Effects of Repetitive Transcranial Magnetic Stimulation and Multicomponent Therapy in Patients With Fibromyalgia: A Randomized Controlled Trial.

OBJECTIVE: Fibromyalgia (FM) is a chronic painful condition partly due to alterations in pain modulation by the central nervous system. Multicomponent therapy (MT) and repetitive transcranial magnetic stimulation (rTMS) have both been reported as pain modulators in patients with FM. The aim of this study was to compare the effects of rTMS on pain with a combination of MT and rTMS versus MT alone. METHODS: Thirty-nine FM patients with visual analog scale (VAS) results for pain of ≥40 mm were randomized to active or sham rTMS (high-frequency, primary motor cortex M1) plus 12 weeks of MT (3 sessions per week combining aerobic training, pool-based exercises, and relaxation). Repetitive TMS was started 2 weeks prior to MT and maintained until the end of the program (week 14). Assessments were achieved at baseline, at week 14, and at 6 months (week 40) after completion of the program. The main criterion was pain reduction, as assessed by the weekly mean self-reported level of pain (reported daily). Secondary outcomes were cardiorespiratory fitness (graded maximal exercise test), cardiac autonomic adaptations, and FM impact (using scales for FM impact, depression, sleep efficiency, and pain catastrophizing). RESULTS: The reduction of the weekly mean of pain reported daily did not differ significantly between groups (using repeated measures of analysis of variance [ANOVA]). Two-way ANOVAs showed that pain VAS results, as well as cardiorespiratory fitness, quality of life, depression, and catastrophizing, improved significantly at week 14 and remained stable until week 40. Neither cardiac autonomic adaptations nor sleep efficiency changed significantly. CONCLUSION: Repetitive TMS did not reduce pain in patients with FM who followed the MT program.

Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers.

The new anticoagulants dabigatran and rivaroxaban can be responsible for haemorrhagic complications. As for any anticoagulant, bleeding management is challenging. We aimed to test the effect of all putative haemostatic agents on the anticoagulant activity of these new drugs using thrombin generation tests. In an ex vivo study, 10 healthy white male subjects were randomised to receive rivaroxaban (20 mg) or dabigatran (150 mg) in one oral administration. After a two weeks washout period, they received the other anticoagulant. Venous blood samples were collected just before drug administration (H0) and 2 hours thereafter. Reversal of anticoagulation was tested in vitro using prothrombin complex concentrate (PCC), rFVIIa or FEIBA® at various concentrations. Rivaroxaban affects quantitative and kinetic parameters, including the endogenous thrombin potential (ETP-AUC and more pronouncedly the thrombin peak), the lag-time and time to peak. PCC strongly corrected ETP-AUC, whereas rFVIIa only modified the kinetic parameters. FEIBA corrected all parameters. Dabigatran specially affects the kinetics of thrombin generation with prolonged lag-time and time to peak. Although PCC increased ETP-AUC, only rFVIIa and FEIBA corrected the altered lag-time. For both anticoagulants, lower doses of FEIBA, corresponding to a quarter to half the dose usually used, have potential reversal profile of interest. In conclusion, some non-specific reversal agents appear to be able to reverse the anticoagulant activity of rivaroxaban or dabigatran. However, clinical evaluation is needed regarding haemorrhagic situations, and a meticulous risk-benefit evaluation regarding their use in this context is required.

Effect of Gelsemium 5CH and 15CH on anticipatory anxiety: a phase III, single-centre, randomized, placebo-controlled study.

Therapeutics to treat or prevent anxiety are numerous but many people choose to try non-conventional medicine such as homeopathy. This study aimed at evaluating the effectiveness of Gelsemium 5CH and 15CH on provoked anxiety in healthy volunteers, in comparison with placebo. This was a double-blind, single-centre, randomized, placebo-controlled study. Eligible healthy men or women aged from 18 to 40 years without a history of psychiatric disorders were randomly allocated to receive Gelsemium 5 or 15CH or placebo. Anxiety was proved by performance of the Stroop colour word test (SCWT). The primary end-point was anxiety assessed by the State measure of the State-Trait Anxiety Inventory (STAI-S) as the absolute value and difference with baseline, according to the treatment received. We included 180 healthy volunteers. The distribution into each treatment group was homogenous. There was no statistical difference between groups for the values of STAI-S at baseline, just before the SCWT and the difference between these times (1.8 [0.20 to 3.4], 1.0 [-0.6 to 2.6] and 1.4 [-0.3 to 3.0] for Gelsemium 15CH, 5CH and placebo respectively). Likewise, no statistical difference was observed between groups in anxiety as measured by a Visual Analogue Scale and the Competitive State Anxiety Inventory. Mean arterial pressure and heart rate significantly increased (P < 0.001) but no interaction between time prior to provoked anxiety and treatment was shown (P = 0.59 and P = 0.46, respectively). Gelsemium 5CH and 15CH do not prevent anticipatory anxiety in the conditions used in this study.