Trials
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Randomized Controlled Trial Comparative Study
Evaluation of different doses of transcutaneous nerve stimulation for pain relief during labour: a randomized controlled trial.
Pain during labour is one of the most intense pain that women may experience in their lifetime. There are several non-pharmacological analgesic methods to relieve pain during labour, among them transcutaneous electrical nerve stimulation (TENS). TENS is a low-frequency electrotherapy technique, analgesic type, generally used in musculoskeletal pathology, but it has also come to be used as an alternative treatment during labour. The purpose of this study is to investigate the pain-relieving effect of a TENS application during labour and to find out the most effective dose. ⋯ TENS with high frequencies modified in time as well as high pulse width are effective for relieving labour pain, and they are well considered by pregnant participants.
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Lung dysfunction commonly occurs after cardiopulmonary bypass (CPB). Randomized evidence suggests that the presence of expiratory flow limitation (EFL) in major abdominal surgery is associated with postoperative pulmonary complications. Appropriate lung recruitment and a correctly set positive end-expiratory pressure (PEEP) level may prevent EFL. According to the available data in the literature, an adequate ventilation strategy during cardiac surgery is not provided. The aim of this study is to assess whether a mechanical ventilation strategy based on optimal lung recruitment with a best PEEP before and after CPB and with a continuous positive airway pressure (CPAP) during CPB would reduce the incidence of respiratory complications after cardiac surgery. ⋯ This study will help to establish a correct ventilatory strategy before, after, and during CPB. The main purpose is to establish if a ventilation based on a simple and feasible respiratory test may preserve lung function in cardiac surgery.
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Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretroviral therapy (ART). Mortality is driven in part by limited availability of amphotericin-based treatment, drug-induced toxicities of amphotericin B deoxycholate and prolonged hospital admissions. A single, high-dose of liposomal amphotericin (L-AmB, Ambisome) on a fluconazole backbone has been reported as non-inferior to 14 days of standard dose L-AmB in reducing fungal burden. This trial examines whether single, high-dose L-AmB given with high-dose fluconazole and flucytosine is non-inferior to a seven-day course of amphotericin B deoxycholate plus flucytosine (the current World Health Organization [WHO] recommended treatment regimen). ⋯ A safe, sustainable and easy to administer regimen of L-AmB that is non-inferior to seven days of daily amphotericin B deoxycholate therapy may reduce the number of adverse events seen in patients treated with amphotericin B deoxycholate and shorten hospital admissions, providing a highly favourable and implementable alternative to the current WHO recommended first-line treatment.
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Despite the positive outcomes of the use of noninvasive positive pressure ventilation (NPPV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), NPPV fails in approximately 15% of patients with AECOPD, possibly because the inspiratory pressure delivered by conventional low-intensity NPPV is insufficient to improve ventilatory status for these patients. High-intensity NPPV, a novel form that delivers high inspiratory pressure, is believed to more efficiently augment alveolar ventilation than low-intensity NPPV, and it has been shown to improve ventilatory status more than low-intensity NPPV in stable AECOPD patients. Whether the application of high-intensity NPPV has therapeutic advantages over low-intensity NPPV in patients with AECOPD remains to be determined. The high-intensity versus low-intensity NPPV in patients with AECOPD (HAPPEN) study will examine whether high-intensity NPPV is more effective for correcting hypercapnia than low-intensity NPPV, hence reducing the need for intubation and improving survival. ⋯ The HAPPEN study will be the first randomized controlled study to investigate whether high-intensity NPPV better corrects hypercapnia and reduces the need for intubation and mortality in AECOPD patients than low-intensity NPPV. The results will help critical care physicians decide the intensity of NPPV delivery to patients with AECOPD.
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In recent years, experience on the application of adaptive designs in confirmatory clinical trials has accumulated. Although planning such trials comes at the cost of additional operational complexity, adaptive designs offer the benefit of flexibility to update trial design and objectives as data accrue. In 2007, the European Medicines Agency (EMA) provided guidance on confirmatory clinical trials with adaptive (or flexible) designs. In order to better understand how adaptive trials are implemented in practice and how they may impact medicine approval within the EMA centralised procedure, we followed on 59 medicines for which an adaptive clinical trial had been submitted to the EMA Scientific Advice (SA) and analysed previously in a dedicated EMA survey of scientific advice letters. We scrutinized in particular the submission of the corresponding medicines for a marketing authorisation application (MAA). We also discuss the current regulatory perspective as regards the implementation of adaptive designs in confirmatory clinical trials. ⋯ Adaptive designs are now well established in the drug development landscape. If properly pre-planned, adaptations can play a key role in the success of some of these trials, for example to help successfully select the most promising dose regimens for phase II/III trials. Interim analyses can also enable stopping of trials for futility when they do not hold their promises. Type I error rate control, trial integrity and results consistency between the different stages of the analyses are fundamental aspects to be discussed thoroughly. Engaging early dialogue with regulators and implementing the scientific advice received is strongly recommended, since much experience in discussing adaptive designs and assessing their results has been accumulated.