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The Cochrane Database of Systematic... May 2021The World Health Organization (WHO) recommends that people of all ages take regular and adequate physical activity. If unable to meet the recommendations due to health...
BACKGROUND
The World Health Organization (WHO) recommends that people of all ages take regular and adequate physical activity. If unable to meet the recommendations due to health conditions, international guidance advises being as physically active as possible. Evidence from community interventions of physical activity indicate that people living with medical conditions are sometimes excluded from participation in studies. In this review, we considered the effects of activity-promoting interventions on physical activity and well-being in studies, as well as any adverse events experienced by participants living with inherited or acquired neuromuscular diseases (NMDs). OBJECTIVES: To assess the effects of interventions designed to promote physical activity in people with NMD compared with no intervention or alternative interventions.
SEARCH METHODS
On 30 April 2020, we searched Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, and ClinicalTrials.Gov. WHO ICTRP was not accessible at the time.
SELECTION CRITERIA
We considered randomised or quasi-randomised trials, including cross-over trials, of interventions designed to promote physical activity in people with NMD compared to no intervention or alternative interventions. We specifically included studies that reported physical activity as an outcome measure. Our main focus was studies in which promoting physical activity was a stated aim but we also included studies in which physical activity was assessed as a secondary or exploratory outcome.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane procedures.
MAIN RESULTS
The review included 13 studies (795 randomised participants from 12 studies; number of participants unclear in one study) of different interventions to promote physical activity. Most studies randomised a minority of invited participants. No study involved children or adolescents and nine studies reported minimal entry criteria for walking. Participants had one of nine inherited or acquired NMDs. Types of intervention included structured physical activity support, exercise support (as a specific form of physical activity), and behaviour change support that included physical activity or exercise. Only one included study clearly reported that the aim of intervention was to increase physical activity. Other studies reported or planned to analyse the effects of intervention on physical activity as a secondary or exploratory outcome measure. Six studies did not report results for physical activity outcomes, or the data were not usable. We judged 10 of the 13 included studies at high or unclear risk of bias from incomplete physical activity outcome reporting. We did not perform a meta-analysis for any comparison because of differences in interventions and in usual care. We also found considerable variation in how studies reported physical activity as an outcome measure. The studies that reported physical activity measurement did not always clearly report intention-to-treat (ITT) analysis or whether final assessments occurred during or after intervention. Based on prespecified measures, we included three comparisons in our summary of findings. A physical activity programme (weight-bearing) compared to no physical activity programme One study involved adults with diabetic peripheral neuropathy (DPN) and reported weekly duration of walking during and at the end of a one-year intervention using a StepWatch ankle accelerometer. Based on the point estimate and low-certainty evidence, intervention may have led to an important increase in physical activity per week; however, the 95% confidence interval (CI) included the possibility of no difference or an effect in either direction at three months (mean difference (MD) 34 minutes per week, 95% CI -92.19 to 160.19; 69 participants), six months (MD 68 minutes per week, 95% CI -55.35 to 191.35; 74 participants), and 12 months (MD 49 minutes per week, 95% CI -75.73 to 173.73; 70 participants). Study-reported effect estimates for foot lesions and full-thickness ulcers also included the possibility of no difference, a higher, or lower risk with intervention. A sensor-based, interactive exercise programme compared to no sensor-based, interactive exercise programme One study involved adults with DPN and reported duration of walking over 48 hours at the end of four weeks' intervention using a t-shirt embedded PAMSys sensor. It was not possible to draw conclusions about the effectiveness of the intervention from the very low-certainty evidence (MD -0.64 hours per 48 hours, 95% CI -2.42 to 1.13; 25 participants). We were also unable to draw conclusions about impact on the Physical Component Score (PCS) for quality of life (MD 0.24 points, 95% CI -5.98 to 6.46; 35 participants; very low-certainty evidence), although intervention may have made little or no difference to the Mental Component Score (MCS) for quality of life (MD 5.10 points, 95% CI -0.58 to 10.78; 35 participants; low-certainty evidence). A functional exercise programme compared to a stretching exercise programme One study involved adults with spinal and bulbar muscular atrophy and reported a daily physical activity count at the end of 12 weeks' intervention using an Actical accelerometer. It was not possible to draw conclusions about the effectiveness of either intervention (requiring compliance) due to low-certainty evidence and unconfirmed measurement units (MD -8701, 95% CI -38,293.30 to 20,891.30; 43 participants). Functional exercise may have made little or no difference to quality of life compared to stretching (PCS: MD -1.10 points, 95% CI -5.22 to 3.02; MCS: MD -1.10 points, 95% CI -6.79 to 4.59; 49 participants; low-certainty evidence). Although studies reported adverse events incompletely, we found no evidence of supported activity increasing the risk of serious adverse events.
AUTHORS' CONCLUSIONS
We found a lack of evidence relating to children, adolescents, and non-ambulant people of any age. Many people living with NMD did not meet randomised controlled trial eligibility criteria. There was variation in the components of supported activity intervention and usual care, such as physical therapy provision. We identified variation among studies in how physical activity was monitored, analysed, and reported. We remain uncertain of the effectiveness of promotional intervention for physical activity and its impact on quality of life and adverse events. More information is needed on the ITT population, as well as more complete reporting of outcomes. While there may be no single objective measure of physical activity, the study of qualitative and dichotomous change in self-reported overall physical activity might offer a pragmatic approach to capturing important change at an individual and population level.
Topics: Bias; Exercise; Health Promotion; Humans; Muscle Stretching Exercises; Neuromuscular Diseases; Outcome Assessment, Health Care; Quality of Life; Randomized Controlled Trials as Topic; Resistance Training; Time Factors; Walking
PubMed: 34027632
DOI: 10.1002/14651858.CD013544.pub2 -
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 -
Respiration; International Review of... 2021Chronic hypercapnic respiratory failure induces considerable morbidity and mortality in patients with myotonic dystrophy type 1 (DM1). This study systematically reviews...
INTRODUCTION
Chronic hypercapnic respiratory failure induces considerable morbidity and mortality in patients with myotonic dystrophy type 1 (DM1). This study systematically reviews the effects of noninvasive home mechanical ventilation (HMV) on gas exchange, quality of life, survival, and compliance in DM1 patients.
METHODS
A systematic Medline and Embase search was performed (January 1995 to January 2020). Records were screened for eligibility criteria, data were extracted from included studies, and risk of bias was assessed. We present findings mainly using a narrative synthesis.
RESULTS
Twenty-eight relevant full-text articles were screened for eligibility criteria. Nine studies were included. Randomized controlled trials were not found. Studies had either an observational (n = 8) or interventional (n = 1) design. In the pooled data analysis, HMV showed to improve mean oxygen saturation with 4.8% and decreased mean carbon dioxide values with 3 mm Hg. Compliance varied widely between studies, from no use to more than 12 h per day. Quality of life was not studied extensively, but some studies reported positive effects of HMV on symptoms of chronic respiratory failure. HMV may improve survival in DM1 patients with chronic hypercapnic respiratory failure.
CONCLUSION
This review shows that HMV can improve gas exchange and relieve symptoms with a possible survival benefit in DM1 patients with chronic hypercapnic respiratory failure. Future studies should focus on developing strategies to optimize the timing of HMV initiation and to promote compliance.
Topics: Adult; Humans; Myotonic Dystrophy; Noninvasive Ventilation; Patient Compliance; Pulmonary Gas Exchange; Quality of Life; Respiratory Insufficiency
PubMed: 33965950
DOI: 10.1159/000515453 -
The Journal of Pain Nov 2021Chronic pain is a frequent, yet under-recognized and under-assessed problem in people with muscular dystrophies (MDs). Knowledge of the prevalence and characteristics of... (Meta-Analysis)
Meta-Analysis
Chronic pain is a frequent, yet under-recognized and under-assessed problem in people with muscular dystrophies (MDs). Knowledge of the prevalence and characteristics of chronic pain, and its impact on function and quality of life is limited and lacks systematic exploration. This article aims to systematically review and synthesize existing literature that addresses chronic pain prevalence, characteristics and impact in people with different types of MDs. The present meta-analysis showed that the estimated prevalence of chronic pain in MDs is high and appears to be similar across different diagnostic groups: 68% (95% CI: 52%-82%) in FSHD, 65% (95% CI: 51%-77%) in DM, 62% (95% CI: 50%-73%) in BMD/DMD, and 60% (95% CI: 48%-73%) in LGMD, although it should be noted that heterogeneity was high in some diagnostic groups. On average, people with FSHD and DM present with moderate pain intensity. The lumbar spine, shoulders and legs are the most frequent sites of chronic pain among people with FSHD, DM, BMD/DMD, and LGMD, with little variation. Diffuse pain across multiple body sites was reported by a notable proportion of these individuals. Chronic pain has a negative impact on daily life activities in people with MDs, and may also contribute to decreased quality of life. The protocol for this review has been published on PROSPERO (CRD42020168096). PERSPECTIVES: This is the first systematic review and meta-analysis exploring the prevalence, and nature and impact of chronic pain in people with MDs. The present study demonstrates how common chronic pain is across various MD populations and highlights the need for better recognition and understanding of the nature and impact of pain from health professionals.
Topics: Chronic Pain; Humans; Muscular Dystrophies; Prevalence
PubMed: 33933682
DOI: 10.1016/j.jpain.2021.04.001 -
Developmental Medicine and Child... Sep 2021To synthesize clinical and scientific evidence regarding the instruments available to assess upper-limb function in paediatric patients with neuromuscular disease (NMD).
AIM
To synthesize clinical and scientific evidence regarding the instruments available to assess upper-limb function in paediatric patients with neuromuscular disease (NMD).
METHOD
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines (Prospective Registry of Systematic Reviews no. CRD42020140343). Two independent reviewers searched the PubMed/MEDLINE, LILACS, Embase, and Scopus databases. Inclusion criteria were cross-sectional or longitudinal studies or randomized controlled trials that used scales or questionnaires to assess upper-limb function in paediatric patients with NMDs. The COSMIN Risk of Bias checklist and criteria for good measurement properties were applied to assess the methodological quality of the instruments.
RESULTS
In total, 34 articles and 12 instruments were included. The Brooke Upper Extremity (n=16) and Performance of Upper Limb (PUL) (n=12) instruments were the most used tools. The PUL and Duchenne muscular dystrophy (DMD) Upper Limb patient-reported outcome measures (PROMs) tested more measurement properties and provided higher methodological quality scores for patients with DMD. Likewise, the Revised Upper Limb Module (RULM) was the most suitable instrument for patients with spinal muscular atrophy. No instrument has been devised to assess upper-limb function in patients with Charcot-Marie-Tooth disease and no other disease-specific instruments were found.
INTERPRETATION
The PUL, DMD Upper Limb PROM, and RULM are the most suitable instruments to assess upper-limb function in the two most prevalent paediatric NMDs. The identified gaps and methodological flaws of the available instruments indicate a need to develop high-quality instruments to assess other types of paediatric NMDs. What this paper adds The most suitable observer-rater instrument to assess upper-limb function in Duchenne muscular dystrophy (DMD) is the Performance of Upper Limb. The most suitable observer-rater instrument to assess upper-limb function in spinal muscular atrophy is the Revised Upper Limb Module. The DMD Upper Limb patient-reported outcome measure is recommended to assess the upper-limb performance of patients with DMD. Literature gaps and methodological flaws indicate the need to develop high-quality instruments to assess other types of paediatric neuromuscular disease.
Topics: Activities of Daily Living; Adolescent; Child; Cross-Sectional Studies; Disability Evaluation; Disease Progression; Humans; Longitudinal Studies; Neuromuscular Diseases; Patient Outcome Assessment; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Upper Extremity
PubMed: 33834485
DOI: 10.1111/dmcn.14887 -
Public Health Apr 2021A systematic narrative literature review was undertaken to assess the acceptability of childhood screening interventions to identify factors to consider when planning or...
OBJECTIVES
A systematic narrative literature review was undertaken to assess the acceptability of childhood screening interventions to identify factors to consider when planning or modifying childhood screening programs to maximize participation and uptake.
STUDY DESIGN
This is a systematic narrative literature review.
METHODS
Electronic databases were searched (MEDLINE, EMBASE, PsycINFO via Ovid, CINAHL, and Cochrane Library) to identify primary research studies that assessed screening acceptability. Studies were categorized using an existing theoretical framework of acceptability consisting of seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy. A protocol was developed and registered with PROSPERO (registration no. CRD42018099763) RESULTS: The search identified 4529 studies, and 46 studies met the inclusion criteria. Most studies involved neonatal screening. Programs identified included newborn blood spot screening (n = 22), neonatal hearing screening (n = 13), Duchenne muscular dystrophy screening (n = 4), cystic fibrosis screening (n = 3), screening for congenital heart defects (n = 2), and others (n = 2). Most studies assessed more than one construct of acceptability. The most common constructs identified were affective attitude (how a parent feels about the program) and intervention coherence (parental understanding of the program, and/or the potential consequences of a confirmed diagnosis).
CONCLUSIONS
The main acceptability component identified related to parental knowledge and understanding of the screening process, the testing procedure(s), and consent. The emotional impact of childhood screening mostly explored maternal anxiety. Further studies are needed to examine the acceptability of childhood screening across the wider family unit. When planning new (or refining existing) childhood screening programs, it is important to assess acceptability before implementation. This should include assessment of important issues such as information needs, timing of information, and when and where the screening should occur.
Topics: Child; Humans; Infant; Infant, Newborn; Mass Screening; Neonatal Screening; Parents; Patient Acceptance of Health Care
PubMed: 33831694
DOI: 10.1016/j.puhe.2021.02.005 -
Clinical Pharmacology and Therapeutics Dec 2021Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with type 1 SMA...
Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease characterized by loss of motor neurons and muscle atrophy. Untreated infants with type 1 SMA do not achieve major motor milestones, and death from respiratory failure typically occurs before 2 years of age. Individuals with types 2 and 3 SMA exhibit milder phenotypes and have better functional and survival outcomes. Herein, a systematic literature review was conducted to identify factors that influence the prognosis of types 1, 2, and 3 SMA. In untreated infants with type 1 SMA, absence of symptoms at birth, a later symptom onset, and a higher survival of motor neuron 2 (SMN2) copy number are all associated with increased survival. Disease duration, age at treatment initiation, and, to a lesser extent, baseline function were identified as potential treatment-modifying factors for survival, emphasizing that early treatment with disease-modifying therapies (DMT) is essential in type 1 SMA. In patients with types 2 and 3 SMA, factors considered prognostic of changes in motor function were SMN2 copy number, age, and ambulatory status. Individuals aged 6-15 years were particularly vulnerable to developing complications (scoliosis and progressive joint contractures) which negatively influence functional outcomes and may also affect the therapeutic response in patients. Age at the time of treatment initiation emerged as a treatment-effect modifier on the outcome of DMTs. Factors identified in this review should be considered prior to designing or analyzing studies in an SMA population, conducting population matching, or summarizing results from different studies on the treatments for SMA.
Topics: Cholestenones; Humans; Muscular Atrophy, Spinal; Observational Studies as Topic; Oligonucleotides; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33792051
DOI: 10.1002/cpt.2247 -
Journal of Neuromuscular Diseases 2021Variants in the LMNA gene, encoding lamins A/C, are responsible for a growing number of diseases, all of which complying with the definition of rare diseases....
BACKGROUND
Variants in the LMNA gene, encoding lamins A/C, are responsible for a growing number of diseases, all of which complying with the definition of rare diseases. LMNA-related disorders have a varied phenotypic expression with more than 15 syndromes described, belonging to five phenotypic groups: Muscular Dystrophies, Neuropathies, Cardiomyopathies, Lipodystrophies and Progeroid Syndromes. Overlapping phenotypes are also reported. Linking gene and variants with phenotypic expression, disease mechanisms, and corresponding treatments is particularly challenging in laminopathies. Treatment recommendations are limited, and very few are variant-based.
OBJECTIVE
The Treatabolome initiative aims to provide a shareable dataset of existing variant-specific treatment for rare diseases within the Solve-RD EU project. As part of this project, we gathered evidence of specific treatments for laminopathies via a systematic literature review adopting the FAIR (Findable, Accessible, Interoperable, and Reusable) guidelines for scientific data production.
METHODS
Treatments for LMNA-related conditions were systematically collected from MEDLINE and Embase bibliographic databases and clinical trial registries (Cochrane Central Registry of Controlled Trials, clinicaltrial.gov and EudraCT). Two investigators extracted and analyzed the literature data independently. The included papers were assessed using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.
RESULTS
From the 4783 selected articles by a systematic approach, we identified 78 papers for our final analysis that corresponded to the profile of data defined in the inclusion and exclusion criteria. These papers include 2 guidelines/consensus papers, 4 meta-analyses, 14 single-arm trials, 15 case series, 13 cohort studies, 21 case reports, 8 expert reviews and 1 expert opinion. The treatments were summarized electronically according to significant phenome-genome associations. The specificity of treatments according to the different laminopathic phenotypical presentations is variable.
CONCLUSIONS
We have extracted Treatabolome-worthy treatment recommendations for patients with different forms of laminopathies based on significant phenome-genome parings. This dataset will be available on the Treatabolome website and, through interoperability, on genetic diagnosis and treatment support tools like the RD-Connect's Genome Phenome Analysis Platform.
Topics: Cardiomyopathies; Humans; Lamin Type A; Laminopathies; Lipodystrophy; Muscular Dystrophies; Phenotype; Rare Diseases
PubMed: 33682723
DOI: 10.3233/JND-200596 -
Neuropathology : Official Journal of... Feb 2021Brain involvement in myotonic dystrophy type 1 (DM1) is characterized by heterogeneous cognitive, behavioral, and affective symptoms and imaging alterations indicative...
Brain involvement in myotonic dystrophy type 1 (DM1) is characterized by heterogeneous cognitive, behavioral, and affective symptoms and imaging alterations indicative of widespread grey and white matter involvement. The aim of the present study was to systematically review the literature on brain pathology in DM1. We conducted a structured search in EMBASE (index period 1974-2017) and MEDLINE (index period 1887-2017) on December 11, 2017, using free text and index search terms related to myotonic dystrophy type 1 and brain structures or regions. Eligible studies were full-text studies reporting on microscopic brain pathology of DM1 patients without potentially interfering comorbidity. We discussed the findings based on the anatomical region and the nature of the anomaly. Neuropathological findings in DM1 can be classified as follows: (1) protein and nucleotide deposits; (2) changes in neurons and glial cells; and (3) white matter alterations. Most findings are unspecific to DM1 and may occur with physiological aging, albeit to a lesser degree. There are similarities and contrasts with Alzheimer's disease; both show the appearance of neurofibrillary tangles in the limbic system without plaque occurrence. Likewise, there is myelin loss and gliosis, and there are dilated perivascular spaces in the white matter resemblant of cerebral small vessel disease. However, we did not find evidence of lacunar infarction or microbleeding. The various neuropathological findings in DM1 are reflective of the heterogeneous clinical and neuroimaging features of the disease. The strength of conclusions from this study's findings is bounded by limited numbers of participants in studies, methodological constraints, and lack of assessed associations between histopathology and clinical or neuroimaging findings.
Topics: Brain; Gray Matter; Humans; Inclusion Bodies; Myotonic Dystrophy; Neurofibrillary Tangles; Neuroimaging; White Matter
PubMed: 33599033
DOI: 10.1111/neup.12721 -
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