			Home About us Contact

Primary End Point (primary + end_point)

Distribution by Scientific Domains

Medical Sciences	100%

Distribution within Medical Sciences

Cardiovascular Disease	25%
Neurology	16%

Selected Abstracts

Transcatheter versus Surgical Closure of Secundum Atrial Septal Defect in Adults: Impact of Age at Intervention.

CONGENITAL HEART DISEASE, Issue 3 2007
A Concurrent Matched Comparative Study
Abstract Objectives., To compare the short- and mid-term outcomes of surgical (SUR) vs. transcatheter closure of secundum atrial septal defect (ASD) using Amplatzer septal occluder (ASO) in adults with a very similar spectrum of the disease; and to identify predictors for the primary end point. Design., Single-center, concurrent comparative study. Surgically treated patients were randomly matched (2:1) by age, sex, date of procedure, ASD size, and hemodynamic profile. Setting., Tertiary referral center. Patients., One hundred sixty-two concurrent patients with ASD submitted to ASO (n = 54) or SUR closure (n = 108) according with their preferences. Main Outcome Measures., Primary end point was a composite index of major events including failure of the procedure, important bleeding, critical arrhythmias, serious infections, embolism, or any major cardiovascular intervention-related complication. Predictors of these major events were investigated. Results., Atrial septal defects were successfully closed in all patients, and there was no mortality. The primary event rate was 13.2% in ASO vs. 25.0% in SUR (P = .001). Multivariate analysis showed that higher rate of events was significantly associated with age >40 years; systemic/pulmonary output ratio <2.1; and systolic pulmonary arterial pressure >50 mm Hg; while in the ASO group the event rate was only associated with the ASD size (>15 cm2/m2; relative risk = 1.75, 95% confidence interval 1.01,8.8). There were no differences in the event-free survival curves in adults with ages <40 years. Conclusions., The efficacy for closure ASD was similar in both groups. The higher morbidity observed in SUR group was observed only in the patients submitted to the procedure with age >40 years. The length of hospital stay was shorter in the ASO group. Surgical closure is a safe and effective treatment, especially in young adults. There is certainly nothing wrong with continuing to do surgery in countries where the resources are limited. [source]

Budesonide in previously untreated autoimmune hepatitis

LIVER INTERNATIONAL, Issue 5 2005
Johannes Wiegand
Abstract: Background: Autoimmune hepatitis (AIH) is a chronic liver disease that is effectively treated with immunosuppressive therapy. Predniso(lo)ne, often in combination with azathioprine, is the basic therapeutic option to induce remission. However, this regimen can cause numerous side effects. The aim of the present study was to evaluate budesonide as a treatment option in the induction of remission in patients with previously untreated AIH. Methods: Between October 1998 and August 1999, 12 patients were treated with 3 mg budesonide thrice daily for 3 months in this open one-arm multicenter phase IIa study. Primary end point was induction of remission indicated by a drop of aspartate aminotransferase and alanine aminotransferase levels below two times the upper limit of normal. Results: Seven of the 12 patients (58%) reached complete remission, three patients (25%) had a partial response. Thus, 10/12 individuals (83.3%) responded to therapy. Therapy was tolerated well in 10/12 cases (83.3%). Conclusions: Budesonide monotherapy was effective in the induction of remission and well tolerated in treatment naïve patients with AIH. It should be further evaluated in prospective controlled trials and should be compared to predniso(lo)ne both in monotherapy and in combination with azathioprine. [source]

Reversion and Maintenance of Sinus Rhythm in Patients with Permanent Atrial Fibrillation by Internal Cardioversion Followed by Biatrial Pacing

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2002
NIKOLAOS FRAGAKIS
FRAGAKIS, N., et al.: Reversion and Maintenance of Sinus Rhythm in Patients with Permanent Atrial Fibrillation by Internal Cardioversion Followed by Biatrial Pacing. Patients in atrial fibrillation (AF) who fail external cardioversion are usually regarded as in permanent AF. Internal cardioversion may revert many such patients into sinus rhythm (SR) but the majority relapse rapidly into AF. We investigated whether internal cardioversion followed by biatrial pacing is an effective to restore and subsequently maintain SR in patients with permanent AF. Patients in permanent AF underwent internal cardioversion that was followed by biatrial temporary pacing for 48 hours. Those who remained in SR received a permanent biatrial pacemaker programmed to a rate responsive mode with a lower rate 90 beats/min. Primary end point of the study included maintenance in SR 3 months after internal cardioversion. Sixteen patients (14 men, 57 ± 11 years) were cardioverted. The median duration of AF was 24 months (quartiles, Q1= 8.5 and Q3= 102) and mean left atrium diameter was 48 ± 04 mm. A permanent biatrial pacemaker was implanted in 11 patients. At a mean follow-up of 15 months (range 4 to 24), 8 patients remained in SR for more than 3 months. AF was eliminated in 5 patients, while in two a second internal cardioversion on amiodarone was required. Antiarrhythmic therapy was used in half of our population and did not predict the long-term maintenance of SR. Following internal cardioversion with continuous biatrial pacing, 50% of patients with permanent AF were maintained for prolonged periods in SR. This is a new modality of treatment of permanent AF directed to the maintenance of SR that provides a further therapeutic option in end-stage AF. [source]

Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis,

ANNALS OF NEUROLOGY, Issue 2 2009
Sanne Piepers MD
Objective To determine whether valproic acid (VPA), a histone deacetylase inhibitor that showed antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclinical studies, is safe and effective in amyotrophic lateral sclerosis (ALS) using a sequential trial design. Methods Between April 2005 and January 2007, 163 ALS patients received VPA 1,500mg or placebo daily. Primary end point was survival. Secondary outcome measure was decline of functional status measured by the revised ALS Functional Rating Scale. Analysis was by intention to treat and according to a sequential trial design. This trial was registered with ClinicalTrials.gov (number NCT00136110). Results VPA did not affect survival (cumulative survival probability of 0.72 in the VPA group [standard error (SE), 0.06] vs 0.88 in the placebo group [SE, 0.04] at 12 months, and 0.59 in the VPA group [SE, 0.07] vs 0.68 in the placebo group [SE, 0.08] at 16 months) or the rate of decline of functional status. VPA intake did not cause serious adverse reactions. Interpretation Our finding that VPA, at a dose used in epilepsy, does not show a beneficial effect on survival or disease progression in patients with ALS has implications for future trials with histone deacetylase inhibitors in ALS and other neurodegenerative diseases. The use of a sequential trial design allowed inclusion of only half the number of patients required for a classic trial design and prevented patients from unnecessarily continuing potentially harmful study medication. Ann Neurol 2009;66:227,234 [source]

Clinical and Hemodynamic Effects of Nesiritide (B-Type Natriuretic Peptide) in Patients With Decompensated Heart Failure Receiving , Blockers

CONGESTIVE HEART FAILURE, Issue 2 2005
William T. Abraham MD
The use of , blockers in congestive heart failure presents a therapeutic challenge for patients with acute episodes of decompensation. Such patients may be less responsive to positive inotropic agents, whereas the beneficial effects of nesiritide, which are not dependent on the ,-adrenergic receptor signal-transduction pathway, may be preserved. This analysis of the Vasodilation in the Management of Acute CHF trial evaluated the safety and efficacy of nesiritide in decompensated congestive heart failure patients receiving , blockers. The Vasodilation in the Management of Acute CHF trial was a multicenter, randomized, controlled evaluation of nesiritide in 489 hospitalized patients with decompensated congestive heart failure. One hundred twenty-three patients were on chronic ,-blocker therapy at enrollment (31 randomized to placebo, 50 to nesiritide, and 42 to nitroglycerin). Primary end points included pulmonary capillary wedge pressure and dyspnea evaluation at 3 hours. Patients receiving nesiritide, but not IV nitroglycerin, had significantly reduced pulmonary capillary wedge pressure vs. placebo at 3 hours regardless of ,-blocker use. The use of , blockers did not alter the beneficial effects of nesiritide on systemic blood pressure, heart rate, or dyspnea evaluation. In nesiritide-treated subjects, safety profiles were similar regardless of ,-blocker use. Thus, the clinical and hemodynamic benefits and safety of nesiritide are preserved in decompensated congestive heart failure patients receiving chronic , blockade. [source]

Is there a prognostic role for C-reactive protein in ischemic stroke?

ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010
G. Corso
Corso G, Bottacchi E, Brusa A, Di Benedetto M, Giardini G, Lia C, Reggiani M, Veronese Morosini M. Is there a prognostic role for C-reactive protein in ischemic stroke? Acta Neurol Scand: 122: 209,216. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, We investigated the relationship between C-reactive protein (CRP)-values in the acute phase of stroke and the risk of further fatal and non-fatal ischemic events. Materials and methods,,, We analysed 462 consecutive incident ischemic strokes. Patients were divided into two subgroups on the basis of a CRP cut-off level of 9 mg/l. Primary end points were any new vascular fatal and non-fatal event recorded during the follow-up period. Results,,, During a follow-up of 2.27 years, in 132 patients occurred a primary end point. Patients with CRP values ,9 mg/l had more frequently primary end point. The hazard ratio (HR) for cardiovascular events was 3.59; 1.93 for cerebrovascular events; 7.43 for vascular deaths and 5.78 for death from any cause. Cox proportional hazard multivariate analysis identified CRP values ,9 (HR = 4.19, 95% CI: 1.85,9.50, P = 0.001), the lack of secondary prevention therapy at discharge (HR = 4.35, 95% CI: 1.87,10.1, P = 0.001), age >70 years (HR = 3.09, 95% CI: 1.04,9.24, P = 0.04) as independent predictors of fatal events. Conclusions,,, CRP levels ,9 mg/l, evaluated in incident ischemic stroke within 24 h, predict a higher risk of further ischemic events and mortality. [source]

Transcatheter versus Surgical Closure of Secundum Atrial Septal Defect in Adults: Impact of Age at Intervention.

Eslicarbazepine Acetate: A Double-blind, Add-on, Placebo-controlled Exploratory Trial in Adult Patients with Partial-onset Seizures

EPILEPSIA, Issue 3 2007
Christian Elger
Summary:,Objective: To explore the efficacy and safety of eslicarbazepine acetate (BIA 2-093), a new antiepileptic drug, as adjunctive therapy in adult patients with partial epilepsy. Methods: A multicenter, double-blind, randomized, placebo-controlled study was conducted in 143 refractory patients aged 18,65 years with ,4 partial-onset seizures/month. The study consisted of a 12-week treatment period followed by a 1-week tapering off. Patients were randomly assigned to one of three groups: treatment with eslicarbazepine acetate once daily (QD, n = 50), twice daily (BID, n = 46), or placebo (PL, n = 47). The daily dose was titrated from 400 mg to 800 mg and to 1,200 mg at 4-week intervals. The proportion of responders (patients with a ,50% seizure reduction) was the primary end point. Results: The percentage of responders versus baseline showed a statistically significant difference between QD and PL groups (54% vs. 28%; 90% CI =,,, ,14; p = 0.008). The difference between the BID (41%) and PL did not reach statistical significance (90% CI =,,, ,1; p = 0.12). A significantly higher proportion of responders in weeks 5,8 was found in the QD group than in the BID group (58% vs. 33%, respectively, p = 0.022). At the end of the 12-week treatment, the number of seizure-free patients in the QD and BID groups was 24%, which was significantly different from the PL group. The incidence of adverse events was similar between the treatment groups and no drug-related serious adverse events occurred. Conclusion: Eslicarbazepine acetate was efficacious and well tolerated as an adjunctive therapy of refractory epileptic patients. [source]

Clinical Implications of QRS Duration and QT Peak Prolongation in Patients with Suspected Coronary Disease Referred for Elective Cardiac Catheterization

ANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2008
M. Nadeem Attar M.D., M.R.C.P.
Background: The electrocardiogram (ECG) remains a simple, universally available, and prognostically powerful investigation in heart failure, and acute coronary syndromes. We sought to assess the prognostic utility of clinical, angiographic, and simple ECG parameters in a large cohort of patients undergoing elective cardiac catheterization (CC) for known or suspected coronary artery disease. Methods: Consecutive consenting patients undergoing CC for coronary disease were enrolled at a single tertiary center. Patient data, drug therapy, catheter reports, and ECG recordings were prospectively recorded in a validated electronic archive. The primary outcome measure was death or nonfatal myocardial infarction (MI) over 1 year or until percutaneous or cardiac surgical intervention. Independent prognostic markers were identified using the Cox proportional hazard model. Results: A total of 682 individuals were recruited of whom 17(2.5%) died or suffered a nonfatal MI in 1 year. In multivariate analysis QRS duration (ms) (HR 1.03 95% CI 1.01,1.05, P = 0.003), extent of coronary disease (HR 2.01 95% CI 1.24,3.58, P = 0.006), and prolonged corrected QT peak interval in lead I (HR 1.02 95% CI 1.00,1.03, P = 0.044) were independently associated with death or nonfatal MI. Receiver-operator characteristic (ROC) analysis for the multivariate model against the primary end point yielded an area under the curve of 0.759 (95% CI 0.660,0.858), P < 0.001. Conclusions: QRS duration and QT peak are independently associated with increased risk of death or nonfatal MI in stable patients attending for coronary angiography. [source]

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti,tumor necrosis factor , therapy

ARTHRITIS & RHEUMATISM, Issue 7 2010
Jing Cui
Objective Anti,tumor necrosis factor , (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (,DAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ,DAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39,0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41,1.99). Conclusion Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections. [source]

Effectiveness of rituximab treatment in primary Sjögren's syndrome: A randomized, double-blind, placebo-controlled trial,

ARTHRITIS & RHEUMATISM, Issue 4 2010
J. M. Meijer
Objective To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sjögren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. Methods Patients with active primary SS, as determined by the revised American,European Consensus Group criteria, and a rate of stimulated whole saliva secretion of ,0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. Results Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean ± SD age of the patients receiving rituximab was 43 ± 11 years and the disease duration was 63 ± 50 months, while patients in the placebo group were age 43 ± 17 years and had a disease duration of 67 ± 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness,like disease. Conclusion These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS. [source]

Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: The randomized, double-blind, phase ii/iii systemic lupus erythematosus evaluation of rituximab trial,

ARTHRITIS & RHEUMATISM, Issue 1 2010
Joan T. Merrill
Objective B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE. Methods Patients entered with ,1 British Isles Lupus Assessment Group (BILAG) A score or ,2 BILAG B scores despite background immunosuppressant therapy, which was continued during the trial. Prednisone was added and subsequently tapered. Patients were randomized at a ratio of 2:1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. Results In the intent-to-treat analysis of 257 patients, background treatment was evenly distributed among azathioprine, mycophenolate mofetil, and methotrexate. Fifty-three percent of the patients had ,1 BILAG A score at entry, and 57% of the patients were categorized as being steroid dependent. No differences were observed between placebo and rituximab in the primary and secondary efficacy end points, including the BILAG-defined response, in terms of both area under the curve and landmark analyses. A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups. Safety and tolerability were similar in patients receiving placebo and those receiving rituximab. Conclusion The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse. No differences were noted between placebo and rituximab in the primary and secondary end points. Further evaluation of patient subsets, biomarkers, and exploratory outcome models may improve the design of future SLE clinical trials. [source]

Golimumab, a human anti,tumor necrosis factor , monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: Twenty-four,week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis,

ARTHRITIS & RHEUMATISM, Issue 8 2009
Paul Emery
Objective To assess the safety and efficacy of golimumab in methotrexate (MTX),naive patients with active rheumatoid arthritis (RA). Methods MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1). Results An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P = 0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P = 0.049) and between group 3 (40.5%; P = 0.038) but not group 4 (36.5%; P = 0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound ,5.2%; predefined delta value for noninferiority ,10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively. Conclusion Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns. [source]

Golimumab, a new human tumor necrosis factor , antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four,week efficacy and safety results of a randomized, placebo-controlled study,

ARTHRITIS & RHEUMATISM, Issue 4 2009
Arthur Kavanaugh
Objective To assess the efficacy and safety of golimumab in patients with active psoriatic arthritis (PsA). Methods Adult patients with PsA who had at least 3 swollen and 3 tender joints and active psoriasis were randomly assigned to receive subcutaneous injections of placebo (n = 113), golimumab 50 mg (n = 146), or golimumab 100 mg (n = 146) every 4 weeks through week 20. Efficacy assessments through week 24 included the American College of Rheumatology 20% improvement criteria (ACR20), the Psoriasis Area and Severity Index (PASI) in patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, the Short Form 36 Health Survey (SF-36), the disability index of the Health Assessment Questionnaire (HAQ), the Nail Psoriasis Severity Index (NAPSI), the physician's global assessment of psoriatic nail disease, and enthesitis (using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score [MASES] index). Results At week 14, 48% of all patients receiving golimumab, 51% of patients receiving golimumab 50 mg, and 45% of patients receiving golimumab 100 mg achieved an ACR20 response (the primary end point), compared with 9% of patients receiving placebo (P < 0.001 for all comparisons). Among the 74% of patients in whom at least 3% of the body surface area was affected by psoriasis at baseline, 40% of those in the golimumab 50 mg group and 58% of those in the golimumab 100 mg group had at least 75% improvement in the PASI at week 14 (major secondary end point), compared with 3% of placebo-treated patients (P < 0.001 for both doses). Significant improvement was observed for other major secondary end points (the HAQ and the SF-36), the NAPSI, the physician's global assessment of psoriatric nail disease, and the PsA-modified MASES index in each golimumab group compared with placebo. This efficacy was maintained through week 24. Golimumab was generally well tolerated. Conclusion Treatment with golimumab at doses of 50 mg and 100 mg significantly improved active PsA and associated skin and nail psoriasis through week 24. [source]

Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: A randomized placebo-controlled study,

ARTHRITIS & RHEUMATISM, Issue 4 2009
Gudrun E. Norby
Objective Patients with systemic lupus erythematosus (SLE), with or without end-stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE. Methods Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40,80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5,6-year trial, and then invited to continue in a 2-year open-label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7,8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures. Results Fluvastatin reduced low-density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3,40%), from a mean ± SD of 4.0 ± 0.9 mmoles/liter to 2.8 ± 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7,27.5%), from 6.4 ± 0.9 mmoles/liter to 5.1 ± 1.1 mmoles/liter. Compared with placebo-treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9,119.4], P = 0.064). Conclusion Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole. [source]

Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: A randomized, double-blind, placebo-controlled, dose-ranging study,

ARTHRITIS & RHEUMATISM, Issue 4 2008
Jonathan Kay
Objective To assess the efficacy, safety, and pharmacology of subcutaneous administration of golimumab in patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX). Methods Patients were randomly assigned in a double-blinded manner to receive injections of placebo plus MTX or 50 mg or 100 mg golimumab every 2 or 4 weeks plus MTX through week 48. Patients originally assigned to receive injections every 2 weeks had the interval increased to every 4 weeks starting at week 20. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. The study was powered to detect a difference in the primary end point when the combined golimumab groups and at least 1 of the individual dose groups were compared with placebo. Results The primary end point was attained. Sixty-one percent of patients in the combined golimumab plus MTX dose groups achieved an ACR20 response at week 16 compared with 37% of patients in the placebo plus MTX group (P = 0.010). In addition, 79% of patients in the group receiving 100 mg golimumab every 2 weeks achieved an ACR20 response (P < 0.001 versus placebo). Through week 20 (after which patients receiving placebo were switched to active infliximab therapy), serious adverse events were reported in 9% of patients in the combined golimumab groups and in 6% of patients in the placebo group. Conclusion Golimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well tolerated in patients with an inadequate response to MTX. [source]

Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: A double-blind, randomized, placebo-controlled trial

ARTHRITIS & RHEUMATISM, Issue 5 2007
Henrike van Dongen
Objective To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). Methods The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. Results In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). Conclusion This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients. [source]

Is there a prognostic role for C-reactive protein in ischemic stroke?

Safety of Selective Serotonin Reuptake Inhibitor Use Prior to Coronary Artery Bypass Grafting

CLINICAL CARDIOLOGY, Issue 6 2010
Glen L. Xiong MD
Background Selective serotonin reuptake inhibitors (SSRIs) have been shown to increase bleeding risks. This study examined the association of perioperative coronary artery bypass grafting (CABG) bleeding risks and SSRI use prior to CABG. Hypothesis SSRI may be associated with increased bleeding risks after CABG resulting in elevated reoperation rates due to bleeding complications. Methods Patients who underwent CABG between 1999 and 2003 (n = 4794) were identified in a tertiary medical center. SSRI use (n = 246) was determined using inpatient pharmacy records. Outcomes included primary end point of reoperation due to bleeding complications and other secondary measures. Multivariate regression models were constructed to adjust for baseline differences between SSRI and control groups. Results Reoperation due to bleeding complications among SSRI users was not significantly different (odds ratio [OR]: 1.14 (0.52,2.47); P = 0.75) compared to the control group. Other secondary outcomes and 30-day mortality (2.0% in SSRI vs 2.1% in control group; P = 0.92) between the 2 groups were similar. However, the adjusted total volume of postoperative red blood cell (RBC) units transfused was higher in the SSRI group. Conclusion We conclude that there is no compelling evidence to limit the use of SSRIs among patients with coronary artery disease who undergo CABG given the current evidence. Further research may be needed on individual SSRI medications. Copyright © 2010 Wiley Periodicals, Inc. [source]

Yellow Nail Syndrome in Three Siblings: A Randomized Double-Blind Trial of Topical Vitamin E

PEDIATRIC DERMATOLOGY, Issue 4 2006
Emily M. Lambert M.D.
It has rarely been reported in children and this is the first report of congenital yellow nails in siblings. The purpose of this study was to determine whether topical vitamin E applied to the nail plates and periungual skin would affect the growth rate or appearance of the fingernails in patients with congenital yellow nail syndrome. This study was the first trial of a treatment for this entity in children and the largest randomized double blind trial to date. We found that vitamin E solution had no significant effect (p = 0.84) on fingernail growth or the global appearance score (p = 1.0) when compared with placebo. The average growth rates and global assessment scores improved and onycholysis and onychomadesis decreased from baseline with both vitamin E and placebo treatment, although these were not primary end points of the study. Topical vitamin E did not result in a statistically significant improvement when compared with oil alone for the treatment of the nails in our three patients with yellow nail syndrome. However, it is interesting and perhaps clinically useful that both vitamin E and placebo oil improved the condition of the nails. [source]

Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: Results of a randomized, double-blind, placebo-controlled trial,

ARTHRITIS & RHEUMATISM, Issue 9 2010
Lesley M. Arnold
Objective To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia. Methods A double-blind, placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4,6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2-measure composite response required achievement of ,30% improvement from baseline in the pain score and a rating of "very much improved" or "much improved" on the Patient's Global Impression of Change (PGIC) scale. The 3-measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF-36) physical component summary (PCS) score. Results After 12 weeks of stable-dose treatment, a significantly greater proportion of milnacipran-treated patients compared with placebo-treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2-measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3-measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran-treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24-hour and weekly recall pain score, PGIC score, SF-36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P = 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo-adjusted rate of 15.8%). Conclusion Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia. [source]

Safety and efficacy of rituximab in systemic lupus erythematosus: Results from 136 patients from the French autoimmunity and rituximab registry

ARTHRITIS & RHEUMATISM, Issue 8 2010
Benjamin Terrier
Objective A number of open-label studies have suggested the potential benefit of rituximab (RTX) in systemic lupus erythematosus (SLE). However, in 2 recent randomized controlled trials (RCTs) of RTX, the primary end points were not met. We undertook this study to evaluate the safety and efficacy of RTX in off-trial patients with SLE seen in regular clinical practice. Methods We analyzed prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with RTX. Results One hundred thirty-six patients received treatment for SLE. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was 11.3 ± 8.9 at baseline. Severe infections were noted in 12 patients (9%), corresponding to a rate of 6.6/100 patient-years. Most severe infections occurred within the first 3 months after the last RTX infusion. Five patients died, due to severe infection (n = 3) or refractory autoimmune disease (n = 2). Overall response was observed in 80 of 113 patients (71%) by the SELENA,SLEDAI assessment. Efficacy did not differ significantly between patients receiving RTX monotherapy and those receiving concomitant immunosuppressive agents (who had higher baseline disease activity). Articular, cutaneous, renal, and hematologic improvements were noted in 72%, 70%, 74%, and 88% of patients, respectively. Among responders, 41% experienced a relapse of disease, with a response in 91% after retreatment with RTX. Conclusion Data from the AIR registry show a satisfactory tolerance profile and clinical efficacy of RTX in patients with SLE. The contrasting results with those from recent RCTs leave open the question of the therapeutic use of RTX in SLE. Additional controlled studies with new designs are needed to define the place of RTX in the therapeutic arsenal for SLE. [source]

Treatment of Acute Renal Failure in the Intensive Care Unit: Lower Costs by Intermittent Dialysis Than Continuous Venovenous Hemodiafiltration

ARTIFICIAL ORGANS, Issue 8 2009
Stefan Farese
Abstract Intermittent and continuous renal replacement therapies (RRTs) are available for the treatment of acute renal failure (ARF) in the intensive care unit (ICU). Although at present there are no adequately powered survival studies, available data suggest that both methods are equal with respect to patient outcome. Therefore, cost comparison between techniques is important for selecting the modality. Expenditures were prospectively assessed as a secondary end point during a controlled, randomized trial comparing intermittent hemodialysis (IHD) with continuous venovenous hemodiafiltration (CVVHDF). The outcome of the primary end points of this trial, that is, ICU and in-hospital mortality, has been previously published. One hundred twenty-five patients from a Swiss university hospital ICU were randomized either to CVVHDF or IHD. Out of these, 42 (CVVHDF) and 34 (IHD) were available for cost analysis. Patients' characteristics, delivered dialysis dose, duration of stay in the ICU or hospital, mortality rates, and recovery of renal function were not different between the two groups. Detailed 24-h time and material consumption protocols were available for 369 (CVVHDF) and 195 (IHD) treatment days. The mean daily duration of CVVHDF was 19.5 ± 3.2 h/day, resulting in total expenditures of ,436 ± 21 (21% for human resources and 79% for technical devices). For IHD (mean 3.0 ± 0.4 h/treatment), the costs were lower (,268 ± 26), with a larger proportion for human resources (45%). Nursing time spent for CVVHDF was 113 ± 50 min, and 198 ± 63 min per IHD treatment. Total costs for RRT in ICU patients with ARF were lower when treated with IHD than with CVVHDF, and have to be taken into account for the selection of the method of RRT in ARF on the ICU. [source]

Phase II study of induction chemotherapy with paclitaxel, ifosfamide, and carboplatin (TIC) for patients with locally advanced squamous cell carcinoma of the head and neck

CANCER, Issue 2 2002
Dong M. Shin M.D.
Abstract BACKGROUND This Phase II trial was conducted to determine the response rate, particularly of the primary sites, tolerability, and toxicity of induction chemotherapy of paclitaxel, ifosfamide, and carboplatin for patients with previously untreated locally advanced squamous cell carcinoma of the head and neck (SCCHN). We also hypothesized that improved complete response (CR) rates with the induction chemotherapy may render better survival rates with subsequently delivered definitive local treatment. METHODS All eligible patients with locally advanced SCCHN received two courses of induction chemotherapy and underwent repeated head and neck examination and computed tomography or magnetic resonance imaging scans. If the patients achieved responses (CR or partial [PR]), they received two more courses of chemotherapy before undergoing definitive local treatment. Induction chemotherapy consisted of paclitaxel (T; 175 mg/m2 in a 3-hour infusion) on Day 1, ifosfamide (I; 1000 mg/m2 in a 2-hour infusion) on Days 1,3 with intravenous mesna (200 mg/m2 before and 400 mg/m2 after ifosfamide), and carboplatin (C) using the Calvert formula for the area under the plasma concentration-versus-time curve of 6 on Day 1, repeated every 3,4 weeks. Prophylactic hematopoietic growth factors or antibiotics were not used in this study. Definitive local treatment was given based on the investigators' preference. RESULTS Fifty-four patients were registered and 52 patients were assessable for response to induction chemotherapy; 2 were not evaluable. After four courses of induction chemotherapy, the CR rates of the primary and lymph node sites were 60%, and 41%, respectively. For both primary and lymph node sites, there were 31% CRs and 50% PRs with an overall response rate of 81%. Five (9%) patients developed neutropenic fever, all of whom recovered with antibiotic therapy. Two (4%) patients had infection without neutropenia and recovered without any complication. Grade 3/4 thrombocytopenia and anemia occurred in three (6%) and four (7%) patients, respectively. Grade 3/4 fatigue developed in four (7%), arthralgia/myalgia in two (4%), peripheral neuropathy in two (4%), and orthostatic hypotension in two (4%) patients. One patient died of severe anaphylaxis although a maximized resuscitation effort was made. With a median follow-up of 22 months, the organ preservation rate was about 81% (42 of 52 patients). Although survival rates were not primary end points in this study, with a median follow-up of 22 months, 43 (83%) patients are still alive. Overall 1 and 2-year survival rates were 88% and 82%, respectively. Disease-free 1 and 2-year survival rates were 88% and 77% respectively. CONCLUSIONS TIC induction chemotherapy is associated with a high CR rate at the primary sites and with excellent survival and organ preservations rates with subsequently delivered definitive local therapy. The regimen was also well tolerated in the majority of patients. The TIC regimen should be developed further in the context of induction chemotherapy followed by concomitant chemoradiotherapy or with specific molecular targeted agents. Cancer 2002;95:322,30. © 2002 American Cancer Society. DOI 10.1002/cncr.10661 [source]