Lara Siebeling

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. The 1-min sit-to-stand test predicts mortality in COPD patients and can easily be implemented across practice settings http://ow.ly/mxrPx

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. The aim of this study was to assess the association of serum 25-hydroxyvitamin D with exacerbations and mortality in primary care patients with COPD. METHODS In the main analysis, we included 356 patients with COPD (GOLD [Global Initiative for Chronic Obstructive Lung Disease] stages II-IV, free from exacerbations for ≥ 4 weeks) from a prospective cohort study in Dutch and Swiss primary care settings. We used negative binomial and Cox regression to assess the association of 25-hydroxyvitamin D with (centrally adjudicated) exacerbations and mortality, respectively. RESULTS Baseline mean ± SD serum 25-hydroxyvitamin D concentration was 15.5 ± 8.9 ng/dL, and 274 patients (77.0%) had 25-hydroxyvitamin D deficiency (< 20 ng/dL). Compared with patients with severe 25-hydroxyvitamin D deficiency (< 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 ratio, 1.01 [95% CI, 0.77-1.57] vs 1.00 [95% CI, 0.62-1.61], respectively). In patients with desirable concentrations (> 30 ng/dL, n = 24 [6.7%]), the risk was lower, although not significantly (incidence rate ratio, 0.72 [95% CI, 0.37-1.42]). In patients taking vitamin D supplements, using different cutoffs 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. CONCLUSIONS 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.

Characteristics of Dutch and Swiss primary care COPD patients – baseline data of the ICE COLD ERIC study

Introduction International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts (ICE COLD ERIC) is a prospective cohort study with chronic obstructive pulmonary disease (COPD) patients from Switzerland and The Netherlands designed to develop and validate practical COPD risk indices that predict the clinical course of COPD patients in primary care. This paper describes the characteristics of the cohorts at baseline. Material and methods Standardized assessments included lung function, patient history, self-administered questionnaires, exercise capacity, and a venous blood sample for analysis of biomarkers and genetics. Results A total of 260 Dutch and 151 Swiss patients were included. Median age was 66 years, 57% were male, 38% were current smokers, 55% were former smokers, and 76% had at least one and 40% had two or more comorbidities with cardiovascular disease being the most prevalent one. The use of any pulmonary and cardiovascular drugs was 84% and 66%, respectively. Although lung function results (median forced expiratory volume in 1 second [FEV1] was 59% of predicted) were similar across the two cohorts, Swiss patients reported better COPD-specific health-related quality of life (Chronic Respiratory Questionnaire) and had higher exercise capacity. Discussion COPD patients in the ICE COLD ERIC study represent a wide range of disease severities and the prevalence of multimorbidity is high. The rich variation in these primary care cohorts offers good opportunities to learn more about the clinical course of COPD.

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 level.

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.

The ADO index as a predictor of two-year mortality in general practice-based chronic obstructive pulmonary disease cohorts.

Background: Existing prediction models for mortality in chronic obstructive pulmonary disease (COPD) patients have not yet been validated in primary care, which is where the majority of patients receive care. Objectives: Our aim was to validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2-year mortality in 2 general practice-based COPD cohorts. Methods: Six hundred and forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV were enrolled by their general practitioners and followed for 2 years. The ADO regression equation was used to predict a 2-year risk of all-cause mortality in each patient and this risk was compared with the observed 2-year mortality. Discrimination and calibration were assessed as well as the strength of association between the 15-point ADO score and the observed 2-year all-cause mortality. Results: Fifty-two (8.1%) patients died during the 2-year follow-up period. Discrimination with the ADO index was excellent with an area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall, the predicted and observed risks matched well and visual inspection revealed no important differences between them across 10 risk classes (p = 0.68). The odds ratio for death per point increase according to the ADO index was 1.50 (95% CI 1.31-1.71). Conclusions: The ADO index showed excellent prediction properties in an out-of-population validation carried out in COPD patients from primary care settings.

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.

Voorspellen van kwaliteit van leven van COPD-patiënten

SamenvattingSiebeling L, Ter Riet, G. Voorspellen van kwaliteit van leven van COPD-patiënten. Huisarts Wet 2015;58(10):522-5. Het proefschrift van Siebeling betreft een internationaal prospectief cohortonderzoek met eerstelijns-COPD-patiënten. Het primaire doel is het ontwikkelen van predictiemodellen voor ziektegerelateerde kwaliteit van leven (KvL) en het secundaire doel betreft exacerbaties en sterfte. Deze modellen moeten bruikbaar zijn voor huisartsen en mogen dus alleen predictoren bevatten die beschikbaar zijn in de huisartsenpraktijk. Er zijn verschillende modellen om de sterftekans bij COPD-patiënten te voorspellen. Vanuit het perspectief van de patiënt is het voorspellen van het ziektebeloop in termen van KvL en exacerbaties waarschijnlijk belangrijker. Daarnaast zijn bestaande modellen veelal niet toepasbaar in de huisartsenpraktijk. Voor het instellen van het juiste behandelplan voor de individuele patiënt kan het voor huisartsen nuttig zijn als ze een inschatting kunnen maken van het te verwachten beloop van deze klinisch belangrijke uitkomstmaten. Voorgaande COPD-gerelateerde KvL blijkt de sterkste voorspeller van toekomstige KvL. Bij patiënten informeren naar kortademigheid, vermoeidheid, emotionele beperkingen en de manier waarop ze met COPD omgaan levert belangrijke informatie op over toekomstige KvL en is in iedere huisartsenpraktijk toepasbaar.AbstractSiebeling L, Ter Riet, G. Predicting the quality of life of COPD patients. Huisarts Wet 2015;58(10):522-5. The PhD thesis of Lara Siebeling describes an international prospective cohort study of COPD patients in general practice. The main aim of the study was to develop prediction models for the health-related quality of life (HR-QoL) of these patients, with secondary aims the prediction of exacerbations and mortality. As these models are intended for use in general practice, they should include only predictors that are available or that can be measured in general practice. Although there are several models to predict the mortality risk of patients with COPD, from the patient’s perspective, models that predict the course of the disease in terms of HR-QoL and exacerbations are probably more important. Moreover, existing models are often not appropriate for use in general practice. In order to make a tailored treatment plan for the individual patient, it would be helpful if the general practitioner could estimate how these important clinical outcomes are expected to change during the course of the disease. Previous COPD-associated HR-QoL appeared to be the strongest predictor of future HR-QoL. Asking patients about shortness of breath, fatigue, emotional limitations, and how they cope with COPD provides important information about future HR-QoL, information that can be acquired in every general practice.