4. Electronic Theses and Dissertations (ETDs) - Faculties submissions
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Item Histo-morphological Perturbations in the Testes of Diabetic Sprague Dawley Rat Following Atripla® And Alcohol Co-administration(University of the Witwatersrand, Johannesburg, 2023-08) Owembabazi, Elna; Nkomozepi, Pilani; Mbajiorgu, Ejikeme FelixA decline in male fertility is increasingly becoming a major concern in this millennium. However, the associated effects of diabetes, alcohol abuse, and cART use and their interaction which are clinically important in male reproductive health have not received proper attention. Each of these conditions (diabetes, alcohol abuse, and cART use) has been shown to negatively impact the male reproductive system. Moreover, diabetes, alcohol abuse, and cART are intricately connected and thus can and occur simultaneously in an individual, a scenario that might provoke severe reproductive dysfunctions. Therefore, this study investigated the impact of diabetes, alcohol abuse, cART use, and their combinations on testicular histomorphometry, reproductive hormone profile, oxidative and inflammatory markers, germ cell proliferation and apoptosis, and androgen receptor expression. A total of forty-eight HIV naive rats (48) were divided into two main groups, non-diabetic and diabetic groups, which were further subdivided into four subgroups consisting of six rats each. The non-diabetic groups (1-4); Group 1; Control, Group 2: Alcohol treated (A), Group 3: combination antiretroviral therapy treated (cART), and Group 4: alcohol plus cART treated (A+cART). The diabetic groups (5-8); Group 5: diabetic only (DM), Group 6: diabetic treated with alcohol (DM+A), Group 7: diabetic treated with cART (DM+cART), and Group 8: diabetic treated with both alcohol and cART (DM+A+cART). The rats were fed normal rat chow and terminated after 90 days of treatment. Blood was drawn through a cardiac puncture into plain vacutainers, thereafter, animals were perfused with 0.1M phosphate buffer, and the testes harvested, weighed, and then fixed in 10% neutral buffered formalin for histology and immunohistochemistry analysis. During the experimental period, hyperglycemia, low glucose tolerance, and polydipsia were observed in the diabetic groups (5-8) only. Though, a general decrease in testis weight, volume, and size was found in all treated groups compared to the control group, a significant (p˂0.05) decrease was detected in the DM+A group only. With exception of the DM+A+cART group, the epithelial area fraction, epithelial height, and tubule area and diameter reduced significantly in all treated groups. The luminal area fraction and luminal diameter which significantly reduced in cART, DM, and DM+cART groups, were increased in A+cART. Further, connective tissue and interstitial area fractions increased significantly in all treated groups. The spermatogonia increased significantly in A, cART, DM, and DM+A+cART groups relative to control group, but reduced significantly in DM+A. However, spermatocytes, round spermatids, and elongated spermatids decreased significantly in all treated groups, with exception of spermatocytes of the alcohol group. All treated groups showed a decrease in the number of Sertoli cells relative to the control but a significant decrease was only found in the DM+A group, but all treated groups had significantly decreased Leydig cell diameter and volume. Johnsen’s testicular score was significantly reduced in A, A+cART, DM, and DM+A treated groups. Additionally, varying severity of seminiferous tubules (ST) lesions such as shrinkage of ST, lifting of epithelium, widened intercellular space, karyolysis, epithelial sloughing, ST atrophy, multinucleated giant cells, and germinal epithelium derangement were observed in the treated animal groups. Further, the thickness ST basement membrane increased significantly in cART, DM, and DM+cART groups but testis capsule thickness increased significantly in A+cART, DM+A, and DM+A+cART groups. The testicular interstitial connective tissue fibers viz. collagen, reticulin, and elastin reduced significantly in all treated groups, except for the reticulin which was non-significantly decreased in the alcohol (A) group. Furthermore, luteinizing hormone was significantly elevated in A and A+cART groups but significantly reduced in the DM+A+cART group. However, follicle-stimulating hormone increased significantly in all treated groups, with exception of DM+cART group. Testosterone levels were significantly reduced in DM, DM+A, and DM+A+cART groups, but no significant difference (p>0.05) was found in the inhibin B level in all treated groups compared to the control. In addition, the intensity and number of Sertoli and Leydig cells expressing androgen receptor were significantly reduced in all treated groups, except for the number of Sertoli cells expressing androgen receptor in the alcohol group. Expression of inflammatory markers (IL-1β, TNF-α, and IL-6) was upregulated in all treated groups, with exception of IL-1β of the A+cART group and TNF-α of cART and A+cART groups. The markers for oxidative stress (iNOS, MDA, and 8-OHDG) and apoptosis (caspase 3) were upregulated in all treated groups, with exception of MDA in the alcohol group. Though, the number of germ cells expressing proliferation marker Ki-67 was significantly reduced in all treated groups, the staining intensity was significantly increased compared to the control group. The results show that diabetes, alcohol abuse, cART, and their combinations have deleterious effects on the testicular histoarchitecture and function, which are suggested to result from the upregulation of oxidants and cytokines and androgen receptor depletion. The results further suggest that the interaction arising from a co-presence of cART and alcohol in diabetic condition could mildly diminish their independent effects due to their common cytochrome P450 metabolic pathway. This study yielded invaluable data on the contribution of cART alcohol-diabetes interaction on the male reproductive functioning/dysfunction and hopefully will help clinicians in managing reproductive challenges in patients of this category.Item HbA1c Control in Type 2 Diabetic Patients with Coronary Artery Disease(University of the Witwatersrand, Johannesburg, 2023-10) Mhlaba, Lona; Tsabedze, Nqoba; Mpanya, DineoBackground: Type 2 diabetes mellitus (T2DM) patients with coronary artery disease (CAD) have an increased risk of recurrent cardiovascular events. These patients require optimal glucose control to prevent the progression of atherosclerotic cardiovascular disease (ASCVD). Current guideline recommendations target an HbA1c ≤7% to mitigate this risk. This study evaluated the level of HbA1c control in T2DM patients with CAD. Methods: This retrospective study assessed consecutive patients who presented with CAD to the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) between April 2017 and December 2019. The study included T2DM patients on anti-diabetic medication with angiographically confirmed CAD. HbA1c control was assessed using the HbA1c level measured at the index presentation and during the most recent follow-up visit. Results: The study population comprised 262 T2DM patients with a mean age was 61.3 ±10.4 years. Among the T2DM patients, 188 (71.8%) were males. At index presentation, 110 (42.1%) T2DM patients presented with ST-segment elevation myocardial infarction, 69 (26.4%) had non-ST-segment elevation myocardial infarction, 43 (16.5%) had unstable angina, and 39 (14.9%) had stable angina. The baseline median systolic blood pressure was higher in patients with an HbA1c ≤7% [136 mmHg (Interquartile range (IQR): 117-151) vs 124 mmHg (IQR: 112-142), p= 0.0121], compared to those with an HbA1c level above 7%. Furthermore, T2DM with an HbA1c ≤7% also had a higher median diastolic blood pressure [85 mmHg (IQR: 75.5-97) vs 78 mmHg (IQR: 71-88), p=0.0205]. After a median follow-up of 16.5 months (IQR: 7-29), 28.7% of the study participants had an HbA1c ≤7%. On multivariable regression analysis, patients with ST-segment depression on the resting electrocardiogram and index presentation had optimal glycaemic control (Odds ratio: 0.27, CI: 0.12-0.59, p= 0.001). Conclusion: After a median follow-up duration of 16.5 months, only 28.7% of T2DM patients with CAD had optimal glycaemic control. This finding underscores the substantial unmet need for optimal diabetes control in this very high-risk group.Item Clinical Characteristics and Outcomes of Patients with COVID Admitted to a Tertiary Care Centre: A Retrospective Study at Tshepong Hospital(University of the Witwatersrand, Johannesburg, 2023-11) Dullabh, Dixit Anil; Zachariah, DonIntroduction: In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in China. It has since then rapidly spread across the globe causing millions to die. In March 2020, the WHO declared coronavirus disease 2019 (COVID-19) a pandemic. It’s clinical presentation and outcomes have been variable across the world. Thus, an analysis of the clinical characteristic and outcomes of patients with COVID-19 at a local setting, namely Tshepong Hospital. Objective: To determine the clinical presentation and outcomes, and correlate clinical and biochemical parameters to outcomes of patients admitted with COVID-19 at Tshepong Hospital. Method: This is a single centre retrospective review of all patients with COVID-19 admitted at Tshepong Hospital during the period 1 June – 31 July 2020. The study contains both inferential and descriptive elements. Results: A total of 200 patients were admitted with COVID-19 during this study period, of which 135 were female and 65 males. The mean age was 53 years with no significant gender differences. 63% of patients had hypertension as a coexisting condition while 35% had diabetes mellitus. Presence of co-morbid conditions were associated with severe disease. Dyspnoea (73%) and cough (94%) were the predominant symptoms. Laboratory parameters including elevated white cell count, C-reactive protein, urea, and creatinine were associated with severe disease. Of the 200 patients, 36 were deemed as severe. 34 of these patients required ICU admissions. 17 demised showing a case fatality rate of 8%. Treatment options given were in keeping with guidelines. Conclusion: COVID-19 has proven to be a clinical and therapeutic challenge. Its main factors being its novelty and variable presentation across the globe. This study has shown that a local setting, not all data is congruent with national or global trends. This speaks to the need of more centres and countries looking at their own variation of COVID-19 presentations, thus challenging the clinical and therapeutic decisions around the disease.Item Developing a framework to improve glycaemic control among patients with type 2 diabetes mellitus in Kinshasa, democratic republic of the Congo(University of the Witwatersrand, Johannesburg, 2023) Lubaki, Jean-Pierre FinaDiabetes mellitus is a significant problem globally with a higher impact in developing countries. Glycaemic control is one of the main goals of type 2 diabetes treatment, as it delays or avoids the occurrence of diabetes related complications. In sub-Saharan Africa, including the Democratic Republic of the Congo, glycaemic control rates are sub optimal. This study aimed to develop a framework to improve glycaemic control among patients with type 2 diabetes in Kinshasa, Democratic Republic of the Congo. This project comprises four sub-studies. The first sub-study was a systematic review and meta-analysis of studies published from 2012 to 2022 on the prevalence and factors driving glycaemic control in sub-Saharan Africa. Younger and older age, gender, lower income, absence of health insurance, low level of education, place of residence, family history of diabetes, longer duration of diabetes, pill burden, treatment regimen, side effects, use of statins or antihypertensives, alcohol consumption, smoking, presence of comorbidities/complications, and poor management were associated with poor glycaemic control. On the other hand, positive perceived family support, adequate coping strategies, high diabetes health literacy, dietary adherence, exercise practice, attendance at follow-up visits, and medication adherence were associated with good glycaemic control. The second sub-study was a concurrent parallel mixed methods cross-sectional analytical study among a total of 643 patients with type 2 diabetes — 23 in the qualitative phase and 620 in the quantitative phase — on factors associated with poor glycaemic control in Kinshasa. Five themes were identified as explanations for poor glycaemic control: financial constraints, limited social and relational support, difficulties with lifestyle changes, beliefs and practices about diabetes, and ability to adapt to caring for the illness. The quantitative phase showed that about two-thirds of the participants (67.8%; n=420) had poor glycaemic control and more than half were on insulin monotherapy (53.9%; n=334). No sociodemographic or lifestyle characteristics were associated with poor glycaemic control. Participants on monotherapy with insulin (AOR: 1.72 (95%CI:1.17-2.55)) had increased odds of poor glycaemic control compared to participants on oral hypoglycaemic drugs. In contrast, participants having and those having uncontrolled blood pressure (AOR: 0.60 (95%CI:0.39-0.92)) were less likely to have poor glycaemic control compared to participants having controlled blood pressure. The third sub-study was a qualitative study on the perspectives of 16 healthcare providers and 10 patients with type 2 diabetes on improving glycaemic control in Kinshasa. From the healthcare providers statements regarding improving glycaemic control, three themes were identified: strengthening the healthcare system, supporting persons with diabetes/population, and adopting supportive health policies. From the persons with diabetes perspectives three themes were also identified: need for support for caring of the illness, need for enhanced knowledge about diabetes, and the need for better communication with healthcare providers. Using the results of the first three studies, the fourth sub-study, a Delphi study, brought together 36 experts on the management of diabetes, who developed and agreed on the following strategies for improving glycaemic control in Kinshasa: strengthening the healthcare system, enhancing the awareness of diabetes, alleviating the financial burden of diabetes, enhancing the adoption of lifestyle modifications, and reducing the proportion of undiagnosed diabetes. These five strategies included a total of 39 potential interventions. Strengthening the healthcare system for better care promotes better organization and provision of services for diabetes care. Enhancing the awareness of diabetes among the population/patients stresses the need to develop and share information about diabetes through the most appreciated channels by the population. Alleviating the financial burden of diabetes targets for the long-term the need for universal health coverage, and meanwhile, encouraging the development of community-based health insurance. It also includes the search for a reduction in costs of diabetes medicines and materials through public-private partnerships. Enhancing the adoption of lifestyle modifications in our setting passes through the provision of accurate information on the content of lifestyle changes, and developing realistic exercise and dietary plans. Reducing the proportion of undiagnosed patients with diabetes needs to increase the detection of diabetes by targeting high risk groups at the level of primary care settings. This study highlighted the need to ensure that patients with type 2 diabetes benefitted from the full package required for diabetes care in a broader framework of managing non-communicable diseases in Kinshasa