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Causal inference methods have been applied in various fields where researchers want to establish causal effects between different phenomena. The goal of causal inference is to estimate treatment effects by comparing outcomes had units received treatment versus outcomes had units not received treatment. We focus on estimating treatment effects in three different projects. We first proposed linear unbiased estimators (LUEs) for general causal effects under the assumption that treatment effects are additive. Under the assumption of additivity, the set of estimands considered grows as contrasts in exposures are now equivalent. Furthermore, we identified a subset of LUEs that forms an affine basis for LUEs, and we characterized LUEs with minimum integrated variance through defining conditions on the support of the estimator. We also estimated the effect of drug-induced homicide (DIH) prosecutions reported by the media on unintentional drug overdose deaths, which have never been empirically assessed, using various models. Using a difference-in-differences-like logistic generalized additive model (GAM) with smoothed time effects where we assumed a constant treatment effect, we found that DIH prosecutions reported by the media were associated with a potential harmful effect (risk ratio: 1.064; 95% CI: (1.012, 1.118)) on drug overdose deaths. Upon further research, however, there are potential issues using a constant treatment effect model in a setting where treatment is staggered and treatment effects are heterogeneous. Therefore, we also used a GAM with a linear link function where we assumed that treatment effects may depend on the treatment duration. With this second model, we estimated a risk ratio for having any DIH prosecutions reported by the media of 0.956 (95% CI: (0.824, 1.110)) and a risk ratio of 0.986 (95% CI: (0.973, 0.999)) for the effect of being exposed to DIH prosecutions reported by the media for each additional six months. Despite being statistically significant, the effects were not practically significant. However, the results call for further research on the effect of DIH prosecutions on drug overdose deaths. Lastly, we shift our focus to Structural Nested Mean Models (SNMMs). We extended SNMMs to a new class of estimators which estimate treatment effects of different treatment regimes in the risk ratio scale---the Structural Nested Risk Ratio Model (SNRRM). We further generalized previous work on SNMMs by estimating treatment effects by modeling a function of treatment, which we choose to be any function that can be modeled by generalized linear models, as opposed to just a model for treatment initiation. We applied SNRRMs to estimate the effect of DIH prosecutions reported by the media on drug overdose deaths.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Infections by gastrointestinal nematodes are among the main diseases of the ruminants around the world. These infections cause - in their clinical or subclinical courses a decrease of the productivity of the herds, thus, the economic viability of the ruminant farms is directly related to an adequate control of these parasites. Although the benefits of the use of several practices of alternative control of parasites are proven and, despite of that these practices have been improved through the years, in general, the use of efficacious antiparasitic drugs is imperative to control satisfactorily the helminths of the ruminants. However, the development of parasite resistance to these drugs has become common and, in some cases, parasitic populations are multiple resistant to several classes of anthelmintics and endectocides, and it makes very difficult to control the helminthosis adequately. In this study are shown some experiments conducted with the aim of to find ways to restore the efficacy of the treatments, for recovering the usefulness of active ingredients for which the gastrointestinal nematodes of ruminants became resistant. Efficacy tests of the drugs were made using Fecal Egg Count Reduction Tests (FECRT) and larvae cultures, for the identification of the genus of nematodes existing, before and after the treatments. We evaluated the anthelmintic action of high concentrated (long acting) drugs, overdoses (high dosages), commercial combinations of drugs and combinations of chemicals, formulated with basis in previous efficacy tests for each active ingredient alone. These combinations, done from drugs sold separately, gave us the best results. Based in these observations, we are proposing a new approach regarding helminth control in multi-resistant populations, by using combinations of drugs with different mechanisms of action on the parasites, and taking advantage of the efficacy tests, performed before the choose of drugs, and then, to prove the results obtained with the combinations done particularly for each herd. / As infecções por nematódeos do trato gastrintestinal estão entre as principais enfermidades de ruminantes ao redor do mundo. Essas infecções, clínicas ou subclínicas, impactam negativamente a produtividade dos rebanhos, e a viabilidade econômica dos mesmos está diretamente relacionada a um controle adequado desses parasitas. Embora estejam comprovados os benefícios de utilizarem-se diversas práticas de controle alternativo de parasitas, as quais vêm sendo aprimoradas ao longo dos anos, em geral, a utilização de fármacos antiparasitários eficazes sobre os helmintos que infectam os ruminantes ainda é essencial para que se obtenham resultados satisfatórios. No entanto, o desenvolvimento de resistência parasitária a tais fármacos tem se tornado cada vez mais comum e, em alguns casos, as populações de parasitas já apresentam resistência múltipla a várias classes de anti-helmínticos e endectocidas, comprometendo o adequado controle das helmintoses. Neste estudo apresentam-se experimentos que foram conduzidos com o objetivo de encontrarem-se meios de restabelecer a eficácia dos tratamentos, recuperando-se a utilidade de princípios ativos para os quais os nematódeos gastrintestinais de rebanhos de ruminantes já tenham desenvolvido resistência. Foram utilizados testes de eficácia com base na redução da contagem de ovos nas fezes dos animais após os tratamentos (FECRT), e em culturas de larvas para a identificação dos gêneros de nematódeos presentes nessas amostras. Avaliaram-se os efeitos anti-helmínticos de fármacos de alta concentração (longa ação), de superdosagens, de combinações comerciais e de combinações de drogas elaboradas com base em estudos prévios de eficácia das mesmas (isoladamente), utilizando-se para isso, fármacos comercializados separadamente. Os melhores resultados foram obtidos, justamente, com estas últimas. Propõe-se, a partir destas constatações, uma nova abordagem em relação ao controle antiparasitário em populações de helmintos multi-resistentes, utilizando-se a combinação de diferentes fármacos (com princípios ativos e mecanismos de ação distintos), e valendo-se de testes de eficácia para a escolha dos fármacos e para a comprovação dos resultados obtidos com suas combinações especificamente em cada rebanho.

The purpose of this study is to explore professional drug addiction care workers’ attitudes towards harm reduction interventions. The data collection was conducted through digital survey mailed to mangers and staff. In total 73 individuals choose to answer the survey. The biopsychosocial perspective and stigmatization theory were used to theoretically reflect on the results. Most respondents reported positive attitudes towards maintenance treatment, needle exchange programs and overdose prevention with naloxone. The result also shows that the majority of respondents’ have a negative attitude towards injection rooms and decriminalization of drugs for personal use. Moreover, staff with higher education reported more positive attitudes towards maintenance treatment, needle exchange, injection rooms and decriminalization of drugs for personal use. In conclusion, it is important to recognize and spread new developments and evidence-based research regarding harm reduction and decriminalization of narcotics drugs. Based on the respondents’ negative attitudes towards implement injection rooms and decriminalize drugs for personal use, but also the improvement of staffs’ attitudes that present study found it is supposed that neglecting prohibition and showing zero tolerance towards personal use will probably disappear in the future even in Sweden.

Målet med studien er å undersøke og beskrive ansatte i lavterskel botiltak sine erfaringer med overdoser hos beboere. Gjennom å belyse den ofte tause kunnskapen de ansatte i lavterskeltiltak har om hva som karakteriserer en overdosesituasjon, er studiens hensikt å systematisere og presentere denne erfaringskunnskapen, og gjennom det kunne bidra til en kvalitetsforbedring av den tjenesten som ytes til beboerne.Datainnsamlingen ble gjort gjennom fokusgruppeintervjuer med ansatte på lavterskel botiltak. Flere av kodegruppene som ble arbeidet frem i analysen var tema i begge fokusgruppene. Temaene var overganger, tilgang, å legge lokk på det vanskelige, å dempe kriser og relasjonen til andre. Disse ble igjen rekontekstualisert til «min virkelighet» og «den rusfrie virkelighet,» sammenfattet som «når virkeligheten strammer grepet.»Hovedfunnet i studien er at ansatte opplever at det er når virkeligheten strammet grepet, når rusens dempende slør ikke kan holde virkelighetens krav på avstand, at risikoen for overdoser oppstår. Dette taler for viktigheten av gode relasjoner til hjelpeapparatet, og at de ansatte kjenner til hva som beveger seg i den enkelte beboers liv. / Objectives: This study aimed to investigate and describe how employees working in low threshold housing facilities experience overdosing by facility residents. We also aimed to enlighten the often silent employee knowledge about the characteristics of an overdose situation, thus enhancing the quality of resident services.Materials and Methods: Data was collected through focus group interviews with employees working in low-threshold housing facilities. Many of the code terms identified through data analysis were common to both employees and residents (e.g., “transitions,” “access,” “putting a lid on the difficulties,” “attenuating crises,” and “relation to others.” We recontextualized these codes to “my reality” and “drug-free reality,” or “when reality kicks in.”Results: Our study determined that employees recognize the risk of overdosing as the point at which reality kicks in (i.e., when the attenuating effect of the drugs can no longer keep reality at distance).Conclusion: This study shows that employees are fully aware of residents’ lives and activities. Therefore, policies that maintain good employee relationships with and within the different social and health services may contribute significantly to overdose prevention. / <p>ISBN 978-91-86739-07-2</p>

Après des décennies d'amélioration, l'espérance de vie a stagné dans plusieurs pays à faible mortalité ces dernières années, avec, dans certains cas, quelques reculs. L’augmentation de la mortalité due à la grippe et aux surdoses de drogue, en particulier dans la génération des baby-boomers, a été le principal responsable de cette stagnation de l’espérance de vie. Cette découverte était inattendue, car il est considéré que la mortalité extrinsèque – par opposition à la mortalité intrinsèque due à des maladies dégénératives se déclarant souvent aux grands âges – joue un rôle négligeable dans les changements actuels d'espérance de vie. Pour la même raison, les tendances temporelles de la mortalité extrinsèque n’ont guère retenu l’attention des chercheurs. Les crises périodiques dues aux épidémies de grippe et à la crise des opioïdes sont considérées comme les principaux déterminants des variations de la mortalité extrinsèque. Cependant, des preuves récentes suggèrent que les effets de cohorte jouent un rôle important dans la modulation de la mortalité extrinsèque, mais que de telles influences sont encore mal connues. L'objectif principal de cette thèse est d'examiner le rôle des effets de cohorte sur l’évolution de la mortalité extrinsèque dans les dernières décennies, avec un accent particulier mis sur la grippe et les causes de décès comportementales. Plus spécifiquement, elle vise à (1) déterminer les différences par cohorte de mortalité par la grippe et l’influence des expositions précoces au virus sur cette mortalité; (2) analyser le désavantage de mortalité des baby-boomers au Canada et aux États-Unis en identifiant la contribution des causes comportementales à ce désavantage; et (3) développer un outil méthodologique permettant à la fois l'analyse visuelle de la dynamique temporelle des effets non linéaires d'âge, de période et de cohorte (APC) et la comparaison entre divers phénomènes ou populations. Pour ces analyses, nous utilisons des micro-données de mortalité provenant de systèmes de statistiques de l’état civil au Canada et aux États-Unis. Nous utilisons également les taux de mortalité et de fécondité de divers pays pour généraliser l'analyse visuelle des effets non linéaires à d'autres phénomènes démographiques que la mortalité. Les analyses ont été réalisées en appliquant des modèles de Serfling pour l’estimation de la mortalité par grippe, des mesures démographiques permettant une décomposition par cause des variations de la mortalité, des techniques de lissage pour identifier les tendances et des approches statistiques et visuelles sur des configurations de Lexis pour l’analyse des effets APC. Les résultats, sous la forme de trois articles scientifiques, montrent que malgré des fluctuations marquées au cours des années calendrier (période), les cohortes de naissance ont une influence indépendante et durable sur la mortalité liée à la grippe ou due au comportement. Les principaux résultats du premier article suggèrent que deux mécanismes modulent la mortalité grippale au fil des cohortes. Pour la population jeune et adulte, les risques de mortalité par cohortes dépendent du contraste en le premier virus auquel on est vraisemblablement exposé (le virus laissant« l’empreinte antigénique ») et le virus rencontré à l’âge adulte, au moment de l’épidémie sous observation. Des modifications significatives du risque de décès ont ainsi été observées lors d’épidémies de grippes pour les cohortes nées lors d'importants changements antigéniques (par exemple, une diminution significative du risque pour les cohortes nées entre 1957 et 1968). Pour les âges plus avancés, nous n’avons pas identifié de tels effets de cohorte « ponctuels », mais plutôt un effet de cohorte de plus longue haleine, qui aura conduit à un déclin progressif de la mortalité par grippe entre 1959 et 2016. En nous inspirant des théories dites de technophysio ou de cohort morbidity phenotype, nous attribuons ce déclin à des changements s’étant produit bien avant, c’est-à-dire à l’amélioration marqué des conditions sanitaires qui a eu lieu entre 1900 et 1930, au moment où les cohortes concernées venaient au monde et dont elles ont pu bénéficier. Les travaux du deuxième article de cette thèse révèlent que la plupart des excès de mortalité chez les baby-boomers au Canada et aux États-Unis sont dus à des causes comportementales. Le désavantage des baby-boomers résulte de plusieurs effets de cohortes sur des causes comportementales différentes, et non pas d'effets de période ponctuels affectant la même cohorte aux âges différents, un mécanisme alternatif qui pourrait expliquer la «pénalité des boomers». Les baby-boomers présentaient respectivement un risque d'hépatite C et de mortalité par drogue trois fois et deux fois plus élevé que les cohortes voisines. La contribution méthodologique des graphique de courbure APC, présentée dans le troisième article, nous a permis d'analyser la dynamique des effets non linéaires au fil du temps, à travers divers phénomènes et populations. Cette technique offre une plus grande flexibilité que les modèles statistiques ou autres graphiques de Lexis. Les résultats présentés dans cette thèse montrent l'importance d'analyser les effets de cohortes sur la mortalité extrinsèque. Nos résultats indiquent que même en présence de perturbations de période importantes affectant la mortalité extrinsèque à la plupart des âges, les effets de cohorte se sont maintenus au fil du temps. Ces résultats suggèrent également que les politiques publiques peuvent améliorer considérablement la santé de la population en formulant des politiques qui prennent en compte la sensibilité différentielle des cohortes aux facteurs de risque et en fournissant un soutien social aux cohortes les plus vulnérables. / After decades of improvement, life expectancy momentarily declined during 2014-15 in several high income countries, with subsequent reversals in some cases. The main sources of this stagnation have been increases in mortality from influenza and drug overdoses, mainly for the baby-boomer generation. This trend is unexpected because it has long been assumed that extrinsic mortality, which is due to causes originating outside the body – in opposition to intrinsic mortality from degenerative diseases at old ages –, plays a negligible role in life expectancy changes. For this reason, the temporal patterns of extrinsic mortality have received little attention in demographic research. Period crises such as influenza epidemics and the opioid crisis are considered the main determinants of variations of extrinsic mortality. However, despite recent evidence suggesting that cohort effects have an important role in modulating extrinsic mortality, little is known about this relationship. The main objective of this dissertation is to help fill this gap by examining cohort influences on extrinsic mortality change, with a particular emphasis on influenza and behavioral causes. More specifically, we aim (1) to quantify cohort differences in mortality from influenza and the influence of early life exposures to the virus on subsequent influenza mortality; (2) to analyze the baby boomers’ disadvantage in mortality in Canada and the United States, while identifying the contributions of behavioral causes to this disadvantage; and (3) to develop a methodological tool that can be used to both conduct visual analysis of the temporal dynamics of nonlinear Age-Period-Cohort (APC) effects, and compare these dynamics across various phenomena or populations. To achieve these goals, we use micro-level mortality data from vital statistics in Canada and the United States. We also employ death and fertility rates from various countries to generalize the visual analysis of nonlinear effects to other demographic phenomena. The analyses were conducted by applying Serfling models for the estimation of influenza mortality, demographic measures for the decomposition of cause-specific mortality changes, smoothing techniques for the identification of trends, and statistical and visual approaches on the Lexis configuration for the analysis of APC effects. The results, in the form of three scientific articles, show that despite marked fluctuations over calendar years (periods), birth cohorts have an independent and sustained influence on influenza and mortality from behavioral causes. The main results from the first paper suggest that two mechanisms modulated influenza mortality over cohorts. For the young and adult population, the mortality risks over cohorts depend of the contrast between the first virus to which individuals were exposed (the virus producing an antigenic imprinting) and the virus encountered in adulthood during the observed epidemic. For this age segment, significant changes in risk were found during influenza epidemics among cohorts born during important antigenic shifts (e.g., a decrease in risk for cohorts born between 1957 and 1968). For older ages, we did not identify such “punctual” cohort effects but rather a smooth and monotonic change in cohort effects that might have driven a progressive decline in influenza mortality between 1959 and 2016. Inspired by so-called cohort morbidity phenotype and technophysio evolution theories, we attributed this decline to changes produced earlier, i.e., to the sharp sanitary improvements occurred between 1900 and 1930, when the concerned cohorts were born and when they could have benefited. Findings from the second paper revealed that most of the baby boomers’ excess mortality in Canada and the United States is driven by behavioral causes of death. The “boomer disadvantage” resulted from multiple cohort effects on behavioral-related mortality, and not from punctual period effects affecting the same cohort at different ages. Among the baby boomers, the risk of dying from hepatitis C was almost three times higher, and the risk of dying from drug-related causes was almost two times higher, than among the adjacent cohorts. These results were obtained using an innovative methodology developed in the third paper, which allowed us to analyze the dynamics of nonlinear effects over time through APC curvature plots. This technique provides greater flexibility than statistical models or other Lexis plots, and it has been shown to be applicable to other demographic phenomena, such as fertility. The findings presented in this dissertation offer evidence of the importance of analyzing cohort effects on extrinsic mortality. Our results indicate that even in the presence of substantial period disturbances affecting extrinsic mortality at most ages, cohort effects were sustained over time. These findings also suggest that public policies can significantly improve the health of the population by formulating policies that take into account the differential sensitivity of cohorts to risk factors and by providing social support to the most vulnerable cohorts.