A scoping review to create a framework for the steps in developing condition-specific preference-based instruments de novo or from an existing non-preference-based instrument: use of item response theory or Rasch analysis.

BACKGROUND: There is no widely accepted framework to guide the development of condition-specific preference-based instruments (CSPBIs) that includes both de novo and from existing non-preference-based instruments. The purpose of this study was to address this gap by reviewing the published literature on CSPBIs, with particular attention to the application of item response theory (IRT) and Rasch analysis in their development. METHODS: A scoping review of the literature covering the concepts of all phases of CSPBI development and evaluation was performed from MEDLINE, Embase, PsychInfo, CINAHL, and the Cochrane Library, from inception to December 30, 2022. RESULTS: The titles and abstracts of 1,967 unique references were reviewed. After retrieving and reviewing 154 full-text articles, data were extracted from 109 articles, representing 41 CSPBIs covering 21 diseases or conditions. The development of CSPBIs was conceptualized as a 15-step framework, covering four phases: 1) develop initial questionnaire items (when no suitable non-preference-based instrument exists), 2) establish the dimensional structure, 3) reduce items per dimension, 4) value and model health state utilities. Thirty-nine instruments used a type of Rasch model and two instruments used IRT models in phase 3. CONCLUSION: We present an expanded framework that outlines the development of CSPBIs, both from existing non-preference-based instruments and de novo when no suitable non-preference-based instrument exists, using IRT and Rasch analysis. For items that fit the Rasch model, developers selected one item per dimension and explored item response level reduction. This framework will guide researchers who are developing or assessing CSPBIs.

A Systematic Review of the Cost-Effectiveness of Cleft Care in Low- and Middle-Income Countries: What is Needed?

OBJECTIVE: The objective of this paper is to conduct a systematic review that summarizes the cost-effectiveness of cleft lip and/or palate (CL/P) care in low- and middle-income countries (LMICs) based on existing literature. DESIGN: We searched eleven electronic databases for articles from January 1, 2000 to December 29, 2020. This study is registered in PROSPERO (CRD42020148402). Two reviewers independently conducted primary and secondary screening, and data extraction. SETTING: All CL/P cost-effectiveness analyses in LMIC settings. PATIENTS, PARTICIPANTS: In total, 2883 citations were screened. Eleven articles encompassing 1,001,675 patients from 86 LMICs were included. MAIN OUTCOME MEASURES: We used cost-effectiveness thresholds of 1% to 51% of a country's gross domestic product per capita (GDP/capita), a conservative threshold recommended for LMICs. Quality appraisal was conducted using the Joanna Briggs Institute (JBI) checklist. RESULTS: Primary CL/P repair was cost-effective at the threshold of 51% of a country's GDP/capita across all studies. However, only 1 study met at least 70% of the JBI criteria. There is a need for context-specific cost and health outcome data for primary CL/P repair, complications, and existing multidisciplinary management in LMICs. CONCLUSIONS: Existing economic evaluations suggest primary CL/P repair is cost-effective, however context-specific local data will make future cost-effectiveness analyses more relevant to local decision-makers and lead to better-informed resource allocation decisions in LMICs.

Clinical manifestations and health outcomes associated with Zika virus infections in adults: A systematic review.

BACKGROUND: Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. METHODS: This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. FINDINGS: We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. CONCLUSIONS: The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.

Systems thinking in health technology assessment: a scoping review.

OBJECTIVE: Our objective was to assess how, and to what extent, a systems-level perspective is considered in decision-making processes for health interventions by illustrating how studies define the boundaries of the system in their analyses and by defining the decision-making context in which a systems-level perspective is undertaken. METHOD: We conducted a scoping review following the Joanna Briggs Institute methodology. MEDLINE, EMBASE, Cochrane Library, and EconLit were searched and key search concepts included decision making, system, and integration. Studies were classified according to an interpretation of the "system" of analysis used in each study based on a four-level model of the health system (patient, care team, organization, and/or policy environment) and using categories (based on intervention type and system impacts considered) to describe the decision-making context. RESULTS: A total of 2,664 articles were identified and 29 were included for analysis. Most studies (16/29; 55%) considered multiple levels of the health system (i.e., patient, care team, organization, environment) in their analysis and assessed multiple classes of interventions versus a single class of intervention (e.g., pharmaceuticals, screening programs). Approximately half (15/29; 52%) of the studies assessed the influence of policy options on the system as a whole, and the other half assessed the impact of interventions on other phases of the disease pathway or life trajectory (14/29; 48%). CONCLUSIONS: We found that systems thinking is not common in areas where health technology assessments (HTAs) are typically conducted. Against this background, our study demonstrates the need for future conceptualizations and interpretations of systems thinking in HTA.

Impact of direct-acting antiviral regimens on mortality and morbidity outcomes in patients with chronic hepatitis c: Systematic review and meta-analysis.

The long-term effects of direct-acting antiviral therapies (DAAs) for chronic hepatitis C (CHC) remain uncertain. The objective of this systematic review and meta-analysis was to assess the impact of DAAs on CHC progression and mortality. We searched Ovid MEDLINE, Ovid EMBASE and PubMed databases (January 2011 to March 2020) for studies that compared the efficacy of DAAs to a non-DAA control in patients with CHC. Main outcomes were the adjusted hazard ratios (HRs) for mortality, liver decompensation, HCC occurrence and recurrence. Pooled estimates of HRs were determined using random-effects meta-analyses with inverse variance weighting, with sensitivity analyses and meta-regression to explore the effects of clinical factors. We identified 39 articles for the primary analysis. Compared with unexposed individuals, patients treated with DAA had a reduced risk of death (HR; CI = 0.44; 0.38-0.52), decompensation (HR; CI = 0.54; 0.38- 0.76) and HCC occurrence (HR; CI = 0.72; 0.61- 0.86). The protective effect of DAA on HCC recurrence was less clear (HR; CI = 0.72; 0.44-1.16). Sustained virologic response (SVR) attainment was a significant predictor of reduced mortality (HR; CI = 0.33; 0.23-0.46), decompensation (HR; CI = 0.11; 0.05-0.24), HCC occurrence (HR; CI = 0.31; 0.27-0.37) and HCC recurrence (HR; CI = 0.32; 0.20-0.51). Meta-regression showed no evidence of effect modification by patient age, sex, presence of cirrhosis or length of follow-up. In conclusion, our findings show protective effects of DAA treatment and DAA-related SVR on CHC progression and mortality.

A Protocol for a Scoping Review Comparative Bibliometric Analysis of Infectious Disease Research in Africa.

Introduction: Evidence on authorship trends of health research conducted about or in Africa shows that there is a lack of local researchers in the first and last authorship positions, with high income country collaborations taking up these positions. The differences in authorship calls into question power imbalances in global health research and who benefits from the production of new discoveries and innovations. Health studies may further go on to inform policy and clinical practice within the region having an impact on public health. This paper aims to compare the differences in authorship between COVID-19 and relevant infectious diseases in Africa. Materials and Methods: We will conduct a bibliometric analysis comparing authorship for COVID-19 research during a public health emergency with authorship for four other infectious diseases of relevance to Africa namely: Ebola, Zika Virus (ZIKV), Tuberculosis (TB) and Influenza. Our scoping review will follow the framework developed by Arksey and O'Malley and reviewed by Levac et al. We will search MEDLINE (Ovid), African Index Medicus (AIM), Eastern Mediterranean Region (IMEMR) Index Medicus, Embase (Ovid), and Web of Science (Clarivate). We will compare the different trends of disease research between the selected diseases. This study is registered with OSF registries and is licensed with the Academic Free License version 3.0. The open science registration number is 10.17605/OSF.IO/5ZPGN.

Health-Related Quality of Life in Neurological Disorders Most Commonly Associated With Zika-Virus Infection: A Systematic Review.

OBJECTIVES: In this systematic review, we synthesize the current evidence on health-related quality of life (HRQoL) for the two of the most relevant outcomes of Zika virus infection in humans, microcephaly and Guillain-Barré Syndrome (GBS). METHODS: We searched the following databases: MEDLINE, Embase, CINAHL, LILACS, WHO's ICTRP clinical trials registries database and PROSPERO. Search terms included quality of life, microcephaly, and Guillain-Barré Syndrome. We included primary studies where HRQoL was quantitatively assessed for microcephaly and GBS using validated instruments. We used the Joanna Briggs Institute Critical Appraisal Tools to assess the risk of bias of individual studies. RESULTS: From a total of 1,657 abstracts screened and 66 full texts reviewed, 21 studies met the eligibility criteria; one study for microcephaly and 20 for GBS. Adjusted disutilities for microcephaly compared to a normative childhood utility ranged from -0.745 to -0.820. For GBS, time traded-off the expected lifetime ranged from 16 days to 3 years. HRQoL follows the clinical course of GBS, with lower scores in the first months, recovery within the first year post onset, and stabilization after one year. CONCLUSIONS: Included studies reported a wide range of HRQoL for GBS, due in part to a high level of heterogeneity in methods, inclusion criteria, follow-up and reporting of results. Opportunities exist for primary studies assessing the longitudinal HRQoL over the entire course of the diseases to inform clinical practice, economic evaluations and health policy.

A Systematic Review and Meta-Analysis of Health Utilities in Patients With Chronic Hepatitis C.

BACKGROUND: Chronic hepatitis C (CHC) is among the most burdensome infectious diseases in the world. Health utilities are a valuable tool for quantifying this burden and conducting cost-utility analysis. OBJECTIVE: Our study summarizes the available data on utilities in CHC patients. This will facilitate analyses of CHC treatment and elimination strategies. METHODS: We searched MEDLINE, Embase, and the Cochrane Library for studies measuring utilities in CHC patients. Utilities were pooled by health state and utility instrument using meta-analysis. A further analysis used meta-regression to adjust for the effects of clinical status and methodological variation. RESULTS: Fifty-one clinical studies comprising 15 053 patients were included. Based on the meta-regression, patients' utilities were lower for more severe health states (predicted mean EuroQol-5D-3L utility for mild/moderate CHC: 0.751; compensated cirrhosis: 0.671; hepatocellular carcinoma: 0.662; decompensated cirrhosis: 0.602). Patients receiving interferon-based treatment had lower utilities than those on interferon-free treatment (0.647 vs 0.733). Patients who achieved sustained virologic response (0.786) had higher utilities than those with mild to moderate CHC. Utilities were substantially higher for patients in experimental studies compared to observational studies (coefficient: +0.074, P < .05). The time tradeoff instrument was associated with the highest utilities, and the Health Utilities Index 3 was associated with the lowest utilities. CONCLUSION: Chronic hepatitis C is associated with a significant impairment in global health status, as measured by health utility instruments. Impairment is greater in advanced disease. Experimental study designs yield higher utilities-an effect not previously documented. Curative therapy can alleviate the burden of CHC, although further research is needed in certain areas, such as the long-term impacts of treatment on utilities.

Mapping the evidence on health equity considerations in economic evaluations of health interventions: a scoping review protocol.

BACKGROUND: Equity in health has become an important policy agenda around the world, prompting health economists to advance methods to enable the inclusion of equity in economic evaluations. Among the methods that have been proposed to explicitly include equity are the weighting analysis, equity impact analysis, and equity trade-off analysis. This is a new development and a comprehensive overview of trends and concepts of health equity in economic evaluations is lacking. Thus, our objective is to map the current state of the literature with respect to how health equity is considered in economic evaluations of health interventions reported in the academic and gray literature. METHODS: We will conduct a scoping review to identify and map evidence on how health equity is considered in economic evaluations of health interventions. We will search relevant electronic, gray literature and key journals. We developed a search strategy using text words and Medical Subject Headings terms related to health equity and economic evaluations of health interventions. Articles retrieved will be uploaded to reference manager software for screening and data extraction. Two reviewers will independently screen the articles based on their titles and abstracts for inclusion, and then will independently screen a full text to ascertain final inclusion. A simple numerical count will be used to quantify the data and a content analysis will be conducted to present the narrative; that is, a thematic summary of the data collected. DISCUSSION: The results of this scoping review will provide a comprehensive overview of the current evidence on how health equity is considered in economic evaluations of health interventions and its research gaps. It will also provide key information to decision-makers and policy-makers to understand ways to include health equity into the prioritization of health interventions when aiming for a more equitable distribution of health resources. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered with Open Science Framework (OSF) Registry on August 14, 2019 (https://osf.io/9my2z/registrations).

Picturing ELSI+: a visual representation of ethical, legal, and social issues, and patient experiences in Health Technology Assessment in Canada.

OBJECTIVES: Consideration of ethical, legal, and social issues plus patient values (ELSI+) in health technology assessment (HTA) is challenging because of a lack of conceptual clarity and the multi-disciplinary nature of ELSI+. We used concept mapping to identify key concepts and inter-relationships in the ELSI+ domain and provide a conceptual framework for consideration of ELSI+ in HTA. METHODS: We conducted a scoping review (Medline and EMBASE, 2000-2016) to identify ELSI+ issues in the HTA literature. Items from the scoping review and an expert brainstorming session were consolidated into eighty ELSI+-related statements, which were entered into Concept Systems® Global MAX™ software. Participants (N = 38; 36 percent worked as researchers, 21 percent as academics; 42 percent self-identified as HTA experts) sorted the statements into thematic groups, and rated them on importance in making decisions about adopting technologies in Canada, from 1 (not at all important) to 5 (extremely important). We used Concept Systems® Global MAX™ software to create and analyze concept maps with four to sixteen clusters. RESULTS: Our final ELSI+ map consisted of five clusters, with each cluster representing a different concept and the statements within each cluster representing the same concept. Based on the concepts, we named these clusters: patient preferences/experiences, patient quality of life/function, patient burden/harm, fairness, and organizational. The highest mean importance ratings were for the statements in the patient burden/harm (3.82) and organizational (3.92) clusters. CONCLUSIONS: This study suggests an alternative approach to ELSI+, based on conceptual coherence rather than academic disciplines. This will provide a foundation for incorporating ELSI+ into HTA.

Health outcomes attributable to carbapenemase-producing Enterobacteriaceae infections: A systematic review and meta-analysis.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) pose a significant global health threat. OBJECTIVE: To conduct a systematic review of health outcomes and long-term sequelae attributable to CPE infection. METHODS: We followed PRISMA reporting guidelines and published our review protocol on PROSPERO (CRD42018097357). We searched Medline, Embase, CINAHL and the Cochrane Library. We included primary studies with a carbapenem-susceptible control group in high-income countries, published in English. Quality appraisal was completed using Joanna Briggs Institute checklists. We qualitatively summarized frequently reported outcomes and conducted a meta-analysis. RESULTS: Our systematic review identified 8,671 studies; 17 met the eligibility criteria for inclusion. All studies reported health outcomes; none reported health-related quality-of-life. Most studies were from Europe (65%), were conducted in teaching or university-affiliated hospitals (76%), and used case-control designs (53%). Mortality was the most commonly reported consequence of CPE-infections; in-hospital mortality was most often reported (62%). Our meta-analysis (n = 5 studies) estimated an absolute risk difference (ARD) for in-hospital bloodstream infection mortality of 0.25 (95% confidence interval [CI], 0.17-0.32). Duration of antibiotic therapy (range, 4-29.7 vs 1-23.6 days) and length of hospital stay (range, 21-87 vs 15-43 days) were relatively higher for CPE-infected patients than for patients infected with carbapenem-susceptible pathogens. Most studies (82%) met >80% of their respective quality appraisal criteria. CONCLUSIONS: The risk of in-hospital mortality due to CPE bloodstream infection is considerably greater than carbapenem-susceptible bloodstream infection (ARD, 0.25; 95% CI, 0.17-0.32). Health outcome studies associated with CPE infection are focused on short-term (eg, in-hospital) outcomes; long-term sequelae and quality-of-life are not well studied. TRIAL REGISTRATION: PROSPERO (CRD42018097357).

Estimation of fibrosis progression rates for chronic hepatitis C: a systematic review and meta-analysis update.

OBJECTIVES: Mathematical models are increasingly important in planning for the upcoming chronic hepatitis C (CHC) elimination efforts. Such models require reliable natural history inputs to make accurate predictions on health and economic outcomes. Yet, hepatitis C virus disease progression is known to vary widely in the literature and published inputs are currently outdated. The objectives of this study were to obtain updated estimates of fibrosis progression rates (FPR) in treatment-naïve patients with CHC and to explore sources of heterogeneity. DESIGN: A systematic review was conducted using Ovid-MEDLINE, Ovid-EMBASE and PubMed databases (January 1990 to January 2018) to identify observational studies of hepatic fibrosis in treatment-naïve patients with CHC. OUTCOMES: Stage-constant FPRs were estimated for each study given the reported fibrosis scores and duration of infection. Stage-specific FPRs (ie, F0→F1; F1→F2; F2→F3; F3→F4) were estimated using Markov maximum likelihood estimation. Estimates were pooled using random-effects meta-analysis and heterogeneity was evaluated by stratification and random-effects meta-regression. RESULTS: The review identified 111 studies involving 131 groups of patients (n=42 693). The pooled stage-constant FPR was 0.094 (95% CI 0.088 to 0.100); stage-specific FPRs were F0→F1: 0.107 (95% CI 0.097 to 0.118); F1→F2: 0.082 (95% CI 0.074 to 0.091); F2→F3: 0.117 (95% CI 0.107 to 0.129); F3→F4: 0.116 (95% CI 0.104 to 0.131). Stratified analysis revealed substantial variation in progression by study population. Meta-regression indicated associations between progression and infection age, duration, source, viral genotype and study population. Findings indicate that FPRs display substantial heterogeneity across study populations and pooled values from more homogenous subpopulations should be considered when estimating prognosis. CONCLUSIONS: This large meta-analysis presents updated prognostic estimates for CHC derived from newer studies using better diagnostic methods and improves estimates for important patient populations in terms of clinical policy (eg, injection drug users, non-clinical populations, liver clinic patients) and should be a valuable resource for patients, clinicians and clinical policymakers.

Gender differences in the provision of key post-arrest interventions for out-of-hospital cardiac arrest (OHCA) patients-protocol for a systematic review.

BACKGROUND: Evidence shows that the implementation of optimal post-arrest care significantly increases survival and functional outcomes among patients who experience an out-of-hospital cardiac arrest (OHCA). However, differences in OHCA survival have been reported between men and women, suggesting underlying differences in post-arrest care. This systematic review will evaluate gender differences in the provision of key post-arrest interventions. METHODS: Eligible studies will be identified through systematic searches of relevant databases. Randomized controlled trials and observational studies of adult patients will be eligible for inclusion if they report gender-specific data on the provision of one or more guideline-based post-arrest interventions in OHCA patients who survived to hospital admission. Two independent reviewers will perform both the title and abstract and full-text screening along with data abstraction for the selected studies. Study quality will be assessed using a modified Cochrane Risk of Bias tool for RCTs or the ROBINS-I tool for observational studies. The strength of evidence for each included study will be assessed using a modified Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. DISCUSSION: To our knowledge, this systematic review will be the first to address the association between patient gender and the provision of post-arrest care. The findings from this systematic review will provide valuable insight to gender disparities in the provision of post-arrest care. This systematic review was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This protocol observes the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012003096.

Antiviral treatment for treatment-naïve chronic hepatitis B: systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Chronic hepatitis B (CHB) infection poses a significant burden to public health worldwide. Most cases are clinically silent until late in the disease course. The main goal of current therapy is to improve survival and quality of life by preventing disease progression to cirrhosis and liver failure, and consequently hepatocellular carcinoma development. The objective of this review is to provide a contemporary and comprehensive evaluation of the effectiveness of treatment options. METHODS: We performed a systematic review of peer-reviewed literature for randomized controlled trials involving treatment-naïve CHB adult population who received antiviral therapy. The endpoints were virologic response (VR), normalization of alanine aminotransferase (ALT norm), HBeAg loss, HBeAg seroconversion, and HBsAg loss for the HBeAg-positive population; and VR and ALT norm for the HBeAg-negative population. Network meta-analysis (NMA) was performed to synthesize evidence on the efficacy of treatment. RESULTS: Forty-two publications were selected. Twenty-three evaluated HBeAg-positive population, 13 evaluated HBeAg-negative population, and six evaluated both. We applied NMA to the efficacy outcomes of the two populations separately. Treatment strategies were ranked by the probability of achieving outcomes, and pairwise comparisons calculated from NMA were reported in odds ratios (OR). For HBeAg-positive population, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) were the best for VR; OR vs adefovir = 14.29, 95% CI 7.69-25 and 12.5, 95% CI 4.35-33.33 respectively. TAF was the best for achieving ALT norm (OR vs placebo = 12.5, 95% CI 4.55-33.33), HBeAg loss, and seroconversion (OR vs entecavir/TDF combination = 3.03, 95% CI 1.04-8.84 and 3.33, 95% CI 1.16-10 respectively). In the HBeAg-negative population, TDF and TAF were the best for VR (OR vs adefovir = 9.79, 95% CI 2.38-42.7 and 11.71, 95% CI 1.03-150.48 respectively). Telbivudine and TAF were the best for ALT norm. Certain nucleos(t)ide combinations also had high probability of achieving positive outcomes. CONCLUSIONS: Our results are consonant with current clinical guidelines and other evidence reviews. For both HBeAg-positive and HBeAg-negative populations, TDF and TAF are the most effective agents for virologic suppression, and TAF is effective across all outcomes.

Comparative Effectiveness of the Core Components of Cardiac Rehabilitation on Mortality and Morbidity: A Systematic Review and Network Meta-Analysis.

A systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating the core components of cardiac rehabilitation (CR), nutritional counseling (NC), risk factor modification (RFM), psychosocial management (PM), patient education (PE), and exercise training (ET)) was undertaken. Published RCTs were identified from database inception dates to April 2017, and risk of bias assessed using Cochrane's tool. Endpoints included mortality (all-cause and cardiovascular (CV)) and morbidity (fatal and non-fatal myocardial infarction (MI), coronary artery bypass surgery (CABG), percutaneous coronary intervention (PCI), and hospitalization (all-cause and CV)). Meta-regression models decomposed treatment effects into the main effects of core components, and two-way or all-way interactions between them. Ultimately, 148 RCTs (50,965 participants) were included. Main effects models were best fitting for mortality (e.g., for all-cause, specifically PM (hazard ratio HR = 0.68, 95% credible interval CrI = 0.54⁻0.85) and ET (HR = 0.75, 95% CrI = 0.60⁻0.92) components effective), MI (e.g., for all-cause, specifically PM (hazard ratio HR = 0.76, 95% credible interval CrI = 0.57⁻0.99), ET (HR = 0.75, 95% CrI = 0.56⁻0.99) and PE (HR = 0.68, 95% CrI = 0.47⁻0.99) components effective) and hospitalization (e.g., all-cause, PM (HR = 0.76, 95% CrI = 0.58⁻0.96) effective). For revascularization (including CABG and PCI individually), the full interaction model was best-fitting. Given that each component, individual or in combination, was associated with mortality and/or morbidity, recommendations for comprehensive CR are warranted.

Systematic review and network meta-analysis of stroke prevention treatments in patients with atrial fibrillation.

BACKGROUND: In the last 4 years, four novel oral anticoagulants have been developed as alternatives to warfarin and antiplatelet agents for stroke prevention in atrial fibrillation (AF) patients. The objective of this review was to estimate the comparative effectiveness of all antithrombotic treatments for AF patients. MATERIALS AND METHODS: Data sources were Medline Ovid (1946 to October 2015), Embase Ovid (1980 to October 2015), and the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 9, 2015). Randomized controlled trials of AF patients were selected if they compared at least two of the following: placebo, aspirin, aspirin and clopidogrel combination therapy, adjusted-dose warfarin (target international normalized ratio 2.0-3.0), dabigatran, rivaroxaban, apixaban, and edoxaban. Bayesian network meta-analyses were conducted for outcomes of interest (all stroke, ischemic stroke, myocardial infarction, overall mortality, major bleeding, and intracranial hemorrhage). RESULTS: Based on 16 randomized controlled trials of 96,826 patients, all oral anticoagulants were more effective than antiplatelet agents at reducing the risk of ischemic stroke and all strokes. Compared to warfarin, dabigatran 150 mg (rate ratio 0.65, 95% credible interval 0.52-0.82) and apixaban (rate ratio 0.82, 95% credible interval 0.69-0.97) reduced the risk of all strokes. Dabigatran 150 mg was also more effective than warfarin at reducing ischemic stroke risk (rate ratio 0.76, 95% credible interval 0.59-0.99). Aspirin, apixaban, dabigatran 110 mg, and edoxaban were associated with less major bleeding than warfarin. CONCLUSION: All oral anticoagulants reduce the risk of stroke in AF patients. Some novel oral anticoagulants are associated with a lower stroke and/or major bleeding risk than warfarin. In addition to the safety and effectiveness of drug therapy, as reported in this study, individual treatment recommendations should also consider the patient's underlying stroke and bleeding risk profile.

Disparities in a provision of in-hospital post-arrest interventions for out-of-hospital cardiac arrest (OHCA) in the elderly population-protocol for a systematic review.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a significant cause of death in developed countries. The majority of OHCA patients are elderly (≥65 years), and it was documented that they were less likely than younger patients to receive the evidence-based interventions, even though the improvement in survival in the elderly age group was higher than in younger population. Our goal is to investigate any disparity in the provision of post-arrest care for the elderly with OHCA and a sustained return of spontaneous circulation (ROSC). METHODS/DESIGN: Eight relevant, electronic databases will be systematically searched to identify eligible studies. The searches will be supplemented with gray literature searching of theses, dissertations, and hand searching of pertinent journals. Two independent reviewers will screen the titles and abstracts and select studies for full text analysis using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) method, and both will extract information from the selected studies employing a form based on the Data Extraction Template for Cochrane Reviews. A team of three reviewers will assess the quality of the studies with the modified Downs and Black scale. Statistical methods for evidence synthesis, such as meta-analysis and meta-regression, will be applied to compare and combine the evidence regarding the association between age and intervention provision/utilization, adjusting for a number of significant confounders, such as patient characteristics and co-morbidities and availability of intervention techniques, as well as study specific characteristics. The strength of evidence from the selected studies will be assessed using a modified Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. DISCUSSION: The findings obtained from this systematic review should inform whether disparity exists in the provision of post-arrest care for the elderly (≥ 65 years old) with OHCA or not. Addressing this problem has a potential to substantially increase the number of > 65-year-old, long-term survivors. The results of our review might also point to the gaps in the published literature that specifically examines disparity in provision of care for this population. This systematic review was designed in accordance with the Preferred Reporting Guidelines for Systematic reviews and Meta-analyses (PRISMA statement), while the protocol follows the Preferred Reporting items for Systematic review and Meta-analysis protocols (PRISMA-P) statement. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015027822.