Recently Published Projects

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.

Objectives: Background: The first entry complications at laparoscopy in obese individuals is unclear. The role of the entry device rather than technique in the course of complications is a necessary evaluation to further understand first access injuries. Purpose: To summarise findings from both randomised and observational studies assessing first access injuries in obese patients according to the characteristics of the entry device utilised. Data Sources: Embase, Cochrane Library, Scopus, PubMed including MEDLINE, Web of Science and Clinicaltrials.gov were searched for eligible articles published in English with no date limits. Study Selection: 2 authors screened article abstracts to retrieve trials investigating laparoscopic first access injuries with eligibility resting on studies that recruited obese individuals and providing device type with outcomes detailing all injuries sustained. Data Extraction: The screening authors extracted data documenting the obese class of patients enrolled in the trials, alongside the type of entry device employed and the resultant complications incurred in establishing abdominal entry.

Objectives: Purpose: To systematically review the evidence on screening and treating asymptomatic adults with obstructive sleep apnea (OSA) or those with unrecognized symptoms for OSA. Data Sources: PubMed/MEDLINE, the Cochrane Library, Embase, and trial registries through August 23, 2021; reference lists of retrieved articles; outside experts; and reviewers, with surveillance of the literature through September 23, 2022. Study Selection: Two investigators independently selected English-language studies using a priori criteria. Eligible studies included randomized, controlled trials (RCTs) of screening for or treatment of OSA reporting on health outcomes, studies evaluating accuracy of screening questionnaires or clinical prediction tools in asymptomatic adults with OSA or persons with unrecognized symptoms of OSA, and systematic reviews of treatment reporting on changes in blood pressure (BP) and apnea-hypopnea index (AHI) scores. Data Extraction: One investigator extracted data and a second checked accuracy. Two reviewers independently rated data quality for all included studies using predefined criteria. Data Synthesis: No reviewed RCT directly compared screening with no screening. In two studies (702 total participants), the screening accuracy measured as AUC of the Multivariable Apnea Prediction (MVAP) score followed by unattended home sleep testing for detecting severe OSA syndrome (AHI ≥30 and Epworth Sleepiness Scale [ESS] score >10) was 0.80 (95% confidence interval [CI], 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90), respectively. Studies evaluating the Snoring, Tiredness, Observed apnea, blood Pressure, Body mass index, Age, Neck circumference, Gender (STOP-BANG) Questionnaire (k=4) and the Berlin Questionnaire (BQ) (k=2) enrolled different populations and used different criteria for a positive screening test. Recent systematic reviews of positive airway pressure (PAP) and mandibular advancement devices (MADs) show an association between PAP and MAD and reduction in BP and AHI, however reduction in BP outcomes versus inactive control is relatively small (2 to 3 mm Hg). Meta-analysis found that PAP compared with any control was associated with a significantly larger reduction in ESS score change (pooled mean difference, -2.33 [95% CI, -2.75 to -1.90]; 47 trials, 7,024 participants), modest improvement in sleep-related quality of life (QOL) (standardized mean difference, 0.30 [95% CI, 0.19 to 0.42]; 18 trials, 3,083 participants), and improved general health-related QOL measured by the SF-36 mental health component summary score change (2.20 [95% CI, 0.95 to 3.44]; 15 trials, 2,345 participants) and SF-36 physical health component summary score change (pooled mean difference, 1.53 [95% CI, 0.29 to 2.77]; 13 trials, 2,031 participants). Meta-analysis also found that use of MADs was associated with a significantly larger ESS score change than controls (pooled mean difference, -1.67 [95% CI, -2.09 to -1.25]; 10 trials, 1,540 participants). Reporting of other health outcomes was sparse; no included trial found significant benefit associated with PAP or MAD on mortality, cardiovascular outcomes, stroke, or motor vehicle accidents. Common adverse effects of PAP and MADs included oral or nasal dryness, irritation, and pain, among others. Limitations: Two studies assessing the accuracy of the MVAP score oversampled participants at high risk of OSA and those with OSA syndrome. No study prospectively evaluated screening Screening for Obstructive Sleep Apnea in Adults v RTI–UNC EPC tools to report calibration or clinical utility for improving health outcomes. Three studies assessing the accuracy of the STOP-BANG and two assessing the BQ enrolled different populations and used different criteria for positive screening tests. Most included trials assessing the benefit of PAP and MADs reported outcomes over a relatively short duration (12 weeks or less), and most pooled estimates showing improvement in excessive sleepiness or QOL (except benefit of PAP for improving ESS scores) fell short of the range considered to be a minimal clinically important difference. Populations enrolled in trials of treatment were referred for treatment; no trial enrolled populations who were identified by screening in primary care. Conclusions: The accuracy and clinical utility of potential screening tools for OSA that could be used in primary care settings are uncertain. PAP and MADs reduce AHI, BP and ESS score. Trials of PAP have not established whether treatment reduces mortality or improves most other health outcomes, except for its modest improvement in sleep-related QOL and general health–related QOL.