Modelling CD4 count and mortality in a cohort of patients initiated on HAART.

Master of Science in Statistics. University of KwaZulu-Natal. Durban, 2018.Longitudinally measured data and time-to-event or survival data are often associated in some ways, and are traditionally analyzed separately (Asar et al., 2015). However, separate analyses are not applicable in this case because they may lead to inefficient or biased results. To remedy this, joint models optimally incorporate all available information (longitudinal and survival data) simultaneously (Wulfsohn & Tsiatis, 1997). Furthermore incorporating all sources of data improves the predictive capability of the joint model and lead to more informative inferences for the purpose of decision-making (Seyoum & Temesgen, 2017). The primary goal of this analysis was to determine the effect of repeatedly measured CD4 counts on mortality. The standard time-to-event models require that the time-dependent covariates of interest are external; where the value of the covariate at a future time point is not affected by the occurrence of the event. This requirement would not be fulfilled in this setting, since the repeatedly measured outcome is directly related to the mortality mechanism. Hence, a joint modeling approach was required. We applied the methods developed in this thesis to the CAPRISA AIDS Treatment program (CAT). We also sought to determine if the patients’ baseline BMI (Body mass index), baseline age, gender, baseline viral load, baseline CD8 count, baseline TB status and clinic site, influence the evolution of the CD4 count over time. Various linear mixed models were fitted to the CD4 count, adjusting for repeated measurements, as well as including intercept and slope as random effects. Different types of covariance structures were assessed and the spatial spherical correlation structure was found to be the best fit. The Cox PH model was employed to model mortality. Finally the joint model for longitudinal and time-to-event data was fitted. Out of the 4014 patients, 1457 (36.30%) were male. There were more patients presenting without TB at ART initiation, 3042 (75.78%) compared to those with prevalent TB, 972 (24.22%). Results from the multivariable random effects model showed that the patients gender, age, baseline viral load and baseline CD8 cell count had statistically significant influences on the rate of change in CD4 cell count over time. The un-adjusted and adjusted hazards regression both found CD4:CD8 ratio, viral load, gender and age of patients to be significant predictors of mortality. The result from the joint model in this study indicated that CD4 count change due to HAART and mortality had been influenced jointly by gender, age, baseline viral load, baseline CD8 count, time (in years) , CD4:CD8 ratio and by the interaction effects of time (in years) with TB status, baseline viral load and baseline CD8 cell count. CD4 count proved to be significantly associated with mortality, after adjusting for age, gender and other potential confounders Model diagnostics were performed for validating model assumptions, and our joint model fitted quite well with fairly good diagnostic attributes. The methods that were developed in this thesis were applied to the CAPRISA AIDS Treatment program (CAT) between June 2004 to December 2013

Using joint models to study the association between CD4 count and the risk of death in TB/HIV data

BACKGROUND: The association structure linking the longitudinal and survival sub-models is of fundamental importance in the joint modeling framework and the choice of this structure should be made based on the clinical background of the study. However, this information may not always be accessible and rationale for selecting this association structure has received relatively little attention in the literature. To this end, we aim to explore four alternative functional forms of the association structure between the CD4 count and the risk of death and provide rationale for selecting the optimal association structure for our data. We also aim to compare the results obtained from the joint model to those obtained from the time-varying Cox model. METHODS: We used data from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) AIDS Treatment programme, the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) study, an open-label, three armed randomised, controlled trial between June 2005 and July 2010 (N=642). In our analysis, we combined the early and late integrated arms and compared results to the sequential arm. We utilized the Deviance Information Criterion (DIC) to select the final model with the best structure, with smaller values indicating better model adjustments to the data. RESULTS: Patient characteristics were similar across the study arms. Combined integrated therapy arms had a reduction of 55% in mortality (HR:0.45, 95% CI:0.28-0.72) compared to the sequential therapy arm. The joint model with a cumulative effects functional form was chosen as the best association structure. In particular, our joint model found that the area under the longitudinal profile of CD4 count was strongly associated with a 21% reduction in mortality (HR:0.79, 95% CI:0.72-0.86). Where as results from the time-varying Cox model showed a 19% reduction in mortality (HR:0.81, 95% CI:0.77-0.84). CONCLUSIONS: In this paper we have shown that the “current value” association structure is not always the best structure that expresses the correct relationship between the outcomes in all settings, which is why it is crucial to explore alternative clinically meaningful association structures that links the longitudinal and survival processes

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

Bayesian spatial modelling of intimate partner violence and associated factors among adult women and men : evidence from 2019/2020 Rwanda demographic and health survey

DATA AVAILABILITY : 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/ specific to our project but are available from the DHS team upon request.BACKGROUND : Intimate partner violence (IPV) remains a global public health concern for both men and women. Spatial mapping and clustering analysis can reveal subtle patterns in IPV occurrences but are yet to be explored in Rwanda, especially at a lower small-area scale. This study seeks to examine the spatial distribution, patterns, and associated factors of IPV among men and women in Rwanda. METHODS : This was a secondary data analysis of the 2019/2020 Rwanda Demographic and Health Survey (RDHS) individual-level data set for 1947 women aged 15–49 years and 1371 men aged 15–59 years. A spatially structured additive logistic regression model was used to assess risk factors for IPV while adjusting for spatial effects. The districtlevel spatial model was adjusted for fixed covariate effects and was implemented using a fully Bayesian inference within the generalized additive mixed effects framework. RESULTS : IPV prevalence amongst women was 45.9% (95% Confidence interval (CI): 43.4–48.5%) while that for men was 18.4% (95% CI: 16.2–20.9%). Using a bivariate choropleth, IPV perpetrated against women was higher in the North-Western districts of Rwanda whereas for men it was shown to be more prevalent in the Southern districts. A few districts presented high IPV for both men and women. The spatial structured additive logistic model revealed higher odds for IPV against women mainly in the North-western districts and the spatial effects were dominated by spatially structured effects contributing 64%. Higher odds of IPV were observed for men in the Southern districts of Rwanda and spatial effects were dominated by district heterogeneity accounting for 62%. There were no statistically significant district clusters for IPV in both men or women. Women with partners who consume alcohol, and with controlling partners were at significantly higher odds of IPV while those in rich households and making financial decisions together with partners were at lower odds of experiencing IPV. CONCLUSION : Campaigns against IPV should be strengthened, especially in the North-Western and Southern parts of Rwanda. In addition, the promotion of girl-child education and empowerment of women can potentially reduce IPV against women and girls. Furthermore, couples should be trained on making financial decisions together. In conclusion, the implementation of policies and interventions that discourage alcohol consumption and control behaviour, especially among men, should be rolled out.https://bmcpublichealth.biomedcentral.comam2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-beingSDG-05:Gender equalit

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

Bayesian spatial modelling of intimate partner violence and associated factors among adult women and men: evidence from 2019/2020 Rwanda Demographic and Health Survey

Abstract Background Intimate partner violence (IPV) remains a global public health concern for both men and women. Spatial mapping and clustering analysis can reveal subtle patterns in IPV occurrences but are yet to be explored in Rwanda, especially at a lower small-area scale. This study seeks to examine the spatial distribution, patterns, and associated factors of IPV among men and women in Rwanda. Methods This was a secondary data analysis of the 2019/2020 Rwanda Demographic and Health Survey (RDHS) individual-level data set for 1947 women aged 15–49 years and 1371 men aged 15–59 years. A spatially structured additive logistic regression model was used to assess risk factors for IPV while adjusting for spatial effects. The district-level spatial model was adjusted for fixed covariate effects and was implemented using a fully Bayesian inference within the generalized additive mixed effects framework. Results IPV prevalence amongst women was 45.9% (95% Confidence interval (CI): 43.4–48.5%) while that for men was 18.4% (95% CI: 16.2–20.9%). Using a bivariate choropleth, IPV perpetrated against women was higher in the North-Western districts of Rwanda whereas for men it was shown to be more prevalent in the Southern districts. A few districts presented high IPV for both men and women. The spatial structured additive logistic model revealed higher odds for IPV against women mainly in the North-western districts and the spatial effects were dominated by spatially structured effects contributing 64%. Higher odds of IPV were observed for men in the Southern districts of Rwanda and spatial effects were dominated by district heterogeneity accounting for 62%. There were no statistically significant district clusters for IPV in both men or women. Women with partners who consume alcohol, and with controlling partners were at significantly higher odds of IPV while those in rich households and making financial decisions together with partners were at lower odds of experiencing IPV. Conclusion Campaigns against IPV should be strengthened, especially in the North-Western and Southern parts of Rwanda. In addition, the promotion of girl-child education and empowerment of women can potentially reduce IPV against women and girls. Furthermore, couples should be trained on making financial decisions together. In conclusion, the implementation of policies and interventions that discourage alcohol consumption and control behaviour, especially among men, should be rolled out

Hen egg white bovine colostrum supplement reduces symptoms of mild/moderate COVID-19: a randomized control trial

Aim: The ability of a hen egg white bovine colostrum supplement to prevent severe COVID-19 was tested in a double-blind randomized control study. Methods: Adults with mild/moderate COVID-19, risk factors for severe disease, and within 5 days of symptom onset were assigned to the intervention (n = 77) or placebo (n = 79) arms. Symptoms were documented until day 42 post-enrollment and viral clearance was assessed at 11–13 days post-symptom onset. Results: One participant developed severe COVID-19. The severe-type symptom score was lower in the active arm at 11–13 days post-symptom onset (p = 0.049). Chest pain, fever/chills, joint pain/malaise, and sore throat were significantly less frequent in the active arm. No differences in viral clearance were observed. Conclusion: The intervention reduced symptoms of mild/moderate COVID-19. Clinical Trial Registration: DOH-27-062021-9191 (South African National Clinical Trials Register

Hen egg white bovine colostrum supplement reduces symptoms of mild/moderate COVID-19: a randomized control trial: Supplementary files

Aim: The ability of a hen egg white bovine colostrum supplement to prevent severe COVID-19 was tested in a double-blind randomized control study. Methods: Adults with mild/moderate COVID-19, risk factors for severe disease, and within 5 days of symptom onset were assigned to the intervention (n = 77) or placebo (n = 79) arms. Symptoms were documented until day 42 post-enrollment and viral clearance was assessed at 11–13 days post-symptom onset. Results: One participant developed severe COVID-19. The severe-type symptom score was lower in the active arm at 11–13 days post-symptom onset (p = 0.049). Chest pain, fever/chills, joint pain/malaise, and sore throat were significantly less frequent in the active arm. No differences in viral clearance were observed. Conclusion: The intervention reduced symptoms of mild/moderate COVID-19.</p