Marie Townsend

How should we measure function in patients with chronic heart and lung disease

To elucidate the characteristics of measures of function in patients with chronic heart failure and chronic lung disease we administered four functional status questionnaires, a 6-min walk test and a cycle ergometer exercise test, to 43 patients limited in their day to day activities as a result of their underlying heart or lung disease. Correlations between these measures were calculated using Spearmans rank order correlation coefficient. The walk test correlated well with the cycle ergometer (r = 0.579), and almost as well with the four functional status questionnaires (r = 0.473-0.590) as the questionnaires did with one another (0.423-0.729). On the other hand, correlations between cycle ergometer results and the questionnaires was in each case 0.295 or lower, and none of these correlations reached statistical significance. These results suggest that exercise capacity in the laboratory can be differentiated from functional exercise capacity (the ability to undertake physically demanding activities of daily living) and that the walk test provides a good measure of function in patients with heart and lung disease.

A comparison of Likert and visual analogue scales for measuring change in function

Many controlled trials rely on subjective measures of symptoms or quality of life as primary outcomes. The relative merits of different response options for these measures is an important, but largely unexplored, issue. Therefore, we compared the responsiveness of seven-point Likert vs visual analogue scales (VAS) in a questionnaire measuring quality of life in chronic lung disease. The VAS and seven-point scale versions of the questionnaire were administered to 28 patients before and after completing an inpatient respiratory rehabilitation program of known benefit. For all four dimensions of the questionnaire (dyspnea, fatigue, emotional function, and mastery) the VAS showed a larger improvement than the seven-point scale when both were standardized on a scale of 0-10. However, in each case the variability of the improvement was greater using the VAS. The difference in improvement between the two scales was not statistically significant. We conclude that the two methods of presenting response options show comparable responsiveness. The ease of administration and interpretation of the seven-point scale recommend its use in clinical trials.

A controlled trial of digoxin in congestive heart failure

Because of conflicting results from studies examining the usefulness of digoxin in congestive heart failure (CHF) patients in sinus rhythm, a cross-over trial was conducted in which 20 patients received 7 weeks of digoxin titrated to a level of 1.54 to 2.56 nmol/liter and 7 weeks of matched placebo. The order of treatments was determined by random allocation and patients, clinicians and research staff were blind to allocation. In patients with deteriorating condition, the treatment period was terminated and outcome measures were obtained. If deterioration occurred during the first period, the patient was crossed over without the code being broken. Seven patients required premature termination of study periods because of increasing symptoms of CHF. All 7 were taking placebo at the time (p = 0.016). Small differences in dyspnea (p = 0.044), walking test score (p = 0.055), clinical assessment of CHF (p = 0.036) and ejection fraction (p = 0.004) favored the digoxin treatment group. Patients with more severe CHF were more likely to benefit from digoxin administration. It was concluded that oral digoxin, in doses titrated to produce a serum level of 1.54 to 2.56 nmol/liter, improved quality of life and functional exercise capacity in some patients with CHF in sinus rhythm.

Should study subjects see their previous responses

To test the relative merits of administering questionnaires with previous responses available (the informed condition) or unavailable (the blind condition), we administered blind and informed versions of a quality of life questionnaire to two groups of patients. One, a group of 43 stable subjects with chronic cardiorespiratory disease, were seen three times at fortnightly intervals; a separate series of 13 patients with chronic lung disease were evaluated before and after optimization of therapy. In the stable patients the informed strategy resulted in substantial decrease in the variance in the measurement of dyspnea, fatigue, and of emotional function. Large improvements in dyspnea, fatigue, and emotional function seen in patients undergoing treatment optimization were comparable using blind and informed methods. These results suggest that by letting patients see their previous responses we can decrease the sample size needed to detect changes in quality of life in clinical trials.

Acute Response to Bronchodilator: An Imperfect Guide for Bronchodilator Therapy in Chronic Airflow Limitation

We conducted a four-period cross-over randomized trial in which we found that patients with chronic airflow limitation demonstrated symptomatic improvement with both inhaled albuterol and oral theophylline. The response, however, was not uniform. We therefore tested the ability of acute change in forced expired volume in one second (FEV1) following inhaled beta agonist to predict long-term symptomatic response to albuterol and theophylline. We found that the reproducibility of acute change in FEV1 over three repetitions was poor (intraclass correlation 0.17). Furthermore, the mean improvement FEV1 following inhaled albuterol across the three repetitions did not relate closely to symptomatic response to either albuterol or theophylline. We conclude that acute response to inhaled beta agonist is not useful for identifying patients with chronic airflow limitation who are likely to benefit from bronchodilator treatment.

SHOULD STUDY SUBJECTS SEE THEIR PREVIOUS RESPONSES: DATA FROM A RANDOMIZED CONTROL TRIAL

To test the relative merits of administering questionnaires with previous responses available (the informed condition) or unavailable (the blind condition), we administered blind and informed versions of a quality of life questionnaire (the Chronic Respiratory Disease Questionnaire, or CRQ) in a randomized, double-blind trial of bronchodilators in chronic airflow limitation. The responsiveness of the two methods, as reflected in the p-values associated with salbutamol and theophylline effects were comparable for three of the four dimensions of the CRQ. The data suggested possible increased responsiveness of the informed method for the emotional function dimension of the questionnaire. Changes in the informed CRQ dyspnea and fatigue dimensions showed stronger correlations with changes in spirometry, 6 minute walk distance, and rating of dyspnea after the walk test than did blind administration. Further, changes in all four CRQ dimensions showed stronger correlations with corresponding global ratings using the informed questionnaire. These results suggest that by letting study subjects see their previous responses the validity of subjective measures of health status in clinical trials can be improved.

Health-related quality-of-life assessment of prenatal diagnosis: chorionic villi sampling and amniocentesis.

This study assesses the health-related quality-of-life (HRQL) effects of chorionic villi sampling (CVS) and genetic amniocentesis (GA), including both process and outcomes of prenatal diagnosis. The HRQL of 126 women participating in a randomized controlled clinical trial of CVS versus GA in Toronto and Hamilton, Ontario, was assessed in four interviews at weeks 8, 13, 18, and 22 of pregnancy. Statistical analyses included analysis of variance, repeated measures analysis of covariance, chi-square, Fishers exact test, Students t-tests, and paired t-tests. Utility scores for patients undergoing CVS exceeded those for GA patients at week 18 (p = 0.04). Utility scores for hypothetical health states did not differ significantly by trial arm. CVS results in slightly improved HRQL during prenatal diagnosis. This advantage needs to be weighed against the high disutility patients attach to infrequent outcomes associated with pregnancy losses, equivocal diagnoses, and diagnostic inaccuracy.

Treatment of cryptosporidiosis with spiramycin in AIDS. An «N of 1» trial

We describe a randomized, double-blind, placebo-controlled, crossover trial with spiramycin in a single patient with acquired immune deficiency syndrome (AIDS) and a severe secretory diarrhea caused by cryptosporidium. Spiramycin, a potentially harmful antibiotic, had no clinical or microbiological effect in this patient. The application of the single patient (N of 1) trial to common clinical problems is a simple way to analyze the value of different therapeutic approaches. The time-consuming, expensive, multi-patient trial with ultimate extrapolation to the individual patient can be avoided. Single-patient trials can influence management and improve patient care and have potentially wide use in patients with gastrointestinal disease.