Assessing patient-reported outcomes in asthma and COPD patients: which can be recommended in clinical practice?

PURPOSE OF REVIEW: There is a clear need for simple and reliable patient-reported outcome measures for chronic obstructive pulmonary disease (COPD) and asthma in daily practice. The purpose of this review is to facilitate the choice for clinicians of patient-reported outcomes which they can use in their daily practice. RECENT FINDINGS: More than 50 patient-reported outcome measures for asthma and COPD exist and clinicians are often left confused on which to use. Four tools (two for asthma and two for COPD) can be suggested based on validity/reliability, responsiveness, practicality and are particularly convenient in terms of time to measure. SUMMARY: On the basis of ample evidence, the COPD assessment test and the clinical COPD questionnaire for COPD and asthma control questionnaire and the asthma control test for asthma can be recommended for use in both primary care and other clinical settings. A simple guide figured as smiley faces has been designed to assist physicians to easily select the appropriate measure. With the current direction of thinking into treatable traits, targeted measures that evaluate the upper airways like the control of allergic rhinitis and asthma test may also be more used in the future.

Irrational prescribing of over-the-counter (OTC) medicines in general practice: testing the feasibility of an educational intervention among physicians in five European countries.

BACKGROUND: Irrational prescribing of over-the-counter (OTC) medicines in general practice is common in Southern Europe. Recent findings from a research project funded by the European Commission (FP7), the "OTC SOCIOMED", conducted in seven European countries, indicate that physicians in countries in the Mediterranean Europe region prescribe medicines to a higher degree in comparison to physicians in other participating European countries. In light of these findings, a feasibility study has been designed to explore the acceptance of a pilot educational intervention targeting physicians in general practice in various settings in the Mediterranean Europe region. METHODS: This feasibility study utilized an educational intervention was designed using the Theory of Planned Behaviour (TPB). It took place in geographically-defined primary care areas in Cyprus, France, Greece, Malta, and Turkey. General Practitioners (GPs) were recruited in each country and randomly assigned into two study groups in each of the participating countries. The intervention included a one-day intensive training programme, a poster presentation, and regular visits of trained professionals to the workplaces of participants. Reminder messages and email messages were, also, sent to participants over a 4-week period. A pre- and post-test evaluation study design with quantitative and qualitative data was employed. The primary outcome of this feasibility pilot intervention was to reduce GPs' intention to provide medicines following the educational intervention, and its secondary outcomes included a reduction of prescribed medicines following the intervention, as well as an assessment of its practicality and acceptance by the participating GPs. RESULTS: Median intention scores in the intervention groups were reduced, following the educational intervention, in comparison to the control group. Descriptive analysis of related questions indicated a high overall acceptance and perceived practicality of the intervention programme by GPs, with median scores above 5 on a 7-point Likert scale. CONCLUSIONS: Evidence from this intervention will estimate the parameters required to design a larger study aimed at assessing the effectiveness of such educational interventions. In addition, it could also help inform health policy makers and decision makers regarding the management of behavioural changes in the prescribing patterns of physicians in Mediterranean Europe, particularly in Southern European countries.

Depressive symptoms in postmenopausal women: results from the MEDIS Study.

Data regarding the factors associated with depressive symptoms are limited, especially in postmenopausal women. The aim of this study was to investigate to what extent depressive symptoms were present in postmenopausal women, to explore characteristics associated with depressive symptoms and to determine if time since menopause was independently associated with depressive symptoms. Data collected within the Mediterranean Islands (MEDIS) Study, a health and nutrition survey of elderly people living on Mediterranean islands was used. A total of 851 postmenopausal women living in various Greek islands, Cyprus, and Malta participated in the study. Depressive symptoms were evaluated using the Geriatric Depression Scale (GDS). Age-adjusted logistic regression analysis showed that a year's increase in the time since menopause increased the likelihood of postmenopausal women having severe depressive symptoms by 3% (odds ratio [OR] per 1 year = 1.03, 95% CI 1.001-1.05). This positive association was also evident when other potential confounding factors (i.e, living conditions, financial status, physical activity, adherence to the Mediterranean diet, smoking habits, and several clinical conditions) were also taken into account in multivariable analyses. Primary health care practitioners and public health care authorities could use the findings of this study to identify depressive symptoms early in postmenopausal women.

Impact of the financial crisis on adherence to treatment of a rural population in Crete, Greece.

BACKGROUND: The global economic crisis has affected Greece. Data on patients' adherence to medications for chronic diseases are missing. The objective of this study was to identify to what extent the financial crisis and the repeated pharmacists strike have influenced patients adherence to therapy. DESIGN: A quantitative and qualitative study in rural Crete was designed and implemented in February 2013 with the use of a pretested questionnaire with opened and closed questions. Setting Rural practices in a well-defined geographical area of Crete. SUBJECT: The questionnaire was addressed in all patients that visited the rural practices with chronic or acute diseases for two consecutive weeks. Main Outcome(s) and Measure(s): Age, annual income, adherence to therapy, patient's views and feelings. RESULTS: 288 patients participated. The mean age was 68±6.87. The majority of the patients have lowered the doses of several medications by themselves as they weren't able to afford the cost ie; all patients receiving insulin had lowered the dosages; 46.42% of patients with COPD or asthma had stopped their medications completely, decreased dosages or used similar medications that had in the past; patients with dislipidemia received their medications as suggested only in 51.8%. Patients with cardiovascular diseases received their medications as suggested in 75.6% while the rest have dismissed or skipped dosages. Most common emotions reported were those of sadness, fear, stress, anxiety and isolation. CONCLUSIONS: The economic crisis has influenced patients' adherence to therapy in rural areas as well as their psychological and emotional status. There is an urgent need for action within the context of primary care.

Control of Allergic Rhinitis and Asthma Test (CARAT): dissemination and applications in primary care.

Asthma frequently occurs in association with allergic rhinitis and a combined management approach has been suggested. The Control of Allergic Rhinitis and Asthma Test (CARAT) is the first questionnaire to assess control of both diseases concurrently. However, to have an impact on healthcare it needs to be disseminated and adopted. In this paper we discuss the dissemination of CARAT in different countries and its possible applications in primary care. At present, the adaptation of CARAT for use in different languages and cultures is being led by volunteer researchers and clinicians in 15 countries. Website and smartphone applications have been developed, and a free open model of distribution was adopted to contribute to the dissemination of CARAT. Examples of dissemination activities include distribution of leaflets and posters, educational sessions on the use of the questionnaire in the follow-up of patients, development of clinical studies, collaborations with professional organisations and health authorities, and the inclusion of CARAT in clinical guidelines. The adoption of innovations is an important challenge in healthcare today, and research on the degree of success of dissemination strategies using suitable methods and metrics is much needed. We propose that CARAT can be used in a range of settings and circumstances in primary care for clinical, research and audit purposes, within the overall aim of increasing awareness of the level of disease control and strengthening the partnership between patients and doctors in the management of asthma and rhinitis.

Assessing health status in COPD. A head-to-head comparison between the COPD assessment test (CAT) and the clinical COPD questionnaire (CCQ).

BACKGROUND: Health status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management. We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St. George Respiratory Questionnaire (SGRQ). METHODS: We administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits. Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits. Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires. RESULTS: We enrolled 90 COPD patients. Cronbach's alpha for both CAT and CCQ was high (0.86 and 0.89, respectively). Patients with severe COPD reported worse health status compared to milder subgroups. CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01). Both questionnaires exhibited a weak correlation with lung function (rho = -0.35;CAT and rho = -0.41; CCQ, p < 0.01). Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98). The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ. Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations. More than half of patients preferred CCQ instead of CAT. CONCLUSIONS: The CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients' preference and are both valid and reliable questionnaires to assess health status in COPD patients.

Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation.

BACKGROUND: Little is known about the effect of smoking cessation on airway inflammation. Secretory Leukocyte Protease Inhibitor (SLPI), Clara Cell protein 16 (CC16), elafin and human defensin beta-2 (HBD-2) protect human airways against inflammation and oxidative stress. In this longitudinal study we aimed to investigate changes in sputum and nasal lavage SLPI, CC16, elafin and HBD-2 levels in healthy smokers after 6 and 12 months of smoking cessation. METHODS: Induced sputum and nasal lavage was obtained from healthy current smokers (n = 76) before smoking cessation, after 6 months of smoking cessation (n = 29), after 1 year of smoking cessation (n = 22) and from 10 healthy never smokers. SLPI, CC16, elafin and HBD-2 levels were measured in sputum and nasal lavage supernatants by commercially available ELISA kits. RESULTS: Sputum SLPI and CC-16 levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.005 and p = 0.08 respectively). SLPI and CC16 levels did not differ before and 6 months after smoking cessation (p = 0.118 and p = 0.543 respectively), neither before and 1 year after smoking cessation (p = 0.363 and p = 0.470 respectively). Nasal lavage SLPI was decreased 12 months after smoking cessation (p = 0.033). Nasal lavage elafin levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.007), but there were no changes 6 months and 1 year after smoking cessation. CONCLUSIONS: Only nasal lavage SLPI decrease after 1 year after smoking cessation. We may speculate that there is an ongoing inflammatory process stimulating the production of counter-regulating proteins in the airways of healthy ex-smokers.

Measuring the burden of herpes zoster and post herpetic neuralgia within primary care in rural Crete, Greece.

BACKGROUND: Research has indicated that general practitioners (GPs) have good clinical judgment in regards to diagnosing and managing herpes zoster (HZ) within clinical practice in a country with limited resources for primary care and general practice. The objective of the current study was to assess the burden of HZ and post herpetic neuralgia (PHN) within rural general practices in Crete, Greece. METHODS: The current study took place within a rural setting in Crete, Greece during the period of November 2007 to November 2009 within the catchment area in which the Cretan Rural Practice-based Research Network is operating. In total 19 GP's from 14 health care units in rural Crete were invited to participate, covering a total turnover patient population of approximately 25, 000 subjects. For the purpose of this study an electronic record database was constructed and used as the main tool for monitoring HZ and PHN incidence. Stress related data was also collected with the use of the Short Anxiety Screening Test (SAST). RESULTS: The crude incidence rate of HZ was 1.4/1000 patients/year throughout the entire network of health centers and satellite practices, while among satellite practices alone it was calculated at 1.3/1000 patients/year. Additionally, the standardised incidence density within satellite practices was calculated at 1.6/1000 patients/year. In regards to the stress associated with HZ and PHN, the latter were found to have lower levels of anxiety, as assessed through the SAST score (17.4 ± 3.9 vs. 21.1 ± 5.7; p = 0.029). CONCLUSIONS: The implementation of an electronic surveillance system was feasible so as to measure the burden of HZ and PHN within the rural general practice setting in Crete.

Functional status measurement in COPD: a review of available methods and their feasibility in primary care.

AIM: Guidelines advocate that improvement in functional status should be a major goal in COPD treatment. Many tools are available to assess aspects of functional status. This review aims to categorize systematically the available tools based on their construct (i.e. what the tool intends to measure) and to rate the tools for use in the primary care setting. METHODS: PubMed was searched with the keywords 'functional status' or 'physical capacity' or 'functional capacity' and 'COPD'. All tools were categorised and rated on their measurement properties, feasibility, and usage in primary care COPD patients. The tools were divided into four constructs - functional capacity, functional performance, functional reserve, and capacity utilisation - and used the following modes of measurement: laboratory tests; semi-laboratory tests; field tests; and patient-reported outcomes. RESULTS: The PubMed search resulted in 364 articles. Thirty-two tools were identified and rated. CONCLUSIONS: In primary care, the 6-minute walking distance test is the most reliable semi-laboratory functional capacity test, but is not very practical. The pedometer is the best functional performance field test. The Medical Research Council (MRC) dyspnoea questionnaire and the functional status domain of the Clinical COPD Questionnaire (CCQ) are the best patient-reported outcome tools to assess functional performance.

A systematic review of the role of vitamin insufficiencies and supplementation in COPD.

BACKGROUND: Pulmonary inflammation, oxidants-antioxidants imbalance, as well as innate and adaptive immunity have been proposed as playing a key role in the development of COPD. The role of vitamins, as assessed either by food frequency questionnaires or measured in serum levels, have been reported to improve pulmonary function, reduce exacerbations and improve symptoms. Vitamin supplements have therefore been proposed to be a potentially useful additive to COPD therapy. METHODS: A systematic literature review was performed on the association of vitamins and COPD. The role of vitamin supplements in COPD was then evaluated. CONCLUSIONS: The results of this review showed that various vitamins (vitamin C, D, E, A, beta and alpha carotene) are associated with improvement in features of COPD such as symptoms, exacerbations and pulmonary function. High vitamin intake would probably reduce the annual decline of FEV1. There were no studies that showed benefit from vitamin supplementation in improved symptoms, decreased hospitalization or pulmonary function.

Investigating sensitivity, specificity, and area under the curve of the Clinical COPD Questionnaire, COPD Assessment Test, and Modified Medical Research Council scale according to GOLD using St George's Respiratory Questionnaire cutoff 25 (and 20) as reference.

BACKGROUND: In the GOLD (Global initiative for chronic Obstructive Lung Disease) strategy document, the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC) scale are recommended for the assessment of symptoms using the cutoff points of CCQ ≥1, CAT ≥10, and mMRC scale ≥2 to indicate symptomatic patients. The current study investigates the criterion validity of the CCQ, CAT and mMRC scale based on a reference cutoff point of St George's Respiratory Questionnaire (SGRQ) ≥25, as suggested by GOLD, following sensitivity and specificity analysis. In addition, areas under the curve (AUCs) of the CCQ, CAT, and mMRC scale were compared using two SGRQ cutoff points (≥25 and ≥20). MATERIALS AND METHODS: Two data sets were used: study A, 238 patients from a pulmonary rehabilitation program; and study B, 101 patients from primary care. Receiver-operating characteristic (ROC) curves were used to assess the correspondence between the recommended cutoff points of the questionnaires. RESULTS: Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥25 were: study A, 0.99, 0.43, and 0.96 for CCQ ≥1, 0.92, 0.48, and 0.89 for CAT ≥10, and 0.68, 0.91, and 0.91 for mMRC ≥2; study B, 0.87, 0.77, and 0.9 for CCQ ≥1, 0.76, 0.73, and 0.82 for CAT ≥10, and 0.21, 1, and 0.81 for mMRC ≥2. Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥20 were: study A, 0.99, 0.73, and 0.99 for CCQ ≥1, 0.91, 0.73, and 0.94 for CAT ≥10, and 0.66, 0.95, and 0.94 for mMRC ≥2; study B, 0.8, 0.89, and 0.89 for CCQ ≥1, 0.69, 0.78, and 0.8 for CAT ≥10, and 0.18, 1, and 0.81 for mMRC ≥2. CONCLUSION: Based on data from these two different samples, this study showed that the suggested cutoff point for the SGRQ (≥25) did not seem to correspond well with the established cutoff points of the CCQ or CAT scales, resulting in low specificity levels. The correspondence with the mMRC scale seemed satisfactory, though not optimal. The SGRQ threshold of ≥20 corresponded slightly better than SGRQ ≥25, recently suggested by GOLD 2015, with the established cutoff points for the CCQ, CAT, and mMRC scale.

The minimal clinically important difference of the Control of Allergic Rhinitis and Asthma Test (CARAT): cross-cultural validation and relation with pollen counts.

BACKGROUND: The Control of Allergic Rhinitis and Asthma Test (CARAT) monitors control of asthma and allergic rhinitis. AIMS: To determine the CARAT's minimal clinically important difference (MCID) and to evaluate the psychometric properties of the Dutch CARAT. METHODS: CARAT was applied in three measurements at 1-month intervals. Patients diagnosed with asthma and/or rhinitis were approached. MCID was evaluated using Global Rating of Change (GRC) and standard error of measurement (s.e.m.). Cronbach's alpha was used to evaluate internal consistency. Spearman's correlation coefficients were calculated between CARAT, the Asthma Control Questionnaire (ACQ5) and the Visual Analog Scale (VAS) on airway symptoms to determine construct and longitudinal validity. Test-retest reliability was evaluated with intra-class correlation coefficient (ICC). Changes in pollen counts were compared with delta CARAT and ACQ5 scores. RESULTS: A total of 92 patients were included. The MCID of the CARAT was 3.50 based on GRC scores; the s.e.m. was 2.83. Cronbach's alpha was 0.82. Correlation coefficients between CARAT and ACQ5 and VAS questions ranged from 0.64 to 0.76 (P < 0.01). Longitudinally, correlation coefficients between delta CARAT scores and delta ACQ5 and VAS scores ranged from 0.41 to 0.67 (P < 0.01). Test-retest reliability showed an ICC of 0.81 (P < 0.01) and 0.80 (P < 0.01). Correlations with pollen counts were higher for CARAT than for ACQ5. CONCLUSIONS: This is the first investigation of the MCID of the CARAT. The CARAT uses a whole-point scale, which suggests that the MCID is 4 points. The CARAT is a valid and reliable tool that is also applicable in the Dutch population.

Studying the burden of community-acquired pneumonia in adults aged ≥50 years in primary health care: an observational study in rural Crete, Greece.

BACKGROUND: Community-acquired pneumonia (CAP) is a potentially life-threatening condition that often requires hospitalisation particularly in the elderly population or in patients with comorbidities. AIMS: The aims of this study were to estimate the CAP frequency and severity in a well-defined primary healthcare setting in rural Crete, to record patient characteristics, their immunisation status and to estimate hospitalisation frequency and determinants. METHODS: An observational study was designed and implemented in a rural setting within the prefecture of Heraklion in the island of Crete, Greece. Eligible patients were those aged 50 years or above, presenting with CAP based on signs and symptoms and positive X-ray findings. RESULTS: A total of 124 CAP cases were recorded, 40 of which (32.3%) were hospitalised. Τhe age-standardised CAP incidence was estimated to be 236.7 cases per 100,000 persons aged ≥50 years. Forty-three patients (35.2%) were vaccinated against pneumococcus. The most frequent chronic illnesses were heart disease (64.5%), chronic obstructive pulmonary disease (32.5%), and type 2 diabetes (21%). Hospitalisation determinants included advanced age (≥74 years, Odds ratio (OR) 7.13; P value=0.001; 95% confidence interval (CI), 2.23-22.79), obesity (OR 3.36, P=0.037; 95% CI, 1.08-10.52), ≥40 pack-years of smoking (OR 3.82, P value=0.040; 95% CI, 1.07-18.42), presence of multimorbidity (OR 5.77, P value=0.003; 95% CI, 1.81-18.42) and pneumococcal vaccination (OR 0.29, P value=0.041; 95% CI, 0.09-0.95). CONCLUSIONS: This study highlighted patient characteristics and aspects of CAP epidemiology in the context of a rural primary care setting in southern Europe where limited data have been published until now.

The use of health status questionnaires in the management of chronic obstructive pulmonary disease patients in clinical practice.

Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone. Both questionnaires are designed to provide the clinician information enabling a more personalized disease approach and subsequent management. Although both Clinical COPD Questionnaire and COPD Assessment Test have good discriminate properties, their use as prognostic markers of severity and their ability to modify disease management has not yet been fully established. New studies are needed to further determine their value on several disease outcomes.

Primary care COPD patients compared with large pharmaceutically-sponsored COPD studies: an UNLOCK validation study.

BACKGROUND: Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS). There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care. OBJECTIVE: We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials. METHODS: Baseline data of seven primary care databases (n=3508) from Europe were compared to baseline data of the LPCS. In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria. RESULTS: Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p=0.03), predominantly male (MD 12.4; p=0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p=0.01). There were large differences in GOLD stage distribution compared to primary care patients. Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥ 1 and ≥ 2 exacerbations, although results were not statistically significant. Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥ 1 exacerbations per year and 12% had ≥ 2 exacerbations per year. The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT). CONCLUSION: Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations. More research is needed to determine the effect of pharmacological treatment in mild to moderate patients. We encourage future guideline makers to involve primary care populations in their recommendations.

Trends in metabolic syndrome risk factors among adolescents in rural Crete between 1989 and 2011.

OBJECTIVE: To investigate all the important factors contributing to the development of metabolic syndrome (MetS) as well as to explore the changes of these factors, over time, by comparing adolescent populations of rural areas of Heraklion, Crete, for the years 2011 and 1989. DESIGN: This study was carried out within two rural areas of the Heraklion region in Crete, Greece. The 1989 study was conducted in the village of Agia Varvara and the respective 2011 study within the municipality of Minoa Pediados. The study population consisted of 150 high school students (97 girls and 69 boys) in 1989 and 66 (30 girls and 36 boys) elementary (6th grade) and high school students in 2011, aged from 12 to 14 years old. Anthropometric, blood pressure and biochemical information was obtained. RESULTS: Of the MetS risk factors studied, only obesity incidence was found higher in 2011 compared to 1989 (obese adolescents 1.3% in 1989 versus 21.2% in 2011, p<0.001). On the other hand, hypertension levels were higher in 1989 compared to 2011 (46.7% versus 6.3%, respectively, p<0.001). In addition, glucose and LDL-C levels were lower in 2011. CONCLUSIONS: The present study supports the fact that there are significant changes in metabolic risk factors through time in adolescent populations of Crete, mainly due to the rise in obesity levels as well as to the decrease in hypertension, total cholesterol and LDL- cholesterol, as observed from the comparison of the years 1989 and 2011.