Guidance synthesis. Medical research for and with older people in Europe: proposed ethical guidance for good clinical practice: ethical considerations.

INTRODUCTION: In Europe the population is ageing rapidly. Older people are taking many medicinal products daily and these may not necessarily be suitable for them. Publications show that older patients are underrepresented in clinical trials, especially those over 75 years, with multiple co-morbidities, concomitant treatments and/or frailty. This document provides a summary of recommendations on ethical aspects of clinical trials with older people, who may in some cases be considered a vulnerable patient population. The EFGCP's Geriatric Medicine Working Party (GMWP) has developed this guidance to promote such research and to support health care professionals in their efforts. ETHICAL, SCOPE AND CONTEXT: The definition of a geriatric patient is reviewed. Frail and vulnerable patients, who are a minority of geriatric patients, should be included whenever it is relevant. The legal context is described. THE PROCESS OF INFORMED CONSENT: All adults should be presumed capable of consent, unless proven otherwise; informed consent must be sought for all older people who are able to consent. A simple, short and easy-to-understand information sheet and consent form will contribute to improving the readability and understanding of the older participant. A participant guide and the use of a simple tool to ensure decision making capacity, are recommended. Whenever older people are unable to consent, their assent should be sought systematically using adequate information, in addition to seeking the consent of their legal or authorised representative as appropriate. ETHICS COMMITTEES: Research ethics committees need internal and/or external geriatric expertise to balance the benefits and risks of research in older people and to appreciate and recognise their autonomy. DESIGN AND ANALYSES: Design and Analyses should be adapted to the objectives with appropriate outcomes and are not different from other clinical trials. CONCLUSIONS: The absence of proper recruitment or insufficient presence of older patients in clinical development plans for new medicinal products is detrimental; there is a need to improve evidence-based knowledge, understanding and management of their conditions and treatment. The aim of this guidance is to facilitate clinical research for and with the older patient population. The long version of the guidance will be available on the EFGCP's website: www.efgcp.be/.

Changes in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status following a 12 month cardiac exercise rehabilitation programme.

OBJECTIVE: To examine and evaluate improvements in cardiorespiratory fitness, psychological wellbeing, quality of life, and vocational status in postmyocardial infarction patients during and after a comprehensive 12 month exercise rehabilitation programme. SUBJECTS: The sample population comprised 124 patients with a clinical diagnosis of myocardial infarction (122 men and two women). INTERVENTIONS: 62 patients were randomly allocated to a regular weekly aerobic training programme, three times a week for 12 months, and compared with 62 matched controls who did not receive any formal exercise training. A five year follow up questionnaire/interview was subsequently conducted on this population to determine selected vocational/lifestyle changes. RESULTS: Significant improvements in cardiorespiratory fitness (p < 0.01-0.001), psychological profiles (p < 0.05-0.001), and quality of life scores (p < 0.001) were recorded in the treatment population when compared with their matched controls. Although there were no significant differences in mortality, a larger percentage of the regular exercisers resumed full time employment and they returned to work earlier than the controls. Controls took lighter jobs, lost more time from work, and suffered more non-fatal reinfarctions (p < 0.05-0.01). CONCLUSIONS: Regularly supervised and prolonged aerobic exercise training improves cardiorespiratory fitness, psychological status, and quality of life. The trained population also had a reduction in morbidity following myocardial infarction, and significant improvement in vocational status over a five year follow up period.

Effect of a novel potent platelet-activating factor antagonist, modipafant, in clinical asthma.

Platelet-activating factor (PAF), proposed as an important inflammatory mediator in asthma, reproduces several of the features of asthma, such as microvascular leakage, mucus secretion, bronchoconstriction, and possibly increased airway responsiveness. Modipafant (UK-80,067) is the (+)-enantiomer of UK-74,505, a potent and specific PAF antagonist. We have assessed the effect of modipafant over 28 d in adult subjects with moderately severe asthma in a placebo-controlled parallel group study. A total of 218 patients with asthma were enrolled into the single-blind run-in, of whom 120 (93 males and 27 females, mean age 41.0 yr) entered the double-blind treatment phase after demonstrating symptomatic asthma in the final week of the single-blind run-in phase. Patients could take up to 1600 micrograms inhaled corticosteroid and an inhaled beta 2 agonist as rescue medication. A total of 59 patients with asthma took modipafant (one 50 mg capsule twice daily), and 61 took matched placebo. There was no significant difference between placebo and modipafant in diurnal variation in PEF, morning and evening PEF, clinic FEV1, rescue bronchodilator usage, symptom score, or airway responsiveness. We previously showed that the racemate UK-74,505 had no effect on antigen challenge, and this study shows that the active (+)-enantiomer modipafant has no effect in chronic asthma. This suggests that PAF is not an important mediator in asthma.

Effect of nifedipine on physiologic shunting and oxygenation in chronic obstructive pulmonary disease.

PURPOSE: To assess changes in physiologic shunting and oxygenation following short-term treatment with nifedipine in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease. PATIENTS AND METHODS: Changes in pulmonary vascular pressure, pulmonary vascular resistance, venous admixture, and systemic arterial oxygen tension following sublingual administration of 20 mg of nifedipine were studied in 18 patients (13 men, 5 women; mean age of 59.7 [SD 7.2] years) using Swan-Ganz catheterization. These patients had a mean peak expiratory flow rate of 112 (SD 27) L/min (mean 22.2 [SD 12.2]% of predicted value), mean forced expiratory volume in 1 second (FEV1) of 0.84 (SD 0.23) L (mean 31.2 [SD 8.5]% of predicted value), mean FEV1/forced vital capacity ratio of 31.6 (SD 4.5), and mean carbon monoxide diffusing capacity of 6.8 (SD 1.96) mmol/min/kPa. RESULTS: There was a significant decrease in mean pulmonary vascular resistance (562 to 371 dyne sec.cm-5) and a significant reduction in the mean pulmonary arterial pressure (mean 32.8 to 23.6 mm Hg). Pulmonary venous admixture, however, increased significantly from the baseline mean of 44.6% (SD 16.1) to a mean of 56% (SD 15.6), and the mean arterial oxygen tension decreased from 5.8 (SD 1.3) kPa to 4.5 (SD 0.8) kPa at 60 minutes following drug administration (p < 0.001). CONCLUSION: The role of nifedipine in the treatment of pulmonary hypertension secondary to chronic bronchitis may be limited because of its deleterious effect on venous admixture.

Nedocromil sodium in adults with asthma dependent on inhaled corticosteroids: a double blind, placebo controlled study.

Eighty nine adults with asthma who were receiving inhaled corticosteroid and bronchodilator treatment took part in a double blind, randomised, placebo controlled trial of nedocromil sodium, 4 mg four times daily by inhalation. During a run in period of two to four weeks corticosteroid treatment was reduced when possible to produce a comparable level of symptoms across the trial population. The test treatment was then taken for four weeks, with the severity of asthma recorded daily by patients and assessed at two weekly hospital visits. There was an improvement in symptoms in the patients taking nedocromil sodium by comparison with those having the placebo, the differences being significant for diary card PEF readings, asthma symptom scores, and bronchodilator usage at night. The mean difference between the two groups was 18 l/min for PEF, 0.42 for daytime asthma score, and 1.73 puffs in 24 hours for bronchodilator usage. These results suggest that asthmatic patients who require inhaled steroids show better control of their asthma with the addition of nedocromil sodium than of placebo over a four week period after reduction of the dosage of their inhaled steroids.

Positive Kveim reaction in eosinophilic pneumonia.

The Kveim test is generally regarded as highly specific for sarcoidosis. We report two patients with pulmonary eosinophilia who had positive Kveim reactions. This association has not been previously reported.

The effect of nebulized bronchodilator therapy on intraocular pressures in patients with glaucoma.

A controlled double-blind crossover study of ocular complications associated with nebulized ipratropium bromide and salbutamol therapy for respiratory distress was undertaken in 46 chronic bronchitis patients. There was no significant rise in intraocular pressure or change in anterior chamber angle in patients with open-angle glaucoma, narrow-angle glaucoma or control subjects following treatment with either drug. However, when the two drugs were used in combination, intraocular pressure rose in patients with narrow-angle glaucoma but not in patients with open-angle glaucoma or in control subjects. Transient angle closure was seen in five of these patients. Intraocular pressures did not rise when swimming goggles were used to protect the eyes or when antiglaucoma treatment was continued. Nebulized bronchodilator therapy is safe in nonglaucomatous patients and those with open-angle glaucoma. Ocular complications can follow combined ipratropium bromide and salbutamol nebulization in patients with narrow-angle glaucoma, but can be prevented by using the drugs separately, protecting the eyes and ensuring continued antiglaucoma measures.