OBJETIVO Avaliar as evidências quanto à associação entre síndrome metabólica e periodontite através de uma revisão sistemática da literatura e metanálise de estudos observacionais. MATERIAIS E MÉTODOS Os estudos foram acessados através de busca nas bases eletrônicas Medline, EMBASE e Biblioteca Cochrane e de busca manual para identificar estudos, observacionais, originais, realizados com população adulta, que avaliaram a associação entre síndrome metabólica e doença periodontal. Os estudos deveriam mencionar critério de diagnóstico para síndrome metabólica e pelo menos uma medida clínica para o diagnóstico de periodontite e apresentar as medidas de efeito através de razão de chance (OR), risco relativo (RR) ou taxa de prevalência (PR). Os dados foram extraídos por dois investigadores, de maneira independente. A metanálise dos estudos incluídos foi realizada utilizando-se modelos randômicos. RESULTADOS A revisão sistemática incluiu 17 estudos observacionais, que preencheram os critérios de inclusão. Na metanálise foram incluídos 11 estudos, totalizando dados de 38.189 pacientes. Encontrou-se associação entre síndrome metabólica e periodontite com um OR de 1,78 (IC 95% 1,38- 2,30), e heterogeneidade de i2=93%. Para investigar a alta heterogeneidade foram (1) rodadas análises sequenciais, excluindo-se um estudo por vez, (2) metarregressão avaliando-se isoladamente idade, tabagismo, critério de diagnóstico para síndrome metabólica e exame periodontal completo versus parcial, (3) análise de subgrupos analisando-se em separado estudos em população asiática e não asiática e análise de sensibilidade. A heterogeneidade foi reduzida de forma significativa quando subdividiu-se os estudos com origem em população asiática (OR 2,06, IC 95% 1,60– 2,85, i2= 83,1%) e em população não asiática (OR 1,12 IC 95% 1,04- 1,68, i2=65,3%). CONCLUSÃO Os achados deste estudo reportam uma associação significativa entre síndrome metabólica e doença periodontal. A falta de um número suficiente de estudos longitudinais impede que se estabeleça a direção desta associação. Devido a alta heterogeneidade encontrada, estudos de intervenção bem controlados são necessários para que se conheça a magnitude dessa associação. / PURPOSE To investigate the association of metabolic syndrome and periodontitis by means of a systematic review and a meta-analysis of observational studies. RESEARCH DESIGN AND METHODS The electronic databases Medline, EMBASE and The Cochrane Library were searched for observational studies that evaluated the association of Metabolic Syndrome and Periodontitis. Hand search was also done. Data extraction was performed by two reviewers independently. Pooled effect estimates were obtained by using random-effects meta-analysis. RESULTS Systematic review included 17 studies that fulfilled the inclusion criteria. Meta-analysis was done with 11 studies, providing data of 38.189 patients. The results showed that there is an association estimated in an OR of 1,78 (95%IC 1,38- 2,30) between metabolic syndrome and periodontitis. A high heterogeneity was present (i2=93%). To investigate heterogeneity (1) the meta-analysis was re-ran excluding studies one at a time, (2) univariate metaregression was performed analyzing smoke status, metabolic syndrome criteria and parcial versus complete periodontal record, (3) subgroup analysis splitting studies in those performed with Asiatic populations and with non-Asiatic populations and sensitivity analysis. The heterogeneity was reduced significantly when subgroup analysis was done, for Asiatic population an OR of 2,06 (95% IC 1,60-2,85) and i2= 83,1% and for non-Asiatic population an OR of 1,12 (95% IC 1,04- 1,68) and i2=65,3% were found. CONCLUSION This study showed a significant association between metabolic syndrome and periodontitis. The lack of longitudinal studies in this area prevent from setting the direction of this association. Due to the high heterogeneity found, interventional and well controlled studies are encouraged to elucidate the magnitude of this association.

Objectives: The thesis comprises two parts. Firstly, a systematic review (SR) systematically examined meta-analytic studies assessing the prevalence of sexual abuse in childhood. A meta-analysis sought to systematically identify and synthesise data from studies providing prevalence estimates of contact and non-contact child sexual abuse (CSA) as self-reported by adolescents within the past 10 years. Methods: Consistent with Cochrane Collaboration guidelines, the systemic review adopted a comprehensive search of electronic databases and additional sources, including communication with authors working in the field, and the use of ancestry and descendency approaches between February 2013 and March 2014. The meta-analysis also adopted an equally systematic search conducted from March 2013 to June 2014. Assessment of quality and risk of bias were conducted on the included studies using PRISMA criteria and STROBE guidelines. Results: The systematic review identified six meta-analytic studies for review. The quality of studies and the range of definitional and methodological factors studied varied; results sections were well covered, whereas, quality and risk of bias within studies were generally poorly addressed. Prevalence estimates varied considerably and high heterogeneity was consistent across all analyses. Nine population studies measuring prevalence of contact and non-contact CSA were included in the meta-analysis. Meta-analyses were conducted overall and across male and female populations. Prevalence estimates varied considerably across studies, with contact CSA ranging from 2% to 39.8% and overall non-contact CSA, estimates ranged from 1% to 24.6%. Substantial heterogeneity was present across all analyses and therefore findings should be interpreted with caution. Nevertheless, the findings were thought-provoking and most likely due to differences in definitions of CSA and inconsistent use of validated instruments. Conclusions: Child sexual abuse is an international problem which is highly pervasive across all societies and populations studied. Females consistently report higher rates of CSA than males, and some Asian countries, namely China, produce relatively lower CSA estimates, even controlling for a wide range of methodological factors and study characteristics. The considerable heterogeneity was apparent both between and within studies and it appears likely based on the current findings, and in the context of previous research, that there are a wide range of methodological and socio-demographic factors which moderate CSA prevalence estimates. More specifically, the lack of a universally recognised definition of CSA proves especially problematic for researchers. The issue is further complicated by use of non-standardised instruments and inconsistent reporting and dissemination of findings. There is a need for future epidemiological studies to adhere to universal guidelines using standard definitions, standardisation of instruments and standardisation of reporting and dissemination to facilitate development of health policies, resource allocation and prevention initiatives for clinical and social services.

Objectives: This thesis includes two distinct pieces of work. A systematic literature review (SLR) aimed to identify, organise and evaluate constructs and measures of adjustment and adaptation to retirement (AAR), as these are currently used in the literature. A meta-analysis (MA) sought to systematically evaluate the evidence of the relationship between retirement and self-reported symptoms of depression in later life. Methods: For the SLR, a comprehensive list of electronic databases, and additional sources, were searched (March-May 2013). The identified constructs of AAR were evaluated in relation to their content, clarity and frequency of use. The identified measures were evaluated in relation to pre-defined psychometric properties and frequency of use. For the MA, an equally comprehensive search strategy was used (December 2012-March 2013). A metaanalysis and systematic assessment of risk of bias were carried out on the studies eventually included. Results: In the SLR, 27 measures of AAR were put forward for evaluation, and 6 distinct clusters of constructs of AAR were identified. AAR is defined inconsistently in this literature. Most measures that are used to assess these constructs are adapted or imported from other contexts (e.g. mental health, well-being, life-satisfaction). The 7 measures that related specifically to AAR (‘retirement satisfaction and role adjustment’) lacked detailed psychometric information. Eight non-randomised studies were included in the MA, 5 cohort studies and 3 cross-sectional studies. Studies were grouped and analysed according to these two design-type subgroups There was evidence of high dispersion of effect sizes, variable risk of bias and methodological and statistical heterogeneity between studies in both sub-groups – cohort (Q=640.728, df =4, p<0.001), cross-sectional (Q=76.611, df=2, p<0.001). Summary effects were therefore not meaningful. Sensitivity and sub-group analyses did not account for high heterogeneity of effect sizes. Conclusions: The SLR concluded that the variability in outcomes of research on AAR found in this literature may be underpinned, in part, by the different constructs and measures that are used. The 27 measures evaluated did not seem, at face-value, to measure the same construct; their psychometric properties also varied. The interpretation of outcomes, and comparisons between studies, in this area is hindered by this inconsistency. The MA concluded that the relationship between retirement and self-reported depressive symptoms seems to be complex and variable. Effect-sizes of individual studies were small, non-significant and highly dispersed, and heterogeneity of true effects was high. These results may be limited by confounding factors in primary studies. This is discussed and contextualised in relation to the use of non-randomised studies in meta-analysis.

Unlike achieved fertility, fertility intentions are often positively correlated with education. However, the conditions under which such a positive relationship exists are not yet well known. Using 86 pieces of research covering 13 European countries that were published between 1990 and 2011, we assess in a quantitative manner the temporal and cross-country variation in the relationship between educational attainment and reproductive intentions. Because of the sequential nature of reproductive decisions and the gendered nature of each individual's life course, we look separately at childless women and women with one child, and compare women with men. Our findings show that both first and second birth intentions and educational attainment are positively correlated, but that this relationship - which is stronger for men than for women - tends to disappear when the normative value of a two-child family is reached. Structural labour market characteristics explain a good portion of the cross-country variance: the educational slope of first and second birth intentions is steeper in countries with large shares of women in vulnerable employment situations or in part-time employment, and is flatter in countries with gender-equal labour force participation and large shares of women in highly qualified employment.

Tax compliance varies across sociodemographic categories. However, research on the relationships between compliance and age, sex, education as well as income level shows inconsistent results, both regarding the direction of the relationship and its size. The current meta-analyses target to merge findings in survey studies on age, sex, education, and income and estimate the strength of the impact on compliance by taking into account geographical regions. In four meta-analyses, comprising 459 samples (N = 614,286) from 111 countries published between 1958 and 2012, average estimated effect sizes were small, ranging from r = 0.12 for the relationship between compliance and age, r = 0.06 for sex, r = -0.02 for education to r = -0.04 for income. These effects are more pronounced in Western countries. It thus appears sociodemographic characteristics have little impact on compliance, but nevertheless should be controlled for in tax research.

The objective of this paper is to provide a robust understanding of the magnitude and direction of effect of urban green space on human health outcomes. This relationship has been studied using a variety of health and green space measures and multiple approaches to collect health data. Due to the various approaches used to study the relationship between green space and health, it is difficult to clearly understand the general relationship. In order to have a robust and clear understanding of the relationship between green space and human health, it is necessary to do a meta-analysis that considers all the approaches to assessing green space, health, and health data. Overall, the average estimated effect shows that surrounding urban green space improves human health by 1.14 fold (~u=0.13 (95% CI: (0.07-0.19)). The magnitude of effect increased when accounting for perceived health and when using greenness as the urban green space measure (~u=0.29 (95% CI: (-0.06-0.63)). In conclusion we can now objectively imply that health can be improved with increased surrounding green space. Further, that the magnitude depends on how studies assess green space and health measures, as well as how health data is collected.

This thesis was motivated by data from the Emerging Risk Factors Collaboration (ERFC), a large individual participant data (IPD) meta-analysis of risk factors for coronary heart disease(CHD). Cardiovascular disease is the largest cause of death in almost all countries in the world, therefore it is important to be able to characterise the shape of risk factor–CHD relationships. Many of the risk factors for CHD considered by the ERFC are subject to substantial measurement error, and their relationship with CHD non-linear. We firstly consider issues associated with modelling the risk factor–disease relationship in a single study, before using meta-analysis to combine relationships across studies. It is well known that classical measurement error generally attenuates linear exposure–disease relationships, however its precise effect on non-linear relationships is less well understood. We investigate the effect of classical measurement error on the shape of exposure–disease relationships that are commonly encountered in epidemiological studies, and then consider methods for correcting for classical measurement error. We propose the application of a widely used correction method, regression calibration, to fractional polynomial models. We also consider the effects of non-classical error on the observed exposure–disease relationship, and the impact on our correction methods when we erroneously assume classical measurement error. Analyses performed using categorised continuous exposures are common in epidemiology. We show that MacMahon’s method for correcting for measurement error in analyses that use categorised continuous exposures, although simple, does not provide the correct shape for nonlinear exposure–disease relationships. We perform a simulation study to compare alternative methods for categorised continuous exposures. Meta-analysis is the statistical synthesis of results from a number of studies addressing similar research hypotheses. The use of IPD is the gold standard approach because it allows for consistent analysis of the exposure–disease relationship across studies. Methods have recently been proposed for combining non-linear relationships across studies. We discuss these methods, extend them to P-spline models, and consider alternative methods of combining relationships across studies. We apply the methods developed to the relationships of fasting blood glucose and lipoprotein(a) with CHD, using data from the ERFC.

Osteoporotic fractures are a major and increasing clinical and public health concern internationally. Identification of individuals at high risk for fragility fractures may enable us to target preventive interventions more effectively. In this thesis, I aimed to evaluate novel risk factors for osteoporosis and develop a fracture risk assessment model among the middle-aged and older people. I used data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, which is a large population-based prospective study started in 1993. About 25,000 men and women were assessed at baseline and about 15,000 of them returned for a second examination 4 years later. All participants are followed up to the present for clinical events including fractures. My work is in two parts. For the first part, I examined the risk of fracture associated with some novel or less well studied risk factors. These risk factors included change in height over time, respiratory function, physical activity and body fat mass. We found that men and women with annual height loss &gt;0.5 cm are at increased risk of hip and any fracture (relative risk=1.9 (95% CI 1.3-2.7) per cm/year height loss). One litre lower forced expiratory volume in 1 second (FEV1) was associated with a 2-fold risk of hip fracture in men and women. We also observed a non-linear association, independent of body mass index, between increasing body fat mass and lower fracture risk in women but not in men. I performed a systematic review and meta-analysis of studies evaluating the association between physical activity and hip fractures. Using a new validated questionnaire in EPIC-Norfolk, we observed varying relationships between physical activity in different domains of life and fracture risk in men and women. For the second part of the thesis, I developed a biostatistical model to calculate 10-year risk of developing a fracture among EPIC-Norfolk study participants. This model incorporates clinical and radiological assessments known to be associated with fractures and can be extended to other risk factors assessed in other prospective cohorts. This helps clinicians to achieve a better estimate of the prospective risk of fracture in their patients. I applied this model to compare the predictive value of two different clinical assessment methods for osteoporosis, namely dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS). We found that that the predictive power of QUS is comparable to, and independent of, predictive power of DXA. In summary, my studies have added to our knowledge about some novel and easy-to-use risk factors of osteoporosis and proposed a practical method to merge and utilise data from different risk factors for estimation of fracture risk in individuals.

Antiplatelet therapy with clopidogrel is widely used in patients with coronary artery disease, but the recent development of the new P2Y12 receptor antagonists prasugrel and ticagrelor will increase treatment options. An overview of systematic reviews was performed to summarize available evidence on clopidogrel. Current data on prasugrel and ticagrelor were identified by a systematic review and used for an indirect treatment comparison (ITC) of the drugs against each other and versus placebo in the absence of head-to-head clinical trials. Adjusted indirect comparison according to Bucher, Bayesian methods for mixed treatment comparisons using Winbugs, and generalized linear mixed models using SAS were employed for ITC, yielding almost identical results: prasugrel was favored regarding stent thrombosis and ticagrelor regarding major bleeding. However, substantial differences in trial design were identified, demanding caution when interpreting these results. On the basis of the obtained results, a randomized controlled trial was designed within the gap of current evidence.

The study of ethnicity in bullying research has yielded inconsistent findings regarding the involvement and prevalence rates among ethnic majority and minority groups. On one hand, individual studies using ethnic group membership as a demographic variable indicate that ethnic minority groups are at times more or less likely to experience or perpetrate bullying compared to White students. On the other hand, contextual factors such as ethnic diversity have yielded more consistent findings showing that increased ethnic diversity is associated with lower bullying victimization among ethnic minority students. The role of ethnicity in bullying and peer victimization was examined in this dissertation by investigating both individual and contextual variables. Studies 1 and 2 consisted of two meta-analyses that systematically addressed comparisons between ethnic majority (i.e., White) and minority students (i.e., Black, Asian, Hispanic) on bullying perpetration and peer victimization. Results indicated small and non-significant overall effect sizes; however, methodological moderators suggested that ethnic groups differ on bullying and peer victimization across countries, measurements, and age groups. Study 3 examined school ethnic composition and bullying involvement in a population-based, ethnically diverse Canadian sample. Results indicated that ethnic minority students experienced less bullying victimization in schools with a higher proportion of ethnic minority peers. School ethnic composition was not associated with bullying victimization for White students or bullying perpetration across both ethnic groups. Taken together, these studies suggest that ethnicity as a demographic variable is not sufficient to account for differences in bullying involvement and that contextual variables are more adequate at explaining patterns of bullying across ethnic groups within the larger school and societal contexts.