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.

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BackgroundIn 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 methodsData 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).ResultsBased 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.ConclusionAll 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.

ObjectivesMathematical 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.DesignA 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.OutcomesStage-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.ResultsThe 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.ConclusionsThis 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.

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: 10.074, 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.

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.

Chronic hepatitis C (CHC) is a leading cause of hepatic fibrosis and cirrhosis. The level of fibrosis is traditionally established by histology, and prognosis is estimated using fibrosis progression rates (FPRs; annual probability of progressing across histological stages). However, newer noninvasive alternatives are quickly replacing biopsy. One alternative, transient elastography (TE), quantifies fibrosis by measuring liver stiffness (LSM). Given these developments, the purpose of this study was (i) to estimate prognosis in treatment-naïve CHC patients using TE-based liver stiffness progression rates (LSPR) as an alternative to FPRs and (ii) to compare consistency between LSPRs and FPRs. A systematic literature search was performed using multiple databases (January 1990 to February 2016). LSPRs were calculated using either a direct method (given the difference in serial LSMs and time elapsed) or an indirect method given a single LSM and the estimated duration of infection and pooled using random-effects meta-analyses. For validation purposes, FPRs were also estimated. Heterogeneity was explored by random-effects meta-regression. Twenty-seven studies reporting on 39 groups of patients (N = 5874) were identified with 35 groups allowing for indirect and 8 for direct estimation of LSPR. The majority (~58%) of patients were HIV/HCV-coinfected. The estimated time-to-cirrhosis based on TE vs biopsy was 39 and 38 years, respectively. In univariate meta-regressions, male sex and HIV were positively and age at assessment, negatively associated with LSPRs. Noninvasive prognosis of HCV is consistent with FPRs in predicting time-to-cirrhosis, but more longitudinal studies of liver stiffness are needed to obtain refined estimates.

Over seventy million people worldwide suffer from chronic hepatitis C (CHC), which can lead to liver failure and hepatocellular carcinoma (HCC). 1 Worldwide, an estimated 400,000 deaths per year can be attributed to liver disease caused by hepatitis C virus (HCV). 1 Until recently, interferon (IF)-based drug regimens were the mainstay of treatment for HCV. 2 However, most of these drugs caused side effects, required up to 48 weeks of therapy and had relatively low sustained virologic response (SVR) rates, a welldocumented surrogate indicator for HCV cure. 2 The introduction of direct-acting antivirals (DAAs) in 2011 revolutionized treatment for HCV. DAAs quickly became the recommended first-line treatment