Browsing by Subject "Biostatistics"
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- ItemOpen AccessEarly life lead exposure as a risk factor for aggressive and violent behaviours in young adults: A retrospective systematic review(2020) Obamuyide, Henry; Matzopoulos, Richard; Kredo,TamaraOver 1.3 million individuals die each year from preventable violence. Many of these violent acts are perpetrated by youths. Despite several initiatives, the prevalence of youth violence remains high. Early life lead exposure is a possible cause of aggressive and violent behaviour in young adults. Several aggregate-level and individual-level studies report an increase in risk of violent behaviour with increasing lead exposure. However, the evidence base for the role of lead in violence is conflicting as many other studies did not support this claim. No systematic synthesis of current evidence at the individual level exists to critically assess this association. Therefore, we planned to conduct a systematic review and meta-analysis of studies examining the relationship between lead exposure in early life and the later development of aggressive and violent behaviour in young adulthood at the individual level. Extensive literature searches, including of grey literature, were performed to identify potentially relevant articles. Studies for inclusion were screened by two reviewers and selected using pilot-tested eligibility form. The two reviewers independently assessed risk of bias and carried out data extraction before analysis. A systematic review and meta-analysis of currently available evidence was carried out. Searches were conducted between September 2019 and October 2019. We identified a total of 2182 reports, out of which six studies in 7 publications were eligible. All of the studies were conducted in high income countries, though a few recruited participants from low-income communities. There were varying definitions of violence, ranging from very narrow to wide and the outcomes were measured as either a count or binary variable. Despite the diversity in study settings, the direction of findings was remarkably homogenous. For studies reporting dichotomous variable, the odds of being arrested or convicted for violent behaviour increases with increasing blood lead level (OR 1.13 to 1.16 with each 5µg/dl rise in blood lead) after controlling for other variables. For the studies reporting count outcome, blood lead may explain up to 63% of the variability in arrest or conviction rates after adjusting for co-variates (IRR for each 5µg/dl rise in blood lead level:1.1 to 1.13). Overall, using a random-effect model with restricted maximum likelihood estimation method, blood lead was associated with a higher risk of exhibiting violent behaviour (OR 1.16; 95% CI 1.10 – 1.23). There was insufficient data to perform sensitivity analyses based on study design, quality of studies or conduct a dose response meta-analysis. We found that an increased exposure to lead in childhood is associated with a higher risk of being arrested or convicted for violent behaviour in young adulthood. In this context, environmental lead control may help to reduce the prevalence of aggressive and violent behaviour in young adults and should be integrated into violence prevention strategies. Despite the ubiquity of environmental lead, the importance of violence as a public health and social concern and the considerable debate their association has generated, we found very few good quality studies that reported enough methodological detail for evidence synthesis. More studies with better quality and from different settings need to be conducted.
- ItemOpen AccessEvidence-based vaccinology: supporting evidence-informed considerations to introduce routine hepatitis A immunization in South Africa(2023) Patterson, Jenna; Kagina, Benjamin; Cleary Susan; Muloiwa, Rudzani; Hussey, Gregory; Silal, SheetalHepatitis A is a vaccine preventable disease caused by the Hepatitis A Virus (HAV). Currently, South Africa is classified by the World Health Organization (WHO) as a high hepatitis A endemic region where 90% of children are assumed to be “naturally immunised” following HAV exposure before the age of 10 years old. In high hepatitis A endemic settings, routine vaccination against HAV is not necessary due to high rates of “natural immunization”. Recent data suggest a possible shift from high to intermediate HAV endemicity may be occurring in South Africa. Countries with intermediate HAV endemicity and no routine hepatitis A vaccination program have a high risk of experiencing hepatitis A outbreaks and high costs associated with care. Currently, there is no routine vaccination program against HAV in South Africa. The aim of this PhD was to generate evidence for decision making on whether a routine vaccination program against HAV should be considered for introduction into the South African Expanded Program on Immunizations (EPI-SA). The objectives included gathering context-specific evidence on the epidemiologic features of hepatitis A, clinical characteristics of the disease, hepatitis A vaccine characteristics and cost of case management. Using this evidence, the PhD estimated the future epidemiology of hepatitis A and impacts of routine hepatitis A vaccination scenarios in the country. The PhD's overall methods were informed by the principles of Evidence-Based Vaccinology for developing vaccine recommendations. The project included a mixed-methods approach: systematic reviews, a retrospective clinical folder review, mathematical modelling, and economic evaluation. A dynamic transmission model was built to forecast the future epidemiology of hepatitis A and to simulate the impacts of several different childhood hepatitis A vaccination strategies in South Africa. Selected findings have been published in relevant peer-reviewed journals. In addition, a technical dossier was prepared to submit to the South African National Advisory Group on Immunization (NAGI) on behalf of the Hepatitis A Working Group for considerations of introducing hepatitis A vaccination into the South African EPI.
- ItemOpen AccessHIV-related knowledge and antiretroviral therapy outcomes (ART) in HIV infected women initiating ART during pregnancy(2018) Brown, Karryn; Lesosky, MaiaThe characteristics of South Africa’s HIV epidemic mean that approximately 28% of women presenting for antenatal care, are HIV-infected. Maternal HIV-infection can lead to mother-to-child transmission (MTCT) of HIV during pregnancy, labour, delivery or breastfeeding if viral load (VL) is not well controlled by antiretroviral therapy (ART). Globally, 90% of pediatric infections occur via MTCT, though lifelong ART is reducing the rate of new infections. Full benefits of ART can only be realized when ART adherence is high. Evidence from South Africa and elsewhere has shown that ART adherence in pregnant and postpartum women is suboptimal. Potential drivers of suboptimal adherence may include poor or inadequate knowledge of HIV and ART. This thesis investigates how HIV-infected pregnant and postpartum women’s knowledge of HIV and ART-related information may be associated with ART adherence as evaluated by HIV VL measures. Components of this thesis include the research protocol, a literature review of previous studies exploring the relationship between knowledge and HIV-related health outcomes in Sub-Saharan Africa and a manuscript describing the results of an investigation into predictors of HIV and ART-related knowledge and the association of knowledge with maternal vireamia (VL>1000copies/mL). This data for analysis came from a cohort of 376 HIV-infected pregnant women, initiating ART during pregnancy, at a primary care antenatal facility in Gugulethu, South Africa. Participants were followed from their first antenatal visit until twelve months postpartum. Knowledge of HIV and ART-related information were assessed at three time points by two knowledge inventories and items were classified as either relating to general knowledge or prevention of MTCT. HIV VL was measured at delivery and twelve months postpartum. Demographic characteristics were surveyed at the first antenatal visit. Analyses included univariable and multivariable regression models to estimate potential predictors of knowledge among demographic and clinical characteristics, as well as to estimate the association between knowledge and maternal vireamia at delivery and twelve months postpartum. We found that HIV and ART knowledge increased marginally over the repeated study visits. Knowledge relating to general HIV or ART information was typically good while knowledge on PMTCT was lacking. Education (OR=-0.52; 95% CI=-0.83- -0.21; P=0.001), previous HIV diagnoses (OR=-0.36; 95% CI=-0.09- 0.63; P=0.009), and weeks on ART at delivery (OR=-0.03; 95% CI=0.00-0.06; P=0.047) were statistically significant predictors of HIV knowledge in adjusted analyses. The associations between the various knowledge outcomes and vireamia at delivery and twelve months postpartum were mixed and generally not statistically significant. In summary, HIV and ART knowledge both increased with increasing time in care and general knowledge was better than knowledge specific to MTCT. Education, timing of HIV diagnoses and time on ART were identified as potential predictors of HIV-related knowledge. Generally, knowledge of HIV or ART was not meaningfully associated with vireamia at delivery or at twelve months postpartum. There remain significant gaps in the knowledge of HIV-infected women, of childbearing age, around how HIV is transmitted and how to reduce the risk of MTCT.
- ItemOpen AccessLatent Variable Models for Longitudinal Outcomes from a Parenting Intervention Study(2019) Mccready, Carlyle; Little, FrancescaThis research project analysed data collected with the use of self-reporting questionnaires and observational video scores in order to determine the level of success achieved by the Sinovuyo Caring Families Programme (SCFP). The SCFP aimed to reduce harsh parenting practices and child behavioural problems in high-risk South African families. This research project examined the use of structural equation modelling (SEM) for longitudinal profiles and latent growth mediation modelling. Improved behaviour was observed in terms of reported child behaviour problems and reported harsh parenting with differences between the intervention and control groups directly after the completion of the 3-month intervention program. Improved behaviour was also observed in terms of reported positive parenting with differences between the intervention and control groups directly after the completion of the 3- month intervention program and at the 12-month follow-up occasion. No improvement in observed child behaviour was mediated through reported positive parenting or reported harsh parenting. Furthermore, the intervention program led to improved positive parenting behaviour directly after the 3-month intervention period, however the improved behaviour of the parent did not act as a mediating variable and no improvement in child behaviour was observed as a result.
- ItemOpen AccessLongitudinal analysis of Brain Metabolite levels for HIV infected Children from ages five to eleven(2020) Van Biljon, Noëlle; Little, Francesca; Meintjes, Ernesta; Holmes, Martha; Robertson, FrancesHIV infected (HIV+) children initiate antiretroviral therapy (ART) early in life and remain on it lifelong. However, the long-term impact of ART and HIV on the maturing brain is not well documented and longitudinal neuroimaging studies are rare, especially in developing countries most heavily impacted by HIV/AIDS where access to imaging resources are limited. We have examined HIV related changes in metabolite level trajectories from 5-11 years in three brain regions using Magnetic Resonance Spectroscopy (MRS). We used univariate linear mixed effect models to identify independent profiles of the metabolites measured in each region of the brain. To explore the metabolite trends in a multivariate setting we generated multilevel mixed effects models, and correlated response models. There was an element of confounding introduced through the change of MRI scanner during the follow-up period and we compare different methods to resolve this issue. Consequently, we did observe differences in metabolite profiles from HIV+ children compared to HIV uninfected (HIV-) controls. This suggests that while these children are on ART treatment, there is still some underlying effect on their neurochemistry which sets their development apart from the normal healthy profiles we expect.
- ItemOpen AccessTemporal interactions of microbiota in longitudinal nasopharyngeal samples and association with lower respiratory tract infection(2019) Rambau, Brian Thabane; Lesosky, MaiaDuring aetiology of respiratory illnesses, it is widely accepted that infection is preceded by nasopharyngeal (NP) colonisation with bacteria and that NP flora develop early in childhood (during the first year of life). The presence of multiple NP bacteria results in competitive and synergistic associations, however temporal organism interactions have rarely been explored due to limited availability of longitudinal data sets, and the complex statistical methods needed. This study aimed to identify, describe and quantify the temporal interactions existing between selected key bacteria colonizing the nasopharynx in young children (up to 1 year old), and to further compare these patterns in children who go on to develop pneumonia compared to those who do not. The significance of the study, as well as the objectives of the study, methods and data analysis plan are outlined in the study protocol (Part A). A summary of what is currently known about NP bacterial species interactions is presented as part of the literature review (Part B). The primary aim of the literature review was to describe the prevalence of NP carriage of four NP colonizing bacteria of interest: S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis in children, as well as identify any risk factors or confounding associations. The literature review furthermore aimed to identify previously described NP bacterial species interaction patterns, as well as providing a summary of statistical approaches previously employed in the studying bacterial interactions. A manuscript presenting the subsequent analysis of these data is included as Part C. This study was a secondary data analysis of 760 infants enrolled in a birth cohort with NP swabs collected every two weeks for the first year of life and additionally at episodes of lower respiratory tract infections (LRTI). Kaplan-Meier estimates were used to visualize time to first carriage. Generalised estimating equations with a logit link and adjusted for repeated measures were used to estimate the time varying association of NP bacteria carriage with development of pneumonia, while enabling adjustment by key confounders. Markov multi state models (MSMs) were used to describe NP bacterial acquisition with age and estimation of clearance probabilities, new acquisition or persistent acquisition. There were 760 individuals included in the analysis, with a total of 16,346 NP samples available and a median 364 person-days (IQR 346 – 365 person-days). S. pneumoniae was predominant, found in >55% of all samples and demonstrating carriage in >95% of individuals at least once by 12 months of age. S. aureus was both less common (25% of samples and 88% of individuals) but also had a strikingly different pattern of first acquisition compared to the other three organisms, demonstrating a rapid increase in carriage prevalence until approximately four weeks and subsequently decreasing. S. pneumoniae had the highest co-carriage prevalence overall with H. influenzae and M. catarrhalis (both 25%) but this varied by age category. In contrast, co-carriage with S. aureus was less prevalent with either S. pneumoniae (12%), H. influenzae (5%) or M. catarrhalis (6%). Co-carriage frequencies differed considerably by age category, at least partially reflecting the relative prevalence of carriage by age. Carriage and co-carriage rates were similar among those children that experienced LRTI compared to those that did not. Seasonal carriage varied, but to a small extent compared to variance by age. Models adjusting for sex, site, season of birth and age found temporally sustained positive associations between the co-carriages of S. pneumoniae with H. influenzae, and M. catarrhalis, but no association with S. aureus. Clear differences occur in the co-carriage patterns of S. pneumoniae with other organisms. The probability of acquisition of S. pneumoniae is modified by earlier carriage of H. influenzae or M. catarrhalis. Positive H. influenzae carriage increases the probability of acquisition of S. pneumoniae with transition probabilities from 0.15 (95% CI 0.14-0.17) to 0.36 (95% CI 0.17, 0.54) after 28 days of age, compared to the same period probability of acquisition of S. pneumoniae alone at 0.015 (95% CI 0.043-0.076) to 0.088 (95% CI 0.075- 0.10). There is no difference in the clearance of S. pneumoniae related to H. influenzae carriage, but clearance of H. influenzae before 6 months of age is far less likely if coming from a state of co-carriage (probability between 0.04 - 0.07) compared to sole carriage (probability 0.23 - 0.12). The only evidence of differences in clearance probability in the models investigating S. pneumoniae and M. catarrhalis are in the probability of M. catarrhalis clearance before 28d which is 0.24 (95% CI 0.15 - 0.38) if carried alone and only 0.058 (55%CI 0.01 - 0.30) if carried with S. pneumoniae, though these confidence intervals overlap.Through this modelling we found positive sustained interactions between S. pneumoniae and both H. influenzae, and M. catarrhalis, where models indicated that preceding carriage or colonisation with either H. influenzae, and M. catarrhalis may increase the risk of colonisation with S. pneumonia. Timing of carriage and overall prevalence of carriage are in line with other findings in similar populations with overall high exposure to S. pneumoniae, H. influenzae, M. catarrhalis during the first year of life and rapid and early exposure to S. aureus. Carriage, co-carriage and transition frequency did not vary appreciably when comparing children who experienced LRTI in the first year of life compared to those who did not, suggesting that overall exposures are similar, but that further modelling is required to understand the specific timing of associations in relations to LRTI.
- ItemOpen AccessThe quality and variation of spirometry reads for testing lung function in children in sub Saharan Africa(2019) Maduna, Dumsile Nontokozo; Lesosky, Maia RoseBackground: Lung function assessments have become the cornerstone of understanding the ever-increasing burden of non-communicable respiratory conditions worldwide. The introduction of pulmonary function testing (PFT) has made maximal expiratory flow/volume (MEFV) measurements the basis of lung function assessments and spirometry the most widely used diagnostic tool for lung function testing. The effectiveness of spirometry to distinguish between normal and abnormal lung function has been realised in adults; however, there is an observed history of misinterpretation in children. The quality of measurements remains a major concern in children and good quality measurements are critical in the diagnosis of any health condition as well as understanding the burden of abnormal lung function in children in low and middleincome countries (LMICs). Objective: This study describes the quality and variation of spirometry reads for evaluating lung function in children in a Malawian population. Methods: This study was conducted according to a protocol developed and granted ethical approval by the Faculty of Health Sciences Human Research Ethics Committee, University of Cape Town (HREC REF 669/2018). The protocol describes the parent study data collection, project analysis plans and ethical and other considerations. Current literature on lung function using spirometry was systematically reviewed and synthesised. The literature review included primary studies and review articles that included spirometry measurement in children from settings in Africa and other low- and middle- income countries. The descriptive study involves secondary analysis of data contributed by the Children Lung Health study, a cross-sectional survey conducted in Malawi. Spirometry measurements from 802 healthy children aged 6-8 years, inexperienced in performing MEFV manoeuvres, are evaluated. Data in the primary study were collected by means of a structured questionnaire which included items on socio-demographic characteristics and spirometry was performed according to the American Thoracic Society and European Respiratory Society (ATS/ERS) guidelines using an Easy on-PC spirometer in the participant‘s home. The ATS/ERS standards for adults and the modified recommendations for children were applied to evaluate quality. Descriptive statistics were used to describe the quality of spirometry indices and univariable logistic regression to identify and describe variables that are predictors of quality. Results: The findings of the study were that many children (34%) failed to reach the complete ATS/ERS quality standards. The end-of-test criteria (forced expiratory time) was the most difficult to meet for children and if this is not met (i.e. exhalation is not complete), the forced vital capacity (FVC) will be underestimated leading to it being misinterpreted. More than 30% of the children failed to meet the repeatability criteria when the relative differences for FVC and forced expiratory volume in the first second (FEV1) was used, yet they are the most appropriate in paediatric practice as compared to absolute differences. Young children were more likely to produce poor quality spirometry as compared to older children. Conclusion: Young children may perform acceptable spirometry according to the modified ATS/ERS recommendations; however, the quality remains suboptimal. Further modification of the already lowered quality standards, seems to be the viable option, but the implications of this clinically has not been evaluated. Other alternatives need to be explored for this group.