Recently Published Projects

Objectives: This SR will assess the healthcare strategies for postpartum individuals. Specifically, the review will address the (comparative) benefits and harms of: ● Alternative strategies for postpartum healthcare delivery (Key Question 1) ● Extension of postpartum healthcare or health insurance coverage (Key Question 2)

Objectives: Structured Abstract Objective: We conducted a targeted evidence update to support the US Preventive Services Task Force in updating its 2016 recommendation on Screening for Chronic Obstructive Pulmonary Disease (COPD). Our review addressed three key questions: 1) Does screening for COPD improve health-related quality of life or reduce morbidity or mortality?, 2) Does treatment of screen-detected or mild to moderate COPD improve health-related quality of life or reduce morbidity or mortality?, 3) What are the adverse effects of COPD treatments in this population?; and one contextual question: 1) Does identifying asymptomatic adults with COPD improve the delivery and uptake of targeted preventive services (e.g., smoking cessation, recommended immunizations, lung cancer screening)? Data Sources: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and CINAHL from January 1, 2015, to January 22, 2021, to identify literature published since the previous recommendation. Because the previous review did not include non-pharmacologic interventions, we supplemented these searches by examining reference lists of relevant recent reviews to identify studies prior to 2015. Study Selection: Two investigators independently reviewed abstracts and full-text articles against a set of a priori inclusion and quality criteria. Inclusion criteria for treatment benefits and harms specified persons with mild (defined as forced expiratory volume in 1 second [FEV1] ≥ 80 percent predicted) to moderate (FEV1 50-79 percent predicted) COPD or a mean population FEV1 ≥ 60 percent predicted. Data Analysis: One investigator abstracted data into an evidence table and a second investigator checked these data. We provide a narrative synthesis of the newly identified evidence for each question; quantitative synthesis was not appropriate due to heterogeneity and few trials for any given intervention and outcome. Results: We found no trials examining the effectiveness of screening or active case finding for COPD on health outcomes. We included 16 trials evaluating the treatment of mild to moderate, or minimally symptomatic, COPD: 3 trials (n=20,058) evaluated long acting beta agonists (LABA), long acting muscarinic antagonists (LAMA), and/or inhaled corticosteroids (ICS), and 13 trials (n=3,657) evaluated non-pharmacologic interventions (i.e., self-management interventions, exercise counseling interventions, supervised exercise and pulmonary rehabilitation interventions, and clinician education interventions). Two trials (SUMMIT and UPLIFT) found that LABA, LAMA, ICS, or LABA/ICS reduced exacerbations or clinically important deterioration in persons with fairly symptomatic moderate COPD. One trial (UPLIFT) found that LAMA, specifically tiotropium, also reduced exacerbations in a subgroup analysis (n=357) of persons with minimal symptoms (i.e., GOLD category A). Overall, there was no consistent benefit observed for any type of non-pharmacologic intervention across a range of patient outcomes. One of the two trials (n=114) evaluating the same exercise-focused web-based intervention in a VA population demonstrated a reduction in COPD exacerbations at 65 weeks. Other trials, not conducted in the US, evaluating more intensive self-management interventions, supervised exercise, and pulmonary rehabilitation interventions in persons with mild to moderate COPD, or minimal symptoms, did not demonstrate a reduction in exacerbations or other outcomes. Only three included trials reported on smoking cessation, vaccination, or lung cancer screening outcomes. These trials, combined with six additional comparative studies evaluating the incremental value of receipt of spirometry on smoking cessation, found no consistent improvement in smoking cessation. Only one trial evaluating a clinician training intervention to improve COPD care reported vaccination outcomes and demonstrated an improvement in uptake of influenza vaccination. None of the included treatment trials that reported adverse effects found significant harms. Two large observational studies in a screen-relevant population demonstrated an association of the initiation of LAMA or LABA with the risk of a serious cardiovascular event in treatment-naïve patients and an association of ICS use with the risk of developing diabetes. Limitations: It is unclear how generalizable the observed treatment benefit, the reduction of exacerbations, is to a screen-detected population, as these findings were primarily in persons with fairly symptomatic moderate COPD. It is unclear if and how small sample sizes, usual care comparators in trials conducted outside the US, and/or poor adherence to the non-pharmacologic interventions contributed to the largely null findings of these trials. The small number of included participants and limited length of followup in the majority of included trials (or their relevant subgroup analyses) limits the ability to detect uncommon harms or longer-term harms. Harms of LABA, LAMA, and ICS demonstrated in the included observational trials should be interpreted in context of the larger body of literature on harms of inhaled therapies. Conclusions: The findings of this targeted evidence update are generally consistent with the findings of the previous systematic review supporting the 2016 recommendation. To date, there are still no comparative studies on the effectiveness of screening or active case finding for COPD on patient health outcomes. The demonstrated benefits of pharmacologic treatment for COPD are still largely limited to persons with moderate airflow obstruction; and there was no consistent benefit observed for a range of non-pharmacologic interventions in mild to moderate COPD, or in minimally symptomatic persons with COPD.

Objectives: To synthesize the evidence on benefits and harms of behavioral counseling interventions to promote a healthy diet and physical activity in adults without known cardiovascular disease (CVD) risk factors to inform a US Preventive Services Task Force recommendation.. All 113 studies were randomized clinical trials (RCTs) of behavioral interventions targeting improved diet, increased physical activity, or decreased sedentary time among adults without known elevated blood pressure, elevated lipids, or impaired fasting glucose.

Objectives: Background: Cardiovascular disease (CVD) is the leading cause of death and colorectal cancer (CRC) is the third leading cause of death in the United States. Purpose: To systematically review evidence for the effectiveness of aspirin to prevent myocardial infarction (MI), stroke, cardiovascular death, and all-cause mortality in those without a history of CVD. In addition, to review evidence for CRC incidence and mortality associated with aspirin use in primary and secondary CVD populations. To further review harms associated with aspirin use. Data Sources: We searched MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials to identify literature that was published between January 2014 and January 14, 2021. We supplemented our searches with reference lists from the previous review, relevant existing systematic reviews, suggestions from experts, and Clinicaltrials.gov to identify ongoing trials. We conducted ongoing surveillance for relevant literature through January 21, 2022. Study Selection: Two investigators independently reviewed identified abstracts and full text articles against a set of a priori inclusion and quality criteria. Data Analysis: One investigator abstracted data into an evidence table and a second investigator checked these data. We conducted Peto fixed effects meta-analyses to estimate the effect size of aspirin in preventing MI, stroke, CVD-related death and all-cause mortality, CRC incidence and mortality, major bleeding, major gastrointestinal (GI) bleeding, intracranial bleeding, hemorrhagic stroke, and extracranial bleeding. Additionally, we conducted sensitivity analyses using Mantel-Haenszel fixed effects and Restricted Maximum Likelihood random effects. Results: We included 13 fair- to good-quality randomized, controlled trials (RCTs) (N=161,680) examining the effectiveness of aspirin for the primary prevention of CVD. Based on pooled analysis of 11 primary CVD prevention trials using aspirin ≤100 mg/day, low-dose aspirin reduces the risk of major CVD events (total MI, total stroke, CVD mortality) by 10 percent (k=11, N=134,470; Peto odds ratio [OR], 0.90 [95% confidence interval (CI), 0.85 to 0.95]), MI by 11 percent (k=11, N=134,470; Peto OR, 0.89 [95% CI, 0.82 to 0.96]), and ischemic stroke by 18 percent (k=5, N=79,334; Peto OR, 0.82 [95% CI, 0.72 to 0.92]) with no differences in CVD mortality (k=11, N=134,470; Peto OR, 0.95 [95% CI, 0.86 to 1.05]) or all-cause mortality (k=11, N=134,470; Peto OR 0.98 [95% CI, 0.93 to 1.03]). Absolute risk reductions in major CVD events in the trials ranged from 0.08 to 2.5 percent. Aspirin’s benefits were similar when trials of all doses were pooled. Sensitivity analyses restricted to more recent trials where usual care includes aggressive risk factor modification including statin therapy show diminished effects of aspirin for major CVD events and total MI but larger effects for total ischemic stroke compared to older trials. A small subset of the trials reporting CVD outcomes also reported CRC outcomes. Based on 4 low-dose aspirin trials (N=86,137) recruiting primary CVD prevention populations, there was no statistically significant association between aspirin and CRC incidence when analyzing randomized trial periods (Peto OR 1.07 [95% CI, 0.92 to 1.24]; trial period 5-10 years). Analysis including post-trial observation periods up to 20 years and including trials with high-dose aspirin up to 500 mg/day (k=2; N=45,015) in primary prevention populations show statistically significant reductions in CRC incidence (0.70 [95% CI, 0.50 to 0.98] and 0.82 [95% CI, 0.69 to 0.98]). Two low-dose aspirin RCTs (N=59,020) in primary CVD prevention populations report CRC mortality during the trial period (5-10 years) showing results concerning for possible harm with one trial demonstrating a statistically significant increase in CRC mortality in older adults. At 18 years of followup, including post-trial observational periods, three primary CVD prevention trials with mean daily aspirin doses ranging from 75 to 500 mg showed aspirin was associated with a decreased risk of CRC mortality (Peto OR 0.76 [95% CI, 0.62 to 0.94]). Low-dose aspirin is associated with a 31 percent increase in intracranial bleeding events (k=11; N=134,470; Peto OR, 1.31 [95% CI, 1.11 to 1.54]), and 53 percent increase in extracranial bleeding events (k=10; N=133,194; Peto OR 1.53 [95% CI, 1.39 to 1.70]). The absolute increases ranged from -0.2 to 0.4 percent for intracranial bleeding events and 0.2 to 0.9 percent for extracranial bleeding events. There is no compelling evidence to suggest that aspirin has a different relative CVD benefit or bleeding risk in specific populations defined by age, sex, race and ethnicity, diabetes status, or baseline 10-year CVD risk. Aspirin’s CVD benefits appear to begin within the first 1-2 years of administration and the bleeding harms begin soon after aspirin initiation; there are limited data for more precise time increments or longer durations. Limitations: Primary CVD prevention trials used different aspirin doses in heterogeneous populations with relatively short study followup, with duration mostly ranging from 4-6 years. Trials reporting CRC incidence and mortality outcomes are limited by short trial duration and multiple comparisons; observational followup of trials are limited by heterogeneity of aspirin doses, duration, indications, and populations with risk of biases and confounding. Estimates of rare bleeding harms are imprecise. Conclusions: In primary prevention populations, low-dose aspirin reduces major CVD events, MI and ischemic stroke, but also increases major GI bleeding, extracranial bleeding, and intracranial bleeding. Our evidence suggests aspirin is associated with a possible long-term reduction in CRC incidence and mortality based on post-trial period observation, but the results are limited for low-dose aspirin among primary CVD prevention populations. More precise real-world U.S.-based estimates for bleeding events in the general population and specific populations with elevated CVD risk are necessary to accurately estimate the net benefit. Depending on CVD risk, this absolute CVD benefit in specific populations could potentially outweigh the bleeding risks. Models to identify these populations are needed.

Objectives: Background: Hormone therapy plays an important role in the clinical management of menopausal symptoms. Because of an increased risk of harms, hormone therapy is currently not recommended for the primary prevention of chronic conditions. Purpose: To update evidence on the effectiveness of hormone therapy in reducing risk of chronic conditions, its adverse effects, and differences among population subgroups for the U.S. Preventive Services Task Force. Data Sources: We searched MEDLINE, the Cochrane Library, and Embase for English-language articles (through October 12, 2021). We conducted searches for unpublished literature by searching ClinicalTrials.gov, HSRProj, the World Health Organization’s International Clinical Trials Registry Platform, and NIH RePORTER. In addition, we reviewed reference lists of pertinent review articles and studies meeting our inclusion criteria. We conducted surveillance of the literature through June 1, 2022. Study Selection: We dually reviewed the literature and included randomized, placebo-controlled trials and large controlled cohort studies that provided information on the primary prevention of chronic conditions with hormone therapy and reported health outcomes. Data Extraction: We abstracted details about participants, study design, analysis, followup, and results; study quality and strength of evidence were rated using established criteria. Data Synthesis: Twenty fair- or good-quality trials and three large controlled cohort studies met eligibility criteria. The Women’s Health Initiative was the largest study and most applicable to the target population. Results of our review indicate differences in the risk-benefit profile between treatment formulations. Women using estrogen only had statistically significantly lower risk (per 10,000 women over 6.8 to 7.2 years) of diabetes (134 fewer cases) and fractures (388 fewer cases) than women taking placebo. However, risk (per 10,000 women over 5.4 to 7.1 years) was statistically significantly increased for gallbladder disease (377 more cases), stroke (79 more cases), and venous thromboembolism (77 more cases). Women using estrogen plus progestin therapy experienced statistically significantly lower risk (per 10,000 women over 5.0 to 5.6 years) for colorectal cancer (34 fewer cases), diabetes (78 fewer cases), and fractures (230 fewer cases) than women taking placebo. Risk (per 10,000 women over 4 to 5.6 years) of invasive breast cancer (51 more cases), probable dementia (88 more cases), gallbladder disease (260 more cases), stroke (52 more cases), and venous thromboembolism (120 more cases) was statistically significantly increased compared with women taking placebo. The risk of urinary incontinence (562 more cases per 10,000 women) was increased during a followup of 1 year. Meta-analyses rendered no statistically significant differences in all-cause mortality between women receiving hormone therapy and those receiving placebo (over 2 to 7.2 years for estrogen-only therapy and over 3.2 to 5.6 years for estrogen plus progestin therapy). Limitations: Few trials or subgroup analyses were powered for prevention outcomes. No comparative evidence on type, dose, and mode of delivery of hormone therapy is available. The applicability of results to younger women who initiate hormone therapy to manage menopausal symptoms and to women of non-White ethnic backgrounds might be limited. Conclusions: Women undergoing hormone therapy for the primary prevention of chronic conditions experience some beneficial effects but also an increased risk of harms.