluates evidence, determines the certainty and magnitude of net benefit, and gives a final letter grade to recommendations. Because direct evidence about prevention is often unavailable, the Task Force usually considers indirect evidence. To guide its selection of indirect evidence, a "chain of evidence" is constructed within an analytic framework. The Task Force examines evidence of various research designs that addresses the key questions within the framework. New terms have been added to describe the USPSTF's judgment about the evidence for each key question: "convincing," "adequate," or "inadequate." For increased clarity, the USPSTF has changed its description of overall evidence of net benefit for the preventive service from "good," "fair," or "poor" quality to "high," "moderate," or "low" certainty. This rating considers the extent to which an uninterrupted chain of evidence exists across the analytic framework. Individual studies will continue to be judged as being of "good," "fair," or "poor" quality. Using outcomes tables, the USPSTF estimates the magnitude of benefits and the magnitude of harms, and synthesizes them into an estimate of the magnitude of net benefit. Although some judgment is required at all steps, the USPSTF strives to make the process as explicit and transparent as possible. The USPSTF anticipates that its methods for making evidence-based recommendations will continue to evolve.

The U.S. Preventive Services Task Force (USPSTF), an independent panel that has provided the gold standard for evidence-based guidelines in prevention for the past 2 decades, continuously refines its methodology. To keep up with the evolving field of evidence- based medicine and to update recommendations in a timely, efficient, and transparent manner, the USPSTF has developed new methods for evidence reviews and recommendation development. This article summarizes the most recent changes in the recommendation development process, including how the USPSTF solicits and prioritizes topics for review, updates evidence reviews and recommendations, and communicates with its audience.

Since 2001, the U.S. Preventive Services Task Force (USPSTF) has worked to refine its methods of evidence review and assessment and to create more usable documents in response to clinicians' needs. These changes have resulted in a revised grading system, as well as a new format and new language for the recommendation statement. This paper focuses on the changes to and the new look of the USPSTF recommendation statement. The new recommendation statement comprises 9 sections. Important changes include standardization of the format of the summary statement to specify what service is being recommended in what population; standardization of the headings in the rationale section; a change in the wording of the grade C recommendation and the I statement; and a new section, called "Other Considerations," in which salient issues related to cost-effectiveness, mandates, and other implementation issues are described.