69832 research outputs found
Sort by
Statistical analysis plan for the LAST ACT clinical trial; a Leukotriene A4 hydrolase Stratified non-inferiority Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis
Get PDF
Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Corticosteroids are currently recommended as an adjunctive therapy in HIV-negative adults with TBM. However, benefit from corticosteroids in TBM may depend upon host
leukotriene A4 hydrolase
(
LTA4H
) genotype and the corresponding inflammatory phenotypes. This article describes the planned analyses for the primary publication of the results of the LAST ACT clinical trial (NCT03100786): ‘Leukotriene A4 hydrolase Stratified Trial of Adjunctive Corticosteroids for HIV-negative adults with Tuberculous meningitis’. The primary hypothesis addressed by the trial is that
LTA4H
genotype, in particular CC or CT genotype, determines whether adjunctive dexamethasone benefits or harms adults with TBM. The trial was an
LTA4H
genotype stratified, parallel group, randomised, double blind, placebo-controlled multi-centre Phase III trial of dexamethasone given for 6–8 weeks in addition to standard anti-tuberculosis drugs.
LTA4H
genotype (CC, CT, TT) was determined in all participants prior to randomisation; only those with CC or CT genotype were randomised to dexamethasone or placebo. All TT genotype participants received dexamethasone because prior data indicated survival was increased by dexamethasone in this genotype. The primary endpoint was all-cause death or new neurological event over the first 12 months after randomisation. We took a hybrid trial-design approach which aims to prove non-inferiority of placebo first but also allows claiming superiority of placebo in case dexamethasone causes substantial harm. This statistical analysis plan expands upon and updates the analysis plan outlined in the published study protocol.
</ns3:p
Effectiveness of Carbon Dioxide Cryotherapy for the Treatment of Localized Cutaneous Leishmaniasis in Ethiopia
Get PDFABSTRACT
Background
Cutaneous leishmaniasis (CL) is a public health problem in Ethiopia. Diagnosis is often delayed, and treatment options are limited. Liquid nitrogen cryotherapy is a recommended treatment but not widely available. Carbon dioxide (CO2) cryotherapy is used for the prevention of cervical cancer and is widely available in Ethiopia and might be a suitable therapy for treating localized CL.
Objectives
The aim of this short report is to assess the effectiveness of carbon dioxide cryotherapy for the treatment of CL in CL treatment centre, Ethiopia.
Methods
We performed a prospective study assessing the effectiveness of CO2 cryotherapy for the treatment of localized CL between September 2022 and June 2023 at an established CL treatment centre.
Results
Seventeen individuals with 24 CL lesions were enrolled. Twelve (70.6%) were confirmed using a skin slit smear and five by histopathology (29.4%). Nine (52.9%) individuals received a single session of CO2 cryotherapy, five received two (29.4%) and three (17.65%) received three sessions of cryotherapy. At Day 90, 16 participants were assessed and 14 (82.4%) had healed.
Conclusions
CO2 cryotherapy shows promise as a potential treatment strategy for CL. Formal evaluations are required
Developing the WHO Mosaic Toolkit to End Stigma and Discrimination in Mental Health : A participatory approach.
Get PDFStigma and discrimination related to mental health are major global challenges that demand urgent, evidence-based responses. The Mosaic Toolkit to End Stigma and Discrimination was developed in response to calls for practical guidance to end stigma and discrimination. This article outlines the co-production process behind the toolkit's creation, carried out from December 2022 to August 2024, through a collaboration between World Health Organization (WHO) Regional Office for Europe, the Global Mental Health Peer Network, and King's College London. The development involved extensive consultation with individuals with lived experience and a wide range of stakeholders, ensuring cultural relevance, inclusivity, and applicability in diverse settings. The toolkit outlines core principles for stigma reduction, an action-oriented process model, illustrative case studies, and supportive resources including advocacy tools. Grounded in the principle of "nothing about us without us" and the power of social contact, the practical strategies within the WHO Mosaic Toolkit offers a concrete path to ending mental health stigma. The next crucial step will involve supporting implementation in real-world contexts to create lasting change. Designed for global application, the toolkit aims to foster dignity, inclusion, and rights-based approaches to end mental health stigma and discrimination
New Ways of Working to Manage and Improve Quality in Integrated Care Systems in England.
Get PDFBACKGROUND: Integrated care systems (ICSs) in England were formally established in July 2022 to coordinate the planning and delivery of health and care services. A key responsibility was to address the quality of these services. Our study aimed to examine how ICSs approach this responsibility and to identify opportunities and barriers experienced in their early establishment and development.
METHODS: A sample of four ICSs were recruited to participate. Interviews and meeting observations were undertaken in two phases (before and after the inception of ICSs) around 12 months apart. A total of 112 interviews were carried out with senior figures in the four ICSs supplemented by observation of relevant meetings and analysis of relevant documents.
RESULTS: Regarding quality, ICSs demonstrated several new ways of working. They set-up new structures for quality governance and created whole-system strategies for quality centred on major responsibilities regarding population health and health inequalities. These strategies required new and relevant metrics to assess quality and outcomes and a greater focus upon co-production in the development of services. They aimed to strike a fine balance between long-standing requirements for quality assurance and new responsibilities for quality improvement (QI). New approaches were underpinned by new collaborations between system partners extending beyond healthcare to include Local Authorities (responsible for social care and public health) and local communities.
CONCLUSION: To address the many challenges of quality, ICSs have created new ways of working cultivating different kinds of collaborative relationships compared to established hierarchical, siloed and top-down ways of working prior to their formation. A focus on improving population health and reducing inequalities has required a shift from "here and now" urgent problem-solving to working with longer timelines. Such changes require patience in the context of political pressure to devote efforts to more salient problems such as waiting lists
Biodiversity pressure from fruit and vegetable consumption in the United Kingdom, India and South Africa varies by product and growing location.
Get PDFIn many countries around the world, fruit and vegetable consumption must increase to improve human health, potentially pressuring local and global biodiversity. Here we use biodiversity-pressure metrics to compare the biodiversity pressures associated with fruits and vegetables consumed in the United Kingdom, India and South Africa. We found that biodiversity pressure for individual crops varies greatly with origin. In all three countries, imported fruits are typically associated with greater pressure than domestically grown fruits. Contrastingly, in India and South Africa, imported vegetables generally have a lower biodiversity pressure than domestically grown vegetables. Oranges, popular in the United Kingdom and South Africa, exert almost three times more biodiversity pressure than bananas-one of the most-consumed fruits in the United Kingdom and India. Our analysis illustrates the quantification of crop-specific biodiversity pressures and provides evidence for the development of more sustainable food systems
Multiplex bead assays enable integrated serological surveillance and reveal cross-pathogen vulnerabilities in Zambezia Province, Mozambique.
Get PDFMultiplex serological assays simultaneously measure antibodies to multiple antigens, furnishing insights into exposure and susceptibility to several pathogens and cross-pathogen vulnerabilities. Our serosurvey tests dried blood spots from 1292 individuals for IgG antibodies to 35 antigens from 18 pathogens using a multiplex bead assay for vaccine preventable diseases, malaria, SARS-CoV-2, neglected tropical diseases, and enteric pathogens in Mozambique. We produce pathogen-specific seroprevalence estimates and age-seroprevalence curves and identify spatial differences in seroprevalence. Rural clusters have higher odds of seropositivity to most NTDs neglected tropical diseases, Plasmodium falciparum malaria, and enteric pathogens, but lower odds of seropositivity to SARS-CoV-2 and vaccine preventable diseases compared to urban clusters. This co-occurrence identifies clusters with high vulnerability to multiple pathogens. We identify a candidate group of antigens that are correlated with high overall vulnerability. Our results demonstrate a role for multiplex serology in integrated disease surveillance to guide control strategies for individual and co-endemic pathogens
Mental health related stigma in a primary care setting in Karnataka, rural India: Service user and carer perspectives.
Get PDFMental health related stigma and discrimination are significant issues requiring urgent global action. There is a particular lack of research on stigma in low-and middle-income countries. This study explores the experiences of service users and their carers who access primary care for treatment of mental health conditions in rural Karnataka, India. Purposive sampling was used to conduct qualitative interviews of service users and their carers. This study highlights several barriers to access mental healthcare that individuals face on a system level. The results also bring to light pervasive experiences of stigmatising attitudes and discriminatory behaviour that participants with mental health conditions face from within their communities. Cohesion within both the family and the community was highlighted as a priority for participants, using a "what matters most" approach. This study brings insights to contribute to the development of locally relevant anti-stigma interventions, promoting access to care, and the human rights and quality of life for individuals with mental health conditions in a rural community in Karnataka, India
HIV-phyloTSI: subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data.
Get PDFBACKGROUND: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. RESULTS: We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. CONCLUSIONS: We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level
A guide on how to measure community engagement and accountability impacts in humanitarian settings
Get PDFThis guidance has been developed for local humanitarian actors and organisations to support rapid measurement of the transformative impacts and long-term contributions of community engagement and accountability programmes in humanitarian and public health crisis responses
Le rejet de l’assurance maladie aux États-Unis après-guerre et la gauche américaine. Le cas Milton Roemer (1916-2001)
No full textEn traitant le « moment 1945 » comme la période de 1943 à 1950, cet article étudie l’échec des réformateurs de la protection sociale aux États-Unis quand ils ont tenté d’instituer une assurance maladie sociale. Il rend compte d’abord, sur le plan historiographique, des raisons pour lesquelles les tentatives législatives de réforme de la santé n’ont pas abouti. Il fournit ensuite une approche individuelle et biographique de cet épisode de la gauche progressiste. Le point de vue de Milton Roemer, responsable de la santé publique, fonctionnaire et universitaire, met en lumière les principales caractéristiques de la politique de santé à ce moment charnière. Il éclaire également l’état d’esprit progressiste qui sous-tend la réforme, exacerbé par l’inquiétude face à la pauvreté rurale, les revendications des syndicats et la justice raciale. Technocratique et concevant l’État comme une force pour le bien, Milton Roemer a finalement été vaincu lorsque le New Deal américain a cédé la place à des valeurs différentes