Substantial hepatic necrosis is prognostic in fulminant liver failure

AIM: To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival. METHODS: Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited substantial necrosis, were identified and included in the study. The histological and clinical data was then analyzed in order to assess the relationship between the extent of necrosis and patient survival, with and without liver transplantation. The patients were grouped based on the etiology of hepatic necrosis. Each of the etiology groups were then further stratified according to whether or not they had received a liver transplant post-index biopsy, and whether or not the patient survived. RESULTS: The core tissue length ranged from 5 to 44 mm with an average of 23 mm. Causes of necrosis included 14 autoimmune hepatitis, 10 drug induced liver injury (DILI), 9 hepatitis virus infection, and 4 unknown origin. Among them, 11 showed submassive (26%-75% of the parenchymal volume) and 26 massive (76%-100%) necrosis. Transplant-free survival was worse in patients with a higher extent of necrosis (40%, 71.4% and 100% in groups with necrosis of 76%-100%, 51%-75% and 26%-50%, respectively). Additionally, transplant-free survival rates were 66.7%, 57.1%, and 25.0% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively. Even after liver transplantation, the survival rate in patients as a result of viral hepatitis remained the lowest (80%, 100%, and 40% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively). CONCLUSION: Adequate liver biopsy with more than 75% necrosis is associated with significant transplant-free mortality that is critical in predicting survival

Trusting the results of model-based economic analyses: Is there a pragmatic validation solution?

Models have become a nearly essential component of health technology assessment. This is because the efficacy and safety data available from clinical trials are insufficient to provide the required estimates of impact of new interventions over long periods of time and for other populations and subgroups. Despite more than five decades of use of these decision-analytic models, decision makers are still often presented with poorly validated models and thus trust in their results is impaired. Among the reasons for this vexing situation are the artificial nature of the models, impairing their validation against observable data, the complexity in their formulation and implementation, the lack of data against which to validate the model results, and the challenges of short timelines and insufficient resources. This article addresses this crucial problem of achieving models that produce results that can be trusted and the resulting requirements for validation and transparency, areas where our field is currently deficient. Based on their differing perspectives and experiences, the authors characterize the situation and outline the requirements for improvement and pragmatic solutions to the problem of inadequate validation

Rheumatoid arthritis treated with 6-months of first-line biologic or biosimilar therapy: an updated systematic review and network meta-analysis.

OBJECTIVES: The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses. METHODS: Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical. RESULTS: Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs. CONCLUSIONS: In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD

Immunogenicity of Fractional Doses of Tetravalent A/C/Y/W135 Meningococcal Polysaccharide Vaccine: Results from a Randomized Non-Inferiority Controlled Trial in Uganda

Meningitis are infections of the lining of the brain and spinal cord and can cause high fever, blood poisoning, and brain damage, as well as result in death in up to 10% of cases. Epidemics of meningitis occur almost every year in parts of sub-Saharan Africa, throughout a high-burden area spanning Senegal to Ethiopia dubbed the “Meningitis Belt.” Most epidemics in Africa are caused by Neisseria meningitidis (mostly serogroup A and W135). Mass vaccination campaigns attempt to control epidemics by administering meningococcal vaccines targeted against these serogroups, among others. However, global shortages of these vaccines are currently seen. We studied the use of fractional (1/5 and 1/10) doses of a licensed vaccine to assess its non-inferiority compared with the normal full dose. In a randomized trial in Uganda, we found that immune response and safety using a 1/5 dose were comparable to full dose for three serogroups (A, Y, W135), though not a fourth (C). In light of current shortages of meningococcal vaccines and their importance in fighting meningitis epidemics around the world, we suggest fractional doses be taken under consideration in mass vaccination campaigns

The French National Authority for Health (HAS) Guidelines for Conducting Budget Impact Analyses (BIA)

International audienceBackgroundBudget impact analysis (BIA) provides short- and medium-term estimates on changes in budgets and health outcomes resulting from the adoption of new health interventions.ObjectiveThe purpose of this study is to present the newly developed French National Authority for Health (HAS) guidelines on budget impact analysis as follows: process, literature review, recommendations and comparisons with other guidelines.MethodsThe development process of the HAS guidelines included a literature review (search dates: January 2000 to June 2016), a retrospective investigation of BIA previously submitted to HAS, a public consultation, international expert reviews and approval from the HAS Board and the Economic and Public Health Evaluation Committee of HAS.ResultsDocuments identified in the literature review included 12 national guidelines, 5 recommendations for good practices developed by national and international society of health economics and 14 methodological publications including recommendations for conducting BIA. Based on its research findings, HAS developed its first BIA guidelines, which include recommendations on the following topics: BIA definition, perspective, populations, time horizon, compared scenarios, budget impact models, costing, discounting, choice of clinical data, reporting of results and uncertainty exploration.ConclusionIt is expected that the HAS BIA guidelines will enhance the usefulness, quality and transparency of BIA submitted by drug manufacturers to HAS. BIA is becoming an essential part of a comprehensive economic assessment of healthcare interventions in France, which also includes cost-effectiveness analysis and equity of access to healthcare