Demographic and epidemiological change has resulted globally in changes in population and individual health, which, in turn, have resulted in changing care needs. Demographic change in South Africa, mainly through a confluence of declining fertility rates and pre-AIDS increases in life expectancy, has produced an ageing population that is expected to continue ageing for at least the next 10 to 15 years. Currently, South Africa’s older population (60 years+) has a much higher annual average percent growth rate than the total population. Having more older persons than ever before implies increased prevalence of frailty, chronic disease and disability through a tendency of declining physical, mental and cognitive functional capacities—hence meaning a larger demand for care. The changing age structure of a population is commonly associated with changes in health, disease and cause of death patterns. Recent research indicates an intensive, quadruple burden of disease, with the major addition of HIV/AIDS to persistent pre-transitional conditions, non-communicable conditions, and high rates of injuries—implying an extensive and diverse need for care. While demographic and epidemiological change have led to an increased demand for care, health system change, shortages in formal public health care delivery, and the spiralling costs of private care have led to decreased availability of formal care. Care-requiring persons therefore may need to rely increasingly on ‘informal care’, defined here as ‘care provided at home to another person who, because of frailty disability or ill-health, cannot manage on his/her own’. Research on informal care in developed nations is well-established and extensive, but has received very little attention in South Africa where it is not clear how many and who it is that are informal carers. The thesis study has hence been conducted to contribute to the limited research in the field of informal care, aiming to establish the national extent of informal care, and to present a demographic and socio-economic profile of informal carers. A multi-stage stratified area cluster probability sample of 2704 persons was drawn from free-living adults in a nationally-representative household survey in 2000. Field data were collected during 2611 individual face-to-face interviews. Basic univariate and logistic regression analyses were conducted. Of the adult population, 27% were found to be informal carers. Significant prevalence differences were found regarding sex, population group, geographic residence, education, employment status, and income. Adjusting for selected demographic characteristics, the significance status and levels of some relationships changed. It is concluded that informal caregiving is widespread in South Africa. While demographic and epidemiological evidence suggest that the reliance on informal carers is expected to increase, many informal carers are struggling to shoulder the physical, mental and financial burden. A national strategy to focus on informal carers is recommended, to raise awareness about their essential role and value in the health care system; to recognize their contributions to population and individual health; to comprehensively support them; and to assess their needs and concerns through ongoing research. / Dissertation (MA (Demography))--University of Pretoria, 2006. / Sociology / unrestricted

Background and Aims: In India, alcohol per capita consumption (APC) has substantially increased over the past 2 decades. Although consumption does vary across the country, consistent state-level data are lacking. We aimed to identify all state-level alcohol exposure estimates since 2000 to (i) model consistent current drinking (CD) (12 months) prevalence estimates for all 36 states/union territories (UT) in 2019 and (ii) compare state-level CD trends with national-level APC trends. Design: A systematic review for studies on the Indian state-level prevalence of CD, lifetime abstinence (LA), alcohol use disorders (AUD) or the quantity of alcohol consumed among current drinkers (QU) was conducted. Subsequently, statistical modelling was applied. Setting: Data were collected and modelled for all Indian states/UTs. Participants: Studies since 2000 referring to the general adult population (≥15 years) of at least one Indian state/UT were eligible. The total sample size covered was 29 600 000 (males: females, 1:1.6). Measurements: Results on LA, AUD and QU were summarized descriptively. For (i) the state-, sex- and age-specific CD prevalence was estimated using random intercept fractional response models. For (ii) random intercept and slope models were performed. Findings: Of 2870 studies identified, 30 were retained for data extraction. LA, AUD and QU data were available for 31, 36 and 12 states/UTs, respectively. CD model estimates ranged from 6.4% (95% CI = 2.1%–18.1%; males) in Lakshadweep and 1.3% (95% CI = 0.7%–2.6%; females) in Delhi to 76.1% (95% CI = 68.1%–82.6%; males) and 63.7% (95% CI = 49.4%–75.7%; females) in Arunachal Pradesh. Over time, CD decreased in most states/UTs in the observed data, contradicting increasing national-level APC trends. Conclusions: Alcohol use (measured as consistent current drinking) in India has large regional variations, with alcohol consumption being most prevalent in the North-East, Chhattisgarh, Telangana, Himachal Pradesh, Punjab and Jharkhand.

La pollution de l’air extérieur est reconnue comme étant une source importante du fardeau économique, environnemental et sanitaire. Bien que les polluants retrouvés dans l’air ambiant soient émis par de nombreuses sources, le transport routier reste une source majeure de pollution particulièrement, les oxydes d’azote. Les polluants issus du trafic routier comme le dioxyde d’azote (NO2) ont été reliés à des problèmes de santé, notamment respiratoires. Cette thèse vise à quantifier l’impact de l’exposition prolongée à la pollution atmosphérique issue du transport routier, dans un contexte québécois, sur la santé respiratoire des enfants âgés de 0 à 12 ans. Afin d’y parvenir, nous avons développé une cohorte de naissances avec des données médicoadministratives et des modèles statistiques pour estimer les associations entre l’exposition prolongée au NO2 et le développement ainsi que l’exacerbation de l’asthme infantile. Nous avons également utilisé des données issues de modèles de transport, d’émissions et de dispersions afin de quantifier les cas d’asthmes incidents attribuables au NO2 issus du transport en 2008 et 2031. L’exposition annuelle ainsi que de l’exposition à la naissance au NO2 a été associée de façon positive au développement de l’asthme. L’exposition annuelle au NO2 a aussi été reliée à l’exacerbation de l’asthme infantile. En plus d’être important, le fardeau de l’asthme infantile attribuable au NO2 issu du transport routier présente une importante variation spatiale dans la région de Montréal. En 2031, on estime que le fardeau absolu ainsi que le fardeau par personne de la pollution issue du trafic routier seront réduits pour l’ensemble de la région. Dans l’ensemble, cette thèse a permis de quantifier l’impact du fardeau du NO2 issu du trafic routier sur la santé respiratoire des enfants. Les résultats de cette recherche suggèrent que des mesures devraient être encouragées pour réduire le fardeau attribuable au transport routier. / Outdoor air pollution is recognized as an important economic, environmental and sanitary burden. Even though air pollutants are emitted by numerous sources, transportation remains an important source of pollutants, particularly nitrous dioxide (NO2). Road traffic pollutants were linked to health issues, chiefly respiratory problems. This thesis aims to quantify the impact of prolonged exposure to road traffic pollutants on respiratory health for children age between 0 to 12 years old, in Québec. We developed a birth cohort using medico administrative data and statistical models in order to estimate the association between prolonged exposure to NO2 and onset or exacerbation of childhood asthma. We also used data obtained from transportation, emission and dispersion models to quantified the burden of asthma attributed to road traffic both in 2008 and 2031. Birth and annual exposure to NO2 are positively linked to childhood asthma onset. Annual NO2 exposure is also associated with the exacerbation of childhood asthma in asthmatic children. In addition of being important the burden associated with transport related air pollution showed important spatial variation in the Montreal region. However the burden associated with road traffic pollution will be reduced in 2031 compared to 2008. Overall this thesis enables us to quantify the burden associated to NO2 generated by road traffic on respiratory health in children. The results of this research suggest that measures should be taken to reduce the burden of road traffic.

Treatment of patients with multiple sclerosis (MS) and development of new therapies have been challenging due to the disease complexity and slow progression, and the limited sensitivity of available clinical outcomes. Modeling and simulation has become an increasingly important component in drug development and in post-marketing optimization of use of medication. This thesis focuses on development of pharmacometric models for characterization and quantification of the relationships between drug exposure, biomarkers and clinical endpoints in relapse-remitting MS (RRMS) following cladribine treatment. A population pharmacokinetic model of cladribine and its main metabolite, 2-chloroadenine, was developed using plasma and urine data. The renal clearance of cladribine was close to half of total elimination, and was found to be a linear function of creatinine clearance (CRCL). Exposure-response models could quantify a clear effect of cladribine tablets on absolute lymphocyte count (ALC), burden of disease (BoD), expanded disability status scale (EDSS) and relapse rate (RR) endpoints. Moreover, they gave insight into disease progression of RRMS. This thesis further demonstrates how integrated modeling framework allows an understanding of the interplay between ALC and clinical efficacy endpoints. ALC was found to be a promising predictor of RR. Moreover, ALC and BoD were identified as predictors of EDSS time-course. This enables the understanding of the behavior of the key outcomes necessary for the successful development of long-awaited MS therapies, as well as how these outcomes correlate with each other. The item response theory (IRT) methodology, an alternative approach for analysing composite scores, enabled to quantify the information content of the individual EDSS components, which could help improve this scale. In addition, IRT also proved capable of increasing the detection power of potential drug effects in clinical trials, which may enhance drug development efficiency. The developed nonlinear mixed-effects models offer a platform for the quantitative understanding of the biomarker(s)/clinical endpoint relationship, disease progression and therapeutic response in RRMS by integrating a significant amount of knowledge and data.

Philosophiae Doctor - PhD / Injuries, and head injuries in particular, are a common cause of childhood, adolescent and young adulthood morbidity and mortality. The risk factors for injuries in general have been well researched. But it remains uncertain whether these factors are similar for specific injuries, such as head injuries. The inter-relationships between individual and environmental risk factors are difficult to study. Whilst much is know of the short-term consequences of head injuries, relatively little information is available on their long-term conseque~ces. The follow-up period in most research is short (often less than 1 year) and studies are weak in terms of design. Studies generally find a variety of social, cognitive and psychological consequences in children and young adults experiencing head injuries. This study assessed in two large, nationally representative samples, a 1946 birth cohort and a 1997 cross-sectional health survey: 1) the occurrence and risk factors for childhood, adolescent and early adulthood head and other injuries, and 2) the long-term cognitive and psychiatric effects of skull injuries. The overall findings for the risk factors across the two data sets and over 5 decades of data collection were strikingly similar. Maleness was a major risk factor for the head and other injuries. Some of the behaviour and personality factors such as hyperactivity and being neurotic, even after adjusting for sex, socioeconomic status and family type, remained significantly related to injuries, particularly those affecting the head region. A clustering of demographic, socioeconomic, family and behavioural risk factors significantly increased the likelihood of injuries, particularly recurring injuries with at least one being a head injury. In the unadjusted analyses socioeconomic status and family type were less consistently related to injuries. The long-term psychiatric and cognitive consequences of skull injuries causing concussion and skull fractures in childhood and early adulthood were negligible. Other childhood factors such as educational ability, behaviour and personality, and level of education achieved were more predictive of psychiatric symptoms and cognitive problems in adulthood. This study suggests that children and adolescents with behavioural and personality problems were at greater risk of head and other injuries in childhood, adolescence and later in adulthood. Children and adolescents with behavioural and personality problems were more likely to live in manual social class families and families with a single parent or stepparent. This combination of behavioural problems and deprived socioeconomic and family circumstances may increase tendencies for violent behaviour, alcohol dependence and manual occupations later in adulthood, which all increase the risk of injuries. There is therefore a need to identify children and adolescents with behavioural and personality problems as early as possible to prevent the impact in the short- and longterm. This will not only reduce the burden of injuries but also the many other consequence of behavioural and personality problems, particularly when located within deprived socioeconomic and family circumstances.