Pharmacokinetic and pharmacodynamic characteristics of isoniazid and rifampicin in patients with multidrug-resistant tuberculosis.

Ph. D. University of Durban-Westville 1998.No abstract available.A summary with literature review is available

The influence of the application of pharmacokinetics on the effects of theophylline utilisation upon members of the Indian population.

Thesis (M.Pharm.)--University of Durban-Westville, 1989.Theophylline is a dimethylated xanthine similar in structure to caffeine which is commonly found in tea, coffee and cola beverages (Hendeles and Weinberger, 1983; Rall, 1985). Clinically, its most important pharmacological action is the ability to relax bronchial smooth muscle throughout the bronchial tree (Persson, 1986). This effect has found extensive use in the treatment of asthma with the drug being recommended as the first line agent for chronic asthma (la/rate et ai, 1986). The observation that both beneficial effects as well as toxicity correlate with serum concentrations and that the drug displays a narrow therapeutic window (Finn et al, 1981; Hendeles and Matthay, 1986) has resulted in the recommendation that theophylline dosing be guided by serum concentration measurements (Hendeles and Weinberger, 1980; Whiting et al, 1984; Fitzpatrick and Moss-Barclay, 1985; Barlow et. al, 1988). However, this recommendation appears to have been largely ignored locally. In 1986, one of the first local Therapeutic Drug Monitoring Clinics for theophylline was established at R K Khan Provincial Hospital in Chatsworth, Durban. Preliminary results from this clinic confirmed the widespread use of standard theophylline dosing regimens and revealed that 68% (n = 44) of patients given these regimens had serum theophylline concentrations below the generally accepted therapeutic range (Pillai and Miller, 1988). Previous studies have assessed the influence of Therapeutic Drug Monitoring programmes in terms of the attainment of 'therapeutic' serum concentrations (Whiting et aI, 1984; Fitzpatrick and Moss-Barclay, 1985). This approach has been criticised and it has been recommended that clinical assessment should be the criterion. The purpose of this study was to investigate the influence of serum concentration monitoring on theophylline utilisation at the R K Khan Hospital in terms of clinical control of asthma symptoms. A secondary purpose of this study was to determine population pharmacokinetic parameters in Indian patients. In order to interpret the serum concentrations and make recommendations on dosage design for individual patients, the Bayesian technique of drug dose optimisation is used (Sheiner et aI, 1972). This technique has been shown to be accurate, precise and easy to use (Sheiner and Beal, 1982; Hurley and McNeil, 1988) particularly with currently available computer software. It has been emphasised, however, that for satisfactory performance of this technique, good initial estimates of the population parameter distributions are important (Whiting et al, 1986). Since this information is not available for the Indian population this study was undertaken. A knowledge of population pharmacokinetics can help one to choose initial dosage, to modify dosage appropriately in response to observed drug levels, to make rational decisions regarding drug regulatory requirements and toinvestigate and elucidate certain research questions in pharmacokinetics (Sheiner, 1984). The NONMEM approach (Sheiner et aI, 1972; 1977), currently the mostsatisfactory method of population pharmacokinetic data analysis is utilised in this study

Care-seeking dynamics among patients with diabetes mellitus and hypertension in selected rural settings in Kenya

Diabetes mellitus and hypertension are two common non-communicable diseases (NCDs) that often coexist in patients. However, health-seeking behaviour in patients with diabetes mellitus or hypertension has not been extensively studied especially in low- and middle-income countries. This study aimed to examine care-seeking dynamics among participants diagnosed with diabetes and/or hypertension across nine counties in rural Kenya. We conducted a cross-sectional study among adults diagnosed with diabetes and/or hypertension through face-to-face interviews. Of the 1100 participants, 69.9% had hypertension, 15.5% diabetes while 14.7% had both. The mean age of the respondents was 64 years. The majority of the respondents (86%) were on allopathic treatment. Hospital admission, having a good self-rated health status and having social support for illness, were positively associated with appropriate health-seeking behaviour while use of alcohol and pharmacy or chemist as source of treatment were negatively associated with appropriate health-seeking behaviour. Our study found a high prevalence of appropriate health-seeking behaviour among respondents with the majority obtaining care from government facilities. The results are evidence that improving public health care services can promote appropriate health-seeking behaviour for non-communicable diseases and thus improve health outcomes

The Next Generation Scientist program: capacity-building for future scientific leaders in low- and middle-income countries

Background Scientific and professional development opportunities for early career scientists in low- and middle- income countries (LMICs) are limited and not consistent. There is a disproportionately low number of biomedical and clinical researchers in LMIC’s relative to their high burden of disease, a disparity that is aggravated by emigration of up to 70% of scientists from their countries of birth for education and employment elsewhere. To help address this need, a novel University-accredited, immersive fellowship program was established by a large public-academic-private network. We sought to describe the program and summarize progress and lessons learned over its first 7-years. Methods Hallmarks of the program are a structured learning curriculum and bespoke research activities tailored to the needs of each fellow. Research projects expose the scientists to state-of-the-art methodologies and leading experts in their fields while also ensuring that learnings are implementable within their home infrastructure. Fellows run seminars on drug discovery and development that reinforce themes of scientific leadership and teamwork together with practical modules on addressing healthcare challenges within their local systems. Industry mentors achieve mutual learning to better understand healthcare needs in traditionally underserved settings. We evaluated the impact of the program through an online survey of participants and by assessing research output. Results More than 140 scientists and clinicians from 25 countries participated over the 7-year period. Evaluation revealed strong evidence of knowledge and skills transfer, and beneficial self-reported impact on fellow’s research output and career trajectories. Examples of program impact included completion of post-graduate qualifications; establishment and implementation of good laboratory- and clinical- practice mechanisms; and becoming lead investigators in local programs. There was a high retention of fellows in their home countries (> 75%) and an enduring professional network among the fellows and their mentors. Conclusions Our experience demonstrates an example for how multi-sectoral partners can contribute to scientific and professional development of researchers in LMICs and supports the idea that capacity-building efforts should be tailored to the specific needs of beneficiaries to be maximally effective. Lessons learned may be applied to the design and conduct of other programs to strengthen science ecosystems in LMICs

Risk reduction of diarrhea and respiratory infections following a community health education program - a facility-based case-control study in rural parts of Kenya

Abstract Background Diarrheal and acute respiratory infections remain a major cause of death in developing countries especially among children below 5 years of age. About 80% of all hospital attendances in Kenya can be attributed to preventable diseases and at least 50% of these preventable diseases are linked to poor sanitation. The purpose of this study was to assess the impact of a community-based health education program, called Familia Nawiri, in reducing the risk of diarrhea and respiratory infections among people living in three rural Kenyan communities. Methods Cases were defined as patients attending the health facility due to diarrhea or a respiratory infection while controls were patients attending the same health facility for a non-communicable disease defined as an event other than diarrhea, respiratory infection. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a logistic regression model to assess the risk of diarrheal or respiratory infection in association with exposure to the health education program. Results There were 324 cases and 308 controls recruited for the study with 57% of the cases and 59% of the controls being male. Overall, 13% of cases vs. 20% of control patients were exposed to the education program. Participants exposed to the program had 38% lower odds of diarrhea and respiratory infections compared to those not exposed to the program (adjusted OR 0.62, 95% CI 0.41–0.96). A similar risk reduction was observed for participants in the study who resided in areas with water improvement initiatives (adjusted OR 0.65, 95% CI 0.47–0.90). Variables in the adjusted model included water improvement projects in the area and toilet facilities. Conclusion Findings from this study suggest participants exposed to the education program and those residing in areas with water improvement initiatives have a reduced risk of having diarrhea or respiratory infection

An open-source mobile digital platform for clinical trial data collection in low-resource settings

Background Governments and pan-African research networks are building durable infrastructure and capabilities for biomedical research in Africa. This offers the opportunity to adopt from the outset innovative approaches and technologies that would be challenging to retrofit into fully established research infrastructures such as those regularly found in high-income countries. In this context we piloted the use of a novel mobile digital health platform, designed specifically for low resource environments, to support high quality data collection in a clinical research study. Objective Our primary aim was to assess the feasibility of a using a mobile digital platform for clinical trial data collection in a low resource setting. Secondarily, we sought to explore the potential benefits of such an approach. Methods The investigative site was a research institute in Nairobi, Kenya. We integrated an open-source platform for mobile data collection commonly utilized in the developing world with an open-source, standard platform for Electronic Data Capture (EDC) in clinical trials. The integration was developed using common data standards (CDISC ODM), maximizing the potential to extend the approach to other platforms. The system was deployed in a pharmacokinetic study involving healthy human volunteers. Results The electronic data collection platform successfully supported conduct of the study. Multi-disciplinary users reported high levels of satisfaction with the mobile application and highlighted substantial advantages when compared with traditional paper record systems. The new system also demonstrated a potential for expediting data quality review. Discussion and Conclusion This pilot study demonstrated the feasibility of using a mobile digital platform for clinical research data collection in low resource settings. Sustainable scientific capabilities and infrastructure are essential to attract and support clinical research studies. Since many research structures in Africa are being developed anew, stakeholders should consider implementing innovative technologies and approaches

Pharmacometrics – Opportunity for Reducing Disease Burden in the Developing World

Pharmacometricians are virtually non-existent in Africa and the developing world. The unrelenting burden of neglected infectious diseases, which are often treated using medicines with narrow effectiveness – safety dose windows, and the growing prevalence of non-communicable diseases represents a significant burden for the patients while affording an opportunity for advancing science. Pharmacometrics is (still) an emerging discipline in the developed world which struggles to integrate into the established ways of conducting drug discovery and development. In Africa, the science and infrastructure is being built without a legacy system representing opportunity amid a need to better define and/or optimize dosing in local populations, or patients with co-morbidities. This paper outlines the business case for pharmacometricians to re-direct their expertise to focus on the disease burden affecting the developing world