A double-blind, randomized, placebo-controlled, parallel-group study of THC/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis
ABSTRACT Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo (p = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point (p = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group (p = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) (p = 0.028) and sleep quality NRS (p = 0.015) scores, both secondary endpoints in phase B, were also statistically significant compared to placebo, with estimated treatment differences of -0.79 and 0.99 points, respectively, in favor of THC/CBD spray treatment. The results of the current investigation were equivocal, with conflicting findings in the two phases of the study. While there were a large proportion of responders to THC/CBD spray treatment during the phase A double-blind period, the primary endpoint was not met due to a similarly large number of placebo responders. In contrast, there was a marked effect in phase B of the study, with an increased time to treatment failure in the THC/CBD spray group compared to placebo. These findings suggest that further studies are required to explore the full potential of THC/CBD spray in these patients.
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ABSTRACT: The early 1990's saw the introduction of a new innovation in component placement technology. By the mid-90's the electronics industry was moving towards complex circuit boards and continuously accelerate through the 90's, but at the start of the new millennium came the most dramatic downturn for the electronics industry. While at present, the electronics market is still subdued; the automotive sector electronics continues to grow steadily. The automotive product spectrum is very wide, but where component placement and assembly processes are concerned this put the focus firmly on quality and process control. In this paper, we discuss the problems encountered by the electronics industry because of its sudden downturn and suggests some solutions to cope with the problems.Manufacturing Engineer 05/2004; DOI:10.1049/me:20040208
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ABSTRACT: Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles (email@example.com).Journal of pain and symptom management 05/2013; 46(1). DOI:10.1016/j.jpainsymman.2013.05.002 · 2.74 Impact Factor
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ABSTRACT: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system affecting young adults that may lead to significant disability. The clinical course varies among the types of the disease as well as among individuals. Herein we provide a brief review of the recent data concerning the clinical presentation, diagnosis, causes, and pathogenesis of MS as well as medication used, followed by the anesthetic considerations of patients diagnosed with the disease. To accomplish this, we conducted a systematic PubMed literature search for articles, using the terms multiple sclerosis, anesthesia, general, regional, perioperative, and preoperative, and we then manually reviewed the references from each pertinent article. Because randomized controlled trials on the field are rare, most information is derived by case reports and case series. We concluded that the disease itself as well as the treatment modalities may have several implications in the conduct of anesthesia and perioperative management of MS patients. General and regional anesthetic techniques have been successfully used. With thorough preoperative evaluation and in depth knowledge of the disease and its complications, the MS patients can be managed safely.Journal of Anesthesia 08/2013; 28(2). DOI:10.1007/s00540-013-1697-2 · 1.12 Impact Factor