848 research outputs found
A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.
OBJECTIVE: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes.
DESIGN: This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day.
RESULTS: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, pâ=â0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, pâ=â0.055]).
CONCLUSION: There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis
Access to health care in South Africa - the influence of race and class
Objectives. The first democratic government elected in South Africa in 1994 inherited huge inequities in health status and health provision across all section of the population. This study set out to assess the impact of the new government's commitment to address these inequities and implement policies to improve population health in general and address inequities in health care in particular. Design. A 1998 household survey assessed many aspects of health delivery, including their own perceived and actual access to health care among different segment of South Africa society. Results. Race was the main predictor of perceived changes in access to health care, with black, coloured and Indian respondents significatly more likely to feel that access had improved since 1994, compared with white respondents. Socio-economic status (SES) was the main predictor of actual access to health care, with low and middle SES classes significantly less likely to access care when ill. Conclusions. One-third of respondents perceived health care access to have improved between 1994 and 1998, and this response was partially determined along racial lines. About one-quarter reported an inability to access health care when they required it, and this response was partially determined along socio-economic lines. This set of contrasting responses suggests that at a political level perceptions are largely influenced by race, but at the operational level actual access is influenced by SES
Southern Africa Consortium for Research Excellence (SACORE): successes and challenges
Copyright © Mandala et al. Open access article
distributed under the terms of CC BY.Published Online November 13, 2014
http://dx.doi.org/10.1016/S2214-109X(14)70321-
Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers.
INTRODUCTION: Increasing parity and age at first full-term pregnancy are established risk factors for breast cancer in the general population. However, their effects among BRCA1 and BRCA2 mutation carriers is still under debate. We used retrospective data on BRCA1 and BRCA2 mutation carriers from the UK to assess the effects of parity-related variables on breast cancer risk. METHODS: The data set included 457 mutation carriers who developed breast cancer (cases) and 332 healthy mutation carriers (controls), ascertained through families seen in genetic clinics. Hazard ratios were estimated by using a weighted cohort approach. RESULTS: Parous BRCA1 and BRCA2 mutation carriers were at a significantly lower risk of developing breast cancer (hazard ratio 0.54, 95% confidence interval 0.37 to 0.81; p = 0.002). The protective effect was observed only among carriers who were older than 40 years. Increasing age at first live birth was associated with an increased breast cancer risk among BRCA2 mutation carriers (p trend = 0.002) but not BRCA1 carriers. However, the analysis by age at first live birth was based on small numbers. CONCLUSION: The results suggest that the relative risks of breast cancer associated with parity among BRCA1 and BRCA2 mutation carriers may be similar to those in the general population and that reproductive history may be used to improve risk prediction in carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
Guardians and research staff experiences and views about the consent process in hospital-based paediatric research studies in urban Malawi: A qualitative study
Background: Obtaining consent has become a standard way of respecting the patientâs rights and autonomy in clinical research. Ethical guidelines recommend that the childâs parent/s or authorised legal guardian provides informed consent for their childâs participation. However, obtaining informed consent in paediatric research is challenging. Parents become vulnerable because of stress related to their childâs illness. Understanding the views held by guardians and researchers about the consent process in Malawi, where there are limitations in health care access and research literacy will assist in developing appropriate consent guidelines.
Methods: We conducted 20 in-depth interviews with guardians of children and research staff who had participated in paediatric clinical trial and observational studies in acute and non-acute settings in the Southern Region of Malawi. Interviews were audio-recorded, transcribed verbatim, and thematically analysed. Interviews were compared across studies and settings to identify differences and similarities in participantsâ views about informed consent processes. Data analysis was facilitated by NVIVO 11 software.
Results: All participants across study types and settings reported that they associated participating in research with therapeutic benefits. Substantial differences were noted in the decision-making process across study settings. Guardians from acute studies felt that the role of their spouses was neglected during consenting, while staff reported that they had problems obtaining consent from guardians when their partners were not present. Across all study types and settings, research staff reported that they emphasised the benefits more than the risks of the study to participants, due to pressure to recruit. Participants from non-acute settings were more likely to recall information shared during the consent process than participants in the acute setting.
Conclusion: The health care context, culture and research process influenced participantsâ understanding of study information across study types and settings. We advise research managers or principal investigators to define minimum requirements that would not compromise the consent process and conduct study specific training for staff. The use of one size fits all consent process may not be ideal. More guidance is needed on how these differences can be incorporated during the consent process to improve understanding and delivery of consent
Flow cytometry method for absolute counting and single-cell phenotyping of mycobacteria
Detection and accurate quantitation of viable Mycobacterium tuberculosis is fundamental to understanding mycobacterial pathogenicity, tuberculosis (TB) disease progression and outcomes; TB transmission; drug action, efficacy and drug resistance. Despite this importance, methods for determining numbers of viable bacilli are limited in accuracy and precision owing to inherent characteristics of mycobacterial cell biology â including the tendency to clump, and âdifferentialâ culturability â and technical challenges consequent on handling an infectious pathogen under biosafe conditions. We developed an absolute counting method for mycobacteria in liquid cultures using a bench-top flow cytometer, and the low-cost fluorescent dyes Calcein-AM (CA) and SYBR-gold (SG). During exponential growth CA+ cell counts are highly correlated with CFU counts and can be used as a real-time alternative to simplify the accurate standardisation of inocula for experiments. In contrast to CFU counting, this method can detect and enumerate cell aggregates in samples, which we show are a potential source of variance and bias when using established methods. We show that CFUs comprise a sub-population of intact, metabolically active mycobacterial cells in liquid cultures, with CFU proportion varying by growth conditions. A pharmacodynamic application of the flow cytometry method, exploring kinetics of fluorescent probe defined subpopulations compared to CFU is demonstrated. Flow cytometry derived Mycobacterium bovis bacillus Calmette-GuĂ©rin (BCG) time-kill curves differ for rifampicin and kanamycin versus isoniazid and ethambutol, as do the relative dynamics of discrete morphologically-distinct subpopulations of bacilli revealed by this high-throughput single-cell technique
Approach to the diagnosis and management of snakebite envenomation in South Africa in humans
Snakebite management is largely driven by expert opinion and consensus. However, there are a few large retrospective studies and
randomised controlled trials that have improved the quality of medical guidance currently available. South African snakes are different in
venomous potential to snakes in other parts of the world, and it behoves the hospital provider and the average medical practitioner to know
the current best practice concepts concerning assessment, treatment and antivenom use. The recent South African Snakebite Symposium
meeting in July 2022 provided an update and national consensus from which this Hospital Care document is derived.https://samajournals.co.za/index.php/samj/indexam2024Family MedicineNon
Approach to the diagnosis and management of snakebite envenomation in South Africa in humans.
Snake bite management is largely driven by expert opinion and consensus, however there are a few large retrospective studies and RCTâs that have improved the quality of medical guidance currently available. South African snakes are different in the venomous potential and it behooves the hospital provider and the average medical practitioner to know the current best practice concepts concerning assessment, treatment and antivenom use. The recent SASS meeting in July 2022 provided an update and national consensus from which this Hospital Care document is derived
Clinical practice guidelines for the diagnosis and surveillance of BAP1 tumour predisposition syndrome.
BRCA1-associated protein-1 (BAP1) is a recognised tumour suppressor gene. Germline BAP1 pathogenic/likely pathogenic variants are associated with predisposition to multiple tumours, including uveal melanoma, malignant pleural and peritoneal mesothelioma, renal cell carcinoma and specific non-malignant neoplasms of the skin, as part of the autosomal dominant BAP1-tumour predisposition syndrome. The overall lifetime risk for BAP1 carriers to develop at least one BAP1-associated tumour is up to 85%, although due to ascertainment bias, current estimates of risk are likely to be overestimated. As for many rare cancer predisposition syndromes, there is limited scientific evidence to support the utility of surveillance and, therefore, management recommendations for BAP1 carriers are based on expert opinion. To date, European recommendations for BAP1 carriers have not been published but are necessary due to the emerging phenotype of this recently described syndrome and increased identification of BAP1 carriers via large gene panels or tumour sequencing. To address this, the Clinical Guideline Working Group of the CanGene-CanVar project in the United Kingdom invited European collaborators to collaborate to develop guidelines to harmonize surveillance programmes within Europe. Recommendations with respect to BAP1 testing and surveillance were achieved following literature review and Delphi survey completed by a core group and an extended expert group of 34 European specialists including Geneticists, Ophthalmologists, Oncologists, Dermatologists and Pathologists. It is recognised that these largely evidence-based but pragmatic recommendations will evolve over time as further data from research collaborations informs the phenotypic spectrum and surveillance outcomes
TB/HIV pleurisy reduces Th17 lymphocyte proportion independent of the cytokine microenvironment
T-helper (Th) 17 cells are a pro-inflammatory subset of CD4+ effector T-cells critical in mucosal immunity. Imbalances in Th17 cell proportion have been implicated in the pathogenesis of several diseases; however, this has not been adequately explored in tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Since Th17 cells are predominantly mucosally associated, we assessed Th17 proportion and associated microenvironment in pleural effusions from patients co-infected with TB/HIV. Our results show that TB+HIV+ pleurisy results in significantly reduced frequency of CD4+IL-17+RORC+STAT3+ Th17 cells compared to TBâHIVâex vivo (p = 0.0054) and was confirmed in conditioned media studies in vitro (p = 0.0001). This was not associated with alterations in Th17 polarising cytokines IL-6, IL-21 and IL-23 or changes in Th17 signature cytokines IL-17A and F. However, the mRNA expression of Th17 signalling molecules, IL-6 (p = 0.0022), IL-6R (p = 0.0247), IL-1ÎČ (p = 0.0022) and signal transducer and activator (STAT) 3 (p = 0.0022) were significantly upregulated. Notably, TB+HIV+ pleural fluid contained significantly higher concentrations of IL-1ÎČ (p = 0.0008), IL-22 (p = 0.0115), IL-31 (p = 0.0210), TNF-α (p = 0.0251) and IFN-Îł (p = 0.0026) than TBâHIVâ pleural fluid ex vivo. Taken together, this suggests a reduced portion of Th17 lymphocytes in TB/HIV pleurisy is independent of locally mediated cytokine polarisation.The National
Research Foundation, KwaZulu-Natal Research Institute for Tuberculosis
and HIV and College of Health Sciences, University of
KwaZulu-Natal.http://intl.elsevierhealth.com/journals/tube2017-07-31hb2016Physiolog
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