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.

Describing the state of a research network: A mixed methods approach to network evaluation.

Diabetes Action Canada Strategy for Patient-Oriented Research (SPOR) Network in Chronic Disease was formed in 2016 and is funded primarily through the Canadian Institutes of Health Research (CIHR). We propose a novel mixed-methods approach to a network evaluation integrating the State of Network Evaluation framework and the Canadian Academy of Health Sciences (CAHS) preferred framework and indicators. We measure key network themes of connectivity, health and results, and impact and return on investment associated with health research networks. Our methods consist of a longitudinal cross-sectional network survey of members and social network analysis to examine Network Connectivity and assess the frequency of interactions, the topics discussed during them, and how networking effectively facilitates interactions and collaboration among members. Network Health will be evaluated through semistructured interviews, a membership survey inquiring about satisfaction and experience with the Network, and a review of documentary sources related to funding and infrastructure to evaluate Network Sustainability. Finally, we will examine Network Results and Impact using the CAHS preferred framework and indicators to measure returns on investment in health research across the five domains of the CAHS framework, which include: advancing knowledge, capacity building, informing decision making, health impact, and economic and social impact. Indicators will be assessed with various methods, including bibliometric analyses, review of relevant documentary sources (annual reports), member activities informing health and research policy, and Patient Partner involvement. The Network Evaluation will provide members and stakeholders with information for planning, improvements, and funding future Network endeavors.

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.

Understanding factors critical to the implementation of ehealth in chronic disease management: a realist review protocol.

INTRODUCTION: Canadians are living longer, many with multiple chronic conditions. This population of older, frail Canadians continues to grow in size as do concurrent demands for community-based, outpatient and ambulatory models of care. Ideally, a multifaceted, proactive, planned and integrated care model includes ehealth. Although several factors are known to facilitate the implementation of ehealth in chronic disease management (CDM), for example, adequate support, usability, alignment of programme objectives, there is a growing body of inconclusive evidence on what is critical for implementation. We aim to achieve a fulsome understanding of factors critical to implementation by conducting a realist review-an approach suitable for understanding complex interventions. Our proposed review will identify factors critical to the implementation of ehealth in CDM (heart failure, chronic obstructive pulmonary disease, chronic kidney disease and/or diabetes (type 1 or 2)) without limitations to care setting, language, publication year or geography. Findings will be presented in configurations of contexts, mechanisms and outcomes (CMOs). METHODS AND ANALYSIS: A search strategy will be iteratively developed based on the concepts of 'implementation' and 'adoption' of 'ehealth' interventions used within 'CDM' to identify the peer-reviewed and grey literature published before 31 March 2021 from five databases (Medline, Embase, Cochrane, CINAHL and PsychInfo) on ehealth interventions actively involving a healthcare provider for CDM among adults. Data extraction and synthesis will be guided by Realist and Meta-review Evidence Synthesis: Evolving Standards (RAMESES) guidelines informing core concepts of CMOs, and a study output will include a middle-range-theory describing the implementation of ehealth in CDM. ETHICS AND DISSEMINATION: Findings will be published in an open-access peer-reviewed journal and presented at relevant conferences. A multistakeholder (patients, caregivers, healthcare providers and practitioners, decision-makers and policy-makers) perspective will be used in our dissemination approach. No formal ethics approval is required for this review. PROSPERO REGISTRATION NUMBER: CRD42020208275.

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).

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).

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.

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.

The Effect of Cardiac Rehabilitation on Health-Related Quality of Life in Patients With Coronary Artery Disease: A Meta-analysis.

BACKGROUND: The clinical effectiveness of cardiac rehabilitation (CR) on health-related quality of life (HRQOL) is an area that has not been consistently explored. The objective of this systematic review was to evaluate the effectiveness of providing any core component of CR on HRQOL domains. METHODS: We performed a meta-analysis and meta-regression of randomized controlled trials (RCTs) on the core components of CR. RCTs included adult patients with diagnosed coronary artery disease via angiography, myocardial infarction, angina, or who had undergone coronary revascularization. The Cochrane Library, MEDLINE, EMBASE, CINAHL, SCI-EXPANDED, Psych INFO, and Web of Science were searched from inception to April 27, 2017. Outcomes included overall, physical, emotional, and social HRQOL. Outcomes were reported as standardized mean change (SMC) with 95% confidence intervals (CIs). Effect size changes of 0.2, 0.5, and 0.8 SD units reflect a small, moderate, and large effect, respectively. RESULTS: Forty-nine reports of 41 RCTs with 11,747 patients were included. Summary effect sizes were: overall HRQOL SMC, 0.28 (95% CI, 0.05-0.50), physical HRQOL SMC, 0.47 (95% CI, 0.13-0.81), emotional HRQOL SMC, 0.37 (95% CI, -0.02 to 0.77), and social HRQOL SMC, 0.13 (95% CI, -0.06 to 0.32). Meta-regression revealed type of CR intervention and year of publication as positive statistically significant treatment effect modifiers. CONCLUSIONS: Receiving CR was shown to improve HRQOL, with exercise-, nonexercise-, and psychological-based interventions playing a vital role. Although these improvements in HRQOL were modest they still reflect an incremental benefit compared with receiving usual care.

Comparative effectiveness of the different components of care provided in heart failure clinics-protocol for a systematic review and network meta-analysis.

BACKGROUND: Heart failure (HF) is a complex chronic condition, leading to frequent hospitalization, decreased quality of life, and increased mortality. Current guidelines recommend that multidisciplinary care be provided in specialized HF clinics. A number of studies have demonstrated the effectiveness of these clinics; however, there is a wide range in the services provided across different clinics. This network meta-analysis will aim to identify the aspects of HF clinic care that are associated with the best outcomes: a reduction in mortality, hospitalization, and visits to emergency department (ED) and improvements to quality of life. METHODS: Relevant electronic databases will be systematically searched to identify eligible studies. Controlled trials and observational cohort studies of adult (≥ 18 years of age) patients will be eligible for inclusion if they evaluate at least one component of guideline-based HF clinic care and report all-cause or HF-related mortality, hospitalizations, or ED visits or health-related quality of life assessed after a minimum follow-up of 30 days. Both controlled trials and observational studies will be included to allow us to compare the efficacy of the interventions in an ideal context versus their effectiveness in the real world. Two reviewers will independently perform both title and abstract full-text screenings and data abstraction. Study quality will be assessed through a modified Cochrane risk of bias tool for randomized controlled trials (RCTs) or the ROBINS-I tool for observational studies. The strength of evidence will be assessed using a modified Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. Network meta-analysis methods will be applied to synthesize the evidence across included studies. To contrast findings between study designs, data from RCTs will be analyzed separately from non-randomized controlled trials and cohort studies. We will estimate both the probability that a particular component of care is the most effective and treatment effects for specified combinations of care. DISCUSSION: To our knowledge, this will be the first study to evaluate the comparative effectiveness of the different components of care offered in HF clinics. The findings from this systematic review will provide valuable insight about which components of HF clinic care are associated with improved outcomes, potentially informing clinical guidelines as well as the design of future care interventions in dedicated HF clinics. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017058003.

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.

Diagnostic accuracy of level IV portable sleep monitors versus polysomnography for obstructive sleep apnea: a systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. In-laboratory, overnight type I polysomnography (PSG) is the current "gold standard" for diagnosing OSA. Home sleep apnea testing (HSAT) using portable monitors (PMs) is an alternative testing method offering better comfort and lower costs. We aimed to systematically review the evidence on diagnostic ability of type IV PMs compared to PSG in diagnosing OSA. METHODS: Participants: patients ≥16 years old with symptoms suggestive of OSA;intervention: type IV PMs (devices with < 2 respiratory channels); comparator: in-laboratory PSG; outcomes: diagnostic accuracy measures;studies: cross-sectional, prospective observational/experimental/quasi-experimental studies; information sources: MEDLINE and Cochrane Library from January 1, 2010 to May 10, 2016. All stages of review were conducted independently by two investigators. RESULTS: We screened 6054 abstracts and 117 full-text articles to select 24 full-text articles for final review. These 24 studies enrolled a total of 2068 patients with suspected OSA and evaluated 10 different PMs with one to six channels. Only seven (29%) studies tested PMs in the home setting. The mean difference (bias) between PSG-measured and PM-measured apnea-hypopnea index (AHI) ranged from - 14.8 to 10.6 events/h. At AHI ≥ 5 events/h, the sensitivity of type IV PMs ranged from 67.5-100% and specificity ranged from 25 to 100%. CONCLUSION: While current evidence is not very strong for the stand-alone use of level IV PMs in clinical practice, they can potentially widen access to diagnosis and treatment of OSA. Policy recommendations regarding HSAT use should also consider the health and broader social implications of false positive and false negative diagnoses.