Fatigue in patients with chronic disease:results from the population-based Lifelines Cohort Study

(1) To evaluate the prevalence of severe and chronic fatigue in subjects with and without chronic disease; (2) to assess to which extent multi-morbidity contributes to severe and chronic fatigue; and (3) to identify predisposing and associated factors for severe and chronic fatigue and whether these are disease-specific, trans-diagnostic, or generic. The Dutch Lifelines cohort was used, including 78,363 subjects with (n = 31,039, 53 ± 12 years, 33% male) and without (n = 47,324, 48 ± 12 years, 46% male) ≥ 1 of 23 chronic diseases. Fatigue was assessed with the Checklist Individual Strength-Fatigue. Compared to participants without a chronic disease, a higher proportion of participants with ≥ 1 chronic disease were severely (23% versus 15%, p < 0.001) and chronically (17% versus 10%, p < 0.001) fatigued. The odds of having severe fatigue (OR [95% CI]) increased from 1.6 [1.5–1.7] with one chronic disease to 5.5 [4.5–6.7] with four chronic diseases; for chronic fatigue from 1.5 [1.5–1.6] to 4.9 [3.9–6.1]. Multiple trans-diagnostic predisposing and associated factors of fatigue were found, explaining 26% of variance in fatigue in chronic disease. Severe and chronic fatigue are highly prevalent in chronic diseases. Multi-morbidity increases the odds of having severe and chronic fatigue. Several trans-diagnostic factors were associated with fatigue, providing a rationale for a trans-diagnostic approach

Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19

BACKGROUND An increasing number of subjects are recovering from COVID-19, raising the need for tools to adequately assess the course of the disease and its impact on functional status. We aimed to assess the construct validity of the Post-COVID-19 Functional Status (PCFS) Scale among adult subjects with confirmed and presumed COVID-19. METHODS Adult subjects with confirmed and presumed COVID-19, who were members of an online panel and two Facebook groups for subjects with COVID-19 with persistent symptoms, completed an online survey after the onset of infection-related symptoms. The number and intensity of symptoms were evaluated with the Utrecht Symptom Diary, health-related quality of life (HrQoL) with the 5-level EQ-5D questionnaire, impairment in work and activities with the Work Productivity and Activity Impairment questionnaire and functional status with the PCFS Scale. RESULTS 1939 subjects were included in the analyses (85% women, 95% non-hospitalized during infection) about 3 months after the onset of infection-related symptoms. Subjects classified as experiencing 'slight', 'moderate' and 'severe' functional limitations presented a gradual increase in the number/intensity of symptoms, reduction of HrQoL and impairment in work and usual activities. No differences were found regarding the number and intensity of symptoms, HrQoL and impairment in work and usual activities between subjects classified as experiencing 'negligible' and 'no' functional limitations. We found weak-to-strong statistical associations between functional status and all domains of HrQoL (r: 0.233-0.661). Notably, the strongest association found was with the 'usual activities' domain of the 5-level EQ-5D questionnaire. CONCLUSION We demonstrated the construct validity of the PCFS Scale in highly-symptomatic adult subjects with confirmed and presumed COVID-19, 3 months after the onset of symptoms

Peripheral endothelial function is positively associated with maximal aerobic capacity in patients with chronic obstructive pulmonary disease

Background: Patients with COPD are frequently diagnosed with cardiovascular disease. Peripheral endothelial dysfunction is an underlying mechanism and can be used as an early marker of cardiovascular impairment. To date, little is known on the association between peripheral endothelial dysfunction, cardiovascular risk factors and measurements of exercise capacity in patients with COPD. Therefore, we aimed to determine the relation between endothelial function and patient characteristics, cardiovascular risk factors and (micro)vascular and functional performance in patient with CODP.Methods: Clinical and demographic data of patients with COPD were measured during routine pre-rehabilitation assessment. Cardiovascular risk factors, including blood pressure, ankle brachial index, arterial stiffness and retinal vessel widths were obtained. Peripheral endothelial function was measured using the EndoPAT-2000. Functional performance was assessed using cardiopulmonary exercise test, constant work rate test and six-minute walk test.Results: 40 patients with COPD completed the study protocol (65% males; mean age: 62.8 +/- 7.3 years; mean FEV1: 45.8 +/- 17.5 %pred). Peripheral endothelial dysfunction was observed in 55% of the patients. Patients with peripheral endothelial dysfunction had significantly worse aerobic exercise capacity and higher prevalence of cardiovascular risk factors. Stepwise multivariate regression models identified sex, systolic blood pressure and maximal aerobic capacity as independent correlates of peripheral endothelial function. After correction for sex, age and systolic blood pressure, there was a significant partial correlation between peripheral endothelial function and maximal aerobic capacity (R = 0.51, p = 0.004).Conclusion: Peripheral endothelial function was positively associated with maximal aerobic capacity, when correcting for sex, age and systolic blood pressure. Establishing peripheral endothelial dysfunction as a determinant of impaired aerobic capacity in COPD can be valuable for developing interventions aiming to improve aerobic capacity, and in turn cardiovascular health.</p

Dose response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults

<p>Background &amp; aims: Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D₂ or D₃ is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D₃ and assessed the dose which results in mean serum 25(OH)D₃ concentrations between 75 and 100 nmol/L. Methods: This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 μg calcifediol or 20 μg vitamin D₃ per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D₃, 25(OH)D₃, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) and 24,25-dihydroxyvitamin D₃ (24,25(OH)₂D₃). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated. Results: Supplementation with 20 μg vitamin D₃ increased 25(OH)D₃ concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 μg calcifediol increased 25(OH)D₃ levels &gt;75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D₃ levels stabilizing between 84 and 89 nmol/L in the 10 μg calcifediol group. A significant association was observed between the changes in 25(OH)D₃ and 24,25(OH)₂D₃ (R² = 0.83, P &lt; 0.01), but not between 25(OH)D₃ and 1,25(OH)₂D₃ (R² = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period. Conclusions: Calcifediol supplementation rapidly and safely elevates serum 25(OH)D₃ concentrations to improve vitamin D status in older adults. A daily dose of 10 μg calcifediol allows serum 25(OH)D₃ concentrations to be maintained between 75 and 100 nmol/L. Trial registration number: NCT01868945.</p

Differential Response to 12 Weeks of Once-Daily Tiotropium/Olodaterol Fixed Dose Combination in Patients with COPD:A Multidimensional Response Profiling in the TORRACTO Study

Purpose: Long-acting bronchodilators (LABD), in general, reduce respiratory symptoms, improve exercise endurance time and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, there might be heterogeneity in improvement for several outcomes on an individual level. Therefore, we aimed to profile the multidimensional response in patients receiving tiotropium/olodaterol (T/O) using self-organizing maps (SOM).Materials and Methods: This is a secondary analysis of the TORRACTO study: a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effects of T/O (2.5/5 and 5/5 mu g) compared with placebo after 6 and 12 weeks of treatment in patients with COPD. In the current study, we used endurance time, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), inspiratory capacity (IC) at rest and IC at isotime (ICiso) to identify clusters by means of SOM in patients treated with T/O.Results: Six clusters with distinct response profiles were generated at week 12 in COPD patients receiving T/O (n = 268). Patients in cluster 1 improved significantly on all outcomes, whilst cluster 5 showed strong improvement in endurance time (357s); contrarily, FEV1, FVC, ICrest and ICiso decreased when compared to baseline.Conclusion: Individual responses on endurance time and pulmonary function after 12 weeks of T/O are heterogeneous. This study identified clusters in COPD patients with markedly different multidimensional response on LABD

A pilot study on the feasibility and effectiveness of treadmill-based perturbations for assessing and improving walking stability in chronic obstructive pulmonary disease

BACKGROUND: Falls risk is elevated in chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the contributing factors. Here, we examined the feasibility of, and initial responses to, large walking perturbations in COPD, as well as the adaptation potential of people with COPD to repeated walking perturbations that might indicate potential for perturbation-based balance training in COPD. METHODS: 12 participants with COPD undergoing inpatient pulmonary rehabilitation and 12 age-gender-matched healthy control participants walked on an instrumented treadmill and experienced repeated treadmill-belt acceleration perturbations (leading to a forward balance loss). Three-dimensional motion capture was used to quantify the stability of participants body position during perturbed walking. Feasibility, stability following the initial perturbations and adaptation to repeated perturbations were assessed. FINDINGS: Using perturbations in this manner was feasible in this population (no harness assists and participants completed the minimum number of perturbations). No clear, specific deficit in reactive walking stability in COPD was found (no significant effects of participant group on stability or recovery step outcomes). There were mixed results for the adaptability outcomes which overall indicated some adaptability to repeated perturbations, but not to the same extent as the healthy control participants. INTERPRETATION: Treadmill-based perturbations during walking are feasible in COPD. COPD does not appear to result in significant deficits in stability following sudden perturbations and patients do demonstrate some adaptability to repeated perturbations. Perturbation-based balance training may be considered for fall prevention in research and practice in people with COPD

A pilot study on the feasibility and effectiveness of treadmill-based perturbations for assessing and improving walking stability in chronic obstructive pulmonary disease

BACKGROUND: Falls risk is elevated in chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the contributing factors. Here, we examined the feasibility of, and initial responses to, large walking perturbations in COPD, as well as the adaptation potential of people with COPD to repeated walking perturbations that might indicate potential for perturbation-based balance training in COPD. METHODS: 12 participants with COPD undergoing inpatient pulmonary rehabilitation and 12 age-gender-matched healthy control participants walked on an instrumented treadmill and experienced repeated treadmill-belt acceleration perturbations (leading to a forward balance loss). Three-dimensional motion capture was used to quantify the stability of participants body position during perturbed walking. Feasibility, stability following the initial perturbations and adaptation to repeated perturbations were assessed. FINDINGS: Using perturbations in this manner was feasible in this population (no harness assists and participants completed the minimum number of perturbations). No clear, specific deficit in reactive walking stability in COPD was found (no significant effects of participant group on stability or recovery step outcomes). There were mixed results for the adaptability outcomes which overall indicated some adaptability to repeated perturbations, but not to the same extent as the healthy control participants. INTERPRETATION: Treadmill-based perturbations during walking are feasible in COPD. COPD does not appear to result in significant deficits in stability following sudden perturbations and patients do demonstrate some adaptability to repeated perturbations. Perturbation-based balance training may be considered for fall prevention in research and practice in people with COPD