Interventions for Weight Management in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Body mass index (BMI) of the 95th or greater percentile for age and sex is common among young people, and its prevalence has increased in recent decades. Objective: To examine the benefits and harms of weight management interventions initiated in health care settings among children and adolescents with high BMI. Data Sources: MEDLINE via Ovid, PsycINFO via Ovid, and the Cochrane Central Registry of Controlled Trials through January 12, 2023; ongoing surveillance through January 26, 2024. Study Selection: English-language studies of weight management interventions (behavioral and pharmacologic, including liraglutide, semaglutide, orlistat, and phentermine/topiramate) among children aged 2 to 18 years with high BMI (eg, ≥85th or ≥95th percentile for age and sex) conducted in or recruited from health care settings. Data Extraction and Synthesis: One investigator abstracted data; a second checked for accuracy. Outcomes with sufficient evidence for meta-analysis were pooled using random-effects models. Main Outcomes and Measures: BMI and other weight-related outcomes, cardiometabolic measures, quality of life, physical activity, dietary pattern scores, and harms. Results: Fifty-eight randomized clinical trials (RCTs) were included (N = 10 143). Behavioral interventions were associated with small reductions in BMI and other weight outcomes after 6 to 12 months (28 RCTs [n = 4494]; mean difference in change between groups, -0.7 [95% CI, -1.0 to -0.3]). Larger effects were seen in interventions with higher contact hours and that offered physical activity sessions. Reporting was sparse for outcomes other than BMI, with few significant findings. Semaglutide and phentermine/topiramate had the largest effects on BMI (eg, 1 RCT [n = 201] for semaglutide; mean difference, -6.0 [95% CI, -7.3 to -4.6]). The very few studies that evaluated outcomes after medication discontinuation showed immediate weight regain. Gastrointestinal adverse effects were common with liraglutide, semaglutide, and orlistat. Serious adverse effects were rare, but no studies had follow-up longer than 17 months. Conclusions and Relevance: In the short term, weight management interventions led to lower BMI in children and adolescents, with no evidence of serious harm. Evidence is lacking about how weight management interventions affect BMI beyond 1 year and after medication discontinuation and about longer-term effects on other outcomes.

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 Preeclampsia and Related Morbidity and Mortality: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Preeclampsia is a hypertensive disorder of pregnancy that poses serious maternal and infant health risks. Previous systematic reviews have established benefits of low-dose aspirin taken during pregnancy to prevent preeclampsia and its sequelae. Objective: To update evidence for the US Preventive Services Task Force (USPSTF) on effectiveness of aspirin use in preventing preeclampsia in individuals at increased risk based on clinical risk factors or measurements associated with higher disease incidence than in the general population. Data Sources: Studies from previous USPSTF review (2014), literature published January 2013 through May 15, 2020, in MEDLINE, PubMed (for publisher-supplied records only), EMBASE, and Cochrane Central Register of Controlled Trials. Ongoing surveillance through January 22, 2021. Study Selection: Good- and fair-quality randomized clinical trials (RCTs) of low-dose aspirin use during pregnancy to prevent preeclampsia among individuals at increased risk; studies conducted in general populations to evaluate potential harms. Data Extraction and Synthesis: Dual article screening and risk-of-bias assessment. Study data abstracted into prespecified forms, checked for accuracy. Random-effects meta-analysis. Main Outcomes and Measures: Diagnosis of preeclampsia; adverse pregnancy health outcomes and complications including eclampsia, perinatal mortality, preterm birth, small for gestational age, and potential bleeding harms or infant/child harms from aspirin exposure. Results: A total of 23 randomized clinical trials (RCTs) (N = 26 952) were included; 18 were conducted among participants at increased preeclampsia risk. Aspirin dosages ranged from 50 mg/d to 150 mg/d. Most trials enrolled majority White populations selected based on a range of risk factors. The incidence of preeclampsia among the trials of participants at increased risk ranged from 4% to 30%. Aspirin use was significantly associated with lower risk of preeclampsia (pooled relative risk [RR], 0.85 [95% CI, 0.75-0.95]; 16 RCTs [n = 14 093]; I2 = 0%), perinatal mortality (pooled RR, 0.79 [95% CI, 0.66-0.96]; 11 RCTs [n = 13 860]; I2 = 0%), preterm birth (pooled RR, 0.80 [95% CI, 0.67-0.95]; 13 RCTs [n = 13 619]; I2 = 49%), and intrauterine growth restriction (pooled RR, 0.82 [95% CI, 0.68-0.99]; 16 RCTs [n = 14 385]; I2 = 41%). There were no significant associations of aspirin use with risk of postpartum hemorrhage (pooled RR, 1.03 [95% CI, 0.94-1.12]; 9 RCTs [n = 23 133]; I2 = 0%) and other bleeding-related harms, or with rare perinatal or longer-term harms. Absolute risk reductions for preeclampsia associated with aspirin use ranged from -1% to -6% across larger trials (n >300) and were greater in smaller trials. For perinatal mortality, absolute risk reductions ranged from 0.5% to 1.1% in the 3 largest trials. Conclusions and Relevance: Daily low-dose aspirin during pregnancy was associated with lower risks of serious perinatal outcomes for individuals at increased risk for preeclampsia, without evident harms.

Behavioral Counseling Interventions to Prevent Sexually Transmitted Infections: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Increasing rates of preventable sexually transmitted infections (STIs) in the US pose substantial burdens to health and well-being. Objective: To update evidence for the US Preventive Services Task Force (USPSTF) on effectiveness of behavioral counseling interventions for preventing STIs. Data Sources: Studies from the previous USPSTF review (2014); literature published January 2013 through May 31, 2019, in MEDLINE, PubMed (for publisher-supplied records only), PsycINFO, and Cochrane Central Register of Controlled Trials. Ongoing surveillance through May 22, 2020. Study Selection: Good- and fair-quality randomized and nonrandomized controlled intervention studies of behavioral counseling interventions for adolescents and adults conducted in primary care settings were included. Studies with active comparators only or limited to individuals requiring specialist care for STI risk-related comorbidities were excluded. Data Extraction and Synthesis: Dual risk of bias assessment, with inconsistent ratings adjudicated by a third team member. Study data were abstracted into prespecified forms. Pooled odds ratios (ORs) were estimated using the DerSimonian and Laird method or the restricted maximum likelihood method with Knapp-Hartung adjustment. Main Outcomes and Measures: Differences in STI diagnoses, self-reported condom use, and self-reported unprotected sex at 3 months or more after baseline. Results: The review included 37 randomized trials and 2 nonrandomized controlled intervention studies (N = 65 888; 13 good-quality, 26 fair-quality) recruited from primary care settings in the US. Study populations were composed predominantly of heterosexual adolescents and young adults (12 to 25 years), females, and racial and ethnic minorities at increased risk for STIs. Nineteen trials (n = 52 072) reported STI diagnoses as outcomes (3 to 17 months' follow-up); intervention was associated with reduced STI incidence (OR, 0.66 [95% CI, 0.54-0.81; I2 = 74%]). Absolute differences in STI acquisition between groups varied widely depending on baseline population STI risk and intervention effectiveness, ranging from 19% fewer to 4% more people acquiring STI. Thirty-four trials (n = 21 417) reported behavioral change outcomes. Interventions were associated with self-reported behavioral change (eg, increased condom use) that reduce STI risk (OR, 1.31 [95% CI, 1.10-1.56; I2 = 40%, n = 5253). There was limited evidence on persistence of intervention effects beyond 1 year. No harms were identified in 7 studies (n = 3458) reporting adverse outcomes. Conclusions and Relevance: Behavioral counseling interventions for individuals seeking primary health care were associated with reduced incidence of STIs. Group or individual counseling sessions lasting more than 2 hours were associated with larger reductions in STI incidence, and interventions of shorter duration also were associated with STI prevention, although evidence was limited on whether the STI reductions associated with these interventions persisted beyond 1 year.

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.

Primary Care Screening for Abdominal Aortic Aneurysm: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

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.

Interventions to Prevent Perinatal Depression: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Depression during pregnancy and the postpartum period is relatively common and can have adverse effects on both mother and child. Objective: To systematically review benefits and harms of primary care-relevant interventions to prevent perinatal depression, a major or minor depressive episode during pregnancy or up to 1 year after childbirth, to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMED (for publisher-supplied records only), PsycINFO, and the Cochrane Central Register of Controlled Trials; surveillance through December 5, 2018. Study Selection: Randomized clinical trials (RCTs) and nonrandomized controlled intervention studies of interventions (eg, behavior-based, antidepressants, dietary supplements) to prevent perinatal depression in general populations of pregnant and postpartum individuals or in those at increased risk of perinatal depression. Large cohort studies were considered for harms of antidepressant use only. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and quality rated included studies. Random-effects meta-analysis was used to estimate the benefits of the interventions. Main Outcomes and Measures: Depression status; depression symptoms; maternal, infant, and child health outcomes. Results: Fifty studies (N = 22 385) that met inclusion criteria were identified. Counseling interventions were the most widely studied interventions. Compared with controls, counseling interventions were associated with a lower likelihood of onset of perinatal depression (pooled risk ratio [RR], 0.61 [95% CI, 0.47-0.78]; 17 RCTs [n = 3094]; I2 = 39.0%). The absolute difference in the risk of perinatal depression ranged from 1.3% greater reduction in the control group to 31.8% greater reduction in the intervention group. Health system interventions showed a benefit in 3 studies (n = 5321) and had a pooled effect size similar to that of the counseling interventions, but the pooled effect was not statistically significant using a method appropriate for pooling a small number of studies (restricted maximum likelihood RR, 0.58 [95% CI, 0.22-1.53]; n = 4738; I2 = 66.3%; absolute risk reduction range, -3.1% to -13.1%). None of the behavior-based interventions reported on harms directly. A smaller percentage of participants prescribed sertraline had a depression recurrence compared with those prescribed placebo (7% vs 50%, P = .04) at 20 weeks postpartum in 1 very small RCT (n = 22 analyzed) but with an increased risk of adverse effects to the mother. Conclusions and Relevance: Counseling interventions can be effective in preventing perinatal depression, although most evidence was limited to women at increased risk for perinatal depression. A variety of other intervention approaches provided some evidence of effectiveness but lacked a robust evidence base and need further research.

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.

Screening for Cervical Cancer With High-Risk Human Papillomavirus Testing: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Cervical cancer can be prevented with detection and treatment of precancerous cell changes caused primarily by high-risk types of human papillomavirus (hrHPV), the causative agents in more than 90% of cervical cancers. Objective: To systematically review benefits and harms of cervical cancer screening for hrHPV to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials from January 2011 through February 15, 2017; surveillance through May 25, 2018. Study Selection: Randomized clinical trials (RCTs) and cohort studies comparing primary hrHPV screening alone or hrHPV cotesting (both hrHPV testing and cytology) with cytology (Papanicolaou [Pap] test) screening alone. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and quality rated included studies; data were qualitatively synthesized. Main Outcomes and Measures: Invasive cervical cancer; cervical intraepithelial neoplasia (CIN); false-positive, colposcopy, and biopsy rates; psychological harms. Results: Eight RCTs (n = 410 556), 5 cohort studies (n = 402 615), and 1 individual participant data (IPD) meta-analysis (n = 176 464) were included. Trials were heterogeneous for screening interval, number of rounds, and protocol. For primary hrHPV screening, evidence was consistent across 4 trials demonstrating increased detection of CIN 3 or worse (CIN 3+) in round 1 (relative risk [RR] range, 1.61 [95% CI, 1.09-2.37] to 7.46 [95% CI, 1.02-54.66]). Among 4 hrHPV cotesting trials, first-round CIN 3+ detection was not significantly different between screening groups; RRs for cumulative CIN 3+ detection over 2 screening rounds ranged from 0.91 to 1.13. In first-round screening, false-positive rates for primary hrHPV screening ranged from 6.6% to 7.4%, compared with 2.6% to 6.5% for cytology. For cotesting, false-positives ranged from 5.8% to 19.9% in the first round of screening, compared with 2.6% to 10.9% for cytology. First-round colposcopy rates were also higher, ranging 1.2% to 7.9% for primary hrHPV testing, compared with 1.1% to 3.1% for cytology alone; colposcopy rates for cotesting ranged from 6.8% to 10.9%, compared with 3.3% to 5.2% for cytology alone. The IPD meta-analysis of data from 4 cotesting trials and 1 primary hrHPV screening trial found lower risk of invasive cervical cancer with any hrHPV screening compared with cytology alone (pooled RR, 0.60 [95% CI, 0.40-0.89]). Conclusions and Relevance: Primary hrHPV screening detected higher rates of CIN 3+ at first-round screening compared with cytology. Cotesting trials did not show initial increased CIN 3+ detection. Both hrHPV screening strategies had higher false-positive and colposcopy rates than cytology, which could lead to more treatments with potential harms.

Behavioral Counseling to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Known Cardiovascular Disease Risk Factors: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Unhealthful dietary patterns, low levels of physical activity, and high sedentary time increase the risk of cardiovascular disease. OBJECTIVE: To systematically review the evidence on the benefits and harms of behavioral counseling for the primary prevention of cardiovascular disease in adults without known cardiovascular risk factors to inform the US Preventive Services Task Force. DATA SOURCES: MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, and PsycINFO for studies published in the English language between January 1, 2013, and May 25, 2016, and ongoing surveillance in targeted publications through March 24, 2017. Studies included in the previous review were reevaluated for inclusion. STUDY SELECTION: Randomized clinical trials of behavioral interventions targeting improved diet, increased physical activity, decreased sedentary time, or a combination of these among adults without known hypertension, dyslipidemia, diabetes, or impaired fasting glucose. DATA EXTRACTION AND SYNTHESIS: Independent critical appraisal and data abstraction by 2 reviewers. MAIN OUTCOMES AND MEASURES: Cardiometabolic health and intermediate outcomes, behavioral outcomes, and harms related to interventions. RESULTS: Eighty-eight studies (N = 121 190) in 145 publications were included. There was no consistent benefit of the interventions on all-cause or cardiovascular mortality or morbidity (4 trials [n = 51 356]) or health-related quality of life (10 trials [n = 52 423]). There was evidence of small, statistically significant between-group mean differences for systolic blood pressure (-1.26 mm Hg [95% CI, -1.77 to -0.75]; 22 trials [n = 57 953]), diastolic blood pressure (-0.49 mm Hg [95% CI, -0.82 to -0.16]; 23 trials [n = 58 022]), low-density lipoprotein cholesterol level (-2.58 mg/dL [95% CI, -4.30 to -0.85]; 13 trials [n = 5554]), total cholesterol level (-2.85 mg/dL [95% CI, -4.95 to -0.75]; 19 trials [n = 9325]), and body mass index (-0.41 [95% CI, -0.62 to -0.19]; 20 trials [n = 55 059]) at 6 to 12 months as well as small-to-modest associations with dietary and physical activity behaviors. There was no evidence of greater incidence of serious adverse events, injuries, or falls in intervention vs control participants. CONCLUSIONS AND RELEVANCE: Diet and physical activity behavioral interventions for adults not at high risk for cardiovascular disease result in consistent modest benefits across a variety of important intermediate health outcomes across 6 to 12 months, including blood pressure, low-density lipoprotein and total cholesterol levels, and adiposity, with evidence of a dose-response effect, with higher-intensity interventions conferring greater improvements. There is very limited evidence on longer-term intermediate and health outcomes or on harmful effects of these interventions.

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.

Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force.

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.

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

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

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

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

Behavioral counseling to promote a healthy lifestyle in persons with cardiovascular risk factors: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Most Americans do not meet diet and physical activity recommendations despite known health benefits. PURPOSE: To systematically review the benefits and harms of lifestyle counseling interventions in persons with cardiovascular risk factors for the U.S. Preventive Services Task Force. DATA SOURCES: MEDLINE, PsycINFO, the Database of Abstracts of Reviews of Effects, and the Cochrane Central Register of Controlled Trials (January 2001 to October 2013); experts; and existing systematic reviews. STUDY SELECTION: Two investigators independently reviewed 7218 abstracts and 553 articles against a set of inclusion and quality criteria. DATA EXTRACTION: Data from 74 trials were abstracted by one reviewer and checked by a second. DATA SYNTHESIS: At 12 to 24 months, intensive lifestyle counseling in persons selected for risk factors reduced total cholesterol levels by an average of 0.12 mmol/L (95% CI, 0.16 to 0.07 mmol/L) (4.48 mg/dL [CI, 6.36 to 2.59 mg/dL]), low-density lipoprotein cholesterol levels by 0.09 mmol/L (CI, 0.14 to 0.04 mmol/L) (3.43 mg/dL [CI, 5.37 to 1.49 mg/dL]), systolic blood pressure by 2.03 mm Hg (CI, 2.91 to 1.15 mm Hg), diastolic blood pressure by 1.38 mm Hg (CI, 1.92 to 0.83 mm Hg), fasting glucose levels by 0.12 mmol/L (CI, 0.18 to 0.05 mmol/L) (2.08 mg/dL [CI, 3.29 to 0.88 mg/dL]), diabetes incidence by a relative risk of 0.58 (CI, 0.37 to 0.89), and weight outcomes by a standardized mean difference of 0.25 (CI, 0.35 to 0.16). Behavioral changes in dietary intake and physical activity were generally concordant with changes in physiologic outcomes. LIMITATION: Sparse reporting of patient health outcomes, longer-term follow-up of outcomes, and harms. CONCLUSION: Intensive diet and physical activity behavioral counseling in persons with risk factors for cardiovascular disease resulted in consistent improvements across various important intermediate health outcomes up to 2 years. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Low-dose aspirin for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. PURPOSE: To systematically review benefits and harms of low-dose aspirin for preventing morbidity and mortality from preeclampsia. DATA SOURCES: MEDLINE, Database of Abstracts of Reviews of Effects, PubMed, and Cochrane Central Register of Controlled Trials (January 2006 to June 2013); previous systematic reviews, clinical trial registries, and surveillance searches for large studies (June 2013 to February 2014). STUDY SELECTION: Randomized, controlled trials (RCTs) to assess benefits among women at high preeclampsia risk and RCTs or large cohort studies of harms among women at any risk level. English-language studies of fair or good quality were included. DATA EXTRACTION: Dual quality assessment and abstraction of studies. DATA SYNTHESIS: Two large, multisite RCTs and 13 smaller RCTs of high-risk women (8 good-quality) were included, in addition to 6 RCTs and 2 observational studies of average-risk women to assess harms (7 good-quality). Depending on baseline risk, aspirin use was associated with absolute risk reductions of 2% to 5% for preeclampsia (relative risk [RR], 0.76 [95% CI, 0.62 to 0.95]), 1% to 5% for intrauterine growth restriction (RR, 0.80 [CI, 0.65 to 0.99]), and 2% to 4% for preterm birth (RR, 0.86 [CI, 0.76 to 0.98]). No significant perinatal or maternal harms were identified, but rare harms could not be ruled out. Evidence on long-term outcomes was sparse, but 18-month follow-up from the largest trial found no developmental harms. LIMITATIONS: Benefits may have been overestimated due to small-study effects. Predictive intervals were not statistically significant. Future studies could shift findings toward the null. CONCLUSION: Daily low-dose aspirin beginning as early as the second trimester prevented clinically important health outcomes. No harms were identified, but long-term evidence was limited.

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

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

Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force.

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