Design of novel drug delivery polymeric complexes via innovative crosslinking reactions

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the Degree of Master of Science in Medicine (Pharmacy), JohannesburgThis thesis presents a multifaceted approach which comprehensively describes the design of novel drug delivery polymeric complexes through the application of innovative crosslinking reactions. These reactions have been built on the statistical and mathematical principles governing the technique of Design of Experiments. At the outset, pertinent aspects covering the importance of rate-controlled drug delivery in achieving superior therapeutics is presented. In addition, the fundamental mechanisms which regulate the complex behaviour of polymeric materials are outlined, placing emphasis on the mathematical models which demonstrate the critical need to be able to synchronize the processes of matrix hydration, relaxation, disentanglement, erosion and dissolution. Initially, the Plackett-Burman Design was evaluated to develop a crosslinked polymeric oilisphere device for the in vitro site-specific delivery of Mentha piperita oil. This design proved to be highly successful in rapidly identifying the appropriate release rate-modifying variables through the application of stepwise regression optimization and Artificial Neural Networks.IT201

Evaluating the IRI topside model for the South African region: An overview of the modelling techniques

The representation of the topside ionosphere (the region above the F2 peak) is critical because of the limited experimental data available. Over the years, a wide range of models have been developed in an effort to represent the behaviour and the shape of the electron density (Ne) profile of the topside ionosphere. Various studies have been centred around calculating the vertical scale height (VSH) and have included (a) obtaining VSH from Global Positioning System (GPS) derived total electron content (TEC), (b) calculating the VSH from ground-based ionosonde measurements, (c) using topside sounder vertical Ne profiles to obtain the VSH. One or a combination of the topside profilers (Chapman function, exponential function, sech-squared (Epstein) function, and/or parabolic function) is then used to reconstruct the topside Ne profile. The different approaches and the modelling techniques are discussed with a view to identifying the most adequate approach to apply to the South African region’s topside modelling efforts. The IRI-2001 topside model is evaluated based on how well it reproduces measured topside profiles over the South African region. This study is a first step in the process of developing a South African topside ionosphere model

Admission policies as enablers and disablers of children’s rights to basic education: Stakeholders’ perceptions

In this article we report on a qualitative study done in Pretoria, South Africa, in which we investigated the experiences of 2 representatives of the Gauteng Department of Education (GDE); School Governing Body (SGB) spokespersons from 4 schools located in the Gauteng province, 2 representatives of the Federation of SGBs, 4 principals from 4 schools, and 4 parents from 4 schools regarding public primary schools’  admission policies and practices as enablers or disablers of children’s rights to basic education. Using  structured, open-ended interviews, qualitative data were generated to explore the  experiences of the  participants on the public primary schools’ admission policies and practices as enablers or disablers of a  right to basic education. We argue that the implementation of school admission policies as enabler to  access to basic  education must be based on a system of rights and corresponding obligations  established by the Constitution of the Republic  of South Africa, 1996, and the various legislative and  policy frameworks. The findings of the study reveal that the learner  admission system in South African  public schools remains problematic, which in turn aids as a disabler of children’s right to basic education

Chronic Serratiaodorifera Infra-vesical, Extra-peritoneal Pelvic Abscess: an Unexpected Finding in a Healthy 18 year Old Girl

Background: Serratiaodorifera (S. odorifera), a rare nosocomial human pathogen, is responsible for a few cases and outbreaks of sepsis in very sick hospitalized patients.Case Report: We report the case of an 18 year old healthy female patient with a chronic, deep, extra-peritoneal pelvic infection by S. odorifera in a Human Immunodeficiency Virus (HIV) endemic region. She had no  constitutional symptoms. In the Serratia genus, Serratiamarcescens is the most pathogenic, infecting virtually all human organ systems, where-as S. odoriferararely infects healthy patients. Our patient presented with chronicmild pelvic pain. Radiological evaluation revealed a cystic mass lesion of 80mm diameter which was thought to be an ovarian cyst. The mass could not be found at laparotomy. Repeat radiological evaluation revealed that the mass was extra-peritoneal with very thick walls. It was located para-vaginally, below and in front of the urinary bladder. Laparoscopic exploration nine months after laparotomy revealed an abscess with 200ml of pus. She was treated with antibiotics. Anaerobic culture yielded a profuse growth of S.odorifera. Histopathological tissue review confirmed a chronic suppurative abscess. We believe this was a community acquired S.  odorifera infection affecting an otherwise healthy patient. The patient was discharged home well eight days later.Key words: chronic pelvic abscess, community acquired, HIV infection, immunodeficiency, Serratiaodorifer

"Well, not me, but other women do not register because..."- Barriers to seeking antenatal care in the context of prevention of mother-to-child transmission of HIV among Zimbabwean women: a mixed-methods study.

BACKGROUND: While barriers to uptake of antenatal care (ANC) among pregnant women have been explored, much less is known about how integrating prevention of mother-to-child transmission (PMTCT) programmes within ANC services affects uptake. We explored barriers to uptake of integrated ANC services in a poor Zimbabwean community. METHODS: A cross-sectional survey was conducted among post-natal women at Mbare Clinic, Harare, between September 2010 and February 2011. Collected data included participant characteristics and ANC uptake. Logistic regression was conducted to determine factors associated with ANC registration. In-depth interviews were held with the first 21 survey participants who either did not register or registered after twenty-four weeks gestation to explore barriers. Interviews were analysed thematically. RESULTS: Two hundred and ninety-nine participants (mean age 26.1 years) were surveyed. They came from ultra-poor households, with mean household income of US$181. Only 229 (76.6$10-increase in household income 1.02 (95% confidence interval, CI, 1.0-1.04), as was education which interacted with having planned the pregnancy (OR for planned pregnancy with completed ordinary level education 3.27 (95%CI 1.55-6.70). Divorced women were less likely to register than married women, OR 0.20 (95%CI 0.07-0.58). In the qualitative study, barriers to either ANC or PMTCT services limited uptake of integrated services. Women understood the importance of integrated services for PMTCT purposes and theirs and the babies' health and appeared unable to admit to barriers which they deemed "stupid/irresponsible", namely fear of HIV testing and disrespectful treatment by nurses. They represented these commonly recurring barriers as challenges that "other women" faced. The major proffered personal barrier was unaffordability of user fees, which was sometimes compounded by unsupportive husbands who were the breadwinners. CONCLUSION: Women who delayed/did not register were aware of the importance of ANC and PMTCT but were either unable to afford or afraid to register. Addressing the identified challenges will not only be important for integrated PMTCT/ANC services but will also provide a model for dealing with challenges as countries scale up 'treat all' approaches

Manuscript title: Facilitators and barriers to cotrimoxazole prophylaxis among HIV exposed babies: a qualitative study from Harare, Zimbabwe.

BACKGROUND: Implementation of cotrimoxazole prophylaxis (CTX-p) among HIV-exposed infants (HEI) is poor in southern Africa. We conducted a study to investigate barriers to delivery of CTX-p to HEI in Zimbabwe at each step of the care cascade. Here we report findings of the qualitative component designed to investigate issues related to adherence conducted among women identified as HIV positive whose babies were started on CTX-p postnatally. Of note, Zimbabwe also provided nevirapine prophylaxis for HIV exposed babies, so the majority were giving nevirapine and CTX-p to their babies. METHODS: Between Feb-Dec 2011, the first 20 HIV infected mothers identified were invited for in-depth interview 4-5months postnatally. Interviews were recorded, transcribed, translated and analysed thematically. RESULTS: All women desired their baby's health above all else, and were determined to do all they could to ensure their wellbeing. They did not report problems remembering to give drugs. The baby's apparent good health was a huge motivator for continued adherence. However, most women reported that their husbands were less engaged in HIV care, refusing to be HIV tested and in some cases stealing drugs prescribed for their wives for themselves. In two instances the man stopped the woman from giving CTX-p to the baby either because of fear of side effects or not appreciating its importance. Stigma continues to be an important issue. Mothers reported being reluctant to disclose their HIV status to other people so found it difficult to collect prescription refills from the HIV clinic for fear of being seen by friends/relatives. Some women reported that it was hard to administer the drugs if there were people around at home. Other challenges faced were stock-outs of CTX-p at the clinic, which occurred three times in 2011. The baby would then go without CTX-p if the woman could not afford buying at a private pharmacy. CONCLUSIONS: The study highlights that adherence knowledge and desire alone is insufficient to overcome the familial and structural barriers to maintaining CTX-p. Improving adherence to CTX-p among HEI will require interventions to improve male involvement, reduce HIV stigma in communities and ensure adequate supply of drugs

A retrospective analysis of climate adaptation strategies and implications for food and nutrition security among small-scale farmers in South Africa

With the ever-increasing climate change, actions to reduce its negative impact while improving food and nutrition security are critical. This review is a retrospective analysis of climate adaptation strategies and implications for food and nutrition security among small-scale farmers in South Africa. The review used bibliometric analysis and Preferred Reporting Items for Systematic Reviews and Meta-Analysis to track research on implications of adaptation on food and nutrition security, identify adaptation strategies with implications on food and nutrition security and discuss the implications. The analysis shows a steady growth in the research field; however, whether the pace will accelerate the achievement of Sustainable Development Goal 2 by 2030 is unknown. Institutional research collaboration is notable, although weak. The co-occurrence of keywords reflects Climate-Smart Agriculture and food and nutrition linkages, emphasizes the importance of farmers’ perceptions on adopting measures to enhance food and nutrition security and illustrates the risk-vulnerability-resilience nexus. Adaptation measures with implications on food and nutrition security are varied, ranging from individual efforts to government-led initiatives. We recommend strengthening institutional research collaboration to accelerate the pace towards achieving zero hunger, food security and nutrition by 2030. It is also important to have an inclusive policy framework that addresses farmers’ adaptation needs