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Journal of Orthopaedic Surgery and... Feb 2022A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker (BMD) muscular dystrophies are located at the severe end of the spectrum that primarily affects skeletal muscle. Progressive muscle weakness in these purely genetic disorders encourages families with a positive history for genetic counseling to prevent a recurrence, which requires an accurate prevalence of the disorder. Here, we provide a systematic review and meta-analysis to determine the prevalence of DMD and BMD worldwide.
METHOD
The current systematic review and meta-analysis was carried out using Cochrane seven-step procedure. After determining the research question and inclusion and exclusion criteria, the MagIran, SID, ScienceDirect, WoS, ProQuest, Medline (PubMed), Embase, Cochrane, Scopus, and Google Scholar databases were searched to find relevant studies using defined keywords and all possible keyword combinations using the AND and OR, with no time limit until 2021. The heterogeneity of studies was calculated using the I test, and the publication bias was investigated using the Begg and Mazumdar rank correlation test. Statistical analysis of data was performed using Comprehensive Meta-Analysis software (version 2).
RESULTS
A total of 25 articles involving 901,598,055 people were included. The global prevalence of muscular dystrophy was estimated at 3.6 per 100,000 people (95 CI 2.8-4.5 per 100,000 people), the largest prevalence in the Americans at 5.1 per 100,000 people (95 CI 3.4-7.8 per 100,000 people). According to the subgroup analysis, the prevalence of DMD and BMD was estimated at 4.8 per 100,000 people (95 CI 3.6-6.3 per 100,000 people) and 1.6 per 100,000 people (95 CI 1.1-2.4 per 100,000 people), respectively.
CONCLUSION
Knowing the precise prevalence of a genetic disorder helps to more accurately predict the likelihood of preventing its occurrence in families. The global prevalence of DMD and BMD was very high, indicating the urgent need for more attention to prenatal screening and genetic counseling for families with a positive history.
Topics: Dystrophin; Humans; Muscle Weakness; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Mutation; Prevalence
PubMed: 35168641
DOI: 10.1186/s13018-022-02996-8 -
Muscle & Nerve Mar 2022Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness, loss of ambulation (LOA), and early mortality. In this review we have synthesized... (Review)
Review
Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness, loss of ambulation (LOA), and early mortality. In this review we have synthesized published data on the clinical course of DMD by genotype. Using a systematic search implemented in Medline and Embase, 53 articles were identified that describe the clinical course of DMD, with pathogenic variants categorizable by exon skip or stop-codon readthrough amenability and outcomes presented by age. Outcomes described included those related to ambulatory, cardiac, pulmonary, or cognitive function. Estimates of the mean (95% confidence interval) age at LOA ranged from 9.1 (8.7-9.6) years among 90 patients amenable to skipping exon 53 to 11.5 (9.5-13.5) years among three patients amenable to skipping exon 8. Although function worsened with age, the impact of genotype was less clear for other outcomes (eg, forced vital capacity and left ventricular ejection fraction). Understanding the distribution of pathogenic variants is important for studies in DMD, as this research suggests major differences in the natural history of disease. In addition, specific details of the use of key medications, including corticosteroids, antisense oligonucleotides, and cardiac medications, should be reported.
Topics: Child; Dystrophin; Genotype; Humans; Muscular Dystrophy, Duchenne; Stroke Volume; Ventricular Function, Left
PubMed: 34878187
DOI: 10.1002/mus.27463 -
Orphanet Journal of Rare Diseases May 2021Duchenne muscular dystrophy (DMD) is a severe rare progressive inherited neuromuscular disorder, leading to loss of ambulation (LOA) and premature mortality. The... (Review)
Review
BACKGROUND
Duchenne muscular dystrophy (DMD) is a severe rare progressive inherited neuromuscular disorder, leading to loss of ambulation (LOA) and premature mortality. The standard of care for patients with DMD has been treatment with corticosteroids for the past decade; however a synthesis of contemporary data describing the clinical course of DMD is lacking. The objective was to summarize age at key clinical milestones (loss of ambulation, scoliosis, ventilation, cardiomyopathy, and mortality) in the corticosteroid-treatment-era.
METHODS
A systematic review was conducted using MEDLINE and EMBASE. The percentage experiencing key clinical milestones, and the mean or median age at those milestones, was synthesized from studies from North American populations, published between 2007 and 2018.
RESULTS
From 5637 abstracts, 29 studies were included. Estimates of the percentage experiencing key clinical milestones, and age at those milestones, showed heterogeneity. Up to 30% of patients lost ambulation by age 10 years, and up to 90% by 15 years of age. The mean age at scoliosis onset was approximately 14 years. Ventilatory support began from 15 to 18 years, and up to half of patients required ventilation by 20 years of age. Registry-based estimates suggest that 70% had evidence of cardiomyopathy by 15 years and almost all by 20 years of age. Finally, mortality rates up to 16% by age 20 years were reported; among those surviving to adulthood mortality was up to 60% by age 30 years.
CONCLUSIONS
Contemporary natural history studies from North America report that LOA on average occurs in the early teens, need for ventilation and cardiomyopathy in the late teens, and death in the third or fourth decade of life. Variability in rates may be due to differences in study design, treatment with corticosteroids or other disease-modifying agents, variations in clinical practices, and dystrophin mutations. Despite challenges in synthesizing estimates, these findings help characterize disease progression among contemporary North American DMD patients.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Cardiomyopathies; Child; Disease Progression; Dystrophin; Humans; Muscular Dystrophy, Duchenne; Young Adult
PubMed: 34022943
DOI: 10.1186/s13023-021-01862-w -
Restorative treatments of dystrophin expression in Duchenne muscular dystrophy: A systematic review.Annals of Clinical and Translational... Sep 2020To evaluate the effect of pharmacological treatments that increase the synthesis of dystrophin in Duchenne muscular dystrophy (DMD). Systematic searches were carried out... (Meta-Analysis)
Meta-Analysis
To evaluate the effect of pharmacological treatments that increase the synthesis of dystrophin in Duchenne muscular dystrophy (DMD). Systematic searches were carried out in MEDLINE, EMBASE, and Web of Science, and in gray literature from inception to December 2019. Clinical trials addressing the effect of restorative treatments of dystrophin expression in children and adolescents with DMD on functional outcomes {(6-minute walking distance [6MWD], other timed functional tests [TFTs], The North Star Ambulatory Assessment)}, dystrophin expression, cardiorespiratory function, and biochemical tests were included. The DerSimonian-Laird method was used to calculate the pooled estimates for functional outcomes. Eleven studies were included in the systematic review and five in the meta-analysis. Eteplirsen showed a significant effect on 6MWD, Δ6MWD = 67.3 m (95% CI: 27.32, 107.28), and Δ6MWD = 151.0 m (95% CI: 36.15, 265.85) at 48 weeks and 3 years, respectively. In the systematic review, analyzing individually the clinical trials using Ataluren and Drisapersen showed a nonsignificant effect on 6MWD. However, the meta-analysis showed a significant effect on 6MWD for Ataluren and Drisapersen, Δ6MWD = 18.3 m (95% CI: 1.0, 35.5) and Δ6MWD = 21.5 m (95% CI: 4.7, 38.3), respectively. There were no significant differences according to baseline age for Drisapersen. Similarly, the meta-analysis showed effect in TFT with Ataluren. All drugs induced a partial synthesis of dystrophin, and exon skipping was obtained with Eteplirsen and Drisapersen. Eteplirsen also improved forced vital capacity (Δ%pFVC = 1.8%) and maximal inspiratory pressure (Δ%pMIP = 4.4%). Eteplirsen and Ataluren could modestly reduce disease progression. However, more trials are needed to confirm its efficacy, as well as quality of life and cost-utility studies.
Topics: Dystrophin; Humans; Morpholinos; Muscular Dystrophy, Duchenne; Oligonucleotides; Outcome Assessment, Health Care; Oxadiazoles
PubMed: 33325654
DOI: 10.1002/acn3.51149 -
Pharmacological Reports : PR Oct 2020Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration and results in...
BACKGROUND
Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration and results in functional decline, loss of ambulation and early death of young men due to cardiac or respiratory failure. Although the major cause of the disease has been known for many years-namely mutation in the DMD gene encoding dystrophin, one of the largest human genes-DMD is still incurable, and its treatment is challenging.
METHODS
A comprehensive and systematic review of literature on the gene, cell, and pharmacological experimental therapies aimed at restoring functional dystrophin or to counteract the associated processes contributing to disease progression like inflammation, fibrosis, calcium signaling or angiogenesis was carried out.
RESULTS
Although some therapies lead to satisfying effects in skeletal muscle, they are highly ineffective in the heart; therefore, targeting defective cardiac and respiratory systems is vital in DMD patients. Unfortunately, most of the pharmacological compounds treat only the symptoms of the disease. Some drugs addressing the underlying cause, like eteplirsen, golodirsen, and ataluren, have recently been conditionally approved; however, they can correct only specific mutations in the DMD gene and are therefore suitable for small sub-populations of affected individuals.
CONCLUSION
In this review, we summarize the possible therapeutic options and describe the current status of various, still imperfect, strategies used for attenuating the disease progression.
Topics: Animals; Dystrophin; Heart; Humans; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Mutation
PubMed: 32691346
DOI: 10.1007/s43440-020-00134-x -
Orphanet Journal of Rare Diseases Jun 2020Duchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. A recent systematic review and meta-analysis of global DMD epidemiology... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duchenne Muscular Dystrophy (DMD) is a rare disorder caused by mutations in the dystrophin gene. A recent systematic review and meta-analysis of global DMD epidemiology is not available. This study aimed to estimate the global overall and birth prevalence of DMD through an updated systematic review of the literature.
METHODS
MEDLINE and EMBASE databases were searched for original research articles on the epidemiology of DMD from inception until 1st October 2019. Studies were included if they were original observational research articles written in English, reporting DMD prevalence and/or incidence along with the number of individuals of the underlying population. The quality of the studies was assessed using a STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist adapted for observational studies on rare diseases. To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using random-effects logistic models for overall and birth prevalence and within two different underlying populations (i.e. all individuals and in males only), separately. Heterogeneity was assessed using Cochran's Q-test along with its derived measure of inconsistency I.
RESULTS
A total of 44 studies reporting the global epidemiology of DMD were included in the systematic review and only 40 were included in the meta-analysis. The pooled global DMD prevalence was 7.1 cases (95% CI: 5.0-10.1) per 100,000 males and 2.8 cases (95% CI: 1.6-4.6) per 100,000 in the general population, while the pooled global DMD birth prevalence was 19.8 (95% CI:16.6-23.6) per 100,000 live male births. A very high between-study heterogeneity was found for each epidemiological outcome and for all underlying populations (I > 90%). The test for funnel plot asymmetry suggested the absence of publication bias. Of the 44 studies included in this systematic review, 36 (81.8%) were assessed as being of medium and 8 (18.2%) of low quality, while no study was assessed as being of high quality.
CONCLUSIONS
Generating epidemiological evidence on DMD is fundamental to support public health decision-making. The high heterogeneity and the lack of high quality studies highlights the need to conduct better quality studies on rare diseases.
Topics: Humans; Incidence; Male; Muscular Dystrophy, Duchenne; Prevalence; Rare Diseases
PubMed: 32503598
DOI: 10.1186/s13023-020-01430-8 -
Journal of Managed Care & Specialty... Apr 2020Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM),... (Comparative Study)
Comparative Study
Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Agboola, Fluetsch, Rind, and Pearson are employed by ICER. Lin reports support from ICER during work on this economic model and grants from Mount Zion Health Fund, National Institutes of Health (National Cancer Institute and National Heart, Lung, and Blood Institute), and the Tobacco-Related Diseases Research Program, unrelated to this work. Walton reports support from ICER for work on this economic model and unrelated consulting fees from Baxter.
Topics: Cost-Benefit Analysis; Dystrophin; Exons; Humans; Immunosuppressive Agents; Models, Economic; Morpholinos; Muscular Dystrophy, Duchenne; Oligonucleotides; Oligonucleotides, Antisense; Prednisone; Pregnenediones; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32223597
DOI: 10.18553/jmcp.2020.26.4.361 -
Osteoarthritis and Cartilage Open Mar 2020Proteomic studies of the secretome of skeletal muscle cells can help us understand the processes that govern the synthesis, systemic interactions and organization of... (Review)
Review
BACKGROUND
Proteomic studies of the secretome of skeletal muscle cells can help us understand the processes that govern the synthesis, systemic interactions and organization of skeletal muscle and identify proteins that are involved in muscular adaptations to exercise, ageing and degeneration. In this systematic review, we aimed to summarize recent mass-spectrometry based proteomics discoveries on the secretome of skeletal muscle cells in response to disease, exercise or metabolic stress.
METHODS
A literature search was performed in the Medline/Ovid and Scopus electronic bibliographic databases. Only papers reporting the analysis of the secretome by mass spectrometry were included.
RESULTS
A total of 19 papers met the inclusion criteria for this systematic review. These papers included comparative analysis of differentially expressed proteins between healthy and unhealthy muscle cells and comparison of the secretome of skeletal muscle cells during myogenesis and after insulin stimulation or exercising. The proteins were separated into several categories and their differential secretion was compared. In total, 654 proteins were listed as being present in the secretome of muscle cells. Among them, 30 proteins were differentially regulated by physical exercise, 130 during myogenesis, 114 by dystrophin deficiency, 26 by muscle atrophy, 27 by insulin stimulation and finally 176 proteins secreted by insulin-resistant muscle cells.
CONCLUSIONS
This systematic review of the secretome of skeletal muscle cell in health and disease provides a comprehensive overview of the most regulated proteins in pathological or physiological conditions. These proteins might be therapeutic targets or biochemical markers of muscle diseases.
PubMed: 36474563
DOI: 10.1016/j.ocarto.2019.100019