The importance of baseline viral load when assessing relative efficacy in treatment-naïve HBeAg-positive chronic hepatitis B: a systematic review and network meta-analysis.

BACKGROUND: To date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B (CHB). We undertook baseline-adjusted and unadjusted analyses using the same data to explore the impact of baseline viral load (BVL) on CHB treatment response. METHODS: We searched Embase, Medline, Medline in Process and the Cochrane CENTRAL databases for randomised clinical trials (RCTs) of monotherapy interventions at licensed doses for use in CHB. Search strategies comprised CHB disease and drug terms (a combination of controlled vocabulary and free text terms) and also a bespoke RCT filter.The NMA was undertaken in WinBUGs using fixed and random effects methods, using data obtained from a systematic review. Individual patient data (IPD) from an entecavir clinical trial were used to quantify the impact of different baseline characteristics (in particular undetectable viral load (UVL) at 1 year) on relative treatment effect. Study level mean baseline values from all identified studies were used. Results were generated for UVL and presented as relative risks (RRs) and 95% credible intervals (CrIs) using entecavir as reference treatment. RESULTS: Overall, for all eight relevant interventions we identified 3,000 abstracts. Following full text review a total of 35 (including the contents of six clinical study reports) met the inclusion critera; 19 were in hepatitis B e antigen (HBeAg)-positive patients and 14 of the 19 contained outcome information of relevance to the NMA.Entecavir and tenofovir studies had heterogeneous patient populations in terms of BVL (mean values 9.29 and 8.65 log10 copies/ml respectively). After adjusting UVL for BVL using an informative prior based on the IPD analysis, the difference between entecavir and tenofovir was not statistically significant (RR 1.27, 95% CrI 0.96 to 1.47-fixed effects). A similar conclusion was found in all sensitivity analyses. Adjusted tenofovir results were more consistent with observed clinical trial response rates. CONCLUSIONS: This study demonstrates the importance of adjusting for BVL when assessing the relative efficacy of CHB interventions in achieving UVL. This has implications for both clinical and economic decision making

A comparison of four fibrosis indexes in chronic HCV: Development of new fibrosis-cirrhosis index (FCI)

<p>Abstract</p> <p>Background</p> <p>Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers.</p> <p>Methods</p> <p>We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)].</p> <p>Results</p> <p>Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%.</p> <p>Conclusions</p> <p>The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.</p

Solving the Urban Transit Routing Problem Using a Cat Swarm Optimization-Based Algorithm

Presented in this research paper is an attempt to apply a cat swarm optimization (CSO)-based algorithm to the urban transit routing problem (UTRP). Using the proposed algorithm, we can attain feasible and efficient (near) optimal route sets for public transportation networks. It is, to our knowledge, the first time that cat swarm optimization (CSO)-based algorithm is applied to cope with this specific problem. The algorithm’s efficiency and excellent performance are demonstrated by conducting experiments with both real-world as well as artificial data. These specific data have also been used as test instances by other researchers in their publications. Computational results reveal that the proposed cat swarm optimization (CSO)-based algorithm exhibits better performance, using the same evaluation criteria, compared to most of the other existing approaches applied to the same test instances. The differences of the proposed algorithm in comparison with other published approaches lie in its main process, which is a modification of the classic cat swarm optimization (CSO) algorithm applied to solve the urban transit routing problem. This modification in addition to a variation of the initialization process, as well as the enrichment of the algorithm with a process of improving the final solution, constitute the innovations of this contribution. The UTRP is studied from both passenger and provider sides of interest, and the algorithm is applied in both cases according to necessary modifications

A Comparative Study of Modern Heuristics on the School Timetabling Problem

In this contribution a comparative study of modern heuristics on the school timetabling problem is presented. More precisely, we investigate the application of two population-based algorithms, namely a Particle Swarm Optimization (PSO) and an Artificial Fish Swarm (AFS), on the high school timetabling problem. In order to demonstrate their efficiency and performance, experiments with real-world input data have been performed. Both algorithms proposed manage to create feasible and efficient high school timetables, thus fulfilling adequately the timetabling needs of the respective high schools. Computational results demonstrate that both algorithms manage to reach efficient solutions, most of the times better than existing approaches applied to the same school timetabling input instances using the same evaluation criteria

A Generic Two-Phase Stochastic Variable Neighborhood Approach for Effectively Solving the Nurse Rostering Problem

algorithm

The effect of antioxidant supplementation on bacterial translocation after intestinal ischemia and reperfusion

The intestine is highly sensitive to ischemia/reperfusion (I/R) injury. Intestinal I/R may cause local tissue injury and disruption of the intestinal mucosal barrier, allowing the passage of viable bacteria and endotoxins from the gastrointestinal lumen to distant organs. This phenomenon, known as bacterial translocation (BT), may lead to systemic disorders with high morbidity and mortality. Oxidative stress mediators such as reactive oxygen species, polymorphonuclear neutrophils and nitric oxide are believed to contribute to the intestinal I/R injury. Many antioxidants have shown protective effects against I/R injury of various organs. The present article provides an overview of studies investigating the effect of antioxidant supplementation on BT after intestinal I/R. © 2016 Informa UK Limited, trading as Taylor &amp; Francis Group