Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial.

BACKGROUND: Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. METHODS: This observer-blind, randomized, placebo-controlled study enrolled adults aged 18-64years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. RESULTS: Over a study period of 2years, 15,044 participants were enrolled (mean age±standard deviation: 35.5±14.7years; 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p<0.001; systemic: IIV3 46.6% vs placebo 39.1%, p<0.001). CONCLUSIONS: The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain. Funded by CSL Limited, ClinicalTrials.gov identifier NCT00562484.

Injectable collagenase Clostridium histolyticum: a new nonsurgical treatment for Dupuytren's disease.

PURPOSE: The Collagenase Option for the Reduction of Dupuytren's (CORD) II study investigated the efficacy and safety of injectable Xiaflex (collagenase clostridium histolyticum), in patients with Dupuytren's contracture. METHODS: This was a prospective, randomized, placebo-controlled trial with 90-day double-blind and 9-month open-label phases. We randomized patients with contractures affecting metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joints 2 to 1 to collagenase (0.58 mg) or placebo. Cords received a maximum of 3 injections. Cord disruption was attempted the day after injection using a standardized finger extension procedure. Primary end point was reduction in contracture to 0° to 5° of normal 30 days after the last injection. RESULTS: We enrolled 66 patients; 45 cords (20 MCP to 25 PIP joints) received collagenase and 21 cords (11 MCP to 10 PIP joints) received placebo in the double-blind phase. Statistically significantly more cords injected with collagenase than placebo met the primary end point (44.4% vs 4.8%; p <. 001). The mean percentage decrease in degree of joint contracture from baseline to 30 days after last injection was 70.5% ± 29.2% in the collagenase group and 13.6% ± 26.1% in the placebo group (p < .001). The mean increase in range of motion was significantly greater in the collagenase (35.4° ± 17.8°) than in the placebo (7.6° ± 14.9°; p < .001) group. Efficacy after open-label treatment was similar to that after the double-blind phase: 50.7% of all joints achieved 0° to 5° of normal. More patients were satisfied with collagenase (p < .001). No joint had recurrence of contracture. One patient had a flexion pulley rupture and one patient underwent routine fasciectomy to address cord proliferation and sensory abnormality. No tendon ruptures or systemic allergic reactions were reported. Most adverse events were related to the injection or finger extension procedure. CONCLUSIONS: Collagenase clostridium histolyticum is the first Food and Drug Administration-approved, nonsurgical treatment option for adult Dupuytren's contracture patients with a palpable cord that is highly effective and well tolerated. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial.

BACKGROUND: Enhanced influenza vaccines are needed to provide improved protection for elderly individuals. The intradermal vaccination route was hypothesized to provide immunogenicity superior to that provided by the intramuscular vaccination route. METHODS: In a multicenter, randomized study, 1107 volunteers >60 years of age received intradermal trivalent inactivated influenza vaccine containing 15 or 21 microg of hemagglutinin per strain or intramuscular control vaccine. Intradermal vaccines used a novel microinjection system designed to ensure easy, convenient, consistent vaccination. The primary end points of the study were the strain-specific hemagglutination inhibition geometric mean titers (GMTs) noted 21 days after vaccination. Groups were compared using noninferiority and superiority analyses. RESULTS: For each strain, the GMTs noted in association with each intradermal vaccine were superior to those noted with the intramuscular control (adjusted P< .0001). Seroprotection rates, seroconversion rates, and mean titer increases were also superior for intradermally administered vaccine in all but one of the analyses undertaken. Systemic reactogenicity was comparable between routes. Local injection site reactions, particularly erythema but not pain, were more commonly associated with intradermal vaccination. CONCLUSIONS: For the first time, the intradermal vaccination route has been used to elicit immune responses significantly superior to those noted in association with the conventional intramuscular vaccination route. This was done using an easy-to-use, reliable microinjection system. This superior response is expected to enhance annual protection against influenza in this vulnerable population. TRIAL REGISTRATION: Clinicaltrials.gov registry number: NCT00296829.

Ropinirole is effective in the long-term management of restless legs syndrome: a randomized controlled trial.

The objective of this study was to investigate the long-term efficacy of ropinirole in patients with restless legs syndrome (RLS) and to assess the potential for relapse after the discontinuation of active treatment. Patients with primary RLS (n = 202) received single-blind ropinirole for 24 weeks. Patients meeting treatment continuation criteria were randomized to double-blind treatment with ropinirole or placebo for a further 12 weeks. The primary efficacy variable was the proportion of patients relapsing during double-blind treatment. Additional efficacy measures included time to relapse, withdrawals due to lack of efficacy, improvement on the Clinical Global Impression-Improvement (CGI-I) scale, change in International Restless Legs Scale (IRLS) score during double-blind treatment, and changes in sleep and quality of life (QoL) parameters. Significantly fewer patients relapsed on ropinirole than on placebo (32.6% vs. 57.8%; P = 0.0156). Time to relapse was longer with ropinirole and more patients withdrew due to lack of efficacy with placebo. Patients showed improvements in IRLS and CGI-I scores, sleep and QoL parameters with single-blind ropinirole, which were better maintained when ropinirole was continued during the double-blind phase, but reduced with placebo. Ropinirole was well tolerated; adverse events were typical for dopamine agonists. Ropinirole was highly effective and well tolerated in the long-term management of RLS, with pharmacological effect over 36 weeks.

Acarbose improves glycemic control in overweight type 2 diabetic patients insufficiently treated with metformin.

OBJECTIVE: To investigate the efficacy and safety of acarbose as add-on therapy in overweight type 2 patients with diabetes inadequately controlled by metformin. RESEARCH DESIGN AND METHODS: This study adopted a multicenter, randomized, double-blind, placebo-controlled, parallel group design. After a 4-week placebo run-in period, subjects were randomized to either acarbose (titrated up to 100 mg b.i.d.) or placebo. The primary efficacy variable was the change in HbA(1c) from baseline to the end of the 24-week treatment period. Change in fasting blood glucose was assessed as a secondary efficacy parameter. RESULTS: The intention-to-treat analysis from baseline to week 24 (81 patients for HbA(1c) and 82 for fasting blood glucose) showed statistically significant differences between acarbose and placebo treatment in HbA(1c) (1.02%; 95% CI 0.543-1.497; P = 0.0001) and fasting blood glucose (1.132 mmol/l; 95% CI 0.056-2.208; P = 0.0395) (adjusted least square means). In all, 18 patients (47%) in the acarbose group were classified as responders with a > or =5% reduction in HbA(1c) (relative to baseline) at the end point compared to 6 (14%) in the placebo group (P = 0.001). The safety profiles were similar for both treatment groups except for the higher incidence of gastrointestinal side effects during acarbose therapy. CONCLUSIONS: The addition of acarbose to metformin monotherapy provides an efficacious and safe alternative for glycemic improvement in overweight type 2 patients inadequately controlled by metformin alone.