Survival modelling and analysis of HIV/AIDS patients on HIV care and antiretroviral treatment to determine longevity prognostic factors

Philosophiae Doctor - PhDThe HIV/AIDS pandemic has been a torment to the African developmental agenda, especially the Southern African Development Countries (SADC), for the past two decades. The disease and condition tends to affect the productive age groups. Children have also not been spared from the severe effects associated with the disease. The advent of antiretroviral treatment (ART) has brought a great relief to governments and patients in these regions. More people living with HIV/AIDS have experienced a boost in their survival prospects and hence their contribution to national developmental projects. Survival analysis methods are usually used in biostatistics, epidemiological modelling and clinical research to model time to event data. The most interesting aspect of this analysis comes when survival models are used to determine risk factors for the survival of patients undergoing some treatment or living with a certain disease condition. The purpose of this thesis was to determine prognostic risk factors for patients' survival whilst on ART. The study sought to highlight the risk factors that impact the survival time negatively at different survival time points. The study utilized a sample of paediatric and adult datasets from Namibia and Zimbabwe respectively. The paediatric dataset from Katutura hospital (Namibia) comprised of the adolescents and children on ART, whilst the adult dataset from Bulawayo hospital (Zimbabwe) comprised of those patients on ART in the 15 years and above age categories. All datasets used in this thesis were based on retrospective cohorts followed for some period of time. Different methods to reduce errors in parameter estimation were employed to the datasets. The proportional hazards, Bayesian proportional hazards and the censored quantile regression models were utilized in this study. The results from the proportional hazards model show that most of the variables considered were not signifcant overall. The Bayesian proportional hazards model shows us that all the considered factors had different risk profiles at the different quartiles of the survival times. This highlights that by using the proportional hazards models, we only get a fixed constant effect of the risk factors, yet in reality, the effect of risk factors differs at different survival time points. This picture was strongly highlighted by the censored quantile regression model which indicated that some variables were significant in the early periods of initiation whilst they did not significantly affect survival time at any other points in the survival time distribution. The censored quantile regression models clearly demonstrate that there are significant insights gained on the dynamics of how different prognostic risk factors affect patient survival time across the survival time distribution compared to when we use proportional hazards and Bayesian propotional hazards models. However, the advantages of using the proportional hazards framework, due to the estimation of hazard rates as well as it's application in the competing risk framework are still unassailable. The hazard rate estimation under the censored quantile regression framework is an area that is still under development and the computational aspects are yet to be incorporated into the mainstream statistical softwares. This study concludes that, with the current literature and computational support, using both model frameworks to ascertain the dynamic effects of different prognostic risk factors for survival in people living with HIV/AIDS and on ART would give the researchers more insights. These insights will then help public health policy makers to draft relevant targeted policies aimed at improving these patients' survival time on treatment

Association of the acute:chronic workload ratio and wellness scores in premier league male hockey players

Background: The relationship between acute:chronic workload ratios (ACWR) and the incidence of injury, as well as the relationship between subjective wellness scores and training load, is unclear in hockey players. Objectives: This study investigated these relationships to determine if the ACWR is a useful workload management tool for field hockey players. In addition, the study investigated the association between specific subjective wellness scores (fatigue, sleep quality, general muscle soreness, mood and stress level) and the acute:chronic workload ratio and training load. The study also assessed the association between individual players’ training loads with the self-reported wellness scores. Methods: Fourteen male field hockey players from the men’s first team at the University of the Witwatersrand participated in the study over ten weeks during a premier league competition phase. A Google form was completed within thirty minutes of every training session/match. This form consisted of questions that allowed for the calculation of the ACWR. Results: No incidence of injury was reported during the ten- week period. ACWR scores ranged between 0.67 and 1.87. The ACWR was associated with general muscle soreness (p = 0.010) and training load was associated with fatigue (p = 0.002), sleep quality (p = 0.05), general muscle soreness (p = 0.004), and mood (p=0.025). Conclusion: There may be some merit in the use of subjective wellness measures as workload management tools in field hockey. Further research is required to determine if there is an optimal ACWR for this sport

Mapping evidence on the burden of breast, cervical, and prostate cancers in Sub-Saharan Africa : a scoping review

BACKGROUND : Cancer remains a major public health problem, especially in Sub-Saharan Africa (SSA) where the provision of health care is poor. This scoping review mapped evidence in the literature regarding the burden of cervical, breast and prostate cancers in SSA. METHODS : We conducted this scoping review using the Arksey and O’Malley framework, with five steps: identifying the research question; searching for relevant studies; selecting studies; charting the data; and collating, summarizing, and reporting the data. We performed all the steps independently and resolved disagreements through discussion. We used Endnote software to manage references and the Rayyan software to screen studies. RESULTS : We found 138 studies that met our inclusion criteria from 2,751 studies identified through the electronic databases. The majority were retrospective studies of mostly registries and patient files (n = 77, 55.8%), followed by cross-sectional studies (n = 51, 36.9%). We included studies published from 1990 to 2021, with a sharp increase from 2010 to 2021. The quality of studies was overall satisfactory. Most studies were done in South Africa (n = 20) and Nigeria (n = 17). The majority were on cervical cancer (n = 93, 67.4%), followed by breast cancer (67, 48.6%) and the least were on prostate cancer (48, 34.8%). Concerning the burden of cancer, most reported prevalence and incidence. We also found a few studies investigating mortality, disability-adjusted life years (DALYs), and years of life lost (YLL). CONCLUSIONS : We found many retrospective record review cross-sectional studies, mainly in South Africa and Nigeria, reporting the prevalence and incidence of cervical, breast and prostate cancer in SSA. There were a few systematic and scoping reviews. There is a scarcity of cervical, breast and prostate cancer burden studies in several SSA countries. The findings in this study can inform policy on improving the public health systems and therefore reduce cancer incidence and mortality in SSA.The National Science Foundation.https://www.frontiersin.org/journals/public-healthdm2022School of Health Systems and Public Health (SHSPH

Prevalence and factors associated with self-reported HIV testing among adolescent girls and young women in Rwanda : evidence from 2019/20 Rwanda Demographic and Health Survey

AVAILABILITY OF DATA AND MATERIALS : The dataset generated and analysed during the current study are not publicly available since we received a data access letter from the DHS team https://dhsprogram.com/ specifc to our project but are available from the DHS team upon request.BACKGROUND : HIV/AIDS remains a major public health problem globally. The majority of people living with HIV are from Sub-Saharan Africa, particularly adolescent girls and young women (AGYW) aged 15-24 years. HIV testing is crucial as it is the gateway to HIV prevention, treatment, and care; therefore this study determined the prevalence and factors associated with self-reported HIV testing among AGYW in Rwanda. METHODS : We conducted secondary data analysis on the AGYW using data extracted from the nationally representative population-based 2019/2020 cross-sectional Rwanda Demographic and Health Survey (DHS). We described the characteristics of study participants and determined the prevalence of HIV testing and associated factors using the multivariable logistic regression model. We adjusted all our analyses for unequal sampling probabilities using survey weights. RESULTS : There were a total of 5,732 AGYW, with the majority (57%) aged 15-19 years, 83% were not living with a man, 80% were from rural areas, 29% were from the East region, and 20% had a history of pregnancy. Self-reported HIV testing prevalence was 55.4% (95%CI: 53.7 to 57.0%). The odds of ever having an HIV test were significantly higher for those aged 20-24 years (aOR 2.87, 95%CI: 2.44 to 3.37); with higher education (aOR 2.41, 95%CI:1.48 to 3.93); who were rich (aOR 2.06, 95%CI:1.57 to 2.70); with access to at least one media (aOR 1.64, 95%CI: 1.14 to 2.37); who had ever been pregnant (aOR 16.12, 95%CI: 9.60 to 27.07); who ever had sex (aOR 2.40, 95%CI: 1.96 to 2.95); and those who had comprehensive HIV knowledge (aOR 1.34, 95%CI: 1.17 to 1.54). CONCLUSIONS : We report an unmet need for HIV testing among AGYW in Rwanda. We recommend a combination of strategies to optimize access to HIV testing services, especially among the 15-19 years adolescent girls, including facility-based testing, school and community outreach, awareness campaigns on HIV testing, and home-based testing through HIV self-testing.http://www.biomedcentral.com/bmcpublichealtham2023School of Health Systems and Public Health (SHSPH

Estimated SARS-CoV-2 infection rate and fatality risk in Gauteng Province, South Africa : a population-based seroepidemiological survey

DATA AVAILABILITY : De-identified individual-level data and data sets generated during the current study are available for researchers who provide a methodologically sound proposal. If approved, the requestor must sign a data-use agreement. Additionally, the study protocol is available on request. All requests must be addressed to the corresponding author. Data will be available 3 months after publication of this manuscript.BACKGROUND : Limitations in laboratory testing capacity undermine the ability to quantify the overall burden of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. METHODS : We undertook a population-based serosurvey for SARS-CoV-2 infection in 26 subdistricts, Gauteng Province (population 15.9 million), South Africa, to estimate SARS-CoV-2 infection, infection fatality rate (IFR) triangulating seroprevalence, recorded COVID-19 deaths and excess-mortality data. We employed three-stage random household sampling with a selection probability proportional to the subdistrict size, stratifying the subdistrict census-sampling frame by housing type and then selecting households from selected clusters. The survey started on 4 November 2020, 8 weeks after the end of the first wave (SARS-CoV-2 nucleic acid amplification test positivity had declined to <10% for the first wave) and coincided with the peak of the second wave. The last sampling was performed on 22 January 2021, which was 9 weeks after the SARS-CoV-2 resurgence. Serum SARS-CoV-2 receptor-binding domain (RBD) immunoglobulin-G (IgG) was measured using a quantitative assay on the Luminex platform. RESULTS : From 6332 individuals in 3453 households, the overall RBD IgG seroprevalence was 19.1% [95% confidence interval (CI): 18.1–20.1%] and similar in children and adults. The seroprevalence varied from 5.5% to 43.2% across subdistricts. Conservatively, there were 2 897 120 (95% CI: 2 743 907–3 056 866) SARS-CoV-2 infections, yielding an infection rate of 19 090 per 100 000 until 9 January 2021, when 330 336 COVID-19 cases were recorded. The estimated IFR using recorded COVID-19 deaths (n = 8198) was 0.28% (95% CI: 0.27–0.30) and 0.67% (95% CI: 0.64–0.71) assuming 90% of modelled natural excess deaths were due to COVID-19 (n = 21 582). Notably, 53.8% (65/122) of individuals with previous self-reported confirmed SARS-CoV-2 infection were RBD IgG seronegative. CONCLUSIONS : The calculated number of SARS-CoV-2 infections was 7.8-fold greater than the recorded COVID-19 cases. The calculated SARS-CoV-2 IFR varied 2.39-fold when calculated using reported COVID-19 deaths (0.28%) compared with excess-mortality-derived COVID-19-attributable deaths (0.67%). Waning RBD IgG may have inadvertently underestimated the number of SARS-CoV-2 infections and conversely overestimated the mortality risk. Epidemic preparedness and response planning for future COVID-19 waves will need to consider the true magnitude of infections, paying close attention to excess-mortality trends rather than absolute reported COVID-19 deaths.The Bill and Melinda Gates Foundation.https://academic.oup.com/ijehj2023Family Medicin

Developing excellence in biostatistics leadership, training and science in Africa: How the Sub-Saharan Africa Consortium for Advanced Biostatistics (SSACAB) training unites expertise to deliver excellence

The increase in health research in sub-Saharan Africa (SSA) has generated large amounts of data and led to a high demand for biostatisticians to analyse these data locally and quickly.  Donor-funded initiatives exist to address the dearth in statistical capacity, but few initiatives have been led by African institutions. The Sub-Saharan African Consortium for Advanced Biostatistics (SSACAB) aims to improve biostatistical capacity in Africa according to the needs identified by African institutions, through (collaborative) masters and doctoral training in biostatistics. We describe the SSACAB Consortium, which comprises 11 universities and four research institutions- supported by four European universities. SSACAB builds on existing resources to strengthen biostatistics for health research with a focus on supporting biostatisticians to become research leaders; building a critical mass of biostatisticians, and networking institutions and biostatisticians across SSA.  In 2015 only four institutions had established Masters programmes in biostatistics and SSACAB supported the remaining institutions to develop Masters programmes. In 2019 the University of the Witwatersrand became the first African institution to gain Royal Statistical Society accreditation for a Biostatistics MSc programme. A total of 150 fellows have been awarded scholarships to date of which 123 are Masters fellowships (41 female) of which with 58 have already graduated. Graduates have been employed in African academic (19) and research (15) institutions and 10 have enrolled for PhD studies. A total of 27 (10 female) PhD fellowships have been awarded; 4 of them are due to graduate by 2020. To date, SSACAB Masters and PhD students have published 17 and 31 peer-reviewed articles, respectively. SSACAB has also facilitated well-attended conferences, face-to-face and online short courses. Pooling the limited biostatistics resources in SSA, and combining with co-funding from external partners is an effective strategy for the development and teaching of advanced biostatistics methods, supervision and mentoring of PhD candidates

Water Poverty and Rural Development: Evidence from South Africa

Using household data from the 2009 General Household Survey, this paper examines the role of natural resource scarcity in rural development in South Africa, with a particular focus on water scarcity. It seeks to examine whether there is a direct link between household water and economic poverty of rural households, with households’ total monthly income used as an indicator of economic poverty. An adaptation of a comprehensive water poverty index, which considers water access, quality, use, and water-related environmental aspects is used to measure household-level water poverty. The empirical analysis uses an instrumental variable estimation framework in order to deal with the potential endogeneity between water and economic poverty. Results support the existence of a direct link between water and economic poverty, with water-poor households likely to be economically poor. In particular, the results suggest that access to good quality water from a reliable source significantly enhances rural households’ economic status. Also, access to water determines the realized impact of overall water poverty on a household’s economic status. The paper thus cautions development policy not to treat water and economic poverty in isolation; there is need for development policy in South Africa to streamline water use in rural development. In addition, development policies need to take into account the role of household heterogeneity in conditioning both household water and economic poverty levels

Diabetic control and compliance using glycated haemoglobin (HbA1C) testing guidelines in public healthcare facilities of Gauteng province, South Africa

Objective This study aimed at evaluating diabetic control and compliance with testing guidelines, across healthcare facilities of Gauteng Province, South Africa, as well as factors associated with time to achieve control. South Africa’s estimated total unmet need for care for patients with type 2 diabetes mellitus is 80%. Research design, methods and findings The data of 511 781 patients were longitudinally evaluated. Results were reported by year, age category, race, sex, facility and test types. HbA1C of ≤7% was reported as normal, >7 - ≤9% as poor control and >9% as very poor control. The chi-squared test was used to assess the association between a first-ever HbA1C status and variables listed above. The Kaplan-Meier analysis was used to assess probability of attaining control among those who started with out-of-control HbA1C. The extended Cox regression model assessed the association between time to attaining HbA1C control from date of treatment initiation and several covariates. We reported hazard ratios, 95% confidence intervals and p-values. Data is reported for 511 781 patients with 705 597 laboratory results. Poorly controlled patients constituted 51.5%, with 29.6% classified as very poor control. Most poorly controlled patients had only one test over the entire study period. Amongst those who started with poor control status and had at least two follow-up measurements, the likelihood of achieving good control was higher in males (adjusted Hazard Ratio (aHR) = 1.16; 95% CI:1.12–1.20; pConclusion This study highlights poor adherence to guidelines for diabetes monitoring

Factors associated with adherence to HIV testing guidelines among HIV negative female sex workers in Kampala Uganda

Background: Frequent HIV testing at intervals of every three to six months is recommended among HIV negative female sex workers as the first entry point to HIV prevention and treatment. In this study, we examined the extent to which HIV negative female sex workers adhere to the testing guidelines by measuring the frequency of testing in the last 12 months and identified associated factors among female sex workers in Kampala Uganda. Methods: We conducted a cross-sectional study using structured questionnaires. Using equal probability selection method, 12 hotspots were selected, and 200 participants interviewed based on proportional allocation in each hotspot. We used descriptive statistics to describe female sex workers’ characteristics, and multivariable logistic regression model to determine the factors associated with their adherence to the HIV testing guidelines. Adherence to the HIV testing guidelines was defined as having tested three or more times in the last 12 months. Factors with p-value ≤0.05 significance level were considered statistically significant. Results: From the 200 study participants, 43% were aged 25-30 years, joined sex work between the ages of 18 to 24 years, 49% had attained primary and 41% secondary school respectively. 88% reported HIV testing status, of which 56% had tested three or more times in the 12 months preceding the survey. Attaining secondary education, was independently associated with adherence to the HIV testing guidelines (OR 1.86, 95% CI: 1.01 - 3.44, p=0.047). Those that had tested for STIs in the last three months (OR= 2.13, 95% CI: 0.95 - 4.74, p=0.065) and accessed HIV testing in a drop-in centre (OR= 5.90, 95% CI: 0.71 - 49.1, p=0.101) had higher odds of adhering to the HIV testing guidelines Conclusion: This study found suboptimal adherence to the HIV testing guidelines among HIV negative female sex workers. Interventions such as HIV self-testing that improve access to, and frequency of HIV testing need to be taken to scale. There is need for rigorous behaviour change program evaluation to continually refine understanding of the message mix, to ensure simplified and easy to comprehend awareness messages are designed for female sex workers with no formal education

Effects of modulated electro-hyperthermia (mEHT) on two and three year survival of locally advanced cervical cancer patients

Simple Summary More than 80% of global cervical cancer cases and deaths occur in Low-to-Middle-Income Countries. Improving the efficacy of treatments without increasing the costs in these regions is therefore imperative. The aim of our Phase III Randomised Controlled Trial was to investigate the effects of the addition of a mild heating technology, modulated electro-hyperthermia, to chemoradiotherapy protocols for the management of locally advanced cervical cancer patients in a resource-constrained setting. We previously reported on the positive outcomes on local disease control, quality of life, and early toxicity. Our recent results showed a significant improvement in two and three year disease free survival, without any significant changes to the toxicity profile, and with an improvement in quality of life, alongside a cost saving over three years. The effect was most significant in patients with Stage III disease, and a significant systemic effect was observed in patients with distant nodal metastases. (1) Background: Modulated electro-hyperthermia (mEHT) is a mild to moderate, capacitive-coupled heating technology that uses amplitude modulation to enhance the cell-killing effects of the treatment. We present three year survival results and a cost effectiveness analysis from an ongoing randomised controlled Phase III trial involving 210 participants evaluating chemoradiotherapy (CRT) with/without mEHT, for the management of locally advanced cervical cancer (LACC) in a resource constrained setting (Ethics Approval: M120477/M704133; ClinicalTrials.gov ID: NCT033320690). (2) Methods: We report hazard ratios (HR); odds ratio (OR), and 95% confidence intervals (CI) for overall survival and disease free survival (DFS) at two and three years in the ongoing study. Late toxicity, quality of life (QoL), and a cost effectiveness analysis (CEA) using a Markov model are also reported. (3) Results: Disease recurrence at two and three years was significantly reduced by mEHT (HR: 0.67, 95%CI: 0.48-0.93, p = 0.017; and HR: 0.70, 95%CI: 0.51-0.98, p = 0.035; respectively). There were no significant differences in late toxicity between the groups, and QoL was significantly improved in the mEHT group. In the CEA, mEHT + CRT dominated the model over CRT alone. (4) Conclusions: CRT combined with mEHT improves QoL and DFS rates, and lowers treatment costs, without increasing toxicity in LACC patients, even in resource-constrained settings