Measuring respiratory symptoms in clinical trials of COPD: reliability and validity of a daily diary.

BACKGROUND: Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease. OBJECTIVE: To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). METHODS: Qualitative: patient focus group and interviews to address content validity. Quantitative: secondary data analyses to test reliability and validity. RESULTS: Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male. Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure. Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male. Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score. Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively. VALIDITY: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms). RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05). E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001). CONCLUSIONS: Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD. Further study of sensitivity to change is warranted.

Psychometric analysis of the Three-Factor Eating Questionnaire-R21: results from a large diverse sample of obese and non-obese participants.

BACKGROUND: The 21-item Three-Factor Eating Questionnaire (TFEQ-R21) is a scale that measures three domains of eating behavior: cognitive restraint (CR), uncontrolled eating (UE) and emotional eating (EE). OBJECTIVES: To assess the factor structure and reliability of TFEQ-R21 (and if necessary, refine the structure) in diverse populations of obese and non-obese individuals. DESIGN: Data were obtained from obese adults in a United States/Canadian clinical trial (n=1741), and overweight, obese and normal weight adults in a US web-based survey (n=1275). Confirmatory factor analyses were employed to investigate the structure of TFEQ-R21 using baseline data from the clinical trial. The model was refined to obtain adequate fit and internal consistency. The refined model was then tested using the web-based data. Relationships between TFEQ domains and body mass index (BMI) were examined in both populations. RESULTS: Clinical data indicated that TFEQ-R21 needed refinement. Three items were removed from the CR domain, producing the revised version TFEQ-R18V2 (Comparative Fit Index (CFI)=0.91). Testing TFEQ-R18V2 in the web-based sample supported the revised structure (CFI=0.96; Cronbach's coefficient alpha of 0.78-0.94). Associations with BMI were small. In the clinical study, the CR domain showed a significant and negative association with BMI. On the basis of the web-based survey, it was shown that the relationship between BMI and CR is population-dependent (obese versus non-obese, healthy versus diabetics). CONCLUSIONS: In two independent datasets, the TFEQ-R18V2 showed robust factor structure and good reliability. It may provide a useful tool for characterizing UE, CR and EE.

Evaluating the Power of Food Scale in obese subjects and a general sample of individuals: development and measurement properties.

BACKGROUND: The Power of Food Scale (PFS) was developed to assess the psychological impact of today's food-abundant environments. OBJECTIVE: To evaluate the structure of the PFS in diverse populations of obese and nonobese individuals. DESIGN: Data were obtained from obese adults in a clinical trial for a weight management drug (n=1741), and overweight, obese and normal weight adults in a Web-based survey (n=1275). Exploratory and confirmatory factor analyses were used to investigate the PFS structure using the clinical data. The model developed was then tested using the Web-based data. Relationships between PFS domains and body mass index (BMI) were examined. Logistic regression was used in the Web-based survey to evaluate the association between obesity status and PFS scores. RESULTS: Clinical data indicated that the scale was best represented by a 15-item version with three subscale domains and an aggregate domain (average of three domains); this was confirmed with data from the Web-based survey (Comparative Fit Index: 0.95 and 0.94 for the clinical and Web-based studies, respectively). Cronbach's alpha for both data sets was high, ranging from 0.81 to 0.91. The relationships between BMI and each domain were weak (and approximately linear). A full category increase in PFS domain score (range 1-5) increased the odds of being obese 1.6-2.3 times. CONCLUSIONS: The 15-item PFS is best represented by three domains and an aggregate domain. The PFS may provide a useful tool to evaluate the effects of obesity treatments on feelings of being controlled by food in an obesogenic food environment.

Health-related quality of life in patients receiving reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation.

Reduced-intensity conditioning allogeneic HSCT (RIC) has less regimen-related morbidity and mortality than myeloablative allogeneic HSCT (MT) offering allogeneic transplantation to patients otherwise excluded. Whether these advantages improve health-related quality of life (HRQL) is unknown. We examined the HRQL effects of RIC and MT in patients with hematological diseases pre-transplant (baseline), days 0, 30, 100, 1 and 2 years following HSCT. HRQL was measured using the Short Form-36 Health Survey and the Functional Assessment of Cancer Therapy - General and BMT. Data were analyzed using mixed linear modeling adjusting for baseline HRQL differences. Patients (RIC=41, MT=35) were predominately male (67%), in remission/stable disease (65%) with an Eastern Cooperative Oncology Group status

Effect of domperidone on the health-related quality of life of patients with symptoms of diabetic gastroparesis.

OBJECTIVE: To describe the health-related quality of life (HRQOL) of patients with insulin-treated diabetes and symptoms of diabetic gastroparesis and to assess the impact of domperidone on HRQOL in these patients. RESEARCH DESIGN AND METHODS: This two-phase multicenter study was part of a safety and efficacy investigation. Phase I involved 4-week single-blind treatment with domperidone 20 mg q.i.d. (n=269). Patients demonstrating significant symptomatic improvement (n=208) continued to phase 11, a 4-week, double-blind, parallel-group study with patients receiving placebo (n=103) or domperidone (n=105). Patients completed the Medical Outcomes Study Short-Form-36 Health Survey at selection and at the end of each phase. Physical component summary (PCS) and mental component summary (MCS) scores served as primary parameters, and the eight subscales were secondary parameters. RESULTS: HRQOL scores of subjects enrolled in the trial were significantly lower than norms from the general population and people with diabetes (P < 0.001). Subjects experiencing symptomatic improvement after 4 weeks of single-blind treatment demonstrated significant improvement in all HRQOL parameters (P < 0.001); PCS, MCS, and six subscale scores of nonresponders did not change. Between-group change score differences were significant for PCS, MCS, and seven subscales (P < 0.05 to P < 0.001). During phase II, the domperidone group maintained their HRQOL; the placebo group showed a significant decline in PCS and four subscales (P < 0.05). The between-group difference in the PCS score change was statistically significant (-1.77 vs. 0.65, P=0.05). CONCLUSIONS: Results suggest that patients with symptoms of diabetic gastroparesis experience notable HRQOL impairment and that symptomatic relief with domperidone is accompanied by improvements in HRQOL that can be sustained over 4 weeks of treatment.

Seizure frequency and the health-related quality of life of adults with epilepsy.

OBJECTIVE: To compare the health-related quality of life (HRQL) of a nonsurgical sample of adults with epilepsy with that of age- and gender-equivalent norms, and to analyze the relative importance of seizure frequency, time since last seizure, gender, and comorbidity on HRQL in the epilepsy sample. METHODS: Data were obtained from 139 adults with epilepsy from three US centers and published norms on the Medical Outcomes Study Short-Form 36 (SF-36). Patients were classified according to number of seizures over the prior 4 weeks (zero, one to five, six or more). Bivariate and multivariate modeling was used. RESULTS: HRQL scores for seizure-free patients were similar to the general population. Significant differences between seizure frequency groups were found for seven domains and the physical and mental component summary scales of the SF-36 (p<0.001). No differences were found in bodily pain. The largest differences were in physical role and social functioning, and general health (p<0.001). In the multivariate model, seizure frequency was a significant inverse predictor of HRQL across all domains (p<0.01 to 0.001). Men reported poorer physical function than women (p<0.05), and patients with a comorbid condition had poorer HRQL in the areas of pain (p<0.05) and general health perception (p<0.01). Time since last seizure was not related uniquely to HRQL. CONCLUSIONS: Seizure-free adults can have HRQL levels comparable with those of the general population. As seizure frequency increases, patients report more impaired HRQL, regardless of time since last seizure, gender, and comorbid status. Potential for difficulties in HRQL should be considered in clinical assessment and in evaluating treatment outcomes.

Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators.

The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.

Integrating patient preferences into health outcomes assessment: the multiattribute Asthma Symptom Utility Index.

STUDY OBJECTIVE: To develop and evaluate a brief, easy-to-administer symptom assessment scale for use as a preference-based outcome measure in clinical trials and cost-effectiveness studies in asthma. DESIGN: Cross-sectional survey with 2-week reproducibility assessment. SETTING: Ambulatory care: university asthma and allergy center. PARTICIPANTS: One hundred sixty-one adults with asthma, 59% female, mean age 35+/-11 years. Mean FEV1 percent predicted was 86+/-17%. INTERVENTIONS: The 11-item Asthma Symptom Utility Index (ASUI). MEASUREMENTS AND RESULTS: Mean ASUI score for this sample was 0.71+/-0.23, with a range from 0.02 to 1.0. The ASUI was reproducible (intraclass correlation coefficient = 0.74) and able to distinguish patients known to differ on disease severity according to clinician ratings (p < 0.001) and by an asthma disease severity scale score (p < 0.001). The instrument was also significantly correlated with FEV1 percent predicted (r = 0.27, p < 0.001), the Asthma Quality of Life Questionnaire (r = 0.77, p < 0.001), and the Health Utilities Index Mark 2 (r = 0.36, p < 0.001). CONCLUSION: The results of this study support the reliability and validity of the ASUI, suggesting it will be a useful, complementary patient outcome measure for clinical trials and cost-effectiveness studies comparing treatment alternatives for persons with asthma.

Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. DOM-USA-5 Study Group.

The purpose of this clinical study was to determine the efficacy, tolerability, and impact on quality of life of domperidone--a specific peripherally acting dopamine antagonist--in the management of symptoms of gastroparesis, a common and potentially debilitating condition in patients with diabetes mellitus. In the first phase of this multicenter, two-phase withdrawal study, 287 diabetic patients with symptoms of gastroparesis of at least 6 months' duration received domperidone 20 mg QID in a single-masked fashion for 4 weeks. Efficacy was evaluated using a four-point rating scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) for each of the following symptoms: nausea, abdominal distention/bloating, early satiety, vomiting, and abdominal pain. At the end of the first phase, patients with sufficient improvement in their total symptom score (a score < or = 6 and a decrease in score of > or = 5 units from the baseline [selection] visit) were eligible for the 4-week, randomized, placebo-controlled, double-masked withdrawal phase of the study. The impact of domperidone on quality of life was determined using the Medical Outcomes Study Short Form-36 (SF-36). Of 269 patients with data from the single-masked phase, 208 (77%) qualified for entry into the double-masked phase based on a statistically significant improvement in total symptom score, from a mean score of 10.32 at baseline (initial visit) to 3.79 after 4 weeks of single-masked domperidone therapy. During the double-masked phase, patients in the placebo group had significantly greater deterioration in total symptom scores compared with patients in the domperidone group (mean changes of 1.84 and 0.85, respectively). Similar significant differences in favor of domperidone were seen in the secondary efficacy variables (i.e., patients' diary scores and global assessments of symptoms). The tolerability profile of domperidone was similar to that of placebo. Patients who responded to domperidone experienced significant improvements in quality of life, as indicated by the SF-36 physical and mental component summary scores. During the double-masked phase, patients who were randomized to placebo experienced a significant deterioration in the physical component summary score compared with patients in the domperidone group. The results of this study suggest that domperidone 20 mg QID provides significant improvement in the upper gastrointestinal symptoms of diabetic gastroparesis and is well tolerated in patients with this condition.

The relationship between memory performance, perceived cognitive function, and mood in patients with epilepsy.

OBJECTIVE: The low correlations between memory performance and subjective memory may be attributable to disparities between tasks in neuropsychological tests and cognitive experiences of day-to-day living. This study evaluated the relationship between everyday memory performance, perceived cognitive functioning, and mood among patients with epilepsy. METHODS: From three epilepsy centers in the USA, 138 patients were recruited. Everyday memory performance was measured using the Rivermead Behavioural Memory Test (RBMT). Questionnaires assessed perceived cognitive function (cognitive domain, Quality of Life in Epilepsy Inventory, QOLIE-89) and mood (Profile of Mood States, POMS). RESULTS: Memory performance scores were weakly correlated with perceived cognitive functioning (r =0.22, P < 0.01). Perceived cognitive functioning was strongly correlated with mood (r = - 0.75, P < 0.0001). Multiple regression analysis indicated memory performance (RBMT) and mood (POMS) were independent predictors of perceived cognitive functioning (P < 0.02); however, the explained variance for RBMT and POMS combined (R2 = 0.58) is only slightly higher than the predictive value for the POMS score alone (R2 = 0.56). CONCLUSIONS: Memory performance tests provide qualitatively different information than patients' self-reported cognitive difficulties, thus it is important to assess memory performance, perceived cognitive function, and mood separately because the constructs are related but not redundant.

Health-related quality of life assessment in euthymic and depressed patients with bipolar disorder. Psychometric performance of four self-report measures.

The purpose of this study was to evaluate the psychometric properties of selected health-related quality of life (HRQL) self-report measures in 62 euthymic and depressed patients diagnosed with bipolar disorder. Patients completed the Quality of Life in Depression Scale (QLDS), Mental Health Index-17 (MHI-17), Cognitive Function Scale, and Medical Outcomes Study Short Form-36 (SF-36) at baseline and 8 weeks following treatment. Hamilton and Young Rating Scales were used to assess clinical status and validate the HRQL measures. The MHI-17, Cognitive Function Scale, QLDS, and SF-36 social function, vitality, role limitations-emotional, and mental health scales have good reliability and validity, and are responsive to changes in clinical status in patients with bipolar disorder. Although the small sample size limits generalizablity, euthymic and depressed outpatients with bipolar disorder appear to contribute reliable self reports on selected aspects of their quality of life.

Evaluating symptoms in chronic obstructive pulmonary disease: validation of the Breathlessness, Cough and Sputum Scale.

This study examined the reliability and validity of a new measure for evaluating symptoms in patients with chronic obstructive pulmonary disease (COPD): the Breathlessness, Cough and Sputum Scale (BCSS). Designed as a daily diary, the BCSS is a patient-reported outcome measure that asks patients to rate the severity of the three symptoms, each on a 5-point scale; higher scores indicate more severe symptoms. Item scores are summed to yield a total score. Secondary analysis of data were from two multinational trials (n = 629; 765). The BCSS item and total scores exhibited evidence of internal consistency (alpha = 0.70 daily; 0.95 to 0.99 over time) and reproducibility (ICC = 0.77 to 0.88). Correlations (r) with pulmonary function (FEV1 % predicted, PEF) were -0.01 (n.s.) to -0.36 (P < 0.001). Correlations with the St George's Respiratory Questionnaire total and SF-36 Physical Functioning subscale were 0.44 to 0.59 (P < 0.0001). Breathlessness and total scores differentiated patients by disease severity (P < 0.01) and rescue medication use (P < 0.01). Cough, sputum, and total scores increased with sputum volume (r = 0.27, 0.30, 0.31; P < 0.001). Patients for whom treatment was moderately or highly effective reported significant improvements in BCSS scores (P < 0.0001). Results suggest that the BCSS is a reliable, valid, and responsive patient-reported outcome measure of symptom severity in patients with COPD.

Evaluating Health-related quality-of-life outcomes in patients with congestive heart failure. A review of recent randomised controlled trials.

Congestive heart failure (CHF) is a chronic disorder characterised by fatigue, shortness of breath and congestion. Treatment is designed to relieve symptoms, halt or delay progression of the disease, prolong life and, ultimately, improve quality of life. The purpose of this paper is to identify recent trends in the assessment of health-related quality-of-life (HR-QOL) outcomes in randomised, controlled trials evaluating treatment effectiveness in patients with CHF. 41 studies using HR-QOL as an explicit outcome and published in English between 1990 and September 1998 were reviewed. Trends in the measurement of HR-QOL and evidence of treatment effectiveness are presented followed by a discussion of the implications for future research. Results suggest that pharmacological and nonpharmacological treatment regimens can have a positive impact on HR-QOL. However, treatment-related improvement in exercise capacity in patients with CHF was not consistently associated with improvement in all domains of HR-QOL. The primary HR-QOL domain affected by treatment appears to be the performance of daily activities, which may or may not be accompanied by enhanced well-being. This suggests that functional status should be considered a primary HR-QOL end-point in clinical intervention trials. Preference-based or utility assessment, ethnic group differences in treatment effectiveness, caregiver burden and cost effectiveness are understudied outcomes in CHF research.

Psychometric properties of the VSQLQ in black patients with mild hypertension. Vital Signs Quality of Life Questionnaire.

The Vital Signs Quality of Life Questionnaire (VSQLQ) is a condition- and culture-specific measure designed to assess health-related quality of life (HRQL) in black patients with hypertension. This study examined the instrument's reliability and validity when administered via personal interview to patients with mild systemic hypertension. Data were gathered from 304 black patients during the screening visit of a multicenter trial evaluating the efficacy of candesartan cilexetil (ATACAND). In addition to internal consistency and reproducibility, validity was assessed by correlating the VSQLQ with the Short Form-36 (SF-36). Sensitivity to sociodemographic effects and responsiveness to change was also examined. Cronbach's alpha levels were high (0.90, 0.92, 0.92 for frequency, intensity and combined scores, respectively) and the instrument was stable in patients reporting no health change over 8 weeks (ICC = 0.79, 0.79, and 0.80). Correlations between the VSQLQ and the SF-36 were moderate to high (0.32 to - 0.69) and statistically significant (p < 0.001). VSQLQ scores varied by gender, education, and income (p < 0.05). Patients who reported improvement in their general health status also reported significant improvements on the VSQLQ (n = 90; p < 0.05). Results support the reliability and validity of VSQLQ administered via personal interview to black patients with mild systemic hypertension.

Sample sizes and power computation for clinical intervention trials.

The purpose of this article was to describe basic concepts of sample size and power estimation for planning nursing intervention trials and interpreting their results. Simple mathematical calculations, using the formulas presented here, can be used to estimate the number of subjects required to conduct a study with a designated effect size and level of power. These methods are of great importance, since most funding agencies require sample size and power estimations before a grant is awarded. In general, studies with power lower than .7 or .8 need careful consideration before they are implemented. In these situations, it may be wise to consider various alternatives for obtaining study subjects or deleting treatment groups for investigations involving more than two groups. The formulas presented here can also be useful in estimating the power of published research findings. Through a quick calculation, the consumer of nursing research can critically evaluate the meaning of a negative trial and draw appropriate conclusions for future research and practice.

Reliability and validity of the Modified Erikson Psychosocial Stage Inventory in diverse samples.

The Modified Erikson Psychosocial Stage Inventory (MEPSI) is a relatively simple survey measure designed to assess the strength of psychosocial attributes that arise from progression through Erikson's eight stages of development. The purpose of this study was to employ secondary analysis to evaluate the internal-consistency reliability and construct validity of the MEPSI across four diverse samples: healthy young adults, hemophilic men, healthy older adults, and older adults with chronic obstructive pulmonary disease. Special attention was given to the performance of the measure across gender, with exploratory analyses examining possible age cohort and health status effects. Internal-consistency estimates for the aggregate measure were high, whereas subscale reliability levels varied across age groups. Construct validity was supported across samples. Gender, cohort, and health effects offered interesting psychometric and theoretical insights and direction for further research. Findings indicated that the MEPSI might be a useful instrument for operationalizing and testing Eriksonian developmental theory in adults.

Chronic obstructive pulmonary disease: strategies to improve functional status.

People with chronic obstructive pulmonary disease (COPD) experience deterioration in functional status, therefore improving functional status is a major goal of treatment. We reviewed interventions to improve functional status in people with COPD published from 1980 through September 1996. Randomized controlled clinical trials were reviewed to document outcomes in terms of functional capacity and functional performance for the following interventions: pharmacologic therapy including theophylline, inhaled bronchodilators, steroids, antianxiolytics and antidepressants; general exercise strategies including exercise training, exercise and comprehensive pulmonary rehabilitation, and upper extremity training; inspiratory muscle therapy including inspiratory muscle training and inspiratory muscle rest; nutritional therapy; oxygen therapy; and specialized nursing care. Improvements for functional capacity were documented in terms of strength of the inspiratory muscles and upper extremities, walking tests, and peak oxygen uptake. Most interventions were targeted to enhance functional capacity, and few were aimed at enhancing functional performance. Further research is needed to examine the relationship between functional capacity and functional performance and to design and test interventions to improve functional performance.

Functional performance in people with chronic obstructive pulmonary disease: a qualitative analysis.

The variation of functional performance seen in people with chronic obstructive pulmonary disease (COPD) is perplexing. Some patients appear to do well in their day-to-day activities, while others, with the same apparent disease severity, have difficulty. This naturalistic inquiry sought to describe functional performance from the perspective of 12 people with COPD. Thematic analysis was used to identify activities in which these men and women were engaged and the way they perceived activities, symptoms, and treatments within the context of their daily lives. Decisions to perform activities were influenced by a sense of deriving satisfaction, weighed against the discomfort that might occur. Intruders and enablers influenced activity performance. The results of this study provide a useful framework for assessing functional performance and developing interventions that are sensitive to patient values and expectations and that have a greater likelihood of improving life quality.