An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States. METHODS: This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function. RESULTS: Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).

Individual monitoring of medical staff working in interventional radiology in Switzerland using double dosimetry

Physicians who frequently perform fluoroscopic examinations are exposed to high intensity radiation fields. The exposure monitoring is performed with a regular personal dosimeter under the apron in order to estimate the effective dose. However, large parts of the body are not protected by the apron (e.g. arms, head). Therefore, it is recommended to wear a supplemental dosimeter over the apron to obtain a better representative estimate of the effective dose. The over-apron dosimeter can also be used to estimate the eye lens dose. The goal of this study was to investigate the relevance of double dosimetry in interventional radiology. First the calibration procedure of the dosimeters placed over the apron was tested. Then, results of double dosimetry during the last five years were analyzed. We found that the personal dose equivalent measured over a lead apron was underestimated by ∼20% to ∼40% for X-ray beam qualities used in radiology. Measurements made over five-year period confirm that the use of a single under-apron dosimeter is inadequate for personnel monitoring. Relatively high skin dose (>10 mSv/month) would have remained undetected without a second dosimeter placed on the apron.

Adalimumab in Severe and Acute Sciatica (ASAS) : a multicentre, randomized, double-blind, placebo-controlled trial : 1240

Background Based on several experimental results and on a preliminary study, a trial was undertaken to assess the efficacy of adalimumab, a TNF-α inhibitor, in patients with radicular pain due to lumbar disc herniation. Methods A multicentre, double-blind, randomised controlled trial was conducted between May 2005 and December 2007 in Switzerland. Patients with acute (< 12 weeks) and severe (Oswestry Disability index > 50) radicular leg pain and imaging-confirmed lumbar disc herniation were randomised to receive as adjuvant therapy either two subcutaneous injections of adalimumab (40 mg) at 7 days interval or matching placebo. The primary outcome was leg pain, which was recorded every day for 10 days and at 6-weeks and 6- months based on a visual analogue scale (0 to 100). Results Of the 265 patients screened, 61 were enrolled (adalimumab= 31) and 4 were lost to follow-up. Over time, the evolution of leg pain was more favourable in the adalimumab group than in the placebo group (p<0.001). However, the effect size was relatively small and at last follow-up the difference was 13.8 (CI95% -11.5 - 39.0). In the adalimumab group twice as many patients fulfilled the criteria for "responders" and for "low residual disease impact" ( p<0.05) and fewer surgical discectomies were performed (6 versus 13, p=0.04). Conclusion The addition of a short course of adalimumab to the treatment regimen of patients suffering from acute and severe sciatica resulted in a small decrease in leg pain and in significantly fewer surgical procedures.

TLR3 as a biomarker for the therapeutic efficacy of double-stranded RNA in breast cancer.

The discovery of a targeted therapeutic compound along with its companion predictive biomarker is a major goal of clinical development for a personalized anticancer therapy to date. Here we present evidence of the predictive value of TLR3 expression by tumor cells for the efficacy of Poly (A:U) dsRNA in 194 breast cancer patients enrolled in a randomized clinical trial. Adjuvant treatment with double-stranded RNA (dsRNA) was associated with a significant decrease in the risk of metastatic relapse in TLR3 positive but not in TLR3-negative breast cancers. Moreover, we show the functional relevance of TLR3 expression by human tumor cells for the antitumor effects mediated by dsRNA in several preclinical mouse models carried out in immunocompromised animals. These 2 independent lines of evidence relied upon the generation of a novel tool, an anti-TLR3 antibody (40F9.6) validated for routine detection of TLR3 expression on paraffin-embedded tissues. Altogether, these data suggest that dsRNA mediates its therapeutic effect through TLR3 expressed on tumor cells, and could therefore represent an effective targeted treatment in patients with TLR3-positive cancers.

Ambulatory gait analysis results after total knee arthroplasty : arguments for mobile or fixed bearing?

Background: Mobile-bearing knee replacements have some theoretical advantages over fixed-bearing devices. However, very few randomized controlled clinical trials have been published to date, and studies showed little clinical and subjective advantages for the mobile-bearing using traditional systems of scoring. The choice of the ideal outcome measure to assess total joint replacement remains a complex issue. However, gait analysis provides objective and quantifying evidences of treatment evaluation. Significant methodological advances are currently made in gait analysis laboratories and ambulatory gait devices are now available. The goal of this study was to provide gait parameters as a new objective method to assess total knee arthroplasty outcome between patients with fixed- and mobile-bearing, using an ambulatory device with minimal sensor configuration. Methods: This randomized controlled double-blind study included to date 31 patients: the gait signatures of 12 patients with mobile-bearing were compared to the gait signatures of 19 patients with fixed-bearing pre-operatively and post-operatively at 6 weeks, 3 months and 6 months. Each participant was asked to perform two walking trials of 30m long at his/her preferred speed and to complete a EQ-5D questionnaire, a WOMAC and Knee Society Score (KSS). Lower limbs rotations were measured by four miniature angular rate sensors mounted respectively, on each shank and thigh. Results: Better relative differences between pre-operative and post-operative 3 months and 6 months KSS (122% vs 34% at 3 months, 138% vs 36% at 6 months) and KSS function (154% vs 8% at 3 months, 183% vs 42% at 6 months) scores were observed for the fixed-bearing compared to the mobile-bearing. The same better improvements for fixed-bearing were also found with the range of knee angles (Affected side: 31% vs -5% at 3 months, 47% vs 5% at 6 months), (Unaffected side: 16% vs 5% at 3 months, 15% vs 6% at 6 months) and peak swing speeds of shank (Affected side: 18% vs -2% at 3 months, 30% vs 4% at 6 months), (Unaffected side: 8% vs -3% at 3 months, 7% vs 4% at 6 months). Conclusions: A new method for a portable system for gait analysis has been developed with very encouraging results regarding the objective outcome of total knee arthroplasty using mobile- and fixed-bearings.

Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions.

OBJECTIVES: Gouty arthritis patients for whom non-steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0-100 mm visual analogue scale and time to first new flare. METHODS: Two 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)). RESULTS: 82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, -10.7 mm; 95% CI -15.4 to -6.0; p<0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p≤0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR: 0.44; 95% CI 0.32 to 0.60; both p≤0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p≤0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8% (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count. CONCLUSION: Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.

Dix erreurs a ne pas commettre lors de la prise en charge d'une prothèse articulaire infectée en orthopédie [Ten errors to avoid while dealing with infected total joint arthroplasties].

Infections after total joint arthroplasty are rare but come with severe consequences. Timely, adequate and standardized treatment beginning at the onset of symptoms will have a major impact on the handling of this dreaded complication. In absences of clear guidelines, errors are often committed, with occasionally severe consequences for the patient. In this article, the 10 most frequent errors starting with diagnostics till antibiotic and surgical treatment will be discussed.

Anti-TNF therapy in acute sciatica reduces the long-term need for surgery: A three-year follow-up of a randomized double blind placebo controlled trial

Introduction: Two subcutaneous injections of adalimumab in severeacute sciatica have demonstrated a significant benefit on the numberof back surgeries in a short-term randomized controlled clinical trial[1]. This 3-year follow-up study aimed to determine whether theshort-term benefit was sustained over a longer period of time.Methods: Information on surgery was retrieved in 56/61 patients(93%). We used a Cox proportional hazard models to determinefactors predisposing to surgery.Results: Twenty-three (41%) patients had back surgery within 3 years,8/29 (28%) in the adalimumab group and 15/ 27 (56%) in the placebogroup, p = 0.038. Adalimumab injections reduced the need for backsurgery by 61% (Hazard Ratio (HR): 0.39 (95% CI: 0.17-0.92). In amultivariate model, treatment with a TNF-α antagonist remained thestrongest protective factor (HR 0.17, p = 0.002). Other significantpredictors of surgery were a good correlation between symptomsand MRI findings (HR = 11.6, p = 0.04), baseline intensity of leg pain(HR = 1.3, p = 0.06), intensity of back pain (HR = 1.4, p = 0.03)and duration of sickness leave (HR = 1.01 per day, p = 0.03).Conclusion: A short course of adalimumab in patients with severeacute sciatica significantly reduces the need for back surgery.

Simulated joint and muscle forces in reversed and anatomic shoulder prostheses.

Reversed shoulder prostheses are increasingly being used for the treatment of glenohumeral arthropathy associated with a deficient rotator cuff. These non-anatomical implants attempt to balance the joint forces by means of a semi-constrained articular surface and a medialised centre of rotation. A finite element model was used to compare a reversed prosthesis with an anatomical implant. Active abduction was simulated from 0 degrees to 150 degrees of elevation. With the anatomical prosthesis, the joint force almost reached the equivalence of body weight. The joint force was half this for the reversed prosthesis. The direction of force was much more vertically aligned for the reverse prosthesis, in the first 90 degrees of abduction. With the reversed prosthesis, abduction was possible without rotator cuff muscles and required 20% less deltoid force to achieve it. This force analysis confirms the potential mechanical advantage of reversed prostheses when rotator cuff muscles are deficient.