Early childhood constraint therapy for sensory/motor impairment in cerebral palsy: a randomised clinical trial protocol.

INTRODUCTION: Cerebral palsy (CP) is the most common physical disability in childhood. It is a disorder resulting from sensory and motor impairments due to perinatal brain injury, with lifetime consequences that range from poor adaptive and social function to communication and emotional disturbances. Infants with CP have a fundamental disadvantage in recovering motor function: they do not receive accurate sensory feedback from their movements, leading to developmental disregard. Constraint-induced movement therapy (CIMT) is one of the few effective neurorehabilitative strategies shown to improve upper extremity motor function in adults and older children with CP, potentially overcoming developmental disregard. METHODS AND ANALYSIS: This study is a randomised controlled trial of children 12-24197;months corrected age studying the effectiveness of CIMT combined with motor and sensory-motor interventions. The study population will comprise 72 children with CP and 144 typically developing children for a total of N=216 children. All children with CP, regardless of group allocation will continue with their standard of care occupational and physical therapy throughout the study. The research material collected will be in the form of data from high-density array event-related potential scan, standardised assessment scores and motion analysis scores. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board. The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT02567630.

Levetiracetam versus Phenobarbital. Effects in the neurodevelopment in newborns treated for neonatal seizures: a clinical trial

Purpose: To analyze if the use of Phenobarbital compared with Levetiracetam, it’s associated with more neurodevelopmental problems in newborns treated for neonatal seizures. As a secondary objective identify which are the most affected areas of the neurodevelopment: cognition, socio-­‐emotional, motor or language skills.Design: A 5 years long clinical trial administering, with double-­‐blind and a randomized distribution of the sample, Phenobarbital or Levetiracetam for the management of neonatal seizures

Tacrolimus vs. Azathioprine in myasthenia gravis treatment: a multicenter, prospective, randomized, double blind, head to head clinical trial

Current evidences show that tacrolimus could be a good therapeutic option in patients non-responsive to first-line treatments and even it could become one of the first-line drugs for treating MG. Our study will try to determine the effectivity and safety of tacrolimus in 190 myasthenia gravis patients with suboptimal response to azathioprine: after 12 months of treatment they will be randomized to continue with azathioprine or they will be switched to tacrolimus. Patients will follow the allocated treatment during 14 months and the response will be assessed as well as adverse effectsPURPOSE: To compare azathioprine vs. tacrolimus effectivity and safety in MG patients with suboptimal response to azathioprine at 12 monthsDESIGN: A 14 months multicenter, prospective, randomized, double blind, head to head clinical trial

Targeted vs. standard treatment against Helicobacter pylori: safety assessment clinical trial

Helicobacter pylori (H. pylori) is a gram negative bacteria that represents a considerable global burden in the world and is related to many gastrointestinal diseases (peptic ulcer, gastric MALT lymphoma or gastric cancer). Currently the triple standard therapy is less used as there is an increase of the clarithromycin resistance. Therefore patients have to receive several lines of treatment with the consequence of adverse events and the possibility to interrupt the treatment. This is why the main objective is to determine if making a culture and antibiogram to do a targeted treatment cause less adverse events with the same eradication than making an empirical treatment to eradicate H. pylori. The secondary objective is to determine the prevalence of resistance to clarithromycin in the province of GironaThis is a multicentre clinical trial without blinding; patients are selected by non-probabilistic sampling, with a total sample of 868 patients randomized in two equal groups of 434 patients in each group. The study will last 2 years. The endpoints will be to evaluate the adverse events and eradication of each group of patients. Also it will be evaluated the resistance to clarithromycin

Patson Approach versus the Standard Approach for increasing breast reconstruction rates in women undergoing mastectomy. A randomized, controlled, open-label clinical trial

Breast cancer is the most prevalent neoplasm among women in the majority of countries worldwide. Breast cancer treatment include mastectomy which is associated to strong impact in women. Breast reconstruction is an option for many women to re-establish their body image and also to decrease psychological impact. However, breast reconstruction rates are low and many factors are involved in not undergoing breast reconstruction. Patient involvement in the decision-making process increases breast reconstruction rates and is associated to higher satisfaction and less anxiety and depression symptoms. More physician-patient relation and more education in terms of breast reconstruction are needed to achieve our objective. A new approach of medical care, called Patson Approach, is created in order to meet our goal with more patient involvement, as well as, physician and psychological counsellingObjective: to increase breast reconstruction rates in women who are candidates for breast reconstruction after mastectomy and are included in the Patson Approach compared to women included in the Standard ApproachMethods: the study design will be a randomized, controlled, open-label clinical trial. 62 patients will be recruited during two years and randomly divided in two groups, 31 will be included in the Standard Approach and 31 will be included in the Patson Approach. Preoperative and postoperative appointments are established in order to do a follow-up of the patients and collect all the data

Effectiveness of an illustrated home exercise guide on promoting urinary continence during pregnancy: a pragmatic randomized clinical trial

OBJETIVO: Avaliar a efetividade de um manual de orientação de exercícios domiciliares (MOED) para o assoalho pélvico (AP) na promoção da continência urinária em gestantes primigestas.MÉTODOS: Ensaio clínico com 87 participantes, avaliadas 6 vezes durante a gestação e divididas aleatoriamente em 3 grupos: Grupo supervisionado (Gsup), que praticou exercícios com supervisão; Grupo observado (Gobs), que praticou exercícios sem supervisão, e Grupo referência (Gref), que não praticou exercícios. Incontinência urinária (IU) (desfecho primário) e força muscular perineal (FMP) (desfecho secundário) foram avaliadas por intermédio de diário de perdas urinárias e perineometria, respectivamente. Foram utilizados o teste de Kruskal-Wallis, seguido do teste post hoc de Dunn, para variáveis contínuas, e o teste do χ2 e testes Z, com correções de Bonferroni, para proporções, com nível de significância de 5%.RESULTADOS: O Gsup e o Gobs apresentaram 6,9% de gestantes incontinentes, enquanto o Gref apresentou 96,6% de incontinentes. Quanto à FMP, o Gsup e o Gobs apresentaram valores médios de contração de 10 e 8,9 cmH2O, respectivamente, enquanto o Gref apresentou valor de 4,7 cmH2O. Ambos os resultados significantes.CONCLUSÃO: A utilização de um MOED é eficaz na promoção da continência urinária e no aumento da FMP em gestantes primigestas, independentemente de supervisão permanente.

Phase 1 Map

Phase 1 Map of the Master Plan showing the Tower and Thistle Complex, along with some additional buildings and the main parking lot. Note the location of the Central Utilities Building to the east differs from it's actual location along the escarpment.

La survie implantaire suite à une réhabilitation par mise en charge immédiate d’une prothèse totale mandibulaire reliée à deux implants non jumelés : une étude pilote expérimentale

Problématique : Les connaissances théoriques et pratiques au sujet de la mise en charge immédiate d’implants non jumelés chez les édentés sont limitées. Objectifs : Cette étude avait pour but de : (1) déterminer le taux de survie implantaire de 2 implants non jumelés supportant une prothèse totale mandibulaire suite à une mise en charge immédiate, (2) évaluer les changements des niveaux osseux et de stabilité implantaire survenus sur ces 2 implants durant une période de 4 mois et les comparer à un implant témoin, et (3) décrire les complications cliniques associées à ce mode de mise en charge. Méthodologie : Chez 18 individus édentés (âge moyen de 62±7 ans), cette étude de phase I avec un design pré/post a évalué les résultats cliniques suivant la mise en charge immédiate (<48 heures) de 2 implants non jumelés par une prothèse totale mandibulaire. À l’aide de radiographies périapicales, de sondages osseux et d’analyses de la fréquence en résonnance, les niveaux osseux péri-implantaires (en mm) et les niveaux de stabilité implantairte (en ISQ) de ces 2 implants insérés dans la région parasymphysaire ont été évalués à la chirurgie (T0) et au suivi de 4 mois (T1). Un implant non submergé et sans mise en charge inséré dans la région de la symphyse mandibulaire a été utilisé comme témoin. Les données ont été analysées avec des modèles mixtes linéaires, la méthode de Tukey ajustée, l’analyse de variance de Friedman et des tests de rang signés de Wilcoxon. Résultats : De T0 à T1, 3 implants mis en charge immédiatement ont échoué chez 2 patients. Le taux de survie implantaire obtenu était donc de 91,7% (33/36) et, par patient, de 88,9% (16/18). Aucun implant témoin n’a échoué. Les changements osseux documentés radiologiquement et par sondage autour des implants mis en charge immédiatement étaient, respectivement, de -0,2 ± 0,3 mm et de -0,5 ± 0,6 mm. Les pertes d’os de support implantaire n’ont pas été démontrées statistiquement différentes entre les implants avec mise en charge immédiate et les témoins. Les niveaux moyens de stabilité implantaire ont augmenté de 5 ISQ indépendamment de la mise en charge. Les niveaux moyens d’ISQ n’ont pas été démontrés statistiquement différents entre les implants avec mise en charge immédiate et les témoins à T0 ou T1. Cinq des 18 patients n’ont expérimenté aucune complication clinique, alors que 9 en ont eu au moins deux. Hormis les échecs implantaires, aucune de ces complications n’a entraîné de changements au protocole. Conclusion : Les résultats à court terme suggèrent que : (1) le taux de survie implantaire suite au protocole immédiat est similaire à ceux rapportés lors d’un protocole de mise en charge conventionnel (2) les changements d’os de support implantaire et de stabilité ne sont pas différents comparativement à ceux d’un implant témoin, (3) un niveau élevé d’expérience clinique et chirurgicale est requis pour effectuer les procédures et pour gérer les complications associées. Ces résultats préliminaires devraient être confirmés dans une étude clinique de phase II.

An adaptive approach to implementing bivariate group sequential clinical trial designs

In clinical trials, situations often arise where more than one response from each patient is of interest; and it is required that any decision to stop the study be based upon some or all of these measures simultaneously. Theory for the design of sequential experiments with simultaneous bivariate responses is described by Jennison and Turnbull (Jennison, C., Turnbull, B. W. (1993). Group sequential tests for bivariate response: interim analyses of clinical trials with both efficacy and safety endpoints. Biometrics 49:741-752) and Cook and Farewell (Cook, R. J., Farewell, V. T. (1994). Guidelines for monitoring efficacy and toxicity responses in clinical trials. Biometrics 50:1146-1152) in the context of one efficacy and one safety response. These expositions are in terms of normally distributed data with known covariance. The methods proposed require specification of the correlation, ρ between test statistics monitored as part of the sequential test. It can be difficult to quantify ρ and previous authors have suggested simply taking the lowest plausible value, as this will guarantee power. This paper begins with an illustration of the effect that inappropriate specification of ρ can have on the preservation of trial error rates. It is shown that both the type I error and the power can be adversely affected. As a possible solution to this problem, formulas are provided for the calculation of correlation from data collected as part of the trial. An adaptive approach is proposed and evaluated that makes use of these formulas and an example is provided to illustrate the method. Attention is restricted to the bivariate case for ease of computation, although the formulas derived are applicable in the general multivariate case.

Decision-theoretic designs for phase II clinical trials allowing for competing studies

This article describes an approach to optimal design of phase II clinical trials using Bayesian decision theory. The method proposed extends that suggested by Stallard (1998, Biometrics54, 279–294) in which designs were obtained to maximize a gain function including the cost of drug development and the benefit from a successful therapy. Here, the approach is extended by the consideration of other potential therapies, the development of which is competing for the same limited resources. The resulting optimal designs are shown to have frequentist properties much more similar to those traditionally used in phase II trials.

An illustration of the modelling of cost and efficacy data from a clinical trial

Health care providers, purchasers and policy makers need to make informed decisions regarding the provision of cost-effective care. When a new health care intervention is to be compared with the current standard, an economic evaluation alongside an evaluation of health benefits provides useful information for the decision making process. We consider the information on cost-effectiveness which arises from an individual clinical trial comparing the two interventions. Recent methods for conducting a cost-effectiveness analysis for a clinical trial have focused on the net benefit parameter. The net benefit parameter, a function of costs and health benefits, is positive if the new intervention is cost-effective compared with the standard. In this paper we describe frequentist and Bayesian approaches to cost-effectiveness analysis which have been suggested in the literature and apply them to data from a clinical trial comparing laparoscopic surgery with open mesh surgery for the repair of inguinal hernias. We extend the Bayesian model to allow the total cost to be divided into a number of different components. The advantages and disadvantages of the different approaches are discussed. In January 2001, NICE issued guidance on the type of surgery to be used for inguinal hernia repair. We discuss our example in the light of this information. Copyright © 2003 John Wiley & Sons, Ltd.