Brittany U Burda

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 β-carotene prevented CVD or cancer, and β-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.

Diagnostic and Predictive Accuracy of Blood Pressure Screening Methods With Consideration of Rescreening Intervals: A Systematic Review for the U.S. Preventive Services Task Force

Nearly 1 in 3 U.S. adults has high blood pressure (BP), including two thirds of those aged 60 years or older (1). Elevated BP is the largest contributing risk factor to all-cause and cardiovascular mortality (2). Despite the clear importance of accurate diagnosis of high BP, recommendations for BP measurement protocols and rescreening intervals are not based on systematic reviews of the literature (3, 4), and recommended protocols, such as repeated measurements, are rarely followed in routine health care settings (59). To help address these issues, newer measurement methods have been developed to reduce error, simplify performance of repeated measurements, evaluate BP throughout the 24-hour cycle, and allow use in nonmedical settings. Evidence-based measurement methods and rescreening intervals could improve the benefits and efficiency of BP screening. In 2007, the U.S. Preventive Services Task Force (USPSTF) reaffirmed its 2003 A recommendation to screen for high BP in adults aged 18 years or older (10). In 2003, a synthesis of indirect evidence for BP screening found good-quality evidence that treatment of high BP in adults substantially decreases the incidence of cardiovascular events (11). Both reviews found that screening and treatment for high BP cause few major harms (11, 12). Given the strong evidence base for the previous recommendations and recently updated guidelines for BP control (4, 13), the USPSTF did not believe that updating the indirect evidence path was necessary. However, the previous systematic reviews did not identify a BP measurement reference standard, address diagnostic accuracy of BP measurement methods and protocols, or determine the most appropriate rescreening interval. Our evidence review was designed to address these important aspects of screening for high BP and update the direct evidence of benefits and harms of screening. Methods To conduct this review, we developed an analytic framework with 5 key questions (Appendix Figure 1) that examined direct evidence for the benefits and harms of screening for high BP (key questions 1 and 5, respectively), diagnostic accuracy of office BP measurement (OBPM) (key question 2), prediction of cardiovascular events by BP method and diagnostic accuracy of nonoffice measurement (key question 3), and rescreening interval (key question 4). Detailed methods are available in our full evidence report (14). The analytic framework, review questions, and methods for locating and qualifying evidence were posted on the USPSTF Web site for public comment before we started the review, and the final versions reflect public input. Appendix Figure 1. Analytic framework. ABPM = ambulatory blood pressure monitoring; BP = blood pressure; CHD = coronary heart disease; CVD = cardiovascular disease; ESKD = end-stage kidney disease; HBPM = home blood pressure monitoring; HF = heart failure. * Defined as the threshold for pharmacologic treatment. Data Sources and Searches We searched MEDLINE, PubMed, the Cochrane Central Register of Controlled Trials, and CINAHL from 2003 through 8 August 2014 to update benefits and harms of screening for high BP. We searched the same databases (excluding CINAHL) through 24 February 2014 as follows: starting in 1992 (to allow for implementation of the first guidelines for validation of BP monitoring devices [15]) for prediction of cardiovascular events by BP method and diagnostic accuracy of nonoffice measurement, and starting in 1966 (the beginning of MEDLINE) for rescreening interval. On the basis of the findings from these updated searches, we did not further update them because any studies we found would probably not have changed the overall conclusions. We also searched bibliographies of relevant reviews, included studies, and publication lists of highly referenced studies. Study Selection Two investigators independently reviewed abstracts and full-text articles against prespecified inclusion and exclusion criteria (14). We required all studies to have enrolled untreated adults and to have been conducted in countries rated as very high on the 2013 Human Development Index (16). For prediction of cardiovascular events, we allowed studies that included treated patients because a proportion of persons followed over time would inevitably begin treatment. Ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM) devices were eligible for use in confirming an initially elevated OBPM result. For screening benefits and harms, cardiovascular events we analyzed included fatal or nonfatal myocardial infarction; sudden cardiac death; stroke; heart failure; atrial fibrillation; transient ischemic attack; end-stage kidney disease; or a composite of any of the aforementioned events, excluding cardiovascular symptoms, angina, revascularization, carotid intimamedia thickness, and left ventricular hypertrophy. For diagnostic accuracy of OBPM, we included studies that compared different office-based devices or measurement protocols and reported sensitivity, specificity, predictive values, or concordance (for example, ). For diagnostic accuracy of confirmatory BP measurement methods, eligible study populations had an initial elevated office BP at screening, which allowed for reporting or calculation of the positive predictive value (PPV). For prediction of cardiovascular events, eligible studies followed a cohort of patients over time and reported the associations (hazard or risk ratios) of BP as a continuous variable, measured by at least 2 methods at baseline, with data on overall mortality or cardiovascular events collected during follow-up. For rescreening interval, we included studies that followed cohorts of initially nonhypertensive adults over time and reported hypertension incidence at rescreening intervals of up to 6 years. Data Extraction and Quality Assessment One investigator abstracted data from all included studies, and a second checked for accuracy. Two investigators independently assessed the quality of included studies by using predefined, design-specific criteria (1719). We rated study quality as good, fair, or poor and excluded all poor-quality studies (17). We resolved disagreements about quality through discussion with a third investigator. Where reported, studies with various threats to internal validity were downgraded to fair-quality according to USPSTF standards (17). Data Synthesis and Analysis We qualitatively described the results on the benefits and harms of screening. Per our protocol, we first calculated the diagnostic accuracy of OBPM by using the recommendations of the American Heart Association as the reference standard because there is no gold standard for BP measurement (3). With the subsequent identification of ABPM as the best predictor of cardiovascular events, we calculated the diagnostic accuracy of OBPM and confirmatory BP measurement methods by using ABPM as the reference standard where possible. We qualitatively described all diagnostic accuracy results because data were insufficient for quantitative synthesis. For prediction of cardiovascular events, we combined fatal and nonfatal events within outcome categories (cardiovascular, stroke, and cardiac). Risk was most commonly reported as the hazard ratio associated with each 10mm Hg increase in systolic BP and each 5mm Hg increase in diastolic BP. We converted hazard ratios to these common increments if they were reported differently (14). We depicted the hazard ratios in forest plots for qualitative evaluation; because of the small numbers of studies for each outcome and heterogeneity across studies, we did not calculate summary meta-analytic estimates of risk to determine the best BP measurement method for prediction. We conducted exploratory meta-analyses to compare ABPM protocols (24-hour, daytime, and nighttime) by generating estimates of cardiovascular events or mortality risk for each protocol by using the DerSimonianLaird random-effects method (20). In sensitivity analyses, these results were compared to estimates generated by using profile likelihood (21) and KnappHartung methods (22). For rescreening, we pooled reported incidence rates across all studies to generate a weighted mean incidence at yearly intervals (reported within0.5 year). We qualitatively examined within-study comparisons among a priori subgroups of age, BP, sex, body mass index (BMI), smoking status, and race/ethnicity (14). When constructing the overall summary of evidence (Appendix Table 1), we evaluated included studies within the context of each review question for consistency of results for important outcomes and relevance to primary care. Appendix Table 1. Overall Summary of Evidence, by Key Question Role of the Funding Source Staff from the Agency for Healthcare Research and Quality (AHRQ) provided oversight for the project and assisted in external review of the companion draft evidence synthesis. Liaisons for the USPSTF helped to resolve issues about the scope of the review but were not involved in the conduct of the review. Results We reviewed 19309 abstracts and 1171 articles for possible inclusion (Appendix Figure 2). Appendix Figure 2. Summary of evidence search and selection. KQ = key question. * Surveillance search results through August 2014 for trials reporting direct benefits of screening were not included; no additional trials were identified. Benefits of Screening for High BP For direct evidence of screening benefit, we included only randomized, controlled trials (RCTs) that reported changes in health outcomes as a result of screening for hypertension compared with no screening. We identified 1 good-quality cluster RCT of a community pharmacybased BP screening program targeting adults aged 65 years or older (23). Trained volunteer health educators also provided participants with educational materials and resources to support self-management. This trial found fewer annual composite cardiovascular-related hospitalizations in the intervention group than in t

Liquid-Based Cytology and Human Papillomavirus Testing to Screen for Cervical Cancer: A Systematic Review for the U.S. Preventive Services Task Force

BACKGROUND Screening programs using conventional cytology have successfully reduced cervical cancer, but newer tests might enhance screening. PURPOSE To systematically review the evidence on liquid-based cytology (LBC) and high-risk human papillomavirus (HPV) screening for U.S. Preventive Services Task Force use in updating its 2003 recommendation. DATA SOURCES MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2000 through September 2010. STUDY SELECTION Two independent reviewers selected fair- to good-quality English-language studies that compared LBC or HPV-enhanced primary screening with conventional cytology in countries with developed population-based screening for cervical cancer. DATA EXTRACTION At least 2 independent reviewers critically appraised and rated the quality of studies and used standardized abstraction forms to extract data about test performance for detecting cervical intraepithelial neoplasia (CIN) and cancer and screening-related harms. DATA SYNTHESIS On the basis of 4 fair- to good-quality studies (141 566 participants), LBC had equivalent sensitivity and specificity to conventional cytology. Six fair- to good-quality diagnostic accuracy studies showed that 1-time HPV screening was more sensitive than cytology for detecting CIN3+/CIN2+ but was less specific. On the basis of 2 fair- to good-quality randomized, controlled trials (RCTs) (120 533 participants), primary HPV screening detected more cases of CIN3 or cancer in women older than 30 years. Four fair- to good-quality diagnostic accuracy studies and 4 fair- to good-quality RCTs showed mixed results of cotesting (HPV plus cytology) in women aged 30 years or older compared with cytology alone, with no clear advantage over primary HPV screening. Incomplete reporting of results for all screening rounds, including detection of disease and colposcopies, limits our ability to determine the net benefit of HPV-enhanced testing strategies. LIMITATION Resources were insufficient to gather unpublished data, short-term trial data showed possible ascertainment bias, and most RCTs used protocols that differed from current U.S. practice. CONCLUSION Evidence supports the use of LBC or conventional cytology for cervical cancer screening, but more complete evidence is needed before HPV-enhanced primary screening is widely adopted for women aged 30 years or older.

Screening for and treatment of suicide risk relevant to primary care: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND In 2009, suicide accounted for 36 897 deaths in the United States. PURPOSE To review the accuracy of screening instruments and the efficacy and safety of screening for and treatment of suicide risk in populations and settings relevant to primary care. DATA SOURCES Citations from MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, and CINAHL (2002 to 17 July 2012); gray literature; and a surveillance search of MEDLINE for additional screening trials (July to December 2012). STUDY SELECTION Fair- or good-quality English-language studies that assessed the accuracy of screening instruments in primary care or similar populations and trials of suicide prevention interventions in primary or mental health care settings. DATA EXTRACTION One investigator abstracted data; a second checked the abstraction. Two investigators rated study quality. DATA SYNTHESIS Evidence was insufficient to determine the benefits of screening in primary care populations; very limited evidence identified no serious harms. Minimal evidence suggested that screening tools can identify some adults at increased risk for suicide in primary care, but accuracy was lower in studies of older adults. Minimal evidence limited to high-risk populations suggested poor performance of screening instruments in adolescents. Trial evidence showed that psychotherapy reduced suicide attempts in high-risk adults but not adolescents. Most trials were insufficiently powered to detect effects on deaths. LIMITATION Treatment evidence was derived from high-risk rather than screening-detected populations. Evidence relevant to adolescents, older adults, and racial or ethnic minorities was limited. CONCLUSION Primary care-feasible screening tools might help to identify some adults at increased risk for suicide but have limited ability to detect suicide risk in adolescents. Psychotherapy may reduce suicide attempts in some high-risk adults, but effective interventions for high-risk adolescents are not yet proven. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Conflict of interest in clinical practice guideline development: a systematic review.

Background There is an emerging literature on the existence and effect of industry relationships on physician and researcher behavior. Much less is known, however, about the effects of these relationships and other conflicts of interest (COI) on clinical practice guideline (CPG) development and recommendations. We performed a systematic review of the prevalence of COI and its effect on CPG recommendations. Methodology/Principal Findings We searched Medline (1980 to March, 2011) for studies that examined the effect of COI on CPG development and/or recommendations. Data synthesis was qualitative. Twelve studies fulfilled inclusion criteria; 9 were conducted in the US. All studies reported on financial relationships of CPG authors with the pharmaceutical industry; 1 study also examined relationships with diagnostic testing and insurance companies. The majority of guidelines had authors with industry affiliations, including consultancies (authors with relationship, range 6–80%); research support (4–78%); equity/stock ownership (2–17%); or any COI (56–87%). Four studies reported multiple types of financial interactions for individual authors (number of types per author: range 2 to 10 or more). Data on the effect of COI on CPG recommendations were confined to case studies wherein authors with specific financial ties appeared to benefit from the related CPG recommendations. In a single study, few authors believed that their relationships influenced their recommendations. No studies reported on intellectual COI in CPGs. Conclusions/Significance There are limited data describing the high prevalence of COI among CPG authors, and only case studies of the effect of COI on CPG recommendations. Further research is needed to explore this potential source of bias.

Primary Care Screening for and Treatment of Depression in Pregnant and Postpartum Women: Evidence Report and Systematic Review for the US Preventive Services Task Force

IMPORTANCE Depression is a source of substantial burden for individuals and their families, including women during the pregnant and postpartum period. OBJECTIVE To systematically review the benefits and harms of depression screening and treatment, and accuracy of selected screening instruments, for pregnant and postpartum women. Evidence for depression screening in adults in general is available in the full report. DATA SOURCES MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials through January 20, 2015; references; and government websites. STUDY SELECTION English-language trials of benefits and harms of depression screening, depression treatment in pregnant and postpartum women with screen-detected depression, and diagnostic accuracy studies of depression screening instruments in pregnant and postpartum women. DATA EXTRACTION AND SYNTHESIS Two investigators independently reviewed abstracts and full-text articles and extracted data from fair- and good-quality studies. Random-effects meta-analysis was used to estimate the benefit of cognitive behavioral therapy (CBT) in pregnant and postpartum women. MAIN OUTCOMES AND MEASURES Depression remission, prevalence, symptoms, and related measures of depression recovery or response; sensitivity and specificity of selected screening measures to detect depression; and serious adverse effects of antidepressant treatment. RESULTS Among pregnant and postpartum women 18 years and older, 6 trials (n = 11,869) showed 18% to 59% relative reductions with screening programs, or 2.1% to 9.1% absolute reductions, in the risk of depression at follow-up (3-5 months) after participation in programs involving depression screening, with or without additional treatment components, compared with usual care. Based on 23 studies (n = 5398), a cutoff of 13 on the English-language Edinburgh Postnatal Depression Scale demonstrated sensitivity ranging from 0.67 (95% CI, 0.18-0.96) to 1.00 (95% CI, 0.67-1.00) and specificity consistently 0.87 or higher. Data were sparse for Patient Health Questionnaire instruments. Pooled results for the benefit of CBT for pregnant and postpartum women with screen-detected depression showed an increase in the likelihood of remission (pooled relative risk, 1.34 [95% CI, 1.19-1.50]; No. of studies [K] = 10, I2 = 7.9%) compared with usual care, with absolute increases ranging from 6.2% to 34.6%. Observational evidence showed that second-generation antidepressant use during pregnancy may be associated with small increases in the risks of potentially serious harms. CONCLUSIONS AND RELEVANCE Direct and indirect evidence suggested that screening pregnant and postpartum women for depression may reduce depressive symptoms in women with depression and reduce the prevalence of depression in a given population. Evidence for pregnant women was sparser but was consistent with the evidence for postpartum women regarding the benefits of screening, the benefits of treatment, and screening instrument accuracy.

Risk Factors and Other Epidemiologic Considerations for Cervical Cancer Screening: A Narrative Review for the U.S. Preventive Services Task Force

Despite the success of cervical cancer screening programs, questions remain about the appropriate time to begin and end screening. This review explores epidemiologic and contextual data on cervical cancer screening to inform decisions about when screening should begin and end. Cervical cancer is rare among women younger than 20 years. Screening for cervical cancer in this age group is complicated by lower rates of detection and higher rates of false-positive results than in older women. Methods used to diagnose and treat cervical intraepithelial neoplasia have important potential adverse effects. High-risk human papillomavirus infections and abnormalities on cytologic and histologic examination have relatively high rates of regression. Accordingly, cervical cancer screening in women younger than 20 years may be harmful. The incidence of, and mortality rates from, cervical cancer and the proportion of U.S. women aged 65 years or older who have had a Papanicolaou smear within 3 years have decreased since 2000. Available evidence supports discontinuation of cervical cancer screening among women aged 65 years or older who have had adequate screening and are not otherwise at high risk. Further reductions in the burden of cervical cancer in older women are probably best achieved by focusing on screening those who have not been adequately screened.

Screening for Obesity and Intervention for Weight Management in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood. Objective To systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force. Data Sources MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites. Surveillance continued through December 5, 2016. Study Selection English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings. Data Extraction and Synthesis Two investigators independently reviewed abstracts and full-text articles, then extracted data from fair- and good-quality trials. Random-effects meta-analysis was used to estimate the benefits of lifestyle-based programs and metformin. Main Outcomes and Measures Weight or excess weight (eg, body mass index [BMI]; BMI z score, measuring the number of standard deviations from the median BMI for age and sex), cardiometabolic outcomes, quality of life, other health outcomes, harms. Results There was no direct evidence on the benefits or harms of screening children and adolescents for excess weight. Among 42 trials of lifestyle-based interventions to reduce excess weight (N = 6956), those with an estimated 26 hours or more of contact consistently demonstrated mean reductions in excess weight compared with usual care or other control groups after 6 to 12 months, with no evidence of causing harm. Generally, intervention groups showed absolute reductions in BMI z score of 0.20 or more and maintained their baseline weight within a mean of approximately 5 lb, while control groups showed small increases or no change in BMI z score, typically gaining a mean of 5 to 17 lb. Only 3 of 26 interventions with fewer contact hours showed a benefit in weight reduction. Use of metformin (8 studies, n = 616) and orlistat (3 studies, n = 779) were associated with greater BMI reductions compared with placebo: −0.86 (95% CI, −1.44 to −0.29; 6 studies; I2 = 0%) for metformin and −0.50 to −0.94 for orlistat. Groups receiving lifestyle-based interventions offering 52 or more hours of contact showed greater improvements in blood pressure than control groups: −6.4 mm Hg (95% CI, −8.6 to −4.2; 6 studies; I2 = 51%) for systolic blood pressure and −4.0 mm Hg (95% CI, −5.6 to −2.5; 6 studies; I2 = 17%) for diastolic blood pressure. There were mixed findings for insulin or glucose measures and no benefit for lipids. Medications showed small or no benefit for cardiometabolic outcomes, including fasting glucose level. Nonserious harms were common with medication use, although discontinuation due to adverse effects was usually less than 5%. Conclusions and Relevance Lifestyle-based weight loss interventions with 26 or more hours of intervention contact are likely to help reduce excess weight in children and adolescents. The clinical significance of the small benefit of medication use is unclear.

Quality of Clinical Practice Guidelines for Glycemic Control in Type 2 Diabetes Mellitus

Background Several studies have reported that clinical practice guidelines (CPGs) in a variety of clinical areas are of modest or variable quality. The objective of this study was to evaluate the quality of an international cohort of CPGs that provide recommendations on pharmaceutical management of glycemic control in patients with type 2 diabetes mellitus (DM2). Methods and Findings We searched the National Guideline Clearinghouse (NGC) on February 15th and June 4th, 2012 for CPGs meeting inclusion criteria. Two independent assessors rated the quality of each CPG using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. Twenty-four guidelines were evaluated, and most had high scores for clarity and presentation. However, scope and purpose, stakeholder involvement, rigor of development, and applicability domains varied considerably. The majority of guidelines scored low on editorial independence, and only seven CPGs were based on an underlying systematic review of the evidence. Conclusions The overall quality of CPGs for glycemic control in DM2 is moderate, but there is substantial variability among quality domains within and across guidelines. Guideline users need to be aware of this variability and carefully appraise and select the guidelines that they apply to patient care.

Conflict of interest policies for organizations producing a large number of clinical practice guidelines.

Background Conflict of interest (COI) of clinical practice guideline (CPG) sponsors and authors is an important potential source of bias in CPG development. The objectives of this study were to describe the COI policies for organizations currently producing a significant number of CPGs, and to determine if these policies meet 2011 Institute of Medicine (IOM) standards. Methodology/Principal Findings We identified organizations with five or more guidelines listed in the National Guideline Clearinghouse between January 1, 2009 and November 5, 2010. We obtained the COI policy for each organization from publicly accessible sources, most often the organizations website, and compared those polices to IOM standards related to COI. 37 organizations fulfilled our inclusion criteria, of which 17 (46%) had a COI policy directly related to CPGs. These COI policies varied widely with respect to types of COI addressed, from whom disclosures were collected, monetary thresholds for disclosure, approaches to management, and updating requirements. Not one organizations policy adhered to all seven of the IOM standards that were examined, and nine organizations did not meet a single one of the standards. Conclusions/Significance COI policies among organizations producing a large number of CPGs currently do not measure up to IOM standards related to COI disclosure and management. CPG developers need to make significant improvements in these policies and their implementation in order to optimize the quality and credibility of their guidelines.