Elizabeth O'Connor

Effectiveness of Weight Management Interventions in Children: A Targeted Systematic Review for the USPSTF

CONTEXT: Targeted systematic review to support the updated US Preventive Services Task Force (USPSTF) recommendation on screening for obesity in children and adolescents. OBJECTIVES: To examine the benefits and harms of behavioral and pharmacologic weight-management interventions for overweight and obese children and adolescents. METHODS: Our data sources were Ovid Medline, PsycINFO, the Education Resources Information Center, the Database of Abstracts of Reviews of Effects, the Cochrane databases, reference lists of other reviews and trials, and expert recommendations. After 2 investigators reviewed 2786 abstracts and 369 articles against inclusion/exclusion criteria, we included 15 fair- to good-quality trials in which the effects of treatment on weight, weight-related comorbidities, and harms were evaluated. Studies were quality rated by 2 investigators using established criteria. Investigators abstracted data into standard evidence tables. RESULTS: In the available research, obese (or overweight) children and adolescents aged 4 to 18 years were enrolled, and no studies targeted those younger than 4 years. Comprehensive behavioral interventions of medium-to-high intensity were the most effective behavioral approach with 1.9 to 3.3 kg/m2 difference favoring intervention groups at 12 months. More limited evidence suggests that these improvements can be maintained over the 12 months after the end of treatments and that there are few harms with behavioral interventions. Two medications combined with behavioral interventions resulted in small (0.85 kg/m2 for orlistat) or moderate (2.6 kg/m2 for sibutramine) BMI reduction in obese adolescents on active medication; however, no studies followed weight changes after medication use ended. Potential adverse effects were greater than for behavioral interventions alone and varied in severity. Only 1 medication (orlistat) has been approved by the US Food and Drug Administration for prescription use in those aged ≥12 years. CONCLUSIONS: Over the past several years, research into weight management in obese children and adolescents has improved in quality and quantity. Despite important gaps, available research supports at least short-term benefits of comprehensive medium- to high-intensity behavioral interventions in obese children and adolescents.

Effectiveness of Primary Care-Relevant Treatments for Obesity in Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force

BACKGROUND Overweight and obesity in adults are common and adversely affect health. PURPOSE To summarize effectiveness and harms of primary care-relevant weight-loss interventions for overweight and obese adults. DATA SOURCES MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2005 to September 2010; systematic reviews for identifying trials before 2005. STUDY SELECTION Two investigators appraised 6498 abstracts and 648 articles. Clinical trials were included if control groups received minimal interventions. Articles were rated as good, fair, or poor by using design-specific criteria. DATA EXTRACTION One investigator abstracted study characteristics and findings for good- and fair-quality studies; a second checked them. DATA SYNTHESIS Behaviorally based treatment resulted in 3-kg (6.6-lb) greater weight loss in intervention than control participants after 12 to 18 months, with more treatment sessions associated with greater loss. Limited data suggest weight-loss maintenance for 1 year or more. Orlistat plus behavioral intervention resulted in 3-kg (6.6-lb) more weight loss than did placebo after 12 months. Metformin resulted in less weight loss. Data on effects of weight-loss treatment on long-term health outcomes (for example, death and cardiovascular disease) were insufficient. Weight-loss treatment reduced diabetes incidence in participants with prediabetes. Effects on intermediate outcomes (for example, lipids and blood pressure) were mixed and small. Data on serious medication harms were insufficient. Medications commonly caused withdrawals due to gastrointestinal symptoms. LIMITATIONS Few studies reported health outcomes. Behaviorally based treatments were heterogeneous and specific elements were not well-described. Many studies could not be pooled because of insufficient reporting of variance data. Medication trials had high attrition, lacked postdiscontinuation data, and were inadequately powered for rare adverse effects. CONCLUSION Behaviorally based treatments are safe and effective for weight loss and maintenance. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Primary Care-Relevant Interventions to Prevent Falling in Older Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force

BACKGROUND Falls among older adults are both prevalent and preventable. PURPOSE To describe the benefits and harms of interventions that could be used by primary care practitioners to prevent falling among community-dwelling older adults. DATA SOURCES The reviewers evaluated trials from a good-quality systematic review published in 2003 and searched MEDLINE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL from the end of that reviews search date to February 2010 to identify additional English-language trials. STUDY SELECTION Two reviewers independently screened 3423 abstracts and 638 articles to identify randomized, controlled trials (RCTs) of primary care-relevant interventions among community-dwelling older adults that reported falls or fallers as an outcome. Trials were independently critically appraised to include only good- or fair-quality trials; discrepancies were resolved by a third reviewer. DATA EXTRACTION One reviewer abstracted data from 61 articles into standardized evidence tables that were verified by a second reviewer. DATA SYNTHESIS Overall, the included evidence was of fair quality. In 16 RCTs evaluating exercise or physical therapy, interventions reduced falling (risk ratio, 0.87 [95% CI, 0.81 to 0.94]). In 9 RCTs of vitamin D supplementation, interventions reduced falling (risk ratio, 0.83 [CI, 0.77 to 0.89]). In 19 trials involving multifactorial assessment and management, interventions with comprehensive management seemed to reduce falling, although overall pooled estimates were not statistically significant (risk ratio, 0.94 [CI, 0.87 to 1.02]). Limited evidence suggested that serious clinical harms were no more common for older adults in intervention groups than for those in control groups. LIMITATIONS Interventions and methods of fall ascertainment were heterogeneous. Data on potential harms of interventions were scant and often not reported. CONCLUSION Primary care-relevant interventions exist that can reduce falling among community-dwelling older adults. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Screening for Depression in Adult Patients in Primary Care Settings: A Systematic Evidence Review

Major depressive disorder (MDD) is common, with an estimated lifetime prevalence of 13.2%. In primary care settings, prevalence estimates of MDD range from 5% to 13% in all adults (1, 2), with lower estimates in those older than 55 years (6% to 9%) (3, 4). Primary care practitioners manage approximately one third to one half of nonelderly adults (5, 6) and almost two thirds of older adults (7) who received treatment for MDD. The severity of depressive symptoms in patients who receive treatment in primary care is equivalent to that of patients treated in psychiatric settings (8). For example, approximately 43% of such primary care patients report some degree of suicidal ideation within the previous week (8, 9). In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended screening adults for depression in clinical practices that have systems to ensure accurate diagnosis, effective treatment, and follow-up. Subsequent reviewers have concluded that screening does not improve health outcomes (10), but care management systems for depressed patients improve depression remission rates (11). Commentators on these divergent reviews have been divided (12, 13). We conducted this systematic review to aid the USPSTF in updating its 2002 recommendation for adult depression screening in primary care. We sought to 1) identify evidence published since the previous review on the benefits of screening for depression in primary care and integrate it with the previously identified evidence and 2) review the evidence in several areas in which evidence was insufficient at the time of the previous review or not was examined by the previous review (14). This includes the benefits of depression treatment in older adults, the harms of depression screening, and the harms of depression treatment with antidepressant medications. Methods Scope of the Review We developed an analytic framework (Appendix Figure 1) and 5 key questions that focused on the evidence that the USPSTF required to update its recommendation by using the USPSTFs methods (15). Appendix Figure 1. Analytic framework and key questions. SSRI = selective serotonin reuptake inhibitor. 1. Is there direct evidence that screening for depression among adults and elderly patients in primary care reduces morbidity and/or mortality? 1a. What is the effect of clinician feedback of screening test results (with or without additional care management support) on depression response and remission in screening-detected depressed patients receiving usual care? 2. What are the adverse effects of screening for depressive disorders in adults and elderly patients in primary care? 3. Is antidepressant and/or psychotherapy treatment of elderly depressed patients effective in improving health outcomes? 4. What are the adverse effects of antidepressant treatment (particularly selective serotonin reuptake inhibitors [SSRIs] and other second-generation drugs) for depression in adults and elderly patients? This article discusses methods and results for key questions 1, 1a, and 4. Detailed methods and results for the remaining key questions are in the full report (16). Data Sources and Searches We used the Database of Abstracts of Reviews of Effects, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE, and PsycINFO to search for relevant systematic reviews, meta-analyses, and primary studies published in English from January 1998 to December 2007. The full report provides the search strategies (16). Study Selection Two investigators reviewed 4088 abstracts published in English and 412 full-text articles (Appendix Figure 2) against key questionspecific inclusion and exclusion criteria (Appendix Table 1). Articles for key questions 1 and 1a were limited to randomized and controlled clinical trials that were conducted in primary care or similar settings. Key question 1 trials compared outcomes in screened and unscreened patients. Trials for key question 1a were required to have used the screening results for care decisions for intervention recipients and not for the control participants. Outcomes for these 2 questions were focused on depression response and remission. Appendix Figure 2. Search results and article flow, by key question. KQ = key question. * Numbers differ slightly from the full report (16) because only articles relevant to the more limited body of literature discussed in this publication are included in this figure. Appendix Table 1. Inclusion and Exclusion Criteria for KQs Discussed We focused our review of harms of treatment (key question 4) on already-synthesized evidence, supplemented by large observational studies. Methods for incorporating systematic reviews and meta-analyses are detailed elsewhere (Appendix Table 2). We examined serious adverse effects associated with antidepressant treatment, including suicide-related events (completed suicide, serious self-harm or attempted suicide, suicidal ideation, or suicidal behavior [usually defined to include suicide attempts, preparatory acts, or nonfatal serious self-harm]), and serious psychiatric events, including hospitalization. For older adults, we also considered evidence of serious medical events (for example, upper gastrointestinal bleeding) that were associated with SSRI and other second-generation antidepressant use. We examined rates of early discontinuation as a proxy for less serious adverse effects, particularly discontinuation due to adverse effects as a measure of tolerability. We focused on second-generation antidepressants (SSRIs in particular) because of their preponderance of use in the United States (17, 18). Appendix Table 2. Use of Existing Systematic Reviews Updated Searching and Study Examination Because of the delay between completion of the systematic review and publication, we repeated our search strategy through February 2009. We reviewed 800 abstracts against inclusion and exclusion criteria, and 21 seemed to meet criteria for this systematic review. After examining results of each of these new studies (as described in the abstracts), we determined that they would be unlikely to change our conclusions. Appendix Table 3 lists these studies. Appendix Table 3. Studies Found in Bridge Search With Possible Inclusion or Exclusion Criteria Data Extraction and Quality Assessment Two investigators rated articles for quality by using design-specific quality criteria on the basis of the USPSTF methods (15). The National Institute for Health and Clinical Excellence (19) criteria (for all study designs) and the Oxman criteria (20) (for systematic reviews) supplemented these methods. One investigator abstracted data from included studies into evidence tables and another verified it. The full review shows complete quality criteria (16). Regulatory reviews provided unique challenges and could not be evaluated by using typical quality criteria. For example, their search approach was different because they can mandate that manufacturers supply requested data. Because of the large number of trials (often in the hundreds) and proprietary information involved, however, they did not provide detailed information about individual trials. Data Synthesis and Analysis Data synthesis was primarily qualitative because of clinical heterogeneity. For cohort studies included for key question 4, we calculated absolute event rates and CIs for suicide-related events on the basis of reported data if this information was not provided. The 95% CIs were calculated on the basis of a Poisson distribution by using the GENMOD procedure (SAS software, version 8.2, SAS Institute, Cary, North Carolina) with the RISK option. Similarly, for the meta-analyses of antidepressant trials included for key question 4, we calculated missing CIs by using the FREQ procedure. Role of Funding Source The Agency for Healthcare Research and Quality funded this work, provided project oversight, and assisted in external review of the draft report but had no role in the design, conduct, or reporting of the review. The authors worked with 4 USPSTF members at key points throughout the review process to develop the analytic framework and key questions and resolve issues about scope and approach. The draft systematic review was reviewed by 6 experts and was revised on the basis of their feedback. Results Key Question 1 Is there direct evidence that screening for depression among adults and elderly patients in primary care reduces morbidity and/or mortality? One fair-quality randomized, controlled trial (RCT) of primary care patients reported mixed results when screened participants were compared with an unscreened usual care group (21) (Table). Concerns about the follow-up sample, however, limit our confidence in the results. At 3-month follow-up, the proportion of people who met criteria for depression, according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, was similar in the screened (37%) and usual care groups (46%) (P= 0.19), although power to detect a population-level effect was inadequate (n= 218). After the investigators controlled for baseline severity of depression (which differed between the screened and usual care groups in the full randomized sample), the mean reduction in symptom counts derived from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, was similar for the 2 groups (1.6 in screened patients vs. 1.5 in unscreened patients; P= 0.21). However, among the subset of patients who were depressed at baseline, screened patients were more likely than unscreened patients to be in complete remission at follow-up (1 symptom of depression in 48% of those screened vs. 27% of those not screened; P< 0.05). Only patients from 1 of the 2 study sites were included in the follow-up sample. At this site, only those with a diagnosis of depression at baseline and a random sample of the remaining participants (oversampling those with depressive sympt

Screening for Child and Adolescent Depression in Primary Care Settings: A Systematic Evidence Review for the US Preventive Services Task Force

CONTEXT. Depression among youth is a disabling condition that is associated with serious long-term morbidities and suicide. OBJECTIVE. To assess the health effects of routine primary care screening for major depressive disorder among children and adolescents aged 7 to 18 years. METHODS. Medline, the Cochrane Central Registry of Controlled Trials, PsycInfo, the Cochrane Database of Systematic Reviews, recent systematic reviews, experts, and bibliographies from selected studies were the data sources. The studies selected were fair- and good-quality (on the basis of US Preventive Services Task Force criteria) controlled trials of screening and treatment (selective serotonin reuptake inhibitor and/or psychotherapy), diagnostic accuracy studies, and large observational studies that reported adverse events. Two reviewers quality-graded each article. One reviewer abstracted relevant information into standardized evidence tables, and a second reviewer checked key elements. RESULTS. We found no data describing health outcomes among screened and unscreened populations. Although the literature on diagnostic screening test accuracy is small and methodologically limited, it indicates that several screening instruments have performed fairly well among adolescents. The literature on treatment efficacy of selective serotonin reuptake inhibitors and/or psychotherapy is also small but includes good-quality randomized, controlled trials. Available data indicate that selective serotonin reuptake inhibitors, psychotherapy, and combined treatment are effective in increasing response rates and reducing depressive symptoms. Not all specific selective serotonin reuptake inhibitors, however, seem to be efficacious. Selective serotonin reuptake inhibitor treatment was associated with a small absolute increase in risk of suicidality (ie, suicidal ideation, preparatory acts, or attempts). No suicide deaths occurred in any of the trials. CONCLUSIONS. Limited available data suggest that primary care–feasible screening tools may accurately identify depressed adolescents and treatment can improve depression outcomes. Treating depressed youth with selective serotonin reuptake inhibitors may be associated with a small increased risk of suicidality and should only be considered if judicious clinical monitoring is possible.

Behavioral Counseling to Promote Physical Activity and a Healthful Diet to Prevent Cardiovascular Disease in Adults: A Systematic Review for the U.S. Preventive Services Task Force

BACKGROUND Poor diet and lack of physical activity can worsen cardiovascular health, yet most Americans do not meet diet and physical activity recommendations. PURPOSE To assist the U.S. Preventive Services Task Force in updating its previous recommendations by systematically reviewing trials of physical activity or dietary counseling to prevent cardiovascular disease. DATA SOURCES MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials (2001 to January 2010), experts, and existing systematic reviews. STUDY SELECTION Two investigators independently reviewed 13 562 abstracts and 481 articles against a set of a priori inclusion criteria and critically appraised each study by using design-specific quality criteria. DATA EXTRACTION AND ANALYSIS Data from 73 studies (109 articles) were abstracted by one reviewer and checked by a second reviewer. Random-effects meta-analyses were conducted for multiple intermediate health and behavioral outcomes. DATA SYNTHESIS Long-term observational follow-up of intensive sodium reduction counseling showed a decrease in the incidence of cardiovascular disease; however, other direct evidence for reduction in disease morbidity is lacking. High-intensity dietary counseling, with or without physical activity counseling, resulted in changes of -0.3 to -0.7 kg/m(2) in body mass index (adiposity), -1.5 mm Hg (95% CI, -0.9 to -2.1 mm Hg) in systolic blood pressure, -0.7 mm Hg (CI, -0.6 to -0.9 mm Hg) in diastolic pressure, -0.17 mmol/L (CI, -0.09 to -0.25 mmol/L) (-6.56 mg/dL [CI, -3.47 to -9.65 mg/dL]) in total cholesterol level, and -0.13 mmol/L (CI, -0.06 to -0.21 mmol/L) (-5.02 mg/dL [CI, -2.32 to -8.11 mg/dL]) in low-density lipoprotein cholesterol level. Medium- and high-intensity counseling resulted in moderate to large changes in self-reported dietary and physical activity behaviors. LIMITATIONS Meta-analyses for some outcomes had large statistical heterogeneity or evidence for publication bias. Only 11 trials followed outcomes beyond 12 months. CONCLUSION Counseling to improve diet or increase physical activity changed health behaviors and was associated with small improvements in adiposity, blood pressure, and lipid levels. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Screening for Cognitive Impairment in Older Adults: A Systematic Review for the U.S. Preventive Services Task Force

BACKGROUND Earlier identification of cognitive impairment may reduce patient and caregiver morbidity. PURPOSE To systematically review the diagnostic accuracy of brief cognitive screening instruments and the benefits and harms of pharmacologic and nonpharmacologic interventions for early cognitive impairment. DATA SOURCES MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials through December 2012; systematic reviews; clinical trial registries; and experts. STUDY SELECTION English-language studies of fair to good quality, primary care–feasible screening instruments, and treatments aimed at persons with mild cognitive impairment or mild to moderate dementia. DATA EXTRACTION Dual quality assessment and abstraction of relevant study details. DATA SYNTHESIS The Mini-Mental State Examination (k = 25) is the most thoroughly studied instrument but is not available for use without cost. Publicly available instruments with adequate test performance to detect dementia include the Clock Drawing Test (k = 7), Mini-Cog (k = 4), Memory Impairment Screen (k = 5), Abbreviated Mental Test (k = 4), Short Portable Mental Status Questionnaire (k = 4), Free and Cued Selective Reminding Test (k = 2), 7-Minute Screen (k = 2), and Informant Questionnaire on Cognitive Decline in the Elderly (k = 5). Medications approved by the U.S. Food and Drug Administration for Alzheimer disease (k = 58) and caregiver interventions (k = 59) show a small benefit of uncertain clinical importance for patients and their caregivers. Small benefits are also limited by common adverse effects of acetylcholinesterase inhibitors and limited availability of complex caregiver interventions. Although promising, cognitive stimulation (k = 6) and exercise (k = 10) have limited evidence to support their use in persons with mild to moderate dementia or mild cognitive impairment. LIMITATION Limited studies in persons with dementia other than Alzheimer disease and sparse reporting of important health outcomes. CONCLUSION Brief instruments to screen for cognitive impairment can adequately detect dementia, but there is no empirical evidence that screening improves decision making. Whether interventions for patients or their caregivers have a clinically significant effect in persons with earlier detected cognitive impairment is still unclear. 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

Low-Dose Aspirin for Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force

Preeclampsia is a leading cause of maternal death, affecting 2% to 8% of pregnancies globally (1, 2). It affected 3.8% of U.S. deliveries in 2010, and the rate of severe preeclampsia has increased over the past 3 decades (3). Perinatal mortality is nearly 2 times higher in pregnancies affected by preeclampsia (4), with 12% of maternal deaths due to the condition (5). Serious illness is more common, with more than one third of serious maternal morbidity and 15% of preterm births related to preeclampsia (6, 7). Preeclampsia is defined as hypertension (blood pressure 140/90 mm Hg) and proteinuria (presence of 0.3 g of protein in a 24-hour period) observed during the second half of pregnancy (>20 weeks of gestation) (8, 9). It is also classified as having severe features with any of the following: blood pressure above 160/110 mm Hg, thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, or cerebral or visual disturbances (9). Preeclampsia with or without severe features can evolve rapidly into eclampsia or the hemolysis, elevated liver enzymes, and low platelets syndrome, sometimes leading to systemic complications and maternal death (10, 11). Poor perinatal health outcomes are associated with preeclampsia, primarily due to increased risk for intrauterine growth restriction (IUGR) or medically initiated preterm delivery. Once preeclampsia develops, the only effective treatment is delivery, with serious neonatal harms when remote from term (<34 weeks of gestation). Current understanding of preeclampsia pathophysiology suggests that it may be a collection of syndromes with different precipitating factors and outcomes (12). Early in pregnancy, aberrations in placental development can result in placental ischemia and release of inflammatory and oxidative stress factors into the maternal bloodstream. In addition, even with normal placentation, preexisting hypertension, diabetes, and other inflammatory conditions (such as lupus) may activate systemic inflammatory and oxidative stress processes, as can twin or higher-order pregnancies. Accurate prediction of who will develop preeclampsia and have serious complications is not currently possible (1315). The most consistent predictors of high risk are previous preeclampsia, certain medical conditions (diabetes, chronic hypertension, renal disease, autoimmune diseases, and the antiphospholipid syndrome), and multifetal pregnancy (16). Moderately elevated risk for preeclampsia is associated with nulliparity (first birth), advanced maternal age (40 years), between-pregnancy interval of more than 10 years, high body mass index (35 kg/m2), and family history of preeclampsia (mother or sister). Risk factors with less consistent evidence include changes in paternity between pregnancies, history of migraine headaches (17, 18), and asthma (17, 1922). Predictive models combining various biomarkers, patient risk factors, and clinical readings hold promise but are not yet sufficiently validated for clinical use (10, 2325). Previous comprehensive systematic reviews have found antiplatelets (primarily low-dose aspirin) to be beneficial for the prevention of preeclampsia among women at heightened risk (26, 27). We conducted this systematic review to support the U.S. Preventive Services Task Force (USPSTF) in updating its 1996 recommendation, which is no longer active. Methods Detailed methods are outlined in our full evidence report (28). This review addressed 3 key questions (Appendix Figure 1). First, is low-dose aspirin effective for reducing adverse maternal and perinatal health outcomes among women at increased risk for preeclampsia? Second, is low-dose aspirin effective for preventing preeclampsia among women at increased risk for the condition? Third, are there harms to the woman and fetus associated with aspirin use during pregnancy? Appendix Figure 1. Analytic framework and key questions. ARDS = acute respiratory distress syndrome; HELLP = hemolysis, elevated liver enzymes, and low platelets. *Abbreviated list of health outcomes. See Appendix Table 2 for a full list. Data Sources and Searches In addition to considering all studies from the previous USPSTF review, we performed a comprehensive search of MEDLINE, PubMed, the Database of Abstracts of Reviews of Effects, and the Cochrane Central Register of Controlled Trials for studies published between January 2006 and 1 June 2013. We also examined the reference lists from existing systematic reviews to identify potentially eligible studies, including an individual-patient data (IPD) meta-analysis published by the Perinatal Antiplatelet Review of International Studies (PARIS) Collaboration (27) and a 2007 Cochrane review (26). We searched ClinicalTrials.gov for ongoing trials (May 2013). Between the last search date and this publication, we actively monitored published literature for potentially important new trials or other large observational studies directly relevant to our key questions; none were identified. Study Selection Two investigators independently reviewed abstracts and full-text articles for inclusion according to predetermined criteria. We resolved discrepancies through consensus with a third investigator. To evaluate benefits of aspirin prophylaxis, we included any study that used a risk selection approach aimed at achieving a sample of women at high risk for preeclampsia. The trials could define risk on the basis of medical history, pregnancy characteristics, or clinical measurements known to be associated with risk for the condition. Although preeclampsia occurs more often in first births than in subsequent ones, prevalence rates are relatively low (approximately 4%) compared with other high-risk groups. Because aspirin treatment based only on this risk factor has not been supported, trials with nulliparity as the sole risk factor were not included for evaluation of benefits. We used broader inclusion criteria to identify possible harms of aspirin exposure during pregnancy. The trials of women at high risk were combined with trials of women at low or average risk exposed to daily low-dose aspirin. Large prospective observational studies were also included to assess harms but were not included in pooled analyses. We included interventions that compared patients receiving 50 to 150 mg of aspirin with a placebo or no treatment group and excluded studies of nonaspirin antiplatelet medications or aspirin combined with another active substance. We also excluded studies that we rated as poor-quality on the basis of the USPSTF quality rating standards (29) and studies not published in English. Data Extraction and Quality Assessment Two investigators critically appraised all included studies independently using the USPSTFs design-specific criteria (29), which we supplemented with the National Institute for Health and Care Excellence methodology checklists (30) and the Newcastle-Ottawa Scale (31). According to the USPSTF criteria, a good-quality study met all prespecified standards. A fair-quality study did not meet (or it was unclear whether it met) at least 1 criterion, but it also had no known limitation that could invalidate its results. A poor-quality study had a single fatal flaw or multiple important limitations that could seriously bias its results. Discrepancies were resolved through discussion of identified limitations and consultation with a third investigator, if necessary. One investigator extracted study details and results, and a second investigator reviewed the abstracted information. Data Synthesis and Analysis We used the metan procedure in Stata, version 11.2 (StataCorp, College Station, Texas), for all reported meta-analyses and the metaan procedure for sensitivity analyses (32). For dichotomous outcomes, we entered the number of events and nonevents and estimated pooled random-effects risk ratios by using the DerSimonianLaird method for all outcomes, except those in which fewer than 10% of the participants had the event (33), for which we used a fixed-effects MantelHaenszel model (34). We also included prediction intervals in forest plots of random-effects models, which provided an estimate of where the effect size from 95% of newly conducted trials would fall, assuming that the between-study variability in the included trials held for new trials (35). The prediction intervals are shown on the forest plots by the horizontal lines that extend from the diamond representing the 95% CI of the pooled estimate. Potential sources of heterogeneity in effect size by aspirin timing, dosage, and preeclampsia risk determination were identified a priori and explored using meta regression and visual inspection of sorted forest plots. We used the I 2 and chi-square statistics to assess statistical heterogeneity. To evaluate small-study effects, we examined funnel plots and used the Begg or Peter test depending on the outcome distribution (36, 37). We used profile likelihood estimation to conduct sensitivity analyses for the pooled effects because the DerSimonianLaird method can overestimate CI precision in meta-analysis, particularly when fewer than 10 studies or when smaller studies with few events are pooled (38). Role of the Funding Source This study was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the work of the USPSTF. Members of the USPSTF and the AHRQ medical officer assisted in the development of the reviews scope. Approval from AHRQ was required before the manuscript could be submitted for publication, but the authors are solely responsible for its content and the decision to submit it for publication. Results Our literature search yielded 544 unique citations. From these, we reviewed the full text of 75 articles. Twenty-three studies (27 articles) met our inclusion criteria (Appendix Figure 2 and Appendix Table 1). Appendix Figure 2. Summary of evidence search and selection. The diagram excludes 51 RefMan (Thomson Reuters, Philadelph

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.