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Importance Type 2 diabetes is common and is a leading cause of morbidity and disability. Objective To review the evidence on screening for prediabetes and diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources PubMed/MEDLINE, Cochrane Library, and trial registries through September 2019; references; and experts; literature surveillance through May 21, 2021. Study Selection English-language controlled studies evaluating screening or interventions for prediabetes or diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when at least 3 similar studies were available. Main Outcomes and Measures Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results The review included 89 publications (N = 68 882). Two randomized clinical trials (RCTs) (25 120 participants) found no significant difference between screening and control groups for all-cause or cause-specific mortality at 10 years. For harms (eg, anxiety or worry), the trials reported no significant differences between screening and control groups. For recently diagnosed (not screen-detected) diabetes, 5 RCTs (5138 participants) were included. In the UK Prospective Diabetes Study, health outcomes were improved with intensive glucose control with sulfonylureas or insulin. For example, for all-cause mortality the relative risk (RR) was 0.87 (95% CI, 0.79 to 0.96) over 20 years (10-year posttrial assessment). For overweight persons, intensive glucose control with metformin improved health outcomes at the 10-year follow-up (eg, all-cause mortality: RR, 0.64 [95% CI, 0.45 to 0.91]), and benefits were maintained longer term. Lifestyle interventions (most involving >360 minutes) for obese or overweight persons with prediabetes were associated with reductions in the incidence of diabetes (23 RCTs; pooled RR, 0.78 [95% CI, 0.69 to 0.88]). Lifestyle interventions were also associated with improved intermediate outcomes, such as reduced weight, body mass index, systolic blood pressure, and diastolic blood pressure (pooled weighted mean difference, −1.7 mm Hg [95% CI, −2.6 to −0.8] and −1.2 mm Hg [95% CI, −2.0 to −0.4], respectively). Metformin was associated with a significant reduction in diabetes incidence (pooled RR, 0.73 [95% CI, 0.64 to 0.83]) and reduction in weight and body mass index. Conclusions and Relevance Trials of screening for diabetes found no significant mortality benefit but had insufficient data to assess other health outcomes; evidence on harms of screening was limited. For persons with recently diagnosed (not screen-detected) diabetes, interventions improved health outcomes; for obese or overweight persons with prediabetes, interventions were associated with reduced incidence of diabetes and improvement in other intermediate outcomes.

Importance Office blood pressure (BP) measurements are not the most accurate method to diagnose hypertension. Home BP monitoring (HBPM) and 24-hour ambulatory BP monitoring (ABPM) are out-of-office alternatives, and ABPM is considered the reference standard for BP assessment. Objective To systematically review the accuracy of oscillometric office and home BP measurement methods for correctly classifying adults as having hypertension, defined using ABPM. Data Sources PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and DARE databases and the American Heart Association website (from inception to April 2021) were searched, along with reference lists from retrieved articles. Data Extraction and Synthesis Two authors independently abstracted raw data and assessed methodological quality. A third author resolved disputes as needed. Main Outcomes and Measures Random effects summary sensitivity, specificity, and likelihood ratios (LRs) were calculated for BP measurement methods for the diagnosis of hypertension. ABPM (24-hour mean BP ≥130/80 mm Hg or mean BP while awake ≥135/85 mm Hg) was considered the reference standard. Results A total of 12 cross-sectional studies (n = 6877) that compared conventional oscillometric office BP measurements to mean BP during 24-hour ABPM and 6 studies (n = 2049) that compared mean BP on HBPM to mean BP during 24-hour ABPM were included (range, 117-2209 participants per analysis); 2 of these studies (n = 3040) used consecutive samples. The overall prevalence of hypertension identified by 24-hour ABPM was 49% (95% CI, 39%-60%) in the pooled studies that evaluated office measures and 54% (95% CI, 39%-69%) in studies that evaluated HBPM. All included studies assessed sensitivity and specificity at the office BP threshold of 140/90 mm Hg and the home BP threshold of 135/85 mm Hg. Conventional office oscillometric measurement (1-5 measurements in a single visit with BP ≥140/90 mm Hg) had a sensitivity of 51% (95% CI, 36%-67%), specificity of 88% (95% CI, 80%-96%), positive LR of 4.2 (95% CI, 2.5-6.0), and negative LR of 0.56 (95% CI, 0.42-0.69). Mean BP with HBPM (with BP ≥135/85 mm Hg) had a sensitivity of 75% (95% CI, 65%-86%), specificity of 76% (95% CI, 65%-86%), positive LR of 3.1 (95% CI, 2.2-4.0), and negative LR of 0.33 (95% CI, 0.20-0.47). Two studies (1 with a consecutive sample) that compared unattended automated mean office BP (with BP ≥135/85 mm Hg) with 24-hour ABPM had sensitivity ranging from 48% to 51% and specificity ranging from 80% to 91%. One study that compared attended automated mean office BP (with BP ≥140/90 mm Hg) with 24-hour ABPM had a sensitivity of 87.6% (95% CI, 83%-92%) and specificity of 24.1% (95% CI, 16%-32%). Conclusions and Relevance Office measurements of BP may not be accurate enough to rule in or rule out hypertension; HBPM may be helpful to confirm a diagnosis. When there is uncertainty around threshold values or when office and HBPM are not in agreement, 24-hour ABPM should be considered to establish the diagnosis.

Background Multiple national organizations recommend screening and counseling adults for unhealthy alcohol use. Methods An evidence-based approach to screening and counseling using Epic electronic health record (EHR) tools was implemented in a general medicine clinic. A dissemination package with actionable steps for clinics and systems wishing to implement similar processes was then produced. To evaluate the initial implementation and quality improvement project, run charts were created to track patients screened, patients counseled, and fidelity to protocols, and members of the original project team were interviewed to assess facilitators and barriers. The draft dissemination package was revised after feedback from health system representatives (key informants). Results More than 9,000 patients (73.9% of those eligible) were screened in 20 months. Sixty-four percent of patients with positive initial screens had documented screening-related assessment; 39.7% (141/355) were offered counseling when indicated. Initial project team members identified EHR tools, clinic leadership, quality improvement culture, a multidisciplinary team, and training for providers and nurses as facilitators; and competing demands, patient population size, and nursing staff/resident turnover as barriers. Six key informants evaluated the dissemination package. Most rated 10 of the 12 sections as very useful; all rated components specific to implementing alcohol screening and counseling as very useful. Ratings for general guidance on implementing evidence-based services in primary care were more mixed. Conclusion Evidence-based screening and counseling for unhealthy alcohol use can be implemented with EHR tools. A dissemination guide was viewed favorably by key informants and can serve as a guide for other clinics and systems.

Background Unhealthy alcohol use is a leading cause of preventable deaths in the USA and is associated with many societal and health problems. Less than a third of people who visit primary care providers in the USA are asked about or ever discuss alcohol use with a health professional. Methods/design This study is an adaptive, randomized, controlled trial to evaluate the effect of primary care practice facilitation and telehealth services on evidence-based screening, counseling, and pharmacotherapy for unhealthy alcohol use in small-to-medium-sized primary care practices. Study participants will include primary care practices in North Carolina with 10 or fewer providers. All enrolled practices will receive a practice facilitation intervention that includes quality improvement (QI) coaching, electronic health record (EHR) support, training, and expert consultation. After 6 months, practices in the lower 50th percentile (based on performance) will be randomized to continued practice facilitation or provision of telehealth services plus ongoing facilitation for the next 6 months. Practices in the upper 50th percentile after the initial 6 months of intervention will continue to receive practice facilitation alone. The main outcome measures include the number (and %) of patients in the target population who are screened for unhealthy alcohol use, screen positive, and receive brief counseling. Additional measures include the number (and %) of patients who receive pharmacotherapy for AUD or are referred for AUD services. Sample size calculations determined that 35 practices are needed to detect a 10% increase in the main outcome (percent screened for unhealthy alcohol use) over 6 months. Discussion A successful intervention would significantly reduce morbidity among adults from unhealthy alcohol use by increasing counseling and other treatment opportunities. The study will produce important evidence about the effect of practice facilitation on uptake of evidence-based screening, counseling, and pharmacotherapy for unhealthy alcohol use when delivered on a large scale to small and medium-sized practices. It will also generate scientific knowledge about whether embedded telehealth services can improve the use of evidence-based screening and interventions for practices with slower uptake. The results of this rigorously conducted evaluation are expected to have a positive impact by accelerating the dissemination and implementation of evidence related to unhealthy alcohol use into primary care practices. Trial registration ClinicalTrials.govNCT04317989. Registered on March 23, 2020.

Evidence-based depression treatment in primary care is well established. However, clinicians are less likely to be trained to diagnose and treat anxiety disorder, which is frequently comorbid, poses an independent risk for suicidality, and complicates disease management. The University of North Carolina's Internal Medicine Clinic developed a measurement-guided approach to identifying and treating anxiety disorder using the seven-item Generalized Anxiety Disorder Scale, treatment algorithms, medication charts, case-based training for best practices, onsite behavioral counseling, and psychiatric consultation. NAMASTE (new anxiety management algorithm standardizing treatment experience) offers a treatment approach for primary care and addresses a major unmet need in public health and medical education.

Controversy over blood pressure (BP) treatment targets for individuals with diabetes is in part due to conflicting perspectives about generalizability of available trial data.The authors sought to estimate how results from the largest clinical trial of intensive BP treatment among adults with diabetes would generalize to the U.S.The authors used transportability methods to reweight individual patient data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial (N = 4,507) of intensive (goal systolic BP 120 mm Hg) versus standard (goal systolic BP 140 mm Hg) treatment to better represent the demographic and clinical risk factors of the U.S. population of adults with diabetes (data from NHANES [National Health and Nutrition Examination Survey] 2005 to 2014, n = 1,943). The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Analysis used weighted Cox proportional hazards regression models with robust standard errors.The ACCORD BP sample had less racial/ethnic diversity and more elevated cardiovascular risk factors than the NHANES participants. Weighted results significantly favored intensive BP treatment, unlike unweighted results (hazard ratio for primary outcome in intensive versus standard treatment in weighted analyses: 0.67, 95% confidence interval: 0.49 to 0.91; in unweighted analyses: hazard ratio: 0.88, 95% confidence interval: 0.73 to 1.07). Over 5 years, the weighted results estimate a number needed to treat of 34, and number needed to harm of 55.After reweighting to better reflect the U.S. adult population with diabetes, intensive BP therapy was associated with significantly lower risk for cardiovascular events. However, data were limited among racial/ethnic minorities and those with lower cardiovascular risk.

Objectives The USPSTF recommends lung cancer screening to adults aged 55 to 80 years who are current or former heavy smokers. Guidelines also recommend a thorough patient understanding of harms, including overdiagnosis, prior to screening. Many US medical centers, both academic and community, have screening programs and publish information about screening on their websites. Because websites could influence patients’ perceptions of screening benefits and harms, and subsequent decisions, some experts have expressed concern about persuasive or overly optimistic portrayals of screening in patient-facing websites. We evaluated the reporting of overdiagnosis on these websites in relation to the reporting of benefits, other harms, and suggested next steps for patients. Method Our study sample included lung cancer screening program websites found through a standardized web search from two types of institutions: 1) academic medical centers associated with all (n=152) US allopathic medical schools; 2) a state-matched random sample of community (non-academic) lung cancer screening programs drawn from a list of all (n=1779) American College of Radiology designated lung cancer screening centers. Two investigators independently evaluated each website for the reporting of overdiagnosis, benefits, other harms, and recommendations for next steps. Discrepancies were resolved by consensus. Analysis included bivariate comparisons between reporting rates for overdiagnosis and other harms and benefits. Results We identified 81 academic centers and 81 community centers (total n=162) with screening websites. Overdiagnosis was reported on 11 (6.7%) websites and more frequently on academic sites (13.6% vs 0.0%, p Conclusions Overdiagnosis was uncommonly reported by academic medical center lung cancer screening websites and was absent from community-based screening program websites. It was the least commonly reported harm and was noted significantly less than benefits of screening. Websites noting overdiagnosis were more likely to report potential harms of screening and to recommend patients weigh the harms and benefits of screening themselves and in consultation with their primary care provider. Research is needed to determine how portrayal of screening-related harms and benefits in this setting may contribute to imbalanced perceptions of harms and benefits and how these perceptions influence patient screening decisions.

BACKGROUND Naltrexone trials have demonstrated improved outcomes for patients with alcohol use disorders. Hospital initiation of naltrexone has had limited study. OBJECTIVE To describe the implementation and impact of a process for counseling hospitalized patients with alcohol withdrawal about naltrexone. DESIGN A pre-post study analysis. SETTING A tertiary academic center. PATIENTS Patients hospitalized for alcohol withdrawal. INTERVENTION (1) Provider education about the efficacy and contraindications of naltrexone and (2) algorithms for evaluating patients for naltrexone. MEASUREMENTS The percentages of patients counseled about and prescribed naltrexone before discharge and the percentages of pre- and postintervention patients with 30-day emergency department (ED) revisits and rehospitalizations. RESULTS We identified 128 patient encounters before and 114 after implementation. The percentage of patients counseled about naltrexone rose from 1.6% preimplementation to 63.2% postimplementation (P

The U.S. Preventive Services Task Force (USPSTF) is an independent body of experts who make evidence-based recommendations about clinical preventive services using a transparent and objective process. Developing recommendations on a clinical preventive service requires evidence of its effect on health outcomes. Health outcomes are symptoms, functional levels, and conditions that affect a patient's quantity or quality of life and are measured by assessments of physical or psychologic well-being. Intermediate outcomes are pathologic, physiologic, psychologic, social, or behavioral measures related to a preventive service. Given the frequent lack of evidence on health outcomes, the USPSTF uses evidence on intermediate outcomes when appropriate. The ultimate goal is to determine precisely a consistent relationship between the direction and magnitude of change in an intermediate outcome with a predictable resultant direction and magnitude of change in the health outcomes. The USPSTF reviewed its historical use of intermediate outcomes, reviewed methods of other evidence-based guideline-making bodies, consulted with other experts, and reviewed scientific literature. Most important were the established criteria for causation, tenets of evidence-based medicine, and consistency with its current standards. Studies that follow participants over time following early treatment, stratify patients according to treatment response, and adjust for important confounders can provide useful information about the association between intermediate and health outcomes. However, such studies remain susceptible to residual confounding. The USPSTF will exercise great caution when making a recommendation that depends on the evidence linking intermediate and health outcomes because of inherent evidence limitations.

Unhealthy alcohol use is a leading causes of preventable death in the United States. Reducing unhealthy alcohol use should be a high priority for health care providers. Well-validated screening instruments are available, and behavioral counseling interventions delivered in primary care can reduce risky drinking. For people with alcohol use disorder, treatment programs with or without medication can reduce consumption and promote abstinence. To overcome barriers to implementation of screening for alcohol use and subsequent delivery of appropriate interventions in primary care settings, support systems, changes in staffing or roles, formal protocols, and additional provider and staff training may be required.

BACKGROUND The emerging dual imperatives of personalized medicine and technologic advances make population screening for preventable conditions resulting from genetic alterations a realistic possibility. Lynch syndrome is a potential screening target due to its prevalence, penetrance, and the availability of well-established, preventive interventions. However, while population screening may lower incidence of preventable conditions, implementation without evidence may lead to unintentional harms. We examined the literature to determine whether evidence exists that screening for Lynch-associated mismatch repair (MMR) gene mutations leads to improved overall survival, cancer-specific survival, or quality of life. Documenting evidence and gaps is critical to implementing genomic approaches in public health and guiding future research. MATERIALS AND METHODS Our 2014-2015 systematic review identified studies comparing screening with no screening in the general population, and controlled studies assessing analytic validity of targeted next-generation sequencing, and benefits or harms of interventions or screening. We conducted meta-analyses for the association between early or more frequent colonoscopies and health outcomes. RESULTS Twelve studies met our eligibility criteria. No adequate evidence directly addressed the main question or the harms of screening in the general population. Meta-analyses found relative reductions of 68% for colorectal cancer incidence (relative risk: 0.32, 95% confidence interval: 0.23-0.43, three cohort studies, 590 participants) and 78% for all-cause mortality (relative risk: 0.22, 95% confidence interval: 0.09-0.56, three cohort studies, 590 participants) for early or more frequent colonoscopies among family members of people with cancer who also had an associated MMR gene mutation. CONCLUSION Inadequate evidence exists examining harms and benefits of population-based screening for Lynch syndrome. Lack of evidence highlights the need for data that directly compare benefits and harms.

Importance Hearing loss is common in older adults and associated with adverse health and social outcomes. Objective To update the evidence review on screening for hearing loss in adults 50 years or older to inform the US Preventive Services Task Force. Data sources MEDLINE, Cochrane Library, EMBASE, and trial registries through January 17, 2020; references; and experts; literature surveillance through October 8, 2020. Study selection English-language studies of accuracy, screening, and interventions for screen-detected or newly detected hearing loss. Data extraction and synthesis Dual review of abstracts, full-text articles, and study quality. Meta-analysis of screening test accuracy studies. Main outcomes and measures Quality of life and function, other health and social outcomes, test accuracy, and harms. Results Forty-one studies (N = 26 386) were included, 18 of which were new since the previous review. One trial enrolling US veterans (n = 2305) assessed the benefits of screening; there was no significant difference in the proportion of participants experiencing a minimum clinically important difference in hearing-related function at 1 year (36%-40% in the screened groups vs 36% in the nonscreened group). Thirty-four studies (n = 23 228) evaluated test accuracy. For detecting mild hearing loss (>20-25 dB), single-question screening had a pooled sensitivity of 66% (95% CI, 58%-73%) and a pooled specificity of 76% (95% CI, 68%-83%) (10 studies, n = 12 637); for detecting moderate hearing loss (>35-40 dB), pooled sensitivity was 80% (95% CI, 68%-88%) and pooled specificity was 74% (95% CI, 59%-85%) (6 studies, n = 8774). In 5 studies (n = 2820) on the Hearing Handicap Inventory for the Elderly-Screening to detect moderate hearing loss (>40 dB), pooled sensitivity was 68% (95% CI, 52%-81%) and pooled specificity was 78% (95% CI, 67%-86%). Six trials (n = 853) evaluated amplification vs control in populations with screen-detected or recently detected hearing loss over 6 weeks to 4 months. Five measured hearing-related function via the Hearing Handicap Inventory for the Elderly; only 3 that enrolled veterans (n = 684) found a significant difference considered to represent a minimal important difference (>18.7 points). Few trials reported on other eligible outcomes, and no studies reported on harms of screening or interventions. Conclusions and relevance Several screening tests can adequately detect hearing loss in older adults; no studies reported on the harms of screening or treatment. Evidence showing benefit from hearing aids on hearing-related function among adults with screen-detected or newly detected hearing loss is limited to studies enrolling veterans.

Importance Lung cancer is the leading cause of cancer-related death in the US. Objective To review the evidence on screening for lung cancer with low-dose computed tomography (LDCT) to inform the US Preventive Services Task Force (USPSTF). Data sources MEDLINE, Cochrane Library, and trial registries through May 2019; references; experts; and literature surveillance through November 20, 2020. Study selection English-language studies of screening with LDCT, accuracy of LDCT, risk prediction models, or treatment for early-stage lung cancer. Data extraction and synthesis Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled because of heterogeneity of populations and screening protocols. Main outcomes and measures Lung cancer incidence, lung cancer mortality, all-cause mortality, test accuracy, and harms. Results This review included 223 publications. Seven randomized clinical trials (RCTs) (N = 86 486) evaluated lung cancer screening with LDCT; the National Lung Screening Trial (NLST, N = 53 454) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON, N = 15 792) were the largest RCTs. Participants were more likely to benefit than the US screening-eligible population (eg, based on life expectancy). The NLST found a reduction in lung cancer mortality (incidence rate ratio [IRR], 0.85 [95% CI, 0.75-0.96]; number needed to screen [NNS] to prevent 1 lung cancer death, 323 over 6.5 years of follow-up) with 3 rounds of annual LDCT screening compared with chest radiograph for high-risk current and former smokers aged 55 to 74 years. NELSON found a reduction in lung cancer mortality (IRR, 0.75 [95% CI, 0.61-0.90]; NNS to prevent 1 lung cancer death of 130 over 10 years of follow-up) with 4 rounds of LDCT screening with increasing intervals compared with no screening for high-risk current and former smokers aged 50 to 74 years. Harms of screening included radiation-induced cancer, false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, and increases in distress. For every 1000 persons screened in the NLST, false-positive results led to 17 invasive procedures (number needed to harm, 59) and fewer than 1 person having a major complication. Overdiagnosis estimates varied greatly (0%-67% chance that a lung cancer was overdiagnosed). Incidental findings were common, and estimates varied widely (4.4%-40.7% of persons screened). Conclusions and relevance Screening high-risk persons with LDCT can reduce lung cancer mortality but also causes false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, increases in distress, and, rarely, radiation-induced cancers. Most studies reviewed did not use current nodule evaluation protocols, which might reduce false-positive results and invasive procedures for false-positive results.

Numerous guidelines have been developed over the past decade regarding treatments for Posttraumatic stress disorder (PTSD). However, given differences in guideline recommendations, some uncertainty exists regarding the selection of effective PTSD therapies. The current manuscript assessed the efficacy, comparative effectiveness, and adverse effects of psychological treatments for adults with PTSD. We searched MEDLINE, Cochrane Library, PILOTS, Embase, CINAHL, PsycINFO, and the Web of Science. Two reviewers independently selected trials. Two reviewers assessed risk of bias and graded strength of evidence (SOE). We included 64 trials; patients generally had severe PTSD. Evidence supports efficacy of exposure therapy (high SOE) including the manualized version Prolonged Exposure (PE); cognitive therapy (CT), cognitive processing therapy (CPT), cognitive behavioral therapy (CBT)-mixed therapies (moderate SOE); eye movement desensitization and reprocessing (EMDR) and narrative exposure therapy (low-moderate SOE). Effect sizes for reducing PTSD symptoms were large (e.g., Cohen's d ~-1.0 or more compared with controls). Numbers needed to treat (NNTs) were

The US Preventive Services Task Force recommends that individuals at high risk for lung cancer consider benefits and harms before pursuing lung cancer screening. Medical centers develop websites for their lung cancer screening programs, but to date little is known about the websites' portrayal of benefits and harms or what next steps they recommend for individuals considering screening.To assess the presentation of potential benefits and harms and recommended next steps on lung cancer screening program websites.Cross-sectional content analysis of 162 lung cancer screening program websites of academic medical centers (n = 81) and state-matched community medical centers (n = 81) that were randomly selected from American College of Radiology lung cancer screening-designated centers was conducted. The study was performed from December 1, 2018, to January 31, 2019.Website presentation of screening-associated benefits and harms was the primary outcome. Benefit was defined as any description related to the potential reduction in lung cancer mortality. Harms were based on the US Preventive Services Task Force recommendations and included false positives, false negatives, overdiagnosis, radiation exposure, and incidental findings. The secondary outcome was next steps that are recommended by websites.Overall, the 162 lung cancer screening program websites described the potential benefits more frequently than they described any potential harms (159 [98%] vs 78 [48%], P .01). False-positive findings were the most frequently reported (72 [44%]) potential harm. Community centers were less likely than academic centers to report any potential harm (32 [40%] vs 46 [57%], P = .03), potential harm from radiation (20 [25%] vs 35 [43%], P = .01), and overdiagnosis (0% vs 11 [14%], P .01). One hundred nineteen websites (73%) did not explicitly recommend that individuals personally consider the potential benefits and harms of screening; community centers were less likely than academic centers to give this recommendation (15 [19%] vs 28 [35%], P = .02). Most institutions (157 [97%]) listed follow-up steps for screening, but few institutions (35 [22%]) recommended that individuals discuss benefits and harms with a health care professional.Information on public-facing websites of US lung cancer screening programs appears to lack balance with respect to portrayal of potential benefits and harms of screening. Important harms, such as overdiagnosis, were commonly ignored in the sites evaluated, and most of the centers did not explicitly guide individuals toward a guideline-recommended, shared decision-making discussion of harms and benefits.

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.

BACKGROUND: The transition from pediatric to adult care is a critical period for young adults with childhood-onset conditions. General internists are tasked with participating in the care of this vulnerable population. Existing guidelines regarding transition do not fully address structural or organizational characteristics of practices that facilitate transition. Moreover, literature regarding transition has focused on pediatric subspecialty settings, leaving internists with little guidance after transfer. OBJECTIVES: To better understand post-transfer transitional care by describing care models that primary care providers have implemented, and examining common features of generalist physicians’ experiences providing transitional care. DESIGN: Qualitative methods, semi-structured interviews. PARTICIPANTS: Nineteen generalist-trained physicians from across the USA, engaged in transition-focused and/or ongoing care of adolescents and young adults with childhood-onset conditions. APPROACH: Content and grounded theory analyses. KEY RESULTS: Participants included nineteen physicians from seventeen institutions. Most (89%) were from academic medical centers. About 80% had completed a combined internal medicine-pediatrics residency. About 70% worked with clinic staff who were dedicated to transition. Practice structures fell into four main care models: (1) primary care in adult settings; (2) transition support and primary care in pediatric settings; (3) a blend of pediatric and adult care elements forming a bridge during transition; and (4) a transition consultative service. Most provided primary care for adults with childhood-onset conditions within larger adult-oriented primary care practices. Common features across interviews included taking extra time with patients both during and between visits and an interdisciplinary team-based approach. Shared practice strategies and philosophies emphasized care coordination, focus on the whole patient beyond immediate health concerns, and willingness to learn from practice and from families. CONCLUSIONS: Participants used disparate care models. Common features and strategies among interviews highlight key functions and attributes of transitional care across settings, suggest important elements of care post-transfer, and clarify the role of generalists.

Background The management of histologically dysplastic naevi (HDN) with re-excision vs. observation remains controversial because of lack of evidence about associated melanoma outcomes. Objectives To assess published data on the development of biopsy-site primary cutaneous melanoma among biopsy-proven HDN managed with either re-excision or observation. Methods A systematic review of all published data: a total of 5293 records were screened, 18 articles were assessed in full text and 12 studies met inclusion criteria. No controlled trials were identified. Results Most studies (11 of 12, 92%) were retrospective chart reviews, and one was both a cross-sectional and cohort study. Many studies (nine of 12, 75%) had no head-to-head comparison groups and either only reported HDN that were re-excised or observed. A total of 2673 (1535 observed vs. 1138 re-excised) HDN of various grades were included. Follow-up varied between 2 weeks and 30 years. Nine studies reported that no melanomas developed. Eleven biopsy-site melanomas developed across three of the studies, six among observed lesions (0·39%) and five among re-excised lesions (0·44%). Conclusions Based upon the available evidence the rates of biopsy-site primary melanoma were similarly low among observed lesions and re-excised lesions. This suggests that HDNs can be observed with minimal adverse melanoma-associated outcomes. However, all included articles were of low quality and further prospective trials could better guide clinical decision making.

The use of antipsychotics, particularly second generation antipsychotics, among children and adolescents has increased markedly during the past 20 years. Existing evidence gaps make this practice controversial and hinder treatment decision-making. This article describes and prioritizes future research needs regarding antipsychotic treatment in youth, focusing on within-class and between-class drug comparisons with regard to key population subgroups, efficacy and effectiveness outcomes, and adverse event outcomes. Using as a foundation a recent systematic review of antipsychotic treatment among youth, which was completed by a different Evidence-based Practice Center, we worked with a diverse group of 12 stakeholders representing researchers, funders, health care providers, patients, and families to identify and prioritize research needs. From an initial list of 16 evidence gaps, we enumerated 6 high-priority research needs: 1) long-term comparative effectiveness across all psychiatric disorders; 2) comparative long-term risks of adverse outcomes; 3) short-term risks of adverse events; 4) differentials of efficacy, effectiveness, and safety for population subgroups; 5) comparative effectiveness among those with attention-deficit/hyperactivity disorder and disruptive behavior disorders and common comorbidities; 6) comparative effectiveness among those with bipolar disorder and common comorbidities. In this article, we describe these future research needs in detail and discuss study designs that could be used to address them.

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 ( 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.

Background: It is unclear whether testing for novel risk factors, such as a cardiovascular genetic risk score (cGRS), improves clinical decision making or health outcomes when used for targeting statin initiation in the primary prevention of atherosclerotic cardiovascular disease (ASCVD). Our objective was to estimate the cost-effectiveness of cGRS testing to inform clinical decision making about statin initiation in individuals with low-to-intermediate (2.5%–7.5%) 10-year predicted risk of ASCVD. Methods and Results: We evaluated the cost-effectiveness of testing for a 27-single-nucleotide polymorphism cGRS comparing 4 test/treat strategies: treat all, treat none, test/treat if cGRS is high, and test/treat if cGRS is intermediate or high. We tested a set of clinical scenarios of men and women, aged 45 to 65 years, with 10-year ASCVD risks between 2.5% and 7.5%. Our primary outcome measure was cost per quality-adjusted life-year gained. Under base case assumptions for statin disutility and cost, the preferred strategy is to treat all patients with ASCVD risk >2.5% without cGRS testing. For certain clinical scenarios, such as a 57-year-old man with a 10-year ASCVD risk of 7.5%, cGRS testing can be cost-effective under a limited set of assumptions; for example, when statins cost $15 per month and statin disutility is 0.013 (ie, willing to trade 3 months of life in perfect health to avoid 20 years of statin therapy), the preferred strategy (using a willingness-to-pay threshold of $50 000 per quality-adjusted life-year gained) is to test and treat if cGRS is intermediate or high. Overall, the results were not sensitive to assumptions about statin efficacy and harms. Conclusions: Testing for a 27-single-nucleotide polymorphism cGRS is generally not a cost-effective approach for targeting statin therapy in the primary prevention of ASCVD for low- to intermediate-risk patients.

Background Guideline developers and other users of systematic reviews need information about whether a medical or preventive intervention is likely to benefit or harm some patients more (or less) than the average in order to make clinical practice recommendations tailored to these populations. However, guidance is lacking on how to include patient subpopulation considerations into the systematic reviews upon which guidelines are often based. In this article, we describe methods developed to consistently consider the evidence for relevant subpopulations in systematic reviews conducted to support primary care clinical preventive service recommendations made by the U.S. Preventive Services Task Force (USPSTF). Proposed approach Our approach is grounded in our experience conducting systematic reviews for the USPSTF and informed by a review of existing guidance on subgroup analysis and subpopulation issues. We developed and refined our approach based on feedback from the Subpopulation Workgroup of the USPSTF and pilot testing on reviews being conducted for the USPSTF. This paper provides processes and tools for incorporating evidence-based identification of important sources of potential heterogeneity of intervention effects into all phases of systematic reviews. Key components of our proposed approach include targeted literature searches and key informant interviews to identify the most important subpopulations a priori during topic scoping, a framework for assessing the credibility of subgroup analyses reported in studies, and structured investigation of sources of heterogeneity of intervention effects. Conclusions Further testing and evaluation are necessary to refine this proposed approach and demonstrate its utility to the producers and users of systematic reviews beyond the context of the USPSTF. Gaps in the evidence on important subpopulations identified by routinely applying this process in systematic reviews will also inform future research needs.

Unhealthy alcohol use is the third leading cause of preventable death in the United States. The U.S. Preventive Services Task Force (USPSTF) recommends screening for unhealthy alcohol use but little is known about how best to do so. We used quality improvement techniques to implement a systematic approach to screening and counseling primary care patients for unhealthy alcohol use. Components included use of validated screening and assessment instruments; an evidence-based two-visit counseling intervention using motivational interviewing techniques for those with risky drinking behaviors who did not have an alcohol use disorder (AUD); shared decision making about treatment options for those with an AUD; support materials for providers and patients; and training in motivational interviewing for faculty and residents. Over the course of one year, we screened 52% (N = 5,352) of our clinic's patients and identified 294 with positive screens. Of those 294, appropriate screening-related assessments and interventions were documented for 168 and 72 patients, respectively. Although we successfully implemented a systematic screening program and structured processes of care, ongoing quality improvement efforts are needed to screen the rest of our patients and to improve the consistency with which we provide and document appropriate interventions.

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.

Objective To evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) and 2 or more prior antidepressant treatment failures (often referred to as treatment-resistant depression [TRD]). These patients are less likely to recover with medications alone and often consider nonpharmacologic treatments such as rTMS. Data sources We searched MEDLINE, EMBASE, the Cochrane Library, PsycINFO, and the International Pharmaceutical Abstracts for studies comparing rTMS with a sham-controlled treatment in TRD patients ages 18 years or older. Study selection We included 18 good- or fair-quality TRD studies published from January 1, 1980, through March 20, 2013. Data extraction We abstracted relevant data, assessed each study's internal validity, and graded strength of evidence for change in depressive severity, response rates, and remission rates. Results rTMS was beneficial compared with sham for all outcomes. rTMS produced a greater decrease in depressive severity (high strength of evidence), averaging a clinically meaningful decrease on the Hamilton Depression Rating Scale (HDRS) of more than 4 points compared with sham (mean decrease = -4.53; 95% CI, -6.11 to -2.96). rTMS resulted in greater response rates (high strength of evidence); those receiving rTMS were more than 3 times as likely to respond as patients receiving sham (relative risk = 3.38; 95% CI, 2.24 to 5.10). Finally, rTMS was more likely to produce remission (moderate strength of evidence); patients receiving rTMS were more than 5 times as likely to achieve remission as those receiving sham (relative risk = 5.07; 95% CI, 2.50 to 10.30). Limited evidence and variable treatment parameters prevented conclusions about which specific treatment options are more effective than others. How long these benefits persist remains unclear. Conclusions For MDD patients with 2 or more antidepressant treatment failures, rTMS is a reasonable, effective consideration.

Pharmacogenomics offers the hope of greater individualization of treatment. Therapies that exemplify the promise of pharmacogenomics include anticoagulation with warfarin and the use of antiplatelet medications (eg, clopidogrel) for secondary prevention after acute coronary syndrome. Good evidence of clinical utility must be obtained before pharmacogenomic testing is widely implemented.

Research needs are many in the current health care environment. In this article, we describe a novel method developed by the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center Program for prioritizing areas for future research. Using a recent- ly published systematic review as a foundation, investigators worked with a diverse group of 10 stakeholders to identify and prioritize research needs. We enumerate 13 high-priority research needs, as determined by stakeholders who represented researchers, funders, health care providers, and patients and families, and discuss considerations for specific study designs. Our findings suggest that future research on integrating mental health and primary care should focus first on a) identifying methods of integrating primary care into specialty mental health settings, b) identifying cross-cutting strategies for integration across multiple mental health diagnostic categories as opposed to a separate strategy for each diagnostic category, and c) examining the use of information technology for integrating mental and general medical health care. Other priorities for consideration include examining the economic and organizational sus- tainability of successful integration models, identifying dissemination methods for various settings, examining the business case for integration as well as methods of payment, assessing the cost-effectiveness of integration, and identifying key components of successful strategies. The importance of sustainability and economic justification for integrated care strategies was a recurring theme in discussions with the stake- holders. The ability to sustain integrated care in everyday practice remains to be proved and will depend in part on the level of incentives and sup- port provided through payment system reform, as well as the ability of practices to provide care efficiently.

Objectives: In response to the need for an evidence-based review of factors within long-term care settings that affect the quality of care, this review compared characteristics of nursing homes and other residential long-term care settings for people with dementia and their informal family caregivers with respect to health and psychosocial outcomes. Design Databases were searched for literature published between 1990 and March 2012 that met review criteria, including that at least 80% of the subject population had dementia. Results Fourteen articles meeting review criteria that were of at least fair quality were found: four prospective cohort studies, nine randomized controlled trials (RCTs), and one nonrandomized controlled trial. Overall, low or insufficient strength of evidence was found regarding the effect of most organizational characteristics, structures, and processes of care on health and psychosocial outcomes for people with dementia and no evidence for informal caregivers. Findings of moderate strength of evidence indicate that pleasant sensory stimulation reduces agitation for people with dementia. Also, although the strength of evidence is low, protocols for individualized care and to improve function result in better outcomes for these individuals. Finally, outcomes do not differ between nursing homes and residential care or assisted living settings for people with dementia except when medical care is indicated. Conclusion: Given the paucity of high-quality studies in this area, additional research is needed to develop a sufficient evidence base to support consumer selection, practice, and policy regarding the best settings and characteristics of settings for residential long-term care of people with dementia.

Context Traumatic events are prevalent worldwide; trauma victims seek help in numerous clinical and emergency settings. Using effective interventions to prevent post-traumatic stress disorder (PTSD) is increasingly important. This review assessed the efficacy, comparative effectiveness, and harms of psychological, pharmacologic, and emerging interventions to prevent PTSD. Evidence acquisition The following sources were searched for research on interventions to be included in the review: MEDLINE; Cochrane Library; CINAHL; EMBASE; PILOTS (Published International Literature on Traumatic Stress); International Pharmaceutical Abstracts; PsycINFO; Web of Science; reference lists of published literature; and unpublished literature (January 1, 1980 to July 30, 2012). Two reviewers independently selected studies, extracted data or checked accuracy, assessed study risk of bias, and graded strength of evidence. All data synthesis occurred between January and September 2012. Evidence synthesis Nineteen studies covered various populations, traumas, and interventions. In meta-analyses of three trials (from the same team) for people with acute stress disorder, brief trauma-focused cognitive behavioral therapy was more effective than supportive counseling in reducing the severity of PTSD symptoms (moderate-strength); these two interventions had similar results for incidence of PTSD (low-strength); depression severity (low-strength); and anxiety severity (moderate-strength). PTSD symptom severity after injury decreased more with collaborative care than usual care (single study; low-strength). Debriefing did not reduce incidence or severity of PTSD or psychological symptoms in civilian traumas (low-strength). Evidence about relevant outcomes was unavailable for many interventions or was insufficient owing to methodologic shortcomings. Conclusions Evidence is very limited regarding best practices to treat trauma-exposed individuals. Brief cognitive behavioral therapy may reduce PTSD symptom severity in people with acute stress disorder; collaborative care may help decrease symptom severity post-injury.

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.

BACKGROUND: Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has considerably changed treatment options for rheumatoid arthritis (RA) over the past decade. Very little information is available on comparative discontinuation rates of the biologics. OBJECTIVE: To compare treatment discontinuations for 9 biologic DMARDs in adults with RA. METHODS: We searched electronic databases through May 2012 to retrieve randomized controlled trials (RCTs) of patients with RA that compared biologic DMARDs with placebo or another biologic DMARD. The primary outcome was treatment discontinuation during the blinded phase of the trials, measured as overall withdrawals, withdrawals resulting from lack of efficacy, and withdrawals resulting from adverse events. Random-effects meta-analysis estimated the effect size for individual agents, and adjusted indirect comparisons were made between biologics using mixed treatment comparisons (MTC) meta-analysis. RESULTS: Forty-four trials were included in the analysis. In comparison with placebo, biologics were less likely to be withdrawn because of lack of efficacy (OR 0.22, 95% CI 0.17 to 0.27) and more likely to be withdrawn because of an adverse event (OR 1.41, 95% CI 1.16 to 1.70). Based on the MTC, certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates resulting from lack of efficacy than adalimumab, anakinra, and infliximab. Anakinra had higher relative withdrawal rates resulting from lack of efficacy than most other biologics. Certolizumab and infliximab had more, while etanercept had fewer, withdrawals because of adverse events than most other drugs. CONCLUSIONS: Based on MTC using data from RCTs, differences in discontinuation rates were observed, generally favoring certolizumab, etanercept, and rituximab over other biologic DMARDs. These potential differences need to be further explored in head-to-head trials or well-conducted observational studies.

Aims: To evaluate the impact of systematic reviews on research funded by the Agency for Healthcare Research and Quality (AHRQ) through Evidence-based Practice Centers (EPCs), and to identify barriers to and facilitators for the effects of these documents on future research. Methods & materials: Two AHRQ systematic reviews were selected as case studies to evaluate their impact on future research. Key citations generated by these reports were identified through ISI Web of Science and PubMed Central and traced forward to identify effects on subsequent studies through citation analysis from updated systematic reviews on the topics. Requests for applications and program announcements from the NIH Guide for Grants and Contracts website were reviewed and dissemination data were obtained from AHRQ. Finally, interviews were conducted with 13 key informants to help identify short-, medium- and long-term impacts of the EPC reviews. Results: The measurable impact of the two EPC reviews is demonstrably greater on short-term outcomes (greater awareness of the issues) than on medium-term (e.g., the generation of new knowledge) or long-term outcomes (e.g., changes in patient practice or health outcomes). Factors such as the topic and the timing of the report relative to the development of the field may explain the impact of these two AHRQ reports. The degree to which the new research can be directly attributed to the AHRQ reviews remains unclear. Key informants discussed several benefits stemming from the EPC reports, including providing a foundation for the research community on which to build, heightening awareness of the gaps in knowledge, increasing the quality of research and sparking new directions of research. However, the degree to which these reports were influential hinged on several factors including marketing efforts, the very nature of the reports and other influences external to the EPC domain. Conclusions: The findings outlined in this article illustrate the importance of numerous factors influencing future research: the breadth, specificity and readiness of the topic for more research, ongoing developments in the field, availability of funding and active engagement of champions. AHRQ and the EPCs may be able to improve the likelihood of impact by creating more targeted products, planning for and expanding dissemination activities, improving the readability and other attributes of the reports themselves, and actively involving funders early on and throughout the process of creating and publishing the reviews.

Low literacy skills are common and associated with a variety of poor health outcomes. This may be particularly important in patients with chronic illnesses such as chronic obstructive pulmonary disease (COPD) that require appropriate inhaler technique to maintain quality of life and avoid exacerbations.To explore the impact of a literacy-sensitive self-management intervention on inhaler technique scores in COPD patients and to determine if effects differ by literacy.Randomized controlled trial.Ninety-nine patients with COPD.Patients were randomly assigned to a one-on-one self-management educational intervention or usual care. The intervention focused on inhaler technique, smoking cessation, and using a COPD action plan.At baseline, an inhaler technique assessment, literacy assessment, health-related quality of life questionnaires, and pulmonary function tests were completed. Inhaler technique was re-evaluated after two to eight weeks.Mean age 63, 65% female, 69% Caucasian, moderate COPD severity on average, 36% with low literacy, moderately impaired health-related quality of life, and similar baseline metered dose inhaler technique scores. Patients in the intervention group had greater mean improvement from baseline in metered dose inhaler technique score compared to those in the usual care group (difference in mean change 2.1, 95% CI 1.1, 3.0). The patients in the intervention group also had greater mean improvements in metered dose inhaler technique score than those in the usual care group whether they had low health literacy (difference in mean change 2.8, 95% CI 0.6, 4.9) or higher health literacy (1.8, 95% CI 0.7, 2.9).A literacy-sensitive self-management intervention can lead to improvements in inhaler technique, with benefits for patients with both low and higher health literacy.

Background Clopidogrel's effectiveness is likely reduced significantly for prevention of thrombotic events after acute coronary syndrome (ACS) in patients exhibiting a decreased ability to metabolize clopidogrel into its active form. A genetic mutation responsible for this reduced effectiveness is detectable by genotyping. Ticagrelor is not dependent on gene-based metabolic activation and demonstrated greater clinical efficacy than clopidogrel in a recent secondary prevention trial. In 2011, clopidogrel will lose its patent protection and likely will be substantially less expensive than ticagrelor. Objective To determine the cost-effectiveness of ticagrelor compared with a genotype-driven selection of antiplatelet agents. Methods A hybrid decision tree/Markov model was used to estimate the 5-year medical costs (in 2009 US$) and outcomes for a cohort of ACS patients enrolled in Medicare receiving either genotype-driven or ticagrelor-only treatment. Outcomes included life years and quality-adjusted life years (QALYs) gained. Data comparing the clinical performance of ticagrelor and clopidogrel were derived from the Platelet Inhibition and Patient Outcomes trial. Results The incremental cost-effectiveness ratio (ICER) for universal ticagrelor was $10,059 per QALY compared to genotype-driven treatment, and was most sensitive to the price of ticagrelor and the hazard ratio for death for ticagrelor compared with clopidogrel. The ICER remained below $50,000 per QALY until a monthly ticagrelor price of $693 or a 0.93 hazard ratio for death for ticagrelor relative to clopidogrel. In probabilistic analyses, universal ticagrelor was below $50,000 per QALY in 97.7% of simulations. Conclusion Prescribing ticagrelor universally increases quality-adjusted life years for ACS patients at a cost below a typically accepted threshold.

Genomic screening of the general adult population: key concepts for assessing net benefit with systematic evidence reviews

Child maltreatment, also referred to as child abuse and neglect, can result in lifelong negative consequences.To update the evidence on interventions provided in or referable from primary care to prevent child maltreatment for the US Preventive Services Task Force.PubMed, Cochrane Library, EMBASE, and trial registries through December 18, 2017; references; experts; literature surveillance through July 17, 2018.English-language fair- and good-quality randomized clinical trials that (1) included children with no known exposure to maltreatment and no signs or symptoms of current or past maltreatment, (2) evaluated interventions feasible in a primary care setting or that could result from a referral from primary care, and (3) reported abuse or neglect outcomes or proxies for abuse or neglect (eg, injury with a specificity for abuse, visits to the emergency department, hospitalization).Two reviewers independently assessed titles/abstracts, full-text articles, and study quality; a third resolved conflicts when needed. When at least 3 similar trials were available, random-effects meta-analyses were conducted.Direct measures (including reports to child protective services and removal of the child from the home) or proxy measures of abuse or neglect; behavioral, emotional, mental, or physical well-being; and harms.Twenty-two trials (33 publications) were included (N = 11 132). No significant association was found between interventions and reports to child protective services within 1 year of intervention completion (10.6% vs 11.9%; pooled odds ratio [OR], 0.94 [95% CI, 0.72-1.23]; 10 trials [n = 2444]) or removal of the child from the home within 1 to 3 years of follow-up (3.5% vs 3.7%; pooled OR, 1.09 [95% CI, 0.16-7.28]; 4 trials [n = 609]). No statistically significant associations were observed between interventions and outcomes for emergency department visits in the short term (2 years), hospitalizations, child development, school performance, and prevention of death. Nonsignificant results from single trials led to a conclusion of insufficient evidence for injuries, failure to thrive, failure to immunize, school attendance, and other measures of abuse or neglect. Inconsistent results led to a conclusion of insufficient evidence for long-term (≥2 years) outcomes for reports to child protective services (ORs range from 0.48 to 1.13; 3 trials [n = 1690]), emergency department visits (1 of 2 trials reported significant differences) and internalizing and externalizing behavior symptoms (3 of 6 trials reported reductions in behavior difficulties). No eligible trials on harms of interventions were identified.Interventions provided in or referable from primary care did not consistently prevent child maltreatment. No evidence on harms is available.

Importance Unhealthy alcohol use is common, increasing, and a leading cause of premature mortality. Objective To review literature on the effectiveness and harms of screening and counseling for unhealthy alcohol use to inform the US Preventive Services Task Force. Data Sources MEDLINE, PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials through October 12, 2017; literature surveillance through August 1, 2018. Study Selection Test accuracy studies and randomized clinical trials of screening and counseling to reduce unhealthy alcohol use. Data Extraction and Synthesis Independent critical appraisal and data abstraction by 2 reviewers. Counseling trials were pooled using random-effects meta-analyses. Main Outcomes and Measures Sensitivity, specificity, drinks per week, exceeding recommended limits, heavy use episodes, abstinence (for pregnant women), and other health, family, social, and legal outcomes. Results One hundred thirteen studies (N = 314 466) were included. No studies examined benefits or harms of screening programs to reduce unhealthy alcohol use. For adolescents (10 studies [n = 171 363]), 1 study (n = 225) reported a sensitivity of 0.73 (95% CI, 0.60 to 0.83) and specificity of 0.81 (95% CI, 0.74 to 0.86) using the AUDIT-C (Alcohol Use Disorders Identification Test–Consumption) to detect the full spectrum of unhealthy alcohol use. For adults (35 studies [n = 114 182]), brief screening instruments commonly reported sensitivity and specificity between 0.70 and 0.85. Two trials of the effects of interventions to reduce unhealthy alcohol use in adolescents (n = 588) found mixed results: one reported a benefit in high-risk but not moderate-risk drinkers, and the other reported a statistically significant reduction in drinking frequency for boys but not girls; neither reported health or related outcomes. Across all populations (68 studies [n = 36 528]), counseling interventions were associated with a decrease in drinks per week (weighted mean difference, −1.6 [95% CI, −2.2 to −1.0]; 32 studies [37 effects; n = 15 974]), the proportion exceeding recommended drinking limits (odds ratio [OR], 0.60 [95% CI, 0.53 to 0.67]; 15 studies [16 effects; n = 9760]), and the proportion reporting a heavy use episode (OR, 0.67 [95% CI, 0.58 to 0.77]; 12 studies [14 effects; n = 8108]), and an increase in the proportion of pregnant women reporting abstinence (OR, 2.26 [95% CI, 1.43 to 3.56]; 5 studies [n = 796]) after 6 to 12 months. Health outcomes were sparsely reported and generally did not demonstrate group differences in effect. There was no evidence that these interventions could be harmful. Conclusions and Relevance Among adults, screening instruments feasible for use in primary care are available that can effectively identify people with unhealthy alcohol use, and counseling interventions in those who screen positive are associated with reductions in unhealthy alcohol use. There was no evidence that these interventions have unintended harmful effects.

Importance Atrial fibrillation is the most common arrhythmia and increases the risk of stroke. Objective To review the evidence on screening for nonvalvular atrial fibrillation with electrocardiography (ECG) and stroke prevention treatment in asymptomatic adults 65 years or older to inform the US Preventive Services Task Force. Data Sources MEDLINE, Cochrane Library, and trial registries through May 2017; references; experts; literature surveillance through June 6, 2018. Study Selection English-language randomized clinical trials (RCTs), prospective cohort studies evaluating detection rates of atrial fibrillation or harms of screening, and systematic reviews evaluating stroke prevention treatment. Eligible treatment studies compared warfarin, aspirin, or novel oral anticoagulants (NOACs) with placebo or no treatment. Studies were excluded that focused on persons with a history of cardiovascular disease. Data Extraction and Synthesis Dual review of abstracts, full-text articles, and study quality. When at least 3 similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures Detection of previously undiagnosed atrial fibrillation, mortality, stroke, stroke-related morbidity, and harms. Results Seventeen studies were included (n = 135 300). No studies evaluated screening compared with no screening and focused on health outcomes. Systematic screening with ECG identified more new cases of atrial fibrillation than no screening (absolute increase, from 0.6% [95% CI, 0.1%-0.9%] to 2.8% [95% CI, 0.9%-4.7%] over 12 months; 2 RCTs, n = 15 803), but a systematic approach using ECG did not detect more cases than an approach using pulse palpation (2 RCTs, n = 17 803). For potential harms, no eligible studies compared screening with no screening. Warfarin (mean, 1.5 years) was associated with a reduced risk of ischemic stroke (relative risk [RR], 0.32 [95% CI, 0.20-0.51]) and all-cause mortality (RR, 0.68 [95% CI, 0.50-0.93]) and with increased risk of bleeding (5 trials, n = 2415). Participants in treatment trials were not screen detected, and most had long-standing persistent atrial fibrillation. A network meta-analysis reported that NOACs were associated with a significantly lower risk of a composite outcome of stroke and systemic embolism (adjusted odds ratios compared with placebo or control ranged from 0.32-0.44); the risk of bleeding was increased (adjusted odds ratios, 1.4-2.2), but confidence intervals were wide and differences between groups were not statistically significant. Conclusions and Relevance Although screening with ECG can detect previously unknown cases of atrial fibrillation, it has not been shown to detect more cases than screening focused on pulse palpation. Treatments for atrial fibrillation reduce the risk of stroke and all-cause mortality and increase the risk of bleeding, but trials have not assessed whether treatment of screen-detected asymptomatic older adults results in better health outcomes than treatment after detection by usual care or after symptoms develop.

Background. Most patients receiving warfarin are managed in outpatient office settings or anticoagulation clinics that require frequent visits for monitoring. Objective. To measure the amount and value of time required of patients for chronic anticoagulation therapy with warfarin. Design/Participants. Prospective observation of a cohort of adult patients treated at a university-based anticoagulation program. Measurements. Participants completed a questionnaire and a prospective diary of the time required for 1 visit to the anticoagulation clinic, including travel, waiting, and the clinic visit. The authors reviewed subjects’ medical records to obtain additional information, including the frequency of visits to the anticoagulation clinic. They used the human capital method to estimate the value of time. Results. Eighty-five subjects completed the study. The mean (median) total time per visit was 147 minutes (123). Subjects averaged 15 visits per year (14) and spent 39.0 hours (29.3) per year on their visits. Other anticoagulation-related activities, such as communication with providers, pharmacy trips, and extra time preparing food, added an average of 52.7 hours (19.0) per year. The mean annual value of patient time spent traveling, waiting, and attending anticoagulation visits was $707 (median $591). The mean annual value when also including other anticoagulation-related activities was $1799 (median $1132). Conclusions. The time required of patients for anticoagulation visits was considerable, averaging approximately 2.5 hours per visit and almost 40 hours per year. Methods for reducing patient time requirements, such as home-based testing, could reduce costs for patients, employers, and companions.

Warfarin has a narrow therapeutic window and the hemorrhagic or thrombotic implications of over- or under-dosing can be devastating. Moreover, there is substantial individual variation in response to warfarin. This review describes the genetic and clinical factors associated with warfarin dosing, including recent developments. The pivotal role of CYP2C9 and VKORC1 is emphasized because polymorphisms of these two genes account for approximately 40% of the variation in dose requirements. Recent studies have reported that polymorphisms in CYP4F2 might account for between 2 and 7% of the variation. Large studies published recently, including the Warfarin Genetics (WARG) study and the International Warfarin Pharmacogenetic Consortium, have added to our understanding of factors relating to warfarin dosing. Several prospective studies have evaluated genotype-guided dosing, but these have found negative results or were poorly designed. Whether genotype-guided dosing is clinically beneficial remains unclear, but studies are currently underway that will help to determine this.

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.