Introdução: Vancomicina, considerada o antibiótico de primeira escolha para o tratamento de infecções estafilocócicas, é eliminada por filtração glomerular, e a sua administração deve ser individualizada de acordo com a função renal. As diretrizes atuais recomendam doses e níveis séricos maiores, para aumentar as chances de bons resultados clínicos. Questiona-se se esta estratégia causaria maior nefrotoxicidade. Objetivos: Comparar a frequência de injúria renal aguda (IRA) em pacientes com suspeita de infecção estafilocócica tratados com vancomicina ou com outros antimicrobianos com o mesmo perfil terapêutico em um hospital terciário. Analisar a associação do uso de vancomicina com o desenvolvimento de IRA nestes pacientes. Avaliar os fatores de risco associados ao desenvolvimento de IRA nos pacientes tratados com vancomicina. Identificar os fatores de risco associados à letalidade precoce e tardia nos pacientes com suspeita de infecção estafilocócica tratados com vancomicina ou outros antimicrobianos com o mesmo perfil terapêutico. Métodos: Foram analisados os prontuários dos pacientes com suspeita de infecção estafilocócica que receberam os antimicrobianos vancomicina, teicoplanina, oxacilina, daptomicina ou linezolida por pelo menos três dias nos anos de 2010 e 2011 em um hospital terciário. Analisou-se a frequência de IRA associada ao uso de vancomicina (critério KDIGO) e. por regressão logística, se o uso de vancomicina foi associado ao desenvolvimento de IRA. Avaliou-se por regressão logística os fatores de risco associados ao desenvolvimento de IRA no grupo de pacientes tratados com vancomicina. Analisou-se por regressão de Cox os fatores de risco para letalidades intra-hospitalar, seis meses e até um ano após a internação. Resultados: Foram incluídos 591 pacientes, dos quais 508 foram expostos à vancomicina e 83 foram expostos a teicoplanina, oxacilina, linezolida, ou daptomicina. IRA ocorreu em 28,5% dos pacientes que utilizaram vancomicina e em 14,5% dos que utilizaram outros antimicrobianos (p < 0,001). O grupo de pacientes tratados com vancomicina apresentou parâmetros sugestivos de maior gravidade, como maior frequência de culturas positivas para estafilococos, hipotensão grave, contagem de leucócitos em sangue periférico mais elevada e níveis séricos maiores de lactato, procalcitonina e PCR. Quando pacientes que desenvolveram IRA foram comparados com pacientes que mantiveram a função renal estável, observou-se que o uso de vancomicina, a duração do tratamento e nível sérico de vancomicina foram significativamente maiores entre os primeiros. Vancomicina foi identificada como fator independente para o desenvolvimento de IRA na regressão logística. Os fatores de riscos independentes para o desenvolvimento de IRA no grupo exposto à vancomicina foram uso de medicamentos nefrotóxicos ou que alteram a função renal, uso de medicamento vasopressor e concentração sérica de vancomicina >= 20 mg/L. Vancomicina não se associou a letalidade em nenhum dos períodos estudados, enquanto IRA se associou de forma independente à letalidade precoce e tardia. Conclusões: Estes resultados indicam que a vancomicina apresenta nefrotoxicidade significativa e que os seus níveis séricos devem ser obrigatoriamente avaliados. O uso de medicamentos nefrotóxicos ou que alteram a função renal deve ser, quando possível, evitado ou suspenso em pacientes tratados com vancomicina. O desenvolvimento de IRA, mas não o uso de vancomicina, foi fator independente para letalidade, reforçando que este antimicrobiano pode ser utilizado quando indicado, desde que se previna o desenvolvimento de IRA / Introduction: Vancomycin is considered the first choice antibiotic for treatment of staphylococcus infection. Vancomycin is eliminated through glomerular filtration, and so it is administration must be individualized according the renal function. Current treatment guidelines recommend higher doses and blood levels in order to increase the odds for an adequate clinical outcome. On the other hand, this strategy might cause higher vancomycin-associated nephrotoxicity. Objectives: To analyze the frequency of acute kidney injury (AKI) development in patients with suspicion of staphylococcus infection treated with vancomycin, or other antibiotics with the same therapeutic profile in a tertiary hospital. To analyze the association of vancomycin with AKI development in those patients. To analyze the risk factors for AKI development in vancomycin-treated patients. To identify the risk factors associated to early and late mortality in patients with suspicion of staphylococcus infection treated with vancomycin, or other antibiotics with the same therapeutic profile in a tertiary hospital.Methodology:We analyzed the files of all the patients with suspicion of staphylococcus infection treated with vancomycin, teicoplanin, oxacillin, daptomycin, or linezolid antibiotics for at least three days during the years of 2010 and 2011 in a tertiary hospital.The frequency of AKI development (KDIGO criteria) was assessed. Using logistic regression we assessed if vancomycin use was an independent risk factor for AKI development and the risk factors for AKI development in the group of patients treated with vancomycin. We assessed, using Cox regression, the risk factors for in-hospital, six months and one year after hospitalization mortality. Results: We included 591 patients in the final analysis, 508 using vancomycin and 83 using other antibiotics (teicoplanin, oxacillin, daptomycin, or linezolid). AKI developed in 28.5% of the vancomycin group compared with 14.5% in the other antibiotics group (p < 0.001). Patients treated with vancomycin showed parameters suggesting higher clinical severity, such as higher percent of staphylococcus positive cultures, severe hypotension, higher leukocytes blood count, higher serum levels of lactate, procalcitonin and CRP. When patients developing AKI were compared with patients maintaining preserved renal function, the first group showed a statistically significant higher frequency of vancomycin use, longer vancomycin treatment and higher vancomycin through levels. Using logistic regression vancomycin was identified as an independent risk factor for AKI development. The independent risk factors for AKI development in the vancomycin group were simultaneous use of vancomycin and other nephrotoxic drugs or drugs that influence renal function, vasopressor drugs use and blood levels of vancomycin >= 20 mg/L. Vancomycin was not associated with mortality in any studied time, whereas AKI was an independent risk factor for early and late mortality. Conclusions: These results indicate that vancomycin is associated with significative nephrotoxicity and that its blood levels must be mandatorily assessed. The use of drugs that are nephrotoxic or influence renal function must be, when feasible, avoided or halted in vancomycin-treated patients. AKI development, but not vancomycin use, was an independent risk factor for mortality, reinforcing the perception that vancomycin can be used when necessary, since AKI development is prevented

INTRODUÇÃO: A simpatectomia é o tratamento de escolha para hiperidrose localizada primária. A evolução da técnica visa à melhora dos resultados operatórios e à minimização dos efeitos colaterais, sendo o principal deles o suor reflexo. Esse suor reflexo pode afetar a satisfação em longo prazo, e pode variar conforme as estações do ano, juntamente com a satisfação dos pacientes com os resultados da operação. No entanto, não há dados objetivos quanto ao efeito da sazonalidade sobre os resultados operatórios e sobre os fatores relacionados à satisfação. Os objetivos do presente estudo são: avaliação da variabilidade sazonal sobre o grau das resoluções da sudorese palmar e plantar, bem como a incidência e a intensidade do suor reflexo e análise da influência desses fatores sobre a satisfação; avaliação da dor como fator relacionado à satisfação imediata; avaliação da segurança dos métodos de expansão pulmonar pós-operatória com e sem drenagem pleural e relação dos mesmos à dor. MÉTODOS: Estudo clínico, prospectivo, em duas fases. A primeira, para avaliação de fatores imediatos relacionados à satisfação (fatores antropométricos, dor, presença e intensidade do suor reflexo, grau de resolução da sudorese palma r e plantar, época do ano em que a simpatectomia foi realizada) e segurança dos métodos de expansão pulmonar, cujo desenho é prospectivo, aleatorizado e cego. A segunda, para as avaliações tardias e sazonais dos fatores relacionados à satisfação (fatores antropométricos, presença e intensidade do suor reflexo, grau de resolução da sudorese palmar e plantar), possui desenho prospectivo de coorte. Foram eleitos para o estudo pacientes com hiperidrose palmo-plantar primária submetidos à simpatectomia torácica videoassistida; o período de inclusão foi de 16 meses e o seguimento médio final de 623,63 ± 15,13 dias. Foram então avaliados no período de hospitalização (avaliação da dor, método de expansão pulmonar e do pneumotórax residual) e no sétimo dia de pós-operatório (dor, resultados operatórios e satisfação). Então, tardiamente, na primavera, no verão e no outono/inverno (resultados operatórios e satisfação). Foram considerados resultados operatórios os graus de resolução palmar e plantar e a presença e a intensidade do suor reflexo. Foram estudadas como variáveis independentes relacionadas à satisfação a época do ano onde a simpatectomia foi feita, a dor, os graus de resolução palmar e plantar, presença e intensidade do suor reflexo e fatores antropométricos, a saber, idade, gênero, etnia, índice de massa corporal. RESULTADOS: Foram incluídos 82 pacientes consecutivos, sendo que 80 completaram o seguimento imediato e 75 completaram todo o seguimento. Os resultados operatórios (resolução palmar e plantar, presença e intensidade do suor compensatório) tiveram variação entre todas as estações do ano. A satisfação teve igual variação sazonal e os fatores que estiveram relacionados à queda da satisfação foram distintos, conforme a estação do ano. A drenagem pleural tubular fechada e a expansão com Valsalva foram igualmente eficientes quanto à presença de pneumotórax residual, porém a drenagem pleural em selo d\'água aumentou o tempo cirúrgico e a dor pós-operatória nas primeiras 12 horas; o pneumotórax residual não aumentou a dor. CONCLUSÕES: OS melhores resultados operatórios foram obtidos imediatamente e na primavera, os piores no verão e em nível intermediário no outono/inverno. Na primavera, o único parâmetro relacionado à queda na satisfação foi a não resolução plantar; já no verão e no outono/inverno, foi a presença do suor reflexo, indepedente da sua intensidade. A drenagem pleural tubular fechada teve desempenho inferior à expansão pulmonar sob visão direta com manobra de Valsalva. O pneumotórax residual não influenciou a intensidade dor pós-operatória. / INTRODUCTION: Sympathectomy is the treatment of choice for primary and localized hyperhidrosis. Efforts in evolution of this technique have the aim to improve the surgical results and minimizing the collateral effects, witch told to be the sudomotor reflex. This sudomotor reflex could influence the long term satisfaction; it also could change between the seasons of the year, as well as the satisfaction could change in this matter. However, there is no objective data regarding the influence of the seasonality over the surgical results and satisfaction. The objectives of this study is to assess the seasonal variability of palmar and plantar resolution, as well as the incidence of sudomotor reflex and its intensity; to correlate this factors with satisfaction. To evaluate the pain as a factor related to immediate satisfaction; to assess the safety of lung expansion methods and relate this with postoperative pain. METHODS: A two stage prospective clinical assay. The first stage consists of assessment of the immediate factors related to satisfaction (anthropometrics factors, pain, presence and intensity of the sudomotor reflex, palmar and plantar resolutions, season of the year in witch the operation was performed) and the safety of lung expansion methods; it is a prospective, randomized and blinded study. The second stage is a cohort study, assessing the late factors related to satisfaction (anthropometrics factors, presence and intensity of the sudomotor reflex and palmar and plantar resolutions), under distinct climatic situations. There were included patients with typical palmar and plantar primary hyperhidrosis treated by thoracic video-assisted sympathectomy; the inclusion period was 16 months and the final follow-up time was 623 ± 15,13 days in average. They were assessed in hospital stay (pain, lung expansion technique and residual pneumothorax) and at seventh postoperative day (pain, surgical results and satisfaction). Thereafter they were assessed in spring, summer and autumn/winter (surgical results and satisfaction). The surgical results were palmar and plantar resolutions and presence and intensity of the sudomotor reflex. The independent variables related to satisfaction were season of the year in that the sympathectomy was performed, pain, palmar and plantar resolutions, sudomotor reflex (presence and intensity) and anthropometric parameters (age, gender, ethnics, body mass index). RE8UL T8: 82 consecutives patients were included; thereafter, 80 completed the immediate assess and 75 completed the long term follow-up. The surgical results (palmar and plantar resolutions, presence and intensity of the sudomotor reflex) had significant variation throughout the seasons of the year. Equally, the satisfaction had significant variation, as well as the factor related to dissatisfaction, throughout the seasons of the year. The underwater pleural drainage and the lung expansion with Valsalva maneuver were equally efficient in matter of residual pneumothorax; however the underwater pleural drainage was more painful and more operating time consuming; the residual pneumothorax do not increased the postoperative pain. CONCLUSIONS: The best results are obtained in immediate postoperative period and in spring; the worst results are seen in spring; the intermediate results are obtained in autumn/winter. In the spring, the unique factor related to dissatisfaction was the non resolution of plantar hyperhidrotic symptoms; in the summer and in the autumn/winter the presence of the sudomotor reflex, independently of its intensity, was related to dissatisfaction. The underwater pleural drainage should not be indicating after thoracic video-assisted sympathectomy for lung expansion. The residual pneumothorax does not influence the postoperative pain.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-12T12:13:46Z No. of bitstreams: 1 milenemachadominateli.pdf: 5060284 bytes, checksum: 446ee2d6824758d7358e4ba2cb4f755a (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-12T15:46:30Z (GMT) No. of bitstreams: 1 milenemachadominateli.pdf: 5060284 bytes, checksum: 446ee2d6824758d7358e4ba2cb4f755a (MD5) / Made available in DSpace on 2017-05-12T15:46:30Z (GMT). No. of bitstreams: 1 milenemachadominateli.pdf: 5060284 bytes, checksum: 446ee2d6824758d7358e4ba2cb4f755a (MD5) Previous issue date: 2015-07-13 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Vernonia polyanthes Less, família Asteraceae, popularmente conhecida no Brasil como assa-peixe, tem sido utilizada no tratamento de afecções do aparelho respiratório, problemas renais e gastrointestinais, feridas, fraturas e torções, contusões e luxações e, ainda, indicada como tônica, emenagoga, diurética e cicatrizante. O objetivo deste trabalho foi avaliar o potencial toxicológico e as atividades anti-inflamatória tópica e cicatrizante e desenvolver um creme dermatológico a partir do extrato etanólico das folhas de V. polyanthes Less. Folhas secas e pulverizadas foram submetidas à extração em etanol PA por maceração estática seguida de rotaevaporação para obtenção do extrato etanólico de V. polyanthes (EEVP). Parâmetros bioquímicos, hematológicos, morfológicos e histopatológicos foram determinados em ratos Wistar após 15 e 30 dias de tratamento por via oral com 100, 200 e 400 mg/kg de EEVP. O creme dermatológico do extrato etanólico de V. polyanthes (cEEVP) foi desenvolvido nas concentrações 0,10, 0,25 e 0,50% seguido de estudo de estabilidade. A atividade anti-inflamatória tópica de cEEVP foi avaliada pelos métodos de edema de orelha induzido por óleo de cróton, fenol e ácido araquidônico, enquanto EEVP e cEEVP foram usados no ensaio da atividade cicatrizante através de induções de lesões cutâneas. Análises histopatológicas e avaliação da atividade das enzimas mieloperoxidase (MPO) e N-Acetil-β-D-glicorominidase (NAG) complementaram os ensaios farmacológicos. Na avaliação da toxicidade, EEVP não alterou os parâmetros bioquímicos, hematológicos e histopatológicos, mas promoveu modificações nos níveis lipídicos e enzimas hepáticas nos grupos tratados com EEVP. O cEEVP apresentou conformidades adequadas no estudo de estabilidade e juntamente com o EEVP demonstrou efeitos anti-inflamatório tópico e cicatrizante. Os resultados poderão contribuir com a Política Nacional de Plantas Medicinais e Fitoterápicos através da difusão do conhecimento e da comprovação científica das aplicações terapêuticas de V. polyanthes. / Vernonia polyanthes Less, Asteraceae family, popularly known in Brazil as assa-peixe, has been used to treat diseases of the respiratory tract, kidney and gastrointestinal problems, wounds, fractures and sprains, bruises and dislocations, and also indicated as tonic, emmenagogue, diuretic and healing. The aim of this work was to investigate the toxicological potential and topical anti-inflammatory and healing activities and develop a dermatological cream from the ethanol extract of V. polyanthes leaves. Dried and powdered leaves were extracted in ethanol PA by static maceration for obtaining dry ethanol extract (EEVP) using a rotaevaporator. Parameters Biochemical, hematologic, morphological and histopathological were determined in Wistar rats after 15 and 30 days of treatment orally with 100, 200 and 400 mg/kg EEVP. Dermatological cream of EEVP (cEEVP) was developed at the concentrations of 0.10, 0.25 and 0.50% and evaluated through stability study. The topical anti-inflammatory activity of cEEVP was assessed by ear edema induced by croton oil, phenol and arachidonic acid, while the wound healing activity was performed by cutaneous lesions test using EEVP and cEEVP. Histopathological analysis and evaluation of the myeloperoxidase (MPO) and N-acetyl-β-D-glicorominidase (NAG) activities were also determined. In the evaluation of toxicity, EEVP did not modify the biochemical, hematological and histopathological parameters, but promoted alterations in lipid and liver enzymes levels. The cEEVP showed adequate conformities in the stability study and together with the EEVP demonstrated topical anti-inflammatory and wound healing effects. The results may contribute to the National Policy of Medical Plants and Herbal through the dissemination of knowledge and scientific evidence of the therapeutic applications of V. polyanthes.

Syftet är att beskriva symtom och biverkningar som kvinnor med avancerad bröstcancer och cytostatikabehandling rapporterat i ett datoriserat rapporteringssystem före läkarbesök. Undersöka tillfredsställelsen med detta system; se om det finns en skillnad mellan äldre och yngre; undersöka kvinnornas uppfattning om vad som kan förbättras i uppföljningen av symtom/biverkningar samt stödet från läkare. Detta är en kvantitativ, deskriptiv tvärsnittsstudie baserat på rapporteringssystemets databas samt enkätundersökning.   Biverkningarna trötthet, smärta och nervpåverkan rapporterades mest frekvent. Tidsåtgången för rapportering ansågs utav de flesta vara kort eller mycket kort och formuläret upplevdes av majoriteten vara ganska lätt till mycket lätt att använda oberoende av datorvana. Läkaren ansågs från hög grad till mycket hög grad vara ett stöd i att hantera symtom och biverkningar av två tredjedelar av respondenterna. Hälften ansåg att rapporterade biverkningar och symtom uppmärksammades av läkaren i hög grad till mycket hög grad.   Undersökningen bekräftar det tidigare forskning visat om datoriserade rapporteringssystem i vården, att de är funktionella oavsett ålder samt att intresse finns för att använda dessa i större utsträckning. På grund av litet urval och relativt stort bortfall i enkätstudien kan dock inga direkta slutsatser dras men undersökningen antyder att behov finns att vidareutveckla rapporteringssystemet. / The aim of the study is to describe symptoms and side effects that women with advanced breast cancer and chemotherapy reported in an adverse drug reporting system before seeing their oncologist; examine the satisfaction with this system; if there are any differences between older and younger women; the women’s opinion of what improvements could be done in the follow-up of the symptoms/side effects and the support from the oncologist. This is a quantitative, descriptive cross-sectional study based on the database of the adverse drug reporting system and the questionnaire survey.   The side effects fatigue, pain and peripheral neuropathy were most frequently reported. The time consumption for reporting was considered short or very short and the majority thought that the questionnaire was fairly easy to very easy to use independent of computer habits. The oncologists where considered from a high extent to a very high extent being a support in handling the symptoms/side effects by two thirds of the respondents. Two fourths felt that the oncologists attended reported symptoms/side effects from a high extent to a very high extent. Because of a small sample and a relatively large drop-out no real conclusions can be drawn except the need for further development of the system.

La radiothérapie externe (EBRT en anglais pour External Beam Radiotherapy) est l'un des traitements référence du cancer de prostate. Les objectifs de la radiothérapie sont, premièrement, de délivrer une haute dose de radiations dans la cible tumorale (prostate et vésicules séminales) afin d'assurer un contrôle local de la maladie et, deuxièmement, d'épargner les organes à risque voisins (principalement le rectum et la vessie) afin de limiter les effets secondaires. Des modèles de probabilité de complication des tissus sains (NTCP en anglais pour Normal Tissue Complication Probability) sont nécessaires pour estimer sur les risques de présenter des effets secondaires au traitement. Dans le contexte de la radiothérapie externe, les objectifs de cette thèse étaient d'identifier des paramètres prédictifs de complications rectales et vésicales secondaires au traitement; de développer de nouveaux modèles NTCP permettant l'intégration de paramètres dosimétriques et de paramètres propres aux patients; de comparer les capacités prédictives de ces nouveaux modèles à celles des modèles classiques et de développer de nouvelles méthodologies d'identification de motifs de dose corrélés à l'apparition de complications. Une importante base de données de patients traités par radiothérapie conformationnelle, construite à partir de plusieurs études cliniques prospectives françaises, a été utilisée pour ces travaux. Dans un premier temps, la fréquence des symptômes gastro-Intestinaux et génito-Urinaires a été décrite par une estimation non paramétrique de Kaplan-Meier. Des prédicteurs de complications gastro-Intestinales et génito-Urinaires ont été identifiés via une autre approche classique : la régression logistique. Les modèles de régression logistique ont ensuite été utilisés dans la construction de nomogrammes, outils graphiques permettant aux cliniciens d'évaluer rapidement le risque de complication associé à un traitement et d'informer les patients. Nous avons proposé l'utilisation de la méthode d'apprentissage de machine des forêts aléatoires (RF en anglais pour Random Forests) pour estimer le risque de complications. Les performances de ce modèle incluant des paramètres cliniques et patients, surpassent celles des modèle NTCP de Lyman-Kutcher-Burman (LKB) et de la régression logistique. Enfin, la dose 3D a été étudiée. Une méthode de décomposition en valeurs populationnelles (PVD en anglais pour Population Value Decomposition) en 2D a été généralisée au cas tensoriel et appliquée à l'analyse d'image 3D. L'application de cette méthode à une analyse de population a été menée afin d'extraire un motif de dose corrélée à l'apparition de complication après EBRT. Nous avons également développé un modèle non paramétrique d'effets mixtes spatio-Temporels pour l'analyse de population d'images tridimensionnelles afin d'identifier une région anatomique dans laquelle la dose pourrait être corrélée à l'apparition d'effets secondaires. / External beam radiotherapy (EBRT) is one of the cornerstones of prostate cancer treatment. The objectives of radiotherapy are, firstly, to deliver a high dose of radiation to the tumor (prostate and seminal vesicles) in order to achieve a maximal local control and, secondly, to spare the neighboring organs (mainly the rectum and the bladder) to avoid normal tissue complications. Normal tissue complication probability (NTCP) models are then needed to assess the feasibility of the treatment and inform the patient about the risk of side effects, to derive dose-Volume constraints and to compare different treatments. In the context of EBRT, the objectives of this thesis were to find predictors of bladder and rectal complications following treatment; to develop new NTCP models that allow for the integration of both dosimetric and patient parameters; to compare the predictive capabilities of these new models to the classic NTCP models and to develop new methodologies to identify dose patterns correlated to normal complications following EBRT for prostate cancer treatment. A large cohort of patient treated by conformal EBRT for prostate caner under several prospective French clinical trials was used for the study. In a first step, the incidence of the main genitourinary and gastrointestinal symptoms have been described. With another classical approach, namely logistic regression, some predictors of genitourinary and gastrointestinal complications were identified. The logistic regression models were then graphically represented to obtain nomograms, a graphical tool that enables clinicians to rapidly assess the complication risks associated with a treatment and to inform patients. This information can be used by patients and clinicians to select a treatment among several options (e.g. EBRT or radical prostatectomy). In a second step, we proposed the use of random forest, a machine-Learning technique, to predict the risk of complications following EBRT for prostate cancer. The superiority of the random forest NTCP, assessed by the area under the curve (AUC) of the receiving operative characteristic (ROC) curve, was established. In a third step, the 3D dose distribution was studied. A 2D population value decomposition (PVD) technique was extended to a tensorial framework to be applied on 3D volume image analysis. Using this tensorial PVD, a population analysis was carried out to find a pattern of dose possibly correlated to a normal tissue complication following EBRT. Also in the context of 3D image population analysis, a spatio-Temporal nonparametric mixed-Effects model was developed. This model was applied to find an anatomical region where the dose could be correlated to a normal tissue complication following EBRT.

Les événements indésirables médicamenteux (EIM) regroupent à la fois les effets indésirables des médicaments (ADR : Adverse Drug Reactions), considérés comme non évitables et les erreurs médicamenteuses (EM), considérées comme évitables. L’objectif de cette thèse est d’étudier les EIM conduisant à une admission en réanimation.Dans un premier temps, nous avons effectué une revue systématique de la littérature portant sur l’incidence des hospitalisations en réanimation pour EIM. Au total, 11 études ont été intégrées. L’incidence des EIM nécessitant une admission en réanimation variait de 0,37 à 27,4 %. Au total, 17,5 à 85,7 % de ces EIM étaient jugés évitables. Nous avons mené dans un second temps une étude observationnelle d’une durée d’un an dans un service de réanimation médicale d’un hôpital universitaire. Cette étude avait pour objectif d’évaluer l’incidence, l’évitabilité, la sévérité, le coût des EIM responsables d’admissions en réanimation et d’identifier les causes amorces à l’origine des EM.Au total, 743 séjours ont été inclus dont 102 (13,7 %) étaient liés à une EM et 71 (9,6 %) à un ADR. Le taux d’événements évitables était ainsi de 0,59. La non-observance des patients à leur traitement médicamenteux était la principale cause amorce des EM (n = 31/102). Les 102 séjours évitables liés à une EM représentaient un total de 528 journées d’hospitalisation en réanimation, occupant ainsi en moyenne 1,4 lit par jour sur une période d’un an pour un coût total de 747 651 €.Ce travail conclue sur la nécessité d’effectuer des études complémentaires afin d’évaluer les moyens à mettre en œuvre pour réduire l’incidence des EIM responsables d’admissions en réanimation. / Adverse drug events (ADE) include adverse drug reactions (ADR), considered as not preventable and medication errors (ME), considered as preventable. The aim of this thesis is to describe ADE responsible for ICU admissions. First, we conducted a systematic review dealing with the incidence of ADE requiring ICU admission in adult patients. A total of 11 studies were included in the meta-analysis. The reported incidences of ADE requiring ICU admission ranged from 0.37 to 27.4%. Preventable events accounted for 17.5 to 85.7% of the events.To get more insight into this topic and to complete the published data, we performed a one-year observational study in a medical ICU of a teaching parisian hospital. The objectives of the study were to estimate the incidence of ICU admissions due to ADE, to assess preventability, severity and costs of these ADE and to determine the leading causes of medication errors (preventable ADE). A total of 743 admissions were included with 102 stays (13.7%) related to ME and 71 (9.6%) related to ADR. Medication non-compliance was the main leading cause of ME (n = 31/102). The 102 medication error-related admissions accounted for a total of 528 days of hospitalization in the ICU, requiring a mean of 1.4 ICU beds per day over the one-year period, with an associated total cost amounting to 747,651 €.This work concludes that further studies should be performed to assess ways to reduce the incidence of ADE responsible for ICU admissions.

Purpose: Previous clinical studies have suggested a positive effect of low-frequency pulsed electromagnetic fields (PEMF) on wound healing and inflammation in the eye. We tried to test the value of PEMF treatment in a hyphema animal model with well-defined conditions. Methods: After injection of citrated autologous blood for the production of hyphema, 16 rabbit eyes were treated with 10 or 20 mT for 60 min on 4 days within the postoperative week. Two control groups with hyphema alone (n = 8) and PEMF irradiation without hyphema (n = 4) were also included. The rate of resorption was recorded daily. Histopathologic evaluation was performed. Results: The incidence of endothelial cell damage and fibrotic clots was markedly reduced in the 10-mT group while the resorption time of 8 days was identical with the control group. In the 20-mT group, the complication rate and the resorption time was increased versus the control group. Conclusions: The use of PEMF treatment is of some, however, limited value as it did not reduce the resorption time of hyphema but displayed a dose-dependent, beneficial influence on some serious side effects. Future clinical studies with low-dose PEMF irradiation are justified and should determine the optimal dosage and suitable indications of PEMFs as an adjunctive treatment in ocular inflammation or trauma. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

L’électroconvulsivothérapie (ECT), anciennement connue sous le nom «d’électrochoc», est utilisée dans le traitement de plusieurs pathologies psychiatriques, notamment la dépression majeure réfractaire au traitement. La crainte d’effets secondaires cognitifs en limite l’utilisation, malgré les nombreuses améliorations qui ont eu lieu depuis son invention en 1938. Le choix des tests cognitifs à inclure dans le suivi clinique demeure sujet de discussion, peu de données étant disponibles sur les impacts cognitifs des techniques modernes d’ECT. La présente étude a donc pour but de faire une revue systématique des effets secondaires cognitifs des pratiques modernes de l’ECT, et de faire la revue des tests cognitifs utilisés dans le suivi clinique. En ce sens, 91 études ont été sélectionnées selon les standards PRISMA et incluses pour méta-analyse, pour un total de 3762 patients; les tests cognitifs ont été séparés en 11 différents domaines; les résultats aux tests cognitifs pré-ECT ont été comparés aux résultats post-ECT à 3 différents temps, soit immédiatement post-ECT (moins de 24h), court terme (moins d’un mois) et long terme (plus d’un mois). Malgré une hétérogénéité élevée, les données montrent un impact à court terme négatif léger à modéré, surtout sur la mémoire autobiographique, la mémoire verbale et la fluidité verbale; au contraire, les fonctions exécutives sont améliorées rapidement après l’ECT. On observe à long terme une amélioration sur presque tous les domaines cognitifs. Certaines populations sont davantage à risque d’effets secondaires, montrant par exemple une atteinte de la fluidité verbale inversement proportionnelle à l’âge. Le Mini-Mental (MMSE), bien qu’il soit le plus utilisé dans la littérature, semble limité pour le suivi des effets secondaires cognitifs de l’ECT. / Electroconvulsive therapy (ECT) remains one of the most effective treatments for major depressive disorder but remains highly stigmatised. Fear of cognitive side effects limit its use, even after numerous improvements of the ECT techniques since its discovery in 1938. Uncertainties persist regarding the best cognitive tests to be included in ECT clinical follow-up, as there are only few systematised data of the cognitive impact of modern ECT techniques. The current study is a systematic review of the most frequent cognitive side effects following ECT and a review of the cognitive tests used in clinical follow up. A total of 91 studies published from 2000, with an aggregated sample of 3762 individuals were included. Standardized cognitive tests were separated into 10 different cognitive domains for analysis. Comparisons between cognitive measures included pre-ECT baseline with post-ECT cognitive measures at three times: immediate effects (within 24h post-ECT), subacute (within one month post-ECT), and long-term (more than one month post-ECT). Although studies showed high heterogeneity, Hedges’ g revealed small to medium effect sizes for short-term effects post-ECT, with individuals presenting a decrease in autobiographical memory, verbal fluency, and verbal memory. The impact on verbal fluency showed an inverse correlation with age, being significantly greater in younger adults. Conversely, executive functions improved significantly post-ECT. Long-term effects showed an improvement on almost all cognitive domains. According to the literature, the Mini-Mental State Examination is the most common screening test used in ECT, but its clinical utility is extremely limited to track post-ECT cognitive changes.

OBJECTIVES: The aim of our study was to assess clinical presentation of early-onset schizophrenia spectrum disoders (EO-SSD), the time to first improvement and efficacy associated with selected atypical (AAPs) and typical (TAPs) antipsychotics, as well as two main side effects - weight gain and treatment-emergent extrapyramidal symptoms (EPSs) during the treatment in patients with EO-SSD. METHODS: This was a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs (risperidone, olanzapine, ziprasidone, quetiapine and clozapine) and TAPs (haloperidol, perphenazine and sulpiride), for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 173 patients (85 males, 88 females; mean age 15.8±1.6 years); their treatment included 297 treatment trials. Data on premorbid adjustment, prodromal symptoms and psychopathology at admission, as well as comorbidity were evaluated based on the patients' medical records. The time to first improvement could be estimated in 258 treatment trials; of these, 195 (76%) comprised AAPs and 63 (24%) TAPs. The time to first improvement was assessed in agreement with the methodology established for retrospective studies as the number of treatment days prior to the first record of improvement...

MUDr. Olga Matoušková - the dissertation theses The influence of individual genetic predisposition to the pharmacokinetics and pharmacodynamics of chosen opioids ABSTRACT Introduction: The aim of this thesis is to study the influence of polymorphism of CYP2D6 and MDR1 on the pharmacokinetics and pharmacodynamics of tramadol in healthy volunteers using measurement. A secondary objective is to evaluate these polymorphisms in relation to the analgesic efficacy and side effects of piritramide for acute postoperative pain. Materials and methods: In two prospective work studying the influence of genetic predisposition on the pharmacokinetic and pharmacodynamic parameters of tramadol, we included a total of 90 healthy volunteers. Clinical studies on opioid analgesia and influence of genetic predisposition to the pharmaco-therapeutic effects and side effects in patients with acute postoperative pain, we included a total of 161 patients with acute postoperative pain. Polymorphism genotyping CYP2D6 and MDR1 gene we performed PCR - RFLP analysis, to determine concentrations of tramadol and metabolite, we used gas and liquid chromatography and pharmacodynamic effects of opioids was evaluated by pupilometric measurement and visual analogue scale. Results and conclusion: Variability of the opioid effect is influenced by...