897 resultados para phase I studies
Resumo:
Background: Considerable variation in the prevalence of childhood asthma and its symptoms (wheezing) has been observed in previous studies and there is evidence that the prevalence has been increasing over time. Methods: We have systematically reviewed the reported prevalence and time trends of wheezing symptoms among children, worldwide and within the same country over time. All studies comprising more than 1000 persons and meeting certain other quality criteria published over a 16-year period, between January 1990 and December 2005, are reported and a comparison of ISAAC (International Study of Asthma and Allergies in Childhood) and non-ISAAC studies is made, in part as a way of expanding the power to examine time trends (the older studies tend to be non-ISAAC), but also to examine possible methodological differences between ISAAC and non-ISAAC questions. Results: A wide range of current prevalence of wheeze was observed between and within countries over time. The UK had the highest recorded prevalence of 32.2% in children aged 13–14 in 1994–5 and Ethiopia had the lowest prevalence, 1.7% in children aged 10–19 in 1996. All studies in Australia and the UK were compared using multiple logistic regression. ISAAC phase I and III studies reported significantly higher prevalence of current wheeze (OR = 1.638) compared with non-ISAAC studies, after adjusting for various other factors (country, survey year, age of child, parental vs child response to the survey). Australia showed a significantly higher prevalence of current wheezing (OR = 1.343) compared with the UK, there was a significant increase in the prevalence odds ratio per survey year (2.5% per year), a significant decrease per age of child (0.7% per year), and a significantly higher response in current wheezing if the response was self-completed by the child (OR = 1.290). These factors, when explored separately for ISAAC and non-ISAAC studies, showed very different results. In ISAAC studies, or non-ISAAC studies using ISAAC questions, there was a significant decrease in current wheezing prevalence over time (2.5% per year). In non-ISAAC studies, which tend to cover an earlier period, there was a significant increase (2.6% per year) in current wheezing prevalence over time. This is very likely to be a result of prevalence of wheezing increasing from the 1970s up to the early 1990s, but decreasing since then. Conclusion: The UK has the highest recorded prevalence of wheezing and Ethiopia the lowest. Prevalence of wheezing in Australia and the UK has increased from the 1970s up to the early 1990s, but decreased since then and ISAAC studies report significantly higher prevalences than non-ISAAC studies.
Resumo:
Background:
Internationally, nurse-directed protocolised-weaning has been evaluated by measuring its impact on patient outcomes. The impact on nurses’ views and perceptions has been largely ignored.
Aim:
To determine the change in intensive care nurses’ perceptions, satisfaction, knowledge and attitudes following the introduction of nurse-directed weaning. Additionally, views were obtained on how useful protocolised-weaning was to practice.
Methods:
The sample comprised nurses working in general intensive care units in three university-affiliated hospitals. Nurse-directed protocolised-weaning was implemented in one unit (intervention group); two ICUs continued with usual doctor-led practice (control group). Nurses’ perceptions, satisfaction, knowledge and attitudes were measured by self-completed questionnaires before (Phase I) and after the implementation of nurse-directed weaning (Phase II) in all units.
Results:
Response rates were 79% (n=140n=140) for Phase 1 and 62% (n=132n=132) for Phase II. Regression-based analyses showed that changes from Phase I to Phase II were not significantly different between the intervention and control groups. Sixty-nine nurses responded to both Phase I and II questionnaires. In the intervention group, these nurses scored their mean perceived level of knowledge higher in Phase II (6.39 vs 7.17, p=0.01p=0.01). In the control group, role perception (4.41 vs 4.22, p=0.01p=0.01) was lower and, perceived knowledge (6.03 vs 6.63, p=0.04p=0.04), awareness of weaning plans (6.09 vs 7.06, p=0.01p=0.01) and satisfaction with communication (5.28 vs 6.19, p=0.01p=0.01) were higher in Phase II. The intervention group found protocolised weaning useful in their practice (75%): this was scored significantly higher by junior and senior nurses than middle grade nurses (p=0.02p=0.02).
Conclusion
We conclude that nurse-directed protocolised-weaning had no effect on nurses’ views and perceptions due to the high level of satisfaction which encouraged nurses’ participation in weaning throughout. Control group changes are attributed to a ‘reactive effect’ from being study participants. Weaning protocols provide a uniform method of weaning practice and are particularly beneficial in providing safe guidance for junior staff.
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PURPOSE: poly(ADP ribose) polymerase inhibition has been shown to potentiate the cytotoxicity of DNA damaging agents. A phase I study of rucaparib and temozolomide showed that full-dose temozolomide could be given during PARP inhibition. We report the results of a phase II study of intravenous rucaparib 12 mg/m(2) and oral temozolomide 200 mg/m(2) on days 1-5 every 28 days in patients with advanced metastatic melanoma. METHODS: Patients with chemotherapy naïve measurable metastatic melanoma, performance status =2 and good end-organ function were recruited. Treatment was given until progression. A two stage phase II design was used, with response rate the primary endpoint. Population pharmacokinetics and pharmacodynamics were also explored. RESULTS: Forty-six patients were recruited with 37 patients receiving at least 2 cycles and 17 patients at least 6 cycles. Myelosuppression occurred with 25 patients (54 %) requiring a 25 % dose reduction in temozolomide. The response rate was 17.4 %, median time to progression 3.5 months, median overall survival 9.9 months, and 36 % of patients were progression-free at 6 months. CONCLUSIONS: This study showed that temozolomide (150-200 mg/m(2)/day) can safely be given with a PARP inhibitory dose of rucaparib, increasing progression-free survival over historical controls in metastatic melanoma patients.
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FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL's prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14-1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.
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The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status.
METHODS: A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions.
RESULTS: Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values.
CONCLUSION: The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal 'natural history' studies, and (2) robust reference values for commercially available devices.
Resumo:
Neste trabalho apresenta-se um quadro teórico de referência para a avaliação do ensino online, que pretende situar as actividades definidas e desenvolvidas pelos docentes no que respeita às Dimensões da Aprendizagem, da Interacção e da Tecnologia. O referencial teórico que baliza este estudo foi desenvolvido tendo em linha de conta directrizes e orientações nacionais e europeias no que diz respeito ao Ensino Superior (ES), em especial em relação à questão da qualidade do ensino e da integração das tecnologias da informação e da comunicação no currículo. Desta forma, pretendeu-se cumprir um dos objectivos desta investigação, ou seja, contribuir para o desenvolvimento de um quadro conceptual enquadrador do pensamento sobre a avaliação do eLearning no ES e, em particular, das actividades de ensino online. Com base nos pressupostos teóricos definidos, desenvolveram-se dois instrumentos de avaliação que permitem perspectivar as percepções de docentes e de alunos em relação às actividades de ensino desenvolvidas online. No sentido de se definir um público-alvo para testar estes instrumentos, levou-se a cabo um estudo empírico que compreende três fases. A Fase I foi de cariz eminentemente exploratório, uma vez que se inquiriram todos os Estabelecimentos de Ensino Superior (EES) portugueses, com vista a caracterizar o panorama nacional no que releva da utilização de plataformas de eLearning por parte dos EES portugueses, outro objectivo deste trabalho. A Fase II constituiu o momento em que se aplicou pela primeira vez o instrumento de avaliação, apenas dirigido aos docentes, uma vez que universo de respondentes, a considerar-se também os alunos, seria de difícil gestão. Na Fase III seleccionou-se um universo mais reduzido (os quatro cursos de 3.º ciclo ministrados em bLearning em Portugal no ano lectivo de 2009/10), o que permitiu efectivar uma avaliação destes cursos na perspectiva dos docentes e também dos alunos (segundo instrumento de avaliação). Analisados os resultados obtidos nestas três fases, termina-se com a convicção de que se trata de um modelo de avaliação do ensino online passível de ser aplicado ao ES. Isto porque permite não só caracterizar os vários cenários de ensino online através das dimensões de avaliação estabelecidas, como também ter uma percepção bastante clara da forma como as directrizes nacionais e europeias relativas ao ES estão a ser implementadas. Por fim, são feitas propostas para investigação futura, em especial no que se refere à disponibilização online dos instrumentos de avaliação criados e ao desenvolvimento de estudos de investigação-acção que permitam a emergência de eventuais ajustes dos instrumentos e a identificação dos efeitos da sua utilização no aperfeiçoamento das práticas de ensino online.
Resumo:
As ciências são um elemento central da cultura contemporânea pelo que a educação científica tem de ser vista como um direito essencial dos cidadãos. A qualidade do ensino das ciências na escola torna-se, portanto, um especial foco de interesse, científico, político e social, ao nível local, nacional, e global. A investigação em educação em ciências tem produzido conhecimentos que permitem compreender os problemas e fundamentar decisões conducentes a um ensino de ciências ajustado aos desafios atuais. Por outro lado, várias organizações internacionais (UE, OCDE e UNESCO) também têm produzido documentos que visam regular as políticas globais de ensino de ciências, assumindo que a educação científica dos cidadãos é uma condição para a prosperidade económica e social de qualquer estado. Assim, atualmente, existe um acervo documental extenso e diverso relativo ao ensino de ciências, pelo que se impõe um exercício de análise e síntese que identifique quais as orientações-chave que devem ser consideradas. O ensino de nível secundário (ISCE2 e ISCE3), sendo uma etapa em que os jovens fazem escolhas pessoais e vocacionais importantes, merece particular atenção, pois diversos estudos revelam que regista níveis preocupantes de abandono e de desinteresse pelas áreas científicas e tecnológicas. Sendo as práticas dos professores um dos principais fatores de inovação e mudança importa sistematizar os conhecimentos científicos que explicam a sua complexidade e podem orientar a promoção da sua qualidade. O estudo que se apresenta situa-se na confluência de todos estes interesses e visou duas finalidades: delimitar um conceito unificador que permita estudar e desenvolver a qualidade das práticas dos professores de ciências de nível secundário; desenvolver um instrumento de inquérito que operacionalize esse conceito, numa perspetiva de investigação, formação e supervisão de práticas de ensino de ciências. O plano da investigação decorreu em duas fases. Na fase I foi delimitado o conceito perfil de ensino do professor de ciências (PEPC); este estrutura-se em três dimensões – didática, epistemológica e psicológica – cujos referenciais teórico-empíricos decorreram de revisão sistemática de literatura e de abordagem empírica de natureza exploratória e qualitativa, baseada em entrevistas a professores de ciências. Na fase II foi construído e validado o questionário do perfil de ensino do professor de ciências (QPEPC); este contém itens empiricamente situados, construídos a partir do discurso dos professores entrevistados na fase I e seguidamente validados. A validação de QPEPC envolveu dois processos de inquérito por questionário e uma metodologia mista de investigação (análise de conteúdo e análise estatística de dados): a primeira validação contou com um painel internacional de 12 especialistas em didática de ciências; a segunda validação envolveu 184 professores de ciências portugueses. Concluindo-se que QPEPC avalia duas dimensões de PEPC, construíram-se índices e modelos gráficos para facilitar a interpretação dos dados recolhidos. Analisaram-se limitações e potencialidades heurísticas de PEPC e QPEPC, enquanto produtos da investigação, perspetivando o seu uso em contextos diversos, nomeadamente futuras investigações e cenários de formação, reflexão e supervisão de professores de ciências.
Resumo:
Sweroside, a major active iridoid in Swertia pseudochinensis Hara, is recognized as an effective agent in the treatment of liver injury. Based on previous reports, the relatively short half-life (64 min) and poor bioavailability (approximately 0.31%) in rats suggested that not only sweroside itself but also its metabolites could be responsible for the observed hepato-protective effect. However, few studies have been carried out on the metabolism of sweroside. Therefore, the present study aimed at identifying the metabolites of sweroside in rat urine after a single oral dose (100 mg/kg). With ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS), the metabolic profile revealed 11 metabolites in rat urine, including phase I, phase II and aglycone-related products. The chemical structures of metabolites were proposed based on accurate mass measurements of protonated or deprotonated molecules and their fragmentation patterns. Our findings showed that the aglycone of sweroside (M05) and its glucuronide conjugate (M06) were principal circulating metabolites in rats. While several other metabolic transformations, occurring via reduction, N-heterocyclization and N-acetylation after deglycosylation, were also observed. Two metabolites (M05 and M06) were isolated from the rat urine for structural elucidation and identifcation of reaction sites. Both M05 and M06 were characterized by 1H, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy. UHPLC/Q-TOF-MS analysis has provided an important analytical platform to gather metabolic profile of sweroside.
Resumo:
The purposes of this report (Phase II of the project) are to specify in mathematical form the individual modules of the conceptual model developed in Phase I, to identify and evaluate sources of data for the model set, and to develop the transport networks necessary to support the models.
Resumo:
Problématique : La majorité des études publiées sur la réhabilitation par mise en charge immédiate de deux implants non jumelés avec une prothèse totale mandibulaire de recouvrement n’ont rapporté que des mesures cliniques objectives et très peu ont évalué les mesures centrées sur le patient, et ce, avec des erreurs de mesure. Aucune étude n’a évalué les attentes des patients vis-à-vis d'un tel protocole. Objectifs : Évaluer les attentes, le niveau de satisfaction ainsi que la qualité de vie reliée à la santé bucco-dentaire des édentés complets suite à un protocole de mise en charge immédiate. Méthodologie : Cet essai clinique de phase 1 utilise un design pré-post afin d’évaluer les mesures centrées sur le patient. Dix-huit individus, complètement édentés et âgés en moyenne de 62,39 ± 7,65 ans, ont reçu une prothèse totale mandibulaire de recouvrement sur deux implants non jumelés suite à un protocole de mise en charge immédiate, conjointement à une prothèse totale conventionnelle maxillaire. Un instrument adapté pour mesurer leurs attentes à l’aide d’échelles visuelles analogues, le questionnaire « McGill Denture Satisfaction Instrument » ainsi que le questionnaire OHIP-20 ont été remis aux patients avant de procéder aux traitements (T0), ainsi qu’aux rendez-vous de suivi à 2 semaines (T1), 1 mois (T2) et 4 mois (T3). De plus, l’inventaire de personnalité révisé (NÉO PI-R) ainsi qu’un questionnaire sociodémographique ont été remplis par les participants. Les « change scores » ont été calculés puis des tests non paramétriques et des analyses de variances en mesures répétées suivies de comparaisons par paires ont été utilisés afin d’analyser les données recueillies. La taille d’effet a été estimée. Résultats : Les participants avaient différentes attentes par rapport à la mise en charge immédiate. Certains s’attendaient à un effet positif à court terme par rapport à leur apparence esthétique (83,3 %) et à leur vie sociale (55,7 %), alors que d’autres avaient des craintes envers leur confort (5,6 %), leur habileté à mastiquer (11,1 %) et à nettoyer leur prothèse inférieure (11,1 %). À 4 mois, le protocole de mise en charge immédiate avait rencontré la majorité des attentes des patients par rapport à l’esthétique (94.4 %), la mastication (83.3 %), la phonétique (61.1 %), le confort (94.4 %), l’hygiène (88.9 %) et leur vie sociale (88.9 %). Une amélioration statistiquement significative de la satisfaction en générale, du confort, de l’esthétique, de la stabilité de la prothèse inférieure et de l’habileté à mastiquer a été notée à 2 semaines (p<0,001). Également, les comparaisons par paires ont révélé une diminution statistiquement significative du score total de l’OHIP-20 (p < 0,001) de même que la majorité des domaines de l’OHIP (p < 0.01), sauf pour l’handicap social qui n’a diminué significativement qu’après 1 mois (p = 0.01). Ces changements (pour la satisfaction et la qualité de vie) sont restés stables au cours des suivis subséquents. Indépendamment des traits de personnalité et des variables sociodémographiques, le protocole immédiat a satisfait 94,4 % des participants et a amélioré leur qualité de vie avec une large magnitude d’effet (d = 1.9; p < 0.001). Bien que deux patients aient perdu des implants au cours du traitement, 100 % des participants étaient d’accord pour recommander cette procédure à leurs pairs. Conclusions: Le protocole de mise en charge immédiate semble satisfaire les patients quelles que soient leurs attentes. Le protocole MCI peut améliorer, à court terme, la qualité de vie des patients totalement édentés. Les résultats prometteurs de la phase 1 devraient être corroborés lors de la 2e phase de cette étude.
Resumo:
Les centrosomes sont de petits organites qui régulent divers processus cellulaires comme la polarité ou la mitose dans les cellules de mammifères. Ils sont composés de deux centrioles entourés par une matrice péricentriolaire. Ces centrosomes sont les principaux centres organisateurs de microtubules. De plus, ils favorisent la formation de cils, des protubérances sur la surface des cellules quiescentes qui sont critiques pour la transduction du signal. Une grande variété de maladies humaines telles que les cancers ou les ciliopathies sont liées à un mauvais fonctionnement des centrosomes et des cils. C’est pourquoi le but de mes projets de recherche est de comprendre les mécanismes nécessaires à la biogénèse et au fonctionnement des centrosomes et des cils. Tout d'abord, j’ai caractérisé une nouvelle protéine centrosomale nommée nephrocystine - 5 (NPHP5). Cette protéine est localisée dans les cellules en interphase au niveau de la région distale des centrioles. Sa déplétion inhibe la migration des centrosomes à la surface cellulaire lors de l’étape précoce de la formation des cils. NPHP5 interagit avec la protéine CEP290 via sa région C-terminale qui est essentielle pour la ciliogenèse. Elle interagit également avec la calmoduline ce qui empêche son auto-agrégation. J’ai démontré que les domaines de liaison de NHPH5 à CEP290 et à la calmoduline, ainsi que son domaine de localisation centrosomale sont séparables. De plus, j’ai démontré que les protéines NPHP5 présentant des mutations pathogènes ne peuvent plus interagir avec CEP290 et ne sont plus localisées aux centrosomes, rendant ainsi ces protéines non fonctionnelles. Enfin, en utilisant une approche pharmacologique pour moduler les événements en aval dans la voie ciliogénique, j’ai montré que la formation des cils peut être restaurée même en absence de NPHP5. D’autre part, j’ai étudié le rôle de NPHP5 dans l'assemblage et le trafic du complexe BBSome dans le cil. Le BBSome est composé de huit sous-unités différentes qui s’assemblent en un complexe fonctionnel dont on sait peu de chose sur la régulation spatiotemporelle de son processus d'assemblage. J’ai précédemment montré que NPHP5 favorisait la formation des cils et que son dysfonctionnement contribuait au développement de néphronophtise (NPHP). Bien que la NPHP et le syndrome de Bardet-Biedl (BBS) soient des ciliopathies qui partagent des caractéristiques cliniques communes, la base moléculaire de ces ressemblances phénotypiques n’est pas comprise. J’ai constaté que NPHP5, localisé à la base du cil, contient deux sites de liaison distincts pour le BBSome. De plus, j’ai démontré que NPHP5 et son partenaire CEP290 interagissent de façon dynamique avec le BBSome pendant la transition de la prolifération à la quiescence. La déplétion de NPHP5 ou CEP290 conduit à la dissociation d’au moins deux sous-unités du BBSome formant alors un sous-complexe dont la capacité de migration dans le cil n’est pas compromise. J’ai montré que le transport des cargos vers le compartiment ciliaire par ce sous-complexe n’est que partiellement altéré. Enfin, j’ai également concentré mes recherches sur une autre protéine centrosomale peu caractérisée. La protéine centrosomale de 76 kDa (Cep76) a été précédemment impliquée dans le maintien d’une duplication unique des centrioles par cycle cellulaire, et dans une interaction avec la kinase cycline-dépendante 2 (CDK2). Cep76 est préférentiellement phosphorylée par le complexe cycline A/CDK2 sur le site unique S83. Cet événement est essentiel pour supprimer l'amplification des centrioles en phase S. J’ai démontré que Cep76 inhibe cette amplification en bloquant la phosphorylation de Plk1 au niveau des centrosomes. D’autre part, Cep76 peut être acétylée au site K279 en phase G2, ce qui régule négativement son activité et sa phosphorylation sur le site S83. Ces études permettent d'améliorer notre compréhension de la biologie des centrosomes et des cils et pourraient conduire au développement de nouvelles applications diagnostiques et thérapeutiques.
Resumo:
Nanocrystalline Fe–Ni thin films were prepared by partial crystallization of vapour deposited amorphous precursors. The microstructure was controlled by annealing the films at different temperatures. X-ray diffraction, transmission electron microscopy and energy dispersive x-ray spectroscopy investigations showed that the nanocrystalline phase was that of Fe–Ni. Grain growth was observed with an increase in the annealing temperature. X-ray photoelectron spectroscopy observations showed the presence of a native oxide layer on the surface of the films. Scanning tunnelling microscopy investigations support the biphasic nature of the nanocrystalline microstructure that consists of a crystalline phase along with an amorphous phase. Magnetic studies using a vibrating sample magnetometer show that coercivity has a strong dependence on grain size. This is attributed to the random magnetic anisotropy characteristic of the system. The observed coercivity dependence on the grain size is explained using a modified random anisotropy model
Resumo:
El Glioblastoma multiforme (GBM), es el tumor cerebral más frecuente, con pronóstico grave y baja sensibilidad al tratamiento inicial. El propósito de este estudio fue evaluar si la Difusión en RM (IDRM), es un biomarcador temprano de respuesta tumoral, útil para tomar decisiones tempranas de tratamiento y para obtener información pronostica. Metodología La búsqueda se realizo en las bases de datos EMBASE, CENTRAL, MEDLINE; las bibliografías también fueron revisadas. Los artículos seleccionados fueron estudios observacionales (casos y controles, cohortes, corte transversal), no se encontró ningún ensayo clínico; todos los participante tenían diagnostico histopatológico de GBM, sometidos a resección quirúrgica y/o radio-quimioterapia y seguimiento de respuesta al tratamiento con IDRM por al menos 6 meses. Los datos extraídos de forma independiente fueron tipo de estudio, participantes, intervenciones, seguimiento, desenlaces (sobrevida, progresión/estabilización de la enfermedad, muerte) Resultados Quince estudios cumplieron los criterios de inclusión. Entre las técnicas empleadas de IDRM para evaluar respuesta radiológica al tratamiento, fueron histogramas del coeficiente aparente de difusion ADC (compararon valores inferiores a la media y el percentil 10 de ADC, con los valores superiores); encontrando en términos generales que un ADC bajo es un fuerte predictor de sobrevida y/o progresión del tumor. (Esto fue significativo en 5 estudios); mapas funcionales de difusion (FDM) (midieron el porcentaje de cambio de ADC basal vs pos tratamiento) que mostro ser un fuerte predictor de sobrevida en pacientes con progresión tumoral. DISCUSION Desafortunadamente la calidad de los estudios fue intermedia-baja lo que hace que la aplicabilidad de los estudios sea limitada.
Resumo:
El dolor oncológico representa una de las principales causas de dolor crónico, siendo los opioides la primera línea de manejo, sin embargo 10% de los pacientes requieren estrategias analgésicas multimodales. La eficacia analgésica de la clonidina como coadyuvante ha sido demostrada para diversos modelos de dolor. Sin embargo no hay revisiones sistemáticas que validen su eficacia y seguridad en dolor crónico oncológico. Se realizó una revisión sistemática de la literatura a noviembre 26 de 2012, encontrando 15 trabajos (12 reportes de caso y tres ensayos clínicos controlados), n=138 pacientes. La intervención tuvo una eficacia entre 44,7 y 100%, mostrando mayor beneficio en pacientes con componente de dolor neuropático. La adición de clonidina fue bien tolerada, siendo la sedación y la disminución en tensión arterial y frecuencia cardiaca los efectos secundarios más frecuentes, con relación dosis dependiente, de resolución espontánea y en ninguno de los casos se documentó lesión secundaria en los pacientes. La vía de administración más frecuente fue neuroaxial (intratecal y peridural). La revisión sistemática no fue susceptible de metaanálisis por la heterogeneidad clínica de los estudios. Los resultados obtenidos sugieren que la adición de clonidina puede ser una opción terapeútica eficaz y segura en los pacientes con dolor crónico oncológico severo refractario a opioides a altas dosis asociado o no a infusión neuroaxial de anestésico local, en especial en presencia de componente neuropático. Sin embargo se identificó la necesidad de un mayor número de ensayos clínicos controlados aleatorios que permitan establecer conclusiones definitivas.
Resumo:
Introducción: los tumores neuroendocrinos gastroenteropancreáticos se diagnostican en estadio avanzado en 60 - 80% de los pacientes y las opciones terapéuticas son limitadas. Se realizó una revisión sobre el beneficio clínico del tratamiento con [177Lu - DOTA - Tyr3] - Octreotate en pacientes con enfermedad metastásica o inoperable. Objetivos: evaluar la eficacia, impacto en calidad de vida y toxicidad de la terapia con 177Lu DOTATE en pacientes con tumores neuroendocrinos gastroenteropancreáticos avanzados. Materiales y Métodos: se condujo una revisión sistemática de la literatura mediante la búsqueda de estudios clínicos prospectivos y retrospectivos en bases electrónicas (MEDLINE, EMBASE, LILACS, SCIELO, OVID y la Biblioteca Cochrane) de cualquier idioma, año y estado de publicación. Se incluyeron 5 estudios, por la heterogeneidad existente entre los estudios no se realizó un metaanálisis. Resultados: la respuesta tumoral global fue del 45 - 57%, la enfermedad permaneció estable en 27% - 38% y progresó en 6% - 21% de casos en las series incluidas. El tiempo libre de progresión osciló entre 31 - 40 meses y la sobrevida global de 31– 51 meses. Se observó toxicidad hematológica grado 3-4 hasta en 9.5% de pacientes. Hubo mejoría significativa en la calidad de vida de pacientes tratados con 177LuDOTATATE. Conclusiones: la terapia con 177Lu- DOTATATE ofrece un beneficio clínico a los pacientes con tumores neuroendocrinos bien diferenciados avanzados por su impacto positivo en calidad de vida, control de síntomas, ralentiza la progresión tumoral y su toxicidad es baja.