The Experts below are selected from a list of 78228 Experts worldwide ranked by ideXlab platform
Patrick Kwan - One of the best experts on this subject based on the ideXlab platform.
-
a randomized double blind placebo controlled multicenter parallel group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial onset seizures
Epilepsia, 2015Co-Authors: Pavel Klein, Michael R Sperling, Jimmy Schiemann, John Whitesides, Wei Liang, Tracy Stalvey, Christian Brandt, Patrick KwanAbstract:SummaryObjective Brivaracetam (BRV), a selective and high-affinity synaptic vesicle protein 2A ligand, is in development as adjunctive treatment for partial-onset (focal) seizures (POS). This phase 3 study (N01358; NCT01261325) aimed to confirm the efficacy and safety/tolerability of BRV in adults (≥16–80 years) with POS. Methods This randomized, double-blind, placebo-controlled, multicenter study enrolled patients with uncontrolled POS despite ongoing treatment with 1–2 antiepileptic drugs. Patients exposed to levetiracetam ≤90 days before visit 1 were excluded. Patients entered an 8-week prospective baseline period, followed by a 12-week treatment period when they were randomized 1:1:1 to placebo (PBO), BRV 100 mg/day, or BRV 200 mg/day, started without up-titration. The co-primary efficacy outcomes were Percent Reduction over placebo in 28-day adjusted POS frequency, and ≥50% responder rate based on Percent Reduction in POS frequency from baseline to the treatment period. Results Seven hundred sixty-eight patients were randomized; 760 were included in the efficacy analysis: 259, 252, and 249 in PBO, BRV 100 mg/day, and BRV 200 mg/day groups, respectively. Percent Reduction over PBO in 28-day adjusted seizure frequency (95% confidence interval [CI]) was 22.8% for BRV 100 mg/day (13.3–31.2%; p < 0.001) and 23.2% for BRV 200 mg/day (13.8–31.6%; p < 0.001). The ≥50% responder rate (odds ratio vs. PBO; 95% CI) was 21.6% for PBO, 38.9% for BRV 100 mg/day (2.39; 1.6–3.6; p < 0.001), and 37.8% for BRV 200 mg/day (2.19; 1.5–3.3; p < 0.001). Treatment-emergent adverse events (TEAEs) occurred in 155 (59.4%) of 261 PBO patients versus 340 (67.6%) of 503 BRV-treated patients (safety population). Discontinuation rates due to TEAEs were 3.8%, 8.3%, and 6.8% for PBO, BRV 100 mg/day, and BRV 200 mg/day, respectively. Most frequent TEAEs (PBO versus BRV) were somnolence (7.7% vs. 18.1%), dizziness (5.0% vs. 12.3%), and fatigue (3.8% vs. 9.5%). Significance Adjunctive BRV 100 and 200 mg/day was efficacious in reducing POS in adults without concomitant levetiracetam use and was well tolerated.
Martin E Johnson - One of the best experts on this subject based on the ideXlab platform.
-
brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults a phase iii randomized double blind placebo controlled trial
Epilepsia, 2014Co-Authors: Victor Biton, Samuel F Berkovic, Bassel Aboukhalil, Michael R Sperling, Martin E JohnsonAbstract:SummaryPurpose Brivaracetam (BRV) is a novel high-affinity synaptic vesicle protein 2A ligand currently being investigated for the treatment of epilepsy. The purpose of this phase III study was to evaluate the efficacy and safety/tolerability of adjunctive BRV in adults with uncontrolled partial-onset (focal) seizures. Methods This was a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose trial (N01253; NCT00464269). Adults aged 16–70 years with well-characterized partial epilepsy not fully controlled despite treatment with one or two antiepileptic drugs (AEDs) were enrolled. Patients who experienced eight or more partial-onset seizures, whether or not secondarily generalized, during the 8-week prospective baseline period were randomized (1:1:1:1) to receive twice-daily placebo (PBO) or BRV (5, 20, or 50 mg/day) without titration. The primary efficacy endpoint was Percent Reduction over PBO in baseline-adjusted partial-onset seizure frequency/week during the 12-week treatment period. Comparison of BRV with PBO was sequential (50, 20 mg/day, then 5 mg/day). Secondary endpoints included ≥50% responder rate and median Percent Reduction from baseline in partial-onset seizure frequency/week. Post hoc analyses included the primary efficacy endpoint evaluated over 28 days and exploratory subanalyses of efficacy by seizure subtype. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs), laboratory tests, electrocardiography, vital signs, and physical and neurologic examinations. Key Findings Of 400 patients randomized, 396 were included in the intent-to-treat (ITT) population (PBO n = 98, BRV 5 mg/day n = 97, BRV 20 mg/day n = 100, BRV 50 mg/day n = 101) and 392 comprised the modified ITT (mITT) population. A total of 361 (91.2%) of 396 patients completed the study. Most patients (78.3%) were receiving two concomitant AEDs. Percent Reduction in partial-onset seizure frequency/week over PBO was −0.9% (p = 0.885) for BRV 5 mg/day, 4.1% (p = 0.492) for BRV 20 mg/day, and 12.8% (p = 0.025) for BRV 50 mg/day (mITT population). Statistical significance was also achieved for the Percent Reduction over PBO in baseline-adjusted partial-onset seizure frequency/28 days for BRV 50 mg/day (22.0%; p = 0.004) but not for the other BRV dose groups. In the BRV 50 mg/day group, statistical significance was also seen for the ≥50% responder rate (BRV 32.7% vs. PBO 16.7%; p = 0.008) and median Percent Reduction from baseline in partial-onset seizure frequency/week (BRV 30.5% vs. PBO 17.8%; p = 0.003). In the exploratory subanalysis by seizure subtype, median Percent Reduction from baseline in seizure frequency/week and ≥50% responder rate were numerically greater than PBO in the BRV 20 and 50 mg/day groups for simple partial, complex partial, and secondarily generalized seizures. BRV was generally well tolerated, with the majority of TEAEs being mild-to-moderate in intensity. Of the TEAEs reported by ≥5% patients, those with a frequency >3% higher than PBO for any dose of BRV compared with PBO were somnolence, dizziness, fatigue, influenza, insomnia, nasopharyngitis, vomiting, diarrhea, urinary tract infection, and nausea. Significance Adjunctive BRV at a daily dose of 50 mg was associated with statistically significant Reductions in seizure frequency compared with PBO. All doses of BRV showed good tolerability throughout the study.
-
adjunctive brivaracetam in adults with uncontrolled focal epilepsy results from a double blind randomized placebo controlled trial
Epilepsia, 2014Co-Authors: Philippe Ryvlin, Konrad J Werhahn, Barbara Blaszczyk, Martin E JohnsonAbstract:Summary Purpose Brivaracetam (BRV) is a novel high-affinity synaptic vesicle protein 2A ligand in clinical development for the treatment of epilepsy. This phase III study (N01252; NCT00490035) evaluated the efficacy and safety/tolerability of BRV (20, 50, and 100 mg/day) compared with placebo (PBO) in patients aged 16–70 years with uncontrolled focal seizures with/without secondary generalization, despite treatment with one to two concomitant antiepileptic drugs at a stable and optimal dosage. Methods This was a double-blind, randomized, placebo-controlled trial conducted across Europe and India. Eligible patients had two or more focal seizures/month for 3 months prior to screening and eight or more focal seizures during the 8-week prospective baseline. Concomitant use of levetiracetam was limited to 20% of randomized patients. Patients were randomized (1:1:1:1) to BRV 20, 50, 100 mg/day or PBO with no up-titration for 12 weeks, followed by down-titration or entry into a long-term follow-up study. The primary efficacy end point was Percent Reduction over PBO in baseline-adjusted focal seizure frequency/week over the 12-week treatment period. Comparison of BRV with PBO was sequential to control for multiplicity (50, 100, 20 mg/day), and thus required BRV to demonstrate superiority over PBO at 50 mg/day to meet the primary efficacy end point. Secondary efficacy variables were median Percent Reduction from baseline in focal seizure frequency/week, ≥50% responder rate, and seizure freedom (all seizure types). Safety assessments included treatment-emergent adverse events (TEAEs). Key Findings Of 399 randomized patients, 398 were included in the intent-to-treat (ITT) and safety populations. Overall, 367 (92.2%) of 398 patients completed the study (BRV: 93.9%, 88.9%, and 94.0% for 20, 50, and 100 mg/day, respectively; PBO: 92.0%) and 345 (86.7%) of 398 patients continued into long-term follow-up studies (BRV: 87.9%, 82.8%, and 88.0% for 20, 50, and 100 mg/day, respectively; PBO: 88.0%). The study did not meet its primary efficacy end point based on the predefined sequential testing strategy. Indeed, Percent Reduction over PBO in baseline-adjusted focal seizure frequency/week (primary efficacy analysis) was 6.8% (p = 0.239), 6.5% (p = 0.261), and 11.7% (p = 0.037) for BRV 20, 50, and 100 mg/day, respectively. Median Percent Reduction from baseline in focal seizure frequency/week was 30.0% (p = 0.019), 26.8% (p = 0.092), and 32.5% (p = 0.004) for BRV 20, 50, and 100 mg/day, respectively, compared with 17.0% for PBO. Responder rates (≥50%) were 27.3% (p = 0.339), 27.3% (p = 0.372), and 36.0% (p = 0.023) for BRV 20, 50, and 100 mg/day, respectively, compared with 20.0% for PBO. Complete seizure freedom was reported by 2/99, 0/99, and 4/100 patients on BRV 20, 50, and 100 mg/day, respectively, compared with 0/100 on PBO. The incidence of TEAEs was higher for BRV 20 (56/99, 56.6%), 50 (62/99, 62.6%), and 100 mg/day (63/100, 63.0%) than PBO (53/100, 53.0%); most TEAEs were mild or moderate in severity. The most frequently reported TEAEs in the BRV groups were headache, somnolence, dizziness, and fatigue. Significance In this study of adjunctive BRV (20–100 mg/day) in adults with uncontrolled focal seizures, the primary efficacy analysis based on the 50 mg/day dose was not statistically significant. However, BRV 100 mg/day reduced baseline-adjusted focal seizure frequency/week by 11.7% over PBO, achieving statistical significance (p = 0.037). Secondary efficacy analyses (Percent Reduction from baseline in focal seizure frequency/week, ≥50% responder rate) provided supportive evidence for the efficacy of BRV 100 mg/day. BRV 20–100 mg/day was well tolerated without up-titration, with a high completion rate.
Chris J Packard - One of the best experts on this subject based on the ideXlab platform.
-
prevention of coronary heart disease with pravastatin in men with hypercholesterolemia
The New England Journal of Medicine, 1995Co-Authors: James Shepherd, Stuart M Cobbe, Ian Ford, Chris Isles, A R Lorimer, Peter W Macfarlane, J H Mckillop, Chris J PackardAbstract:BACKGROUND: Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS: We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS: Pravastatin lowered plasma cholesterol levels by 20 Percent and low-density-lipoprotein cholesterol levels by 26 Percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative Reduction in risk with pravastatin, 31 Percent; 95 Percent confidence interval, 17 to 43 Percent; P < 0.001). There were similar Reductions in the risk of definite nonfatal myocardial infarctions (31 Percent Reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 Percent Reduction, P = 0.13; definite plus suspected cases: 33 Percent Reduction, P = 0.042), and death from all cardiovascular causes (32 Percent Reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 Percent Reduction in the risk of death from any cause in the pravastatin group (95 Percent confidence interval, 0 to 40 Percent; P = 0.051). CONCLUSIONS: Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.
-
prevention of coronary heart disease with pravastatin in men with hypercholesterolemia west of scotland coronary prevention study group
The New England Journal of Medicine, 1995Co-Authors: James Shepherd, Stuart M Cobbe, Ian Ford, Chris Isles, A R Lorimer, Peter W Macfarlane, J H Mckillop, Chris J PackardAbstract:BACKGROUND Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease. METHODS We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points. RESULTS Pravastatin lowered plasma cholesterol levels by 20 Percent and low-density-lipoprotein cholesterol levels by 26 Percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative Reduction in risk with pravastatin, 31 Percent; 95 Percent confidence interval, 17 to 43 Percent; P < 0.001). There were similar Reductions in the risk of definite nonfatal myocardial infarctions (31 Percent Reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 Percent Reduction, P = 0.13; definite plus suspected cases: 33 Percent Reduction, P = 0.042), and death from all cardiovascular causes (32 Percent Reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 Percent Reduction in the risk of death from any cause in the pravastatin group (95 Percent confidence interval, 0 to 40 Percent; P = 0.051). CONCLUSIONS Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.
Marilyn Paradis - One of the best experts on this subject based on the ideXlab platform.
-
adjuvant radiotherapy and chemotherapy in node positive premenopausal women with breast cancer
The New England Journal of Medicine, 1997Co-Authors: Joseph Ragaz, Stewart M Jackson, Ian H Plenderleith, John J Spinelli, Vivian E Basco, Kenneth S Wilson, Margaret A Knowling, Christopher M L Coppin, Marilyn Paradis, Andrew J ColdmanAbstract:Background Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. Methods From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. Results After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 Percent Reduction in the rate of recurrence (relative risk, 0.67; 95 Percent confidence interval, 0.50 to 0.90) and a 29 Percent Reduction in mortality from breast cancer (relative risk, 0.71; 95 perc...
-
adjuvant radiotherapy and chemotherapy in node positive premenopausal women with breast cancer
The New England Journal of Medicine, 1997Co-Authors: Joseph Ragaz, Stewart M Jackson, Ian H Plenderleith, John J Spinelli, Vivian E Basco, Kenneth S Wilson, Margaret A Knowling, Christopher M L Coppin, Nhu D Le, Marilyn ParadisAbstract:BACKGROUND: Radiotherapy after mastectomy to treat early breast cancer has been known since the 1940s to reduce rates of local relapse. However, the routine use of postoperative radiotherapy began to decline in the 1980s because it failed to improve overall survival. We prospectively tested the efficacy of combining radiotherapy with chemotherapy. METHODS: From 1978 through 1986, 318 premenopausal women with node-positive breast cancer were randomly assigned, after modified radical mastectomy, to receive chemotherapy plus radiotherapy or chemotherapy alone. Radiotherapy was given to the chest wall and locoregional lymph nodes between the fourth and fifth cycles of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: After 15 years of follow-up, the women assigned to chemotherapy plus radiotherapy had a 33 Percent Reduction in the rate of recurrence (relative risk, 0.67; 95 Percent confidence interval, 0.50 to 0.90) and a 29 Percent Reduction in mortality from breast cancer (relative risk, 0.71; 95 Percent confidence interval, 0.51 to 0.99), as compared with the women treated with chemotherapy alone. CONCLUSIONS: Radiotherapy combined with chemotherapy after modified radical mastectomy decreases rates of locoregional and systemic relapse and reduces mortality from breast cancer.
Tal Gross - One of the best experts on this subject based on the ideXlab platform.
-
The Effect of Health Insurance Coverage on the Use of Medical Services
American Economic Journal: Economic Policy, 2012Co-Authors: Michael L Anderson, Carlos Dobkin, Tal GrossAbstract:Author(s): Anderson, M; Dobkin, C; Gross, T | Abstract: Substantial uncertainty exists regarding the causal effect of health insurance on the utilization of care. We exploit a sharp change in insurance coverage rates that results from young adults "aging out" of their parents' insurance plans to estimate the effect of insurance coverage on the utilization of emergency department (ED) and inpatient services. Aging out results in an abrupt 5 to 8 Percentage point Reduction in the probability of having health insurance. We find that uninsured status leads to a 40 Percent Reduction in ED visits and a 61 Percent Reduction in inpatient hospital admissions.
-
the effect of health insurance coverage on the use of medical services
National Bureau of Economic Research, 2010Co-Authors: Michael L Anderson, Carlos Dobkin, Tal GrossAbstract:Substantial uncertainty exists regarding the causal effect of health insurance on the utilization of care. Most studies cannot determine whether the large differences in healthcare utilization between the insured and the uninsured are due to insurance status or to other unobserved differences between the two groups. In this paper, we exploit a sharp change in insurance coverage rates that results from young adults "aging out" of their parents' insurance plans to estimate the effect of insurance coverage on the utilization of emergency department (ED) and inpatient services. Using the National Health Interview Survey (NHIS) and a census of emergency department records and hospital discharge records from seven states, we find that aging out results in an abrupt 5 to 8 Percentage point Reduction in the probability of having health insurance. We find that not having insurance leads to a 40 Percent Reduction in ED visits and a 61 Percent Reduction in inpatient hospital admissions. The drop in ED visits and inpatient admissions is due entirely to Reductions in the care provided by privately owned hospitals, with particularly large Reductions at for profit hospitals. The results imply that expanding health insurance coverage would result in a substantial increase in care provided to currently uninsured individuals.
