Childhood asthma is one of the most common chronic diseases worldwide, including in South Africa. There has been substantial evidence on the role of air pollution in asthma exacerbation but limited research on the role of climate change and how the interaction between climate change and air pollution is affecting childhood asthma, specifically in low and middle-income countries (LMICs). Temperature changes can be used as an effect of climate change to investigate the association between climate change, air pollution and childhood asthma. This study, therefore, used a case study approach aimed at examining the interaction between air pollution and temperature in exacerbating childhood asthma focusing on clinical data obtained from Red Cross War Memorial Children's Hospital, air quality data (City of Cape Town) and temperature data (South African Weather Services) for Cape Town, South Africa for three study years (2009, 2014 and 2019). The protocol (Part A) of the mini dissertation describes childhood asthma literature globally and in LMICs and specifically in South Africa. It also discusses the increasing incidences and prevalence of the disease and possible causes such as air pollution and climate change. Furthermore, it discusses the vulnerability of children to the exposure of interest, being air pollution (PM2.5, PM10, NO2 and O3) and climate change (i.e., temperature). Subsequently, the development of air quality standards is discussed, specifically concerning whether they consider the specific children's vulnerability to exposures. The protocol then describes the study population and methodologies for conducting this study. The journal ready article (Part B) presents the findings of the study. Spearman's correlation was used to measure the degree of association between temperature variables and air pollutants. The results indicated that diurnal temperature was associated with PM2.5 (r=0.579: p< 0.01) and PM10 (r=0.505: p< 0.01). A Poisson regression analysis was applied to evaluate the relationship between asthma exacerbation with air pollutants and temperature variables. In a univariate analysis there was a statistically significant relationship between asthma exacerbation and diurnal temperature for 2019, IRR=0.98 (95% CI,0.97 – 0.99) p< 0.05, maximum temperature 2014, IRR=0.99(95% CI, 0.98 - 1.00) p< 0.05 and for 2019, IRR=0.98(95% CI, 0.97 - 0.99) p< 0.01, average temperature 2014, IRR=0.99(95% CI, 0.98 - 1.00) p< 0.05 and for 2019, IRR=0.98(95% CI, 0.97 - 0.99) p< 0.01. Using a multivariate analysis there v of 110 was no significant relationship between childhood asthma exacerbation and air pollutants (PM10, NO2 and O3) except for PM2.5 IRR=0.12(95% CI, 0.01 - 0.81) p< 0.05. Diurnal temperature statistically significant childhood asthma predictor for 2009, IRR=1.02(95% CI, 1.00 - 1.05) p< 0.05 and for 2014, IRR=0.97(95% CI, 0.96 - 0.99) p< 0.01. Temperature increase, therefore, seems to be related to asthma exacerbation. More research is needed on the relationship between diurnal temperature, childhood asthma, and air pollutants to inform adaptation strategies. The findings of this study are important for the development of climate change and health adaptation and prevention strategies in South Africa, particularly in relation to heat adaptation. These findings are also relevant for the development of air quality guidelines and guidelines to address children, as the most vulnerable population to environmental health exposures. The appendices (Part C) present the analyses that were not included in the protocol (Part A) and article (Part B). These also include documents relating to the study such as ethics approval and permission to conduct research by different entities.

Background: Children require a nurturing environment to develop optimally and reach their full potential. A critical component of this environment is the health and well-being of caregivers so that they can provide responsive caregiving. It is believed that parents or caregivers of children with ASD will have poorer health and well-being than parents or caregivers of children without ASD. Therefore, parents of children with ASD may require more support to enable them to provide responsive caregiving to these children. Methods: This study was a quantitative study that employed an analytical, comparative design. The purpose of this study is to determine if there is a significant difference in the health and well-being of parents with children with ASD and parents of children without ASD in the South African context. Two hundred and eight participants from two schools in Kwa-Zulu Natal completed a paper-based survey containing 3 questionnaires relating to health-related quality of life; stress, anxiety and depression and parental self-efficacy. Parenting constructs such as stress, anxiety and parental self-efficacy are measured and described, and the association between Health-related Quality of Life and constructs such as stress, anxiety and parental self-efficacy is explored. It took place at a special needs school in KZN and mainstream school in the same district. Results: The results of this study demonstrated a poorer HRQOL in some of the areas of parents of a child with ASD compared to parents of a child without ASD. The results from this study demonstrate the importance for health practitioners to focus on the parents' health and well-being as part of the child's intervention. Conclusion: Intervention is mainly child-focussed however it is important for practitioners to understand the caregiver's health and well-being as this will have a positive influence of the child and in turn, lead to successful intervention. It is therefore important to have a family-centred approach. The QOL of the parents or caregivers of children with ASD will improve through support and intervention which will positively impact on the child's development. If the caregiver is receiving the appropriate support, their QOL will improve and they will be able to provide nurturing care that the child needs.

Purpose While epilepsy surgery has been shown to reduce seizure frequency and severity and even cures seizures in children with drug-resistant epilepsy, data from middle-income countries (MIC) are lacking. Method This study is a retrospective review of children with drug-resistant epilepsy who underwent surgical treatment at Red Cross War Memorial Children's Hospital (RCWMCH) between 1 January 2000 and 31 December 2021 (HREC: 140/2020). Results During the 21-year study period, 60 patients underwent epilepsy surgery for drugresistant epilepsy. The median age of the children was seven years (IQR 4.81-10.27years) at the time of surgery, with a male predominance of 33 patients. The most common surgical procedure performed was an anterior temporal lobectomy for temporal lobe epilepsy in 19 cases (31.7%), followed by peri-insular hemispherotomy in 9 cases (15.0%) and frontal lobectomy in 8 cases (13.3%). Of the 60 patients, complete records were available for 55 patients noting complications in 11 (20.0%), of which 4 cases (7.3%) had major complications. Notably, 2 patients (3.6%) had new-onset psychiatric symptoms. The long term outcomes after surgery showed 1-year seizure freedom in 32 patients (58.2%); among these, 21 patients (38.2%) could stop ASM one year after surgery, 17 patients (30.9%) had a recurrence of their seizures, and three had to restart ASM after 2-3 years. Eight patients (14.5%) required repeat surgery. The one-year-Modified Engel scoring for the study population was: 1-A in 52.7%, I-B in 3.6%, I-C in 1.8%, II-A in 15.8%, III-A in 10.9%, IV-A in 3.6% and IV-B in 10.9%. The most common histological finding in anterior temporal lobectomy (ATL) was focal cortical dysplasia (FCD), found in 11 patients (57.9%). The periinsular hemispherotomy (PIH) cases had equal numbers of FCD and Rasmussen's encephalitis in 4 patients (44.4%). The number of FCD in this series is much higher than in international data. Conclusion Epilepsy surgery is an effective and attainable intervention for drug-resistant epilepsy in the paediatric population despite limited resources and challenging aetiological profiles. Low complication rates were comparable to international data, with good seizure freedom outcomes.

Smoking cessation can reduce health risk and prevent millions of tobacco-related deaths. However, cessation rates are low in low-and-middle income countries (LMICs), with only a small proportion of smokers intending to quit. Given the paucity of literature to support tobacco cessation programs in LMICs, this study aimed to: 1) identify factors associated with intention to quit smoking, 2) assess the relationship between health care provider quit advice/tobacco screening and utilization of cessation assistance, and 3) examine the relationship between home smoking rule and smoking intensity across three stages of smoking cessation (precontemplation, contemplation and preparation) in LMICs. Data were obtained from the Global Adult Tobacco Survey, 2009-2012, a nationally representative household survey of noninstitutionalized civilians aged 15 years and older. Weighted multivariable regression analyses were conducted using SAS version 9.4. Adjusted odds ratios (OR), percent change in smoking intensity and associated 95% confidence intervals (CI) were estimated. Home smoking rule and exposure to anti-smoking messages were the important factors associated with contemplation and preparation to quit smoking. Approximately 1%, 7%, 9% and 15% used quitline, medical treatment, counseling/cessation clinic and cessation assistance (all three combined), respectively, in the past year. Quit advice was significantly associated with utilization of counseling/cessation clinic (OR=3.89, 95% CI=2.8–5.5), medical treatment (OR=1.71, 95% CI=1.2–2.4) and cessation assistance (OR=2.60, 95% CI=2.0–3.4). Tobacco screening was associated with utilization of counseling/cessation clinic (OR=2.60, 95% CI=1.1–5.9) and medical treatment (OR=1.71, 95% CI=1.2–2.4). Living in a completely smoke-free home was associated with a 22.5% (95% CI=17.1%–28.0%), an 18.6% (95% CI=9.0%–28.2%), and a 19.4% (95% CI=3.9%–34.9%) significant reduction in smoking intensity among smokers in precontemplation, contemplation and preparation, respectively. In conclusion, the results suggest that smoke-free home, anti-smoking campaigns, and health care provider intervention promote smoking cessation in LMICs. Therefore, comprehensive smoke-free policies, anti-smoking media campaigns and integration of tobacco screening and quit advice into the health care system are important for tobacco cessation in LMICs, suggesting the need for full implementation of the World Health Organization Framework Convention for Tobacco Control Articles 8 and 11 – 13.

Increasing rates of adult-onset diabetes in low- to middle-income countries (LMICs) present a growing healthcare concern that requires a regulatory approach and local community engagement. Cross-sector collaboration (CSC) is an effective strategy for improving community health. CSC is not effectively used to manage adult-onset diabetes in LMICs, nor is there public policy advocating CSC in the management of diabetes. This qualitative exploratory case study explored how leadership and resources affect the use of CSC to assist in managing the adult-onset of diabetes in a CSC in Cameroon. A purposeful sampling strategy was used to identify participants for semistructured interviews of 10 executives involved in the CSC. CSC theory provided a theoretical framework. Collected data were organized by audio recording, transcribing, translating, member checking, and thematically coding data using NVivo 12 software. Data from a review of documents and researcher observations were triangulated with interview data. Findings revealed that poverty, access to health care, and rising diabetes prevalence contributed to environmental turbulence. Goal-setting and objectives, intersectoral-communication, fostering trust and respect, and sharing data and motivating people presented leadership effectiveness challenges. The following resource challenges emerged in the CSC: public policy, money, skills and expertise, equipment and supplies, and connection to the target population. This increased scientific understanding could help government policy-makers and nongovernmental organizations expand public policy leading to a decrease in the prevalence and burden of adult-onset diabetes.

INTRODUCTION: Epidemiological transition theory, first postulated by Omran in 1971, provides a useful framework for understanding cause-specific mortality changes and may contribute usefully to predictions about cause-specific mortality. However, understandings of mortality transitions and associated epidemiological changes remain poorly defined for public health practitioners due to lack of evidence from low- and middle-income countries. Therefore, understanding of the concept and development of epidemiological transition theory as well as population burden of premature mortality attributable to risk factors is needed. OBJECTIVES: This thesis aims to understand how epidemiological transition theory has been applied in different contexts, using available evidence on mortality transitions from high, middle- and low- income countries, as well as the contribution of risk factors to mortality transitions, particularly for premature mortality. METHODS: A Medline literature search from 1971 to 2013 was conducted to synthesise published evidence on mortality transition (paper I). A descriptive analysis of trends in cause of death using INDEPTH data was conducted, focusing on specific causes of death in 12 INDEPTH sites in Africa and Asia, using the INDEPTH 2013 standard population structure for appropriate comparisons across sites (paper II). A retrospective dynamic cohort database was constructed from Swedish population registers for the age range 30-69 years during 1991-2006, to measure reductions in premature non-communicable disease mortality using a life table method (paper III). Prospective cohort data from Västerbotten Intervention Programme from 1990 to 2006 were used to measure the magnitude of premature non-communicable disease mortality reductions associated with risk factor changes for each period of time (paper IV). FINDINGS: There were changes in emphasis in research on epidemiological transition over the four decades from 1971 to 2013, from cause of death to wide-ranging aspects of the determinants of mortality with increasing research interests in low-and middle-income countries, with some unconsidered aspects of social determinants contributing to deviations from classic theoretical pathways. Mortality rates declined in most sites, with the annual reductions in premature adult mortality varied across INDEPTH sites, Sweden, which now is at late stage of epidemiological transition stage, achieved a 25% reduction in premature mortality during 1991-2006. Overall downward trends in risk factors have helped to reduce premature mortality in the population of Västerbotten County, but some benefits were offset by other increasing risks. The largest mortality changes accrued from reductions in smoking, hypertension and hypercholesterolaemia. CONCLUSIONS: This thesis established patterns of current epidemiological transition in high, middle-and low-income countries (Asia and Africa), where the theory fits the transition patterns in some countries, but with some needs for further adjustments in other settings, as well as deviations from the classical ET theory in the last four decades. It highlights the need to identify the burden of mortality and morbidity, particularly for reducing mortality occurring before the age of 70 years and its attribution to risk factors, which are a major public health challenge. This informs shifting of public health priorities and resources towards prevention and control of chronic non-communicable disease risk factors.

INTRODUÇÃO: Países de baixa e média renda representam mais de 85% da população mundial de 7 bilhões de pessoas. Nesses países, a população idosa apresentou acelerado crescimento nas últimas décadas. Esse rápido crescimento está sendo acompanhado pelo aumento dos agravos relacionados ao envelhecimento e por mudanças no padrão de morbimortalidade. Entre as condições que têm demonstrado associação com aumento de mortalidade, está a depressão. Porém, grande parte das pesquisas sobre a associação da depressão com mortalidade é de países de alta renda. OBJETIVOS: 1) Investigar a associação entre depressão e mortalidade em idosos de países de baixa e média renda. 2) Investigar a associação de depressão/sintomas depressivos e mortalidade por todas as causas e causas específicas em uma coorte de idosos residentes na zona oeste de São Paulo em um período de 10 anos de seguimento. MÉTODOS: 1) Foi realizada uma revisão sistemática para identificar estudos observacionais que investigaram a associação entre mortalidade e depressão em países de renda média ou baixa. Dois revisores trabalharam independentemente para selecionar artigos, extrair dados e avaliar a qualidade dos estudos. Uma meta-análise foi realizada a partir dos dados extraídos dos estudos incluídos na revisão sistemática. 2) Foi realizado um estudo de coorte utilizando a amostra do \"São Paulo Ageing & Health Study\" (SPAH), investigação que incluiu idosos com 65 anos ou mais, residentes de áreas economicamente menos favorecidas na região Oeste da cidade de São Paulo. Os participantes foram identificados por arrolamento domiciliar e entrevistados em seus domicílios seguindo protocolo padronizado de pesquisa. A definição de depressão e sintomas depressivos foi realizada a partir dos instrumentos Geriatric Mental State (GMS) e Inventário Neuropsiquiátrico (NPI). Os dados de seguimento foram extraídos a partir das declarações de óbitos dos residentes do estado de São Paulo através de procedimento de linkage de dados com os bancos de declarações de óbitos da fundação SEADE. Foram examinadas as associações independentes entre depressão e sintomas depressivos e mortalidade através de modelos de riscos proporcionais de Cox e também foi elaborada curva de sobrevida de Kaplan Meier. RESULTADOS: 1) Foram incluídos 10 estudos, com um total de 13.828 participantes (2.402 deprimidos e 11.426 não-deprimidos) de 6 países (Brasil, 4 artigos; China, 2 artigos; Botswana, Índia, África do Sul e Coréia do Sul, 1 artigo). O risco relativo total não ajustado (RR) de mortalidade em idosos com depressão em relação aos não deprimidos foi de 1,62 (IC95% 1,39-1,88; p < 0,001), com alta heterogeneidade (I2, 66%; IC95% 33-83; p < 0,005). Após o ajuste para o viés de publicação, o RR geral diminuiu para 1,60 (IC95%; 1,37-1,86). Não foram observadas diferenças significativas entre os subgrupos, exceto aqueles definidos pela qualidade do estudo. Os estudos de alta qualidade tiveram um RR agrupado de 1,48 (IC95% 1,32-1,67), enquanto os estudos de baixa qualidade resultaram em um RR agrupado de 1,82 (IC95% 1,25-2,65). 2) Dos 1.967 participantes do SPAH, 443 (22,52%) apresentaram sintomas depressivos e 90 (4,58%) preenchiam critérios para diagnóstico de depressão pela CID-10 no início do seguimento. Foram observados 688 (34,98%) óbitos no seguimento. Presença de sintomas depressivos (HR=1,23; IC95% 1,03-1,46; p=0,022) e depressão (HR=1,75; IC 95% 1,29-2,37; p < 0,001) no início do seguimento estiveram positivamente associadas à mortalidade por todas as causas. Sintomas depressivos (HR=1,26; IC 95% 1,04-1,53; p=0,018) persistiram associados a mortalidade mesmo após controle por variáveis confundidoras, enquanto depressão (HR=1,20; IC95% 0,85-1,67; p=0,296) perdeu significância estatística ao se adicionar ao modelo variáveis relacionadas a comorbidades. Considerando causas especificas de óbitos, sintomas depressivos apresentaram associação significativa com óbitos por doenças cardiovasculares (HR=1,48; IC95% 1,12-1,95; p=0,006) e depressão apresentou associação com óbitos por câncer (HR=2,26; IC95% 1,17-4,36; p=0,015). CONCLUSÃO: A depressão está associada ao excesso de mortalidade em idosos que vivem em países de baixa e média renda. Além disso, esse excesso de mortalidade não difere substancialmente do encontrado em países de alta renda. Já sintomas depressivos e depressão estiveram associados ao aumento de mortalidade em idosos entre os participantes do SPAH. Dado que sintomas depressivos e depressão aumentam o risco de óbito, um melhor entendimento sobre essa relação e estratégias de provisão de serviços de saúde mental, em especial em países de média e baixa renda, são necessários já que essas condições clínicas modificáveis muitas vezes não são reconhecidas ou tratadas adequadamente / INTRODUCTION: Low and middle income countries represent more than 85% of the world population of 7 billion people. In these countries, the elderly population has grown rapidly in recent decades. This rapid growth is being accompanied by the increase in aggravations related to aging and changes in the morbidity and mortality pattern. Among the risk factors that have been shown to be associated with excess mortality are depression. However, much of the research on the association of depression with mortality is from high-income countries. OBJECTIVES: 1) To investigate the association between depression and mortality in the elderly living in low- and middle-income countries 2) To investigate the association of depressive / depressive symptoms and all-cause and specific-cause mortality in a cohort of elderly living in the western zone of São Paulo over a period of 10 years of follow-up. METHODS: 1) A systematic review was conducted to identify observational studies that investigated the association between mortality and depression in middle- and low-income countries. Two reviewers independently worked to select articles, extract data, and evaluate the quality of the studies. A meta-analysis was performed from the data extracted from the studies included in the systematic review. 2) A cohort study was carried out using a sample from the São Paulo Aging and Health Study (SPAH), an investigation that included elderly people aged 65 years and over, from economically disadvantaged areas in the western region of the city of São Paulo. Participants were identified by household survey and interviewed in their homes following a standardized research protocol. The definition of depression and depressive symptoms was performed using the Geriatric Mental State (GMS) and Neuropsychiatric Inventory (NPI) instruments. The follow-up data were extracted from the statements of deaths of the residents of the state of São Paulo through a data linkage procedure with the database of death declarations of the SEADE foundation. We examined the independent associations between depression and depressive symptoms and mortality through Cox proportional hazards models and also elaborated the Kaplan Meier survival curve. RESULTS: 1) Ten studies were included, with a total of 13,828 participants (2,402 depressed and 11,426 non-depressed) from 6 countries (Brazil, 4 articles; China, 2 articles; Botswana, India, South Africa and South Korea, 1 article) were included. The overall unadjusted relative risk (RR) of mortality in depressed relative to non-depressed participants was 1.62 (95% CI 1.39-1.88; p < 0.001), with high heterogeneity (I2=66%; 95% CI 33-83; p < 0.005). After adjustment for publication bias, the RR decreased to 1.60 (95% CI 1.37-1.86; p < 0.001). No significant differences were observed between subgroups except those defined by study quality. The high quality studies had a pooled RR of 1.48 (95% CI 1.32-1.67; p<0.001), while the low quality studies resulted had a pooled RR of 1.82 (95% CI 1.25-2.65; p < 0.005). 2) Of the 1,967 participants, 443 (22.52%) had depressive symptoms and 90 (4.58%) had a diagnosis of depression by ICD-10 at the beginning of follow-up. There were 688 (34.98%) deaths at follow-up. Presence of depressive symptoms (HR=1.23; 95% CI 1.03-1.46; p=0.022) and depression (HR=1.75; 95% CI 1.29-2.37; p < 0.001) at the beginning of follow-up were positively associated with all-cause mortality. Depressive symptoms (HR=1.26; 95% CI 1.04-1.53; p=0.018) persisted associated with mortality even after controlling for confounding variables, while depression (HR=1.20; 95% CI 0.85-1.67; p=0.296) lost association when variables related to comorbidities were added to the model. Considering specific causes of death, depressive symptoms had a significant association with death due to cardiovascular diseases (HR=1.48; 95% CI 1.12-1.95; p=0.006), and depression was associated with cancer deaths (HR=2.26; 95% CI 1.17-4.36; p=0.015). CONCLUSION: Depression is associated with excess mortality in the elderly living in low- and middle-income countries. In addition, this excess mortality does not differ substantially from that found in high-income countries. Depressive symptoms and depression were associated with increased mortality in the elderly. Given that depressive symptoms and depression increase the risk of death, a better understanding of this relationship and strategies for providing mental health services, especially in middle- and low-income countries, are necessary since these modifiable clinical conditions are often not recognized or properly handled

Background: Parent behaviours have a long-lasting impact on the health, education, and behaviour of the young people in their care. Group-based parenting interventions are a promising approach to improve parenting, as well as to prevent and reduce physical and emotional maltreatment of children. While a billion of adolescents live in low- and middle- income countries, few evaluations have examined parenting approaches for families with adolescents in these countries. Objectives: This study was nested within a randomised controlled trial of Sinovuyo Teen, a parenting programme for families with adolescents. The trial took place in rural South Africa in 2015-2016 with 552 families in 40 study clusters. Primary intervention outcomes included parenting and child maltreatment. This dissertation aims to: (1) describe the implementation (attendance, engagement, and fidelity) of the intervention delivered within the evaluation, (2) examine if participant characteristics affected attendance and engagement in the intervention, (3) examine if implementation characteristics affected programme results, and (4) examine if participant characteristics affected programme results. Methods: Programme implementation was assessed through observations of all programme group sessions and the records of the implementing organisation. The analyses also draw on participant self-report data from three time-points (baseline, immediate post-test, and follow-up). The data were analysed using a series of correlation and multilevel regression analyses, presented in three papers. Findings: Attendance levels in the intervention were somewhat lower than in previous similar studies, perhaps due to the role of home visits. Generally, more disadvantaged families participated at similar rates as families with more material and social resources. However, a number of factors affected attendance on individual and family levels, e.g. an overcrowded household, and at the community level, e.g. funeral and grant receipt days. Intervention fidelity was similar to the levels reported in high-income countries, thus suggesting that high implementation quality is feasible in a low-resource setting. There was no consistent impact of the variation in participation and implementation on participant outcomes. Baseline risks did not consistently affect variation in treatment effects, confirming recent findings that families at-risk can benefit from parenting support as much or more than less at-risk families.

Chronic disease is rising globally, but LMICs may require novel approaches to management suited to a low-resource setting. Private health care providers in LMICs have experimented and developed new models for organizing, financing, and delivering care. This thesis examines some of the innovations that have emerged in LMICs to manage chronic disease. Using a common performance measurement framework and drawing from a database of over 1200 innovative health programs, I identify and evaluate 46 programs addressing chronic disease in LMICs. I then go on to identify, innovative practices used by the subset of 19 diabetes focussed programs and catalogue them according to the Chronic Care Model (CCM). Delivery system design is the most commonly used domain of the CCM, which even earlier has shown to have great potential to impact health outcomes. Few of the identified innovations may also have the potential for ‘Reverse innovation’ in high income countries.

Chronic disease is rising globally, but LMICs may require novel approaches to management suited to a low-resource setting. Private health care providers in LMICs have experimented and developed new models for organizing, financing, and delivering care. This thesis examines some of the innovations that have emerged in LMICs to manage chronic disease. Using a common performance measurement framework and drawing from a database of over 1200 innovative health programs, I identify and evaluate 46 programs addressing chronic disease in LMICs. I then go on to identify, innovative practices used by the subset of 19 diabetes focussed programs and catalogue them according to the Chronic Care Model (CCM). Delivery system design is the most commonly used domain of the CCM, which even earlier has shown to have great potential to impact health outcomes. Few of the identified innovations may also have the potential for ‘Reverse innovation’ in high income countries.