scholarly journals What Are Good Muscle Endpoints for Translational Studies?

Author(s):  
Jörn Rittweger

What Are Good Muscle Endpoints for Translational Studies? Jörn Rittweger()1,2 1Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany 2Department of Pediatrics and Adolescent Medicine, University of Cologne, Cologne, Germany © The Author   Abstract Muscles matter to our health because of their size, their involvement in energy metabolism and their relevance for locomotion. Adequate selection of good endpoints is crucial for successfully designing translational studies. At least eight different muscle functions matter to health, namely the mechanical functions of exerting force, velocity, power, elastic storage and braking power, the two metabolic functions of substrate uptake (e.g. carbohydrates, lipids and amino acids) and substrate provision (e.g. lactate and amino acids) and secretory functions. However, specific endpoint tests have been validated for muscle force and power only. Walking speed and grip strength demonstrate good predictive value for hard clinical endpoints, such as disability, loss of autonomy and death. Vertical jump power also has good ecological validity and construct validity, and it depicts excellent test-retest reliability, which is an important advantage with regard to the study of power. Assessment of muscle mass, e.g. by magnetic resonance imaging, dual energy X-ray absorptiometry or bioelectrical impedance, should be considered as an important secondary endpoint to enhance construct validity. Further secondary endpoints should be included wherever they are likely to enhance the plausibility of the study outcome and assessment of test-retest reliability at baseline is always recommended. Well-established methods exist for three relevant muscular endpoints, namely power, strength and muscle mass, and these endpoints lend themselves to utilization in clinical studies. However, such validated methods lack a number of additional muscle functions that are scientifically only emerging. This applies foremost to the metabolic function of muscles but also to its role in storage and dissipation of mechanical energy.

Rheumatology ◽  
2021 ◽  
Author(s):  
Bonny Rockette-Wagner ◽  
Didem Saygin ◽  
Siamak Moghadam-Kia ◽  
Chester Oddis ◽  
Océane Landon-Cardinal ◽  
...  

Abstract Objective Idiopathic inflammatory myopathies (IIM) cause proximal muscle weakness, which affect activities of daily living. Wearable physical activity monitors (PAMs) objectively assess continuous activity with potential clinical usefulness in IIM assessment. We examined the psychometric characteristics for PAM outcomes in IIM. Methods Adult IIM patients were prospectively evaluated (baseline, 3 and 6-months) in an observational study. A waist-worn PAM (ActiGraph GT3X-BT) assessed average step counts/min, peak 1-min cadence, and vector magnitude/min. Validated myositis core set measures (CSM) including manual muscle testing (MMT), physician global disease activity (MD global), patient global disease activity (Pt global), extra-muscular disease activity (Ex-muscular global), HAQ-DI, muscle enzymes, and patient-reported physical function were evaluated. Test-retest reliability, construct validity, and responsiveness were determined for PAM measures and CSM using Pearson correlations and other appropriate analyses. Results 50 adult IIM patients enrolled [mean (SD) age, 53.6 (±14.6); 60% female, 94% Caucasian]. PAM measures showed strong test-retest reliability, moderate-to-strong correlations at baseline with MD global (r=-0.37- -0.48), Pt-global (r=-0.43- -0.61), HAQ-DI (r=-0.47- -0.59) and MMT (r = 0.37–0.52), and strong discriminant validity for categorical MMT and HAQ-DI. Longitudinal association with MD global (r=-0.38- -0.44), MMT (r = 0.50–0.57), HAQ-DI (r=-0.45- -0.55), and functional tests (r = 0.30–0.65) were moderate-to-strong. PAM measures were responsive to MMT improvement (≥10%) and moderate-to-major improvement on ACR/EULAR myositis response criteria. Peak 1-min cadence had the largest effect size and Standardized Response Means (SRMs). Conclusion PAM measures showed promising construct validity, reliability, and longitudinal responsiveness; especially peak 1-min cadence. PAMs provide valid outcome measures for future use in IIM clinical trials.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Marco Monticone ◽  
Cristiano Sconza ◽  
Igor Portoghese ◽  
Tomohiko Nishigami ◽  
Benedict M. Wand ◽  
...  

Abstract Background and aim Growing attention is being given to utilising physical function measures to better understand and manage knee osteoarthritis (OA). The Fremantle Knee Awareness Questionnaire (FreKAQ), a self-reported measure of body-perception specific to the knee, has never been validated in Italian patients. The aims of this study were to culturally adapt and validate the Italian version of the FreKAQ (FreKAQ-I), to allow for its use with Italian-speaking patients with painful knee OA. Methods The FreKAQ-I was developed by means of forward–backward translation, a final review by an expert committee and a test of the pre-final version to evaluate its comprehensibility. The psychometric testing included: internal structural validity by Rasch analysis; construct validity by assessing hypotheses of FreKAQ correlations with the knee injury and osteoarthritis outcome score (KOOS), a pain intensity numerical rating scale (PI-NRS), the pain catastrophising scale (PCS), and the Hospital anxiety and depression score (HADS) (Pearson’s correlations); known-group validity by evaluating the ability of FreKAQ scores to discriminate between two groups of participants with different clinical profiles (Mann–Whitney U test); reliability by internal consistency (Cronbach’s alpha) and test–retest reliability (intraclass correlation coefficient, ICC2.1); and measurement error by calculating the minimum detectable change (MDC). Results It took one month to develop a consensus-based version of the FreKAQ-I. The questionnaire was administered to 102 subjects with painful knee OA and was well accepted. Internal structural validity confirmed the substantial unidimensionality of the FreKAQ-I: variance explained was 53.3%, the unexplained variance in the first contrast showed an eigenvalue of 1.8, and no local dependence was detected. Construct validity was good as all of the hypotheses were met; correlations: KOOS (rho = 0.38–0.51), PI-NRS (rho = 0.35–0.37), PCS (rho = 0.47) and HADS (Anxiety rho = 0.36; Depression rho = 0.43). Regarding known-groups validity, FreKAQ scores were significantly different between groups of participants demonstrating high and low levels of pain intensity, pain catastrophising, anxiety, depression and the four KOOS subscales (p ≤ 0.004). Internal consistency was acceptable (α = 0.74) and test–retest reliability was excellent (ICC = 0.92, CI 0.87–0.94). The MDC95 was 5.22 scale points. Conclusion The FreKAQ-I is unidimensional, reliable and valid in Italian patients with painful knee OA. Its use is recommended for clinical and research purposes.


2017 ◽  
Vol 32 (2) ◽  
Author(s):  
Shannon Gwin ◽  
Paul Branscum ◽  
E. Laurette Taylor

The purpose of this study was to create a valid and reliable instrument to evaluate theory-basedbeliefs towards physical activity among clergy members. Data were collected from 174 clergy that par-ticipated in a 15-item online and paper-based survey. Psychometric properties of the instrument includedconfirmatory factor analysis (construct validity), and cronbach’s alpha (internal consistency reliability).In addition, the stability (test-retest reliability) of each subscale was evaluated with a sub-sample of 30participants. Results show the instrument was both valid and reliable, and will be useful in future studiestargeting this population. Future implications are discussed.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24027-e24027
Author(s):  
Jaba Kokhreidze ◽  
Veleka Allen ◽  
Cristina Ivanescu ◽  
Xiaopan Valerie Yao ◽  
Bin Zhang ◽  
...  

e24027 Background: The ongoing two-part phase 2/3 RESILIENT study (NCT03088813) is investigating the efficacy and safety of liposomal irinotecan monotherapy in patients with SCLC who have progressed on or after first line platinum-based chemotherapy. This exploratory analysis from RESILIENT part 1 was conducted to confirm the psychometric properties of established PRO instruments that had not previously been validated in patients with SCLC. Methods: Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30 (C30) and the EORTC QLQ Lung Cancer 13 (LC13) before treatment assignment (baseline), every 6 weeks thereafter, at treatment discontinuation and at the 30-day follow-up visit. Psychometric methods included descriptive statistics (items and scales), correlations (item-to-item and item-to-total), internal consistency (Cronbach’s α), test-retest reliability (intraclass correlation coefficient [ICC], two-way random effects model), construct validity and sensitivity to change. The analysis included patients who received at least one dose of study drug and completed at least one PRO assessment. Results: Thirty patients were enrolled in RESILIENT part 1 and included in the analysis. At baseline, 68% of patients reported ‘not severe’ or ‘mild’ symptoms. Floor effects (i.e. more than 25% of responses of ‘not at all’) were observed for several of the functioning/impact and symptom scales of the EORTC QLQ C30 and LC13. Moderate to strong correlations were found among most questionnaire items within their respective scales. Acceptable evidence for internal consistency and good test-retest reliability were observed. Selected results for the EORTC QLQ LC13, including dyspnea scales, are shown in the Table. The magnitude of correlations among PRO instruments supported evidence for convergent validity in this sample. Conclusions: In RESILIENT part 1, patients experienced low and tolerable symptoms at enrollment, limiting the potential for further improvement. Overall, these PRO instruments had acceptable psychometric properties (e.g. construct validity, reliability and ability to detect change) in this sample. However, these analyses should be repeated in a larger sample using data from RESILIENT part 2. Clinical trial information: NCT03088813. [Table: see text]


Author(s):  
Katherine L. Marks ◽  
Alessandra Verdi ◽  
Laura E. Toles ◽  
Kaila L. Stipancic ◽  
Andrew J. Ortiz ◽  
...  

Objective The purpose of this study was to examine the psychometric properties of an ecological vocal effort scale linked to a voicing task. Method Thirty-eight patients with nodules, 18 patients with muscle tension dysphonia, and 45 vocally healthy control individuals participated in a week of ambulatory voice monitoring. A global vocal status question was asked hourly throughout the day. Participants produced a vowel–consonant–vowel syllable string and rated the vocal effort needed to produce the task on a visual analog scale. Test–retest reliability was calculated for a subset using the intraclass correlation coefficient, ICC(A, 1). Construct validity was assessed by (a) comparing the weeklong vocal effort ratings between the patient and control groups and (b) comparing weeklong vocal effort ratings before and after voice rehabilitation in a subset of 25 patients. Cohen's d, the standard error of measurement ( SEM ), and the minimal detectable change (MDC) assessed sensitivity. The minimal clinically important difference (MCID) assessed responsiveness. Results Test–retest reliability was excellent, ICC(A, 1) = .96. Weeklong mean effort was statistically higher in the patients than in controls ( d = 1.62) and lower after voice rehabilitation ( d = 1.75), supporting construct validity and sensitivity. SEM was 4.14, MDC was 11.47, and MCID was 9.74. Since the MCID was within the error of the measure, we must rely upon the MDC to detect real changes in ecological vocal effort. Conclusion The ecological vocal effort scale offers a reliable, valid, and sensitive method of monitoring vocal effort changes during the daily life of individuals with and without vocal hyperfunction.


2020 ◽  
Author(s):  
Pim van Oirschot ◽  
Marco Heerings ◽  
Karine Wendrich ◽  
Bram den Teuling ◽  
Marijn B Martens ◽  
...  

BACKGROUND The decline of cognitive processing speed (CPS) is a common dysfunction in persons with multiple sclerosis (MS). The Symbol Digit Modalities Test (SDMT) is widely used to formally quantify CPS. We implemented a variant of the SDMT in MS sherpa, a smartphone app for persons with MS. OBJECTIVE The aim of this study was to investigate the construct validity and test-retest reliability of the MS sherpa smartphone variant of the SDMT (sSDMT). METHODS We performed a validation study with 25 persons with relapsing-remitting MS and 79 healthy control (HC) subjects. In the HC group, 21 subjects were matched to the persons with MS with regard to age, gender, and education and they followed the same assessment schedule as the persons with MS (the “HC matched” group) and 58 subjects had a less intense assessment schedule to determine reference values (the “HC normative” group). Intraclass correlation coefficients (ICCs) were determined between the paper-and-pencil SDMT and its smartphone variant (sSDMT) on 2 occasions, 4 weeks apart. Other ICCs were determined for test-retest reliability, which were derived from 10 smartphone tests per study participant, with 3 days in between each test. Seven study participants with MS were interviewed regarding their experiences with the sSDMT. RESULTS The SDMT scores were on average 12.06% higher than the sSDMT scores, with a standard deviation of 10.68%. An ICC of 0.838 was found for the construct validity of the sSDMT in the combined analysis of persons with MS and HC subjects. Average ICCs for test-retest reliability of the sSDMT for persons with MS, the HC matched group, and the HC normative group were 0.874, 0.857, and 0.867, respectively. The practice effect was significant between the first and the second test of the persons with MS and the HC matched group and trivial for all other test-retests. The interviewed study participants expressed a positive attitude toward the sSDMT, but they also discussed the importance of adapting a smartphone cognition test in accordance with the needs of the individual persons with MS. CONCLUSIONS The high correlation between sSDMT and the conventional SDMT scores indicates a very good construct validity. Similarly, high correlations underpin a very good test-retest reliability of the sSDMT. We conclude that the sSDMT has the potential to be used as a tool to monitor CPS in persons with MS, both in clinical studies and in clinical practice.


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