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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 4. |
- Abulfathi, Ahmed Aliyu, et al.
(författare)
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Clinical Pharmacokinetics and Pharmacodynamics of Rifampicin in Human Tuberculosis
- 2019
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Ingår i: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 58:9, s. 1103-1129
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Forskningsöversikt (refereegranskat)abstract
- The introduction of rifampicin (rifampin) into tuberculosis (TB) treatment five decades ago was critical for shortening the treatment duration for patients with pulmonary TB to 6months when combined with pyrazinamide in the first 2months. Resistance or hypersensitivity to rifampicin effectively condemns a patient to prolonged, less effective, more toxic, and expensive regimens. Because of cost and fears of toxicity, rifampicin was introduced at an oral daily dose of 600mg (8-12mg/kg body weight). At this dose, clinical trials in 1970s found cure rates of >= 95% and relapse rates of < 5%. However, recent papers report lower cure rates that might be the consequence of increased emergence of resistance. Several lines of evidence suggest that higher rifampicin doses, if tolerated and safe, could shorten treatment duration even further. We conducted a narrative review of rifampicin pharmacokinetics and pharmacodynamics in adults across a range of doses and highlight variables that influence its pharmacokinetics/pharmacodynamics. Rifampicin exposure has considerable inter- and intra-individual variability that could be reduced by administration during fasting. Several factors including malnutrition, HIV infection, diabetes mellitus, dose size, pharmacogenetic polymorphisms, hepatic cirrhosis, and substandard medicinal products alter rifampicin exposure and/or efficacy. Renal impairment has no influence on rifampicin pharmacokinetics when dosed at 600mg. Rifampicin maximum (peak) concentration (C-max) > 8.2 mu g/mL is an independent predictor of sterilizing activity and therapeutic drug monitoring at 2, 4, and 6h post-dose may aid in optimizing dosing to achieve the recommended rifampicin concentration of >= 8 mu g/mL. A higher rifampicin C-max is required for severe forms TB such as TB meningitis, with C-max >= 22 mu g/mL and area under the concentration-time curve (AUC) from time zero to 6h (AUC(6)) >= 70 mu g.h/mL associated with reduced mortality. More studies are needed to confirm whether doses achieving exposures higher than the current standard dosage could translate into faster sputum conversion, higher cure rates, lower relapse rates, and less mortality. It is encouraging that daily rifampicin doses up to 35mg/kg were found to be safe and well-tolerated over a period of 12weeks. High-dose rifampicin should thus be considered in future studies when constructing potentially shorter regimens. The studies should be adequately powered to determine treatment outcomes and should include surrogate markers of efficacy such as C-max/MIC (minimum inhibitory concentration) and AUC/MIC.
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| 5. |
- Audet, Carolyn M., et al.
(författare)
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An unrecognized key population? : Traditional treatment practices associated with HIV risk among traditional healers in rural South Africa
- 2020
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Ingår i: AIDS. - : Lippincott Williams & Wilkins. - 0269-9370 .- 1473-5571. ; 34:15, s. 2313-2317
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To understand the risk of HIV acquisition through occupational exposure among rural South African traditional healers, notably via the practice of traditional skin incisions with razors.Design: A random sample of traditional healers living in South Africa participated in a cross-sectional survey that included a rapid HIV test.Setting: Rural Bushbuckridge district of Mpumalanga, South Africa.Participants: Traditional healers.Intervention: Pretest counseling, posttest counseling, and referral to care if HIV seropositive.Main outcome measure(s): HIV infection.Results: Among healers who reported a previous positive test result or accepted an HIV test (96%), HIV prevalence was 30% (95% confidence interval: 23–37%). During their careers, 98% of healers reported conducting at least one ‘vaccination’ (as traditional incisions are called), 32% reported always using gloves when conducting these procedures, 29 (14%) reported patient blood touching their bare skin. Healers who reported exposure to patient blood had a higher HIV prevalence than their nonexposed colleagues (adjusted risk ratio: 2.35, 95% confidence interval: 1.55–3.56, P = 0.001).Conclusion: Nearly all traditional healers are routinely performing minimally invasive skin incisions that could expose them to patient blood. The lack of training and access to personal protective equipment increase their risk of acquisition of blood–borne pathogens, including HIV. Given the widespread practice of traditional skin incisions across southern Africa, and the higher levels of HIV among traditional healers exposed to patient blood, it is likely that traditional healers are a hitherto unrecognized key population at disproportionate risk of acquiring HIV.
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- Ikuteyijo, Olutoyin O., et al.
(författare)
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Demand and supply of adolescent and young adult’s sexual and reproductive health services during COVID-19 in sub-Saharan Africa : a scoping review
- 2024
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Ingår i: International Journal of Population Studies. - : AccScience Publishing. - 2424-8150 .- 2424-8606. ; 10:1
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Forskningsöversikt (refereegranskat)abstract
- The COVID-19 pandemic and its associated containment strategies have significantly impacted the logistics of supplying sexual and reproductive health (SRH) services to adolescents and young adults (AYA) in sub-Saharan Africa (SSA). Studies conducted in the region indicate an increase in sexual activity, particularly among young people, during the pandemic. However, the impact of these changes on their utilization of SRH services remains unclear. This scoping review aims to synthesize the available evidence on the impact of COVID-19 on the SRH behavior and service utilization of AYA. This review focuses on examining the demand and supply of SRH for AYA during the COVID-19 lockdown period (January 2020 – December 2021). Following the Arksey & O’Malley (2005) procedure and the Joanna Briggs Institute (JBI) Reviewer’s Manual (2020), the review encompasses comprehensive search strategies, analysis, and reporting of results. The search for relevant articles was conducted across various databases, including Medline Complete, Africa-Wide, SocINDEX, Academic Search Complete (all through EBSCOhost), Public Health, Social Science & Sociology databases, the Middle East & Africa Database (all through ProQuest), and Web of Science. Articles published between January 2020 and December 2021 were included in this review. The studies discussed in this review shed light on the discrepancies in the demand for and supply of SRH services during the COVID-19 pandemic, exposing a substantial gap in addressing the specific SRH needs of AYA. This review also examines the strategies adopted by countries in SSA to mitigate these effects. Several countries in SSA demonstrated resilience as health providers fulfilled their role, while AYA sought alternatives to mitigate the shortage in the supply chain for SRH services and commodities, often resorting to alternative medicine. The findings underscore the urgency of further research to address the risks imposed by COVID-19 on the utilization of SRH services by AYA in SSA. The evidence presented in this review can inform strategic efforts to ensure the availability and accessibility of SRH services for AYA during any unforeseen emergency or future pandemic.
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| 7. |
- Zhou, Joseph Xu, et al.
(författare)
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Quasi-potential landscape in complex multi-stable systems
- 2012
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 9:77, s. 3539-3553
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Tidskriftsartikel (refereegranskat)abstract
- The developmental dynamics of multicellular organisms is a process that takes place in a multi-stable system in which each attractor state represents a cell type, and attractor transitions correspond to cell differentiation paths. This new understanding has revived the idea of a quasi-potential landscape, first proposed by Waddington as a metaphor. To describe development, one is interested in the 'relative stabilities' of N attractors (N > 2). Existing theories of state transition between local minima on some potential landscape deal with the exit part in the transition between two attractors in pair-attractor systems but do not offer the notion of a global potential function that relates more than two attractors to each other. Several ad hoc methods have been used in systems biology to compute a landscape in non-gradient systems, such as gene regulatory networks. Here we present an overview of currently available methods, discuss their limitations and propose a new decomposition of vector fields that permits the computation of a quasi-potential function that is equivalent to the Freidlin-Wentzell potential but is not limited to two attractors. Several examples of decomposition are given, and the significance of such a quasi-potential function is discussed.
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