Abstract The etiology of musculoskeletal disorders remains largely unclear, pain being the predominant complaint. The prevalence of neck pain (NP), shoulder pain (SP), and low back pain (LBP) increases drastically during adolescence. Potentially modifiable risk factors of NP, SP, and LBP should be identified at that age. First, this study evaluated the prevalence of NP, SP, LBP and peripheral pains (upper or lower extremities) and the prevalence of multiple pains. Second, the study determined the role of a set of potentially modifiable risk factors for adolescents’ NP, SP, and LBP (physical activity, inactivity, sedentary activities in cross-sectional study design and quantity and quality of sleep in follow-up study design). The study population belongs to the 1986 Northern Finland Birth Cohort (NFBC 1986), consisting of 9,479 children with an expected date of birth between July 1, 1985 and June 30, 1986 in the two northernmost provinces of Finland, Oulu and Lapland. NP, SP, and LBP were common at the ages 16 and 18, while medical consultations for these pains were less frequent. The prevalence of pain increased with age. Peripheral pains were rare. Surprisingly many adolescents reported multiple musculoskeletal pains. Girls were more likely to report pain than boys. Both low and high level of physical activity, some risk sport activities, high amount of sedentary activities, and insufficient quantity and quality of sleep increased the risk of NP, SP, and LBP in adolescence. It may be possible to reduce the occurrence of musculoskeletal pain by having a positive impact on potentially modifiable risk factors, such as physical activity, sedentary activities and sleep hygiene. Therefore, intervention studies focusing on these factors are needed in the future. / Tiivistelmä Useimmiten tuki- ja liikuntaelinsairauksien tarkka syy jää epäselväksi ja kipu on niiden pääasiallinen ilmentymä. Niska-, hartia- ja alaselkäkipujen esiintyvyys väestössä nousee merkittävästi teini-iässä. Tämän vuoksi niska-, hartia- ja alaselkäkivun riskitekijöitä tulisikin tutkia nuoruudessa, jotta niihin päästäisiin vaikuttamaan ajoissa. Tässä väitöskirjassa selvitettiin niska-, hartia-, alaselkä- ja laaja-alaisten tuki- ja liikuntaelinkipujen esiintyvyyttä nuorilla. Päätavoite oli kuitenkin tutkia liikunnan, eri urheilulajien, liikkumattomuuden, istumisen ja unen laadun ja määrän yhteyttä niska-, hartia- ja alaselkäkipujen esiintyvyyteen. Tutkimusaineisto muodostui Pohjois-Suomen syntymäkohortin 1986 nuorista, joiden laskettu syntymäaika oli 1.7.1985–30.6.1986. Nuorille lähetettiin 16-vuotiaana postikysely, joka sisälsi tuki- ja liikuntaelinoirekyselyn, kysymyksiä liikunnan, istumisen ja unen määrästä ja laadusta, sekä muista elämäntavoista. Kahden vuoden kuluttua, 18-vuotiaana lähetettiin toinen kysely joka sisälsi mm. tuki- ja liikuntaelinoirekyselyn. Tulokset osoittavat että niska-, hartia- ja alaselkäkivut olivat yleisiä nuoruudessa, joskin hoitoa vaativat kivut ja raajojen kipuoireilu olivat harvinaisia. Laaja-alaiset tuki- ja liikuntaelinkivut olivat odotettua yleisempiä. Tytöt oireilivat enemmän kuin pojat ja oireilu lisääntyi iän myötä. Hyvin aktiivinen liikunnan harrastaminen (6h/vko tai enemmän ripeää liikuntaa) ja erityisesti tietyt riskilajit olivat yhteydessä suurempaan niska-, hartia- ja alaselkäkipujen esiintyvyyteen. Samoin suuri istumisen määrä, riittämätön uni ja huono unen laatu lisäsivät kipujen todennäköisyyttä. Nuorten tuki- ja liikuntaelinkipuja voitaisiin mahdollisesti vähentää vaikuttamalla muunneltavissa oleviin riskitekijöihin, kuten vähentämällä istumista, lisäämällä terveysliikuntaa, sekä parantamalla unitottumuksia. Tämän takia jatkossa tarvitaan näihin riskitekijöihin kohdistuvia interventiotutkimuksia.

Abstract The aim of this thesis was to explore the associations between the use of nervous system medications and suicidal ideation and behaviour in various different diagnostic groups in a large population-based cohort. Information on prescribed antipsychotic, antidepressant, benzodiazepine and antiepileptic medications within the Northern Finland Birth Cohort 1966 was collected from the register of the Social Insurance Institution of Finland and from a postal questionnaire sent to all cohort members in 1997. The presence of suicidal ideation and depression and anxiety symptoms was assessed via the Hopkins Symptom Checklist-25 questionnaire in 1997. Data on suicides were collected from the cause-of-death statistics and on suicide attempts from the Finnish Care Register for Health Care in a 15-year follow up. The use of antipsychotic, antidepressant, or benzodiazepine medication was associated with increased suicidal ideation, suicide attempts, and suicides. Antiepileptic medication was not associated with increased suicidality. The polypharmacy of nervous system medications was associated with increased suicidality. All nervous system medications were associated with increased severity of depression and anxiety symptoms. When depression and anxiety symptoms were taken into account, most of the associations between medication and suicidal ideation were statistically non-significant. Regarding specific groups, among those who did not have psychosis, high doses of antipsychotic medication correlated particularly with increased suicidal ideation even when other symptoms of depression and anxiety were taken into account. Among those with insomnia, the use of antidepressant medication associated with increased suicidal ideation also when other symptoms were taken into account. Although nervous system medication is associated with increased suicidal ideation, the association with other symptoms is also strong, and therefore it could not be stated that medication associates specifically with suicidal ideation. However, certain groups, i.e., non-psychotic subjects with high doses of antipsychotic medication, or subjects with insomnia and using antidepressant medication, should be closely monitored as they could be more vulnerable to suicidal ideation. / Tiivistelmä Tämän väitöstutkimuksen tarkoituksena oli tutkia hermostoon vaikuttavien lääkkeiden, lähinnä psykoosilääkkeiden, masennuslääkkeiden, bentsodiatsepiinien sekä epilepsialääkkeiden, yhteyttä itsetuhoisiin ajatuksiin, itsemurhayrityksiin ja itsemurhiin. Aihetta tutkittiin eri diagnoosiluokissa suuressa väestöaineistossa, Pohjois-Suomen vuoden 1966 syntymäkohortissa. Tieto tutkimushenkilöiden lääkkeenkäytöstä vuodelta 1997 kerättiin Kelan lääkeostorekisteristä sekä postikyselyn avulla. Itsetuhoisten ajatusten ja muiden masennus- ja ahdistusoireiden vakavuutta mitattiin Hopkins Symptom Checklist-25 -kyselyn avulla vuonna 1997. Tieto itsemurhista kerättiin 15 vuoden seurannassa kuolinsyyrekisteristä ja tieto itsemurhayrityksistä hoitoilmoitusrekisteristä. Psykoosilääkkeiden, masennuslääkkeiden ja bentsodiatsepiinien käyttö oli yhteydessä lisääntyneisiin itsetuhoisiin ajatuksiin, itsemurhayrityksiin ja itsemurhiin. Epilepsialääkkeet eivät liittyneet itsetuhoisuuteen. Usean hermostoon vaikuttavan lääkkeen yhtäaikainen käyttö oli yhteydessä lisääntyneeseen itsetuhoisuuteen. Kaikki hermostoon vaikuttavat lääkkeet liittyivät lisääntyneisiin masennus- ja ahdistusoireisiin. Kun lääkityksen yhteys masennus- ja ahdistusoireisiin otettiin huomioon, lääkkeet eivät olleet erityisesti yhteydessä itsetuhoisiin ajatuksiin. Diagnostisten ryhmien välillä ei ollut eroa hermostoon vaikuttavien lääkkeiden ja itsemurhayritysten tai itsemurhien välisessä yhteydessä. Henkilöillä, joilla ei ole psykoosia, suuremmat psykoosilääkeannokset olivat yhteydessä itsetuhoisten ajatusten vakavuuteen kun muiden masennus- ja ahdistusoireiden vakavuus otettiin huomioon. Unettomuudesta kärsivillä henkilöillä masennuslääkkeen käyttö oli liittyi lisääntyneisiin itsetuhoisiin ajatuksiin kun muut oireet huomioitiin. Hermostoon vaikuttavat lääkkeet ovat yhteydessä lisääntyneisiin itsetuhoisiin ajatuksiin, mutta ne ovat myös vahvasti yhteydessä muihin masennus- ja ahdistusoireisiin. Tietyt henkilöt voivat kuitenkin olla erityisen herkkiä nimenomaan itsetuhoisille ajatuksille, ja heitä tulisi seurata erityisen tiiviisti. Tällaisia ovat henkilöt, joilla ei ole psykoosia, mutta jotka käyttävät suuria psykoosilääkeannoksia, sekä vakavasta unettomuudesta kärsivät henkilöt, jotka käyttävät masennuslääkettä.

Magister Public Health - MPH / Introduction: In recent years, cardiovascular disease (CVD) has emerged as a leading cause of death in developing countries. It is important to identify and target people who are at risk,given that a third of all deaths are expected to be due to CVD by 2020. Studies have shown socio-economic patterning in the prevalence of risk factors for CVD, including obesity,smoking and lipid profile. In developed countries, the association between socio-economic status (SES) and CVD risk factors is negative, with a higher prevalence of CVD risk factors among people of lower SES. However, findings from studies in developing countries on this including South Africa has been inconsistent. In addition, there is scant information on differences in socio-economic patterning of CVD risk factors between urban and rural areas in South Africa.Aim: To examine the association between SES indicators and CVD risk factors among an adult population cohort of Black South Africans living in a rural and urban community.Study design: Quantitative cross-sectional analytical study of baseline data of a populationbased cohort of 2000 Black South African men and women aged 30-70 years who are part of the Cape Town arm of the Prospective Urban and Rural Epidemiology (PURE) Study. The study cohort has been established in Mount Frere, Eastern Cape (rural) and Langa, Cape Town(urban) since 2009 and the current work is secondary analysis of the baseline study data.Data collection/synthesis: SES indicators including income, employment status, marital status and completed education were gleaned from the baseline data of the PURE Cape Town study for all study participants. Then CVD risk factors including obesity, hypertension, selfreported diabetes, consumption of tobacco and alcohol consumption were also determined for the same participants. Data analysis: Data was analysed using SPSS version 20 for Windows. Descriptive statistics including frequency counts, percentages, mean and standard deviations (where normal distribution) and median and interquartile range (where non-normal) were used to summarise data on SES and CVD risk factors. This was performed separately for rural and urban study participants. Analytical statistics was used to examine associations between SES indicators and CVD risk factors with risk factors as both dichotomous and multi-level categorical variables. Kendall’s τ rank correlation coefficient was obtained to assess the relationship between the three indicators of SES. Prevalence rates reported with 95% confidence intervals was determined for risk factors across categories of SES indicators. P-values for trends in CVD risk factors were obtained by treating the SES indicators as categorical variables in logistic regression analyses. Multiple logistic regression analysis to estimate independent effects of the different SES indicators on risk factors was performed. In all analyses, P-values < 0.05 were regarded as significant.Results: There was a significant difference in the socioeconomic and CVD risk factors profile of urban and rural participants. Except for hypertension and tobacco use with insignificant higher prevalence in the urban location, all CVD risk factors were significantly higher in urban than rural participants. Some CVD risk factors (hypertension and diabetes) were positively associated with high SES (income) and some others (tobacco use) were negatively associated with employment status. Highest income earners had the highest risk of hypertension (AOR= 2.4, 95% CI 1.5-3.9) and diabetes (AOR= 2.2, 95% CI 1.2-4.1) after adjusting for age, sex and other SES variables. Marital status however showed the most consistent association across all CVD risk factors; widowed participants had a high risk of hypertension (OR=2.1, 95% CI 1.2-3.7) and diabetes (OR=2.0, 95% CI 1.1-3.7), but had the lowest risk of tobacco (OR=0.3, 95% CI 0.14-0.66) and alcohol use (OR=0.3, 95% CI 0.15-0.72). The distribution of CVD risk factors by SES gradient showed inconsistent patterning and difference between the urban and rural participants.Conclusion: In this cohort of adult Black South Africans, high income earning and widowed marital status were associated with higher hypertension and diabetes prevalence, while unemployment was associated with higher tobacco use.Recommendations: CVD risk reduction interventions that recognise the differential susceptibility of individuals in different SES group need to be designed and implemented.Widows and widowers should be given focussed attention in health screening as they may have increased vulnerability to diseases especially CVDs. There is however need for more research to establish the pathway through which SES factors predispose or protect individuals from CVDs.

Magister Public Health - MPH / Introduction: In recent years, cardiovascular disease (CVD) has emerged as a leading cause of death in developing countries. It is important to identify and target people who are at risk,given that a third of all deaths are expected to be due to CVD by 2020. Studies have shown socio-economic patterning in the prevalence of risk factors for CVD, including obesity,smoking and lipid profile. In developed countries, the association between socio-economic status (SES) and CVD risk factors is negative, with a higher prevalence of CVD risk factors among people of lower SES. However, findings from studies in developing countries on this including South Africa has been inconsistent. In addition, there is scant information on differences in socio-economic patterning of CVD risk factors between urban and rural areas in South Africa.Aim: To examine the association between SES indicators and CVD risk factors among an adult population cohort of Black South Africans living in a rural and urban community.Study design: Quantitative cross-sectional analytical study of baseline data of a populationbased cohort of 2000 Black South African men and women aged 30-70 years who are part of the Cape Town arm of the Prospective Urban and Rural Epidemiology (PURE) Study. The study cohort has been established in Mount Frere, Eastern Cape (rural) and Langa, Cape Town(urban) since 2009 and the current work is secondary analysis of the baseline study data.Data collection/synthesis: SES indicators including income, employment status, marital status and completed education were gleaned from the baseline data of the PURE Cape Town study for all study participants. Then CVD risk factors including obesity, hypertension, selfreported diabetes, consumption of tobacco and alcohol consumption were also determined for the same participants. Data analysis: Data was analysed using SPSS version 20 for Windows. Descriptive statistics including frequency counts, percentages, mean and standard deviations (where normal distribution) and median and interquartile range (where non-normal) were used to summarise data on SES and CVD risk factors. This was performed separately for rural and urban study participants. Analytical statistics was used to examine associations between SES indicators and CVD risk factors with risk factors as both dichotomous and multi-level categorical variables.Kendall’s τ rank correlation coefficient was obtained to assess the relationship between the three indicators of SES. Prevalence rates reported with 95% confidence intervals was determined for risk factors across categories of SES indicators. P-values for trends in CVD risk factors were obtained by treating the SES indicators as categorical variables in logistic regression analyses. Multiple logistic regression analysis to estimate independent effects of the different SES indicators on risk factors was performed. In all analyses, P-values< 0.05 were regarded as significant.Results: There was a significant difference in the socioeconomic and CVD risk factors profile of urban and rural participants. Except for hypertension and tobacco use with insignificant higher prevalence in the urban location, all CVD risk factors were significantly higher in urban than rural participants. Some CVD risk factors (hypertension and diabetes) were positively associated with high SES (income) and some others (tobacco use) were negatively associated with employment status. Highest income earners had the highest risk of hypertension (AOR= 2.4, 95% CI 1.5-3.9) and diabetes (AOR= 2.2, 95% CI 1.2-4.1) after adjusting for age, sex and other SES variables. Marital status however showed the most consistent association across all CVD risk factors; widowed participants had a high risk of hypertension (OR=2.1, 95% CI 1.2-3.7) and diabetes (OR=2.0, 95% CI 1.1-3.7), but had the lowest risk of tobacco (OR=0.3, 95% CI 0.14-0.66) and alcohol use (OR=0.3, 95% CI 0.15-0.72). The distribution of CVD risk factors by SES gradient showed inconsistent patterning and difference between the urban and rural participants.Conclusion: In this cohort of adult Black South Africans, high income earning and widowed marital status were associated with higher hypertension and diabetes prevalence, while unemployment was associated with higher tobacco use.Recommendations: CVD risk reduction interventions that recognise the differential susceptibility of individuals in different SES group need to be designed and implemented.Widows and widowers should be given focussed attention in health screening as they may have increased vulnerability to diseases especially CVDs. There is however need for more research to establish the pathway through which SES factors predispose or protect individuals from CVDs.

Orientadores: José Guilherme Cecatti, Rodolfo de Carvalho Pacagnella / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T18:17:52Z (GMT). No. of bitstreams: 1 Polido_CarlaBetinaAndreucci_D.pdf: 9580415 bytes, checksum: 7a66fbe0b5c7b89a2918fd10375d6d95 (MD5) Previous issue date: 2015 / Resumo: Introdução: Morbidade materna grave e near miss materno são indicadores de saúde mais abrangentes, quando comparados à razão de morte materna. Esse conceito recente permite não apenas a identificação do número de mulheres que morrem durante gestação e/ou parto, mas também o estudo da prevalência de condições potencialmente ameaçadoras de vida. No entanto, pouco se conhece sobre as possíveis consequências em longo prazo após esses episódios nos diversos aspectos da vida das sobreviventes. A gestação e o parto podem modificar a resposta sexual feminina, mas poucos estudos avaliaram esse desfecho após eventos de morbidade materna grave. Objetivos: Realizar uma revisão sistemática sobre aspectos de sexualidade, incluindo função sexual, em mulheres que apresentaram qualquer tipo de complicação durante gestação ou parto. Avaliar aspectos da resposta sexual feminina em mulheres com e sem morbidade materna grave. Métodos: Revisão sistemática nas bases de dados PubMed, EMBASE e SciELO, avaliando a associação de morbidade materna geral e grave com alterações da função e/ou resposta sexual feminina. A revisão seguiu o protocolo do método proposto para estudos observacionais (PRISMA). A resposta sexual feminina foi estudada como um dos desfechos da Coorte de Morbidade Materna Grave (COMMAG). O questionário Female Sexual Function Index (FSFI) foi aplicado às mulheres expostas (com antecedente de morbidade grave) e não expostas (com antecedente de gestação sem complicações). Além do FSFI, questões gerais sobre saúde geral e reprodutiva complementaram o estudo. Resultados: Lesões perineais maiores (terceiro e quarto graus) foram avaliadas como desfechos de morbidade geral em 12 estudos, e a morbidade materna grave foi analisada em 2 estudos. A morbidade geral e a grave foram associadas com maior tempo para a retomada da atividade sexual após o parto. A morbidade também se associou a uma maior frequência de dispareunia após o parto. Escores totais do FSFI não foram significativamente diferentes entre grupos de exposição e controle. Pela heterogeneidade entre eles, os estudos individuais permitiram apenas uma síntese qualitativa dos resultados, mas não metanálise. Para avaliação da resposta sexual feminina no COMMAG, foram incluídas 638 mulheres previamente internadas durante gestação ou parto na maternidade do CAISM/UNICAMP. Dessas, 315 tinham antecedente de morbidade materna grave, e 323 eram mulheres sem complicações durante gestação ou parto. Os escores totais médios do FSFI encontrados foram abaixo dos valores de ponto de corte para suspeita de disfunção, sem diferença entre os grupos estudados. Mulheres com antecedente de morbidade materna grave retomaram atividade sexual mais tardiamente após o parto do que as do grupo controle, porém sem diferença entre os grupos a partir do terceiro mês pós-parto. A análise múltipla identificou associação de valores mais baixos de FSFI com baixo de peso materno e ausência de parceria. Conclusões: Alterações da resposta sexual feminina podem ser consequências em longo prazo da ocorrência de episódios de morbidade materna grave. Com o crescimento da população de mulheres que sobrevivem a esses episódios, a abordagem da sexualidade no seguimento dessa população se faz premente / Abstract: Introduction: Severe maternal morbidity and maternal near miss currently are better health indicators than maternal mortality ratio. Together with the identification of women who died during pregnancy and/or childbirth, the new concept allows also to investigate the prevalence of potential life-threatening conditions. However, little is known about possible long-term consequences after those episodes over several aspects of the lives of survivors. It has already been described that uncomplicated pregnancy and childbirth might modify female sexual response. Notwithstanding, only few studies have evaluated aspects of sexuality of women after episodes of severe maternal morbidity. Objectives: To perform a systematic review of aspects of sexuality, including sexual function, in women who had had any kind of complication during pregnancy or childbirth. To evaluate aspects of female sexual response in women with and without severe maternal morbidity. Methods: Investigation included a systematic review through the databases PubMed, EMBASE, and SciELO, assessing general and severe maternal morbidity associated with altered female sexual response. The review followed the protocol method proposed for observational studies (PRISMA). The female sexual response has been studied as one of the outcomes at a retrospective cohort study on maternal severe morbidity (COMMAG). The Female Sexual Function Index questionnaire (FSFI) was applied at exposed women (severe morbidity) and unexposed (pregnancy without complications). Along with FSFI, the survey included also questions on general and reproductive health. Results: Major perineal injuries (3rd and 4th degree) were evaluated as general morbidity outcomes at 12 studies, and severe maternal morbidity was analyzed at 2 studies. Compared to control group, both women exposed to general and severe morbidity delayed resumption of sexual activity after childbirth. The exposed group had also more frequently dyspareunia after childbirth. The mean total FSFI scores were similar at both groups. The heterogeneity of the studies allowed only a qualitative synthesis, and meta-analysis was not feasible. To assess female sexual response at the cohort study, 638 women who delivered at UNICAMP's maternity unit were included. 315 of them were severe maternal morbidity cases, and 323 were women who had had uncomplicated pregnancy or childbirth. The mean total scores of FSFI were similar in both groups, though below cut-off values for suspected dysfunction. Women after severe maternal morbidity resumed sexual activity after birth later, when compared to control group. However, there was no significant difference at three months. Multivariate analysis showed association of lower FSFI scores with maternal low maternal weight and no partner. Conclusions: Altered female sexual response might be a long-term consequence after episodes of severe maternal morbidity. Since there is a growing population of women who survive these episodes, proper evaluation of sexual functioning among those women should be conducted / Doutorado / Saúde Materna e Perinatal / Doutora em Ciências da Saúde

Prematurity is a worldwide problem. Every year, 15 million babies are born prematurely, and 1 million of those babies die because of related complications. The surviving premature babies are struggling to hold on to their lives, and even when they do live, most of them end up having various complications to survive and get stronger. There are physical complications faced on their journey such as having underdeveloped lungs, pneumonia, obesity, sepsis, retinopathy of prematurity, respiratory distress syndrome, bronchopulmonary dysplasia, asthma, wheezing, bronchiolitis, cerebral palsy, and motor impairment. They can also develop mental and behavioral health complications such as depression, seizures developmental delay, schizophrenia, autism spectrum disorder, psychological development disorders, behavioral problems, attention problems, and ADHD later in life. The purpose of this systemic review is to understand the impact of long-term complications of premature birth on individual life and society. We hypothesized that based on data from primary research, nearly one half of the infants will have either physical and/or cognitive/developmental health complications. We hypothesized that infants born premature have more physical complications than cognitive complications and infants born prematurely have more cognitive complications than physical complications. This research was carried out by finding cohort study design studies through Medline, Academic Search Premier, and APA PsychINFO, where the studies will be compiled from 2003 – 2020.

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.

No description available.

Introduction: Cerebrovascular events are a major cause of mortality, disability and healthcare resource use. Despite this, there is a lack of reliable information on their costs and outcomes, particularly related to transient ischaemic attacks (TIA) and minor stroke. Such information is vital to inform decisions about local and national service provision, and to provide reliable estimates for use in cost-effectiveness analyses. Aims This thesis estimates the costs and outcomes of stroke and TIA using data from a population-based study undertaken in a population of over 91,000 individuals in Oxfordshire (the Oxford Vascular Study – OXVASC). In addition, the thesis aims to estimate the short-term cost-effectiveness of two secondary stroke prevention programmes evaluated in a study nested within OXVASC. Methods: Using multiple methods of case ascertainment, 1,282 patients were identified as having suffered a stroke or TIA, of which 1,199 (723 stroke and 476 TIA) patients consented to the study. Follow-up of patients took place at 1, 6, 12 and 24 months, with data collected on patients’ disability, medication usage, living arrangements, and quality of life. Healthcare resource use information was derived from hospital and primary care records, and priced using published unit costs. Findings: Stroke patients had higher case-fatality rates than TIA patients (15% vs. 1%; p<0.001), with 5-year life expectancy being one year longer for TIA patients. For stroke and TIA survivors, the risk of disability remained higher, at around 30% at each of the four follow-ups, than at baseline (17%; p<0.001 for all follow-ups). After standardising for age and gender, average quality of life for stroke and TIA patients combined was significantly lower than English population norms (p<0.001 for all follow-ups). However, when quality of life was compared to population norms by event type, quality of life differences between TIA patients and English population norms no longer remained statistically significant. Important predictors of quality of life included event severity, baseline disability and recurrent vascular events. Total costs were considerably higher 1-year after the initial stroke or TIA than for the year preceding it and, except for day cases, increases were observed for all resource-use categories. Five years after the index event, stroke patients incurred costs of £16,923 (95% CI: 15,149 to 18,858) per patient, significantly higher than those incurred by TIA patients, at £13,904 (95% CI: 11,488 to 16,657; p=0.019). In multivariate analyses, event severity was found to be a significant predictor of inpatient care resource use and costs, as were the presence of recurrent vascular events, especially stroke and coronary events. For non-hospitalised patients, results showed that urgent outpatient specialist assessment and treatment reduced the 90-day risk of fatal or disabling stroke (0.4% vs. 5%, p<0.001) compared with less urgent assessment and treatment. In terms of resource usage, patients who were assessed and treated urgently had lower recurrent stroke hospitalisation (2% vs. 8%; p=0.001), and reduced overall number of days in hospital (average reduction of 4 days; p=0.017). These reductions in hospital resource usage generated savings of £643 per patient assessed and treated urgently in an outpatient clinic (p=0.028). Conclusion: Despite the impact of stroke on death, disability and healthcare resource use, there is a lack of reliable information on costs and outcomes, especially for TIA and minor stroke. Through the use of a population-based study, the gold-standard study design when assessing the incidence and outcomes of TIA and stroke, this thesis provides healthcare decision makers and researchers with a wealth of data on the resource use patterns, costs and outcomes of TIA and stroke patients, and their main predictors.

Background: Subjective cognitive decline (SCD), i.e., the self-perceived feeling of worsening cognitive function, may be the first notable syndrome of preclinical Alzheimer’s disease and other dementias. However, not all individuals with SCD progress. Stability of SCD, i.e., repeated reports of SCD, could contribute to identify individuals at risk, as stable SCD may more likely reflect the continuous neurodegenerative process of Alzheimer’s and other dementias. Methods: Cox regression analyses were used to assess the association between stability of SCD and progression to MCI and dementia in data derived from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). Results: Of 453 cognitively unimpaired individuals with a mean age of 80.5 years (SD = 4.2), 139 (30.7 %) reported SCD at baseline. Over the study period (M = 4.8 years, SD = 2.2), 84 (18.5 %) individuals had stable SCD, 195 (43.1 %) unstable SCD and 174 (38.4 %) never reported SCD. Stable SCD was associated with increased risk of progression to MCI and dementia (unadjusted HR = 1.8, 95 % CI = 1.2–2.6; p < .01), whereas unstable SCD yielded a decreased progression risk (unadjusted HR = 0.5, 95 % CI = 0.4–0.7; p < .001) compared to no SCD. When adjusted for baseline cognitive functioning, progression risk in individuals with stable SCD was significantly increased in comparison to individuals with unstable SCD, but not compared to individuals without SCD. Conclusions: Our results, though preliminary, suggest that stable SCD, i.e., repeated reports of SCD, may yield an increased risk of progression to MCI and dementia compared to unstable SCD. Baseline cognitive scores, though within a normal range, seem to be a driver of progression in stable SCD. Future research is warranted to investigate whether stability could hold as a SCD research feature.