Primary endpoint discrepancies were found in one in ten clinical drug trials. Results of an inception cohort study.

Objective: To identify the occurrence and determinants of protocol-publication discrepancies in clinical drug trials.

Study Design And Setting: All published clinical drug trials reviewed by the Dutch institutional review boards in 2007 were analyzed. Discrepancies between trial protocols and publications were measured among key reporting aspects.

Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands.

Objectives: The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol.

Study Design And Setting: All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators.

Non-Publication Is Common among Phase 1, Single-Center, Not Prospectively Registered, or Early Terminated Clinical Drug Trials.

The objective of this study was to investigate the occurrence and determinants of non-publication of clinical drug trials in the Netherlands.All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followed-up from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination.

Occurrence and determinants of selective reporting of clinical drug trials: design of an inception cohort study.

Introduction: Responsible conduct of research implies that results of clinical trials should be completely and adequately reported. This article describes the design of a cohort study that aims to investigate the occurrence and the determinants of selective reporting in an inception cohort of all clinical drug trials that were reviewed by the Dutch Institutional Review Boards (IRBs) in 2007. It also describes the characteristics of the study cohort.

[Review of multicentre clinical trials is simplified; more trial centres are approved in the first assessment round].

The CCMO (the Dutch Central Committee on Research Involving Human Subjects) has evaluated the External Review Directive. This new directive for multicentre clinical trials reduces the administrative burden in approving medical research involving human subjects. The number of trial centres approved in the primary decision has increased.

[Patient safety in clinical intervention research].

In clinical intervention research, the monitoring of patient safety is essential. In December 2009, a symposium on the role of the different parties involved was organised. Research starts with a robust protocol with a section dealing with interim decision-making and procedures for reporting during the research.

Change in inflammation in out-patient COPD patients from stable phase to a subsequent exacerbation.

Background: Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes. Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes.

Aim: To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations.

Lipid-soluble components in cigarette smoke induce mitochondrial production of reactive oxygen species in lung epithelial cells.

Reactive oxygen species (ROS) present in cigarette smoke (CS) are thought to contribute to the development of COPD. Although CS-ROS can hardly enter airway epithelial cells, and certainly not the circulation, systemic levels of ROS have been found to be elevated in COPD patients. We hypothesize that lipophilic components present in CS can enter airway epithelial cells and increase intracellular ROS production by disturbing mitochondrial function.

Cross-sectional assessment of daily physical activity in chronic obstructive pulmonary disease lung transplant patients.

Background: Information about daily physical activity of chronic obstructive pulmonary disease (COPD) lung transplant patients is relevant for evaluation of the functional recovery of physical capacity after lung transplantation. The objective of this study was to cross-sectionally assess daily physical activity, pulmonary function, physical fitness, fear of physical activity and motivation to exercise in COPD patients who were lung transplant candidates and lung transplant recipients.

Methods: Fifteen COPD lung transplant candidates (5 men and 10 women, mean age 53 years, forced expiratory volume in 1 second [FEV(1)] 20% predicted) and 47 recipients (18 men and 29 women, mean age 55 years, FEV(1) 93% predicted, 39 bilateral and 8 unilateral transplants) were enrolled in this observational study.

Depressive symptoms as predictors of mortality in patients with COPD.

Objective: Prognostic studies of mortality in patients with COPD have mostly focused on physiologic variables, with little attention to depressive symptoms. This stands in sharp contrast to the attention that depressive symptoms have been given in the outcomes of patients with other chronic health conditions. The present study investigated the independent association of depressive symptoms in stable patients with COPD with all-cause mortality.

Anti-inflammatory effects of combined budesonide/formoterol in COPD exacerbations.

Systemic corticosteroids and additional short-acting beta2-agonists are commonly used in exacerbations of chronic obstructive pulmonary disease (COPD). In this double-blind study, the combination of a high-dose inhaled corticosteroid with a rapid-onset long-acting beta2-agonist was evaluated in the treatment of out-patient COPD exacerbations. The primary aim was to compare 14-day treatment effects of budesonide/formoterol to placebo on sputum eosinophils and, secondarily, on other indices of inflammation, forced expiratory flow in one second (FEV(1)), symptoms, health status, and adverse events.

FVC to slow inspiratory vital capacity ratio: a potential marker for small airways obstruction.

Background: The ratio of FVC to slow inspiratory vital capacity (SVC) has been reported to reflect small airways obstruction, but its validity as such is still unclear. The aim of this study was to assess the applicability of the FVC/SVC ratio as a marker of small airways function in patients with bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX), which is a disorder in which predominantly small airways obstruction causes progressive airflow limitation.

Methods: The FVC/SVC ratio was analyzed both cross-sectionally and longitudinally in 39 patients (26 men) with BOS after bilateral LTX (median age, 47 years; interquartile range [IQR], 35 to 54 years), and 36 bilateral lung transplant recipients without BOS (14 men; median age, 46 years; IQR, 41 to 53 years).

Cyclosporin A-induced oxidative stress is not the consequence of an increase in mitochondrial membrane potential.

Cyclosporin A induces closure of the mitochondrial permeability transition pore. We aimed to investigate whether this closure results in concomitant increases in mitochondrial membrane potential (DeltaPsim) and the production of reactive oxygen species. Fluorescent probes were used to assess DeltaPsim (JC-1, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl-carbocyanine iodide), reactive oxygen species [DCF, 5- (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester] and [Ca2+][Fluo-3, glycine N-[4-[6-[(acetyloxy)methoxy]-2,7-dichloro-3-oxo-3H-xanthen-9-yl]-2-[2-[2-[bis[2-[(acetyloxy)methoxy]-2-oxyethyl]amino]-5-methylphenoxy]ethoxy]phenyl]-N-[2-[(acetyloxy)methoxy]-2-oxyethyl]-(acetyloxy)methyl ester] in human kidney cells (HK-2 cells) and in a line of human small cell carcinoma cells (GLC4 cells), because these do not express cyclosporin A-sensitive P-glycoprotein.

Safety of sputum induction during exacerbations of COPD.

Sputum induction (SI) is considered to be a safe tool for assessing airway inflammation in stable patients with COPD, but little is known about its safety during exacerbations. We therefore assessed the safety of SI during COPD exacerbations. SI data from 44 COPD patients were assessed both in the stable phase and during exacerbation.

Cigarette smoke-induced blockade of the mitochondrial respiratory chain switches lung epithelial cell apoptosis into necrosis.

Increased lung cell apoptosis and necrosis occur in patients with chronic obstructive pulmonary disease (COPD). Mitochondria are crucially involved in the regulation of these cell death processes. Cigarette smoke is the main risk factor for development of COPD.

Changes in personal control as a predictor of quality of life after pulmonary rehabilitation.

Objective: Perceptions of mastery and self-efficacy may be related to better outcomes in pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). This study examined (1) whether patients with COPD improved during a rehabilitation programme with respect to quality of life (QoL) and perceptions of self-efficacy and mastery, and (2) whether increased perceptions of mastery and self-efficacy contributed to a higher QoL after rehabilitation.

Methods: Thirty-nine consecutive COPD patients (aged 60.

The relationship between self-efficacy and self-reported physical functioning in chronic obstructive pulmonary disease and chronic heart failure.

In this study, the authors investigated whether self-reported physical functioning of patients with chronic obstructive pulmonary disease (COPD) and chronic systolic heart failure (CHF) was primarily explained by illness-specific differences related to diagnosis or whether more generic factors also contributed to their physical functioning. Consecutive patients with COPD (n = 56; mean age = 67.8, SD = 8.

Incomplete quality of life data in lung transplant research: comparing cross sectional, repeated measures ANOVA, and multi-level analysis.

Background: In longitudinal studies on Health Related Quality of Life (HRQL) it frequently occurs that patients have one or more missing forms, which may cause bias, and reduce the sample size. Aims of the present study were to address the problem of missing data in the field of lung transplantation (LgTX) and HRQL, to compare results obtained with different methods of analysis, and to show the value of each type of statistical method used to summarize data.

Methods: Results from cross-sectional analysis, repeated measures on complete cases (ANOVA), and a multi-level analysis were compared.

Stress, psychological distress, and coping in patients on the waiting list for lung transplantation: an exploratory study.

Little information is available in literature on quality of life, stress and coping during the period patients are waiting for lung transplantation. This study explored potential stressful events that patients experience during the waiting period assessed the level of anxiety and depression and explored the use of coping strategies. Cross sectional analysis were performed.

First study of infliximab treatment in patients with chronic obstructive pulmonary disease.

Rationale: Tumor necrosis factor-alpha is believed to be important in the induction and maintenance of airway inflammation in chronic obstructive pulmonary disease.

Objectives: We aimed to evaluate the effect of the anti-tumor necrosis factor-alpha drug infliximab in patients with chronic obstructive pulmonary disease, with percentage of sputum neutrophils as the primary endpoint.

Methods: We performed an exploratory single-center, double-blind, placebo-controlled, randomized, phase 2 trial in which 22 current smokers with mild-to-moderate chronic obstructive pulmonary disease participated.

Consequences of chronic obstructive pulmonary disease and chronic heart failure: the relationship between objective and subjective health.

This study investigates whether the relationship between objective health parameters and general health perceptions was mediated by symptoms of dyspnoea and physical functioning in patients with chronic obstructive pulmonary disease (COPD) and patients with chronic heart failure (CHF). The different health parameters were organised according to Wilson and Cleary's conceptual model of patient outcomes (Wilson & Cleary (1995). Journal of the American Medical Association, 273, 59-65).

Airway cellular response to two different immunosuppressive regimens in lung transplant recipients.

A number of new immunosuppressive drugs have become available in transplant medicine. We investigated the effects of two different immunosuppressive protocols on bronchoalveolar lavage fluid cellular characteristics in 34 lung transplant recipients who were treated with anti-thymocyte globulin induction therapy, cyclosporine, azathioprine (AZA), and prednisolone (regimen I), compared with 17 recipients receiving basiliximab induction, tacrolimus, AZA, and prednisolone (regimen II). We performed bronchoalveolar lavages between 15 and 40 d post-transplantation, in stable clinical condition and no acute rejection, cytomegalovirus, and/or respiratory tract infection.

Feasibility of sputum induction in lung transplant recipients.

Sputum induction (SI) is nowadays being applied as a non-invasive and safe method to investigate airway inflammation in pulmonary diseases. We investigated the feasibility of SI after lung transplantation (LTX), and compared sputum and bronchoalveolar lavage (BAL) cellular characteristics and interleukin-8 (IL-8) levels. Results were also compared with 11 healthy subjects.