Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis

<p>Abstract</p> <p>Background</p> <p>Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little is known about the pharmacokinetics of rifampin in children. The objective of this study was to evaluate the pharmacokinetics of rifampin in children with tuberculosis, both human immunodeficiency virus type-1-infected and human immunodeficiency virus-uninfected.</p> <p>Methods</p> <p>Fifty-four children, 21 human immunodeficiency virus-infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05 years (<it>P </it>= 0.68), respectively, admitted to a tuberculosis hospital in Cape Town, South Africa with severe forms of tuberculosis were studied approximately 1 month and 4 months after commencing antituberculosis treatment. Blood specimens for analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after dosing. Rifampin concentrations were determined by liquid chromatography tandem mass spectrometry. For two sample comparisons of means, the Welch version of the t-test was used; associations between variables were examined by Pearson correlation and by multiple linear regression.</p> <p>Results</p> <p>The children received a mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and 9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as part of a fixed-dose formulation designed for paediatric use. The mean rifampin area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 μg/hour/ml (<it>P </it>= 0.25) 1 month after starting treatment in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children, respectively, and 16.52 and 17.94 μg/hour/ml (<it>P </it>= 0.59) after 4 months of treatment. The mean calculated 2-hour rifampin concentrations in these human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8 μg/ml (<it>P </it>= 0.20) at 1 month after the start of treatment and 4.0 and 4.6 μg/ml (<it>P </it>= 0.33) after 4 months of treatment. These values are considerably less than the suggested lower limit for 2-hour rifampin concentrations in adults of 8.0 μg/ml and even 4 μg/ml</p> <p>Conclusion</p> <p>Both human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children with tuberculosis have very low rifampin serum concentrations after receiving standard rifampin dosages similar to those used in adults. Pharmacokinetic studies of higher dosages of rifampin are urgently needed in children to assist in placing the dosage of rifampin used in childhood on a more scientific foundation.</p

Peer effects and intentional entrepreneurial behaviour: a systematic literature review and research agenda

What role peers play in individuals’ decisions to become entrepreneurs and to what extent peer effects play a role in influencing behaviours at the various stages of business venturing are important questions for scholars and policymakers. This systematic review takes stock of the recent additions to the literature around the phenomena of peer influence in entrepreneurship. The review identified 2,894 documents which were then narrowed down through three consecutive filtering stages. We thematically analysed the final sample of 27 empirical studies that shed light on how individuals’ peers influence the process and outcomes of these individuals’ entrepreneurial intentions and behaviour, allowing for critical analysis. We propose a conceptual schema of social influence that occurs in interactions among entrepreneurial individuals within business venturing and across the three stages of pre-formation, formation, and growth. Our framework reconciles the conceptual classification around discovering, evaluating and exploiting entrepreneurial opportunities with the mechanisms of social influence affecting entrepreneurial behaviours. Grounded in the findings of the literature review, this framework synthesizes peer influence in entrepreneurship with the tripartite distinction of the behavioural motives recognised in contemporary theories of social influence. We suggest promising directions for further research on how interactions with peers might affect individuals’ entrepreneurial behaviours

Using medians to generate consensus rankings for biological data

International audienc

Anpassung elektrischer Antriebe an Versorgungs- und Prozesssysteme Schlussbericht. Abschlussdatum: November 1983

TIB: RN 2598 (84-231)+a-b / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman