Ventriculoperitoneal Shunt Complications in the European Idiopathic Normal Pressure Hydrocephalus Multicenter Study.

Background: Ventriculoperitoneal shunt (VP-shunt) is the standard of treatment for idiopathic normal pressure hydrocephalus (iNPH). However, a thorough investigation of VP-shunt complications in this population is lacking.

Objective: To present the analysis and the rates of complications progressively occurring during the first year after shunt surgery in the patients with iNPH included in the European multicenter (EU-iNPH) study.

Does idiopathic normal pressure hydrocephalus always mean a poor prognosis?

Objective: The objective was to assess whether idiopathic normal-pressure hydrocephalus (iNPH) has a worse prognosis than other forms of hydrocephalus, as has been suggested.

Methods: A total of 125 patients with chronic hydrocephalus, 75 of whom suffered from iNPH and the remaining (non-INPH) from sNPH or non-communicating hydrocephalus, were shunted using gravitational valves. Clinical state was assessed with our clinical grading (KI) and a co-morbidity index (CMI).

Nonparametric equivalence testing with respect to the median difference.

The problem of comparing two independent groups of univariate data in the sense of testing for equivalence is considered for a fully nonparametric setting. The distribution of the data within each group may be a mixture of both a continuous and a discrete component, and no assumptions are made regarding the way in which the distributions of the two groups of data may differ from each other - in particular, the assumption of a shift model is avoided. The proposed equivalence testing procedure for this scenario refers to the median of the independent difference distribution, i.

Pharmacokinetics, safety, and efficacy of tipranavir boosted with ritonavir alone or in combination with other boosted protease inhibitors as part of optimized combination antiretroviral therapy in highly treatment-experienced patients (BI Study 1182.51).

Background: Given the limited treatment options for patients with high-level resistance, antiretroviral (ARV) regimens based on concomitant use of 2 ritonavir (RTV)-boosted protease inhibitors (PIs) were considered a therapeutic option.

Methods: Boehringer Ingelheim (BI) study 1182.51 examined the pharmacokinetic profile, safety, and efficacy of RTV-boosted tipranavir (TPV/r), alone and in combination with comparator PIs (CPIs) in 315 triple-class-experienced, HIV-infected patients.

Treatment response to ritonavir-boosted tipranavir versus ritonavir-boosted lopinavir in HIV-1 patients with higher lopinavir mutation scores.

Week 48 HIV-RNA treatment response to the protease inhibitor tipranavir co-administered with ritonavir was compared with that of lopinavir co-administered with ritonavir in patients whose baseline isolates had varying lopinavir genotypic mutation scores. With increasing lopinavir mutation scores, the proportion of patients achieving a week 48 treatment response was increased in the tipranavir/ritonavir compared with the lopinavir/ritonavir arm. Tipranavir/ritonavir therapy improves treatment response rates compared with lopinavir/ritonavir in patients whose viruses have reduced susceptibility to lopinavir/ritonavir.

A note on the power of Fisher's least significant difference procedure.

Fisher's least significant difference (LSD) procedure is a two-step testing procedure for pairwise comparisons of several treatment groups. In the first step of the procedure, a global test is performed for the null hypothesis that the expected means of all treatment groups under study are equal. If this global null hypothesis can be rejected at the pre-specified level of significance, then in the second step of the procedure, one is permitted in principle to perform all pairwise comparisons at the same level of significance (although in practice, not all of them may be of primary interest).

Oral p38 mitogen-activated protein kinase inhibition with BIRB 796 for active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

Background & Aims: The p38 mitogen-activated protein kinase (MAPK) regulates the expression of proinflammatory cytokines, which play a critical role in the pathophysiology of Crohn's disease (CD). This study investigated the efficacy and safety of BIRB 796, a highly potent inhibitor of p38 MAPK, in chronic active CD.

Methods: In a multicenter, multinational trial, 284 patients with moderate to severe CD were randomized to receive placebo, or 10, 20, 30, or 60 mg of BIRB 796 twice daily for 8 weeks.

Use of compressed gas precipitation to enhance the dissolution behavior of a poorly water-soluble drug: generation of drug microparticles and drug-polymer solid dispersions.

The classical anticonvulsant drug phenytoin (5,5-diphenyl hydantoin, C(15)H(12)N(2)O(2)) has been used as a model compound to investigate the possibility of enhancing the dissolution rate of poorly water-soluble drugs using dense gas antisolvent techniques. In a first step, microcrystals of neat phenytoin have been generated using the gas antisolvent (GAS) and precipitation with compressed antisolvent (PCA) processes, thereby assessing process performances and elucidating similarities and differences between the two techniques. In a second step, the PCA process has been used to generate solid dispersions of phenytoin in the hydrophilic polymer poly(vinyl-pyrrolidone)-K30 (PVP).

Phase-locked two-line OH planar laser-induced fluorescence thermometry in a pulsating gas turbine model combustor at atmospheric pressure.

Two-line OH planar laser-induced fluorescence (PLIF) thermometry was applied to a swirling CH4/air flame in a gas turbine (GT) model combustor at atmospheric pressure, which exhibited self-excited combustion instability. The potential and limitations of the method are discussed with respect to applications in GT-like flames. A major drawback of using OH as a temperature indicator is that no temperature information can be obtained from regions where OH radicals are missing or present in insufficient concentration.

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation.

Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine.

Background: Calcitonin gene-related peptide (CGRP) may have a causative role in migraine. We therefore hypothesized that a CGRP-receptor antagonist might be effective in the treatment of migraine attacks.

Methods: In an international, multicenter, double-blind, randomized clinical trial of BIBN 4096 BS, a highly specific and potent nonpeptide CGRP-receptor antagonist, 126 patients with migraine received one of the following: placebo or 0.