Cynthia Feltner

Transitional care interventions to prevent readmissions for persons with heart failure: a systematic review and meta-analysis.

Heart failure (HF) is a leading cause of hospitalization and health care costs in the United States (1). Up to 25% of patients hospitalized with HF are readmitted within 30 days (25). Readmissions after an index hospitalization for HF are related to various conditions. An analysis of Medicare claims data from 2007 to 2009 found that 35% of readmissions within 30 days were for HF; the remainder were for diverse indications (for example, renal disorders, pneumonia, and arrhythmias) (2). To reduce rehospitalization of Medicare patients, in October 2012, the Centers for Medicare & Medicaid Services began decreasing reimbursements to hospitals with excessive risk-standardized readmission (6). This policy incentivizes hospitals to develop programs to reduce readmission rates for persons with HF. Despite advances in the quality of acute and chronic HF disease management, knowledge gaps remain about effective interventions to support the transition of care for persons with HF. Interventions designed to prevent readmissions among populations transitioning from one care setting to another are often called transitional care interventions (7, 8). They aim to avoid poor outcomes caused by uncoordinated care, such as preventable readmissions (9). Although no clear set of components defines transitional care interventions, they focus on patient or caregiver education, medication reconciliation, and coordination among health professionals involved in the transition. We conducted a systematic review of transitional care interventions for persons with HF for the Effective Health Care Program of the Agency for Healthcare Research and Quality (AHRQ) (10). We included a broad range of intervention types (Table 1) applicable to adults transitioning from hospital to home that aimed to prevent readmissions. Although 30-day readmissions are the focus of quality measures, we also included readmissions measured over 3 to 6 months because these are common, costly, and potentially preventable (5). The full technical report addressed 5 questions (Appendix Table 1). For this article, we focused on readmission and mortality outcomes. Table 1. Transitional Care Interventions Appendix Table 1. Scope and Key Questions* Methods We developed and followed a standard protocol. A technical report that details methods and includes complete search strategies and additional evidence tables is available at www.effectivehealthcare.ahrq.gov/reports/final.cfm. Data Sources and Searches We searched MEDLINE, the Cochrane Library, and CINAHL for English-language and human-only studies published from 1 July 2007 to late October 2013, and we used a previous technology assessment on a similar topic to identify randomized, controlled trials (RCTs) published before 1 July 2007 (11). An experienced Evidence-based Practice Center librarian conducted the searches, and a second librarian reviewed them. We manually searched reference lists of pertinent reviews, included trials, and background articles on this topic to look for relevant citations our searches might have missed. We searched for relevant unpublished studies using ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. Study Selection We developed inclusion and exclusion criteria with respect to populations, interventions, comparators, outcomes, timing, settings, and study designs (Appendix Table 2). We included studies of adults recruited during or within 1 week of an index hospitalization for HF that compared a transitional care intervention with another eligible intervention or with usual care (that is, routine or standard care, as defined by the primary studies). We required that interventions include 1 or more of the following components: education of patient or caregiver delivered before or after discharge, planned or scheduled outpatient clinic visits (primary care or multidisciplinary heart failure [MDS-HF] clinic), home visits, telemonitoring, structured telephone support (STS), transition coach or case management, or interventions to increase provider continuity. We required studies to report a readmission rate, mortality rate, or the composite outcome (all-cause readmission or mortality). In the full report, we also assessed emergency department visits, acute care visits, hospital days of subsequent readmissions, quality of life, functional status, and caregiver or self-care burden (10). Appendix Table 2. Inclusion and Exclusion Criteria for Studies of Transitional Care Interventions for Patients Hospitalized for HF Data Extraction and Risk-of-Bias Assessment One team member extracted relevant data from each article, and a second team member reviewed all data extractions for completeness and accuracy. We used predefined criteria based on the AHRQ Methods Guide for Comparative Effectiveness Reviews (12) to rate studies as having low, medium, high, or unclear risk of bias. Two reviewers independently assessed risk of bias for each study, and disagreements were resolved by consensus. Data Synthesis and Analysis We categorized intervention types primarily on the basis of the method and environment of delivery, as defined in Table 1. One investigator categorized the intervention, and a second team member reviewed the categorization. Disagreements were resolved by consensus. Given heterogeneity of the clinic-based interventions, we subcategorized these by clinic setting: MDS-HF, nurse-led HF, or primary care. We used DerSimonianLaird random-effects models (13) for meta-analyses of outcomes reported by multiple studies that were sufficiently similar to justify combining results. We ran meta-analyses of trials that reported the number of deaths or number of persons readmitted in each group (and not total readmissions per group). When only the total number of readmissions per group was available, we contacted authors for additional data. When we could not obtain the number of persons readmitted, we did not include the results in meta-analyses; instead, we included the results in qualitative syntheses and considered them when grading the strength of evidence (SOE). For readmission and mortality rates, we calculated risk ratios (RRs). We stratified analyses for each intervention category by outcome timing and separated rates reported at 30 days from those after 30 days (that is, rates reported over 3 to 6 months were combined). We did not include studies rated as high or unclear risk of bias in our main analyses but included them in sensitivity analyses, which are available in the technical report (10); we describe them here only when they differed from primary analyses. We assessed statistical heterogeneity using the chi-square and I 2 statistics (14, 15). We calculated the number needed to treat (NNT) for readmission and mortality outcomes when we had statistically significant findings based on our primary analyses of trials rated as low or medium risk of bias, and we found at least low SOE for benefit. The NNT was derived from the RR and median usual care event rate using methods described in the Cochrane Handbook (16). We conducted meta-analyses using Stata, version 11.1 (StataCorp, College Station, Texas). We did meta-analysis stratified by intensity in each intervention category when variation existed. The results of these subgroup analyses are available in the main report (10); we describe them here only when we found a difference in efficacy based on level of intensity. Given the heterogeneity of included interventions, we could not develop a single measure of intensity that could be applied to all intervention categories. For most interventions, we defined intensity as the duration, frequency, or periodicity of patient contact and categorized each intervention as low-, medium-, or high-intensity. We reserved the low-intensity category for interventions that included 1 episode of patient contact or few resources. We graded SOE as high, moderate, low, or insufficient based on guidance established for the Evidence-based Practice Center program (17). The approach incorporates 4 key domains: risk of bias, consistency, directness, and precision. When only 1 study reported an outcome of interest, we usually graded the SOE as insufficient (primarily due to unknown consistency and imprecision); however, when similar interventions had consistent results at other time points, we graded the SOE as low. Two reviewers assessed each domain for each outcome, and differences were resolved by consensus. Role of the Funding Source The AHRQ funded this review, and AHRQ staff participated in the development of the scope of the work and reviewed draft manuscripts. Approval from AHRQ was required before the manuscript could be submitted for publication, but the authors are solely responsible for the content and the decision to submit it for publication. Results Searches of all sources identified 2419 potentially relevant citations. We included 47 RCTs (Appendix Figure 1). Trial characteristics are shown in Appendix Table 3. Most trials compared a transitional care intervention with usual care; 2 directly compared more than 1 intervention (both rated high risk of bias) (18, 19). In general, trials included adults with a mean age of 70 years who were hospitalized with a primary diagnosis of HF. Most reported HF disease severity based on the New York Heart Association classification and included persons with moderate to severe HF. Twenty-nine trials reported mean ejection fraction. Of these, 27 enrolled persons with a mean ejection fraction less than 0.50 and 7 trials specified a reduced ejection fraction as an inclusion criterion. Across most trials, the majority of patients were prescribed an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. The percentages of patients who were prescribed -blockers at discharge varied widely across trials. Trials were conducted in a range of settings: academic medical centers, Department of Veterans Affairs hospitals,

Screening for Asymptomatic Carotid Artery Stenosis: A Systematic Review and Meta-analysis for the U.S. Preventive Services Task Force

Stroke is a leading cause of death and disability (1). An estimated 7 million U.S. adults have had a stroke, and roughly 75% were first attacks (2). Ischemic strokes account for nearly 90% of all strokes in the United States (3). Carotid artery stenosis (CAS) causes approximately 10% of ischemic strokes (4). Carotid artery stenosis refers to atherosclerotic narrowing of the extracranial carotid arteriesspecifically, the internal carotid arteries or the common and internal carotid arteries. The best available data for the prevalence of asymptomatic CAS from large U.S.-based studies of the general population were published in the 1990s and enrolled adults aged 65 years or older (5, 6). Data published in 1992 showed a prevalence of just more than 1% for CAS of 75% to 99% (6), and those published in 1998 suggested a prevalence of 0.5% for CAS of 70% to 99% (5). Several studies have attempted to estimate the rate of progression of asymptomatic CAS and predict neurologic events (5, 711). The best available data from large U.S.-based studies of the general population revealed a 5-year risk for ipsilateral stroke of 5% for CAS of 70% or greater (5441 participants) (5). The main purpose of this review is to evaluate the current evidence on whether screening asymptomatic adults for CAS reduces the risk for ipsilateral stroke and on harms associated with screening and interventions for CAS. We also evaluated evidence on the incremental benefit of medical therapy and on risk-stratification tools. Despite a D recommendation from the U.S. Preventive Services Task Force in 2007 (12), many surgeries or interventions for asymptomatic CAS continue to be performed, and free or cash-on-the-barrel screenings are offered in public locations across the country (13). Methods We developed an analytic framework (Supplement 1) and key questions (Table 1 of Supplement 2) that guided the review. Detailed methods and additional results are publicly available in our full evidence report (www.uspreventiveservicestaskforce.org) (14). Supplement 1. Analytic Framework for Screening for Asymptomatic Carotid Artery Stenosis Supplement 2. Tables Data Sources and Searches We searched MEDLINE, the Cochrane Library, and EMBASE for English-language articles published through September 2013 (Tables 2 and 3 of Supplement 2). We conducted a targeted update search of MEDLINE for trials published through 31 March 2014 and searched clinical trial registries for unpublished literature. To supplement electronic searches, we reviewed reference lists of included studies and literature suggested by reviewers. Study Selection Two investigators independently reviewed abstracts and full-text articles against prespecified eligibility criteria (Table 4 of Supplement 2). We included studies that focused on asymptomatic adults with CAS and studies that analyzed the asymptomatic group separately. We included randomized, controlled trials (RCTs) of screening for CAS, RCTs and systematic reviews of treatment effectiveness, multi-institution trials or cohort studies that reported harms, and studies that attempted to externally validate risk-stratification tools. For evaluation of accuracy and reliability of ultrasonography, we focused on systematic reviews but also included primary studies that were published after the literature search cutoff of the most recent good-quality systematic review. Data Extraction and Quality Assessment One investigator extracted pertinent information from each article. Another investigator reviewed extractions for completeness and accuracy. Two independent investigators assigned quality ratings (good, fair, or poor) for each study using predefined criteria (14, 15). Disagreements were resolved with team discussion. Poor-quality studies are described in the full report (14). Data Synthesis and Analysis We qualitatively synthesized findings for each key question by summarizing the characteristics and results of included studies in tabular or narrative format. To determine whether meta-analyses were appropriate, we assessed the clinical and methodological heterogeneity of the studies following established guidance (16). We conducted meta-analysis of RCTs that compared carotid endarterectomy (CEA) with medical therapy for relevant outcomes reported by several studies. We used DerSimonianLaird random-effects models to estimate pooled effects (17) and calculated risk differences between CEA and medical therapy to show the absolute differences between groups. Absolute measures are more easily interpreted, show more directly relevant information, and better allow decision makers to assess tradeoffs between benefits and harms (1820). We calculated chi-square and I 2 statistics to assess statistical heterogeneity in effects among studies (21, 22). To allow the comparison of rates of perioperative harms reported in RCTs with those from sources that may be more representative of real-world clinical practice, we conducted meta-analyses of cohort studies that reported perioperative (30-day) stroke or death rates. We also conducted meta-analyses of such rates reported in trials that involved CEA or carotid angioplasty and stenting (CAAS), regardless of the comparator. We conducted sensitivity analyses using profile likelihood random-effects methods when our meta-analyses included few studies (2326). We did not include poor-quality studies in our analyses. Analyses were conducted using Stata, version 11.1 (StataCorp). Role of the Funding Source The Agency for Healthcare Research and Quality funded the review. Members of the U.S. Preventive Services Task Force and Agency for Healthcare Research and Quality assisted in developing the reviews scope and reviewed draft manuscripts, but the authors are solely responsible for the content. Results We included 78 published articles that reported on 56 studies (Figure 1) . Figure 1. Summary of evidence search and selection. WHO ICTRP = World Health Organization International Clinical Trials Registry Platform. Direct Evidence that Screening Reduces Ipsilateral Stroke We found no eligible studies that provided evidence on whether screening reduced ipsilateral stroke. Accuracy and Reliability of Duplex Ultrasonography We included 3 meta-analyses (2729) and 1 fair-quality primary study (30) (Table 5 of Supplement 2). The most recent good-quality meta-analysis (28) included 47 studies published through 2003 that used digital subtraction angiography as the reference standard. It reported sensitivity and specificity for detecting stenosis of 50% or greater (1716 participants) of 98% (95% CI, 97% to 100%) and 88% (CI, 76% to 100%), respectively. Sensitivity and specificity for detecting stenosis of 70% or greater (2140 participants) were 90% (CI, 84% to 94%) and 94% (CI, 88% to 97%). Using data from this meta-analysis, the last evidence report for the U.S. Preventive Services Task Force estimated the sensitivity and specificity for detecting stenosis of 60% or greater as 94% and 92%, respectively (31). The meta-analysis reported wide, clinically important variation in measurement properties among laboratories (28). The findings of the other meta-analyses were generally consistent with these results, but specificity in the primary study was lower (66% for detecting CAS of 70% to 99% [CI, 63% to 71%]; 503 participants) (30). Additional results are provided in our full report (14). Benefits of CEA or CAAS Beyond Medical Therapy We included 3 RCTs (Table 1) described in 12 publications (3243) that compared CEA with medical therapy and 3 systematic reviews described in 5 publications (31, 4447). We found no eligible studies that compared CAAS with medical therapy and no studies that compared CEA with current standard medical therapy. Table 1. Characteristics and Main Results of Included Fair- or Good-Quality Randomized, Controlled Trials of CEA Compared With MM for Asymptomatic CAS* The ACAS (Asymptomatic Carotid Atherosclerosis Study) and the VACS (Veterans Affairs Cooperative Study) were conducted in North America; the ACST (Asymptomatic Carotid Surgery Trial) involved 30 countries, primarily in Europe. Medical therapy varied across trials and was often not clearly defined or standardized. Surgeons with a history of low complication rates were selected. They submitted records of their last 50 cases or previous 24 months of experience with CEA and were selected on the basis of review by a committee or morbidity and mortality rates less than 3%. Our meta-analyses found that fewer persons treated with CEA had perioperative stroke or death or subsequent ipsilateral stroke, perioperative stroke or death or any subsequent stroke, any stroke or death, nonperioperative ipsilateral stroke, and any nonperioperative stroke than those in medical therapy groups (Table 2 and Figure 2). For all-cause mortality, we found no significant difference. Results for sensitivity analyses using profile likelihood methods were very similar to those of our main analyses, with only minor variation in width of CIs (Table 2). Table 2. Summary of Main Results of Meta-analyses Figure 2. Meta-analyses of randomized, controlled trials comparing CEA with medical therapy, by outcome. ACAS = Asymptomatic Carotid Atherosclerosis Study; ACST = Asymptomatic Carotid Surgery Trial; CEA = carotid endarterectomy; MM = medical management; RD = risk difference; VACS = Veterans Affairs Cooperative Study. In the ACST, more than one half (57.8% [166 of 287]) of nonperioperative strokes were disabling or fatal, and the proportional reduction in disabling or fatal stroke (relative risk, 0.61 [CI, 0.41 to 0.92]) was similar to that for any stroke (relative risk, 0.54 [CI, 0.43 to 0.68]) (37). Subgroup analyses of the ACAS showed a statistically significant reduction for men (relative risk reduction, 66% [CI, 36% to 82%]) but not for women (relative risk reduction, 17% [CI, 96% to 65%]) for estimated 5-year rate of perioperative stroke or death and subsequent ipsilateral stroke.

Screening for Obstructive Sleep Apnea in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance Many adverse health outcomes are associated with obstructive sleep apnea (OSA). Objective To review primary care–relevant evidence on screening adults for OSA, test accuracy, and treatment of OSA, to inform the US Preventive Services Task Force. Data Sources MEDLINE, Cochrane Library, EMBASE, and trial registries through October 2015, references, and experts, with surveillance of the literature through October 5, 2016. Study Selection English-language randomized clinical trials (RCTs); studies evaluating accuracy of screening questionnaires or prediction tools, diagnostic accuracy of portable monitors, or association between apnea-hypopnea index (AHI) and health outcomes among community-based participants. Data Extraction and Synthesis Two investigators independently reviewed abstracts and full-text articles. When multiple similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures Sensitivity, specificity, area under the curve (AUC), AHI, Epworth Sleepiness Scale (ESS) scores, blood pressure, mortality, cardiovascular events, motor vehicle crashes, quality of life, and harms. Results A total of 110 studies were included (N = 46 188). No RCTs compared screening with no screening. In 2 studies (n = 702), the screening accuracy of the multivariable apnea prediction score followed by home portable monitor testing for detecting severe OSA syndrome (AHI ≥30 and ESS score >10) was AUC 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90), respectively, but the studies oversampled high-risk participants and those with OSA and OSA syndrome. No studies prospectively evaluated screening tools to report calibration or clinical utility for improving health outcomes. Meta-analysis found that continuous positive airway pressure (CPAP) compared with sham was significantly associated with reduction of AHI (weighted mean difference [WMD], −33.8 [95% CI, −42.0 to −25.6]; 13 trials, 543 participants), excessive sleepiness assessed by ESS score (WMD, −2.0 [95% CI, −2.6 to −1.4]; 22 trials, 2721 participants), diurnal systolic blood pressure (WMD, −2.4 points [95% CI, −3.9 to −0.9]; 15 trials, 1190 participants), and diurnal diastolic blood pressure (WMD, −1.3 points [95% CI, −2.2 to −0.4]; 15 trials, 1190 participants). CPAP was associated with modest improvement in sleep-related quality of life (Cohen d, 0.28 [95% CI, 0.14 to 0.42]; 13 trials, 2325 participants). Mandibular advancement devices (MADs) and weight loss programs were also associated with reduced AHI and excessive sleepiness. Common adverse effects of CPAP and MADs included oral or nasal dryness, irritation, and pain, among others. In cohort studies, there was a consistent association between AHI and all-cause mortality. Conclusions and Relevance There is uncertainty about the accuracy or clinical utility of all potential screening tools. Multiple treatments for OSA reduce AHI, ESS scores, and blood pressure. Trials of CPAP and other treatments have not established whether treatment reduces mortality or improves most other health outcomes, except for modest improvement in sleep-related quality of life.

Hormone therapy for the primary prevention of chronic conditions in postmenopausal women evidence report and systematic review for the US preventive services task force

Importance Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions. Objective To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions. Data Sources MEDLINE, Cochrane Library, EMBASE, and trial registries from June 1, 2011, through August 1, 2016. Surveillance for new evidence in targeted publications was conducted through July 1, 2017. Study Selection English-language randomized clinical trials reporting health outcomes. Data Extraction and Synthesis Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available. Main Outcomes and Measures Beneficial or harmful changes in risks for various chronic conditions. Results Eighteen trials (n = 40 058; range, 142-16 608; mean age, 53-79 years) were included. Women using estrogen-only therapy compared with placebo had significantly lower risks, per 10 000 person-years, for diabetes (−19 cases [95% CI, −34 to −3]) and fractures (−53 cases [95% CI, −69 to −39]). Risks were statistically significantly increased, per 10 000 person-years, for gallbladder disease (30 more cases [95% CI, 16 to 48]), stroke (11 more cases [95% CI, 2 to 23]), venous thromboembolism (11 more cases [95% CI, 3 to 22]), and urinary incontinence (1261 more cases [95% CI, 880 to 1689]). Women using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 person-years, for colorectal cancer (−6 cases [95% CI, −9 to −1]), diabetes (−14 cases [95% CI, −24 to −3), and fractures (−44 cases [95% CI, −71 to −13). Risks, per 10 000 person-years, were significantly increased for invasive breast cancer (9 more cases [95% CI, 1 to 19]), probable dementia (22 more cases [95% CI, 4 to 53]), gallbladder disease (21 more cases [95% CI, 10 to 34]), stroke (9 more cases [95% CI, 2 to 19]), urinary incontinence (876 more cases [95% CI, 606 to 1168]), and venous thromboembolism (21 more cases [95% CI, 12 to 33]). Conclusions and Relevance Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms. The available evidence regarding benefits and harms of early initiation of hormone therapy is inconclusive.

Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

IMPORTANCE Five to ten percent of individuals with latent tuberculosis infection (LTBI) progress to active tuberculosis (TB) disease. Identifying and treating LTBI is a key component of the strategy for reducing the burden of TB disease. OBJECTIVE To review the evidence about targeted screening and treatment for LTBI among adults in primary care settings to support the US Preventive Services Task Force in updating its 1996 recommendation. DATA SOURCES MEDLINE, Cochrane Library, and trial registries, searched through August 3, 2015; references from pertinent articles; and experts. Literature surveillance was conducted through May 31, 2016. STUDY SELECTION English-language studies of LTBI screening, LTBI treatment with recommended pharmacotherapy, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of individuals for whom LTBI screening and treatment is part of public health surveillance or disease management were excluded. DATA EXTRACTION AND SYNTHESIS Two investigators independently reviewed abstracts and full-text articles. When at least 3 similar studies were available, random-effects meta-analysis was used to generate pooled estimates of outcomes. MAIN OUTCOMES AND MEASURES Sensitivity, specificity, reliability, active TB disease, mortality, hepatotoxicity, and other harms. RESULTS The review included 72 studies (n = 51 711). No studies evaluated benefits and harms of screening compared with no screening. Pooled estimates for sensitivity of the TST at both 5-mm and 10-mm induration thresholds were 0.79 (5-mm: 95% CI, 0.69-0.89 [8 studies, n = 803]; 10 mm: 95% CI, 0.71-0.87 [11 studies; n = 988]), and those for IGRAs ranged from 0.77 to 0.90 (57 studies; n = 4378). Pooled estimates for specificity of the TST at the 10-mm and 15-mm thresholds and for IGRAs ranged from 0.95 to 0.99 (34 studies; n = 23 853). A randomized clinical trial (RCT) of 24 weeks of isoniazid in individuals with pulmonary fibrotic lesions and LTBI (n = 27 830) found a reduction in absolute risk of active TB at 5 years from 1.4% to 0.5% (relative risk [RR], 0.35 [95% CI, 0.24-0.52]) and an increase in absolute risk for hepatoxicity from 0.1% to 0.5% (RR, 4.59 [95% CI, 2.03-10.39]) for 24 weeks of daily isoniazid compared with placebo. An RCT (n = 6886) found that 3 months of once-weekly rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing active TB. The risk difference for hepatoxicity comparing isoniazid with rifampin ranged from 3% to 7%, with a pooled RR of 3.29 (95% CI, 1.72-6.28 [3 RCTs; n = 1327]). CONCLUSIONS AND RELEVANCE No studies evaluated the benefits and harms of screening compared with no screening. Both the TST and IGRAs are moderately sensitive and highly specific within countries with low TB burden. Treatment reduced the risk of active TB among the populations included in this review. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.

Occupational and Environmental Exposure to Asbestos

The usefulness of asbestos as an industrial material must be considered to understand the breadth of its public health impact. Since its discovery as an indestructible material centuries ago, it has found countless applications. Few substances rival its engineering and commercial performance.

Genetic polymorphisms and response to medications for alcohol use disorders: a systematic review and meta-analysis

AIM To assess whether response to medications for alcohol use disorders varies by genotype. METHODS Systematic review and meta-analysis. RESULTS We found no studies that assessed the clinical utility of genotype-guided dosing strategies or genotype-guided medication selection, and none randomized by genotype. All included studies assessed the association between genotype and response to medication. Of 15 included studies, eight (n = 1365 participants) assessed variation in naltrexone response and polymorphisms of OPRM1. Our meta-analyses for return to heavy drinking found no significant difference between A allele homozygotes and those with at least one G allele, both without (risk difference: 0.26; 95% CI: -0.01-0.53; n = 174) and with inclusion of studies rated as high or unclear risk of bias (risk difference: 0.14; 95% CI: -0.03-0.3; n = 382). For all other polymorphism-medication pairs, we found just one eligible study. CONCLUSION Estimates of effect for return to heavy drinking suggest it is possible that patients with at least one G allele of A118G polymorphism of OPRM1 might be more likely to respond to naltrexone, but confidence intervals were wide; additional studies are needed to improve confidence in the estimates.

Vision Screening in Children Aged 6 Months to 5 Years: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance Preschool vision screening could allow detection and treatment of vision abnormalities during a critical developmental stage, preserving function and quality of life. Objective To review the evidence on screening for and treatment of amblyopia, its risk factors, and refractive error in children aged 6 months to 5 years to inform the US Preventive Services Task Force. Data Sources MEDLINE, Cochrane Library, CINAHL, and trial registries through June 2016; references; and experts, with surveillance of the literature through June 7, 2017. Study Selection English-language randomized clinical trials (RCTs) or prospective cohort studies that evaluated screening, studies evaluating test accuracy, RCTs of treatment vs inactive controls, and cohort studies or case-control studies assessing harms. Data Extraction and Synthesis Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Studies were not quantitatively pooled because of clinical and methodological heterogeneity. Main Outcomes and Measures Visual acuity, amblyopia, school performance, functioning, quality of life, test accuracy, testability, and harms. Results Forty studies were included (N = 34 709); 34 evaluated test accuracy. No RCTs compared screening with no screening, and no studies evaluated school performance, function, or quality of life. Studies directly assessing earlier or more intensive screening were limited by high attrition. Positive likelihood ratios were between 5 and 10 for amblyopia risk factors or nonamblyogenic refractive error in most studies of test accuracy and were greater than 10 in most studies evaluating combinations of clinical tests. Inability to cooperate may limit use of some tests in children younger than 3 years. Studies with low prevalence (<10%) of vision abnormalities showed high false-positive rates (usually >75%). Among children with amblyopia risk factors (eg, strabismus or anisometropia), patching improved visual acuity of the amblyopic eye by a mean of less than 1 line on a standard chart after 5 to 12 weeks for children pretreated with glasses (2 RCTs, 240 participants); more children treated with patching than with no patching experienced improvement of at least 2 lines (45% vs 21%; P = .003; 1 RCT, 180 participants). Patching plus glasses improved visual acuity by about 1 line after 1 year (0.11 logMAR [95% CI, 0.05-0.17]) for children not pretreated with glasses (1 RCT, 177 participants). Glasses alone improved visual acuity by less than 1 line after 1 year (0.08 logMAR [95% CI, 0.02-0.15], 1 RCT, 177 participants). Conclusions and Relevance Studies directly evaluating the effectiveness of screening were limited and do not establish whether vision screening in preschool children is better than no screening. Indirect evidence supports the utility of multiple screening tests for identifying preschool children at higher risk for vision problems and the effectiveness of some treatments for improving visual acuity outcomes.

Serologic Screening for Genital Herpes: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance Genital herpes simplex virus (HSV) infection is a prevalent sexually transmitted infection. Vertical transmission of HSV can lead to fetal morbidity and mortality. Objective To assess the evidence on serologic screening and preventive interventions for genital HSV infection in asymptomatic adults and adolescents to support the US Preventive Services Task Force for an updated recommendation statement. Data Sources MEDLINE, Cochrane Library, EMBASE, and trial registries through March 31, 2016. Surveillance for new evidence in targeted publications was conducted through October 31, 2016. Study Selection English-language randomized clinical trials (RCTs) comparing screening with no screening in persons without past or current symptoms of genital herpes; studies evaluating accuracy and harms of serologic screening tests for HSV-2; RCTs assessing preventive interventions in asymptomatic persons seropositive for HSV-2. Data Extraction and Synthesis Dual review of abstracts, full-text articles, and study quality; pooled sensitivities and specificities of screening tests using a hierarchical summary receiver operating characteristic curve analysis when at least 3 similar studies were available. Main Outcomes and Measures Accuracy of screening tests, benefits of screening, harms of screening, reduction in genital herpes outbreaks. Results A total of 17 studies (n = 9736 participants; range, 24-3290) in 19 publications were included. No RCTs compared screening with no screening. Most studies of the accuracy of screening tests were from populations with high HSV-2 prevalence (greater than 40% based on Western blot). Pooled estimates of sensitivity and specificity of the most commonly used test at the manufacturers cutpoint were 99% (95% CI, 97%-100%) and 81% (95% CI, 68%-90%), respectively (10 studies; n = 6537). At higher cutpoints, pooled estimates were 95% (95% CI, 91%-97%) and 89% (95% CI, 82%-93%), respectively (7 studies; n = 5516). Use of this test at the manufacturers cutpoint in a population of 100 000 with a prevalence of HSV-2 of 16% (the seroprevalence in US adults with unknown symptom status) would result in 15 840 true-positive results and 15 960 false-positive results (positive predictive value, 50%). Serologic screening for genital herpes was associated with psychosocial harms, including distress and anxiety related to positive test results. Four RCTs compared preventive medications with placebo, 2 in nonpregnant asymptomatic adults who were HSV-2 seropositive and 2 in HSV-2-serodiscordant couples. Results in both populations were heterogeneous and inconsistent. Conclusions and Relevance Serologic screening for genital herpes is associated with a high rate of false-positive test results and potential psychosocial harms. Evidence from RCTs does not establish whether preventive antiviral medication for asymptomatic HSV-2 infection has benefit.

Screening for Intimate Partner Violence, Elder Abuse, and Abuse of Vulnerable Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance Intimate partner violence (IPV), elder abuse, and abuse of vulnerable adults are common and result in adverse health outcomes. Objective To review the evidence on screening and interventions for IPV, elder abuse, and abuse of vulnerable adults to inform the US Preventive Services Task Force. Data Sources MEDLINE, Cochrane Library, EMBASE, and trial registries through October 4, 2017; references; experts; literature surveillance through August 1, 2018. Study Selection English-language randomized clinical trials (RCTs), studies evaluating test accuracy, and cohort studies with a concurrent control group assessing harms. Data Extraction and Synthesis Dual review of titles and abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled, primarily because of heterogeneity of populations, interventions, and outcomes. Main Outcomes and Measures Abuse or neglect, morbidity caused by abuse, test accuracy, and harms. Results Thirty studies were included (N = 14 959). Three RCTs (n = 3759) compared IPV screening with no screening; none found significant improvements in outcomes (eg, IPV or quality of life) over 3 to 18 months and 2 (n = 935) reported no harms of screening. Nine studies assessed tools to detect any past-year or current IPV in women; for past-year IPV (5 studies [n = 6331]), sensitivity of 5 tools ranged from 65% to 87% and specificity ranged from 80% to 95%. The accuracy of 5 tools (4 studies [n = 1795]) for detecting current abuse varied widely; sensitivity ranged from 46% to 94% and specificity ranged from 38% to 95%. Eleven RCTs (n = 6740) evaluated interventions for women with screen-detected IPV. Two enrolling pregnant women (n = 575) found significantly less IPV among women in the intervention group: 1 home visiting intervention (standardized mean difference [SMD], −0.34 [95% CI, −0.59 to −0.08]) and 1 behavioral counseling intervention for multiple risks (IPV, smoking, depression, tobacco exposure) (SMD, −0.40 [95% CI, −0.68 to −0.12]). No studies evaluated screening or interventions for elder abuse or abuse of vulnerable adults. One study assessing a screening tool for elder abuse had poor accuracy (sensitivity, 46% and specificity, 73% for detecting physical or verbal abuse). Conclusions and Relevance Although available screening tools may reasonably identify women experiencing IPV, trials of IPV screening in adult women did not show a reduction in IPV or improvement in quality of life over 3 to 18 months. Limited evidence suggested that home visiting and behavioral counseling interventions that address multiple risk factors may lead to reduced IPV among pregnant or postpartum women. No studies assessed screening or treatment for elder abuse and abuse of vulnerable adults.