Interventions to Prevent Falls in Older Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

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.

Screening for Lipid Disorders in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

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.

Anxiety Screening: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Anxiety is commonly seen in primary care and associated with substantial burden. Objective: To review the benefits and harms of screening and treatment for anxiety and the accuracy of instruments to detect anxiety among primary care patients. Data Sources: MEDLINE, PsychINFO, Cochrane library through September 7, 2022; references of existing reviews; ongoing surveillance for relevant literature through November 25, 2022. Study Selection: English-language original studies and systematic reviews of screening or treatment compared with control conditions and test accuracy studies of a priori-selected screening instruments were included. Two investigators independently reviewed abstracts and full-text articles for inclusion. Two investigators independently rated study quality. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Meta-analysis results were included from existing systematic reviews where available; meta-analyses were conducted on original research when evidence was sufficient. Main Outcomes and Measures: Anxiety and depression outcomes; global quality of life and functioning; sensitivity and specificity of screening tools. Results: Of the 59 publications included, 40 were original studies (N = 275 489) and 19 were systematic reviews (including ≈483 studies [N≈81 507]). Two screening studies found no benefit for screening for anxiety. Among test accuracy studies, only the Generalized Anxiety Disorder (GAD) GAD-2 and GAD-7 screening instruments were evaluated by more than 1 study. Both screening instruments had adequate accuracy for detecting generalized anxiety disorder (eg, across 3 studies the GAD-7 at a cutoff of 10 had a pooled sensitivity of 0.79 [95% CI, 0.69 to 0.94] and specificity of 0.89 [95% CI, 0.83 to 0.94]). Evidence was limited for other instruments and other anxiety disorders. A large body of evidence supported the benefit of treatment for anxiety. For example, psychological interventions were associated with a small pooled standardized mean difference of -0.41 in anxiety symptom severity in primary care patients with anxiety (95% CI, -0.58 to -0.23]; 10 RCTs [n = 2075]; I2 = 40.2%); larger effects were found in general adult populations. Conclusions and Relevance: Evidence was insufficient to draw conclusions about the benefits or harms of anxiety screening programs. However, clear evidence exists that treatment for anxiety is beneficial, and more limited evidence indicates that some anxiety screening instruments have acceptable accuracy to detect generalized anxiety disorder.

Depression and Suicide Risk Screening: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Depression is common and associated with substantial burden. Suicide rates have increased over the past decade, and both suicide attempts and deaths have devastating effects on individuals and families. Objective: To review the benefits and harms of screening and treatment for depression and suicide risk and the accuracy of instruments to detect these conditions among primary care patients. Data Sources: MEDLINE, PsychINFO, Cochrane library through September 7, 2022; references of existing reviews; ongoing surveillance for relevant literature through November 25, 2022. Study Selection: English-language studies of screening or treatment compared with control conditions, or test accuracy of screening instruments (for depression, instruments were selected a priori; for suicide risk, all were included). Existing systematic reviews were used for treatment and test accuracy for depression. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Findings were synthesized qualitatively, including reporting of meta-analysis results from existing systematic reviews; meta-analyses were conducted on original research when evidence was sufficient. Main Outcomes and Measures: Depression outcomes; suicidal ideation, attempts, and deaths; sensitivity and specificity of screening tools. Results: For depression, 105 studies were included: 32 original studies (N=385 607) and 73 systematic reviews (including ≈2138 studies [N ≈ 9.8 million]). Depression screening interventions, many of which included additional components beyond screening, were associated with a lower prevalence of depression or clinically important depressive symptomatology after 6 to 12 months (pooled odds ratio, 0.60 [95% CI, 0.50-0.73]; reported in 8 randomized clinical trials [n=10 244]; I2 = 0%). Several instruments demonstrated adequate test accuracy (eg, for the 9-item Patient Health Questionnaire at a cutoff of 10 or greater, the pooled sensitivity was 0.85 [95% CI, 0.79-0.89] and specificity was 0.85 [95% CI, 0.82-0.88]; reported in 47 studies [n = 11 234]). A large body of evidence supported benefits of psychological and pharmacologic treatment of depression. A pooled estimate from trials used for US Food and Drug Administration approval suggested a very small increase in the absolute risk of a suicide attempt with second-generation antidepressants (odds ratio, 1.53 [95% CI, 1.09-2.15]; n = 40 857; 0.7% of antidepressant users had a suicide attempt vs 0.3% of placebo users; median follow-up, 8 weeks). Twenty-seven studies (n = 24 826) addressed suicide risk. One randomized clinical trial (n=443) of a suicide risk screening intervention found no difference in suicidal ideation after 2 weeks between primary care patients who were and were not screened for suicide risk. Three studies of suicide risk test accuracy were included; none included replication of any instrument. The included suicide prevention studies generally did not demonstrate an improvement over usual care, which typically included specialty mental health treatment. Conclusions and Relevance: Evidence supported depression screening in primary care settings, including during pregnancy and postpartum. There are numerous important gaps in the evidence for suicide risk screening in primary care settings.

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

Importance: Skin cancer is the most common cancer type and is a major cause of morbidity. Objective: To systematically review the benefits and harms of screening for skin cancer to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from June 1, 2015, through January 7, 2022; surveillance through December 16, 2022. Study Selection: English-language studies conducted in asymptomatic populations 15 years or older. Data Extraction and Synthesis: Two reviewers independently appraised the articles and extracted relevant data from fair- or good-quality studies; results were narratively summarized. Main Outcomes and Measures: Morbidity; mortality; skin cancer stage, precursor lesions, or lesion thickness at detection; harms of screening. Results: Twenty studies in 29 articles were included (N = 6 053 411). Direct evidence on screening effectiveness was from 3 nonrandomized analyses of 2 population-based skin cancer screening programs in Germany (n = 1 791 615) and suggested no melanoma mortality benefit at the population level over 4 to 10 years' follow-up. Six studies (n = 2 935 513) provided inconsistent evidence on the association between clinician skin examination and lesion thickness or stage at diagnosis. Compared with usual care, routine clinician skin examination was not associated with increased detection of skin cancer or precursor lesions (5 studies) or stage at melanoma detection (3 studies). Evidence on the association between clinician skin examination and lesion thickness at detection was inconsistent (3 studies). Nine studies (n = 1 326 051) found a consistent positive association between more advanced stage at melanoma detection and increasing risk of melanoma-associated and all-cause mortality. Two studies (n = 232) found little to no persistent cosmetic or psychosocial harms associated with screening. Conclusions and Relevance: A substantial nonrandomized evidence base suggests a clear association between earlier stage at skin cancer detection and decreased mortality risk. However, nonrandomized studies suggest little to no melanoma mortality benefit associated with skin cancer screening with visual skin examination in adolescents or adults and no association between routine clinician skin examination and earlier stage at melanoma detection. Evidence is inconsistent regarding whether clinician skin examination is associated with thinner melanoma lesions at detection.

Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

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.

Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Updated Modeling Study for the US Preventive Services Task Force.

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.

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 US. Objective: To systematically review the effectiveness, test accuracy, and harms of screening for CRC to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2015, to December 4, 2019; surveillance through March 26, 2021. 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 cancers or adenomas, and serious adverse events. Results: The review included 33 studies (n = 10 776 276) on the effectiveness of screening, 59 (n = 3 491 045) on the test performance of screening tests, and 131 (n = 26 987 366) on the harms of screening. In randomized clinical trials (4 trials, n = 458 002), intention to screen with 1- or 2-time flexible sigmoidoscopy vs no screening was associated with a decrease in CRC-specific mortality (incidence rate ratio, 0.74 [95% CI, 0.68-0.80]). Annual or biennial guaiac fecal occult blood test (gFOBT) vs no screening (5 trials, n = 419 966) was associated with a reduction of CRC-specific mortality after 2 to 9 rounds of screening (relative risk at 19.5 years, 0.91 [95% CI, 0.84-0.98]; relative risk at 30 years, 0.78 [95% CI, 0.65-0.93]). In observational studies, receipt of screening colonoscopy (2 studies, n = 436 927) or fecal immunochemical test (FIT) (1 study, n = 5.4 million) vs no screening was associated with lower risk of CRC incidence or mortality. Nine studies (n = 6497) evaluated the test accuracy of screening computed tomography (CT) colonography, 4 of which also reported the test accuracy of colonoscopy; pooled sensitivity to detect adenomas 6 mm or larger was similar between CT colonography with bowel prep (0.86) and colonoscopy (0.89). In pooled values, commonly evaluated FITs (14 studies, n = 45 403) (sensitivity, 0.74; specificity, 0.94) and stool DNA with FIT (4 studies, n = 12 424) (sensitivity, 0.93; specificity, 0.85) performed better than high-sensitivity gFOBT (2 studies, n = 3503) (sensitivity, 0.50-0.75; specificity, 0.96-0.98) to detect cancers. Serious harms of screening colonoscopy included perforations (3.1/10 000 procedures) and major bleeding (14.6/10 000 procedures). CT colonography may have harms resulting from low-dose ionizing radiation. It is unclear if detection of extracolonic findings on CT colonography is a net benefit or harm. Conclusions and Relevance: There are several options to screen for colorectal cancer, each with a different level of evidence demonstrating its ability to reduce cancer mortality, its ability to detect cancer or precursor lesions, and its risk of harms.

Screening for Hypertension in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

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.

Colorectal Cancer Screening: An Updated Modeling Study for the US Preventive Services Task Force.

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations. Objective: To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF. Design, Setting, and Participants: Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer. Exposures: Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed. Main Outcome and Measures: Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies. Results: Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer. Conclusions and Relevance: This microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained.

Interventions to Prevent Illicit and Nonmedical Drug Use in Children, Adolescents, and Young Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Illicit and nonmedical (use in ways other than instructed) drug use is common in adolescents and young adults and increases the risk of harmful outcomes such as injuries, violence, and poorer academic performance. Objective: To review the benefits and harms of interventions to prevent illicit and nonmedical drug use in children, adolescents, and young adults to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMED, PsycINFO, and the Cochrane Central Register of Controlled Trials (January 1, 2013, to January 31, 2019 [children and adolescents]; January 1, 1992, to January 31, 2019 [young adults <25 years]); surveillance through March 20, 2020. Study Selection: Clinical trials of behavioral counseling interventions to prevent initiation of illicit and nonmedical drug use among young people. Data Extraction and Synthesis: Critical appraisal was completed independently by 2 investigators. Data were extracted by 1 reviewer and checked by a second. Random-effects meta-analysis was used to estimate the effect sizes associated with the interventions. Main Outcomes and Measures: Number of times illicit drugs were used; any illicit drug or any cannabis use. Results: Twenty-nine trials (N = 18 353) met inclusion criteria. Health, social, or legal outcomes such as mental health symptoms, family functioning, consequences of drug use, and arrests were reported in 19 trials and most showed no group differences. The effects on illicit drug use in 26 trials among nonpregnant youth (n = 17 811) were highly variable; the pooled result did not show a clinically important or statistically significant association with illicit drug use (standardized mean difference, -0.08 [95% CI, -0.16 to 0.001]; 24 effects [from 23 studies]; n = 12 801; I2 = 57.0%). The percentage of participants using illicit drugs ranged from 2.3% to 38.6% in the control groups and 2.4% to 33.7% in the intervention groups at 3 to 32 months' follow-up. The median absolute risk difference between groups was -2.8%, favoring the intervention group (range, -11.5% to 14.8%). The remaining 3 trials provided a perinatal home-visiting intervention to pregnant Native American youth. One trial (n=322) found a reduction in illicit drug use at 38 months (eg, cannabis use in the previous month, 10.7% in the intervention group and 15.6% in the control group) but not at earlier follow-up assessments. Across all 29 trials, only 1 trial reported on harms and found no statistically significant group differences. Conclusions and Relevance: The evidence for behavioral counseling interventions to prevent initiation of illicit and nonmedical drug use among adolescents and young adults was inconsistent and imprecise, with some interventions associated with reduction in use and others associated with no benefit or increased use. Health, social, and legal outcomes were sparsely reported, and few showed improvements.

Screening for Cognitive Impairment in Older Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Early identification of cognitive impairment may improve patient and caregiver health outcomes. Objective: To systematically review the test accuracy of cognitive screening instruments and benefits and harms of interventions to treat cognitive impairment in older adults (≥65 years) to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, and Cochrane Central Register of Controlled Trials through January 2019, with literature surveillance through November 22, 2019. Study Selection: Fair- to good-quality English-language studies of cognitive impairment screening instruments, and pharmacologic and nonpharmacologic treatments aimed at persons with mild cognitive impairment (MCI), mild to moderate dementia, or their caregivers. Data Extraction and Synthesis: Independent critical appraisal and data abstraction; random-effects meta-analyses and qualitative synthesis. Main Outcomes and Measures: Sensitivity, specificity; patient, caregiver, and clinician decision-making; patient function, quality of life, and neuropsychiatric symptoms; caregiver burden and well-being. Results: The review included 287 studies with more than 280 000 older adults. One randomized clinical trial (RCT) (n = 4005) examined the direct effect of screening for cognitive impairment on patient outcomes, including potential harms, finding no significant differences in health-related quality of life at 12 months (effect size, 0.009 [95% CI, -0.063 to 0.080]). Fifty-nine studies (n = 38 531) addressed the accuracy of 49 screening instruments to detect cognitive impairment. The Mini-Mental State Examination was the most-studied instrument, with a pooled sensitivity of 0.89 (95% CI, 0.85 to 0.92) and specificity of 0.89 (95% CI, 0.85 to 0.93) to detect dementia using a cutoff of 23 or less or 24 or less (15 studies, n = 12 796). Two hundred twenty-four RCTs and 3 observational studies including more than 240 000 patients or caregivers addressed the treatment of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, participants were persons with known cognitive impairment. Medications approved to treat Alzheimer disease (donepezil, galantamine, rivastigmine, and memantine) improved scores on the ADAS-Cog 11 by 1 to 2.5 points over 3 months to 3 years. Psychoeducation interventions for caregivers resulted in a small benefit for caregiver burden (standardized mean difference, -0.24 [95% CI, -0.36 to -0.13) over 3 to 12 months. Intervention benefits were small and of uncertain clinical importance. Conclusions and Relevance: Screening instruments can adequately detect cognitive impairment. There is no empirical evidence, however, that screening for cognitive impairment improves patient or caregiver outcomes or causes harm. It remains unclear whether interventions for patients or caregivers provide clinically important benefits for older adults with earlier detected cognitive impairment or their caregivers.

Screening for Unhealthy Drug Use: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Illicit drug use is among the most common causes of preventable morbidity and mortality in the US. Objective: To systematically review the literature on screening and interventions for drug use to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, Embase, and Cochrane Central Register of Controlled Trials through September 18, 2018; literature surveillance through September 21, 2019. Study Selection: Test accuracy studies to detect drug misuse and randomized clinical trials of screening and interventions to reduce drug use. Data Extraction and Synthesis: Critical appraisal and data abstraction by 2 reviewers and random-effects meta-analyses. Main Outcomes and Measures: Sensitivity, specificity, drug use and other health, social, and legal outcomes. Results: Ninety-nine studies (N = 84 206) were included. Twenty-eight studies (n = 65 720) addressed drug screening accuracy. Among adults, sensitivity and specificity of screening tools for detecting unhealthy drug use ranged from 0.71 to 0.94 and 0.87 to 0.97, respectively. Interventions to reduce drug use were evaluated in 52 trials (n = 15 659) of psychosocial interventions, 7 trials (n = 1109) of opioid agonist therapy, and 13 trials (n = 1718) of naltrexone. Psychosocial interventions were associated with increased likelihood of drug use abstinence (15 trials, n = 3636; relative risk [RR], 1.60 [95% CI, 1.24 to 2.13]; absolute risk difference [ARD], 9% [95% CI, 5% to 15%]) and reduced number of drug use days (19 trials, n = 5085; mean difference, -0.49 day in the last 7 days [95% CI, -0.85 to -0.13]) vs no psychosocial intervention at 3- to 4-month follow-up. In treatment-seeking populations, opioid agonist therapy and naltrexone were associated with decreased risk of drug use relapse (4 trials, n = 567; RR, 0.75 [95% CI, 0.59 to 0.82]; ARD, -35% [95% CI, -67% to -3%] and 12 trials, n = 1599; RR, 0.73 [95% CI, 0.62 to 0.85]; ARD, -18% [95% CI, -26% to -10%], respectively) vs placebo or no medication. While evidence on harms was limited, it indicated no increased risk of serious adverse events. Conclusions and Relevance: Several screening instruments with acceptable sensitivity and specificity are available to screen for drug use, although there is no direct evidence on the benefits or harms of screening. Pharmacotherapy and psychosocial interventions are effective at improving drug use outcomes, but evidence of effectiveness remains primarily derived from trials conducted in treatment-seeking populations.

Interventions to Prevent Falls in Older Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

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.

Screening and Behavioral Counseling Interventions to Reduce Unhealthy Alcohol Use in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Unhealthy alcohol use is common, increasing, and a leading cause of premature mortality. Objective: To review literature on the effectiveness and harms of screening and counseling for unhealthy alcohol use to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials through October 12, 2017; literature surveillance through August 1, 2018. Study Selection: Test accuracy studies and randomized clinical trials of screening and counseling to reduce unhealthy alcohol use. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Counseling trials were pooled using random-effects meta-analyses. Main Outcomes and Measures: Sensitivity, specificity, drinks per week, exceeding recommended limits, heavy use episodes, abstinence (for pregnant women), and other health, family, social, and legal outcomes. Results: One hundred thirteen studies (N = 314 466) were included. No studies examined benefits or harms of screening programs to reduce unhealthy alcohol use. For adolescents (10 studies [n = 171 363]), 1 study (n = 225) reported a sensitivity of 0.73 (95% CI, 0.60 to 0.83) and specificity of 0.81 (95% CI, 0.74 to 0.86) using the AUDIT-C (Alcohol Use Disorders Identification Test-Consumption) to detect the full spectrum of unhealthy alcohol use. For adults (35 studies [n = 114 182]), brief screening instruments commonly reported sensitivity and specificity between 0.70 and 0.85. Two trials of the effects of interventions to reduce unhealthy alcohol use in adolescents (n = 588) found mixed results: one reported a benefit in high-risk but not moderate-risk drinkers, and the other reported a statistically significant reduction in drinking frequency for boys but not girls; neither reported health or related outcomes. Across all populations (68 studies [n = 36 528]), counseling interventions were associated with a decrease in drinks per week (weighted mean difference, -1.6 [95% CI, -2.2 to -1.0]; 32 studies [37 effects; n = 15 974]), the proportion exceeding recommended drinking limits (odds ratio [OR], 0.60 [95% CI, 0.53 to 0.67]; 15 studies [16 effects; n = 9760]), and the proportion reporting a heavy use episode (OR, 0.67 [95% CI, 0.58 to 0.77]; 12 studies [14 effects; n = 8108]), and an increase in the proportion of pregnant women reporting abstinence (OR, 2.26 [95% CI, 1.43 to 3.56]; 5 studies [n = 796]) after 6 to 12 months. Health outcomes were sparsely reported and generally did not demonstrate group differences in effect. There was no evidence that these interventions could be harmful. Conclusions and Relevance: Among adults, screening instruments feasible for use in primary care are available that can effectively identify people with unhealthy alcohol use, and counseling interventions in those who screen positive are associated with reductions in unhealthy alcohol use. There was no evidence that these interventions have unintended harmful effects.

Periodic Screening Pelvic Examination: Evidence Report and Systematic Review for the US Preventive Services Task Force.

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.

Primary Care Interventions to Support Breastfeeding: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Although 80% of infants in the United States start breastfeeding, only 22% are exclusively breastfed up to around 6 months as recommended by a number of professional organizations. Objective: To systematically review the evidence on the benefits and harms of breastfeeding interventions to support the US Preventive Services Task Force in updating its 2008 recommendation. Data Sources: MEDLINE, PubMed, Cumulative Index for Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and PsycINFO for studies published in the English language between January 1, 2008, and September 25, 2015. Studies included in the previous review were re-evaluated for inclusion. Surveillance for new evidence in targeted publications was conducted through January 26, 2016. Study Selection: Review of randomized clinical trials and before-and-after studies with concurrent controls conducted in a developed country that evaluated a primary care-relevant breastfeeding intervention among mothers of full- or near-term infants. Of 211 full-text articles reviewed, 52 studies met inclusion criteria. Thirty-one studies were newly identified, and 21 studies were carried forward from the previous review. Data Extraction and Synthesis: Independent critical appraisal of all provisionally included studies. Data were independently abstracted by one reviewer and confirmed by another. Main Outcomes and Measures: Child and maternal health outcomes, rates and duration of breastfeeding, and harms related to interventions as prespecified before data collection. Results: Fifty-two studies (n = 66 757) in 57 publications were included. Six trials (n = 2219) reported inconsistent effects of the interventions on infant health outcomes; no studies reported maternal health outcomes. Pooled estimates based on random-effects meta-analyses using the DerSimonian and Laird method indicated beneficial associations between individual-level breastfeeding interventions and any breastfeeding for less than 3 months (risk ratio [RR], 1.07 [95% CI, 1.03-1.11]; 26 studies [n = 11 588]), at 3 to less than 6 months (RR, 1.11 [95% CI, 1.04-1.18]; 23 studies [n = 8942]), and for exclusive breastfeeding for less than 3 months (RR, 1.21 [95% CI, 1.11-1.33]; 22 studies [n = 8246]), 3 to less than 6 months (RR, 1.20 [95% CI, 1.05-1.38]; 18 studies [n = 7027]), and at 6 months (RR, 1.16 [95% CI, 1.02-1.32]; 17 studies [n = 7690]). Absolute differences in the rates of any breastfeeding ranged from 14.1% in favor of the control group to 18.4% in favor of the intervention group. There was no significant association between interventions and breastfeeding initiation (RR, 1.00 [95% CI, 0.99-1.02]; 14 studies [n = 9428]). There was limited mixed evidence of an association between system-level interventions and rates of breastfeeding from well-controlled studies as well as for harms related to breastfeeding interventions, including maternal anxiety scores, decreased confidence, and concerns about confidentiality. Conclusions and Relevance: The updated evidence confirms that breastfeeding support interventions are associated with an increase in the rates of any and exclusive breastfeeding. There are limited well-controlled studies examining the effectiveness of system-level policies and practices on rates of breastfeeding or child health and none for maternal health.

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.

Primary care behavioral interventions to prevent or reduce illicit drug use and nonmedical pharmaceutical use in children and adolescents: a systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: Drug use among youths is associated with negative health and social consequences. Even infrequent use increases the risk for serious adverse events by increasing risk-taking behaviors in intoxicated or impaired persons. PURPOSE: To systematically review the benefits and harms of primary care-relevant interventions designed to prevent or reduce illicit drug use or the nonmedical use of prescription drugs among youths. DATA SOURCES: PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials through 4 June 2013; MEDLINE through 31 August 2013; and manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently reviewed 2253 abstracts and 144 full-text articles. English-language trials of primary care-relevant behavioral interventions that reported drug use, health outcomes, or harms were included. DATA EXTRACTION: One investigator abstracted data from good- and fair-quality trials into prespecified evidence tables, and a second investigator checked these data. DATA SYNTHESIS: Six trials were included, 4 of which examined the effect of the intervention on a health or social outcome. One trial found no effect of the intervention on marijuana-related consequences or driving under the influence of marijuana; 3 trials generally found no reduction in depressed mood at 12 or 24 months. Four of the 5 trials assessing self-reported marijuana use found statistically significant differences favoring the intervention group participants (such as a between-group difference of 0.10 to 0.17 use occasions in the past month). Three trials also reported positive outcomes in nonmedical prescription drug use occasions. LIMITATIONS: The body of evidence was small, and there were heterogeneous measures of outcomes of limited clinical applicability. Trials primarily included adolescents with little or no substance use. CONCLUSION: Evidence is inadequate on the benefits of primary care-relevant behavioral interventions in reducing self-reported illicit and pharmaceutical drug use among adolescents. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Primary care-relevant interventions for tobacco use prevention and cessation in children and adolescents: a systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: Interventions to prevent smoking uptake or encourage cessation among young persons might help prevent tobacco-related illness. PURPOSE: To review the evidence for the efficacy and harms of primary care-relevant interventions that aim to reduce tobacco use among children and adolescents. DATA SOURCES: Three systematic reviews that collectively covered the relevant literature; MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, and the Database of Abstracts of Reviews of Effects through 14 September 2012; and manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently reviewed 2453 abstracts and 111 full-text articles. English-language trials of behavior-based or medication interventions that were relevant to primary care and reported tobacco use, health outcomes, or harms were included. DATA EXTRACTION: One investigator abstracted data from good- and fair-quality trials into an evidence table, and a second checked these data. DATA SYNTHESIS: 19 trials (4 good-quality and 15 fair-quality) that were designed to prevent tobacco use initiation or promote cessation (or both) and reported self-reported smoking status or harms were included. Pooled analyses from a random-effects meta-analysis suggested a 19% relative reduction (risk ratio, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, -0.02 [CI, -0.03 to 0.00]) in smoking initiation among participants in behavior-based prevention interventions compared with control participants. Neither behavior-based nor bupropion cessation interventions improved cessation rates. Findings about the harms related to bupropion use were mixed. LIMITATIONS: No studies reported health outcomes. Interventions and measures were heterogeneous. Most trials examined only cigarette smoking. The body of evidence was largely published 5 to 15 years ago. CONCLUSION: Primary care-relevant interventions may prevent smoking initiation over 12 months in children and adolescents.