Associations of the correlates of protection and implication on the statistical power for demonstrating non-inferiority: application of a re-sampling method on a large phase III influenza vaccine clinical trial.

Background: In the later stage of the clinical development of new vaccines it is required to demonstrate their efficacy with the immunogenicity measures established as correlates for disease protection. Evaluation of interpandemic trivalent influenza vaccines is commonly assessed by three immunogenicity measures for each strain in different age groups: Seroprotection, Seroconversion and Geometric Mean Titers. US and European guidelines with respect to this topic have been issued for the licensure of new influenza vaccines.

Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder.

Background: Antagonism of corticotropin-releasing factor (CRF) receptors has been hypothesized as a potential target for the development of novel anxiolytics. This study was designed to determine the safety and efficacy of pexacerfont, a selective CRF-1 receptor antagonist, in the treatment of generalized anxiety disorder (GAD).

Method: This was a multicenter, randomized, double-blind, placebo-controlled and active comparator trial.

MF59-adjuvanted versus non-adjuvanted influenza vaccines: integrated analysis from a large safety database.

Background: Adding adjuvants such as MF59((R)) to influenza vaccines can enhance the immune response. This analysis evaluated the safety profile of MF59-adjuvanted [(+)MF59] compared with non-adjuvanted [(-)MF59] vaccines in a large clinical database.

Methods: Safety data were pooled from 64 clinical trials involving (+)MF59 seasonal and pandemic influenza vaccines.

Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants.

Introduction: Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.

Methods: Patients (N=1,147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2-20 mg/day).

Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes.

Objective: Dapagliflozin, a novel inhibitor of renal sodium-glucose cotransporter 2, allows an insulin-independent approach to improve type 2 diabetes hyperglycemia. In this multiple-dose study we evaluated the safety and efficacy of dapagliflozin in type 2 diabetic patients.

Research Design And Methods: Type 2 diabetic patients were randomly assigned to one of five dapagliflozin doses, metformin XR, or placebo for 12 weeks.

Safety, tolerability and immunogenicity of a mammalian cell-culture-derived influenza vaccine: a sequential Phase I and Phase II clinical trial.

This sequential, observer-blind, randomised, single-centre, combined Phase I and Phase II clinical trial compared the tolerability and immunogenicity of a single intramuscular dose of a novel cell-culture-derived influenza vaccine (CCIV), produced in Madin-Darby canine kidney cells, with a conventional egg-based vaccine. The immunogenicity of both vaccines was assessed by SRH assay, a well-recognized test by EMEA, in compliance with the requirements of the EU Committee for Medicinal Products for Human Use (CHMP). The Phase I part of the trial comprised 40 healthy adults (18-40 years of age); the subsequent Phase II part involved 200 healthy adult (n=80, 18-60 years of age) and elderly (n=120, > or =61 years of age) subjects.

The impact of stabilizing forces on postsurgical recovery in ostomy patients.

Purpose: Patient recovery from life-altering surgery is a complex event requiring interactions among multiple factors that influence recovery. Two such factors are occupational stability and spouse/partner relationship stability.

Methods: We surveyed persons who have undergone ostomy surgery.

The effect of azithromycin on ivermectin pharmacokinetics--a population pharmacokinetic model analysis.

Background: A recent drug interaction study reported that when azithromycin was administered with the combination of ivermectin and albendazole, there were modest increases in ivermectin pharmacokinetic parameters. Data from this study were reanalyzed to further explore this observation. A compartmental model was developed and 1,000 interaction studies were simulated to explore extreme high ivermectin values that might occur.

Plasmodium falciparum malaria vaccines in development.

The development and implementation of a malaria vaccine would constitute a major breakthrough for global health. Recently, numerous new candidates have entered clinical testing, following strategies that are as diverse as the malaria cycle is complex. While promising results have been obtained, some candidate vaccines have not fulfilled expectations.

Two decades of commitment to malaria vaccine development: GlaxoSmithKline Biologicals.

GlaxoSmithKline Biologicals (GSK) is committed to the development of a safe and effective malaria vaccine. Its research program in this field was initiated in 1984 and has been continuously active to this day, making it unparalleled within the vaccine industry. Although it works in partnerships with several leading organizations from the public sector, this effort has required GSK to invest major financial and human resource commitments, and its partners rely heavily on the company's global infrastructure and expertise in research, advanced clinical development, regulatory, large-scale manufacturing, and commercialization.

A clinical development paradigm for cancer vaccines and related biologics.

Therapeutic cancer vaccines are a heterogeneous group of complex biologics with distinctly different clinical characteristics than cytotoxic agents. The current clinical development paradigm used for oncology drug development is based on criteria developed for cytotoxic agents. More flexible and focused developmental guidelines are needed to address the unique characteristics of therapeutic cancer vaccines.

The 'no-touch' method of intermittent urinary catheter insertion: can it reduce the risk of bacteria entering the bladder?

Objective: This in vitro model was designed to determine whether using a no-touch method for catheter preparation and insertion would affect the degree of contamination transmitted to intermittent urinary catheters.

Setting: Northview Laboratories, Northbrook, IL 60062, USA.

Methods: This was a parallel experimental study conducted in vitro at an independent testing laboratory under Good Manufacturing Practices.

Erectile dysfunction: interrelationship with the metabolic syndrome.

Erectile dysfunction (ED) is more commonly seen in men with various components of the metabolic syndrome (a constellation of various cardiovascular and diabetes risk factors). ED can be considered as a risk marker of the metabolic syndrome and its associated conditions. The patient with ED should be thoroughly evaluated for coexisting vascular disease.

A perspective on the current strategies for the treatment of obesity.

The prevalence in obesity has increased dramatically over the past 30 years, more than double in the United States alone. Obesity is associated with an increased risk for type 2 diabetes mellitus, dyslipidemia, hypertension, biliary disease, obstructive sleep apnea, and certain types of cancer. The pathophysiology of obesity is complex, involving behavioral, environmental, and genetic factors.

Randomized, phase II dose-finding studies of a modified tick-borne encephalitis vaccine: evaluation of safety and immunogenicity.

Two clinical studies were conducted to identify the optimal dose of a modified tick-borne encephalitis (TBE) vaccine (FSME-IMMUN "new") in adults. A prospective, randomised, phase II, double-blind dose-finding study with the FSME-IMMUN "new" vaccine was performed in volunteers aged 16-65 years (n=405) to evaluate the immunogenicity and safety of two vaccinations with three vaccine doses (0.6, 1.

Point-of-care testing in diabetes mellitus.

Diabetes mellitus is an excellent case study of the evolution, and successful application, of point-of-care testing. It offers a valuable history of the way in which technology has evolved, and continues to evolve, to meet the needs of patients whilst also providing for a more optimal delivery of care. Diabetes mellitus is also a good exemplar of where test and treatment regimes must operate in complete harmony in order to achieve the greatest benefit.

Tau therapeutics for Alzheimer's disease: the promise and the challenges.

The pathological diagnosis of Alzheimer's disease (AD) depends on the presence of plaques consisting of the beta-amyloid peptide as well as neurofibrillary tangles consisting of paired helical filaments (PHFs) of the tau (tau) protein. The role of each type of pathology in the pathogenesis and progression of AD remains unclear. Previous hypotheses suggested that these two processes were independent, whereas more recent data suggest that there may be a bidirectional interaction between these two pathological processes.

Comparison of pramipexole, fluoxetine, and placebo in patients with major depression.

Pramipexole, a dopamine D2 receptor agonist, was tested in 174 patients with major depression, with or without melancholia and without psychotic features. Three daily dose levels (0.375 mg, 1.

Assessing pharmacokinetic and pharmacodynamic interactions in clinical trials of antiepileptic drugs.

An understanding of the pharmacokinetic and pharmacodynamic properties of a drug is a basic requirement for its clinical use. The investigations of these properties and their timing are fairly clearly defined in the drug development process. Without fundamental knowledge of the pharmacokinetics and pharmacodynamics of a drug, a physician could not use it appropriately, nor would a regulatory agency be likely to approve its use.