Innovative strategies for the elimination of viral hepatitis at a national level: a country case series

Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the enigma-anxiety working group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology

A global investment framework for the elimination of hepatitis B

Background &amp; Aims: More than 292 million people are living with hepatitis B worldwide and are at risk of death from cirrhosis and liver cancer. The World Health Organization (WHO) has set global targets for the elimination of viral hepatitis as a public health threat by 2030. However, current levels of global investment in viral hepatitis elimination programmes are insufficient to achieve these goals.Methods: To catalyse political commitment and to encourage domestic and international financing, we used published modelling data and key stakeholder interviews to develop an investment framework to demonstrate the return on investment for viral hepatitis elimination.Results: The framework utilises a public health approach to identify evidence-based national activities that reduce viral hepatitis-related morbidity and mortality, as well as international activities and critical enablers that allow countries to achieve maximum impact on health outcomes from their investments - in the context of the WHO's 2030 viral elimination targets.Conclusion: Focusing on hepatitis B, this health policy paper employs the investment framework to estimate the substantial economic benefits of investing in the elimination of hepatitis B and demonstrates how such investments could be cost saving by 2030.Lay summary: Hepatitis B infection is a major cause of death from liver disease and liver cancer globally. To reduce deaths from hepatitis B infection, we need more people to be tested and treated for hepatitis B. In this paper, we outline a framework of activities to reduce hepatitis B-related deaths and discuss ways in which governments could pay for them. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</p

A global investment framework for the elimination of hepatitis B

BACKGROUND & AIMS: More than 292 million people are living with hepatitis B worldwide and are at risk of death from cirrhosis and liver cancer. The World Health Organization (WHO) has set global targets for the elimination of viral hepatitis as a public health threat by 2030. However, current levels of global investment in viral hepatitis elimination programmes are insufficient to achieve these goals. METHODS: To catalyse political commitment and to encourage domestic and international financing, we used published modelling data and key stakeholder interviews to develop an investment framework to demonstrate the return on investment for viral hepatitis elimination. RESULTS: The framework utilises a public health approach to identify evidence-based national activities that reduce viral hepatitis-related morbidity and mortality, as well as international activities and critical enablers that allow countries to achieve maximum impact on health outcomes from their investments - in the context of the WHO's 2030 viral elimination targets. CONCLUSION: Focusing on hepatitis B, this health policy paper employs the investment framework to estimate the substantial economic benefits of investing in the elimination of hepatitis B and demonstrates how such investments could be cost saving by 2030. LAY SUMMARY: Hepatitis B infection is a major cause of death from liver disease and liver cancer globally. To reduce deaths from hepatitis B infection, we need more people to be tested and treated for hepatitis B. In this paper, we outline a framework of activities to reduce hepatitis B-related deaths and discuss ways in which governments could pay for them

Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells

Despite a wealth of information about the structure of surface membrane immunoglobulin (smIg) on chronic lymphocytic leukemia (CLL) cells, little is known about epitopes reacting with their binding sites. Probing phage-displayed peptide libraries, we identified and characterized mimetopes for Igs of 4 patients with IGHV mutated CLL (M-CLL) and 4 with IGHV unmutated CLL (U-CLL). Six of these mAbs were representatives of stereotyped B-cell receptors characteristic of CLL. We found that mimetic epitopes for U- and M-CLL Igs differed significantly. M-CLL–derived peptides exhibited better amino acid motifs, were more similar to each other, aligned more easily, and formed tighter clusters than U-CLL–derived peptides. Mono-, oligo-, and polyreactivity of peptides correlated with structural changes within antigen-binding sites of selecting M-CLL mAbs. Although M-CLL–isolated peptides and certain U-CLL mAbs bound more effectively to the selecting mAb, others were not as specific, reacting with M-CLL and U-CLL mAbs; these data suggest that in vivo structurally diverse epitopes could bind smIgs of distinct CLL clones, thereby altering survival and growth. Finally, an M-CLL–derived peptide inhibited, in a dose-dependent manner, binding of its homologous mAb to human B lymphocytes; therefore peptides that inhibit or alter the consequences of antigen-smIg interactions may represent therapeutic modalities in CLL

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes

Understanding patterns of etiologic commonality and heterogeneity for non-Hodgkin lymphomas may illuminate lymphomagenesis. We present the first systematic comparison of risks by lymphoma subtype for a broad range of putative risk factors in a population-based case-control study, including diffuse large B-cell (DLBCL; N = 416), follicular (N = 318), and marginal zone lymphomas (N = 106), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; N = 133). We required at least 2 of 3 analyses to support differences in risk: (1) polytomous logistic regression, (2) homogeneity tests, or (3) dichotomous logistic regression, analyzing all 7 possible pairwise comparisons among the subtypes, corresponding to various groupings by clinical behavior, genetic features, and differentiation. Late birth order and high body mass index (≥ 35) kg/m2) increased risk for DLBCL alone. Autoimmune conditions increased risk for marginal zone lymphoma alone. The tumor necrosis factor G-308A polymorphism (rs1800629) increased risks for both DLBCL and marginal zone lymphoma. Exposure to certain dietary heterocyclic amines from meat consumption increased risk for CLL/SLL alone. We observed no significant risk factors for follicular lymphoma alone. These data clearly support both etiologic commonality and heterogeneity for lymphoma subtypes, suggesting that immune dysfunction is of greater etiologic importance for DLBCL and marginal zone lymphoma than for CLL/SLL and follicular lymphoma