Life In Duchenne Muscular Dystrophy Research Articles

Hope

Duchenne muscular dystrophy (DMD) is a life-shortening genetic condition involving progressive muscular wasting for which there is no hope of recovery at present. The lives of people with DMD, cherished by their families, are systematically marginalised and undervalued by healthcare bureaucracies while enrolment in clinical trials of new treatments offers possibilities of longer-term biomedical solutions. How is hope preserved under such circumstances and what activities can promote a full and meaningful life for those with DMD Ethnographic research within the DMD community in Aotearoa New Zealand provided a basis for addressing these questions and for understanding different concepts of hope and social suffering, the value of life in DMD and disability studies, and how these are shaped by regimes of governmentality.

Pain and health-related quality of life in Duchenne muscular dystrophy: A multiple mediator analysis.

The objective was to investigate the serial mediating effects of daily activities, patient health communication, and disease-specific worry in the relationship between pain intensity and overall generic health-related quality of life (HRQOL) in pediatric patients with Duchenne muscular dystrophy from the patient perspective. Pain Intensity Item, Daily Activities Scale, Communication Scale and Worry Scale from Pediatric Quality of Life Inventory (PedsQL) Duchenne Muscular Dystrophy Module and PedsQL 4.0 Generic Core Scales were completed by 110 pediatric patients with Duchenne muscular dystrophy ages 8-17. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of daily activities, patient health communication, disease-specific worry as intervening variables in the association between the pain intensity predictor variable and overall generic HRQOL. Pain predictive effects on overall generic HRQOL were serially mediated by daily activities, patient health communication, and disease-specific worry. In a predictive analytics model utilizing hierarchical multiple regression analysis with age demographic covariate, patient-reported pain intensity, daily activities, patient health communication, and disease-specific worry accounted for 47% of the variance in overall generic HRQOL (P<0.001), representing a large effect size. Pain intensity, daily activities, patient health communication, and disease-specific worry explain in part the mechanism of pain predictive effects on overall generic HRQOL in pediatric patients with Duchenne muscular dystrophy. Identifying the mediators of pain intensity on overall generic HRQOL from the patient perspective may inform targeted clinical interventions and future patient-centered clinical research to improve overall daily functioning.

Quality of life in Duchenne muscular dystrophy: It's about more than pain management.

This commentary is on the original articles by Huang et al. and Hov et al. on pages 640–663 of this issue.

A comprehensive qualitative framework for health-related quality of life in Duchenne muscular dystrophy

PurposeDuchenne muscular dystrophy (DMD) is a rare x-linked neuromuscular condition predominantly affecting boys and men. There is a paucity of research qualitatively detailing the lived experience of health-related quality of life (HRQoL) for people with DMD. The aim of this study was to identify a comprehensive framework for better understanding HRQoL in DMD.MethodsEighteen boys and men (aged 7 to ≥ 40 years) with DMD were recruited from charity Duchenne UK, a DMD support group, and 5 UK National Health Service Trusts. Semi-structured interviews were conducted using a topic guide informed by a review into HRQoL in DMD. Generic, preference-based, patient-reported outcome measures (PROs) were used as prompts. Interviews were audio recorded, transcribed verbatim and analysed using framework analysis.ResultsThirty-seven themes were coded, within seven categories. Six categories were conceptualised as components of HRQoL (autonomy, daily activities, feelings and emotions, identity, physical aspects, social relationships) and one considered an input (healthcare, support, and environment). Three additional themes were used to code feedback on the generic PROs (CHU-9D, EQ-5D, HUI). Social relationships received most coverage in the data and was noted as an omission from the PROs.ConclusionA 30-item framework for HRQoL in DMD has been developed, which was used as input into a new condition-specific HRQoL PRO and preference-based measure: the DMD-QoL. The data has value in its own right in highlighting the lived experience of HRQoL for people with DMD and as a barometer for assessing the content of HRQoL PROs for use in DMD.

Exercise Training in Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis.

ObjectiveTo evaluate the effects and safety of exercise training, and to determine the most effective exercise intervention for people with Duchenne muscular dystrophy. Exercise training was compared with no training, placebo or alternative exercise training. Primary outcomes were functioning and health-related quality of life. Secondary outcomes were muscular strength, endurance and lung function.Data sourcesA systematic literature search was conducted in Medline, EMBASE, CINAHL, Cochrane Central, PEDro and Scopus.Study selection and data extractionScreening, data extraction, risk of bias and quality assessment were carried out. Risk of bias was assessed using the Cochrane Collaborations risk of bias tools. The certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation.Data synthesisTwelve studies with 282 participants were included. A narrative synthesis showed limited or no improvements in functioning compared with controls. Health-related quality of life was assessed in only one study. A meta-analysis showed a significant difference in muscular strength and endurance in favour of exercise training compared with no training and placebo. However, the certainty of evidence was very low.ConclusionExercise training may be beneficial in Duchenne muscular dystrophy, but the evidence remains uncertain. Further research is needed on exercise training to promote functioning and health-related quality of life in Duchenne muscular dystrophy.LAY ABSTRACTThe aim of this study was to examine the effects of all types of exercise training compared with no training, placebo or alternative exercise training programmes in people with Duchenne muscular dystrophy. The primary outcomes were functioning and health-related quality of life. Secondary outcomes were muscular strength and endurance. A further aim was to evaluate safety and, if possible, to find the most effective exercise training intervention. This review investigates existing research on this topic. The results have been systematically gathered and analysed, to give a broader view of what effect exercise training may have for people with Duchenne muscular dystrophy. The results suggest that exercise training preserves functioning, and benefits muscular strength and endurance. The study was not able to identify the best type of exercise training and prescriptions to use in Duchenne muscular dystrophy. The validity of the results was reduced by the low number of studies included, the low quality of the studies, and diversity in both the interventions and outcome measures used. The results should therefore be interpreted with caution.

Effect of a multicomponent nutritional supplement on functional outcomes for Duchenne muscular dystrophy: A randomized controlled trial

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular condition causing progressive muscle weakness and premature death. Whilst effective treatments such as gene therapy are developed, families often seek complementary therapies such as nutrition supplements to help their son maintain function; however, there is limited evidence supporting the use of nutritional supplements in DMD. This study aimed to compare the effect of a Standard nutritional supplement with an Enhanced nutritional supplement combining three nutriceuticals on functional outcomes in ambulatory boys with Duchenne muscular dystrophy (DMD). A 50-week double blinded, randomized, controlled crossover trial was conducted in four Australian neuromuscular centres. Primary outcome measures were 6-min walk distance (6MWD) and community ambulation (StepWatch™ Activity Monitoring). Secondary outcome measures included body composition and quality of life. Serum 25-hydroxyvitamin D was measured. Twenty-seven boys completed the intervention. Traditional crossover analysis demonstrated the Enhanced supplement compared to the Standard supplement was associated with a difference of+12 (95% CI:-16, 40) metres in 6MWD,+0.5 (95% CI:-53, 54) inactive minutes per day and-95 (95% CI:-887, 696) steps per day. A mixed effect model indicated a potentially clinically important effect of the Enhanced supplement on the 6MWD of+31 (95% CI:-19, 81) metres. Mean serum 25 hydroxyvitamin D levels at week 50 was 94 (95% CI: 84, 104) nmol/L. There was no observable effect of either supplement regime on body composition or quality of life. Whilst a positive effect of the Enhanced supplement on functional outcomes was observed, this finding was inconclusive due to the small sample size. The results do not support the use of combined nutritional supplements to improve body composition or quality of life in DMD. A dose of 2000 IU vitamin D was an adequate dose to raise serum 25-hydroxyvitamin D over 50 weeks. Registry #: ACTRN12610000462088, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12610000462088.

Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation.

Background/AimsPatients with Duchenne muscular dystrophy exhibit significant, ongoing impairments in gastrointestinal (GI) function likely resulting from dysregulated nitric oxide production. Compounds increasing neuronal nitric oxide synthase expression and/or activity could improve GI dysfunction and enhance quality of life for dystrophic patients. We used video imaging and spatiotemporal mapping to identify GI dysfunction in mdx dystrophic mice and determine whether dietary intervention to enhance nitric oxide could alleviate aberrant colonic activity in muscular dystrophy.MethodsFour-week-old male C57BL/10 and mdx mice received a specialized diet either with no supplementation (control) or supplemented (1 g/kg/day) with L-alanine, L-arginine, or L-citrulline for 8 weeks. At the conclusion of treatment, mice were sacrificed by cervical dislocation and colon motility examined by spatiotemporal (ST) mapping ex vivo.ResultsST mapping identified increased contraction number in the mid and distal colon of mdx mice on control and L-alanine supplemented diets relative to C57BL/10 mice (P < 0.05). Administration of either L-arginine or L-citrulline attenuated contraction number in distal colons of mdx mice relative to C57BL/10 mice.ConclusionsGI dysfunction in Duchenne muscular dystrophy has been sadly neglected as an issue affecting quality of life. ST mapping identified regional GI dysfunction in the mdx dystrophic mouse. Dietary interventions to increase nitric oxide signaling in the GI tract reduced the number of colonic contractions and alleviated colonic constriction at rest. These findings in mdx mice reveal that L-arginine can improve colonic motility and has potential therapeutic relevance for alleviating GI discomfort, improving clinical care, and enhancing quality of life in Duchenne muscular dystrophy.

Translation and validation of the Life Satisfaction Index for Adolescents scale with neuromuscular disorders: LSI-A Brazil.

To validate the Life Satisfaction Index for Adolescents (LSI-A) scale, parent version and patient version, for Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA) and limb-girdle muscular dystrophy (LGMD). The parent version of the instrument was divided into Groups A, B, C and D; and the patient version, divided into B, C and D. For the statistical calculation, the following tests were used: Cronbach's α, ICC, Pearson and the ROC Curve. The parent and patient versions of the instrument are presented, with the following results in the overall score, respectively: Cronbach's α, 0.87 and 0.89; reliability, r 0.98 and 0.97; reproducibility, ICC 0.69 and 0.80; sensitivity, 0.78 and 0.72; specificity, 0.5 and 0.69; and accuracy, 64% and 70.4%. According to the validity and reproducibility values, the LSI-A Brazil parent and patient versions, are clinically useful to assess quality of life in DMD, SMA or LGMD and may also be useful for other neuromuscular disorders.

Can in-the-moment diary methods measure health-related quality of life in Duchenne muscular dystrophy?

To investigate whether in-the-moment diary reports of daily experience, taken collectively, are a valid representation of health-related quality of life (HRQL). A total of 35 boys with Duchenne muscular dystrophy (DMD) were recruited through four neuromuscular care providers across Australia. Participants completed the PedsQL™ Generic Core scales and one week of experience-sampling diary reporting on a personal digital assistant. Rasch analysis was undertaken on the diary data to derive a single valid measure score. The resulting measure score for each participant was correlated with the summary score from the PedsQL™ Generic Core scales to examine whether daily experience was representative of HRQL. The daily diary method showed good metric properties, with adequate goodness of fit for data from items and participants suggesting unidimensionality of the construct: quality of everyday experience. The correlation of the daily diary measure score with overall PedsQL™ summary score showed moderate agreement (r=.60, p=0.001). The benefits of measuring daily quality of life include detailed descriptions of day-to-day experiences of children without the need for retrospective recall. Diary methods on an electronic platform or software application for personal devices may be a useful tool to understand HRQL as the repeated measures data provide a detailed experience directly from the child and the platform makes data completion highly motivating.

Quality of life in Duchenne muscular dystrophy: the disability paradox.

This commentary is on the original article by Landfeldt et al. on pages 508–515 of this issue.

G.P.389 - A prospective natural history study to measure progression of physical impairment, activity limitation and quality of life in Duchenne muscular dystrophy

The aim of this study is to characterize the natural history and disease progression of Duchenne muscular dystrophy (DMD), capture biomarkers of safety and disease progression and provide comparative data for the development of rare exons for which formal controlled trials are not feasible. DMD is an X-linked, severely debilitating and fatal neuromuscular disorder caused by a deficiency in dystrophin. The 6-minute walking distance (6MWD) test is a validated endpoint for determination of DMD disease progression. Results from a 3-year, multicentre, exploratory, observational study in subjects with DMD, 3–18 years [life expectancy ≥ 3 years], will be presented. Study visits occurred at 6-month intervals from baseline, mirroring the usual pattern of clinic visits. Ambulant subjects were assessed using the 6MWD test, timed function tests (including rise from floor, 10-m walk/run, four-stair ascent/descent and supine to stand), North Star Ambulatory Assessment and DMD Functioning and Daily Activities Survey. Non-ambulant subjects were evaluated using Egen–Klassifikation. Other evaluations for all subjects included: muscle strength (handheld myometry); range of movement (handheld goniometer); myoset assessments (pinch, hand grip, moviplate); performance of upper limb; pulmonary function; physical examination (major events notable for disease progression: weight, height, body mass index); urinalysis; and blood sampling for biomarker assessment. Electrocardiography, cardiac echo and DEXA scan were assessed for subjects in whom they were performed. Data summaries at each visit are provided. A total of 269 subjects were enrolled from July 2012 to June 2014. This planned interim analysis includes 80 subjects (of whom 5 were non-ambulant) with data for 1 year. Demographic characteristics and changes from study baseline for key endpoints are presented. It is anticipated that data from this natural history study will inform the design of future clinical studies.

Evaluating the Progression of Physical Impairment, Activity Limitation and Quality of Life in Duchenne Muscular Dystrophy (DMD): a Prospective Natural History Study (P2.238)

Evaluating the Progression of Physical Impairment, Activity Limitation and Quality of Life in Duchenne Muscular Dystrophy (DMD): a Prospective Natural History Study (P2.238)

Effects of upper extremity dynamic exercise on respiratory function and quality of life in duchenne muscular dystrophy

Effects of upper extremity dynamic exercise on respiratory function and quality of life in duchenne muscular dystrophy

P294 – 1740 A prospective natural history study of the progression of physical impairment, activity limitation and quality of life in Duchenne muscular dystrophy

activity limitation, and quality of life in Duchenne muscular dystrophy Nathalie Goemans,1 Eugenio Mercuri,2 Allison Morgan,3 Michelle Eagle,4 Fiona Lawrence,3 Rosamund Wilson,5 Laurence Callendret,3 Giles Campion3 1University Hospital Leuven, Leuven, Belgium; 2Policlinico Universitario Agostino Gemelli, Rome, Italy; 3Prosensa Therapeutics BV, Leiden, Netherlands; 4Newcastle University, Newcastle upon Tyne, UK; 5Spica Consultants Ltd, Marlborough, UK P7.1 18th International Congress of the World Muscle Society, Asilomar, CA, USA; October 1–5, 2013

P.7.1 A prospective natural history study of the progression of physical impairment, activity limitation, and quality of life in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is characterized by a progressive and irreversible loss in muscle function, with a predictable sequence of loss of ambulation and upper limb function followed by cardiorespiratory failure. There is currently no cure; however, a multidisciplinary approach to the symptoms and the use of corticosteroids has been shown to delay disease progression and is recommended as standard of care. Within the patient population, decreased muscle function and age at loss of ambulation and cardiorespiratory functions are highly variable. This study aims to describe contemporary natural history in the steroid era by measuring muscle strength and function over time, assessing quality of life (QoL), and measuring biomarkers in patients with DMD. A total of 250 boys with DMD (aged 3–18 years), both ambulant and non-ambulant, are planned to be enrolled at 16 sites across 10 countries and followed every 6 months for 3 years. Standardized outcome measures, including the 6-min walk test, timed tests, North Star Ambulant Assessment, Performance of Upper Limb, pulmonary function testing, and QoL surveys, as well as new exploratory measures, will be assessed by experienced clinical evaluators. Blood and urine samples are to be collected to test biomarkers of disease progression and imaging will be performed by magnetic resonance imaging/magnetic resonance spectroscopy at selected sites. Mutations affecting the DMD gene and concomitant medications will also be recorded. Longitudinal data will also be obtained, including 6-min walk distance, muscle function scores, pulmonary function results, and scores in QoL surveys. Outcome measurements are planned to be assessed by a number of factors, including mutation type and age group. The measures obtained will give a clear picture of the evolution of muscle function and disease progression that could be used as surrogate placebo data in clinical trials involving investigational drugs.

Bone health in boys with Duchenne Muscular Dystrophy on long-term daily deflazacort therapy

Quality of life in Duchenne Muscular Dystrophy (DMD) has improved significantly with corticosteroid treatment. However, corticosteroids decrease bone mass and increase vertebral fragility fracture risk. We report on bone health in 39 boys with DMD on long-term deflazacort (0.9 mg/kg/day) therapy. Bone health was defined by lumbar (L(1)-L(4)) bone mineral density (BMD), long-bone and/or symptomatic vertebral fractures. Lumbar BMD was reported as height-adjusted Z-scores at initiation of deflazacort (T(0)) and 1-2 year intervals thereafter. Subcapital body fat percentage and ambulatory status were recorded. At T(0), 39 boys, aged 6.6 ± 1.6 years had height-adjusted BMD Z-score -0.5 ± 0.8, and 23.5 ± 5.0% body fat. Height-adjusted Z-scores remained stable with years of deflazacort until loss of ambulation and accrual of body fat. Nine long-bone fractures occurred in eight ambulating boys, two before T(0). Seven vertebral fractures occurred in six non-ambulatory boys after ≥ 5 years of deflazacort with height-adjusted Z-score -1.8 ± 0.7, and 47.8 ± 12% body fat. Bone health in DMD is influenced by disease progression, corticosteroids, BMD Z-scores and fat mass accumulation. Adjustments for short stature must be considered during BMD interpretation. Percent body fat and ambulatory status are useful bone health indicators. Routine use of height adjusted Z-scores is advocated for use in routine clinical practice.

Quality of Life in Duchenne Muscular Dystrophy: The Subjective Impact on Children and Parents

Duchenne muscular dystrophy results in a broad spectrum of physical and psychosocial consequences, both to patient and caregivers. This study was aimed to explore health-related quality of life and its possible determinants in Duchenne muscular dystrophy children and in their parents. Caregivers (21 mothers and 6 fathers; mean age, 40.04 years) of 27 Duchenne muscular dystrophy patients (mean age, 11.26 years) completed the validated Children Health Questionnaire-Parent Form 50 and the Family Strain Questionnaire. Children reported significantly lower scores than normative group in 10 of 15 Children Health Questionnaire dimensions. Only the use of wheelchairs (P = .02) and ventilators (P < .001) was significantly associated to lower health-related quality of life in Physical Functioning. On the contrary, Family Strain Questionnaire scores were not influenced by children's characteristics. Despite the presence of Duchenne muscular dystrophy deeply impairs health-related quality of life, some areas of well-being are present both in children and caregivers.

Quality of Life, Physical Disability, and Respiratory Impairment in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) leads to progressive, generalized paresis, and to respiratory failure in the second decade of life. The assumption that severe physical disability precludes an acceptable quality of life is common, but has not been specifically evaluated in DMD. The purpose of this study was to investigate the quality of life in relation to physical disability, pulmonary function, and the need for assisted ventilation in DMD. In 35 patients with DMD, aged 8-33 yr, we assessed physical disability by a score ranging from 9 (no disability) to 80 (complete dependence on care and technical aids), pulmonary function, and health-related quality of life by Short-Form 36 of the medical outcome questionnaire. All patients required a wheelchair and help for dressing and eating. Fourteen patients were on long-term noninvasive positive-pressure ventilation. In ventilated patients, mean +/- SD FVC was 12 +/- 10 % predicted, and the physical disability score was 65 +/- 7. Corresponding values in spontaneously breathing patients were 48 +/- 25 % predicted, and 51 +/- 7, respectively (p < 0.05 for both comparisons between groups). Short-Form 36 physical function scores were massively reduced in both groups (1 +/- 2, and 0 +/- 0, respectively), but vitality, role-emotional, social function, and mental health scores were nearly normal (67-98), and did not differ between groups. Quality of life in DMD is not correlated with physical impairment nor the need for noninvasive positive-pressure ventilation. The surprisingly high quality of life experienced by these severely disabled patients should be taken into consideration when therapeutic decisions are made.