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Garrett Hazelton,1 Sana M Al-Khatib,2,3 Gregg C Fonarow,4 Kevin L Thomas,3 David Hayes,5 Gillian D Sanders,2,3 Susan M Campbell,6 Clyde Yancy,7 Eric D Peterson,2,3 Samuel Sears8 1Department of Psychiatric Medicine, East Carolina University, Greenville, NC, 2Duke Clinical Research Institute, 3Department of Medicine, Duke University School of Medicine, Durham, NC, 4Division of Cardiology, Geffen School of Medicine at UCLA, Los Angeles, CA, 5Mayo Clinic, Rochester, MN, 6WomenHeart, The National Coalition for Women with Heart Disease, Washington, DC, 7Division of Cardiology, Feinburg School of Medicine, Northwestern University, Chicago, IL, 8Departments of Psychology and Cardiology, East Carolina University, Greenville, NC, USA Background: Conveying contemporary treatment options for those at risk of sudden cardiac arrest (SCA) is challenging. The purpose of the present research was to evaluate the quality and usability of available patient educational tools relevant to SCA and its treatment options, such as implantable cardioverter defibrillators (ICDs). We hypothesized that this review would identify gaps in areas of information for the enhancement of patient education and decision-making materials. Methods: We used a formal instrument to assess specific domains of content, development, and effectiveness of 18 available SCA and ICD educational tools. The multidisciplinary review panel included two electrophysiologists, two general cardiologists, a cardiac psychologist, a health services researcher, and a patient advocate. Results: Of the 18 education tools, four were rated as “good, may need revisions, but sufficient for use”, 12 were rated as “marginal, needs revision prior to use”, and two were rated as “poor, inadequate for use”. None of the tools were rated as being of “very good” or “excellent” quality. Conclusion: There appear to be opportunities to improve the quality and completeness of existing educational tools for patients with SCA and ICD. While many tools have been developed, they fall below current standards for supporting informed medical decision-making. Keywords: decision-making, implantable cardioverter defibrillators, patient-centered outcomes research

BACKGROUND: Despite increasing emphasis on the role of clinical decision-support systems (CDSSs) for improving care and reducing costs, evidence to support widespread use is lacking. PURPOSE: To evaluate the effect of CDSSs on clinical outcomes, health care processes, workload and efficiency, patient satisfaction, cost, and provider use and implementation. DATA SOURCES: MEDLINE, CINAHL, PsycINFO, and Web of Science through January 2011. STUDY SELECTION: Investigators independently screened reports to identify randomized trials published in English of electronic CDSSs that were implemented in clinical settings; used by providers to aid decision making at the point of care; and reported clinical, health care process, workload, relationship-centered, economic, or provider use outcomes. DATA EXTRACTION: Investigators extracted data about study design, participant characteristics, interventions, outcomes, and quality. DATA SYNTHESIS: 148 randomized, controlled trials were included. A total of 128 (86%) assessed health care process measures, 29 (20%) assessed clinical outcomes, and 22 (15%) measured costs. Both commercially and locally developed CDSSs improved health care process measures related to performing preventive services (n = 25; odds ratio [OR], 1.42 [95% CI, 1.27 to 1.58]), ordering clinical studies (n = 20; OR, 1.72 [CI, 1.47 to 2.00]), and prescribing therapies (n = 46; OR, 1.57 [CI, 1.35 to 1.82]). Few studies measured potential unintended consequences or adverse effects. LIMITATIONS: Studies were heterogeneous in interventions, populations, settings, and outcomes. Publication bias and selective reporting cannot be excluded. CONCLUSION: Both commercially and locally developed CDSSs are effective at improving health care process measures across diverse settings, but evidence for clinical, economic, workload, and efficiency outcomes remains sparse. This review expands knowledge in the field by demonstrating the benefits of CDSSs outside of experienced academic centers. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study was designed to determine if physicians' attitudes and recommendations surrounding implantable cardioverter-defibrillators (ICDs) are regionally associated with ICD use. METHODS AND RESULTS: A national sample of 9969 members of the American College of Cardiology was surveyed electronically. Responses were merged with rates of ICD implantation from the National Cardiovascular Data Registry. Multivariable regression was used to assess trends between regional use and responses. We received 1210 responses (12%) and used 1124 after exclusions. Across regions, physicians were equally likely to recommend ICDs to males or females with ischemic (~99% for both; P = NS) or nonischemic cardiomyopathy (85 vs. 88% P = 0.85). Significant increasing trends in the probability recommending ICD therapy were found when the patient was 'frail' (21% to 32%; P = .03) or had a life expectancy <1 year (5% to 10%; P = .05). These differences were not associated with attitudes toward ICDs. CONCLUSIONS: Independent of variations in physicians' attitudes towards ICDs, physicians in regions of low ICD use are not less likely to recommend ICDs in situations clearly supported by guidelines while those in regions of high ICD use are more likely to recommend ICDs to patients who might have limited benefit. [ABSTRACT FROM AUTHOR]

Rationale: Isoniazid given daily for 9 months is the standard treatment for latent tuberculosis infection (LTBI), but its effectiveness is limited by poor completion rates. Shorter course regimens and regimens using directly observed therapy result in improved adherence but have higher upfront costs.Objectives: To evaluate the costs and cost-effectiveness of regimens for the treatment of LTBI.Methods: We used a computerized Markov model to estimate total societal costs and benefits associated with four regimens for the treatment of LTBI: self-administered isoniazid daily for 9 months, directly observed isoniazid twice-weekly for 9 months, directly observed isoniazid plus rifapentine once weekly for 3 months, and self-administered rifampin daily for 4 months. In the base-case analysis, subjects were assumed to have newly positive tuberculin skin tests after recent exposure to infectious tuberculosis.Measurements and Main Results: We determined the costs of treatment, quality-adjusted life-years gained, and cases of active tuberculosis prevented. In the base-case analysis, rifampin dominated (less costly with increased benefits) all other regimens except isoniazid plus rifapentine, which was more effective at a cost $48,997 per quality-adjusted life year gained. Isoniazid plus rifapentine dominated all regimens at a relative risk of disease 5.2 times the baseline estimate, or with completion rates less than 34% for isoniazid or 37% for rifampin. Rifampin could be 17% less efficacious than self-administered isoniazid and still be cost-saving compared with this regimen.Conclusions: In our model, rifampin is cost-saving compared with the standard therapy of self-administered isoniazid. Isoniazid plus rifapentine is cost-saving for extremely high-risk patients and is cost-effective for lower-risk patients. [ABSTRACT FROM AUTHOR]

Background: Low-molecular-weight heparins are effective for treating venous thrombosis, but their cost-effectiveness has not been rigorously assessed.Objective: To evaluate the cost-effectiveness of low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis.Design: Decision model.Data Sources: Probabilities for clinical outcomes were obtained from a meta-analysis of randomized trials. Cost estimates were derived from Medicare reimbursement and other sources.Target Population: Two hypothetical cohorts of 60-year-old men with acute deep venous thrombosis.Time Horizon: Patient lifetime.Perspective: Societal.Intervention: Fixed-dose low-molecular-weight heparin or adjusted-dose unfractionated heparin.Outcome Measures: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. An in-patient hospital setting was used for the base-case analysis. Secondary analyses examined outpatient treatment with low-molecular-weight heparin.Results Of Base-case Analysis: Total costs for inpatient treatment were $26,516 for low-molecular-weight heparin and $26,361 for unfractionated heparin. The cost of initial care was higher in patients who received low-molecular-weight heparin, but this was partly offset by reduced costs for early complications. Low-molecular-weight heparin treatment increased quality-adjusted life expectancy by approximately 0.02 years. The incremental cost-effectiveness of inpatient low-molecular-weight heparin treatment was $7820 per QALY gained. Treatment with low-molecular-weight heparin was cost saving when as few as 8% of patients were treated at home.Results Of Sensitivity Analysis: When late complications were assumed to occur 25% less frequently in patients who received unfractionated heparin, the incremental cost-effectiveness ratio increased to almost $75,000 per QALY gained. When late complications were assumed to occur 25% less frequently in patients who received low-molecular-weight heparin, this treatment resulted in a net cost savings. Inpatient low-molecular-weight heparin treatment became cost saving when its pharmacy cost was reduced by 31% or more, when it reduced the yearly incidence of late complications by at least 7%, when as few as 8% of patients were treated entirely as outpatients, or when at least 13% of patients were eligible for early discharge.Conclusions: Low-molecular-weight heparins are highly cost-effective for inpatient management of venous thrombosis. This treatment reduces costs when small numbers of patients are eligible for outpatient management. [ABSTRACT FROM AUTHOR]

Background: Implantable cardioverter defibrillators (ICDs) are remarkably effective in terminating ventricular arrhythmias, but they are expensive and the extent to which they extend life is unknown. The marginal cost-effectiveness of ICDs relative to amiodarone has not been clearly established.Objective: To compare the cost-effectiveness of a third-generation implantable ICD with that of empirical amiodarone treatment for preventing sudden cardiac death in patients at high or intermediate risk.Design: A Markov model was used to evaluate health and economic outcomes of patients who received an ICD, amiodarone, or a sequential regimen that reserved ICD for patients who had an arrhythmia during amiodarone treatment.Measurements: Life-years gained, quality-adjusted life-years gained, costs, and marginal cost-effectiveness.Results: For the base-case analysis, it was assumed that treatment with an ICD would reduce the total mortality rate by 20% to 40% at 1 year compared with amiodarone and that the ICD generator would be replaced every 4 years. In high-risk patients, if an ICD reduces total mortality by 20%, patients who receive an ICD live for 4.18 quality-adjusted life-years and have a lifetime expenditure of $88,400. Patients receiving amiodarone live for 3.68 quality-adjusted life-years and have a lifetime expenditure of $51,000. Marginal cost-effectiveness of an ICD relative to amiodarone is $74,400 per quality-adjusted life-year saved. If an ICD reduces mortality by 40%, the cost-effectiveness of ICD use is $37,300 per quality-adjusted life-year saved. Both choice of therapy (an ICD or amiodarone) and the cost-effectiveness ratio are sensitive to assumptions about quality of life.Conclusions: Use of an ICD will cost more than $50,000 per quality-adjusted life-year gained unless it reduces all-cause mortality by 30% or more relative to amiodarone. Current evidence does not definitively support or exclude a benefit of this magnitude, but ongoing randomized trials have sufficient statistical power to do so. [ABSTRACT FROM AUTHOR]

Background: Data on the benefits of cardiac resynchronization therapy (CRT) in patients with severe heart failure symptoms are limited. We investigated the relative effects of CRT in patients with ambulatory New York Heart Association (NYHA) IV versus III functional class at the time of device implantation., Methods and Results: In this meta-analysis, we pooled patient-level data from the MIRACLE (Multicenter InSync Randomized Clinical Evaluation), MIRACLE-ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation), and COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trials. Outcomes evaluated were time to the composite end point of the first heart failure hospitalization or all-cause mortality, and time to all-cause mortality alone. The association between CRT and outcomes was evaluated using a Bayesian hierarchical Weibull survival regression model. We assessed if this association differed between NYHA III and IV groups by adding an interaction term between CRT and NYHA class as a random effect. A sensitivity analysis was performed by including data from RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure). Our pooled analysis included 2309 patients. Overall, CRT was associated with a longer time to heart failure hospitalization or all-cause mortality (adjusted hazard ratio [aHR], 0.79 [95% credible interval [CI], 0.64-0.99]; posterior probability or P =0.044), with a similar association with time to all-cause mortality (aHR, 0.78 [95% CI, 0.59-1.03]; P =0.083). Associations of CRT with outcomes were not significantly different for those in NYHA III and IV classes (ratio of aHR, 0.72 [95% CI, 0.30-1.27]; P =0.23 for heart failure hospitalization/mortality; ratio of aHR, 0.70 [95% CI, 0.35-1.34]; P =0.27 for all-cause mortality alone). The sensitivity analysis, including RAFT data, did not show a significant relative CRT benefit between NYHA III and IV classes., Conclusions: Overall, there was no significant difference in the association of CRT with either outcome for patients in NYHA functional class III compared with functional class IV.

Background: Women might benefit more than men from cardiac resynchronization therapy (CRT) and do so at shorter QRS durations., Objective: This meta-analysis was performed to determine whether sex-based differences in CRT effects are better accounted for by height, body surface area (BSA), or left ventricular end-diastolic dimension (LVEDD)., Methods: We analyzed patient-level data from CRT trials (MIRACLE, MIRACLE ICD, MIRACLE ICD II, REVERSE, RAFT, COMPANION, and MADIT-CRT) using bayesian hierarchical Weibull regression models. Relationships between QRS duration and CRT effects were examined overall and in sex-stratified cohorts; additional analyses indexed QRS duration by height, BSA, or LVEDD. End points were heart failure hospitalization (HFH) or death and all-cause mortality., Results: Compared with men (n = 5628), women (n = 1439) were shorter (1.62 [interquartile range, 1.57-1.65] m vs 1.75 [1.70-1.80] m; P < .001), with smaller BSAs (1.76 [1.62-1.90] m 2 vs 2.02 [1.89-2.16] m 2 ; P < .001). In adjusted sex-stratified analyses, the reduction in HFH or death was greater for women (hazard ratio, 0.54; credible interval, 0.42-0.70) than for men (hazard ratio, 0.77; credible interval, 0.66-0.89; P interaction = .009); results were similar for all-cause mortality even after adjustment for height, BSA, and LVEDD. Sex-specific differences were observed only in nonischemic cardiomyopathy. The effect of CRT on HFH or death was observed at a shorter QRS duration for women (126 ms) than for men (145 ms). Indexing QRS duration by height, BSA, or LVEDD attenuated sex-specific QRS duration thresholds for the effects of CRT on HFH or death but not on mortality., Conclusion: Although body size partially explains sex-specific QRS duration thresholds for CRT benefit, it is not associated with the magnitude of CRT benefit. Indexing QRS duration for body size might improve selection of patients for CRT, particularly with a "borderline" QRS duration., (Copyright © 2024. Published by Elsevier Inc.)

This study measured the relationship between head-injury exposure and later-in-life cognitive and emotional symptoms in aging collegiate football players who participated in the College Level Aging Athlete Study. Linear regressions examined the relationship between various head-injury exposure variables (head-injury exposure estimate [HIEE], number of diagnosed concussions, and symptomatic hits to the head) and subjective cognitive function, objective cognitive function, and emotional/mood symptoms. Additional regressions evaluated the impact of emotional symptoms on subjective cognitive decline and objective cognitive function. Participants (n = 216) were 50-87 years old (M = 63.4 [8.5]), 91% White, and well-educated (bachelor's/graduate degree = 92%). HIEE did not predict scores on cognitive or emotional/mood symptom measures ( p's > .169). Diagnosed concussions had a small effect on depression symptoms ( p = .002, b  = 0.501, R2 = .052) and subjective cognitive symptoms ( p = .002, b  = 0.383, R2 = .051). An emotional symptom index had a stronger relationship ( p < .001, b  = 0.693, R2 = .362) with subjective cognitive functioning but no significant relationship with objective cognitive function ( p = .052, b = -0.211, R2 = .020). Controlling for emotional symptoms, the relationship between concussions and subjective cognitive symptoms was attenuated ( p = .078, R2 = .011). Findings suggested that head-injury exposure was not significantly related to cognitive or emotional/mood outcomes in former collegiate football players and highlighted the importance of current emotional/mood symptoms on subjective cognitive function.

Aims: Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT)., Methods and Results: Original patient-level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK-HF, MIRACLE, MIRACLE-ICD, MIRACLE-ICD II, RAFT, COMPANION, MADIT-CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1-2, or ≥3. The outcomes of interest were time to all-cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all-cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1-2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all-cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68-0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34-0.86), for 1-2 comorbidities was 0.81 (95% CI 0.67-0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64-1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all-cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65-0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50-0.94), for 1-2 comorbidities was 0.77 (95% CI 0.66-0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55-0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081)., Conclusion: In a meta-analysis of patient-level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all-cause mortality even when several comorbid diseases are present., Clinical Trial Registration: NCT00271154, NCT00251251, NCT00267098, NCT00180271., (© 2023 European Society of Cardiology.)

Background: Cardiac resynchronization therapy (CRT) reduces heart failure hospitalizations (HFH) and mortality for guideline-indicated patients with heart failure (HF). Most patients with HF are aged ≥70 years but such patients are often under-represented in randomized trials., Methods: Patient-level data were combined from 8 randomized trials published 2002-2013 comparing CRT to no CRT (n = 6,369). The effect of CRT was estimated using an adjusted Bayesian survival model. Using age as a categorical (<70 vs ≥70 years) or continuous variable, the interaction between age and CRT on the composite end point of HFH or all-cause mortality or all-cause mortality alone was assessed., Results: The median age was 67 years with 2436 (38%) being 70+; 1,554 (24%) were women; 2,586 (41%) had nonischemic cardiomyopathy and median QRS duration was 160 ms. Overall, CRT was associated with a delay in time to the composite end point (adjusted hazard ratio [aHR] 0.75, 95% credible interval [CI] 0.66-0.85, P = .002) and all-cause mortality alone (aHR of 0.80, 95% CI 0.69-0.96, P = .017). When age was treated as a categorical variable, there was no interaction between age and the effect of CRT for either end point (P > .1). When age was treated as a continuous variable, older patients appeared to obtain greater benefit with CRT for the composite end point (P for interaction = .027) with a similar but nonsignificant trend for mortality (P for interaction = .35)., Conclusion: Reductions in HFH and mortality with CRT are as great or greater in appropriately indicated older patients. Age should not be a limiting factor for the provision of CRT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF)., Methods: Individual-patient-data from four randomized trials investigating CRT-Defibrillators (COMPANION, MADIT-CRT, REVERSE) or CRT-Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all-cause mortality or to all-cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian-Weibull survival regression model adjusting for baseline characteristics., Results: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56-0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55-1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55-0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66-1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70-1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60-0.97)., Conclusion: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF., (© 2023 Wiley Periodicals LLC.)

Background: Benefit from cardiac resynchronization therapy (CRT) varies by QRS characteristics; individual randomized trials are underpowered to assess benefit for relatively small subgroups., Methods: The authors analyzed patient-level data from pivotal CRT trials (MIRACLE [Multicenter InSync Randomized Clinical Evaluation], MIRACLE-ICD [Multicenter InSync ICD Randomized Clinical Evaluation], MIRACLE-ICD II [Multicenter InSync ICD Randomized Clinical Evaluation II], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure], BLOCK-HF [Biventricular Versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block], COMPANION [Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure], and MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy]) using Bayesian Hierarchical Weibull survival regression models to assess CRT benefit by QRS morphology (left bundle branch block [LBBB], n=4549; right bundle branch block [RBBB], n=691; and intraventricular conduction delay [IVCD], n=1024) and duration (with 150-ms partition). The continuous relationship between QRS duration and CRT benefit was also examined within subgroups defined by QRS morphology. The primary end point was time to heart failure hospitalization (HFH) or death; a secondary end point was time to all-cause death., Results: Of 6264 patients included, 25% were women, the median age was 66 [interquartile range, 58 to 73] years, and 61% received CRT (with or without an implantable cardioverter defibrillator). CRT was associated with an overall lower risk of HFH or death (hazard ratio [HR], 0.73 [credible interval (CrI), 0.65 to 0.84]), and in subgroups of patients with QRS ≥150 ms and either LBBB (HR, 0.56 [CrI, 0.48 to 0.66]) or IVCD (HR, 0.59 [CrI, 0.39 to 0.89]), but not RBBB (HR 0.97 [CrI, 0.68 to 1.34]; P interaction <0.001). No significant association for CRT with HFH or death was observed when QRS was <150 ms (regardless of QRS morphology) or in the presence of RBBB. Similar relationships were observed for all-cause death., Conclusions: CRT is associated with reduced HFH or death in patients with QRS ≥150 ms and LBBB or IVCD, but not for those with RBBB. Aggregating RBBB and IVCD into a single "non-LBBB" category when selecting patients for CRT should be reconsidered., Registration: URL: https://www., Clinicaltrials: gov; Unique identifiers: NCT00271154, NCT00251251, NCT00267098, and NCT00180271.

As health care continues to evolve, training the next generation of healthcare leaders is more important than ever. However, many university undergraduate students are not directly exposed to topics such as health policy and management within their coursework or co-curricular engagements. At Duke University, we developed the Student Collaborative on Health Policy (SCOHP) as an inter-disciplinary health policy hub that offers opportunities for learning, engagement, and leadership in the healthcare-related fields for students of all academic backgrounds. We see opportunity for similar student-led groups to be established by student leaders at other institutions, increasing interaction with experts, mentorship and the accessibility of experiential education, service, and leadership in the health care sector., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Thomas, Sandhu, Li, Sanders and Prvu Bettger.)

Background: Hearing loss is a common and costly medical condition. This systematic review sought to identify evidence gaps in published model-based economic analyses addressing hearing loss to inform model development for an ongoing Lancet Commission., Methods: We searched the published literature through 14 June 2020 and our inclusion criteria included decision model-based cost-effectiveness analyses that addressed diagnosis, treatment, or prevention of hearing loss. Two investigators screened articles for inclusion at the title, abstract, and full-text levels. Data were abstracted and the studies were assessed for the qualities of model structure, data assumptions, and reporting using a previously published quality scale., Findings: Of 1437 articles identified by our search, 117 unique studies met the inclusion criteria. Most of these model-based analyses were set in high-income countries ( n  = 96, 82%). The evaluated interventions were hearing screening ( n  = 35, 30%), cochlear implantation ( n  = 34, 29%), hearing aid use ( n  = 28, 24%), vaccination ( n  = 22, 19%), and other interventions ( n  = 29, 25%); some studies included multiple interventions. Eighty-six studies reported the main outcome in quality-adjusted or disability-adjusted life-years, 24 of which derived their own utility values. The majority of the studies used decision tree ( n  = 72, 62%) or Markov ( n  = 41, 35%) models. Forty-one studies (35%) incorporated indirect economic effects. The median quality rating was 92/100 (IQR:72-100)., Interpretation: The review identified a large body of literature exploring the economic efficiency of hearing healthcare interventions. However, gaps in evidence remain in evaluation of hearing healthcare in low- and middle-income countries, as well as in investigating interventions across the lifespan. Additionally, considerable uncertainty remains around productivity benefits of hearing healthcare interventions as well as utility values for hearing-assisted health states. Future economic evaluations could address these limitations., Funding: NCATS 3UL1-TR002553-03S3., Competing Interests: All authors report no conflicts of interest., (© 2021 The Authors.)

Background: Cardiac resynchronization therapy (CRT) has been demonstrated to improve heart failure (HF) symptoms, reverse LV remodeling, and reduce mortality and HF hospitalization (HFH) in patients with a reduced left ventricular (LV) ejection fraction (LVEF). Prior studies examining outcomes based on right ventricular (RV) lead position among CRT patients have provided mixed results. We performed a systematic review and meta-analysis of randomized controlled trials and prospective observational studies comparing RV apical (RVA) and non-apical (RVNA) lead position in CRT., Methods: Our meta-analysis was constructed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and meta-analyses. We searched EMBASE and MEDLINE. Eligible studies reported on at least one of the following outcomes of interest: all-cause mortality, the composite endpoint of death and first HFH hospitalization, change in LVEF, New York Heart Association (NYHA) class improvement, and change in LV end systolic volume (LVESV). We performed meta-analysis summaries using a DerSimonian-Laird random-effects model and conservatively used the Knapp-Hartung approach to adjust the standard errors of the estimated model coefficients., Results: We included nine studies representing a total of 1832 patients. Of those, 1318 (72%) patients had RVA lead placement and 514 (28%) had RVNA lead placement. The mean age of patients was 65.5 ± 4.4 years, and they were predominantly men (69%-97%). There was no statistically significant difference in all-cause mortality by RVA vs. RVNA (OR = 0.77, 95% CI 0.32-1.89; I 2 = 16.7%, p = 0.31), or in the combined endpoint of all-cause mortality and first HFH (OR 0.88, 95% CI 0.62-1.25; I 2 = 0%, p = 0.84). Also, there was no difference between RVA and RVNA for NYHA class improvement (OR = 1.03, 95% CI 0.9-1.17; I 2 = 0%, p = 0.99), change in LVEF (mean difference (MD) = 1.33, 95% CI -1.45 to 4.10; I 2 = 47%; p = 0.093), and change in LVESV (MD = -1.11, 95% CI -3.34 to 1.12; I 2 = 0%; p = 0.92)., Conclusion: This meta-analysis shows that in CRT pacing, RV lead position does not appear to be associated with clinical outcomes or LV reverse remodeling. Further studies should focus on the relationship of RV lead vis-à-vis LV lead location, and its clinical importance., Competing Interests: Declaration of Competing Interest D.P.M. has received research grants from Medtronic and Boston Scientific, consulting fees from Abbott, and speaking fees from Boston Scientific and Zoll. F.A.A: None. F.D: None. G.D·S: None. N.A.L: None. S.M.A. receives research, speaking and consulting fees from Medtronic, research and speaking fees from Abbott, and research fees from Boston Scientific. V.B: None., (Copyright © 2021. Published by Elsevier Inc.)

Background: Although cardiac resynchronization therapy (CRT) is effective for some patients with heart failure and a reduced left ventricular ejection fraction (HFrEF), evidence gaps remain for key clinical and policy areas. The objective of the study was to review the data on the effects of CRT for patients with HFrEF receiving pharmacological therapy alone or pharmacological therapy and an implantable cardioverter-defibrillator (ICD) and then, informed by a diverse group of stakeholders, to identify evidence gaps, prioritize them, and develop a research plan., Methods: Relevant studies were identified using PubMed and EMBASE and ongoing trials using clinicaltrials.gov. Forced-ranking prioritization method was applied by stakeholders to reach a consensus on the most important questions. Twenty-six stakeholders contributed to the expanded list of evidence gaps, including key investigators from existing randomized controlled trials and others representing different perspectives, including patients, the public, device manufacturers, and policymakers., Results: Of the 18 top-tier evidence gaps, 8 were related to specific populations or subgroups of interest. Seven were related to the comparative effectiveness and safety of CRT interventions or comparators, and 3 were related to the association of CRT treatment with specific outcomes. The association of comorbidities with CRT effectiveness ranked highest, followed by questions about the effectiveness of CRT among patients with atrial fibrillation and the relationship between gender, QRS morphology and duration, and outcomes for patients either with CRT plus ICD or with ICD., Conclusions: Evidence gaps presented in this article highlight numerous, important clinical and policy questions for which there is inconclusive evidence on the role of CRT and provide a framework for future collaborative research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Cluster-randomized trials (CRTs) are being increasingly used to test a range of interventions, including medical interventions commonly used in clinical practice. Policies created by the NIH and the Food and Drug Administration (FDA) require the reporting of demographics and the examination of demographic heterogeneity of treatment effect (HTE) for individually randomized trials. Little is known about how frequent demographics are reported and HTE analyses are conducted in CRTs., Objectives: We sought to understand the prevalence of HTE analyses and the statistical methods used to conduct them in CRTs focused on treating cardiovascular disease, cancer, and chronic lower respiratory diseases. Additionally, we also report on the proportion of CRTs that reported on baseline demographics of its populations and conducted demographic HTE analyses., Data Sources: We searched PubMed and Embase for CRTs published between 1/1/2010 and 3/29/2016 that focused on treating the top 3 Center for Disease Control causes of death (cardiovascular disease, chronic lower respiratory disease, and cancer). Evidence Screening And Review: Of 1,682 unique titles, 117 abstracts were screened. After excluding 53 articles, we included 64 CRT publications and abstracted information on study characteristics and demographic information, statistical analysis, HTE analysis, and study quality., Results: Age and sex were reported in greater than 95.3% of CRTs, while race and ethnicity were reported in only 20.3% of CRTs. HTE analyses were conducted in 28.1% (n = 18) of included CRTs and 77.8% (n = 12) were prespecified analyses. Four CRTs conducted a demographic subgroup analysis. Only 6/18 CRTs used interaction testing to determine whether HTE existed., Conclusions: Baseline demographic reporting was high for age and sex in CRTs, but was uncommon for race and ethnicity. HTE analyses were uncommon and was rare for demographic subgroups, which limits the ability to examine the extent of benefits or risks for treatments tested with CRT designs., Competing Interests: MA Starks - none; GD Sanders - none; RR Coeytaux - none; IL Riley - none; LR Jackson - education support from Medtronic and Biotronik; honoraria from Biotronik; AM Brooks - none; KL Thomas - Consultant: Pfizer, BMS, Janssen; KR Choudhury - none; RM Califf - sits on the corporate board for Cytokinetics and is board chair for the People-Centered Research Foundation. He receives personal fees for consulting from Merck, Amgen, Biogen, Genentech, Eli Lilly, and Boehringer Ingelheim. He is also employed as an advisor by Verily Life Sciences (Alphabet); AF Hernandez - consulting fees from Sanofi, Johnson & Johnson, AstraZeneca, and Cortera; research support from Amylin and Scios/Johnson & Johnson. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: More than half of pregnancies in women with systemic lupus erythematosus (lupus) result in adverse outcomes for the mother or the fetus. We sought to identify aspects of current rheumatologic care that could be improved to decrease the frequency of poor outcomes., Methods: Focus groups with clinical rheumatologists, based on the PRECEDE/PROCEED framework, identified factors that influenced care. A group of women with lupus on their reproductive journey contributed to our understanding of the dilemmas and care provided., Results: Medically ill-timed pregnancies and medication non-adherence during pregnancy were identified by rheumatologists as the two key dilemmas in care. We identified several communication gaps as key modifiable barriers to optimal management. The approach to physician-patient communication was often unsuitable to sensitive discussions about pregnancy planning. The communication of treatment plans was frequently hampered by gaps in knowledge and both physician and patient confidence in the data, encouraging non-adherence among nervous patients. Finally, local rheumatologists and obstetricians/gynecologists providers frequently did not communicate, leading to varying treatment plans and confusion for patients., Conclusions: To decrease the frequency of ill-timed pregnancy and medication non-adherence it will be essential to empower rheumatologists, and women with lupus to have open and accurate conversations about pregnancy planning and management.

Background: The comparative safety and effectiveness of treatments to prevent thromboembolic complications in atrial fibrillation (AF) remain uncertain., Purpose: To compare the effectiveness of medical and procedural therapies in preventing thromboembolic events and bleeding complications in adults with nonvalvular AF., Data Sources: English-language studies in several databases from 1 January 2000 to 14 February 2018., Study Selection: Two reviewers independently screened citations to identify comparative studies of treatments to prevent stroke in adults with nonvalvular AF who reported thromboembolic or bleeding complications., Data Extraction: Two reviewers independently abstracted data, assessed study quality and applicability, and rated strength of evidence., Data Synthesis: Data from 220 articles were included. Dabigatran and apixaban were superior and rivaroxaban and edoxaban were similar to warfarin in preventing stroke or systemic embolism. Apixaban and edoxaban were superior and rivaroxaban and dabigatran were similar to warfarin in reducing the risk for major bleeding. Treatment effects with dabigatran were similar in patients with renal dysfunction (interaction P > 0.05), and patients younger than 75 years had lower bleeding rates with dabigatran (interaction P < 0.001). The benefit of treatment with apixaban was consistent in many subgroups, including those with renal impairment, diabetes, and prior stroke (interaction P > 0.05 for all). The greatest bleeding risk reduction was observed in patients with a glomerular filtration rate less than 50 mL/min/1.73 m2 (P = 0.003). Similar treatment effects were observed for rivaroxaban and edoxaban in patients with prior stroke, diabetes, or heart failure (interaction P > 0.05 for all)., Limitation: Heterogeneous study populations, interventions, and outcomes., Conclusion: The available direct-acting oral anticoagulants (DOACs) are at least as effective and safe as warfarin for patients with nonvalvular AF. The DOACs had similar benefits across several patient subgroups and seemed safe and efficacious for a wide range of patients with nonvalvular AF., Primary Funding Source: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069999).

Background:  Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke. Medical therapy for decreasing stroke risk involves anticoagulation, which may increase bleeding risk for certain patients. In determining the optimal therapy for stroke prevention for patients with AF, clinicians use tools with various clinical, imaging and patient characteristics to weigh stroke risk against therapy-associated bleeding risk., Aim:  This article reviews published literature and summarizes available risk stratification tools for stroke and bleeding prediction in patients with AF., Methods:  We searched for English-language studies in PubMed, Embase and the Cochrane Database of Systematic Reviews published between 1 January 2000 and 14 February 2018. Two reviewers screened citations for studies that examined tools for predicting thromboembolic and bleeding risks in patients with AF. Data regarding study design, patient characteristics, interventions, outcomes, quality, and applicability were extracted., Results:  Sixty-one studies were relevant to predicting thromboembolic risk and 38 to predicting bleeding risk. Data suggest that CHADS 2 , CHA 2 DS 2 -VASc and the age, biomarkers, and clinical history (ABC) risk scores have the best evidence for predicting thromboembolic risk (moderate strength of evidence for limited prediction ability of each score) and that HAS-BLED has the best evidence for predicting bleeding risk (moderate strength of evidence)., Limitations:  Studies were heterogeneous in methodology and populations of interest, setting, interventions and outcomes analysed., Conclusion:  CHADS 2 , CHA 2 DS 2 -VASc and ABC scores have the best prediction for stroke events, and HAS-BLED provides the best prediction for bleeding risk. Future studies should define the role of imaging tools and biomarkers in enhancing the accuracy of risk prediction tools., Primary Funding Source:  Patient-Centered Outcomes Research Institute (PROSPERO #CRD42017069999)., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Rheumatologists are essential partners in planning and managing pregnancies in women with lupus. Whether they know the essentials of contraceptive and medical treatment in pregnancy, however, is unknown., Method: Anonymous in-lecture surveys were completed by 270 rheumatologists to assess knowledge of contraceptive effectiveness, emergency contraception, medication teratogenicity, and lupus pregnancy risk assessment., Results: Rheumatologists knew the high effectiveness of the intrauterine device, but over-estimated the effectiveness of injectable medroxyprogesterone and condoms. Almost all identified methotrexate as a teratogen, but only 69% identified cyclophosphamide and 37% mycophenolate. Most rheumatologists knew that lupus activity in pregnancy is the main predictor of pregnancy outcomes, but underestimated the risks of hypertension and race., Conclusion: To improve lupus pregnancy planning and management, rheumatologists would benefit from improved knowledge about contraceptive effectiveness, teratogens, and the risks from non-lupus factors for pregnancy complications.

Aims: Implantable cardioverter-defibrillators (ICDs) are key in the prevention of sudden cardiac death, but outcomes may vary by type of device or programming [single chamber (SC) vs. dual chamber (DC)] in patients without a bradycardia pacing indication. We sought to meta-analyse patient outcomes of randomized trials of SC vs. DC devices or programming., Methods and Results: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane trials databases for relevant studies excluding those published before 2000, involving children, or not available in English. Endpoints included mortality, inappropriate ICD therapies, and implant complications. Endpoints with at least three reporting studies were meta-analysed. We identified eight studies meeting inclusion criteria representing 2087 patients with 16.1 months mean follow-up. Mean age was 62.7 years (SD 1.92); in six studies reporting sex, most patients were male (85%). Comparing patients with a SC or DC ICD or programming, we found similar rates of mortality [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.54-1.68; P = 0.86] and inappropriate therapies (OR 1.46, 95% CI 0.97-2.19; P = 0.07) in five and six studies, respectively. In three studies of SC vs. DC ICDs (but not programming) rates of pneumothorax and lead dislodgement were not different (OR 2.12, 95% CI 0.18-24.72; P = 0.55 and OR 0.87, 95% CI 0.32-2.47; P = 0.83, respectively)., Conclusion: In this meta-analysis of randomized controlled trials comparing SC vs. DC ICD device or programming, there was no significant difference in inappropriate therapies, mortality, pneumothorax, or lead dislodgement. Future studies should compare these devices over longer follow-up and in specific patient populations.

Objectives: In 2016, the Second Panel on Cost-effectiveness in Health and Medicine updated the seminal work of the original panel from 2 decades earlier. The Second Panel had an opportunity to reflect on the evolution of cost-effectiveness analysis (CEA) and to provide guidance for the next generation of practitioners and consumers. In this article, we present key topics for future research and policy., Methods: During the course of its deliberations, the Second Panel discussed numerous topics for advancing methods and for improving the use of CEA in decision making. We identify and consider 7 areas for which the panel believes that future research would be particularly fruitful. In each of these areas, we highlight outstanding research needs. The list is not intended as an exhaustive inventory but rather a set of key items that surfaced repeatedly in the panel's discussions. In the online Appendix , we also list and expound briefly on 8 other important topics., Results: We highlight 7 key areas: CEA and perspectives (determining, valuing, and summarizing elements for the analysis), modeling (comparative modeling and model transparency), health outcomes (valuing temporary health and path states, as well as health effects on caregivers), costing (a cost catalogue, valuing household production, and productivity effects), evidence synthesis (developing theory on learning across studies and combining data from clinical trials and observational studies), estimating and using cost-effectiveness thresholds (empirically representing 2 broad concepts: opportunity costs and public willingness to pay), and reporting and communicating CEAs (written protocols and a quality scoring system)., Conclusions: Cost-effectiveness analysis remains a flourishing and evolving field with many opportunities for research. More work is needed on many fronts to understand how best to incorporate CEA into policy and practice.

Aim: There is limited information on the outcomes after primary prevention implantable cardioverter-defibrillator (ICD) implantation in patients with heart failure (HF) and diabetes. This analysis evaluates the effectiveness of a strategy of ICD plus medical therapy vs. medical therapy alone among patients with HF and diabetes., Methods and Results: A patient-level combined-analysis was conducted from a combined dataset that included four primary prevention ICD trials of patients with HF or severely reduced ejection fractions: Multicenter Automatic Defibrillator Implantation Trial I (MADIT I), MADIT II, Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE), and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). In total, 3359 patients were included in the analysis. The primary outcome of interest was all-cause death. Compared with patients without diabetes (n = 2363), patients with diabetes (n = 996) were older and had a higher burden of cardiovascular risk factors. During a median follow-up of 2.6 years, 437 patients without diabetes died (178 with ICD vs. 259 without) and 280 patients with diabetes died (128 with ICD vs. 152 without). ICDs were associated with a reduced risk of all-cause mortality among patients without diabetes [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.46-0.67] but not among patients with diabetes (HR 0.88, 95% CI 0.7-1.12; interaction P = 0.015)., Conclusion: Among patients with HF and diabetes, primary prevention ICD in combination with medical therapy vs. medical therapy alone was not significantly associated with a reduced risk of all-cause death. Further studies are needed to evaluate the effectiveness of ICDs among patients with diabetes., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Context: Nonpharmacologic treatments for attention-deficit/hyperactivity disorder (ADHD) encompass a range of care approaches from structured behavioral interventions to complementary medicines., Objectives: To assess the comparative effectiveness of nonpharmacologic treatments for ADHD among individuals 17 years of age and younger., Data Sources: PubMed, Embase, PsycINFO, and Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1, 2009 through November 7, 2016., Study Selection: We included studies that compared any ADHD nonpharmacologic treatment strategy with placebo, pharmacologic, or another nonpharmacologic treatment., Data Extraction: Study design, patient characteristics, intervention approaches, follow-up times, and outcomes were abstracted. For comparisons with at least 3 similar studies, random-effects meta-analysis was used to generate pooled estimates., Results: We identified 54 studies of nonpharmacologic treatments, including neurofeedback, cognitive training, cognitive behavioral therapy, child or parent training, dietary omega fatty acid supplementation, and herbal and/or dietary approaches. No new guidance was identified regarding the comparative effectiveness of nonpharmacologic treatments. Pooled results for omega fatty acids found no significant effects for parent rating of ADHD total symptoms ( n = 411; standardized mean difference -0.32; 95% confidence interval -0.80 to 0.15; I 2 = 52.4%; P = .10) or teacher-rated total ADHD symptoms ( n = 287; standardized mean difference -0.08; 95% confidence interval -0.47 to 0.32; I 2 = 0.0%; P = .56)., Limitations: Studies often did not reflect the primary care setting and had short follow-up periods, small sample sizes, variations in outcomes, and inconsistent reporting of comparative statistical analyses., Conclusions: Despite wide use, there are significant gaps in knowledge regarding the effectiveness of ADHD nonpharmacologic treatments., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Davis has participated as a study clinician on a pilot trial of a nonpharmacologic intervention study sponsored by Akili and awarded to Duke; she also served as the Duke site principal investigator on a multisite trial of a nonpharmacologic intervention study sponsored by Akili and awarded to Duke; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

The implantable cardioverter defibrillator (ICD) is a life-saving therapy in various patient populations. Although data on the outcomes of initial ICD implants are abundant, data on ICD replacements, especially in patients with improved left ventricular (LV) function, are scarce. Therefore, it is not known when it is safe to not replace an ICD that has reached the end of battery life. This article reviews data on patients with primary prevention ICDs who have improvement in left ventricular ejection fraction during follow-up and provides some guidance, based on the available evidence, related to circumstances when replacement of an ICD may be forgone., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Many young investigators are interested in cardiovascular (CV) outcomes research; however, the current training experience of early investigators across the United States is uncertain., Methods: From April to November 2014, we surveyed mentees and mentors of early-stage CV outcomes investigators across the United States. We contacted successful grantees of government agencies, members of professional organizations, and trainees in CV outcomes training programs., Results: A total of 185 (of 662) mentees and 76 (of 541) mentors completed the survey. Mentees were equally split by sex; most had completed training >3 years before completing the survey and were clinicians. Mentors were more likely women, mostly ≥20 years posttraining, and at an associate/full professor rank. Mentors reported devoting more time currently to clinical work than when they were early in their career and mentoring 2-4 people simultaneously. More than 80% of mentees started training to become academicians and completed training with the same goal. More than 70% of mentees desired at least 50% research time in future jobs. More than 80% of mentors believed that future investigators would need more than 50% time dedicated to research. Most mentees (80%) were satisfied with their relationship with their mentor and reported having had opportunities to develop independently. Mentors more frequently than mentees reported that funding cutbacks had negatively affected mentees' ability to succeed (84% vs 58%). Across funding mechanisms, mentees were more optimistic than mentors about securing funding. Both mentees and mentors reported greatest preparedness for job/career satisfaction (79% for both) and publications (84% vs 92%) and least preparedness for future financial stability (48% vs 46%) and work-life balance (47% vs 42%)., Conclusions: Survey findings may stimulate future discourse and research on how best to attract, train, and retain young investigators in CV outcomes research. Insights may help improve existing training programs and inform the design of new ones., (Copyright © 2017. Published by Elsevier Inc.)

Background: Outcomes research training programs should prepare trainees to successfully compete for research funding. We examined how early-career investigators' prior and desired training aligns with recently funded cardiovascular (CV) outcomes research., Methods: We (1) reviewed literature to identify 13 core competency areas in CV outcomes research; (2) surveyed early-career investigators to understand their prior and desired training in each competency area; (3) examined recently funded grants commonly pursued by early-career outcomes researchers to ascertain available funding in competency areas; and (4) analyzed alignment between investigator training and funded research in each competency area. We evaluated 185 survey responses from early-career investigators (response rate 28%) and 521 funded grants from 2010 to 2014., Results: Respondents' prior training aligned with funded grants in the areas of clinical epidemiology, observational research, randomized controlled trials, and implementation/dissemination research. Funding in community-engaged research and health informatics was more common than prior training in these areas. Respondents' prior training in biostatistics and systematic review was more common than funded grants focusing on these specific areas. Respondents' desired training aligned similarly with funded grants, with some exceptions; for example, desired training in health economics/cost-effectiveness research was more common than funded grants in these areas. Restricting to CV grants (n=132) and National Heart, Lung, and Blood Institute-funded grants (n=170) produced similar results., Conclusions: Identifying mismatch between funded grants in outcomes research and early-career investigators' prior/desired training may help efforts to harmonize investigator interests, training, and funding. Our findings suggest a need for further consideration of how to best prepare early-career investigators for funding success., (Copyright © 2017. Published by Elsevier Inc.)

Background: Chronic lower extremity venous disease (LECVD) is twice as prevalent as coronary heart disease, and invasive therapies to treat LECVD accounted for an estimated $290 million in Medicare expenditures in 2015. Despite increasing use of these invasive therapies, their comparative effectiveness is unknown., Methods: We conducted a systematic review and meta-analysis of treatments for patients (symptomatic and asymptomatic) with lower extremity varicosities and/or lower extremity chronic venous insufficiency/incompetence/reflux. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 2000 to July 2016. We included comparative randomized controlled trials (RCTs) with >20 patients and observational studies with >500 patients. Short-, intermediate-, and long-term outcomes of placebo, mechanical compression therapy, and invasive therapies (surgical and endovascular) were included. Quality ratings and evidence grading was performed. Random-effects models were used to compute summary estimates of effects., Results: We identified a total of 57 studies representing 105,878 enrolled patients, including 53 RCTs comprised of 10,034 patients. Among the RCTs, 16 were good quality, 28 were fair quality, and 9 were poor quality. Allocation concealment, double blinding, and reporting bias were inadequately addressed in 25 of 53 (47%), 46 of 53 (87%), and 15 of 53 (28.3%), respectively. Heterogeneity in therapies, populations, and/or outcomes prohibited meta-analysis of comparisons between different endovascular therapies and between endovascular intervention and placebo/compression. Meta-analysis evaluating venous stripping plus ligation (high ligation/stripping) compared with radiofrequency ablation revealed no difference in short-term bleeding (odds ratio [OR]=0.30, 95% CI -0.16 to 5.38, P=.43) or reflux recurrence at 1-2 years (OR=0.76, 95% CI 0.37-1.55, P=.44). Meta-analysis evaluating high ligation/stripping versus endovascular laser ablation revealed no difference in long-term symptom score (OR 0.02, 95% CI -0.19 to 0.23, P=.84) or quality of life at 2 years (OR 0.06, 95% CI -0.12 to 0.25, P=.50)., Conclusions: The paucity of high-quality comparative effectiveness and safety data in LECVD is concerning given the overall rise in endovascular procedures. More high-quality studies are needed to determine comparative effectiveness and guide policy and practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Patients who have had an acute coronary syndrome (ACS) event have an increased risk for depression., Purpose: To evaluate the diagnostic accuracy of depression screening instruments and to compare safety and effectiveness of depression treatments in adults within 3 months of an ACS event., Data Sources: MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews from January 2003 to August 2017, and a manual search of citations from key primary and review articles., Study Selection: English-language studies of post-ACS patients that evaluated the diagnostic accuracy of depression screening tools or compared the safety and effectiveness of a broad range of pharmacologic and nonpharmacologic depression treatments., Data Extraction: 2 investigators independently screened each article for inclusion; abstracted the data; and rated the quality, applicability, and strength of evidence., Data Synthesis: Evidence from 6 of the 10 included studies showed that a range of depression screening instruments produces acceptable levels of diagnostic sensitivity, specificity, and negative predictive values (70% to 100%) but low positive predictive values (below 50%). The Beck Depression Inventory-II was the most studied tool. A large study found that a combination of cognitive behavioral therapy (CBT) and antidepressant medication improved depression symptoms, mental health-related function, and overall life satisfaction more than usual care., Limitation: Few studies, no evaluation of the influence of screening on clinical outcomes, and no studies addressing several clinical interventions of interest., Conclusion: Depression screening instruments produce diagnostic accuracy metrics that are similar in post-ACS patients and other clinical populations. Depression interventions have an uncertain effect on cardiovascular outcomes, but CBT combined with antidepressant medication produces modest improvement in psychosocial outcomes., Primary Funding Source: Agency for Healthcare Research and Quality (PROSPERO: CRD42016047032).

Background: No precise tools exist to predict appropriate shocks in patients with a primary prevention ICD. We sought to identify characteristics predictive of appropriate shocks in patients with a primary prevention implantable cardioverter defibrillator (ICD)., Methods: Using patient-level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), we identified patients with any appropriate shock. Clinical and demographic variables were included in a logistic regression model to predict appropriate shocks., Results: There were 1,463 patients randomized to an ICD, and 285 (19%) had ≥1 appropriate shock over a median follow-up of 2.59 years. Compared with patients without appropriate ICD shocks, patients who received any appropriate shock tended to have more severe heart failure. In a multiple logistic regression model, predictors of appropriate shocks included NYHA class (NYHA II vs. I: OR 1.65, 95% CI 1.07-2.55; NYHA III vs. I: OR 1.74, 95% CI 1.10-2.76), lower LVEF (per 1% change) (OR 1.04, 95% CI 1.02-1.06), absence of beta-blocker therapy (OR 1.61, 95% CI 1.23-2.12), and single chamber ICD (OR 1.67, 95% CI 1.13-2.45)., Conclusion: In this meta-analysis of patient level data from MADIT-II and SCD-HeFT, higher NYHA class, lower LVEF, no beta-blocker therapy, and single chamber ICD (vs. dual chamber) were significant predictors of appropriate shocks., (© 2017 Wiley Periodicals, Inc.)

Background: Primary prevention implantable cardioverter defibrillator (ICD) reduce all-cause mortality by reducing sudden cardiac death. There are conflicting data regarding whether patients with more advanced heart failure derive ICD benefit owing to the competing risk of nonsudden death., Methods: We performed a patient-level meta-analysis of New York Heart Association (NYHA) class II/III heart failure patients (left ventricular ejection fraction ≤35%) from 4 primary prevention ICD trials (MADIT-I, MADIT-II, DEFINITE, SCD-HeFT). Bayesian-Weibull survival regression models were used to assess the impact of NYHA class on the relationship between ICD use and mortality., Results: Of the 2,763 patients who met study criteria, 68% (n=1,867) were NYHA II and 52% (n=1,435) were randomized to an ICD. In a multivariable model including all study patients, the ICD reduced mortality (hazard ratio [HR] 0.65, 95% posterior credibility interval [PCI]) 0.40-0.99). The interaction between NYHA class and the ICD on mortality was significant (posterior probability of no interaction=.036). In models including an interaction term for the NYHA class and ICD, the ICD reduced mortality among NYHA class II patients (HR 0.55, PCI 0.35-0.85), and the point estimate suggested reduced mortality in NYHA class III patients (HR 0.76, PCI 0.48-1.24), although this was not statistically significant., Conclusions: Primary prevention ICDs reduce mortality in NYHA class II patients and trend toward reducing mortality in the heterogeneous group of NYHA class III patients. Improved risk stratification tools are required to guide patient selection and shared decision making among NYHA class III primary prevention ICD candidates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: Conflicting data have emerged on the efficacy of implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death (primary prevention ICDs) in patients with nonischemic cardiomyopathy., Objective: To investigate the association of primary prevention ICDs with all-cause mortality in patients with nonischemic cardiomyopathy., Data Sources: PubMed was searched from January 1, 2000, through October 31, 2016, for the terms implantable defibrillator OR implantable cardioverter defibrillator AND non-ischemic cardiomyopathy. Additional references were identified from bibliographies of pertinent articles and queries to experts in this field., Study Selection: Inclusion criteria consisted of a randomized clinical trial design and comparison of the ICD with medical therapy (control) in at least 100 patients with nonischemic cardiomyopathy. In addition, studies had to report on all-cause mortality during a follow-up period of at least 12 months and be published in English. The search yielded 10 studies, of which only 1 met the inclusion criteria. A search of bibliographies of pertinent articles and queries of experts in this field led to 3 additional studies., Data Extraction and Synthesis: The PRISMA guidelines were used to abstract data and assess data quality and validity. Data were pooled using fixed- and random-effects models., Main Outcomes and Measures: The primary end point was all-cause mortality. Before data collection started, primary prevention ICDs were hypothesized to reduce all-cause mortality among patients with nonischemic cardiomyopathy., Results: Four randomized clinical trials met the selection criteria and included 1874 unique patients; 937 were in the ICD group and 937 in the control group. Pooling data from these trials showed a significant reduction in all-cause mortality with an ICD (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008; P = .87 for heterogeneity)., Conclusions and Relevance: Primary prevention ICDs are efficacious at reducing all-cause mortality among patients with nonischemic cardiomyopathy. These findings support professional guidelines that recommend the use of ICDs in such patients.