Wang, Zhen

619 Background: Regorafenib (at a starting dose of 160 mg/day, rego 160), regorafenib (with a weekly dose escalation, rego 80+) and TAS-102, are suggested treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these 3 strategies. Methods: We searched PubMed, Embase, and Cochrane CENTRAL, for randomized controlled trials evaluating TAS 102 or regorafenib in refractory mCRC patients who progressed on/intolerant of previous oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included OS and PFS. The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White’s multivariate meta-regression to pool evidence from direct and indirect comparisons. Results: Six trials (3 of regorafenib and 3 of TAS-102) at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS-102 as monotherapy were superior to BSC in terms of PFS (Rego 160: HR = 0.4, CI 0.26 to 0.63; TAS-102: HR = 0.46, CI 0.40 to 0.52) and OS (Rego 160: HR = 0.67, CI 0.48 to 0.93; TAS-102: HR = 0.67, CI 0.57 to 0.80). Network analysis showed that there was no difference in PFS or OS between Rego 160 and TAS-102. Rego 80+ was superior to BSC in terms of OS (HR = 0.44, CI 0.23 to 0.84) and PFS (HR = 0.37, CI 0.21 to 0.66). There was a numerical advantage for Rego 80+ compared to TAS-102 and Rego 160 (see table). Conclusions: Regorafenib 160 and TAS-102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102. [Table: see text]

Objective To assess gender disparity in outcomes among hospitalised patients with acute myocardial infarction (AMI), acute decompensated heart failure (ADHF) or pneumonia. Design A retrospective cohort study. Setting A tertiary referral centre in Midwest, USA. Participants We evaluated 12 265 adult patients hospitalised with ADHF, 15 777 with AMI and 12 929 with pneumonia, from 1 January 1995 through 31 August 2015. Patients were selected using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary and secondary outcome measures Prevalence of comorbidities, 30-day mortality and 30-day readmission. Comorbidities were chosen from the 20 chronic conditions, specified by the Office of the Assistant Secretary for Health. Logistic regression analysis was conducted adjusting for multiple confounders. Results Prevalence of comorbidities was significantly different between men and women in all three conditions. After adjusting for age, length of stay, multicomorbidities and residence, there was no significant difference in 30-day mortality between men and women in AMI or ADHF, but men with pneumonia had slightly higher 30-day mortality with an OR of 1.19 (95% CI 1.06 to 1.34). There was no significant difference in 30-day readmission between men and women with AMI or pneumonia, but women with ADHF were slightly more likely to be readmitted within 30 days with OR 0.90 (95% CI 0.82 to 0.99). Conclusion Gender differences in the distribution of comorbidities exist in patients hospitalised with AMI, ADHF and pneumonia. However, there is minimal clinically meaningful impact of these differences on outcomes. Efforts to address gender difference may need to be diverted towards targeting overall population health, reducing race/ethnicity disparity and improving access to care.

Objective There exists a paucity of work in the development and testing of theoretical models specific to childhood health disparities even though they have been linked to the prevalence of adult health disparities including high rates of chronic disease. We conducted a systematic review and thematic analysis of existing models of health disparities specific to children to inform development of a unified conceptual framework. Methods We systematically reviewed articles reporting theoretical or explanatory models of disparities on a range of outcomes related to child health. We searched Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus (database inception to 9 July 2015). A metanarrative approach guided the analysis process. Results A total of 48 studies presenting 48 models were included. This systematic review found multiple models but no consensus on one approach. However, we did discover a fair amount of overlap, such that the 48 models reviewed converged into the unified conceptual framework. The majority of models included factors in three domains: individual characteristics and behaviours (88%), healthcare providers and systems (63%), and environment/community (56%), . Only 38% of models included factors in the health and public policies domain. Conclusions A disease-agnostic unified conceptual framework may inform integration of existing knowledge of child health disparities and guide future research. This multilevel framework can focus attention among clinical, basic and social science research on the relationships between policy, social factors, health systems and the physical environment that impact children's health outcomes.

We aimed to develop tools that can facilitate uptake of evidence summarised in systematic reviews by clinical decision makers in health systems. After conducting a systematic review on the management of anxiety in children, we interviewed health system representatives, clinicians and patients to ask about additional information needed for decision-making. Using stakeholders’ feedback and literature searches for contextual and implementation information, we developed two tools (decision aids (DAs)), one for the health system and the second for the clinical encounter. This information mapped to factors of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) Evidence to Decision Framework. The health system DAs provided information on which patients are candidate for treatment, values and preferences, costs and resources, acceptability, impact on health equity, feasibility, drug dosing, alternative therapies, remission rates and prognosis. Health system stakeholders found the DA useful for clinical decision-making and generalisable to other conditions. The encounter DA was produced as cards containing information on issues that drive treatment decisions (effect on symptoms, effect on function, treatment burden, side effects and cost). Patients and parents prioritised the cards and chose the order in which these issues were discussed with clinician. The encounter DA was found to be helpful by patients, parents and clinicians. We conclude that the uptake of evidence summaries by health systems can be enhanced by developing tools that provide contextual and implementation information about clinical care. A dual approach addressing health system stakeholders as well as clinicians and patients is likely feasible and helpful.

AbstractMantle cell lymphoma is characterized by relapse and progressive disease, despite initial response to chemoimmunotherapy. We conducted a systematic review and meta‐analysis to determine the efficacy of rituximab maintenance (RM) therapy in patients with mantle cell lymphoma. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials from database inception through November 1, 2017. Only full‐text articles were included. Prespecified data elements were extracted from each trial. Outcomes of interest included progression‐free survival (PFS) and overall survival (OS). The overall effect was pooled using the Der Simonian‐Laird random effects model. Three randomized controlled trials and four observational studies met our inclusion criteria and were identified in the analyses. Six studies compared RM therapy to observation, and one compared RM therapy to interferon alfa. Meta‐analysis evaluating outcomes of patients treated after ASCT revealed that RM improved for both PFS (HR = 0.33, 95% CI = 0.23‐0.49) and OS (HR of death = 0.35, 95% CI = 0.17‐0.69). A second meta‐analysis of studies evaluating outcomes of patients who are ASCT‐ineligible treated with anthracycline‐based induction therapy revealed that RM improved PFS (HR = 0.38, 95% CI = 0.25‐0.58). There is a paucity of data on the role of RM in ASCT‐ineligible patients and those with relapsed disease. Overall, RM therapy appears to improve PFS and OS in previously untreated patients with mantle cell lymphoma who undergo induction chemoimmunotherapy followed by ASCT.

AbstractBackground & AimsAcute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4.MethodsTwo reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus‐RNA positive vs negative, and to discern important mortality risk factors.ResultsWe identified 65 patients, with median age 58 years (range: 3‐79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus‐RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA.ConclusionAcute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle‐aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis.

Publication bias occurs when studies with statistically significant results have increased likelihood of being published. Publication bias is commonly associated with inflated treatment effect which lowers the certainty of decision makers about the evidence. In this guide we propose that systematic reviewers and decision makers consider the direction and magnitude of publication bias, as opposed to just the binary determination of the presence of this bias, before lowering their certainty in the evidence. Direction of bias may not always exaggerate the treatment effect. The presence of bias with a trivial magnitude may not affect the decision at hand. Various statistical approaches are available to determine the direction and magnitude of publication bias.