3,4-methlenedioxymethamphetamine (MDMA), the main constituent of Ecstasy, is a ring-substituted amphetamine commonly abused in recreational users. High doses of MDMA determined by allometric scaling produce serotonin (5-HT) axon deneveration. Studies suggest that this interspecies scaling does not reflect human use. An 'effects' scale comparing similar behavioral and physiological effects between species has been postulated as more accurate for translational studies. Experiment 1 examined the effects of MDMA on serotonergic forebrain innervation using immunohistochemical labeling targeting the serotonin transporter protein (SERT). Experiments 2 and 3 examined low and high doses of MDMA on spatial memory, prefrontal functioning, and serotonergic neurotoxicity using 'effects' scaling. Long Evans rats were given MDMA regimens of: chronic low dose (daily injections of 1.5 mg/kg for 10 days); binge low dose (2 days of 4 x 1.5 mg/kg spaced 2 hours apart), binge high dose (2 x 7.5 mg/kg sp aced 2 hours apart). Acquisition, retention, and spatial reversal (SR) were measured in a water maze task. A 2.0 mg/kg MDMA drug challenge was then given prior to a serial spatial reversal (SSR) task to assess performance while under the effect of the drug. Attentional set shifting and behavioral flexibility were assessed in an intradimensional extradimensionl (IED) task using odor/texture discriminations. MDMA chronic and binge low doses did not impair water maze or IED performance and produced no reductions in SERT expression. MDMA binge high dose resulted in significant reductions of SERT density in the prefrontal cortex, striatum, cortical mantle, hippocampus, amygdala, and many thalamic nuclei. Despite prominent 5-HT denervation, water maze performance was unaffected. Selective impairment in behavioral flexibility on the IED test was found. / This suggests that low doses of MDMA do not produce long-term deleterious effects. But, high doses of MDMA taken in 'binges' produces widespread loss of forebrain SERT fiber innervation and significant impairments in reversal learning, while leaving attentional set shifting and spatial navigation unscathed. / by Stephanie Brooke Linley. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

O crescente consumo de medicamentos psicoativos (MPA) pela população brasileira e mundial no século XXI, atrelado ao fato de que algumas dessas substâncias podem gerar dependência física e/ou psíquica nos sujeitos que os utilizam, apontam para a necessidade de desenvolver estudos epidemiológicos que forneçam subsídios para o planejamento de intervenções em saúde que garantam o uso racional desses medicamentos. Este estudo transversal visa estimar a prevalência e caracterizar o perfil de utilização de MPA entre usuários de medicamentos atendidos por todas as farmácias das unidades de saúde do município de Ribeirão Preto-SP, relacionando esses achados com fatores associados ao consumo dessas substâncias. Uma amostra de 1355 usuários de medicamentos (psicoativos ou não) foi entrevistada nas filas das referidas farmácias de setembro a dezembro de 2012. Os pesquisadores coletaram dados sociodemográficos e relacionados à saúde dos indivíduos, além de registrarem todos os medicamentos contidos nas prescrições. Em seguida, três instrumentos foram aplicados para avaliar as variáveis clínicas (i) conhecimento dos indivíduos sobre a farmacoterapia, (ii) adesão à farmacoterapia e (iii) qualidade de vida relacionada à saúde (QdV). A prevalência de uso de MPA foi 31,0% (n=420), sendo que os mais prescritos foram antidepressivos (53,5%) e benzodiazepínicos (24,6%). A maioria dos usuários de MPA era do gênero feminino (81,9%), vivia com companheiro (52,6%), não trabalhava (70,7%), possuía plano de saúde privado (69,2%) e renda per capita de até um salário mínimo (54,0%), não realizava acompanhamento com psicólogo (93,3%), não praticava atividade física regular (78,3%), consumia café diariamente (81,0%), não consumia álcool (86,7%), não fumava (81,4%) e não encontrava-se em polifarmácia (62,4%). A idade média foi 54,5 (DP 13,9) e a escolaridade média correspondeu ao Ensino Fundamental incompleto. Pouco mais da metade dos usuários de MPA exibiram conhecimento satisfatório sobre a farmacoterapia e foram considerados aderentes (57,8% e 53,0%, respectivamente) e a maioria não apresentou QdV satisfatória (73,1%). Houve diferença estatisticamente significativa (p<0,05) entre usuários de MPA e não usuários para as variáveis gênero, faixa etária, situação conjugal, moradia, situação profissional, cuidador, acompanhamento com psicólogo, atividade física regular, consumo de álcool, tabagismo, polifarmácia, conhecimento médio sobre a farmacoterapia, adesão média à farmacoterapia, QdV satisfatória, índice médio EQ- 5D e QdV autorreferida média. Os valores de odds ratio (OR) ajustados mostraram que os fatores associados positivamente com o uso de MPA foram gênero feminino (OR = 2,02; IC 95% 1,31; 3,11) e maior idade (ORref./idosos = 0,36; IC 95% 0,13; 0,99). Dentre os usuários de benzodiazepínicos, 51,1% relatou estar em uso desses MPA há dois anos ou mais, dos quais 55,1% eram idosos. Aproximadamente um em cada três indivíduos utilizava pelo menos um MPA no período estudado, sendo que idosos e mulheres apresentaram maiores chances de uso. Os MPA mais prevalentes foram os antidepressivos e os benzodiazepínicos, sendo a maioria dos usuários destes últimos estava em tratamento com esses MPA há mais de dois anos, dos quais mais da metade eram idosos / The increasing consumption of psychoactive drugs (PAD) in Brazil and worldwide, linked to the fact that some of these substances can cause physical and/or psychic dependence in their users, indicate the need to develop epidemiological studies providing support for planning of health interventions so as to ensure the rational use of these medicines. This cross-sectional study aims to estimate the prevalence and characterize the usage profile of PAD among drug users served by all health facilities\' pharmacies in Ribeirão Preto-SP, relating these findings with factors associated with the consumption of these substances. From september to december 2012, a sample of 1355 drug users (psychoactive or not) was interviewed while waiting in the pharmacies to get their medication. The researchers collected sociodemographic and health related data of individuals, in addition to registering all drugs contained in prescriptions. Then, three instruments were applied to assess the clinical variables (i) knowledge of pharmacotherapy, (ii) adherence to the pharmacotherapy and (iii) health related quality of life (QoL). The prevalence of PAD usage was 31,0% (n = 420), and the most prescribed were antidepressants (53,5%) and benzodiazepines (24,6%). Most PAD users were female (81,9%), lived with a partner (52,6%), did not have a job (70,7%), had a private health insurance (69,2%) and income per capita up to the minimum wage (54,0%), did not undergo follow-up with a psychologist (93,3%), did not practice regular physical activity (78,3%), consumed coffee daily (81,0%), did not consume alcohol (86,7%), did not smoke (81,4%) and were not found in polypharmacy (62,4%). The mean age was 54,5 (SD 13,9) and the average schooling corresponded to incomplete primary education. Over half of the users of MPA exhibited satisfactory knowledge about pharmacotherapy and were considered adherent (57,8% and 53,0%, respectively), and most showed no satisfactory QoL (73,1%). There was a statistically significant difference (p <0.05) between PAD users and nonusers for the variables gender, age, marital status, housing, employment status, caregiver, follow up with psychologist, regular physical activity, alcohol consumption, smoking, polypharmacy, average knowledge about pharmacotherapy, mean adherence to pharmacotherapy, satisfactory QoL, mean EQ-5D index and average self-reported QoL. The adjusted odds ratios (OR) showed that the factors positively associated with the PAD use were female gender (OR = 2,02; 95% CI 1,31; 3,11) and age (ORref./elderly = 0,36, 95% CI 0,13; 0,99). Considering benzodiazepines users, 51,1% reported being in use these PAD for at least two years, 55,1% of whom were elderly. Approximately one in three individuals used at least one PAD in the period studied, while the elderly and women were more likely to use. The most prevalent PAD were antidepressants and benzodiazepines, with most users of the latter receiving these MPA for over two years, of which more than half were elderly.

Made available in DSpace on 2016-03-22T17:26:41Z (GMT). No. of bitstreams: 1 silvia minasi.pdf: 479845 bytes, checksum: 49b800674eab694650884dbdb12b8c71 (MD5) Previous issue date: 2012-03-16 / Cross-sectional study to describe the prevalence of psychotropic drug use during hospitalization and at home, conducted with 110 adult patients hospitalized in two university hospitals in Pelotas/RS, which answered to SRQ-20 at beginning of the hospitalization and HAD scale seven days later. Simultaneously, an analysis of daily prescriptions was performed. The prevalence of psychotropic drug use in the households was 24.5% (CI95% 17,1% - 33,8%) while during hospitalization was 52.7% (CI95% 43,0% - 62,2%). Based on the total sample, 32.7% not used at home, but received in the hospital, 4.5% had used psychotropic drugs at home, but had not received when hospitalized. Female gender, presence of previous disease and had already gone into surgery were associated with hospital use, while for household use, only the presence of previous disease and hospitalization non-SUS were significant. The most commonly prescribed psychotropic drugs were anxiolytics, hypnotics and sedatives, followed by antidepressants, neuroleptics and anticonvulsants / Estudo transversal para descrever a prevalência de uso de psicofármacos durante a internação hospitalar e no domicílio, realizado com 110 pacientes adultos internados nos dois hospitais universitários da cidade de Pelotas/RS, que responderam ao SRQ-20 no início da internação e sete dias depois a escala HAD. Simultaneamente, fez-se análise das prescrições diárias. A prevalência de uso de psicofármaco domiciliar foi de 24,5% (IC95% 17,1% - 33,8%) enquanto que durante a internação foi de 52,7% (IC95% 43,0%-62,2%). Do total da amostra, 32,7%, não usavam em casa, mas receberam no hospital; 4,5% já usavam psicofármaco em casa, porém não receberam quando internados. Sexo feminino, presença de transtorno prévio e já ter feito cirurgia estiveram associados ao uso hospitalar, enquanto que para uso domiciliar, apenas a presença de transtorno prévio e a internação não SUS foram significativas. Os medicamentos psicotrópicos mais prescritos foram os ansiolíticos, hipnóticos e sedativos, seguidos pelos antidepressivos, neurolépticos e anticonvulsivantes

Introdução: Os Benzodiazepínicos estão entre as drogas mais prescritas no mundo. Possuem características ansiolíticas, hipnóticas, miorelaxantes e anticonvulsivantes. Estudos prévios evidenciam inadequações nas prescrições de benzodiazepínicos, como uso equivocado para quadros inespecíficos, tratamento prolongado e abuso por idosos. Benzodiazepínicos podem trazer sérios efeitos adversos, sobretudo em idosos, como sonolência diurna, deterioro da memória e funções cognitivas, desequilíbrio e quedas. Objetivos: Analisar a prevalência do uso de benzodiazepínicos nos pacientes do Centro de Atenção Psicossocial (CAPS) de Campo Bom-RS em um período de 24 meses (Junho de 2013 a Maio de 2015), faixa etária, frequência de dispensações, dosagens, CIDs e especialidades dos médicos prescritores; bem como possíveis relações com a função cognitiva, afetiva, e quedas em idosos. Métodos: Estudo transversal, com informações coletadas e tabuladas a partir dos prontuários e prescrições médicas do CAPS Campo Bom, bem como do seu sistema informatizado de gerenciamento (Software Multi 24 Horas). Foram obtidos dados como idade, gênero, identificação dos CIDs; bem como informações sobre prescrições de Benzodiazepínicos, como frequência, quantidade, tipo de medicamento, posologia, profissional prescritor e demais medicamentos utilizados. Critério de inclusão: utilização de qualquer benzodiazepínico disponível na rede SUS: Clonazepam 0,5mg, Clonazepam 2,5 mg/ml, Clonazepam 2mg e Diazepam 5mg. Foram aplicados os testes MEEM e GDS nos pacientes idosos, em entrevistas individuais, nas quais também se avaliou a escolaridade, ocorrência e frequência de quedas, além das comorbidades auto relatadas. Para construção do banco de dados foi utilizado o Software Microsoft® Office Excel® 2007, e para análise estatística o Software PASW V18 (SPSS®). Resultados: O número total de pacientes ativos identificados no CAPS foi de 855 indivíduos, sendo 543 (63,5%) mulheres e 84 idosos (9,8%). A prevalência de utilização de BZD nesta população representou 47,2% (n=404 indivíduos). Foram identificadas 12.680 prescrições médicas dispensadas e, deste total, a prevalência de prescrições de benzodiazepínicos foi de 21,7% (n=2.748). Dentre os pacientes que receberam BZD, 297 (73,5%) eram mulheres e 59 idosos (14,6%), dos quais 56 foram entrevistados. Dentre os idosos entrevistados, 42 (75,0%) possuíram significativa sintomatologia depressiva (GDS≥5) e 32 (57,1%) apresentaram duas ou mais quedas no período de 1 ano. Dezoito pacientes idosos demonstraram fazer uso de dois ou mais BZDs. Houve correlação linear negativa entre os escores do MEEM e do GDS (r = - ,416; p=,002). Houve também uma correlação linear negativa entre o escore do MEEM e número de quedas em idosos (r = -,327 p=,016). Conclusões: Os benzodiazepínicos corresponderam a 21,7 % do total de prescrições do CAPS e do total dos indivíduos 47,2% receberam benzodiazepínicos. Proporcionalmente aos homens, as mulheres tenderam a receber mais prescrições de benzodiazepínicos (p<.001). A prevalência de significativa sintomatologia depressiva nos idosos usuários do CAPS foi alta (75,0%), assim como a incidência de quedas, sendo que mais da metade dos idosos caiu 2 ou mais vezes no período. Identificou-se uma correlação linear negativa entre a função cognitiva como avaliada pelo MEEM e a sintomatologia depressiva avaliada pelo GDS; bem como houve uma correlação linear negativa entre o MEEM e o número de quedas em idosos. / Introduction: Benzodiazepines are among the most prescribed drugs in the world, they have characteristics such as anxiolytic, hypnotic, muscle relaxants and anticonvulsants. Studies have pointed out distortions in benzodiazepines’ prescriptions, such as misuse for unspecific cases, prolonged treatment and use by elderly. Such medications may cause serious damage, particularly in the elderly, and its continued use causes side effects such as daytime somnolence, imbalance, memory and cognitive function loss, increased incidence of falls. Objectives: To assess the prevalence of benzodiazepine use among patients of the Center for Psychosocial Care in Campo Bom-RS within the period of June 2013 to May 2015. The variables analyzed were: age, frequency of dispensations, dosages, ICDs and specialties of prescribing doctors; as well as possible correlations between cognitive function, emotional function and falls in the elderly. Methods: Cross-sectional study, with data collected and tabulated from medical records and prescriptions, as well as from the management system from CAPS (Software Multi 24 hours). Data obtained was age, gender, ICDs identification; as well as frequency of prescriptions, quantity and type of medication, dosage, prescribing professional, others used drugs. Inclusion criteria: Use of any benzodiazepine available in the Health Unic System: Clonazepam 0,5 mg, Clonazepam 2,5 mg/ml, Clonazepam 2 mg and Diazepam 5mg. MMSE and GDS tests have been applied in the elderly, through individual interviews, in which we found about educational level, occurrence and frequency of falls and other self-reported comorbidities. The software Microsoft® Excel® 2007 was used to build database, and for statistical analysis the software PASW V18 (SPSS) was used. Results: The total number of active patients identified at CAPS was 855 individuals, of these 543 were women (63.5%) and 84 elderly (9.8%). The prevalence of benzodiazepines’ use in this population was 47.2 % (n = 404). We have found 12.680 prescriptions dispensed and the prevalence of benzodiazepines’ prescriptions was 21.7 % (n = 2.748). Among patients who received benzodiazepines, 297 (73.5%) were women and 59 elderly (14.6%), of these 56 were interviewed. From the interviewed patients, 42 (75.0%) had significant depressive symptomatology (GDS≥5) and 32 (57.1%) have suffered two or more falls. Eighteen elderly patients demonstrated to use two or more benzodiazepines. There was a negative linear correlation between MMSE and GDS scores (r = -.416, p =.002). There was also a negative linear correlation between MMSE scores and number of falls in elderly (r = -.327 p =. 016). Conclusions: Benzodiazepines accounted for 21.7% of the total CAPS’ prescriptions, and 47.2% individuals treated at CAPS received benzodiazepines. Women tended to receive more prescriptions of benzodiazepines (p <.001) than men. The prevalence of significant depressive symptomatology in the elderly was very high (75.0%). As well as the incidence of falls, since more than half of the elderly patients presented two or more falls in the period. We identified a negative linear correlation between cognitive function as assessed by MMSE and depressive symptoms assessed by the GDS; and there was a negative linear correlation between MMSE and the number of falls in the elderly.

The elderly population is growing in nursing homes (NHs), with an estimated 3 million seniors to be residing in NH facilities by year 2030. Many of these seniors are potentially at risk for falls or infections. NH residents with Alzheimer’s disease or other forms of dementia are also increasing, and they are vulnerable to the adverse effects of medications. Psychotropics are overused in NHs, with approximately half to two thirds of residents receiving one or more psychotropics. Many negative health outcomes, e.g. falls and infections, have been associated with their use. The usage of psychotropic medications among NH residents has been a concern and topic of scrutiny for nearly three decades. In 1986, the Institute of Medicine published a landmark report that identified the overuse of psychotropic medications in NHs. The following year, the federal government passed the Omnibus Budget Reconciliation Act that included reform legislation to address psychotropic drug overuse. Since then, additional policies and initiatives have endeavored to rectify the problem, and scientists have conducted research regarding psychotropics and negative health outcomes. However, newer research within the last decade and at a national level is lacking. Therefore, this dissertation explores the association of psychotropic medications with falls and infections among NH residents using a national dataset, and this document is organized into five chapters. The first chapter discusses the background, significance, and current challenges surrounding psychotropic medication use in NHs. The second chapter delineates the search of the literature and relevant findings. The third chapter describes the methodology upon which this analytics of this dissertation was conducted. The fourth chapter outlines the results from the analyses. Lastly, the fifth chapter provides a synthesis and discussion of the findings and recommendations for health policy, practice, and future research.

Binge drinking is characterised by cycles of ethanol intoxication and withdrawal and is thought to be highly deleterious for the normal functioning of the nervous system. The behavioural and neurophysiological consequences of rapid escalation of blood alcohol concentration and subsequent withdrawal, and their effects on learning and memory and underlying neural circuitry can be studied in suitable animal models. Here, spatial and instrumental learning as well as hippocampal LTP were assessed in C57BL/6J mice for the effects of adolescent intermittent ethanol (AIE) and other ethanol treatments. AIE treatment did not impair spatial or non-spatial memory when tested in adulthood. However, if mice were trained whilst intoxicated during AIE treatment, spatial memory was impaired. Post-training injections of ethanol impaired performance in operant conditioning. A rapid rise and fall in ethanol concentration, prior to stimulation, blocked LTP induction in drug naïve hippocampal slices; an effect that was not seen if the ethanol concentration was gradually increased and decreased. Moreover, AIE treatment caused an NMDA receptor-dependent transient increase in hippocampal LTP. The second part of this study used a novel molluscan model Lymnaea stagnalis and demonstrated that high concentrations of ethanol blocked acquisition and retrieval of an associative memory. However, if acquisition occurred in the presence of ethanol then memory could also be retrieved under ethanol, demonstrating ethanol state dependency. By utilising the cerebral giant cells, a modulatory neuron type with known involvement in memory formation, it was found that ethanol reduced the tonic firing frequency as well as the peak-to-trough and half-width parameters of individual action potentials. The development of in vivo and in vitro ethanol treatment and test protocols, and the findings based on their use, open up new avenues for future systematic investigations on ethanol's effects on behaviour and underlying neural circuitry in both vertebrate and invertebrate model systems.

The metabotropic glutamate receptor, mGluR5, is densely expressed in brain regions involved in incentive learning processes. There is considerable evidence to suggest that following exposure to addictive drugs such as cocaine, adaptations in these brain areas may underlie the development and maintenance of behavioural responses related to addictive processes. The present thesis examines the role of mGluR5 in both incentive learning processes and some behavioural and neurobiological effects of cocaine. First, using a novel mutant mouse line in which mGluR5 is selectively knocked down in cells that express dopamine D1 receptors (D1R), I argue that this mGluR5 population is critically important for specific incentive learning processes. By blocking mGluR5 in wild-type mice with a selective antagonist, I then propose mGluR5 as necessary for the acquisition, but not the expression of an incentive association. Next, I present data showing that mGluR5 on dopaminoceptive neurons are not necessary for the „conditioned rewarding‟ properties of cocaine, measured in the conditioned place preference model, but do contribute to the psychomotor activating effects of cocaine. Finally, I present an immunohistochemistry study that examines cocaine-induced activation of the extracellular-signal related kinase (ERK) pathway. In the mGluR5 knock-down mice, activation of the ERK pathway in the striatum is disrupted following an acute injection of cocaine. Given the importance of the ERK pathway in establishing and maintaining long term memories, I propose that disruption of this pathway could contribute, in part, to some findings reported in the present thesis. Taken together, this thesis will argue that signalling through mGluR5 on D1R expressing neurons is important for the formation of incentive associations, and may contribute to neural adaptations necessary for the development and maintenance of behavioural responses related to addictive processes.

A esquizofrenia é um transtorno mental que provoca a desorganização de diversos processos mentais. Trata-se de uma condição crônica com expressivo impacto em termos de sobrecarga pessoal e social. O tratamento medicamentoso contínuo é necessário para evitar recaídas e manter o paciente no melhor nível de funcionamento possível. Este estudo teve como objetivo compreender o significado da terapêutica medicamentosa para a pessoa com esquizofrenia, em sua perspectiva e na de seu familiar, e formular um modelo teórico sobre o fenômeno estudado. Para tanto, foi adotado como referencial teórico o Interacionismo Simbólico e, como referencial metodológico, a Teoria Fundamentada nos Dados. A pesquisa foi desenvolvida em um Serviço Ambulatorial de Clínica Psiquiátrica de um hospital universitário, um Núcleo de Saúde Mental e um CAPS II, localizados no interior do estado de São Paulo - Brasil. Pelo processo de amostragem teórica, foram selecionados para o estudo 36 pessoas com esquizofrenia e 36 familiares. A entrevista e a observação foram as principais estratégias utilizadas para a obtenção dos dados que foram coletados no período de 2008 a 2010. Os dados coletados foram transcritos e, posteriormente, analisados em três etapas: codificação aberta, axial e seletiva. Verificou-se que, ao ser acometido pela esquizofrenia, o paciente percebe-se \"vivendo dias difíceis\" e identifica no medicamento uma possibilidade de melhora. \"Pesando o custo-benefício do medicamento\" e \"identificando obstáculos e incentivos para o tratamento\" o paciente implementa estratégias \"agindo em busca de alívio\" para o sofrimento causado pela esquizofrenia ou pelo tratamento medicamentoso. Entretanto, esse indivíduo se julga \"permanecendo em um labirinto\", pois não encontra uma saída para livrar-se do transtorno e da necessidade da farmacoterapia. A experiência descrita se centraliza no fenômeno \"CONVIVENDO COM UMA AJUDA QUE ATRAPALHA\" que representa o significado da terapêutica medicamentosa para a pessoa com esquizofrenia. A teoria aqui apresentada fornece uma compreensão abrangente, contextualizada, motivacional e empática da realidade vivenciada pelo paciente. Desse modo, o presente estudo oferece subsídios para o planejamento da assistência a essa clientela e aponta elementos a serem investigados. / Schizophrenia is a mental disorder that provokes the disorganization of several mental processes. It is a chronic condition with considerable impact in terms of personal and social burden. Continuous medication treatment is needed to avoid relapses and maintain the patient at the best possible functioning level. This study aimed to understand the meaning of medication therapy for schizophrenia patients, from their own perspective and that of their relative, and to formulate a theoretical model for the study phenomenon. Therefore, Symbolic Interactionism was adopted as the theoretical framework, and Grounded Theory as the methodological framework. The research was developed at a Psychiatric Clinical Outpatient Service of a teaching hospital, a Mental Health Center and a CAPS II located in the interior of São Paulo State - Brazil. Through a theoretical sampling process, 36 schizophrenia patients and 36 relatives were selected for the study. Interview and observation were the main strategies used for data collection, between 2008 and 2010. The collected data were transcribed and later analyzed in three phases: open, axial and selective coding. It was verified that, when the schizophrenia affects them, the patients perceive that they are \"going through difficult times\" and identify the medication as a possibility for improvement. \"Weighing the cost-benefit of the medication\" and \"identifying treatment obstacles and incentives\", the patients put in practice strategies \"acting in search of relief\" for the suffering the schizophrenia or medication treatment causes. These patients, however, consider that they \"continue in a labyrinth\", as they do not find a way out to get rid of the disorder and the need for the drug therapy. The described experience centers on the phenomenon \"LIVING WITH HELP THAT BOTHERS\", which represents the meaning of the medication therapy for schizophrenia patients. The theory presented here provides a broad, contextualized, motivational and empathetic understanding of the reality these patients experience. Thus, this study offers support to plan care for these clients and appoints elements for further research.

Ces travaux de thèse présentent une approche de pharmaco-épidémiologie explorant l'exposition médicamenteuse chez des patients atteints de lymphome tout au long de leur parcours de soin. L'utilisation des données du Système National d'Information Inter-régimes de l'Assurance Maladie (SNIIRAM) nous a permis de quantifier cette exposition médicamenteuse et de déterminer les facteurs associés dans le contexte de la vie réelle. Les travaux de recherche réalisés au cours de cette thèse répondaient à 3 objectifs. Dans un premier objectif, nous avons souhaité valider l'utilisation du SNIIRAM à des fins de recherche pour améliorer la robustesse des futures études menées sur le lymphome. Après avoir défini plusieurs algorithmes d'identification des cas incidents de lymphome, nous avons testé leur validité par confrontation aux données cliniques exhaustives du Registre des cancers du Tarn. Les paramètres de performance obtenus permettent de considérer les données disponibles dans le SNIIRAM comme un outil puissant pour mener des études pharmaco-épidémiologiques ou médico-économiques sur le Lymphome. Le second objectif était d'explorer l'existence d'une surconsommation de médicaments psychotropes au cours de la phase active de traitement par rapport à une population témoin, sous l'hypothèse d'une initiation accrue de ces médicaments pour pallier les complications psychologiques associées à la prise en charge du Lymphome. Par ailleurs, la chronicisation fréquemment observée de ce type de consommation peut conduire à terme à des complications potentiellement évitables. Pour répondre à cet objectif, nous avons réalisé une étude selon une approche " new-user design ", à partir d'une cohorte de patients incidents de lymphome identifiés dans les données du SNIIRAM à l'échelon régional. Nous avons observé un taux d'initiation supérieur au taux observé en population générale ou chez des patients atteints d'autres pathologies mettant en jeu le pronostic vital (infarctus du myocarde). En fonction de la classe thérapeutique étudiée, 20 à plus de 50% des patients restaient exposés de façon inappropriée (au-delà des recommandations) à ces médicaments. Le troisième objectif a donc été d'explorer les déterminants associés à une utilisation prolongée de médicaments psychotropes dans la phase de l'après-cancer à partir des données de l'Echantillon généraliste des bénéficiaires (EGB). [...] / This thesis presents a pharmacoepidemiology approach to describe drug utilization in lymphomas during their whole care pathway. The use of the French claims database (Système National d'Informations Inter-Régimes de l'Assurance Maladie (SNIIRAM)) allows to exhaustively quantify this drug utilization in real life conditions. This thesis consists of three mains objectives. First, we aimed to develop validated algorithms for the identification of incident cases of lymphoma. For the validation, we used data from a regional Cancer Registry as the gold standard. The purpose of this validation study was to enhance validity of future studies conducted on lymphomas in the SNIIRAM database. The results of this study associated to strengths of this database demonstrate that this approach is of great interest to conduct pharmacoepidemiological or medico-economic studies in lymphomas. Second, we aimed to estimate the incidence of use of psychotropic drugs during the active treatment phase of lymphoma in comparison with control groups. Indeed, the increased probability of developing anxio-depressive disorders after diagnosis could lead to an increased initiation of psychotropic drugs and a potential inappropriate chronic use of these drugs after initiation. Such inappropriate chronic use can unnecessarily expose patients to adverse event. For this aim, we conducted a new-user cohort study using data from the SNIIRAM database. The results of this study revealed that the initiation rate of these drugs is higher than in the general population or for life-threatening diseases such as myocardial infarction. Moreover, we observed an inappropriate prolonged use for a significant fraction of patients (20% to more than 50% according to therapeutic class). On the basis of these findings, the third objective was to identify factors associated with prolonged use of these drugs during survivorship. This study was conducted using data from the General Sample of Beneficiaries (EGB). [...]

Dementia is a major public health problem worldwide. Emerging research indicates that clinical infections and PTSD could be important risk factors for dementia. However, evidence for infections and the risk of dementia primarily examines central nervous system (CNS) infections. Extant epidemiological evidence for systemic bacterial infections and the risk for dementia is limited while that for PTSD and the risk for dementia did not account for psychotropic medications commonly used in management of PTSD and could affect cognitive function. The purpose of this study was to 1) review the evidence for CNS infections as possible causes of Alzheimer’s disease (AD) dementia, and 2) using nationwide Veterans Health Administration databases, conduct original retrospective cohort analyses in nationally representative samples of U.S. veterans aged 56 years and older to determine the associations between systemic bacterial infections, PTSD, and psychotropic PTSD medication use with the risk for developing dementia. Review of the research pertaining to an infectious AD etiology hypothesis including the various mechanisms through which different clinical and subclinical infections could cause or promote the progression of AD, and the concordance between putative infectious agents and the epidemiology of AD showed evidence linking AD to an infectious cause to be largely inconclusive; however, the amount of evidence suggestive of an association is too substantial to ignore. Analysis of the associations between systemic bacterial infections and the risk for dementia showed a significant association between exposure to any systemic bacterial infection and an increased risk for dementia (hazard ratio [HR] = 1.20; 95% confidence interval [CI] = 1.16-1.24) after adjustment for demographic characteristics, and medical and psychiatric comorbidity. In addition, septicemia (HR=1.39; 95%CI=1.16-1.66), bacteremia (HR=1.22; 95%CI=1.0-1.49), osteomyelitis (HR=1.20; 95%CI=1.06-1.37), pneumonia (HR=1.10; 95%CI=1.02-1.19), UTI (HR=1.13; 95%CI=1.08-1.18), and cellulitis (HR=1.14; 95%CI=1.09-1.20) were independently associated with significantly increased risk of developing dementia after adjustment for potential confounders. Analysis of the associations between PTSD and psychotropic PTSD medication use with the risk for dementia showed a significant association between PTSD and the risk for dementia (HR=1.35; 95%CI=1.27-1.43) after adjustment for demographic characteristics, medical and psychiatric comorbidity, and health care utilization. Analysis of the impact of psychotropic PTSD medications including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), benzodiazepines (BZA), novel antidepressants (NA) and atypical antipsychotics (AA) on the association between PTSD and the risk for dementia showed significant interactions between PTSD and use of SSRIs (p<.0001), NAs (p=.0016), and AAs (p<.0001). Multivariate analysis showed a significant association between PTSD and an increased risk for dementia among individuals not using any psychotropic PTSD medications at baseline (HR=1.70; 95%CI=1.58-1.82). PTSD patients using SSRIs (HR=2.10; 95%CI=1.82-2.41), NAs (2.19; 95%CI=1.94-2.48) or AAs (4.56; 95%CI=4.04-5.15) were significantly more likely to develop dementia compared to those without PTSD and not using any psychotropic PTSD medications. PTSD patients using SSRIs (HR=1.24; 95%CI=1.08-1.42), NAs (HR=1.29; 95% CI=1.14-1.46) or AAs (HR=2.69; 95%CI=2.38-3.04) were also significantly more likely to develop dementia compared to those with PTSD and not using any psychotropic PTSD medications. SNRI (HR=1.35; 95%CI=1.26-1.46) and BZA drug use (HR=1.40; 95%CI=1.35-1.45) at baseline was associated with an increased risk for dementia regardless of PTSD diagnosis. These findings indicate; 1) evidence for an infectious AD etiology hypothesis in inconclusive, 2) both severe (e.g. sepsis), and less severe (e.g. cellulitis) systemic bacterial infections are collectively and independently associated with an increased risk of dementia among older U.S. veterans hence prevention of systemic bacterial infections could positively influence the risk for dementia among older adults, and 3) PTSD and psychotropic medication use are associated with an increased risk for dementia among U.S. veterans. Further epidemiologic, clinical, and basic science research is required to elucidate the mechanisms and the associations between infections and the risk for dementia and to determine if the independent and effect modifying impacts of psychotropic PTSD medication use on the risk for dementia are related to differences in PTSD severity, other psychiatric comorbidity, or whether psychotropic PTSD medication use is an independent risk factor for dementia.