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.

No description available.

Hipodermóclise (HDC) é uma importante técnica alternativa para a administração de medicamentos e fluidos pela via subcutânea. É usada com frequência para o controle dos sintomas em pacientes em cuidados paliativos com dificuldade de acesso venoso e que são incapazes de tolerar medicação oral. No entanto, raros estudos abordaram o uso da HDC de uma forma global, para reposição hidroeletrolítica e terapia medicamentosa, tanto na forma contínua quanto intermitente, observando detalhes e complicações do seu uso. Os objetivos deste estudo incluíram caracterizar o uso da HDC para administração de medicamentos, soluções e eletrólitos e avaliar as possíveis complicações locais, identificando também outros fatores que influenciam sua ocorrência. Estudo observacional prospectivo com coleta de dados em prontuário e acompanhamento diário de pacientes internados com câncer avançado, da equipe de Cuidados Paliativos do Instituto do Câncer do Estado de São Paulo (ICESP) em uso de HDC, verificando local de punção, medicamentos administrados e possíveis complicações, acompanhando os detalhes de seu uso. A análise estatística não-paramétrica e método de regressão logística foram realizados. Foram acompanhados 99 pacientes com 243 punções, das quais 166 (68,3%) em coxa e 46 (18,9%) em abdome. Os medicamentos mais utilizados foram morfina em 122 (50,2%) punções, seguido de dipirona em 118 (48,6%) e dexametasona em 86 (35,4%). A solução mais prescrita foi a glicofisiológica em 38 (15,6%) punções, pelo seu aporte calórico. 13,6% das punções (33 de 243) tiveram complicações, sendo apenas seis casos maiores (edema). Complicações ocorreram mais frequentemente até o segundo dia da punção e foram associadas com o número (p=0,007) e o volume (p=0,042) de medicamentos administrados e também com a solução glicofisiológica (p=0,003) e os eletrólitos cloreto de potássio (p=0,037) e cloreto de sódio (p=0,013). Este estudo permitiu o conhecimento de fatores associados a complicações e propõe algumas recomendações, como: individualização da terapia, especialmente relacionada com o volume de escolha, número de medicamentos administrados e evitar a adição de eletrólitos na solução glicofisiológica / Hypodermoclysis (HDC) is an important alternative technique for the administration of drugs and fluids into the subcutaneous tissue. It is frequently used for symptom control in palliative care patients, with difficult venous access and unable to tolerate oral medications. However, few studies address the use of HDC as a whole to fluid replacement and drug therapy, both continuous and intermittent mode, observing details and complications of its use. The objectives of this study included characterizing the use of HDC to administer drugs, solutions and electrolytes and to evaluate possible local complications also identifying other factors influencing their occurrence. Prospective observational study with data collection in medical records and daily monitoring of advanced cancer inpatients of the palliative care team of São Paulo State Cancer Institute (ICESP) in use of HDC, checking infusion site, administered drugs and possible complications, following the details of its use. Non-parametrical statistical analysis and logistic regression were performed. Were followed 99 patients with 243 infusion sites, which 166 (68.3%) in the thigh and 46 (18.9%) in the abdomen. The most commonly used drugs were morphine in 122 (50.2%) infusion sites, followed by dipyrone in 118 (48.6%) and dexamethasone in 86 (35.4%). The most prescribed solution was dextrose 5%/0,9% saline in 38 (15.6%) infusion sites because of its caloric intake. 13.6% of punctures (33 of 243) had complications, only six larger cases (edema). Complications occurred mainly up to the second day of the infusion sites and were associated with the number (p=0,007) and volume (p=0,042) of drugs used as also with 5% dextrose/0.9% saline solution (p=0,003) and NaCl (p=0,037) and KCl (p=0,013) electrolytes. This study has allowed the knowledge of factors associated with complications and proposes some recommendations as: individualization of therapy especially related to the volume of choice, number of drugs administered, and avoid adding electrolytes to the 5% dextrose/0.9% saline solution

OBJETIVOS: Evidências consistentes sugerem que a quimioterapia (QT) sistêmica para o tratamento do câncer pode apresentar efeitos deletérios na cognição levando a prejuízos de memória, atenção, velocidade de processamento e função executiva. A maioria dos estudos anteriores, entretanto, foi realizada em mulheres com câncer de mama, o que levanta a possibilidade de que o déficit possa ter sido causado por alterações hormonais e/ou menopausa precoce induzidas pela QT. Pouco se sabe sobre a toxicidade da QT na cognição de pacientes portadores de câncer coloretal (CCR). O objetivo do estudo foi avaliar os efeitos cognitivos da QT adjuvante baseada em fluorouracil (5FU) associado ou não a oxaliplatina (FLOX) em pacientes portadores de CCR estádios II e III , em comparação a indivíduos com câncer de cólon estádio II de baixo risco não submetidos à QT. METODOLOGIA: Estudo de coorte prospectivo, não intervencionista, unicêntrico, onde os pacientes com CCR foram submetidos a uma avaliação neuropsicológica detalhada, além da avaliação de queixas subjetivas de memória e de sintomas depressivos antes do início da quimioterapia (t1) e após 12 meses de seguimento (t2). Avaliamos ainda o papel da apoliproteína E como preditor de risco para disfunção cognitiva e a presença de lesão de substância branca por ressonância magnética (RM) de crânio. RESULTADOS: Num período de 2 anos, de dezembro de 2012 a dezembro de 2014, 85 pacientes foram recrutados e completaram a avaliação inicial (t1): 26 no grupo controle (sem quimioterapia= QT-) e 59 no grupo casos (quimioterapia= QT+). Dentre os 85 pacientes que participaram da avaliação inicial, 16 foram excluídos da análise do desfecho principal. A maioria dos pacientes era do sexo masculino (60,3%), idosos com idade média de 62,5 anos (DP 9,4) e escolaridade média de 7,6 anos (DP 3,7). Considerando o desfecho primário do escore composto global e também os domínios cognitivos de memória e atenção, não econtramos diferença significativa de desempenho no t1 e t2 entre os grupos. Com relação a função executiva, os pacientes que realizaram QT apresentaram melhor desempenho no t1, entretanto, evoluíram com maior declínio e pior desempenho que os controles no t2 após ajuste para idade, sexo, escolaridade e sintomas depressivos no baseline (beta -1,80; 95%CI -3,50; -0,11, p=0,04). Um subgrupo de 32 pacientes foram submetidos a RM de crânio que não mostrou alterações significativas de substância branca pela técnica de imagem de tensor de difusão (DTI) no seguimento. A presença do alelo ?4 da apolipoproteína E não foi diferente entre os grupos. CONCLUSÃO: Pacientes portadores de câncer colorretal que receberam quimioterapia adjuvante com esquema FLOX apresentaram declínio no desempenho cognitivo no domínio função executiva em comparação a pacientes com doença localizada que não receberam QT após 12 meses de seguimento / PURPOSE: Cognitive dysfunction may occur after chemotherapy in cancer survivors, especially in those that received chemotherapy for breast cancer. The frequency and to which extent such toxicity develops in colorectal cancer (CRC) survivors is unknown. This prospective study evaluated the effects of adjuvant chemotherapy on the cognitive performance of patients with localized CRC in comparison with a control group who did not receive chemotherapy. METHODS: Consecutive patients with localized stages II and III CRC completed neuropsychological assessments, self-reported cognitive complaints questionnaires, and depressive symptoms evaluation before starting fluoropyrimidine-based adjuvant chemotherapy (t1) and after 12 months (t2). Control group was assessed at matching intervals. Blood was collected for apolipoprotein E (APOE) genotyping. Clinical and demographic data were also collected. Diffusion tensor imaging (DTI) data was acquired from a subset of participants at both time-points. RESULTS: From December 2012 to December 2014, 137 patients were approached and 85 patients were recruited: 59 received chemotherapy (CTh+) and 26 did not (CTh-), based on standard recommendation for adjuvant therapy for CRC. The mean age was 62.5 years (SD 9.4), 60% were male, and the mean years of education was 7.6 (SD 3.7). No difference was found on global composite score (p=0.38), attention (p= 0.84) or memory (p= 0.97) between the two groups during the followup (mean 375 days, SD 29). However there was a significant difference on executive function domain, after adjustment for age, sex, education, and depressive symptoms at baseline (beta - 1.80; 95%CI -3.50; -0.11, p=0.04), suggesting worse performance for the CTh+ group. In 32 patients who underwent MRI, there was no significant differences for all DTI indices in any white matter regions between CTh+ and CTh- groups during follow-up. APOE polymorphisms were not predictive of cognitive dysfunction. CONCLUSION: After adjusting for confounding factors, patients with CRC who received adjuvant fluorouracil with or without oxaliplatin presented cognitive decline on executive function after 12 months in comparison with patients with localized disease that did not receive chemotherapy

INTRODUÇÃO: O polivinilpirrolidona-iodo (PVP-I) tópico vem sendo descrito como um agente esclerosante para pleurodese de fácil obtenção, baixo custo e com boa eficácia. Apesar disso, sua segurança ainda não foi estudada de maneira sistemática e alguns autores apresentam restrições ao seu uso por relatos de determinados eventos adversos. OBJETIVOS: descrever a ocorrência de eventos adversos sérios e comuns à pleurodese com PVP-I tópico. Avaliar se existe relação de dose-dependência na ocorrência dos eventos adversos; a efetividade clínica e a qualidade de vida dos pacientes. MÉTODOS: ensaio clínico envolvendo pacientes submetidos a pleurodese com PVP-I tópico, randomizados em dois grupos: grupo 1 com PVP-I tópico a 1% e grupo 2 com PVP-I tópico a 2%. A análise de segurança foi baseada na ocorrência de eventos adversos, graduados de acordo com o Common Terminology Criteria for Adverse Events. Foram realizadas avaliações clínicas e exames complementares no pré-operatório e em vários momentos do seguimento pós-operatório. Os dados clínicos avaliados foram dor, dispnéia, temperatura, pressão arterial, freqüência cardíaca, saturação de oxigênio e acuidade visual. Exames complementares envolveram hemograma, função renal, hepática e tireoidiana, eletrocardiograma e radiografia de tórax. A efetividade clínica foi determinada pela necessidade de procedimentos adicionais após a pleurodese e a qualidade de vida através de questionário específico. RESULTADOS: foram avaliados 60 pacientes, 30 em cada grupo. Predominou o sexo feminino, em 55 pacientes. A média de idade foi de 55,9 ± 11,7 anos. A etiologia mais comum do derrame pleural foi neoplasia de mama em 43 pacientes, seguida por neoplasia pulmonar e de ovário. Foram encontrados 47 eventos adversos sérios relacionados ao procedimento distribuídos em 34 pacientes nos primeiros 30 dias de avaliação. Foram eles: dor, em onze pacientes, hipertensão em dez, empiema em um, hiponatremia em oito pacientes, elevação da fosfatase alcalina, transaminase oxalacética e transaminase pirúvica em dez, três e um pacientes respectivamente e hipocalemia em um paciente. A taxa de sucesso foi de 96% e não houve mudança na qualidade de vida após o procedimento. Na comparação dos grupos não se observou diferença estatística em relação aos dados avaliados. CONCLUSÕES: Os eventos adversos sérios mais esperados após a realização de pleurodese com PVP-I tópico são dor, hipertensão e alguns distúrbios metabólicos. A pleurodese com PVP-I tópico mostrou ser um procedimento eficaz, mas não ofereceu melhora na qualidade de vida dos pacientes. Não se observou relação de dose-dependência na ocorrência dos eventos adversos e na eficácia do procedimento / BACKGROUND: Iodopovidone has been described as a sclerosing agent easily obtained, inexpensive and with good results. Despite this, its safety has not been systematically evaluated and some authors have restrictions to its use because of reports of some adverse events related. OBJECTIVE: To describe the occurrence of common and serious adverse events after iodopovidone pleurodesis. Second endpoints were to describe dose-dependent relation to adverse events, procedure efficacy and patient\'s quality of life. METHODS: clinical trial including patients with recurrent malignant pleural effusion, undergone to pleurodesis, randomized into two groups: group 1 received 1% iodopovidone and group 2 received 2% Iodopovidone. We sought adverse events systematically with clinical and complementary evaluations since before pleurodesis and on several times postoperative. Clinical evaluation involved pain analog scale, dyspnea scale, oxygen saturation, heart frequency, arterial blood pressure, body temperature and visual acuity. Complementary evaluation was done by electrocardiogram, chest x-ray and laboratory tests (hemogram, renal function, liver function and thyroid function). All adverse events were graduated according to the Common Terminology Criteria for Adverse Events (CTCAEV). Efficacy was considered when the patients did not need further pleural procedure after pleurodesis and quality of life analysis was determined by questionnaire. RESULTS: Sixty patients were enrolled, thirty in each group, 55 females and 5 males. Mean age was 55,9 ± 11,7. The mainly etiology of malignant pleural effusion was breast cancer, in 43 patients, followed by lung cancer and ovarian tumor. We found 47 serious adverse events, possibly related to iodopovidone pleurodesis that occurred in 34 patients on 30 days follow-up. Most frequent clinical adverse events of these were pain, eleven patients, hypertension, ten and empyema in one patients. Serious metabolic events founded were hyponatremia in eight patients, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase increased in ten, three and one patients respectively and hypokalemia in one patient. Success rate occurred in 96%. We didn\'t find change on quality of life after pleurodesis. We found no difference in patient\'s demographical data, occurrence of adverse events, efficacy and quality of life between groups. CONCLUSIONS: Observed common and serious adverse events related to iodopovidone pleurodesis were pain, hypertension, and some metabolic alterations. We found good efficacy for iodopovidone pleurodesis, but no significant change in patient\'s quality of life after procedure. This report does not suggest dose-dependent relation for the occurrence of adverse events

Amalgam has been used as a dental restorative material for centuries, but its potential health effects and biopersistance has lead to a decreased use especially in the Nordic countries. New materials have been introduced, partly to replace the mercury containing amalgam and partly because of esthetical reasons. The possible health effects of amalgam have been studied extensively and the material has been replaced with other less well-examined materials during the last few decades. The prevalence of side effects of dental materials is considered to be low in relation to the vast number of dental treatments undertaken. With the introduction of new and more complex materials, side effects related to dental treatment may increase. Epidemiological data suggest that the side effects of dental resins that have almost completely replaced amalgam fillings in Scandinavia, possess a risk for adverse reactions; however, the causal relation has not been fully established. Therefore, the type and extent of side effects caused by resin-based materials are of great interest. The aims of the study were: - to describe the change in health over time for patients with problems related to their dental materials. The hypothesis was that the patients could be divided into subgroups based on their symptoms and that the ability to recover differs between these groups [Paper I]. Furthermore, to determine whether factors such as the replacement of dental restorative materials and follow-up time had any impact on the perceived health. - to assess the long-term development of symptoms and their social consequences among patients referred for diagnosis and treatment of symptoms related to dental materials [Paper II] - to investigate the possible risks with dental restorative materials other than amalgam [Paper III]. - to describe side effects assessed to be caused by resin-based materials that occurred in a group of patients as well as treatment and long-term consequences of the reactions [Paper IV]. A questionnaire was sent to 614 patients [Paper I and II] that had been referred to the School of Dentistry, Umeå, Sweden, with symptoms allegedly caused by dental materials. The questionnaire contained questions on, among others; civil status, present health, medical and dental treatment and other measures and precautions taken because of psychosocial problems related to current employment situation, feelings, self-image and coping behavior. Moreover, information was collected [Paper III] from the Swedish Dental Materials Register 2003 (DentMr), a compilation of MSDS for 487 materials, and information from the user guide of the materials. The Material Safety Data Sheets (MSDS) included in the DentMR were examined regarding the given composition of the products, the occurrence of CAS-numbers and the risk- and safety phrases of the substances. Information was collected [Paper IV] on 36 patients with reactions to resin-based restorative materials from the Swedish National Register of Side-Effects of Dental Materials. Patients with complex symptoms had a more unfavorable long-term prognosis concerning persistent complaints than those with local symptoms only. Furthermore, the results indicate that the patients might experience health improvements after removal of their dental restorative materials. However, the reason for this improvement was unclear. Replacement of dental restorative materials had no significant impact on the ability to recover completely. Our results also indicate a relationship between patients’ self-related health and social consequences in daily life. Those with remaining complex symptoms had more often stopped working or had decreased their work hours because of their symptoms The information about hazards with dental materials seems insufficiently described in MSDS and there might be materials with side effects unknown to both patients and dental professionals. A literature search indicated that some of the listed substances had possible hazards, e.g. substances with embryotoxic and neurotoxic potential. The patients were very heterogeneous; a few with only local symptom free reactions while other had more complex symptoms. The latter group would gain from a multidisciplinary approach, i.e. dental, medical, as well as social and psychological factors have to be considered when developing care management programs for this group of patients. Furthermore, there is a need for stronger regulations of dental materials, such as those applied to pharmaceutical drugs. Finally, it was found that the majority of symptoms suspected to be caused by resin-based materials were local or a combination of local and extra-oral symptoms that appeared within the first 24 hours after treatment. The most frequent adverse effect reported was skin problems/dermatitis. It appears as though immediate reactions to resin based materials are not uncommon and more prevalent than allergic reactions. Still, we have had, difficulties in verifying associations between the dental restorative materials and adverse reactions and also to identify the offending component.

Hipodermóclise (HDC) é uma importante técnica alternativa para a administração de medicamentos e fluidos pela via subcutânea. É usada com frequência para o controle dos sintomas em pacientes em cuidados paliativos com dificuldade de acesso venoso e que são incapazes de tolerar medicação oral. No entanto, raros estudos abordaram o uso da HDC de uma forma global, para reposição hidroeletrolítica e terapia medicamentosa, tanto na forma contínua quanto intermitente, observando detalhes e complicações do seu uso. Os objetivos deste estudo incluíram caracterizar o uso da HDC para administração de medicamentos, soluções e eletrólitos e avaliar as possíveis complicações locais, identificando também outros fatores que influenciam sua ocorrência. Estudo observacional prospectivo com coleta de dados em prontuário e acompanhamento diário de pacientes internados com câncer avançado, da equipe de Cuidados Paliativos do Instituto do Câncer do Estado de São Paulo (ICESP) em uso de HDC, verificando local de punção, medicamentos administrados e possíveis complicações, acompanhando os detalhes de seu uso. A análise estatística não-paramétrica e método de regressão logística foram realizados. Foram acompanhados 99 pacientes com 243 punções, das quais 166 (68,3%) em coxa e 46 (18,9%) em abdome. Os medicamentos mais utilizados foram morfina em 122 (50,2%) punções, seguido de dipirona em 118 (48,6%) e dexametasona em 86 (35,4%). A solução mais prescrita foi a glicofisiológica em 38 (15,6%) punções, pelo seu aporte calórico. 13,6% das punções (33 de 243) tiveram complicações, sendo apenas seis casos maiores (edema). Complicações ocorreram mais frequentemente até o segundo dia da punção e foram associadas com o número (p=0,007) e o volume (p=0,042) de medicamentos administrados e também com a solução glicofisiológica (p=0,003) e os eletrólitos cloreto de potássio (p=0,037) e cloreto de sódio (p=0,013). Este estudo permitiu o conhecimento de fatores associados a complicações e propõe algumas recomendações, como: individualização da terapia, especialmente relacionada com o volume de escolha, número de medicamentos administrados e evitar a adição de eletrólitos na solução glicofisiológica / Hypodermoclysis (HDC) is an important alternative technique for the administration of drugs and fluids into the subcutaneous tissue. It is frequently used for symptom control in palliative care patients, with difficult venous access and unable to tolerate oral medications. However, few studies address the use of HDC as a whole to fluid replacement and drug therapy, both continuous and intermittent mode, observing details and complications of its use. The objectives of this study included characterizing the use of HDC to administer drugs, solutions and electrolytes and to evaluate possible local complications also identifying other factors influencing their occurrence. Prospective observational study with data collection in medical records and daily monitoring of advanced cancer inpatients of the palliative care team of São Paulo State Cancer Institute (ICESP) in use of HDC, checking infusion site, administered drugs and possible complications, following the details of its use. Non-parametrical statistical analysis and logistic regression were performed. Were followed 99 patients with 243 infusion sites, which 166 (68.3%) in the thigh and 46 (18.9%) in the abdomen. The most commonly used drugs were morphine in 122 (50.2%) infusion sites, followed by dipyrone in 118 (48.6%) and dexamethasone in 86 (35.4%). The most prescribed solution was dextrose 5%/0,9% saline in 38 (15.6%) infusion sites because of its caloric intake. 13.6% of punctures (33 of 243) had complications, only six larger cases (edema). Complications occurred mainly up to the second day of the infusion sites and were associated with the number (p=0,007) and volume (p=0,042) of drugs used as also with 5% dextrose/0.9% saline solution (p=0,003) and NaCl (p=0,037) and KCl (p=0,013) electrolytes. This study has allowed the knowledge of factors associated with complications and proposes some recommendations as: individualization of therapy especially related to the volume of choice, number of drugs administered, and avoid adding electrolytes to the 5% dextrose/0.9% saline solution

OBJETIVOS: Evidências consistentes sugerem que a quimioterapia (QT) sistêmica para o tratamento do câncer pode apresentar efeitos deletérios na cognição levando a prejuízos de memória, atenção, velocidade de processamento e função executiva. A maioria dos estudos anteriores, entretanto, foi realizada em mulheres com câncer de mama, o que levanta a possibilidade de que o déficit possa ter sido causado por alterações hormonais e/ou menopausa precoce induzidas pela QT. Pouco se sabe sobre a toxicidade da QT na cognição de pacientes portadores de câncer coloretal (CCR). O objetivo do estudo foi avaliar os efeitos cognitivos da QT adjuvante baseada em fluorouracil (5FU) associado ou não a oxaliplatina (FLOX) em pacientes portadores de CCR estádios II e III , em comparação a indivíduos com câncer de cólon estádio II de baixo risco não submetidos à QT. METODOLOGIA: Estudo de coorte prospectivo, não intervencionista, unicêntrico, onde os pacientes com CCR foram submetidos a uma avaliação neuropsicológica detalhada, além da avaliação de queixas subjetivas de memória e de sintomas depressivos antes do início da quimioterapia (t1) e após 12 meses de seguimento (t2). Avaliamos ainda o papel da apoliproteína E como preditor de risco para disfunção cognitiva e a presença de lesão de substância branca por ressonância magnética (RM) de crânio. RESULTADOS: Num período de 2 anos, de dezembro de 2012 a dezembro de 2014, 85 pacientes foram recrutados e completaram a avaliação inicial (t1): 26 no grupo controle (sem quimioterapia= QT-) e 59 no grupo casos (quimioterapia= QT+). Dentre os 85 pacientes que participaram da avaliação inicial, 16 foram excluídos da análise do desfecho principal. A maioria dos pacientes era do sexo masculino (60,3%), idosos com idade média de 62,5 anos (DP 9,4) e escolaridade média de 7,6 anos (DP 3,7). Considerando o desfecho primário do escore composto global e também os domínios cognitivos de memória e atenção, não econtramos diferença significativa de desempenho no t1 e t2 entre os grupos. Com relação a função executiva, os pacientes que realizaram QT apresentaram melhor desempenho no t1, entretanto, evoluíram com maior declínio e pior desempenho que os controles no t2 após ajuste para idade, sexo, escolaridade e sintomas depressivos no baseline (beta -1,80; 95%CI -3,50; -0,11, p=0,04). Um subgrupo de 32 pacientes foram submetidos a RM de crânio que não mostrou alterações significativas de substância branca pela técnica de imagem de tensor de difusão (DTI) no seguimento. A presença do alelo ?4 da apolipoproteína E não foi diferente entre os grupos. CONCLUSÃO: Pacientes portadores de câncer colorretal que receberam quimioterapia adjuvante com esquema FLOX apresentaram declínio no desempenho cognitivo no domínio função executiva em comparação a pacientes com doença localizada que não receberam QT após 12 meses de seguimento / PURPOSE: Cognitive dysfunction may occur after chemotherapy in cancer survivors, especially in those that received chemotherapy for breast cancer. The frequency and to which extent such toxicity develops in colorectal cancer (CRC) survivors is unknown. This prospective study evaluated the effects of adjuvant chemotherapy on the cognitive performance of patients with localized CRC in comparison with a control group who did not receive chemotherapy. METHODS: Consecutive patients with localized stages II and III CRC completed neuropsychological assessments, self-reported cognitive complaints questionnaires, and depressive symptoms evaluation before starting fluoropyrimidine-based adjuvant chemotherapy (t1) and after 12 months (t2). Control group was assessed at matching intervals. Blood was collected for apolipoprotein E (APOE) genotyping. Clinical and demographic data were also collected. Diffusion tensor imaging (DTI) data was acquired from a subset of participants at both time-points. RESULTS: From December 2012 to December 2014, 137 patients were approached and 85 patients were recruited: 59 received chemotherapy (CTh+) and 26 did not (CTh-), based on standard recommendation for adjuvant therapy for CRC. The mean age was 62.5 years (SD 9.4), 60% were male, and the mean years of education was 7.6 (SD 3.7). No difference was found on global composite score (p=0.38), attention (p= 0.84) or memory (p= 0.97) between the two groups during the followup (mean 375 days, SD 29). However there was a significant difference on executive function domain, after adjustment for age, sex, education, and depressive symptoms at baseline (beta - 1.80; 95%CI -3.50; -0.11, p=0.04), suggesting worse performance for the CTh+ group. In 32 patients who underwent MRI, there was no significant differences for all DTI indices in any white matter regions between CTh+ and CTh- groups during follow-up. APOE polymorphisms were not predictive of cognitive dysfunction. CONCLUSION: After adjusting for confounding factors, patients with CRC who received adjuvant fluorouracil with or without oxaliplatin presented cognitive decline on executive function after 12 months in comparison with patients with localized disease that did not receive chemotherapy

INTRODUÇÃO: O polivinilpirrolidona-iodo (PVP-I) tópico vem sendo descrito como um agente esclerosante para pleurodese de fácil obtenção, baixo custo e com boa eficácia. Apesar disso, sua segurança ainda não foi estudada de maneira sistemática e alguns autores apresentam restrições ao seu uso por relatos de determinados eventos adversos. OBJETIVOS: descrever a ocorrência de eventos adversos sérios e comuns à pleurodese com PVP-I tópico. Avaliar se existe relação de dose-dependência na ocorrência dos eventos adversos; a efetividade clínica e a qualidade de vida dos pacientes. MÉTODOS: ensaio clínico envolvendo pacientes submetidos a pleurodese com PVP-I tópico, randomizados em dois grupos: grupo 1 com PVP-I tópico a 1% e grupo 2 com PVP-I tópico a 2%. A análise de segurança foi baseada na ocorrência de eventos adversos, graduados de acordo com o Common Terminology Criteria for Adverse Events. Foram realizadas avaliações clínicas e exames complementares no pré-operatório e em vários momentos do seguimento pós-operatório. Os dados clínicos avaliados foram dor, dispnéia, temperatura, pressão arterial, freqüência cardíaca, saturação de oxigênio e acuidade visual. Exames complementares envolveram hemograma, função renal, hepática e tireoidiana, eletrocardiograma e radiografia de tórax. A efetividade clínica foi determinada pela necessidade de procedimentos adicionais após a pleurodese e a qualidade de vida através de questionário específico. RESULTADOS: foram avaliados 60 pacientes, 30 em cada grupo. Predominou o sexo feminino, em 55 pacientes. A média de idade foi de 55,9 ± 11,7 anos. A etiologia mais comum do derrame pleural foi neoplasia de mama em 43 pacientes, seguida por neoplasia pulmonar e de ovário. Foram encontrados 47 eventos adversos sérios relacionados ao procedimento distribuídos em 34 pacientes nos primeiros 30 dias de avaliação. Foram eles: dor, em onze pacientes, hipertensão em dez, empiema em um, hiponatremia em oito pacientes, elevação da fosfatase alcalina, transaminase oxalacética e transaminase pirúvica em dez, três e um pacientes respectivamente e hipocalemia em um paciente. A taxa de sucesso foi de 96% e não houve mudança na qualidade de vida após o procedimento. Na comparação dos grupos não se observou diferença estatística em relação aos dados avaliados. CONCLUSÕES: Os eventos adversos sérios mais esperados após a realização de pleurodese com PVP-I tópico são dor, hipertensão e alguns distúrbios metabólicos. A pleurodese com PVP-I tópico mostrou ser um procedimento eficaz, mas não ofereceu melhora na qualidade de vida dos pacientes. Não se observou relação de dose-dependência na ocorrência dos eventos adversos e na eficácia do procedimento / BACKGROUND: Iodopovidone has been described as a sclerosing agent easily obtained, inexpensive and with good results. Despite this, its safety has not been systematically evaluated and some authors have restrictions to its use because of reports of some adverse events related. OBJECTIVE: To describe the occurrence of common and serious adverse events after iodopovidone pleurodesis. Second endpoints were to describe dose-dependent relation to adverse events, procedure efficacy and patient\'s quality of life. METHODS: clinical trial including patients with recurrent malignant pleural effusion, undergone to pleurodesis, randomized into two groups: group 1 received 1% iodopovidone and group 2 received 2% Iodopovidone. We sought adverse events systematically with clinical and complementary evaluations since before pleurodesis and on several times postoperative. Clinical evaluation involved pain analog scale, dyspnea scale, oxygen saturation, heart frequency, arterial blood pressure, body temperature and visual acuity. Complementary evaluation was done by electrocardiogram, chest x-ray and laboratory tests (hemogram, renal function, liver function and thyroid function). All adverse events were graduated according to the Common Terminology Criteria for Adverse Events (CTCAEV). Efficacy was considered when the patients did not need further pleural procedure after pleurodesis and quality of life analysis was determined by questionnaire. RESULTS: Sixty patients were enrolled, thirty in each group, 55 females and 5 males. Mean age was 55,9 ± 11,7. The mainly etiology of malignant pleural effusion was breast cancer, in 43 patients, followed by lung cancer and ovarian tumor. We found 47 serious adverse events, possibly related to iodopovidone pleurodesis that occurred in 34 patients on 30 days follow-up. Most frequent clinical adverse events of these were pain, eleven patients, hypertension, ten and empyema in one patients. Serious metabolic events founded were hyponatremia in eight patients, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase increased in ten, three and one patients respectively and hypokalemia in one patient. Success rate occurred in 96%. We didn\'t find change on quality of life after pleurodesis. We found no difference in patient\'s demographical data, occurrence of adverse events, efficacy and quality of life between groups. CONCLUSIONS: Observed common and serious adverse events related to iodopovidone pleurodesis were pain, hypertension, and some metabolic alterations. We found good efficacy for iodopovidone pleurodesis, but no significant change in patient\'s quality of life after procedure. This report does not suggest dose-dependent relation for the occurrence of adverse events

The Side Effects of Drugs Annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. The purpose of this supplement is to provide a concise reference of the newly available literature to support the existing information regarding the known adverse effects of commonly prescribed medications or abused drugs. The information covers peer-reviewed publications from January 2016 to December 2016. This review focused on CNS stimulants and drugs that suppress appetite. It covers amphetamines (including lisdexamfetamine, methamphetamine and 3,4-methylenedioxymetamphetamine), methylphenidate, atomoxetine, modafinil and armodafinil, methylxanthines (caffeine), monotherapies and combinational therapies that suppress appetite (lorcaserin, phentermine, phentermine/topiramate) and medications used in Alzheimer's disease and cognitive decline (rivastigmine, donepezil and memantine).