8 research outputs found
Intra-arterial treatment for acute ischemic stroke: a meta-analysis
Objective: To assess the potential benefit of treating patients with acute ischemic stroke using intra-arterial methods.
Methods: A meta-analysis of published randomized controlled trials that compared standard therapy with intravenous tissue plasminogen activator (IVtPA) for thrombolysis to intra-arterial therapies in patients with acute stroke was performed. All studies reported were analyzed as one group and studies documenting patients with large vessel obstruction were analyzed as a second group. The standardized mean difference (SMD) and the odds ratio (OR) of the dichotomized outcomes of Modified Rankin Scale (mRS) of these trials was calculated.
Results: Nine trials were identified with 2,711 patients treated. Meta-analysis of all studies, with and without large vessel obstruction documented, showed a significant benefit with intra-arterial therapy (SMD: 0.22 + 0.041; P=0.003). The dichotomized outcomes of mRS of these trials showed significant improvement (OR: 1.66 -2.43 in four of the five treatment arm groups examined). Meta-analysis of all publications with large vessel obstruction documented as an entry criteria showed a greater significant benefit with intra-arterial therapy (SMD: 0.35 + 0.05; P<0.001). The dichotomized outcomes of mRS of these trials showed significant improvement (OR: 1.36 -2.38 in all five treatment arm groups examined). Some heterogeneity was observed between studies.
Conclusion: Treatment of patients with acute ischemic stroke was associated with improved outcomes as measured by mRS. Patient selection, standard treatment, and study treatment factors contributed to the statistical evaluation of inter study heterogeneity and may have contributed to different study outcomes
Development of a large truck safety data needs study plan. Volume I - summary. Final report.
Federal Highway Administration, Office of Research and Development, Washington, D.C.Mode of access: Internet.Author corporate affiliation: Bellomo-McGee, Inc., Vienna, Va.Report covers the period Aug 1984 - Feb 1986Subject code: DEFSubject code: WLSubject code: WMEGSubject code: WT
Development of a large truck safety data needs study plan. Volume II - technical report. Final report.
Federal Highway Administration, Office of Research and Development, Washington, D.C.Mode of access: Internet.Author corporate affiliation: Bellomo-McGee, Inc., Vienna, Va.Report covers the period Aug 1984 - Feb 1986Subject code: DEFSubject code: WLSubject code: WMEGSubject code: WT
Drivers survey on unreported and low-damage accidents involving bumpers. Final report.
National Highway Traffic Safety Administration, Washington, D.C.Mode of access: Internet.Author corporate affiliation: Westat, Inc., Rockville, Md.Report covers the period Oct 1979-Nov 1980. Released Feb 1981. Contract amount $463,148Subject code: DGCP*NUMSubject code: JM*DESubject code: SCE*JMESubject code: WT
Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial
BACKGROUND: Pomalidomide and dexamethasone is a standard of care for patients with multiple myeloma in whom bortezomib and lenalidomide treatment has failed. KEYNOTE-183 assessed efficacy and safety of pomalidomide and dexamethasone with or without pembrolizumab in patients with relapsed or refractory multiple myeloma. Here, we present the findings of an unplanned, ad-hoc interim analysis at the request of the US Food and Drug Administration (FDA). METHODS: KEYNOTE-183 was a randomised, open-label, phase 3 trial done at 97 medical centres across 11 countries (Australia, Canada, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Spain, and USA). Patients aged at least 18 years with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, previously treated with at least two lines of therapy (excluding pomalidomide) and refractory to the last line were randomly assigned 1:1 to the pembrolizumab plus pomalidomide and dexamethasone group or the pomalidomide and dexamethasone group via an interactive voice response or integrated web response system. Patients received oral pomalidomide 4 mg daily on days 1-21 and oral low-dose dexamethasone 40 mg on days 1, 8, 15, and 22 in 28-day cycles, with or without intravenous pembrolizumab 200 mg every 3 weeks. The dual primary endpoints were progression-free survival and overall survival. Efficacy was assessed in all randomly assigned patients and safety was assessed in patients who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT02576977, and it is closed for accrual. FINDINGS: Between Jan 18, 2016, and June 7, 2017, 249 patients were randomly assigned to either the pembrolizumab plus pomalidomide and dexamethasone group (n=125) or the pomalidomide and dexamethasone group (n=124). On July 3, 2017, the FDA established that risks associated with the triple combination outweighed benefits and halted the study. Median follow-up was 8\ub71 months (IQR 4\ub75-10\ub79). Median progression-free survival was 5\ub76 months (95% CI 3\ub77-7\ub75) in the pembrolizumab plus pomalidomide and dexamethasone group versus 8\ub74 months (5\ub79-not reached) in the pomalidomide and dexamethasone group; progression-free survival estimates at 6 months were 48% (95% CI 37-58) versus 60% (49-69) at 6 months (hazard ratio [HR] 1\ub753; 95% CI 1\ub705-2\ub722; p=0\ub798). Median overall survival was not reached (95% CI 12\ub79-not reached) versus 15\ub72 months (12\ub77-not reached; HR 1\ub761; 95% CI 0\ub791-2\ub785; p=0\ub795); overall survival estimates at 6 months were 82% (95% CI 74-88) versus 90% (82-95). Serious adverse events occurred in 75 (63%) of 120 patients in the pembrolizumab plus pomalidomide and dexamethasone group versus 56 (46%) of 121 patients in the pomalidomide and dexamethasone group. Four (3%) treatment-related deaths occurred in the pembrolizumab plus pomalidomide and dexamethasone group (one each of unknown cause, neutropenic sepsis, myocarditis, and Stevens-Johnson syndrome); myocarditis and Stevens-Johnson syndrome were considered related to pembrolizumab. No treatment-related deaths were reported in the pomalidomide and dexamethasone group. INTERPRETATION: The results from this unplanned, FDA-requested, interim analysis showed that the benefit-risk profile of pembrolizumab plus pomalidomide and dexamethasone is unfavourable for patients with relapsed or refractory multiple myeloma. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (Kenilworth, NJ, USA)