Application of generalizability theory confirmed lower reliability of the standard gamble than the feeling thermometer.

OBJECTIVES: Recent studies suggest that rating clinical marker states (CMS) does not improve the measurement properties of the standard gamble (SG) and only slightly improves those of the feeling thermometer (FT). The poor intrarater (test-retest) reliability of CMS may explain their meager performance. Further, lack of interrater reliability may compromise the use of CMS in interpreting health state ratings. The aim of this study was to assess the reliability of CMS ratings for the SG and the FT. STUDY DESIGN AND SETTING: Two similar studies in patients with chronic obstructive pulmonary disease (COPD, n=91) and in patients with gastroesophageal reflux disease (GERD, n=112) provided data for this analysis. Patients rated three different CMS (mild, moderate, and severe disease) twice several weeks apart. We used generalizability theory to calculate reliability coefficients. RESULTS: Test-retest reliability for CMS ratings was higher for the FT compared to the SG (COPD: 0.86 vs. 0.67; GERD: 0.86 vs. 0.67). Interrater reliability was much higher for the FT compared to the SG (COPD: 0.78 vs. 0.46; GERD: 0.71 vs. 0.26). CONCLUSIONS: These results suggest that the markedly poorer reliability of CMS for the SG than the FT is driven largely by poor interrater reliability.

Measuring functional performance in patients with COPD: a discussion of patient-reported outcome measures.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic condition and a major public health concern. Moreover, its prevalence is increasing. COPD commonly affects patient performance of daily activities that people perform in order to meet basic needs, fulfill usual roles, and maintain their health and well-being. What types of activities are affected and to what degree? How do these effects change over time? What impact, positive or negative, do various treatments have on the capacity of patients to perform activities? To address these questions, the concept of activity performance must be defined and appropriately measured. METHODS: This paper presents a model of function that defines functional performance as distinct but related to physiological impairments and functional capacity. A systematic review of the literature was conducted to locate patient-reported outcome (PRO) instruments that have been used to capture functional performance in clinical studies of COPD and have been validated with patients with COPD. The content of each measure was reviewed to assess depth and breadth of coverage. RESULTS: The systematic review yielded nine validated PROs used to capture functional performance in clinical studies of COPD: three are generic; six were designed specifically for use in patients with COPD. Variability in content coverage occurred across the PROs, with some sacrificing depth for breadth. Few of the PROs covered the full range of content as defined in the model. Limiting selected PROs to those that have been used with patients with COPD, while relevant to this population, may preclude other PRO instruments that can measure functional performance. The relevance of another instrument would, however, need to be confirmed with patients with COPD. CONCLUSIONS: Selection of endpoints and instruments for clinical studies of COPD and its treatment must be driven by a clear definition of concepts of interest and the relevance of content areas to patients. Some existing instruments may provide adequate coverage of endpoints or content areas under investigation. Others clearly will not.

Relative responsiveness of the Chronic Respiratory Questionnaire, St. Georges Respiratory Questionnaire and four other health-related quality of life instruments for patients with chronic lung disease.

BACKGROUND: Selection of heath-related quality of life (HRQL) instruments that are most responsive to changes in HRQL prevents investigators from drawing false-negative conclusions about the effectiveness of an intervention. The objective of this study was to compare the responsiveness of the Chronic Respiratory Questionnaire (CRQ), the St. Georges Respiratory Questionnaire (SGRQ) and four other HRQL instruments. METHODS: We enrolled 177 patients with chronic lung disease, primarily COPD (93%), who completed 8 weeks of respiratory rehabilitation. Patients completed the CRQ, the SGRQ and four generic measures (SF-36, Feeling Thermometer, Standard Gamble and Health Utilities index 3) at the beginning of the rehabilitation program and 12 weeks thereafter. We calculated standardized response means (SRMs) for each instrument, from the change score divided by the standard deviation of the change score. RESULTS: We observed the largest SRM for the CRQ (0.24-0.66 for the four CRQ domains on the interviewer-administered and 0.56-0.84 for the self-administered format) and the SGRQ (0.33-0.51 for the three SGRQ domains and total score). The CRQ dyspnea domain was statistically significantly more responsive than any other instrument including the SGRQ. For the SGRQ, the total and impacts domain were significantly more responsive than the generic and preference-based instruments. CONCLUSIONS: This study confirms that the CRQ and SGRQ are substantially more responsive than generic measures, and suggests particularly strong responsiveness for the self-administered CRQ.

Patient understanding, detection, and experience of COPD exacerbations: an observational, interview-based study.

STUDY OBJECTIVES: This study was conducted to gain insight into patients' comprehension, recognition, and experience of exacerbations of COPD, and to explore the patient burden associated with these events. DESIGN: A qualitative, multinational, cross-sectional, interview-based study. SETTING: Patients' homes. PATIENTS: Patients (n = 125) with predominantly moderate-to-very severe COPD (age > or = 50 years; with two or more exacerbations during the previous year). INTERVENTIONS: Patients underwent a 1-h face-to-face interview with a trained interviewer. MEASUREMENTS AND RESULTS: During the preceding year, patients experienced a mean +/- SD of 4.6 +/- 5.4 exacerbations, after which 19.2% (n = 24) believed they had not fully recovered. Although commonly used by physicians, only 1.6% (n = 2) of patients understood the term exacerbation, preferring to use simpler terms, such as chest infection (16.0%; n = 20) or crisis (16.0%; n = 20) instead. Approximately two thirds of patients stated that they were aware of when an exacerbation was imminent and, in most cases, patients recounted that symptoms were consistent from one exacerbation to another. Some patients (32.8%; n = 41), however, reported no recognizable warning signs. At the onset of an exacerbation, 32.8% of patients (n = 41) stated that they reacted by self-administering their medication. Some patients spontaneously mentioned a fear of dying (12.0%; n = 15) or suffocating (9.6%; n = 12) during exacerbations, and effects on activities, mood, and personal/family relationships were frequently reported. Physicians tended to underestimate the psychological impact of exacerbations compared with patient reports. CONCLUSIONS: This study shows that patients with frequent exacerbations have a poor understanding of the term exacerbation. Patient recollections suggest that exacerbation profiles vary enormously between patients but that symptoms/warning signs are fairly consistent within individuals, and are generally recognizable. Exacerbations appear to have a significant impact on patient well-being, including psychological well-being, and this may be underestimated by physicians.

Do clinical marker states improve responsiveness and construct validity of the standard gamble and feeling thermometer: a randomized multi-center trial in patients with chronic respiratory disease.

BACKGROUND: Optimizing the validity and responsiveness of utility measures will enhance their usefulness in randomized trials. We evaluated the impact of clinical marker state (CMS) rating prior to patients' rating their own health on two utility instruments (feeling thermometer (FT) and standard gamble (SG)) in patients with chronic respiratory disease (CRD). METHODS: We randomized 182 patients with CRD to complete the FT (self-administered) and SG with CMS (FT+/SG+, n=91) or without marker states (FT-/SG-, n=91) before and after undergoing respiratory rehabilitation in a multi-center trial. RESULTS: Use of CMS did not influence baseline utility scores. Improvement after therapy on the scale from 0 (dead) to 1.0 (full health) was 0.04 both in FT+ (p=0.03) and FT- (p=0.02; the difference between FT+ and FT- was 0.00, p=0.83). Improvement on the SG was 0.05 in both SG+ (p=0.08) and SG- (p=0.04; difference between SG+ and SG- 0.00, p=0.95). Correlations with other health related quality of life scores were highest for FT+. CONCLUSION: Administration of CMS did not improve responsiveness of the FT but may have improved construct validity. The SG showed limited construct validity and responsiveness that was not influenced by CMS use.

Modification of the asthma quality of life questionnaire (standardised) for patients 12 years and older.

BACKGROUND: The age limit for some adult asthma clinical trials has recently been lowered to 12 years. In this study we have made minor modifications to the standardised version of the adult Asthma Quality of Life Questionnaire (AQLQ(S)) to make it valid for patients 12 years and older (AQLQ12+). METHODS: We have used two clinical trial databases, in which the AQLQ12+ was used, to compare the measurement properties of the questionnaire in patients 12-17 years and patients 18 years and older. A total of 2433 patients (12-75 years), with current asthma and with data that could be evaluated both at randomisation and end of treatment, were included. RESULTS: The analysis showed that internal consistency, responsiveness and correlations with other clinical indices were very similar in patients 12-17 years and patients 18 years and older. CONCLUSION: The measurement properties of the AQLQ12+ are similar in adolescents and adults and therefore the instrument is valid for use in adult studies which include children 12 years and older.

Health-related quality of life is related to COPD disease severity.

BACKGROUND: The aim of this study was to evaluate the association between health-related quality of life (HRQL) and disease severity using lung function measures. METHODS: A survey was performed in subjects with COPD in Sweden. 168 subjects (70 women, mean age 64.3 years) completed the generic HRQL questionnaire, the Short Form 36 (SF-36), the disease-specific HRQL questionnaire; the St George's Respiratory Questionnaire (SGRQ), and the utility measure, the EQ-5D. The subjects were divided into four severity groups according to FEV1 per cent of predicted normal using two clinical guidelines: GOLD and BTS. Age, gender, smoking status and socio-economic group were regarded as confounders. RESULTS: The COPD severity grades affected the SGRQ Total scores, varying from 25 to 53 (GOLD p = 0.0005) and from 25 to 45 (BTS p = 0.0023). The scores for SF-36 Physical were significantly associated with COPD severity (GOLD p = 0.0059, BTS p = 0.032). No significant association were noticed for the SF-36, Mental Component Summary scores and COPD severity. Scores for EQ-5D VAS varied from 73 to 37 (GOLD I-IV p = 0.0001) and from 73 to 50 (BTS 0-III p = 0.0007). The SGRQ Total score was significant between age groups (p = 0.0047). No significant differences in HRQL with regard to gender, smoking status or socio-economic group were noticed. CONCLUSION: The results show that HRQL in COPD deteriorates with disease severity and with age. These data show a relationship between HRQL and disease severity obtained by lung function.

Measurement properties and interpretation of three shortened versions of the asthma control questionnaire.

The Asthma Control Questionnaire (ACQ) measures the adequacy of asthma treatment as identified by international guidelines. It consists of seven items (5 x symptoms, rescue bronchodilator use and FEV1% of predicted normal). A validation study suggested that in clinical studies measurement of FEV1 and bronchodilator use may not be needed but this has never formally been tested in a clinical trial. The aims of this analysis were (1) to examine the measurement properties of three shortened versions of the ACQ (symptoms alone, symptoms plus FEV1 and symptoms plus short-acting beta2-agonist) and (2) to determine whether using the shortened versions would alter the results of a clinical trial. In the randomised trial, 552 adults completed the ACQ at baseline and after 13 and 26 weeks of treatment. The analysis showed that the measurement properties of all four versions of the ACQ are very similar. Agreement between the original ACQ and the reduced versions was high (intraclass correlation coefficients: 0.94-0.99). Mean differences between the ACQ and the shortened versions were less than 0.04 (on the 7-point scale). Clinical trial results using the four versions were almost identical with the mean treatment difference ranging from -0.09 (P=0.17), to -0.13 (P=0.07). For interpretability, the minimal important difference for all four versions was close to 0.5. In conclusion, these three shortened versions of the ACQ can be used in large clinical trials without loss of validity or change in interpretation.

Clinical outcomes and adverse effect monitoring in allergic rhinitis.

The subjective recording in diary cards of symptoms of itch, sneeze, nose running, and blockage, with the use of a rating scale to indicate the level of severity, is usual for clinical trials in allergic rhinitis. The primary outcome measure is usually a composite score that enables a single total symptoms score endpoint. It is appreciated, however, that rhinitis has a greater effect on the individual than is reflected purely by the recording of anterior nasal symptoms. Nasal obstruction is troublesome and may lead to sleep disturbance in addition to impaired daytime concentration and daytime sleepiness. These impairments affect school and work performance. Individuals with rhinitis find it socially embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture these and other aspects of the disease-specific health-related quality of life, questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have been developed and validated for clinical trial use. The adoption of health-related quality of life questionnaires into clinical trials broadens the information obtained regarding the effect of the therapeutic intervention and helps focus on issues relevant to the individual patient. It must be appreciated that it is not only the disease that may adversely affect health-related quality of life; administered therapy, although intended to be beneficial, may also cause health impairment. Adverse-event monitoring is thus essential in clinical trials. The first-generation H 1 -histamines, because of their effect on central H 1 -receptors, are classically associated with central nervous system (CNS) effects such as sedation. Although this is not always perceived by the patient, it is clearly evident with objective performance testing, and positron emission tomography scanning has directly demonstrated the central H 1 -receptor occupancy. The second-generation H 1 -antihistamines have reduced central H 1 -receptor occupancy and considerably reduced or absent CNS sedative effects. Therefore, the CNS effects are entirely avoidable, and the first-generation H 1 -antihistamines should no longer be used in the management of allergic rhinitis. The considerably rarer but potentially very serious cardiac arrhythmogenic effects of H 1 -antihistamines are appreciated to be molecule-specific rather than class-specific. The in vitro screening of new compounds to eliminate the further development of those with cardiotoxicity ideally will lead to this adverse effect being historic. The incorporation of electrocardiogram recording in clinical trials provides direct information relating to prolongation of QT interval corrected for heart rate. Although administered at low doses, intranasal steroids still have the potential for systemic absorption and adverse consequences. However, it is appreciated that meaningful differences exist in the bioavailability of different steroid molecules, and although a small but statistically significant effect on growth in children has been identified with the long-term use of intranasal beclomethasone when administered twice daily for 1 year, this is not evident with all intranasal steroids. In addition, twice-daily intranasal steroid administration may have more effect--from the endocrinologic perspective--than once-daily administration in the morning, which coincides better with the natural diurnal variation in cortisol. Thus, once-daily intranasal steroid administration is preferable, and when used in studies in children, measurement of height change during the study period is an important outcome variable together with other indices of systemic steroid bioavailability (eg, tests of hypothalamic-pituitary-adrenal axis function). These considerations have even greater relevance if children are concurrently also receiving inhaled steroids for asthma, because the total steroid load will be greater.

Psychometric and utility-based measures of health status of asthmatic patients with different disease control level.

OBJECTIVE: To explore the relationship between asthma control level and health-related QOL (HR-QOL), and to understand the role of various psychometric and utility-based methods in studying this relationship. METHODS: Two hundred and twenty-eight consecutive adult outpatients and inpatients at four sites participated in the study. Physicians identified the level of disease control according to the Global Initiative for Asthma (GINA) classification system. Patients filled in three different HR-QOL questionnaires (EuroQol 5-D [EQ-5D], Short-Form 36-item health survey [SF-36], and St George's Respiratory Questionnaire [SGRQ]) and a direct time trade-off question. The Short Form-6D (SF-6D) was used to derive utility values from SF-36 data. RESULTS: All patient-reported evaluation methods could discriminate between patients with different disease control levels, and both generic and disease-specific instruments strongly correlated to each other. The magnitude of differences in HR-QOL between groups with different disease control levels was clinically meaningful. All three HR-QOL measures reflected a relationship between disease control level and HR-QOL, but the actual pattern of the relationship depended on the instrument used. Utilities gained from the EQ-5D index, compared with the SF-6D index, had higher values in the patient group with the best disease control and lower values in the patient group with poor disease control. CONCLUSION: When choosing an instrument to measure the health status of asthmatic patients in clinical studies, the severity range of the study population should be considered. Researchers might prefer to use the EQ-5D in asthma patients with severe disease or poor disease control and the SF-6D in patients with mild disease or good disease control.

A comparison of narrative and table formats for presenting hypothetical health states to patients with gastrointestinal or pulmonary disease.

Traditionally, quality-of-life researchers describe states of health for patients to rate either in narrative form or in table form, but evidence about which format patients prefer is limited. The authors performed 2 randomized studies to test whether patients prefer the table or narrative format and whether the format of presentation influences how patients rate health states. Approximately three-fourths of patients with gastrointestinal disease or chronic airflow limitation preferred the table format. There were no differences in patients' ratings of 3 described health states or of their own health. Investigators should consider using the table presentation for describing health states to subjects who are not familiar with these states of health.

Measuring health-related quality of life in adults during an acute asthma exacerbation.

BACKGROUND: Acute severe asthma can be distressing for patients. It is important to be able to identify the causes of the distress so that these can receive attention in conjunction with the conventional treatment of the airways. STUDY OBJECTIVE: To modify the Asthma Quality of Life Questionnaire (AQLQ) for evaluating patients with acute severe asthma and to test the measurement properties of the Acute Asthma Quality of Life Questionnaire (Acute AQLQ). METHODS: The Acute AQLQ contains the symptom and emotional function items of the AQLQ (n = 11), which are capable of changing over short periods of time. The measurement properties were tested during a clinical trial to compare formoterol and salbutamol in the treatment of acute severe asthma in hospital emergency departments. RESULTS: The 88 patients in the clinical trial provided evidence that the Acute AQLQ has high internal consistency (Cronbach alpha = 0.90) and is very responsive to change in status (p < 0.00001) with a responsiveness index of 2.5. Correlations between the Acute AQLQ and other measures of clinical status provided evidence of the validity of the instrument. CONCLUSION: The Acute AQLQ has strong measurement properties and can be used with confidence to identify the problems that are distressing to patients during an acute asthma exacerbation and to evaluate the effectiveness of interventions.

Asthma treatment needs: a comparison of patients' and health care professionals' perceptions.

BACKGROUND: Patients' perceptions of asthma tend to differ from those of clinicians, who primarily focus on asthma control. Patients' treatment needs and preferences may not be adequately addressed. OBJECTIVE: The aims of this study were as follows: to provide data on unmet treatment needs and to investigate the main finding of a qualitative study using a questionnaire study. METHODS: To assess treatment needs in patients with asthma, focus groups were conducted with patients/parents and clinicians. Based on these results, quantitative surveys of adult patients and parents were performed in the United Kingdom, Germany, and Spain. RESULTS: The UK focus group comprised 11 patients and 8 parents; in Germany, there were 10 patients and 11 parents; in Spain, there were 5 patients and 8 parents. The focus groups showed some differences between clinicians' and patients'/parents' perceptions of treatment. For patients, side effects meant long-term effects (ie, 10-20 years); for clinicians, it meant occasional local problems. The quantitative study comprised 454 participants: 310 adult patients (mean [SD] age, 37.13 [13.12] years) and 142 parents (children's mean [SD] age, 13.98 [1.37] years), plus 2 nonspecified. Some patients reported good asthma control and simultaneously reported frequent exacerbations. Most patients and parents expressed a preference for a simpler regimen using fewer drugs, and most had concerns about their treatment. Although some patients concurred with treatment guidelines, 62.2% tended to rely on reliever medication (ie, bronchodilators). Additionally, 6.9% described their asthma as very well-controlled but reported experiencing asthma symptoms > or =3 days per week. Finally, 1.9% of patients and 2.1% of parents reporting very well-controlled asthma also reported visiting the emergency department or calling a physician for a home visit in the previous 3 months. CONCLUSIONS: Asthma patients and parents of asthmatic children had unmet treatment needs and may interpret medical terminology differently than clinicians.

Measuring symptom response to pharmacological interventions in patients with COPD: a review of instruments used in clinical trials.

OBJECTIVES: To identify and evaluate the instruments used to measure the effect of pharmacological intervention on symptoms of chronic obstructive pulmonary disease (COPD) in clinical trials. DESIGN: An extensive literature search was conducted for articles published in English in a peer-reviewed journal from 1995 to March 2002 which described a randomised controlled clinical trial measuring symptoms of COPD in response to pharmacological interventions. PATIENTS: Patients with any severity of COPD. INTERVENTIONS: Any pharmacological intervention for treatment of COPD. MEASUREMENTS AND RESULTS: A total of 43 eligible articles were identified. The individual symptoms most frequently measured were dyspnoea/breathlessness, chest tightness or discomfort and exacerbations. There was considerable variability in the methods, terminology and symptom measurement instruments used. The most widely used instruments for measuring dyspnoea were the Borg scale, the Baseline Dyspnoea Index and the Transitional Dyspnoea Index. None of the instruments used had published evidence of rigorous psychometric testing. CONCLUSIONS: Numerous methods have been employed to assess the symptoms of COPD in clinical trials, making it difficult to compare the results of different trials. No single measurement instrument predominates, and none of the measures identified in the review have undergone rigorous psychometric testing in this patient population. There is a clear need for a fully developed and validated tool for measuring the effects of therapeutic interventions on symptoms in COPD in clinical trials.

Clinicians tend to overestimate improvements in asthma control: an unexpected observation.

AIM: The original purpose of this study was to determine the Minimal Important Difference for the Asthma Control Questionnaire (ACQ) but an unexpected tendency of clinicians to overestimate improvements in asthma control thwarted the endeavour. We describe the observed clinician bias and discuss its implications for clinical practice and research. METHODS: Ninety-four adults with inadequately controlled asthma received a full clinical consultation with one of nine asthma specialists. Medications were adjusted according to clinical needs. Four weeks later the same clinician estimated change in asthma control on a 15-point scale (-7 = a very great deal worse, 0 = no change, +7 a very great deal better). All patients completed the ACQ before each consultation but responses were not shown to the clinician. RESULTS: Clinicians consistently recorded that patients improved more than their change in ACQ scores suggested (p = 0.018). CONCLUSION: Clinicians should be aware of potential biases that may occur when estimating change in asthma control compared with measuring absolute status at each visit.

The impact of exacerbations on the asthmatic patient's preference scores.

The purpose of this study was to examine the effect of exacerbations on mild to moderate asthmatic patients' preference-based, health-related, quality of life scores and also to describe the effect of these exacerbations on daily life. In a survey, 100 mild to moderate asthmatic patients in the United Kingdom were asked to rate three different health marker states on a scale between 0 (death) and 100 (perfect health), defined as: your asthma of today, a mild exacerbation, and a severe exacerbation of asthma. They were also asked to describe their symptoms and what they did when experiencing an exacerbation. During exacerbations the vast majority of asthmatic patients have significant symptoms and consume a considerable amount of health care resources, which often overlap. The health marker state "your asthma of today" was given a mean score of 81.0, a mild exacerbation a score of 62.1, and a severe exacerbation a score of 25.6, indicating a large impact on patients' daily life and their health-related quality of life. In conclusion, asthmatic patients are severely affected in their health and daily living by mild and severe exacerbations. Considerable effort should be made to reduce the number and severity of exacerbations.

Formoterol used as needed improves health-related quality of life in asthmatic patients uncontrolled with inhaled corticosteroids.

Clinical benefits have been shown to occur when using the long-acting beta2-agonist formoterol 4.5 microg for as-needed medication rather than terbutaline 500 microg in patients with unstable asthma taking an inhaled corticosteroid. This study compared their effects on health-related quality of life and the relation with conventional clinical indices in the same population. 362 asthmatics were randomized to use either formoterol 4.5 microg or terbutaline 500 microg as needed, both inhaled via Turbuhaler. The Asthma Quality of Life Questionnaire (AQLQ) was practised at enrolment and completed by 341 patients after randomization and at 4, 8, and 12 weeks. Clinical indices were measured at the same time points. Mean overall AQLQ scores were comparable at baseline, being 4.90 in the formoterol and 4.82 in the terbutaline group and improved during treatment by 0.41 and 0.17 units, respectively (mean difference 0.24, 95% CI 0.08, 0.39, P<0.005). Mean improvement in the symptom domain was 0.49 units when using formoterol. Correlations between changes in clinical indices and changes in AQLQ scores during the 12-week period were weak (maximum r value=0.37). When used for as-needed medication, formoterol 4.5 microg provided an improvement in asthma-specific quality of life and to a somewhat greater extent than the widely used terbutaline 500 microg. The symptom domain in AQLQ showed almost 0.5 units improvement after formoterol, a change that is considered to be clinically relevant.

Health-related quality of life, utility, and productivity outcomes instruments: ease of completion by subjects with COPD.

An important outcome of any clinical intervention is the change in the subject's own perceived state of health. This can be categorized as health-related quality of life (HRQL), utility (preference-based health state), and daily life performance. 174 Swedish subjects with chronic obstructive pulmonary disease (COPD) (mean age 64.3 PlusMinus; 12 years) completed five self-administered questionnaires: Short Form 36 (SF-36), St George's Respiratory Questionnaire (SGRQ), EuroQol-5D (EQ-5D), Health States-COPD (HS-COPD), and Work Productivity and Activity Impairment Questionnaire for COPD (WPAI-COPD). The subjects scored these outcomes instruments for ease of completion using a 5-point scale. The time taken to complete them was noted and the administrators' opinion of the subjects' comprehension of the questionnaires recorded using a 4-point scale. A score of 1-3 ("very easy" to "acceptable") was recorded by 92% of subjects for the SF-36, 90% for SGRQ, 80% for EQ-5D, 83% for WPAI-COPD, and 53% for HS-COPD. The HS-COPD was graded "very difficult" to complete by 21% of subjects compared with 3-5% of subjects for the other questionnaires. The mean time taken to complete all questionnaires was 39 minutes, and the large majority of subjects scored "good" for understanding by the administrator. Age correlated significantly with the degree of the subject's opinion of the ease of completion of five outcomes instruments, while the influence of gender, socio-economic status and disease severity was not statistically significant.

Factors affecting adherence to asthma treatment: patient and physician perspectives.

AIMS: To identify important factors affecting treatment adherence of patients with asthma and to summarise this information as a guide for physicians. METHODS: Information from literature and interviews with 12 respiratory physicians (four each from France, Spain and UK) and 46 asthma patients was obtained. Factors affecting adherence to asthma treatment were identified, reviewed and a flow chart developed to indicate the relationship between key factors. RESULTS: Major factors influencing adherence included: the patient-physician relationship; the patient's understanding of the disease and its treatment; the patient's beliefs and perception of the disease and its treatment, and, importantly, the patient's willingness to take an active part in his/her asthma management. CONCLUSION: Patient adherence to asthma can be improved, and the likelihood of treatment success increased, by paying attention to the factors that influence patients' willingness to participate in their treatment.

Topoisomerase II-alpha expression in different cell cycle phases in fresh human breast carcinomas.

Topoisomerase II-alpha (topo II alpha) is the key target enzyme for the topoisomerase inhibitor class of anti-cancer drugs. In normal cells, topo II alpha is expressed predominantly in the S/G2/M phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo II alpha is both higher and less dependent on proliferation state in the cell. We studied fresh specimens from 50 cases of primary breast cancer. The expression of topo II alpha in different cell cycle phases was analyzed with two-parameter flow cytometry using the monoclonal antibody SWT3D1 and propidium iodide staining. The expression of topo II alpha was significantly higher in the S/G2/M phase of the cell cycle than in the G0/G1 phase in both DNA diploid and DNA non-diploid tumors. In 18 of 21 diploid tumors, and in 25 of 29 non-diploid tumors, >50% of the topo II alpha-positive cells were in the G0/G1 phase. This significant expression of topo II alpha in the G0/G1 phase of the cell cycle may have clinically important implications for treatment efficacy of topoisomerase II inhibitors.