Tiotropium Respimat inhaler and the risk of death in COPD.

Background: Tiotropium delivered at a dose of 5 μg with the Respimat inhaler showed efficacy similar to that of 18 μg of tiotropium delivered with the HandiHaler inhalation device in placebo-controlled trials involving patients with chronic obstructive pulmonary disease (COPD). Although tiotropium HandiHaler was associated with reduced mortality, as compared with placebo, more deaths were reported with tiotropium Respimat than with placebo.

Methods: In this randomized, double-blind, parallel-group trial involving 17,135 patients with COPD, we evaluated the safety and efficacy of tiotropium Respimat at a once-daily dose of 2.

The Tiotropium Safety and Performance in Respimat Trial (TIOSPIR), a large scale, randomized, controlled, parallel-group trial-design and rationale.

Background: Tiotropium bromide is an effective therapy for COPD patients. Comparing across programs tiotropium Respimat Soft Mist inhaler was at least as efficacious as tiotropium HandiHaler, however, concerns have been raised about tiotropium's safety when given via Respimat.

Methods: The TIOSPIR trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat 5 μg once daily (marketed) and 2.

Randomized clinical study comparing Compeed cold sore patch to acyclovir cream 5% in the treatment of herpes simplex labialis.

Background: Hydrocolloid technology has been proven effective in treating dermal wounds. A previous study showed that a newly developed thin hydrocolloid patch [Compeed cold sore patch (CSP)] provided multiple wound-healing benefits across all stages of a herpes simplex labialis (HSL) outbreak.

Methods: An assessment of CSP efficacy and safety was conducted in an international, multicentre, assessor-blinded study, which enrolled 728 subjects with a history of recurrent HSL.

Childhood appendicitis in the United Kingdom: fifty years of progress.

The number of in-hospital deaths in children aged 0 to 14 years from acute appendicitis in England and Wales has fallen from an annual average of 36.2 in 1963 through 1967 to 1.8 in 1993 through 1997, and the case-fatality rate from 1.

A pooled analysis of adjunctive topiramate in refractory partial epilepsy.

Objectives: To evaluate the impact of different dosages of topiramate (TPM) add-on to stable antiepileptic therapy for refractory partial epilepsy in adults.

Material And Methods: Pooled intention-to-treat analysis of six similarly designed double-blind, placebo-controlled trials, including 481 patients treated with doses of TPM 200, 400, 600 and 800 mg/day, and 265 patients receiving placebo.

Results: Seizures were reduced by >/=50% from baseline in 41% of TPM-treated patients and 15% of placebo-treated patients (P < 0.

A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy.

Objective: To evaluate topiramate as monotherapy in adults and children with recently diagnosed, localization-related epilepsy, comparing two dosages of topiramate in a multicenter, randomized, double-blind study.

Methods: Adults and children (>/=3 years of age) were eligible if the maximum interval since epilepsy diagnosis was 3 years and patients had one to six partial-onset seizures during a 3-month retrospective baseline. At study entry, patients (N = 252) were untreated or receiving one antiepileptic drug for less than 1 month.

Monotherapy trials: presurgical studies.

Presurgical evaluation of patients with refractory partial seizures provides a unique opportunity to perform a placebo-controlled, monotherapy trial. Some patients undergoing presurgical evaluations must have all of their antiepileptic drugs (AEDs) tapered in order to induce seizures and therefore such patients are possible candidates for a placebo-controlled monotherapy trial. Often, EEG monitoring is continued throughout the trial period, thus patients either receiving placebo or whose seizures do not completely respond to the active drug are still evaluated to determine whether or not surgery is feasible, supporting the validity of a trial in this setting.

Proof of efficacy trials: choosing the dose.

It is apparent from current usage of antiepileptic drugs (AEDs) and from retrospective review of their drug development programmes, that the doses currently used in clinical practice differ from those which were used in clinical trials. This raises the question of how dose and titration schedules are selected in early development. An integral component of a drug development programme should be an assessment of dose response.

A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures.

Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerability and prevents cognitive impairment.

Methods: The study is a multicenter, randomized, observer-blinded, parallel-group clinical trial with VPA or TPM given as first-line add-on therapy to steady-state treatment with CBZ.

Topiramate as add-on therapy: pooled analysis of randomized controlled trials in adults.

Purpose: Six double-blind, placebo-controlled trials were conducted with topiramate (TPM) initiated as adjunctive therapy in adults with treatment-resistant partial-onset seizures with or without secondary generalization.

Methods: Because protocols and study populations were similar, data from the studies were pooled and analyzed for 527 patients treated with TPM and 216 treated with placebo.

Results: Seizures were reduced > or =50% in 43% of TPM-treated patients and in 12% of placebo-treated patients (p < 0.

The value of the number-needed-to-treat method in antiepileptic drug trials.

Purpose: There is controversy between clinicians and statisticians on the appropriateness of the number needed to treat (NNT) as a summary statistic to report the effectiveness of a treatment. We examine the two viewpoints and make proposals concerning the reporting of clinical trial results.

Methods: In the context of antiepileptic treatments, we explain the two different viewpoints and illustrate the use of the odds ratio, relative risk, absolute difference, and NNT on the results of randomized clinical trials with topiramate (TPM).

A note on the number needed to treat.

The concept of the average number of patients needed to treat to prevent a single bad outcome is becoming increasingly popular among clinicians. Defined as the inverse of the absolute risk reduction (delta), its sample estimate is denoted as NNT. Here we discuss the mathematical and statistical properties of NNT and show that simple calculations, like taking sums of different NNTs, can give nonsensical results.

A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group.

Objective: To evaluate the efficacy and safety of topiramate as adjunctive therapy for Lennox-Gastaut syndrome in a multicenter, double-blind, placebo-controlled trial.

Background: Conventional antiepileptic drugs are frequently ineffective against multiple-seizure types of Lennox-Gastaut syndrome.

Methods: Ninety-eight patients >1 year to <30 years of age, with slow spike-and-wave patterns on EEG, seizure types including drop attacks, and either a history of or active atypical absence seizures, were assigned to an 11-week, double-blind treatment phase with either topiramate or placebo.

A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Topiramate YP Study Group.

Objective: To evaluate the efficacy and safety of topiramate 6 mg/kg/day in children (age 2 to 16 years) as adjunctive therapy for uncontrolled partial-onset seizures with or without secondarily generalized seizures in a multicenter, randomized, double-blind, placebo-controlled trial.

Methods: Patients with at least six partial-onset seizures during the 8-week baseline phase were treated with either topiramate (n = 41) or placebo (n = 45) for 16 weeks.

Results: Topiramate-treated patients had a greater median percent reduction from baseline in average monthly partial-onset seizure rate than placebo-treated patients (33.

A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Topiramate YTC Study Group.

Background And Objective: Topiramate is effective as adjunctive treatment of partial-onset seizures in adults. The efficacy and safety of topiramate as adjunctive therapy for the treatment of primary generalized tonic-clonic (PGTC) seizures were investigated in a randomized, double-blind, placebo-controlled study.

Methods: Eighty patients, 3 to 59 years old, who experienced three or more PGTC seizures during an 8-week baseline phase were randomly assigned to treatment with either topiramate (n = 39) or placebo (n = 41).

Topiramate monotherapy for partial onset seizures.

Purpose: Evaluation of topiramate (TPM) as monotherapy in patients with uncontrolled partial onset seizures.

Methods: A total of 48 patients were evaluated in a double-blind, parallel-group trial. During a 56-day baseline period, patients had at least eight partial onset seizures while being treated with one or two standard antiepileptic drugs (AEDs).

Topiramate as adjunctive therapy in refractory partial epilepsy: pooled analysis of data from five double-blind, placebo-controlled trials.

A pooled analysis of data from five similarly designed double-blind, placebo-controlled trials of topiramate (TPM) as add-on therapy in patients with partial epilepsy was performed. The pooled analysis allowed evaluation of efficacy end points and response to treatment for a number of study subgroups not statistically evaluable in the individual study analyses due to limited sample sizes. The five trials included 534 patients, 360 who received TPM at target dosages of 200-1,000 mg daily and 174 who received placebo.

Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy.

The efficacy and safety of topiramate 400 mg/day as adjunctive therapy to traditional antieleptic drugs for partial onset seizures with or without secondary generalization were assessed in a double-blind, parallel-group, placebo-controlled trial. Forty-seven patients with at least one seizure per week during an 8 week baseline were randomly assigned to topiramate (N = 23) or placebo (N = 24) double-blind treatment for a 3 week titration and an 8 week stabilization period. Median percent reduction from baseline in monthly seizure frequency during the double-blind phase was not significantly greater in the topiramate group than in the placebo group (41% vs.