7 research outputs found
Novel biomarkers for potential risk stratification of drug induced liver injury (DILI): A narrative perspective on current trends
No full textBackground:Drug induced liver injury (DILI) is an increasing cause of acute liver injury especially with increasing need for pharmacotherapy of widening comorbidities amongst our ever-aging population. Uncertainty however remains regarding both acceptable and widely agreeable diagnostic algorithms as well a clear understanding of mechanistic insights that most accurately underpins it. In this review, we have explored the potential role of emerging novel markers of DILI and how they could possibly be integrated into clinical care of patients.Methods:We explored PUBMED and all other relevant databases for scientific studies that explored potential utility of novel biomarkers of DILI, and subsequently carried out a narrative synthesis of this data. As this is a narrative review with no recourse to patient identifiable information, no ethics committee's approval was sought or required.Results:Novel biomarkers such as microRNA-122 (miR-122) profiles, high mobility group box-1 (HMGB1), glutamate dehydrogenase (GLDH), and cytokeratin-18 (K-18), amongst others do have the potential for reducing diagnostic uncertainties associated with DILI.Conclusion:With the increasing validation of some of the novel liver biomarkers such as K-18, mir-122, HMGB-1, and GLDH, there is the potential for improvement in the diagnostic uncertainty commonly associated with cases of DILI. Copyright - 2019 the Author(s). Published by Wolters Kluwer Health, Inc.Scopu
Community engagement and chronic viral hepatitis public health interventions: a systematic review, meta-analysis, and complementary crowdsourcing open call.
No full textBACKGROUND: Chronic viral hepatitis causes a high burden of morbidity and mortality, especially in low- and middle-income countries (LMICs). While community engagement, which involves stakeholders in addressing health-related issues, has shown promise to enhance hepatitis outcomes, evidence on its impact remains limited. To summarize the current state of knowledge on this topic we performed a systematic review and a crowdsourcing open call. METHODS: A parallel mixed-methods approach was used in this study. The systematic review included publications that evaluated a community-engaged intervention, reported chronic viral hepatitis outcomes, included a comparator group, and were published in English up to 12 March 2025. A random-effects model was used to pool the overall effect of the community-engaged interventions on hepatitis outcomes. To ensure innovative ideas from LMICs were included, we organized a complementary crowdsourcing open call using the WHO/TDR practical guide. Thematic analysis identified key themes in the crowdsourced submissions. FINDINGS: 35 studies were included in the systematic review, and 28 crowdsourced submissions were analyzed. In both the systematic review and open call, community-engaged interventions included peer-based interventions, community health workers, interactive educational programs, and patient advocacy. The meta-analysis, predominantly of studies from high-income countries, found community-engaged interventions significantly improved HBV vaccine completion (RR 1.59, 95% CI 1.15-2.19; I 2 = 88.10%), HBV/HCV test uptake (RR 2.33, 95% CI 1.78-3.06; I 2 = 99.10%), HBV and HCV linkage to chronic viral hepatitis care (RR 1.96, 95% CI 1.46-2.64; I 2 = 96.20%), HBV/HCV treatment adherence (RR 1.14, 95% CI 1.03-1.27; I 2 = 0%), and HCV sustained virologic response (RR 1.50, 95% CI 1.23-1.83; I 2 = 93.90%). Open call submissions, largely from LMICs, highlighted community-led interventions where patients led community-based organizations to advocate for improved access to hepatitis care. INTERPRETATION: Findings underscored the importance of community engagement in chronic viral hepatitis service delivery across the care continuum. Implementing community-engaged interventions can enhance chronic viral hepatitis elimination efforts. FUNDING: National Natural Science Foundation of China
A New Form of Authoritarianism? Rethinking Military Politics in Post-1999 Nigeria
No full textDespite the vast research that has been done on the Nigerian military, virtually all of these studies have failed to critically examine the accepted role of the military in the democratising phase. This is important because the relationship between the political elite and the military in post-military authoritarian states guarantees either democratic consolidation, or its reversal. In Nigeria, despite an appearance of significant progress in subordinating the military institution to democratic civilian authority, the military remains a crucial political actor in the polity. It appears that the military has yet to accept the core democratic principles of civilian oversight of the institution. This thesis, therefore, explores whether a new form of military authoritarianism is emerging in Nigeria, with the aim of understanding Nigeria’s military behaviour in a transitional phase, from prolonged military authoritarianism to democratisation. To examine this military behaviour, Alfred Stepan’s concept of military prerogatives that was used to understand the military’s behaviour in a transitional phase in Latin America is applied to Nigeria.
A crucial understanding of authoritarianism in Nigeria is initially discussed in this study using mainly document analysis strategy to examine whether multi-ethnic states, such as Nigeria, tend to have authoritarian systems. Six hypotheses form the core analysis of this thesis: first, that the military has retained significant military prerogatives; second, that retired military officers are gaining influential political and economic positions; third, autonomous military involvement in human rights abuses since 1999; and fourth, that civilian government oversight remains weak, and facilitates military authoritarianism. These hypotheses are primarily analysed using the elite interview technique. During the first half of 2011, the author conducted field research where serving and retired military officers were interviewed. The fifth hypothesis is that the military has intervened in politics post-1999. The examination of this hypothesis relies primarily on key security-related media reports (mostly newspaper editorials) on the military after 1999. The examination of the final hypothesis, that increases in military expenditures might facilitate a new form of military authoritarianism, relies primarily on descriptive statistical analysis. In addition, this study collated relevant historical materials that relate to the military, utilising national archival collections.
The empirical findings of this research did not identify a new form of military authoritarianism in Nigeria. The study, however, argues that the unrestricted institutional framework accorded the military has contributed significantly to authoritarian practices in the post-military era in Nigeria. This study discovered that there were similarities between the Brazilian and Nigerian militaries in regard to their military spending during their period in power. Both countries had lower defence budgets. Just as in Brazil, it appears that part of the reason the Nigerian military decided to relinquish power in 1999 had to do with its desire to gain a higher budget, something that was precluded in a military government struggling to retain a sense of legitimacy. The military needed a higher budget to modernise and re-professionalise its institution after more than a decade in power. This feature, which the Nigerian military shares with the Brazilian military, appears to justify the application to Nigeria of Alfred Stepan’s concept of military prerogatives.
Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions
No full text© 2020, The Author(s). The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975)
Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study
No full textBackground: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. Methods: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. Findings: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4–4·6), corresponding to 291 992 000 (251 513 000–341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6–2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2–1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. Interpretation: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets. Funding: John C Martin Foundation
Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016 : a modelling study
No full textAbstract: Background The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment. Methods In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden. Findings We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3.9% (95% uncertainty interval [UI] 3.4-4.6), corresponding to 291 992 000 (251 513 000-341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4.8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1.8 (1.6-2.2) million infections were in children aged 5 years, with a prevalence of 1.4% (1.2-1.6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission. Interpretation Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets. Funding John C Martin Foundation. Copyright (c) 2018 Elsevier Ltd. All rights reserved
