scholarly journals The Minimal Clinical Important Difference (MCID) in Annual Rate of Change of Timed Function Tests in Boys with DMD

2021 ◽  
pp. 1-10
Author(s):  
Tina Duong ◽  
Jennifer Canbek ◽  
Marisa Birkmeier ◽  
Leslie Nelson ◽  
Catherine Siener ◽  
...  
Keyword(s):  
Disease Progression ◽  
Muscle Weakness ◽  
Genetic Disorder ◽  
Functional Change ◽  
Rate Of Change ◽  
Minimal Detectable Change ◽  
Natural History Study ◽  
Clinical Endpoints ◽  
Function Tests ◽  
Standard Error Of Measurement

Background: Duchenne muscular dystrophy (DMD) is a rare x-linked recessive genetic disorder affecting 1 in every 5000–10000 [1, 2]. This disease leads to a variable but progressive sequential pattern of muscle weakness that eventually leads to loss of important functional milestones such as the ability to walk. With promising drugs in development to ameliorate the effects of muscle weakness, these treatments must be associated with a clinically meaningful functional change. Objective: The objective of this analysis is to determine both distribution, minimal detectable change (MDC), and anchor-based, minimal clinically important difference, (MCID) of 12 month change values in standardized time function tests (TFT) used to monitor disease progression in DMD. Method: This is a retrospective analysis of prospectively collected data from a multi-center prospective natural history study with the Cooperative International Neuromuscular Research Group (CINRG). This study calculated MDC and MCID values for 3 commonly used timed function tests typically used to monitor disease progression; supine to stand (STS), 10 meter walk/run(10MWT), and 4 stair climb(4SC). MDC used standard error of measurement (SEM) while MCID measurements used the Vignos scale as an anchor to determine clinical change in functional status. Results: All 3 TFT were significantly important clinical endpoints to detect MDC and MCID changes. MDC and MCID 12 month changes were significant in 10MWT(–0.138, –0.212), Supine to Stand (–0.026, –0.023) and 4 stair climb (–0.034, –0.035) with an effect size greater or close to 0.2. Conclusion: The 3 TFT are clinically meaningful endpoints used to establish change in DMD. MCID values were higher than MDC values indicating that an anchor-based approach using Vignos as a clinically meaningful loss of lower extremity abilities is appropriate to assess change in boys with DMD.

scholarly journals In Vivo Assessment of Metabolic Abnormality in Alport Syndrome Using Hyperpolarized [1-13C] Pyruvate MR Spectroscopic Imaging

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 222
Author(s):  
Nguyen-Trong Nguyen ◽  
Eun-Hui Bae ◽  
Luu-Ngoc Do ◽  
Tien-Anh Nguyen ◽  
Ilwoo Park ◽  
...  
Keyword(s):  
Disease Progression ◽  
Alport Syndrome ◽  
Genetic Disorder ◽  
Lactate Production ◽  
Clinical Importance ◽  
Metabolic Imaging ◽  
Renal Metabolism ◽  
Hyperpolarized 13C ◽  
And Control

Alport Syndrome (AS) is a genetic disorder characterized by impaired kidney function. The development of a noninvasive tool for early diagnosis and monitoring of renal function during disease progression is of clinical importance. Hyperpolarized 13C MRI is an emerging technique that enables non-invasive, real-time measurement of in vivo metabolism. This study aimed to investigate the feasibility of using this technique for assessing changes in renal metabolism in the mouse model of AS. Mice with AS demonstrated a significant reduction in the level of lactate from 4- to 7-week-old, while the levels of lactate were unchanged in the control mice over time. This reduction in lactate production in the AS group accompanied a significant increase of PEPCK expression levels, indicating that the disease progression in AS triggered the gluconeogenic pathway and might have resulted in a decreased lactate pool size and a subsequent reduction in pyruvate-to-lactate conversion. Additional metabolic imaging parameters, including the level of lactate and pyruvate, were found to be different between the AS and control groups. These preliminary results suggest that hyperpolarized 13C MRI might provide a potential noninvasive tool for the characterization of disease progression in AS.

scholarly journals Evaluating functional change using the Physical Abilities and Mobility Scale in acute paediatric neurorehabilitation

2020 ◽  
Vol 27 (12) ◽  
pp. 1-11
Author(s):  
David K Young ◽  
Helen E Starace ◽  
Hannah I Boddy ◽  
Keira MD Connolly ◽  
Kieren J Lock ◽  
...  
Keyword(s):  
Brain Injury ◽  
Motor Function ◽  
Acquired Brain Injury ◽  
Functional Change ◽  
Acute Hospital ◽  
Rate Of Change ◽  
Interquartile Range ◽  
Gross Motor ◽  
Gross Motor Function ◽  
Physical Abilities

Background/Aims Childhood acquired brain injury is the leading cause of death and long-term disability among children and young people in the UK. Following a childhood brain injury, function is shown to improve within a specialist neurorehabilitation setting. Little evidence currently exists to demonstrate gross motor functional change within an acute hospital setting. The Physical Abilities and Mobility Scale is a valid and reliable outcome measure for use within inpatient paediatric neurorehabilitation following brain injury. The primary aim of this study was to evaluate how the gross motor function of paediatric patients with a new acquired brain injury changes during an acute hospital admission. Methods Data were collected for all patients admitted as an inpatient to one acute hospital over a 12-month period. The Physical Abilities and Mobility Scale was completed at baseline, at least weekly and again at discharge. Views relating to the utility of the Physical Abilities and Mobility Scale were sought among physiotherapists using the measure in order to inform acceptability. Results A total of 28 patients were included in this study. A Wilcoxon signed rank test was performed, which showed a highly significant improvement in function as scored on the Physical Abilities and Mobility Scale between baseline assessment (median 29.00, interquartile range 25.00–35.50) and discharge (median 85.00, interquartile range 75.00–95.00, Z=-4.624, P<0.001). A total of five patients (17.86%) were referred on for specialist residential neurorehabilitation. A post hoc analysis found that the rate of change of the Physical Abilities and Mobility Scale appeared to have an impact on final discharge destination, with slow improvers 18.60 times more likely to require specialist rehabilitation than others. The Physical Abilities and Mobility Scale was found to be acceptable among physiotherapists using it. Conclusions Children with a new acquired brain injury make significant improvements in gross motor function during a period of acute inpatient neurorehabilitation. Further work should look to refine the measure and gain a full understanding of its clinical utilities.

scholarly journals Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and their reversibility with carbimazole therapy

2002 ◽  
pp. 299-303 ◽  
Author(s):  
R Goswami ◽  
R Guleria ◽  
AK Gupta ◽  
N Gupta ◽  
RK Marwaha ◽  
...  
Keyword(s):  
Lung Function ◽  
Muscle Weakness ◽  
Forced Expiratory Volume ◽  
Clinical Severity ◽  
Diaphragm Muscle ◽  
Graves Disease ◽  
Lung Function Tests ◽  
Diaphragmatic Muscle ◽  
Function Tests ◽  
Diaphragmatic Movement

OBJECTIVES: Dyspnoea is a common complaint among patients with thyrotoxicosis. However, its causative mechanisms have not been identified. We assessed the role of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active Graves' disease. METHODS: Twenty-seven patients (19 female, 8 male) with active Graves' disease were assessed for the clinical severity of dyspnoea, functional (pressure generating capacity) and anatomical aspects (thickness and excursion) of the diaphragm at presentation. The severity of dyspnoea was assessed using a visual analogue scale (VAS) and the 6 min walk test. Lung function tests, diaphragmatic strength (sniff oesophageal pressure, SniffP(oeso)), maximum inspiratory and expiratory pressures, diaphragmatic thickness and movements on real time ultrasonography were evaluated during normal and deep respiration. Twenty of the 27 patients were reassessed after achieving euthyroidism with carbimazole therapy at a mean interval of 5+/-2 months. RESULTS: Reevaluation after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS (59+/-26 to 23+/-13%). Patients covered a similar distance during the 6 min walk before and after euthyroidism. Significant improvement was observed in the vital capacity (2.57+/-0.62 to 2.94+/-0.60 l), forced expiratory volume in the first second (2.21+/-0.49 to 2.45+/-0.47 l), total lung capacity (3.57+/-1.19 to 4.1+/-1.12 l), diaphragmatic movement during deep respiration (5.5+/-1.0 to 6.6+/-1.1 cm) and SniffP(oeso) (68.7+/-23 to 93.1+/-25.2 cmH(2)O). There was no significant change in the distance walked in 6 min, tidal volume, lung diffusion capacity and diaphragmatic thickness. There was no significant correlation between the net change in dyspnoea score and net change in lung function tests, diaphragmatic movement and SniffP(oeso). CONCLUSIONS: Significant functional weakness of diaphragm muscle is present in patients with active Graves' disease. This weakness is more marked during a maximal respiratory manoeuvre, indicating a diminished diaphragmatic reserve which could be the cause of dyspnoea observed on exertion among patients with thyrotoxicosis.

A Longitudinal Study of Quantitative Muscle Strength and Functional Motor Ability in Ambulatory Boys with Duchenne Muscular Dystrophy

2021 ◽  
pp. 1-14
Author(s):  
Cathleen E. Buckon ◽  
Susan E. Sienko ◽  
Eileen G. Fowler ◽  
Anita M. Bagley ◽  
Loretta A. Staudt ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Strength ◽  
Genetic Disorder ◽  
Knee Extensor ◽  
Standard Of Care ◽  
Rate Of Change ◽  
Isokinetic Dynamometry ◽  
Gross Motor

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder, that is characterized by progressive muscle degeneration and loss of ambulation between 7–13 years of age. Novel pharmacological agents targeting the genetic defects and disease mechanisms are becoming available; however, corticosteroid (CS) therapy remains the standard of care. Objective: The purpose of this longitudinal study was to elucidate the effect of CS therapy on the rate of muscle strength and gross motor skill decline in boys with DMD and assess the sensitivity of selected outcome measures. Methods: Eighty-four ambulatory boys with DMD (49–180 months), 70 on CS, 14 corticosteroid naïve (NCS), participated in this 8-year multi-site study. Outcomes included; isokinetic dynamometry, the Standing (STD) and Walking/Running/jumping (WRJ) dimensions of the Gross Motor Function Measure (GMFM), and Timed Function Tests (TFTs). Nonlinear mixed modeling procedures determined the rate of change with age and the influence of steroids. Results: Despite CS therapy the rate of decline in strength with age was significant in all muscle groups assessed. CS therapy significantly slowed decline in knee extensor strength, as the NCS group declined at 3x the rate of the CS group. Concurrently, WRJ skills declined in the NCS group at twice the rate of the CS group. 4-stair climb and 10 meter walk/run performance was superior in the boys on CS therapy. Conclusion: CS therapy slowed the rate of muscle strength decline and afforded longer retention of select gross motor skills in boys on CS compared to boys who were NCS. Isokinetic dynamometry, Walk/Run/Jump skills, and select TFTs may prove informative in assessing the efficacy of new therapeutics in ambulatory boys with DMD.

scholarly journals Quantitative Mechanical Properties of the Relaxed Biceps and Triceps Brachii Muscles in Patients with Subacute Stroke: A Reliability Study of the Myoton-3 Myometer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Li-ling Chuang ◽  
Ching-yi Wu ◽  
Keh-chung Lin ◽  
Shih-yu Lur
Keyword(s):  
Standardized Testing ◽  
Muscle Tone ◽  
Intraclass Correlation ◽  
Minimal Detectable Change ◽  
Intrarater Reliability ◽  
Triceps Brachii ◽  
Muscle Properties ◽  
Subacute Stroke ◽  
Test Retest Reliability ◽  
Standard Error Of Measurement

Objective. Test-retest reliability of the myotonometer was investigated in patients with subacute stroke.Methods. Twelve patients with substroke (3 to 9 months poststroke) were examined in standardized testing position twice, 60 minutes apart, with the Myoton-3 myometer to measure tone, elasticity, and stiffness of relaxed bilateral biceps and triceps brachii muscles. Intrarater reliability of muscle properties was determined using intraclass correlation coefficient (ICC), the standard error of measurement (SEM), and the minimal detectable change (MDC).Results. Intrarater reliability of muscle properties of bilateral biceps and triceps brachii muscles were good (ICCs=0.79–0.96) except for unaffected biceps tone (ICC=0.72). The SEM and MDC of bilateral biceps and triceps brachii muscles indicated small measurement error (SEM%<10%, MDC%<25%).Conclusion. The Myoton-3 myometer is a reliable tool for quantifying muscle tone, elasticity, and stiffness of the biceps and triceps brachii in patients with subacute stroke.

scholarly journals OR29-05 A Natural History Study of Fibrodysplasia Ossificans Progressiva (FOP): 12-Month Outcomes

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Mona Al Mukaddam ◽  
Robert J Pignolo ◽  
Geneviève Baujat ◽  
Matthew A Brown ◽  
Carmen De Cunto ◽  
...  
Keyword(s):  
Natural History ◽  
Physical Function ◽  
Genetic Disorder ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Whole Body ◽  
Joint Involvement ◽  
Mobility Limitations ◽  
Natural History Study ◽  
Total Score Range ◽  
Prospective Longitudinal

Abstract Background: FOP is an ultra-rare, severely disabling genetic disorder characterized by episodic flare-ups and heterotopic ossification (HO) leading to restricted movement, physical disability, and early death. FOP may initially be misdiagnosed in ~90% of individuals leading to unnecessary and often harmful interventions. Patients with FOP are diagnosed and managed by multiple specialties, including endocrinologists. Data from an ongoing, prospective, longitudinal, global, natural history study (NCT02322255) were used to investigate the progression of FOP, HO formation, and impact on physical functioning over time. We present results from the first 12 months of the 3-year study. Methods: Males and females with FOP and a documented ACVR1 R206H mutation participated. HO volume was assessed by low-dose whole body computed tomography (WBCT) scan, excluding the head. All imaging was interpreted at a blinded, central laboratory using pre-specified procedures. Functional outcomes were evaluated using the Cumulative Analogue Joint Involvement Scale (CAJIS; for each joint: score=0 represents &lt;10% involvement, score=1 represents 10–90% involvement, and score=2 represents &gt;90% ankylosed across 15 major joints; total score range 0 to 30 [higher scores indicate more severe mobility limitations]) and the FOP Physical Function Questionnaire (FOP-PFQ; percent total score). Changes from Baseline at Month 12 were evaluated for new HO volume, CAJIS, and FOP-PFQ. Results: Of 114 participants (pts) with Baseline data, 99 (4 to 56 years at enrollment; mean 17 years of age; 56% male) also had a Month 12 assessment. A total of 93 pts had evaluable WBCT scans at Baseline and Month 12 and were included in the HO analysis. In total, 40% (37/93) of pts had new HO over 12 months; the mean volume of new HO in these pts was 57,706 mm3 (SD=100,079 mm3; median=20,753 mm3; range: 522 to 438,826 mm3). Of the pts with new HO, 65% (24/37) reported at least one flare-up (mean rate of 2.3 flare-ups/year). Over 12 months, 60% (56/93) of pts did not have new HO; 43% (24/56) of them reported at least one flare-up (mean rate of 1.8 flare-ups/year). Mean changes from Baseline in CAJIS and FOP-PFQ were minimal: CAJIS: 0.6 (SD=2.4; median=1.0; n=99) and FOP-PFQ: 4.4% (SD=11.2; median=3.7%; n=90); and were similar across pts with or without new HO. Conclusions: In participants with FOP, although deterioration of physical function is expected over a patient’s lifetime, CAJIS and FOP-PFQ scores did not worsen significantly in the relative short-term of this study. However, HO volume, quantified by WBCT, increased over the course of 12 months. These results show that measuring HO may be a viable way to monitor changes in FOP over short periods of time.

scholarly journals Validity and Reliability of a New Optoelectronic System for Measuring Active Range of Motion of Upper Limb Joints in Asymptomatic and Symptomatic Subjects

2019 ◽  
Vol 8 (11) ◽  
pp. 1851
Author(s):  
Rodrigo Martín-San Agustín ◽  
Jose A. García-Vidal ◽  
German Cánovas-Ambit ◽  
Aurelio Arenas-Della Vecchia ◽  
Manuel López-Nicolás ◽  
...  
Keyword(s):  
Upper Limb ◽  
Pearson Correlation ◽  
Minimal Detectable Change ◽  
Validity And Reliability ◽  
Optoelectronic System ◽  
Rater Reliability ◽  
Intra Class Correlation ◽  
Active Range Of Motion ◽  
Upper Limb Movements ◽  
Standard Error Of Measurement

The aim of this study was to evaluate the validity of the Veloflex infrared dynamic angle-meter (Veloflex-IDA) and the intra- and inter-rater reliability when measuring the ranges of motion (ROMs) of the upper limb joints. Thirty-five healthy and 20 symptomatic participants were evaluated. Twelve upper limb movements were measured in two sessions with the Veloflex-IDA, which is a device composed of a camera that tracks the trajectory of retro-reflective markers. In addition, a goniometer was used in the first session to evaluate concurrent validity. Validity and agreement were evaluated by Pearson correlation coefficient (r) and Bland–Altmann plots. Intra- and inter-rater reliability were evaluated using intra-class correlation (ICC), standard error of measurement (SEM), and minimal detectable change (MDC). Both instruments showed excellent correlation for all movements (r range from 0.992 to 0.999). The intra- and inter-rater reliability were excellent (ICC range from 0.95 to 0.99 and 0.90 to 0.98, respectively). Intra-rater reliability showed SEMs <1.38% and <5.19% and inter-rater reliability SEMs <2.26% and <5.22% for asymptomatic and symptomatic, respectively. Veloflex-IDA is a valid and reliable alternative to measure the upper limb joints’ ROM and it can be used in clinical practice and research after basic training.

Sign in / Sign up

Export Citation Format

Share Document