Opportunistic infections (OIs) have been identified as a leading cause of poor outcomes in the ARV therapy (ART) programme. In order to reduce OIs, the Malawi, MoH introduced routine prescription of cotrimoxazole preventive therapy (CPT) in 2005. The MoH also started scaling up a point-of-care electronic medical record (EMR) system in 2007 to improve monitoring and evaluation. This study had the following objectives: i) to quantify prescription of CPT before and after implementing EMR; ii) to compare the difference in CPT prescription before and after implementing EMR. A historically controlled study design was used to compare CPT prescriptions one year before, and one year after implementation of the EMR at two health facilities. The data indicated that there was a significant (P <0.001) decrease in CPT prescribing at one health facility and a significant increase in CPT prescription at another. / Health Studies / M.A. (Public Health)

Metastatic breast cancer treatment has seen few advances in recent years, yet treatment resistance continues to rise, causing disease recurrence. A pilot study was performed to determine the efficacy of ex vivo expansion and reprogramming of tumor-reactive immune cells from experimental metastatic tumor-sensitized mice. Also, phenotypic changes in tumors due to metastasis or tumor microenvironment influences were characterized. Metastatic neu+ mouse mammary carcinoma (mMMC) and its distant relapsing neu-antigen-negative variant (mANV) were investigated in FVBN202 mice. Tumor-reactive central memory CD8+ T cells and activated NK/NKT cells were successfully reprogrammed and expanded during 6-day expansion from mMMC- and/or mANV-sensitized mice, resulting in tumor-specific cytotoxicity. mMMC exhibited a flexible neu-expression pattern and acquired stem-like, tumorigenic phenotype following metastasis while mANV remained stable except decreased tumorigenicity. Myeloid-derived suppressor cell (MDSC) levels were not increased. Adoptive cellular therapy (ACT) with reprogrammed tumor-reactive immune cells may prove effective prophylaxis against metastatic or recurrent breast cancer.

Bypass or resection of the stomach and oesophagus, has long been recognised to result in profound changes in the handling of ingested nutrients. This results in significant morbidity after radical surgery for oesophago-gastric cancer, in particular post-prandial hypoglycaemia, altered appetite, early satiety and noxious post-prandial symptoms. By profiling and challenging the gut hormone axis in healthy volunteers and patients who had undergone total or subtotal gastrectomy, or oesophagectomy, this thesis explores the possible causative mechanisms for the challenges faced by this patient population. In the surgical groups, an oral glucose tolerance test (OGTT) resulted in enhanced secretion of satiety and incretin gut hormones (GLP-1, GIP, PYY) and insulin, followed by hypoglycaemia in a cohort of patients. Continuous glucose monitoring of gastrectomy participants over two weeks of normal lifestyle identified an increased incidence of day and night time hypoglycaemia. RNAseq and mass spectrometry based peptidomics of human and murine enteroendocrine cells in the pre- and post-operative populations revealed no significant change in the underlying cellular pathways for nutrient sensing and gut hormone secretion, indicating that the altered hormone secretion is primarily driven by accelerated nutrient transit, rather than adaptive changes in the gut. Finally, specific blockade of the GLP-1 receptor in post-gastrectomy patients using Exendin 9-39 normalised insulin secretion and prevented reactive hypoglycaemia after an OGTT. In conclusion, profound changes in gut hormone secretion as a result of enhanced nutrient transit after foregut surgery likely underlie the early and late post-prandial symptoms seen in this group, and therapies specifically targeting the gut hormone axis, and GLP-1 in particular, could be the first targeted treatments for post-gastrectomy syndromes.

Opportunistic infections (OIs) have been identified as a leading cause of poor outcomes in the ARV therapy (ART) programme. In order to reduce OIs, the Malawi, MoH introduced routine prescription of cotrimoxazole preventive therapy (CPT) in 2005. The MoH also started scaling up a point-of-care electronic medical record (EMR) system in 2007 to improve monitoring and evaluation. This study had the following objectives: i) to quantify prescription of CPT before and after implementing EMR; ii) to compare the difference in CPT prescription before and after implementing EMR. A historically controlled study design was used to compare CPT prescriptions one year before, and one year after implementation of the EMR at two health facilities. The data indicated that there was a significant (P <0.001) decrease in CPT prescribing at one health facility and a significant increase in CPT prescription at another. / Health Studies / M.A. (Public Health)