902 resultados para Arthritis Clinical-trials


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Introducción: El sincope vasovagal es la principal causa de pérdida transitoria de la consciencia. Las guías internacionales de tratamiento del síncope recomiendan con un nivel de evidencia débil, el implante de marcapasos para pacientes refractarios al tratamiento médico que tienen respuesta cardioinhibitoria. Hasta el momento no existe una revisión sistemática que resuma la mejor evidencia disponible a la fecha sobre la estimulación con marcapasos en síncope vasovagal para disminuir recurrencias. Métodos: Revisión sistemática de la literatura de ensayos clínicos aleatorizados acerca del uso del marcapasos en síncope vasovagal para disminuir recurrencias. Resultados: La búsqueda inicial arrojó un total de 299 resultados, de los cuales solo 8 cumplieron los criterios de selección. Se evaluó la recurrencia de síncopes en el grupo de estimulación con marcapasos comparada con el grupo sin estimulación. Con diferencias metodológicas marcadas en los estudios seleccionados en general no hay una evidencia sólida para asegurar que el marcapasos disminuye recurrencias de síncope vasovagal. Discusión: El marcapasos en síncope vasovagal no tiene efecto benéfico en disminución de recurrencias cuando se implanta a toda la población refractaria al tratamiento médico para disminuir recurrencias. Solamente un grupo con características clínicas muy seleccionadas podría beneficiarse de la estimulación con marcapasos para disminuir recurrencias de síncope. Conclusión: La evidencia disponible sugiere que el marcapasos no tiene efecto en disminución de recurrencias en todo el grupo de pacientes con síncope vasovagal refractarios a tratamiento médico.

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Introducción: La depresión se presenta frecuentemente en pacientes con esquizofrenia, en las diferentes fases de esta y, dada su similitud con diferentes síntomas propios de la esquizofrenia, su identificación resulta difícil. El objetivo del presente estudio es determinar la efectividad y seguridad de la Quetiapina en la disminución de síntomas depresivos comparada con otros antipsicóticos de segunda generación en pacientes con esquizofrenia. Metodología: se realizó una revisión sistemática de la literatura en 6 bases de datos de acuerdo con la metodología PRISMA, que incluyó estudios de efectividad y seguridad de la Quetiapina (Seroquel®) en pacientes con esquizofrenia y depresión. Los desenlaces fueron medidos mediante escalas para depresión, tasas de suicidio y efectos adversos. Resultados: Se incluyeron dos estudios. El estudio de Di Fiorino en 2014, reportó efectividad de Quetiapina en el tratamiento de pacientes psicóticos con depresión con una diferencia de las reducciones de mínimos cuadrados de la escala CDSS de 2.2 IC 95% (0.8 -3.7) frente a risperidona, y de 3.3 (p<0.0001) en la escala HAM-D frente a risperidona. Los efectos adversos presentados con quetiapina fueron: somnolencia, boca seca, hipotensión. No se reportaron muertes por quetiapina. Discusión: La quetiapina demostró ser efectiva y segura en el manejo de los síntomas depresivos en pacientes con esquizofrenia frente a risperidona al valorar la población con escala CDSS. No fueron reportados desenlaces de suicidio en ninguno de los estudios. La calidad de la evidencia es moderada con sesgos metodológicos importantes. Es necesaria la realización de más estudios clínicos aleatorizados y con cegamiento y estudios de metaanálisis en población homogénea

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Dentro del marco del aborto involuntario recurrente (AIR), se han propuesto causas autoinmunes y alogénicas, e implementación de terapias como la inmunización activa con leucocitos alogénicos de la pareja o de donantes. La evidencia disponible en cuanto a la efectividad de estos tratamientos es contradictoria, por lo que se desea realizar una revisión sistemática para evaluar la efectividad de la inmunización activa con leucocitos alogénicos de la pareja o de donantes para esta condición. Se realizó un estudio tipo revisión sistemática de la literatura, usando las siguientes bases de datos: Medline, Embase, Cochrane Library y Scielo. Se realizó una búsqueda a través del registro de ensayos clínicos del Instituto Nacional de Salud de los Estados Unidos (www.clinicaltrials.gov) y, una búsqueda manual a través de las referencias de los estudios seleccionados siguiendo la estrategia de bola de nieve. Se seleccionaron ensayos clínicos y estudios de cohorte analítica, en idioma inglés y español. Se realizó un análisis cuantitativo de la información por medio de un metaanálisis. El tratamiento inmunomodulador con linfocitos puede considerarse como una terapia efectiva para mantener la gestación y lograr recién nacido vivo según resultados estadísticos; sin embargo la calidad de los estudios incluidos es baja, por lo que no se aconseja para la práctica rutinaria. Se sugiere la realización de estudios con metodologías robustas y que apoyen los resultados presentados en esta investigación.

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INTRODUCCIÓN: El 80% de los niños y adolescentes con trastornos del espectro autista (TEA) presenta algún trastorno del sueño, en cuya génesis al parecer intervienen alteraciones en la regulación de la melatonina. El objetivo de este metaanálisis fue determinar la eficacia y seguridad de la melatonina para el manejo de ciertos trastornos del sueño en niños con TEA. MÉTODOS: Tres revisores extrajeron los datos relevantes de los ensayos clínicos aleatorizados doble ciego de alta calidad publicados en bases de datos primarias, de ensayos clínicos, de revisiones sistemáticas y de literatura gris; además se realizó búsqueda en bola de nieve. Se analizaron los datos con RevMan 5.3. Se realizó un análisis del inverso de la varianza por un modelo de efectos aleatorios para las diferencias de medias de los desenlaces propuestos: duración del tiempo total, latencia de sueño y número de despertares nocturnos. Se evaluó la heterogeneidad interestudios con el parámetro I2 RESULTADOS: La búsqueda inicial arrojó 355 resultados, de los cuales tres cumplieron los criterios de selección. La melatonina resultó ser un medicamento seguro y eficaz para aumentar la duración total del sueño y disminuir la latencia de sueño en niños y adolescentes con TEA; hasta el momento la evidencia sobre el número de despertares nocturnos no es estadísticamente significativa. DISCUSIÓN: A la luz de la evidencia disponible, la melatonina es una elección segura y eficaz para el manejo de ciertos problemas del sueño en niños y adolescentes con TEA. Es necesario realizar estudios con mayores tamaños muestrales y comparados con otros medicamentos disponibles en el mercado.

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A nanotecnologia, e a sua aplicação na área da biomedicina, em particular na terapêutica e diagnóstico oncológico, tem sido alvo de um desenvolvimento exponencial, com impacto profundo no que respeita a cuidados de saúde. O cancro é uma das doenças que afecta mais pessoas a nível mundial, com elevados índices de mortalidade, níveis de sofrimento físico e emocional e, encargos para o doente, família e sociedade. É uma doença complexa, e a prática clínica convencional constitui um paradigma, na medida em que se revela insuficiente e extremamente agressiva, expondo o doente a medicamentos citotóxicos, não específicos, com elevada toxicidade sistémica e efeitos adversos. A Nanomedicina, e a exploração das propriedades únicas das nanopartículas, apresenta a potencialidade de melhorar a capacidade de detecção e diagnóstico do cancro e, aumentar a especificidade e efectividade no tratamento das células tumorais. No entanto, o recurso a nanotecnologias continua a ser alvo de alguma controvérsia e cepticismo por parte de alguns elementos das comunidades científicas e académica. Com nanoprodutos já aprovados e utilizados em prática clínica e muitos outros em desenvolvimento e investigação em ensaios clínicos, a realização deste trabalho tem como objectivo compreender os conceitos de nanotecnologia e Nanomedicina, perceber o estado da arte, ponderando as vantagens e desvantagens da abordagem “nano” e a sua real aplicação à terapêutica oncológica.

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Nas últimas décadas, a investigação de antibióticos com novos mecanismos de acção, tem vindo a ser motivada pela contínua emergência de estirpes bacterianas multirresistentes. No entanto, nos últimos anos esse desenvolvimento tem vindo a abrandar, o que representa um grave problema de saúde pública. Antes da era dos antibióticos a fagoterapia representava a terapêutica de primeira linha no tratamento de infecções bacterianas. Como a ausência de recursos impossibilitava a compreensão dos mecanismos de acção moleculares do fago, a fagoterapia era apenas sustentada pelo conhecimento empírico. A ausência de conhecimento associada ao início da era dos antibióticos foram condições suficientes para que a terapêutica fágica fosse posta de parte, à excepção de alguns países da Europa do Leste. De acordo com a literatura disponibilizada por estes países, vários têm sido os casos de sucesso no tratamento de infecções bacterianas, incluindo infecções causadas por estirpes multirresistentes aos antibióticos convencionais. No entanto, contrariamente aos ensaios clínicos, a maioria destes estudos omite informação crítica que impossibilita a interpretação dos respectivos resultados. Actualmente, as novas ferramentas oferecidas pelos avanços biotecnológicos possibilitam não só a compreensão do mecanismo de infecção bacteriana como também permitem compreender melhor a interacção entre os bacteriófagos e o organismo humano. Como tal, no futuro, a fagoterapia pode ser considerada uma alternativa efectiva para solucionar os casos críticos de multirresistência bacteriana aos antibióticos convencionais.

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Background and purpose: Carisbamate is being developed for adjuvant treatment of partial onset epilepsy. Carisbamate produces anticonvulsant effects in primary generalized, complex partial and absence-type seizure models, and exhibits neuroprotective and antiepileptogenic properties in rodent epilepsy models. Phase IIb clinical trials of carisbamate demonstrated efficacy against partial onset seizures; however, its mechanisms of action remain unknown. Here, we report the effects of carisbamate on membrane properties, evoked and spontaneous synaptic transmission and induced epileptiform discharges in layer II-III neurones in piriform cortical brain slices. Experimental approach: Effects of carisbamate were investigated in rat piriform cortical neurones by using intracellular electrophysiological recordings. Key results: Carisbamate (50–400 mmol·L-1) reversibly decreased amplitude, duration and rise-time of evoked action potentials and inhibited repetitive firing, consistent with use-dependent Na+ channel block; 150–400 mmol·L-1 carisbamate reduced neuronal input resistance, without altering membrane potential. After microelectrode intracellular Cl- loading, carisbamate depolarized cells, an effect reversed by picrotoxin. Carisbamate (100–400 mmol·L-1) also selectively depressed lateral olfactory tract-afferent evoked excitatory synaptic transmission (opposed by picrotoxin), consistent with activation of a presynaptic Cl conductance. Lidocaine (40–320 mmol·L-1) mimicked carisbamate, implying similar modes of action. Carisbamate (300–600 mmol·L-1) had no effect on spontaneous GABAA miniature inhibitory postsynaptic currents and at lower concentrations (50–200 mmol·L-1) inhibited Mg2+-free or 4-aminopyridine-induced seizure-like discharges. Conclusions and implications: Carisbamate blocked evoked action potentials use-dependently, consistent with a primary action on Na+ channels and increased Cl- conductances presynaptically and, under certain conditions, postsynaptically to selectively depress excitatory neurotransmission in piriform cortical layer Ia-afferent terminals.

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The different compartments of the gastrointestinal tract are inhabited by populations of micro-organisms. By far the most important predominant populations are in the colon where a true symbiosis with the host exists that is a key for well-being and health. For such a microbiota, 'normobiosis' characterises a composition of the gut 'ecosystem' in which micro-organisms with potential health benefits predominate in number over potentially harmful ones, in contrast to 'dysbiosis', in which one or a few potentially harmful micro-organisms are dominant, thus creating a disease-prone situation. The present document has been written by a group of both academic and industry experts (in the ILSI Europe Prebiotic Expert Group and Prebiotic Task Force, respectively). It does not aim to propose a new definition of a prebiotic nor to identify which food products are classified as prebiotic but rather to validate and expand the original idea of the prebiotic concept (that can be translated in 'prebiotic effects'), defined as: 'The selective stimulation of growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host.' Thanks to the methodological and fundamental research of microbiologists, immense progress has very recently been made in our understanding of the gut microbiota. A large number of human intervention studies have been performed that have demonstrated that dietary consumption of certain food products can result in statistically significant changes in the composition of the gut microbiota in line with the prebiotic concept. Thus the prebiotic effect is now a well-established scientific fact. The more data are accumulating, the more it will be recognised that such changes in the microbiota's composition, especially increase in bifidobacteria, can be regarded as a marker of intestinal health. The review is divided in chapters that cover the major areas of nutrition research where a prebiotic effect has tentatively been investigated for potential health benefits. The prebiotic effect has been shown to associate with modulation of biomarkers and activity(ies) of the immune system. Confirming the studies in adults, it has been demonstrated that, in infant nutrition, the prebiotic effect includes a significant change of gut microbiota composition, especially an increase of faecal concentrations of bifidobacteria. This concomitantly improves stool quality (pH, SCFA, frequency and consistency), reduces the risk of gastroenteritis and infections, improves general well-being and reduces the incidence of allergic symptoms such as atopic eczema. Changes in the gut microbiota composition are classically considered as one of the many factors involved in the pathogenesis of either inflammatory bowel disease or irritable bowel syndrome. The use of particular food products with a prebiotic effect has thus been tested in clinical trials with the objective to improve the clinical activity and well-being of patients with such disorders. Promising beneficial effects have been demonstrated in some preliminary studies, including changes in gut microbiota composition (especially increase in bifidobacteria concentration). Often associated with toxic load and/or miscellaneous risk factors, colon cancer is another pathology for which a possible role of gut microbiota composition has been hypothesised. Numerous experimental studies have reported reduction in incidence of tumours and cancers after feeding specific food products with a prebiotic effect. Some of these studies (including one human trial) have also reported that, in such conditions, gut microbiota composition was modified (especially due to increased concentration of bifidobacteria). Dietary intake of particular food products with a prebiotic effect has been shown, especially in adolescents, but also tentatively in postmenopausal women, to increase Ca absorption as well as bone Ca accretion and bone mineral density. Recent data, both from experimental models and from human studies, support the beneficial effects of particular food products with prebiotic properties on energy homaeostasis, satiety regulation and body weight gain. Together, with data in obese animals and patients, these studies support the hypothesis that gut microbiota composition (especially the number of bifidobacteria) may contribute to modulate metabolic processes associated with syndrome X, especially obesity and diabetes type 2. It is plausible, even though not exclusive, that these effects are linked to the microbiota-induced changes and it is feasible to conclude that their mechanisms fit into the prebiotic effect. However, the role of such changes in these health benefits remains to be definitively proven. As a result of the research activity that followed the publication of the prebiotic concept 15 years ago, it has become clear that products that cause a selective modification in the gut microbiota's composition and/or activity(ies) and thus strengthens normobiosis could either induce beneficial physiological effects in the colon and also in extra-intestinal compartments or contribute towards reducing the risk of dysbiosis and associated intestinal and systemic pathologies.

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In this paper a robust method is developed for the analysis of data consisting of repeated binary observations taken at up to three fixed time points on each subject. The primary objective is to compare outcomes at the last time point, using earlier observations to predict this for subjects with incomplete records. A score test is derived. The method is developed for application to sequential clinical trials, as at interim analyses there will be many incomplete records occurring in non-informative patterns. Motivation for the methodology comes from experience with clinical trials in stroke and head injury, and data from one such trial is used to illustrate the approach. Extensions to more than three time points and to allow for stratification are discussed. Copyright © 2005 John Wiley & Sons, Ltd.

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The proportional odds model provides a powerful tool for analysing ordered categorical data and setting sample size, although for many clinical trials its validity is questionable. The purpose of this paper is to present a new class of constrained odds models which includes the proportional odds model. The efficient score and Fisher's information are derived from the profile likelihood for the constrained odds model. These results are new even for the special case of proportional odds where the resulting statistics define the Mann-Whitney test. A strategy is described involving selecting one of these models in advance, requiring assumptions as strong as those underlying proportional odds, but allowing a choice of such models. The accuracy of the new procedure and its power are evaluated.

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Assaying a large number of genetic markers from patients in clinical trials is now possible in order to tailor drugs with respect to efficacy. The statistical methodology for analysing such massive data sets is challenging. The most popular type of statistical analysis is to use a univariate test for each genetic marker, once all the data from a clinical study have been collected. This paper presents a sequential method for conducting an omnibus test for detecting gene-drug interactions across the genome, thus allowing informed decisions at the earliest opportunity and overcoming the multiple testing problems from conducting many univariate tests. We first propose an omnibus test for a fixed sample size. This test is based on combining F-statistics that test for an interaction between treatment and the individual single nucleotide polymorphism (SNP). As SNPs tend to be correlated, we use permutations to calculate a global p-value. We extend our omnibus test to the sequential case. In order to control the type I error rate, we propose a sequential method that uses permutations to obtain the stopping boundaries. The results of a simulation study show that the sequential permutation method is more powerful than alternative sequential methods that control the type I error rate, such as the inverse-normal method. The proposed method is flexible as we do not need to assume a mode of inheritance and can also adjust for confounding factors. An application to real clinical data illustrates that the method is computationally feasible for a large number of SNPs. Copyright (c) 2007 John Wiley & Sons, Ltd.

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This paper considers the problem of estimation when one of a number of populations, assumed normal with known common variance, is selected on the basis of it having the largest observed mean. Conditional on selection of the population, the observed mean is a biased estimate of the true mean. This problem arises in the analysis of clinical trials in which selection is made between a number of experimental treatments that are compared with each other either with or without an additional control treatment. Attempts to obtain approximately unbiased estimates in this setting have been proposed by Shen [2001. An improved method of evaluating drug effect in a multiple dose clinical trial. Statist. Medicine 20, 1913–1929] and Stallard and Todd [2005. Point estimates and confidence regions for sequential trials involving selection. J. Statist. Plann. Inference 135, 402–419]. This paper explores the problem in the simple setting in which two experimental treatments are compared in a single analysis. It is shown that in this case the estimate of Stallard and Todd is the maximum-likelihood estimate (m.l.e.), and this is compared with the estimate proposed by Shen. In particular, it is shown that the m.l.e. has infinite expectation whatever the true value of the mean being estimated. We show that there is no conditionally unbiased estimator, and propose a new family of approximately conditionally unbiased estimators, comparing these with the estimators suggested by Shen.

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Bayesian decision procedures have recently been developed for dose escalation in phase I clinical trials concerning pharmacokinetic responses observed in healthy volunteers. This article describes how that general methodology was extended and evaluated for implementation in a specific phase I trial of a novel compound. At the time of writing, the study is ongoing, and it will be some time before the sponsor will wish to put the results into the public domain. This article is an account of how the study was designed in a way that should prove to be safe, accurate, and efficient whatever the true nature of the compound. The study involves the observation of two pharmacokinetic endpoints relating to the plasma concentration of the compound itself and of a metabolite as well as a safety endpoint relating to the occurrence of adverse events. Construction of the design and its evaluation via simulation are presented.

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OBJECTIVES: To evaluate the evidence for strategies to prevent falls or fractures in residents in care homes and hospital inpatients and to investigate the effect of dementia and cognitive impairment. DESIGN: Systematic review and meta-analyses of studies grouped by intervention and setting (hospital or care home). Meta-regression to investigate the effects of dementia and of study quality and design. DATA SOURCES: Medline, CINAHL, Embase, PsychInfo, Cochrane Database, Clinical Trials Register, and hand searching of references from reviews and guidelines to January 2005. RESULTS: 1207 references were identified, including 115 systematic reviews, expert reviews, or guidelines. Of the 92 full papers inspected, 43 were included. Meta-analysis for multifaceted interventions in hospital (13 studies) showed a rate ratio of 0.82 (95% confidence interval 0.68 to 0.997) for falls but no significant effect on the number of fallers or fractures. For hip protectors in care homes (11 studies) the rate ratio for hip fractures was 0.67 (0.46 to 0.98), but there was no significant effect on falls and not enough studies on fallers. For all other interventions (multifaceted interventions in care homes; removal of physical restraints in either setting; fall alarm devices in either setting; exercise in care homes; calcium/vitamin D in care homes; changes in the physical environment in either setting; medication review in hospital) meta-analysis was either unsuitable because of insufficient studies or showed no significant effect on falls, fallers, or fractures, despite strongly positive results in some individual studies. Meta-regression showed no significant association between effect size and prevalence of dementia or cognitive impairment. CONCLUSION: There is some evidence that multifaceted interventions in hospital reduce the number of falls and that use of hip protectors in care homes prevents hip fractures. There is insufficient evidence, however, for the effectiveness of other single interventions in hospitals or care homes or multifaceted interventions in care homes.