Life Expectancy in Duchenne Muscular Dystrophy: A Systematic Review and Reconstructed Individual Patient Data Meta-Analysis

Broomfield, Jonathan; Hill, Martha; Crowther, MJ; Guglieri, M.; Abrams, KR

doi:10.2139/ssrn.3795309

Cited by 11 publications

(14 citation statements)

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“…Duchenne muscular dystrophy (DMD) is a progressive X-linked recessive disorder that causes skeletal muscle weakness with involvement of the cardiac and respiratory muscles in the later stages of disease progression [ 1 ]. Patients born after 1990 have a median life expectancy of 28.1 years (95% CI 25.1, 30.3) [ 2 ]. Although currently no cure exists for DMD, comprehensive multidisciplinary care, including assisted ventilation as needed, can prolong the survival, with some individuals surviving into their 40s [ 3 – 5 ].…”

Section: Introductionmentioning

confidence: 99%

Pain characteristics among individuals with Duchenne muscular dystrophy according to their clinical stage

Kim

Park

Shin

2022

BMC Musculoskelet Disord

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Background Assessment of pain is not routine, standardized, or well-understood in individuals with Duchenne muscular dystrophy (DMD), even though pain is a common problem reported by more than half of the patients with DMD. Previous studies in this area included multiple neuromuscular diseases with highly variable phenotypes. Therefore, our aim was to specifically focus on DMD and evaluate the comprehensive pain characteristics according to the disease stages, from ambulatory to late non-ambulatory. Methods This cross-sectional study was conducted in an out-patient pediatric rehabilitation clinic including 148 male participants with confirmed DMD (14.5 ± 5.3 years of age). Face-to-face interviews were conducted using a structured questionnaire concerning the pain frequency, duration, intensity, location, aggravating/relieving factors, pain interference (Brief Pain Inventory), pain phenotype (PainDETECT Questionnaire), and functional ability (DMD Functional Ability Self-Assessment Tool). Pain characteristics were analyzed according to the clinical stage: ambulatory (Amb), early non-ambulatory (ENA), and late non-ambulatory (LNA). Results Of the 148 participants who completed the assessment, 66 (44.6%) reported pain during the previous 4 weeks. There were no differences in the pain duration or intensity among the three groups. Pain location (Amb: calf, ENA: knee, LNA: lumbosacral region), aggravating factor (Amb: ambulation, ENA: transfer, LNA: sitting), and relieving factor (Amb: rest and massage, ENA and LNA: positional change) differed according to the clinical stage. Individuals in the LNA stage reported an increase in the frequency of pain and number of pain sites. The effect of pain on mood was also found to be greater in the LNA group than in the other clinical stages. Conclusion There is a change in the pain characteristics, including the location, aggravating/relieving factors, pain frequency, and pain interference, with the progress of the disease in patients with DMD. Thus, clinicians could more efficiently and critically assess and manage the patients’ pain based on these findings.

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Section: Introductionmentioning

confidence: 99%

Pain characteristics among individuals with Duchenne muscular dystrophy according to their clinical stage

Kim

Park

Shin

2022

BMC Musculoskelet Disord

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“…The second line of convergent consequences of losing the lower part of the hemidesmosomes is the commonly observed detachment of muscle from the basement membrane via loss of focal adhesions and other receptors that might drive muscular dystrophy (Yurchenco et al, 2004). Muscular dystrophy patients die in their early twenties (Broomfield et al, 2021) and also show muscular fibrosis (Zhou and Lu, 2010), i.e. , excessive collagen production that can be ex vivo and in vitro reproduced by either a stiffer environment or more contractile cytoskeleton (Engler et al, 2004; Griffin et al, 2005), hinting at a derailed outside-in or inside-out feedback loop.…”

Section: Discussionmentioning

confidence: 99%

Mechanotransduction coordinates extracellular matrix protein homeostasis promoting longevity inC. elegans

Teuscher

Statzer

Goyala

et al. 2022

Preprint

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Although it is postulated that dysfunctional extracellular matrices (ECM) drive aging and disease, how ECM integrity assures longevity is unknown. Here, using proteomics and in-vivo monitoring of fluorescently tagged ECM proteins, we systematically examined the ECM composition during Caenorhabditis elegans aging revealing three distinct collagen dynamics. We show that age-dependent stiffening of inert collagen was slowed by longevity interventions through prolonged replenishing of collagens. In genetic and automated lifespan screens for the regulators that drive this remodeling, we identify hemidesmosome-containing structures that span from the exoskeletal ECM through the hypodermis, basement membrane ECM, to the muscles, coupling mechanical forces to adjust ECM gene expression across tissues. The hemidesmosome tension-induced adaptation is mediated via transcriptional co-activator YAP. Our data reveal a novel mechanism of mechano-coupling and synchronizing of two functionally distinct and spatially distant ECMs that is indispensable for longevity. Thus, besides signaling molecules, mechanotransduction-coordinated ECM remodeling systemically promotes healthy aging.

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“…A recent metaanalysis of published reports of mortality in DMD showed median survival to be 28.1 years for boys born after 1990, compared with a median survival of 18.1 years for boys born before 1970 and 22.9 years for boys born between 1970 and 1990. 8 Novel licensed treatments for DMD include drugs to promote read-through of nonsense mutations and antisense oligonucleotides to restore the reading frame of the DMD gene, both of which aim to restore dystrophin expression. For any DMD treatment option, early or presymptomatic treatment is likely to yield the best results.…”

Section: Does Delay In Diagnosing Dmd Matter?mentioning

confidence: 99%

“…Despite many promising reports of improving outcomes for boys with DMD, life expectancy is still shortened, and some patients have premature death due to cardiac and respiratory failure. A recent meta‐analysis of published reports of mortality in DMD showed median survival to be 28.1 years for boys born after 1990, compared with a median survival of 18.1 years for boys born before 1970 and 22.9 years for boys born between 1970 and 1990 8 …”

Section: Does Delay In Diagnosing Dmd Matter?mentioning

confidence: 99%

Age at diagnosis for Duchenne muscular dystrophy: Why we must do better

Quinlivan

2022

Muscle and Nerve

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Age at diagnosis for Duchenne muscular dystrophy: Why we must do better This issue of the Journal includes an article by Thomas et al on behalf of the Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet). 1 The authors retrospectively review the age at diagnosis for males born with Duchenne muscular dystrophy (DMD) between 2000 and 2015. It is shown that, despite several initiatives, including education programs for pediatric health-care providers and a published algorithm for those investigating children with developmental delay, there has been no improvement in the age of diagnosis of DMD over a 30-year period. Despite the first signs of the condition appearing at a mean age of 2.7 years, a blood test for serum creatine kinase (CK) was not done until the child was, on average, 4.6 years of age. The mean age of diagnostic testing was 4.9 years for all children born between 2000 and 2015, compared with 5 years for children born between 1982 and 2000. More concerning is the finding that diagnostic confirmation was most frequently delayed in certain ethnic communities, specifically non-Hispanic black (6.7 years) and Hispanic (5.8 years) individuals, compared with non-Hispanic whites (4.5 years) and non-Hispanic others (4.1 years), indicating a potentially significant socioeconomic impact on age of diagnosis.

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Life Expectancy in Duchenne Muscular Dystrophy: A Systematic Review and Reconstructed Individual Patient Data Meta-Analysis

Cited by 11 publications

References 0 publications

Pain characteristics among individuals with Duchenne muscular dystrophy according to their clinical stage

Pain characteristics among individuals with Duchenne muscular dystrophy according to their clinical stage

Mechanotransduction coordinates extracellular matrix protein homeostasis promoting longevity inC. elegans

Age at diagnosis for Duchenne muscular dystrophy: Why we must do better

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