Home About us Contact
|
Home About us Contact | ||
|
|
||
Prevention Trials (prevention + trials)
Selected AbstractsAntiepileptogenesis and Seizure Prevention Trials with Antiepileptic Drugs: Meta-Analysis of Controlled TrialsEPILEPSIA, Issue 4 2001Nancy R. Temkin Summary: ,Purpose: To synthesize evidence concerning the effect of antiepileptic drugs (AEDs) for seizure prevention and to contrast their effectiveness for provoked versus unprovoked seizures. Methods: Medline, Embase, and The Cochrane Clinical Trials Register were the primary sources of trials, but all trials found were included. Minimal requirements: seizure-prevention outcome given as fraction of cases; AED or control assigned by random or quasi-random mechanism. Single abstracter. Aggregate relative risk and heterogeneity evaluated using Mantel,Haenszel analyses; random effects model used if heterogeneity was significant. Results: Forty-seven trials evaluated seven drugs or combinations for preventing seizures associated with fever, alcohol, malaria, perinatal asphyxia, contrast media, tumors, craniotomy, and traumatic brain injury. Effective: Phenobarbital for recurrence of febrile seizures [relative risk (RR), 0.51; 95% confidence interval (CI), 0.32,0.82) and cerebral malaria (RR, 0.36; CI, 0.23,0.56). Diazepam for contrast media,associated seizures (RR, 0.10; CI, 0.01,0.79). Phenytoin for provoked seizures after craniotomy or traumatic brain injury (craniotomy: RR, 0.42; CI, 0.25,0.71; TBI: RR, 0.33; CI, 0.19,0.59). Carbamazepine for provoked seizures after traumatic brain injury (RR, 0.39; CI, 0.17,0.92). Lorazepam for alcohol-related seizures (RR, 0.12; CI, 0.04,0.40). More than 25% reduction ruled out valproate for unprovoked seizures after traumatic brain injury (RR, 1.28; CI, 0.76,2.16), and carbamazepine for unprovoked seizures after craniotomy (RR, 1.30; CI, 0.75,2.25). Conclusions: Effective or promising results predominate for provoked (acute, symptomatic) seizures. For unprovoked (epileptic) seizures, no drug has been shown to be effective, and some have had a clinically important effect ruled out. [source] Topiramate Treatment of Chronic Migraine: A Randomized, Placebo-Controlled Trial of Quality of Life and Other Efficacy MeasuresHEADACHE, Issue 8 2009Stephen Silberstein MD Objective., To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial. Background., We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated. Methods., Variables analyzed included between-treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache-free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine-Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change. Results., The intent-to-treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate- vs placebo-treated subjects were as follows: for ,25% reduction: 68.6% vs 51.6% (P = .005); ,50%: 37.3% vs 28.8% (P = .093); and ,75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache-free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine-Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine-Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062). Conclusions., In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events. [source] Long-Term Migraine Prevention With Topiramate: Open-Label Extension of Pivotal TrialsHEADACHE, Issue 7 2006Alan Rapoport MD Objective.,To demonstrate that topiramate is an effective and generally well-tolerated migraine preventive therapy when used for up to 14 months. Background.,Topiramate 100 and 200 mg/d significantly reduced mean monthly migraine frequency during 2 large, 26-week, randomized, placebo-controlled trials. Only a small number of clinical trials have examined the long-term (,1 year) effectiveness and safety of migraine preventive therapies. Methods.,Five hundred sixty-seven patients with an established history of migraine with or without aura were enrolled in this 8-month, open-label extension of 2 large (49 US and 52 US and Canadian medical centers), randomized, double-blind, placebo-controlled, parallel group, 26-week trials of identical design. To be eligible for the open-label extension, patients were required to have either completed the double-blind phase of the 2 pivotal migraine prevention trials or withdrew after 4 weeks due to lack of efficacy. All eligible patients, regardless of type or dose of study medication (topiramate or placebo) received in the double-blind phase, were titrated to a clinically effective dose of open-label topiramate based on physician judgment of patient response. Efficacy of topiramate was measured as the change in mean monthly migraine frequency. Results.,The mean topiramate dose during the open-label extension phase was 124.7 mg/d and 150.3 mg/d for patients on placebo (n = 159) or topiramate (n = 408), respectively, during the double-blind phase (N = 567, 91% female, mean age 39.4 years). Patients on topiramate for up to 14 months had 2.2 ± 2.4 (mean ± SD) migraines per month after completion of the open-label extension phase (3.4 ± 2.6 at double-blind endpoint). Patients on topiramate during the open-label extension phase only (placebo during the double-blind phase) had 3.0 ± 2.9 migraines per month at open-label extension endpoint (4.9 ± 3.0 migraines per month at double-blind endpoint). Discontinuation rates due to adverse events during the double-blind phase were 22.2% for patients on topiramate and 11.0% for patients on placebo. Discontinuation rates due to adverse events during the open-label extension phase were 8.6% for those patients who had already received topiramate during the double-blind phase and 20.9% for those patients who had previously received placebo. Conclusions.,Patients receiving topiramate experienced a sustained reduction in migraine frequency for up to 14 months. The effectiveness and safety of topiramate was consistent with that observed during 2 26-week pivotal trials. [source] Influence of Gender on Arrhythmia Characteristics and Outcome in the Multicenter UnSustained Tachycardia TrialJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2004ANDREA M. RUSSO M.D. Introduction: Previous studies have demonstrated gender differences in risk of sudden death in patients with ischemic heart disease. The Multicenter UnSustained Tachycardia Trial (MUSTT) evaluated the ability of therapy guided by electrophysiologic (EP) testing to reduce mortality in patients with coronary disease, ejection fraction ,40%, and spontaneous nonsustained ventricular tachycardia. Methods and Results: We analyzed the influence of gender on results of EP testing and outcome of patients enrolled in MUSTT. Women made up 14% of the overall MUSTT population and were less likely than men to have inducible sustained randomizable ventricular arrhythmias (24% vs 36%, P < 0.001). Baseline characteristics differed between men and women. In randomized patients, women were older, more likely to have had an infarction within 6 months, more likely to have a history of heart failure, and more likely to have recent angina prior to enrollment than men (P < 0.05). In the EP-guided therapy group, there was no difference in implantable cardioverter defibrillator implantation rate in men and women (45% vs 53%, P = 0.38). There also were no significant gender influences on risk of arrhythmic death or cardiac arrest (2-year event rate 9% in women and 12% in men, adjusted hazard ratio 0.88) or overall mortality (2-year event rate 32% in women vs 21% in men, adjusted hazard ratio 1.51). Conclusion: The outcome and benefit of EP-guided therapy in this trial did not appear to be influenced by gender. However, due to the small numbers of women in the trial, small differences in outcome may not be apparent. Plans for future primary prevention trials should include careful risk stratification of women who less often have inducible sustained ventricular arrhythmias and better left ventricular function despite more frequent heart failure. [source] Defibrillation Threshold Testing: Tradition or Necessity?PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2009CHRISTOF KOLB M.D. Implantable cardioverter defibrillators (ICDs) have become an essential tool for primary and secondary prevention of sudden cardiac death. Traditionally, defibrillation threshold (DFT) testing is part of the "lege artis" ICD implantation. Taking into consideration that the absolute mortality reduction in primary prevention trials is estimated around 8% and in secondary prevention trials around 7%, it is only in these patients that an acceptable DFT is expected to affect survival. Using a high-energy ICD, the likelihood of obtaining an inadequate DFT is about 2.5%. Thus, the number of patients needed to be subjected to DFT testing in order to avert one potential death is about 500. Application of antitachycardia pacing for rapid ventricular tachycardias further reduces the percentage of patients dependent on reliable ICD defibrillation capability. Thus, the mortality rate that can be prevented by DFT testing is below 0.2%. This contrasts a 0.4% risk of life-threatening complications and a low but not negligible mortality risk owed to the procedure. Although in light of these data the balance between DFT-related risk and benefit seems to tilt toward the former, insights gained from prospective randomized trials will clarify whether the abandonment of routine DFT testing can be claimed on a rightful basis. [source] Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factorsARTHRITIS & RHEUMATISM, Issue 10 2009Carolina Llanos Objective Identifying the frequency of recurrent cardiac manifestations of neonatal lupus (NL) in a second child is critical to understanding the pathogenesis of anti-SSA/Ro,mediated injury and would improve counseling strategies regarding future pregnancies and power the design of clinical prevention trials. Accordingly, this study was undertaken to address the recurrence rates of cardiac NL and associated risk factors in a large US-based cohort. Methods Families enrolled in the Research Registry for Neonatal Lupus were evaluated for rates of recurrence of cardiac NL and potential risk factors, with a focus on pregnancies immediately following the birth of an affected child. Results The overall rate of recurrence of cardiac NL in 161 pregnancies of 129 mothers with anti-SSA/Ro antibodies was 17.4% (95% confidence interval 11.1,23.6%). Analysis of the potential risk factors among 129 mothers with a pregnancy immediately following the birth of a child with cardiac NL showed that the maternal diagnosis was not associated with the outcome in a subsequent pregnancy. In this group, 23% of mothers who were either asymptomatic or had an undifferentiated autoimmune syndrome, compared with 14% of mothers with systemic lupus erythematosus or Sjögren's syndrome, had a second child with cardiac NL (P = 0.25). The recurrence rate was not statistically significantly different in mothers who had taken steroids compared with those who had not taken steroids (16% versus 21%; P = 0.78). The antibody status of the mother was not predictive of outcome in subsequent pregnancies. Moreover, death of the first child with cardiac NL was not predictive of recurrence of cardiac NL in a subsequent pregnancy (P = 0.31). The risk of cardiac NL was similar between male and female children (17.2% versus 18.3%; P = 1.0). Conclusion In this cohort, the overall recurrence rate for cardiac NL was 17%. The recurrence rate appeared to be unaffected by maternal health, use of steroids, antibody status, severity of cardiac disease in the first affected child, or sex of the subsequent child. [source] Statistical Methods for Analyzing Right-Censored Length-Biased Data under Cox ModelBIOMETRICS, Issue 2 2010Jing Qin Summary Length-biased time-to-event data are commonly encountered in applications ranging from epidemiological cohort studies or cancer prevention trials to studies of labor economy. A longstanding statistical problem is how to assess the association of risk factors with survival in the target population given the observed length-biased data. In this article, we demonstrate how to estimate these effects under the semiparametric Cox proportional hazards model. The structure of the Cox model is changed under length-biased sampling in general. Although the existing partial likelihood approach for left-truncated data can be used to estimate covariate effects, it may not be efficient for analyzing length-biased data. We propose two estimating equation approaches for estimating the covariate coefficients under the Cox model. We use the modern stochastic process and martingale theory to develop the asymptotic properties of the estimators. We evaluate the empirical performance and efficiency of the two methods through extensive simulation studies. We use data from a dementia study to illustrate the proposed methodology, and demonstrate the computational algorithms for point estimates, which can be directly linked to the existing functions in S-PLUS or R. [source] Time-Dependent ROC Curves for Censored Survival Data and a Diagnostic MarkerBIOMETRICS, Issue 2 2000Patrick J. Heagerty Summary. ROC curves are a popular method for displaying sensitivity and specificity of a continuous marker, X, for a binary disease variable, D. However, many disease outcomes are time dependent, D(t, and ROC curves that vary as a function of time may be mire appropriate. A common examples of a time-dependent variable is vital status, where D(t) = 1 if a patient has died prior to time t and zero otherwise. We propose summarizing the discrimination potential of a marker X, measured at baseline (t= 0), by calculating ROC Curves for cumulative disease or death incidence by time t, which we denote as ROC(t). A typical complexity with survival data is that observations may be censored. Two ROC curve estimators are proposed that can accommodate censored data. A simple estimator is based on using the Kaplan-Meier estimated for each possible subset X > c. However, this estimator does not guarantee the necessary condition that sensitivity and specificity are monotone in X. An alternative estimator that does guarantee monotonicity is based on a nearest neighbor estimator for the bivariate distribution function of (X, T), where T represents survival time (Akritas, M. J., 1994, Annals of Statistics22, 1299,1327). We present an example where ROC(t) is used to compare a standard and a modified flow cytometry measurement for predicting survival after detection of breast cancer and an example where the ROC(t) curve displays the impact of modifying eligibility criteria for sample size and power in HIV prevention trials. [source] Prevention of sudden cardiac deathCLINICAL CARDIOLOGY, Issue S1 2005Eric N. Prystowsky M.D. Abstract It is often unclear why some patients suffer sudden cardiac death (SCD), or even what risk factors correlate best with the syndrome. This review describes current thinking on the prevention of SCD. Most studies have focused on the prevention of potentially fatal ventricular arrhythmias in patients post myocardial infarction (MI). While pharmacotherapy has a role in the prevention of SCD in patients post MI, the interpretation of drug trials can be problematic. This is because not all patients participating in such trials received optimized medical therapy by today's standards. As a result, trial outcomes for new therapies may not reflect their true efficacy when they are added to a background of best medical care. The two principal prophylactic modalities for SCD studied to date are antiarrhythmic drug therapy and use of an implantable cardioverter defibrillator (ICD). At the present time, antiarrhythmic drugs, such as the class III agent amiodarone, seem to display relatively limited efficacy for the primary prevention of sudden death in most patients post MI. Most clinical trials have found that ICD therapy has a significant mortality benefit in patients at high risk for ventricular arrhythmias. This has been demonstrated in primary prevention trials, and in secondary prevention trials such as Antiarrhythmics Versus Implantable Defibrillators (AVID), which studied patients who survived a near-fatal ventricular arrhythmia. Based on an analysis of secondary prevention trials, the single patient characteristic that best predicted an advantage of ICD therapy over antiarrhythmic drug therapy was a left ventricular (LV) ejection fraction , 35%. Cardiac resynchronization therapy has been established as having a mortality benefit in patients with dyssynchronous LV contraction associated with dilated cardiomyopathy. [source] | |||||||||||||||||||