ICE COLD ERIC – International collaborative effort on chronic obstructive lung disease: exacerbation risk index cohorts – Study protocol for an international COPD cohort study

<p>Abstract</p> <p>Background</p> <p>Chronic Obstructive Pulmonary Disease (COPD) is a systemic disease; morbidity and mortality due to COPD are on the increase, and it has great impact on patients' lives. Most COPD patients are managed by general practitioners (GP). Too often, GPs base their initial assessment of patient's disease severity mainly on lung function. However, lung function correlates poorly with COPD-specific health-related quality of life and exacerbation frequency. A validated COPD disease risk index that better represents the clinical manifestations of COPD and is feasible in primary care seems to be useful. The objective of this study is to develop and validate a practical COPD disease risk index that predicts the clinical course of COPD in primary care patients with GOLD stages 2–4.</p> <p>Methods/Design</p> <p>We will conduct 2 linked prospective cohort studies with COPD patients from GPs in Switzerland and the Netherlands. We will perform a baseline assessment including detailed patient history, questionnaires, lung function, history of exacerbations, measurement of exercise capacity and blood sampling. During the follow-up of at least 2 years, we will update the patients' profile by registering exacerbations, health-related quality of life and any changes in the use of medication. The primary outcome will be health-related quality of life. Secondary outcomes will be exacerbation frequency and mortality. Using multivariable regression analysis, we will identify the best combination of variables predicting these outcomes over one and two years and, depending on funding, even more years.</p> <p>Discussion</p> <p>Despite the diversity of clinical manifestations and available treatments, assessment and management today do not reflect the multifaceted character of the disease. This is in contrast to preventive cardiology where, nowadays, the treatment in primary care is based on patient-specific and fairly refined cardiovascular risk profile corresponding to differences in prognosis. After completion of this study, we will have a practical COPD-disease risk index that predicts the clinical course of COPD in primary care patients with GOLD stages 2–4. In a second step we will incorporate evidence-based treatment effects into this model, such that the instrument may guide physicians in selecting treatment based on the individual patients' prognosis.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Archive NCT00706602</p

Simple functional performance tests and mortality in COPD

Exercise tests are important to characterise chronic obstructive pulmonary disease patients and predict their prognosis, but are often not available outside of rehabilitation or research settings. Our aim was to assess the predictive performance of the sit-to-stand and handgrip strength tests. The prospective cohort study in Dutch and Swiss primary care settings included a broad spectrum of patients (n=409) with Global Initiative for Chronic Obstructive Lung Disease stages II to IV. To assess the association of the tests with outcomes, we used Cox proportional hazards (mortality), negative binomial (centrally adjudicated exacerbations) and mixed linear regression models (longitudinal health-related quality of life) while adjusting for age, sex and severity of disease. The sit-to-stand test was strongly (adjusted hazard ratio per five more repetitions of 0.58, 95% CI 0.40-0.85; p=0.004) and the handgrip strength test moderately strongly (0.84, 95% CI 0.72-1.00; p=0.04) associated with mortality. Both tests were also significantly associated with health-related quality of life but not with exacerbations. The sit-to-stand test alone was a stronger predictor of 2-year mortality (area under curve 0.78) than body mass index (0.52), forced expiratory volume in 1 s (0.61), dyspnoea (0.63) and handgrip strength (0.62). The sit-to-stand test may close an important gap in the evaluation of exercise capacity and prognosis of chronic obstructive pulmonary disease patients across practice settings

Validity and reproducibility of a physical activity questionnaire for older adults: questionnaire versus accelerometer for assessing physical activity in older adults

BACKGROUND: Physical activity (PA) is important in older adults for the maintenance of functional ability. Assessing PA may be difficult. Few PA questionnaires have been compared to activity monitors. We examined reproducibility and validity of the self-administered Longitudinal Ageing Study Amsterdam Physical Activity Questionnaire (LAPAQ) against a triaxial accelerometer (ACTR) (Sensewear(®) Pro) in older adults. METHODS: Participants wore the ACTR continuously for two weeks. After 2 (T [time] = 1) and 4 (T = 2) weeks, participants completed the LAPAQ. Since the LAPAQ asks about 2 weeks' worth of physical activity, the ACTR and LAPAQ coincided at T1. T2 was used to assess the reproducibility of the LAPAQ results only. We calculated Pearson's correlation coefficients (PCC) to examine reproducibility and validity. For visualization, we used scatterplots and Bland-Altman plots. With a receiver operating characteristics (ROC) curve we assessed how well the LAPAQ identifies older adults whose activity level is below official recommendations. RESULTS: A total of 89 persons were included. Of the participants, 48% were men; median age was 73, and median body mass index was 25. The 2-week mean total duration of activity was 2788 (ACTR, T = 1), 2439 (LAPAQ T = 1), and 1994 (LAPAQ T = 2) minutes. As a reference, 2 full weeks contained 20,160 minutes. Reproducibility of the LAPAQ was moderate (PCC 0.68, 95% CI 0.55-0.80). The median difference between LAPAQ at T = 1 and the ACTR (LAPAQ minus ACTR) was -510 minutes and the PCC was 0.25 (95% CI 0.07-0.44). The area under the ROC curve was 0.73 (95% CI 0.59-0.86). CONCLUSION: LAPAQ underestimates PA and seems unsuitable for exact measurement in older adults. However, it may be used to determine if a person's PA level is below the recommended leve

The inaccuracy of patient recall for COPD exacerbation rate estimation and its implications: results from central adjudication

BACKGROUND: COPD exacerbation incidence rates are often ascertained retrospectively through patient recall and self-reports. We compared exacerbation ascertainment through patient self-reports and single-physician chart review to central adjudication by a committee and explored determinants and consequences of misclassification. METHODS: Self-reported exacerbations (event-based definition) in 409 primary care patients with COPD participating in the International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) cohort were ascertained every 6 months over 3 years. Exacerbations were adjudicated by single experienced physicians and an adjudication committee who had information from patient charts. We assessed the accuracy (sensitivities and specificities) of self-reports and single-physician chart review against a central adjudication committee (AC) (reference standard). We used multinomial logistic regression and bootstrap stability analyses to explore determinants of misclassifications. RESULTS: The AC identified 648 exacerbations, corresponding to an incidence rate of 0.60 ± 0.83 exacerbations/patient-year and a cumulative incidence proportion of 58.9%. Patients self-reported 841 exacerbations (incidence rate, 0.75 ± 1.01; incidence proportion, 59.7%). The sensitivity and specificity of self-reports were 84% and 76%, respectively, those of single-physician chart review were between 89% and 96% and 87% and 99%, respectively. The multinomial regression model and bootstrap selection showed that having experienced more exacerbations was the only factor consistently associated with underreporting and overreporting of exacerbations (underreporters: relative risk ratio [RRR], 2.16; 95% CI, 1.76-2.65 and overreporters: RRR, 1.67; 95% CI, 1.39-2.00). CONCLUSIONS: Patient 6-month recall of exacerbation events are inaccurate. This may lead to inaccurate estimates of incidence measures and underestimation of treatment effects. The use of multiple data sources combined with event adjudication could substantially reduce sample size requirements and possibly cost of studies. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT00706602

Prediction of COPD-specific health-related quality of life in primary care COPD patients: a prospective cohort study

Background: Health-related quality of life (HRQL) is an important patient-reported outcome for chronic obstructive pulmonary disease (COPD). Aim: We developed models predicting chronic respiratory questionnaire (CRQ) dyspnoea, fatigue, emotional function, mastery and overall HRQL at 6 and 24 months using predictors easily available in primary care. Methods: We used the “least absolute shrinkage and selection operator” (lasso) method to build the models and assessed their predictive performance. Results were displayed using nomograms. Results: For each domain-specific CRQ outcome, the corresponding score at baseline was the best predictor. Depending on the domain, these predictions could be improved by adding one to six other predictors, such as the other domain-specific CRQ scores, health status and depression score. To predict overall HRQL, fatigue and dyspnoea scores were the best predictors. Predicted and observed values were on average the same, indicating good calibration. Explained variance ranged from 0.23 to 0.58, indicating good discrimination. Conclusions: To predict COPD-specific HRQL in primary care COPD patients, previous HRQL was the best predictor in our models. Asking patients explicitly about dyspnoea, fatigue, depression and how they cope with COPD provides additional important information about future HRQL whereas FEV1 or other commonly used predictors add little to the prediction of HRQL

No association of 25-hydroxyvitamin D with exacerbations in primary care patients with COPD

BACKGROUND: Cross-sectional studies suggest an association of 25-hydroxyvitamin D with exacerbations in patients with COPD but longitudinal evidence from cohort studies is scarce. Our aim was to assess the association of serum 25-hydroxyvitamin D with exacerbations and mortality in primary care patients with COPD. METHODS: We included 356 COPD patients (GOLD stages II-IV, free of exacerbations for ≥4 weeks) from a prospective cohort study in Dutch and Swiss primary care settings in the main analysis where we assessed the association of 25-hydroxyvitamin D with (centrally adjudicated) exacerbations and mortality using negative binomial and Cox regression, respectively. RESULTS: Baseline mean serum 25-hydroxyvitamin D concentration was 15.5 ng/dl (SD 8.9) and 274 patients (77.0%) had 25-hydroxyvitamin D deficiency (&lt;20 ng/dl). Compared to patients with severe 25-hydroxyvitamin D deficiency (&lt;10 ng/dl, n=106 [29.8%]), patients with moderately deficient (10-19.99 ng/dl, n=168 [47.2%]) and insufficient (20-29.99 ng/dl, n=58 [16.3%]) concentrations had the same risk for exacerbations (incidence rate ratios of 1.01 [95% CI 0.77-1.57] and 1.00 [0.62-1.61], respectively). In patients with desirable concentrations (&gt;30 ng/dl, n=24 [6.7%]) the risk was lower, although not statistically significantly (0.72 [0.37-1.42]). Including patients with vitamin D supplements, using different cut-offs for 25-hydroxyvitamin D or competing risk models did not materially change the results. We did not find a statistically significant association of 25-hydroxyvitamin D concentration with mortality. CONCLUSION: This longitudinal study in a real-world COPD population that carefully minimized misclassification of exacerbations and the influence of confounding did not show an association of 25-hydroxyvitamin D with exacerbations and mortality. STUDY REGISTRATION ClinicalTrials.gov (NCT00706602)

Five comorbidities reflected the health status in patients with chronic obstructive pulmonary disease: the newly developed COMCOLD index

OBJECTIVE This study aimed to identify those comorbidities with greatest impact on patient-reported health status in patients with chronic obstructive pulmonary disease (COPD) and to develop a comorbidity index that reflects their combined impact. STUDY DESIGN AND SETTING We included 408 Swiss and Dutch primary care patients with COPD from the International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) in this cross-sectional analysis. Primary outcome was the Feeling Thermometer, a patient-reported health status instrument. We assessed the impact of comorbidities at five cohort assessment times using multiple linear regression adjusted for FEV1, retaining comorbidities with associations P ≤ 0.1. We developed an index that reflects strength of association of comorbidities with health status. RESULTS Depression (prevalence: 13.0%; regression coefficient: -9.00; 95% CI: -13.52, -4.48), anxiety (prevalence: 11.8%; regression coefficient: -5.53; 95% CI -10.25, -0.81), peripheral artery disease (prevalence: 6.4%; regression coefficient: -5.02; 95% CI-10.64, 0.60), cerebrovascular disease (prevalence: 8.8%; regression coefficient: -4.57; 95% CI -9.43, 0.29), and symptomatic heart disease (prevalence: 20.3%; regression coefficient: -3.81; 95% CI -7.23, -0.39) were most strongly associated with the Feeling Thermometer. These five comorbidities, weighted, compose the COMorbidities in Chronic Obstructive Lung Disease (COMCOLD) index. CONCLUSION The COMCOLD index reflects the combined impact of five important comorbidities from patients' perspective and complements existing comorbidity indices that predict death. It may help clinicians focus on comorbidities affecting patients' health status the most

All that glitters isn't gold: A survey on acknowledgment of limitations in biomedical studies

BACKGROUND: Acknowledgment of all serious limitations to research evidence is important for patient care and scientific progress. Formal research on how biomedical authors acknowledge limitations is scarce. OBJECTIVES: To assess the extent to which limitations are acknowledged in biomedical publications explicitly, and implicitly by investigating the use of phrases that express uncertainty, so-called hedges; to assess the association between industry support and the extent of hedging. DESIGN: We analyzed reporting of limitations and use of hedges in 300 biomedical publications published in 30 high and medium -ranked journals in 2007. Hedges were assessed using linguistic software that assigned weights between 1 and 5 to each expression of uncertainty. RESULTS: Twenty-seven percent of publications (81/300) did not mention any limitations, while 73% acknowledged a median of 3 (range 1-8) limitations. Five percent mentioned a limitation in the abstract. After controlling for confounders, publications on industry-supported studies used significantly fewer hedges than publications not so supported (p = 0.028). LIMITATIONS: Detection and classification of limitations was - to some extent - subjective. The weighting scheme used by the hedging detection software has subjective elements. CONCLUSIONS: Reporting of limitations in biomedical publications is probably very incomplete. Transparent reporting of limitations may protect clinicians and guideline committees against overly confident beliefs and decisions and support scientific progress through better design, conduct or analysis of new studies