Heart Failure Post-SARS-CoV-2 Infection in Children with Duchenne Muscular Dystrophy: The Additive Value of Cardiovascular Magnetic Resonance.

In this case series, we describe the diagnosis of post-COVID-19 myocarditis in asymptomatic patients with Duchenne Muscular Dystrophy (DMD) and a mild COVID-19 disease course. These patients were referred for CMR due to electrocardiographic and echocardiographic alterations, which did not exist before COVID-19 infection. CMR identified the presence of severe myocardial inflammation in all patients based on abnormally elevated myocardial T2 ratio, late gadolinium enhancement, native T1 mapping, T2 mapping, and extracellular volume fraction. This was paired with concurrent impairment of left ventricular function. Appropriate treatment was initiated in all cases. Two of the four patients developed episodes of ventricular tachycardia during the following 6 months, and a defibrillator was implanted. Despite the mild clinical presentation, this case series demonstrates the diagnostic strength of CMR in the diagnosis and evaluation of post-COVID-19 myocarditis and serves to increase awareness of this potential complication amongst treating physicians.

Evaluation of Cardiac, Autonomic Functions in Ambulant Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by dystrophin gene mutation resulting in muscle weakness, motor delays, difficulty in standing, and inability to walk by 12 years. As disease progresses, it leads to cardiac and respiratory failure. Evaluation of cardiac autonomic status and echocardiography in DMD patients at a young age can be a potential biomarker to assess disease progression. This study aimed to investigate the younger DMD population of 5-11years of age with mild to moderate cardiac involvement for early detection using non-invasive and cost-effective tools. Genetically confirmed male DMD patients, aged 5-11 years (n = 47), screened from the outpatient department of a tertiary neuroscience institution were subjected to heart rate variability and echocardiographic analysis, and values were correlated with their clinical variables. DMD patients showed a significantly higher difference in HR, interventricular septum, E m/s, and E-wave to A-wave (E/A) ratio than normal values (p < 0.001). Significantly higher HR indicates initial sinus tachycardia and decreased IVD (d), and increased E m/s and E/A ratio mark the onset of cardiac symptoms in DMD patients even though its chamber dimension remains normal and are associated with cardiac muscle fibrosis.

Early immunological responses to the mRNA SARS-CoV-2 vaccine in patients with neuromuscular disorders.

Backgrounds: Intramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine. Methods: Healthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions. Results: Eleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline: <0.40 vs. <0.40, first vaccination, 145 ± 258 vs. 103 ± 1192, and second vaccination, 1528 ± 1265 vs. 1429 ± 944; p = 1.000, 0.909, and 0.736, respectively). A negative correlation was found between antibody titers and residual muscle volume but was not significant (Mercuri scale, r = -0.429, p = 0.249; fat infiltration rate, r = -0.194, p = 0.618). The adverse reactions were comparable between groups. Conclusion: The BNT162b2 vaccine is safe and effective in patients with NMDs.

Why Does It Feel Different? Provider Moral Distress in Removing Unwanted Aggressive Intervention for Conscious Patients (TH123B)

Outcomes: 1. Illustrate increased moral distress associated with removing unwanted aggressive interventions for conscious patients compared to unconscious patients. 2. Demonstrate the importance of the interdisciplinary team in supporting providers experiencing moral distress. When providing end-of-life care, removing unwanted aggressive intervention is more challenging in a conscious patient. If the intent to provide comfort and reduce suffering is the same, why does it feel different when the patient is conscious? This case examines the moral distress experienced by the palliative care team who assisted a conscious patient with Duchenne muscular dystrophy achieve his goal of liberation from the ventilator. A 41-year-old male with Duchenne muscular dystrophy and prior COVID-19 infection presented with respiratory failure. The patient had COVID-19 infection in April 2022 and was ventilator dependent since then. The palliative care team was consulted for goals of care discussion. After extensive discussion with the patient and his family, the patient decided to be disconnected from the ventilator and wanted a peaceful passing because long-term ventilatory support was no longer acceptable to him. He was afraid of being aware of struggling to breathe and requested to be asleep throughout this process. Specifically, he said he wanted "to close my eyes and see [my family] on the other side." When the patient was comfortable and asleep as he and his family desired, he was disconnected from the ventilator and died peacefully with his family around him. During this process, the palliative care team's intent was clear: follow the patient's wishes and provide comfort. Ethically, there is no difference in removing unwanted aggressive interventions between conscious and unconscious patients, but the team experienced significantly more distress in this case. After the patient's death, the interdisciplinary team provided support to help the palliative care team work through the distress experienced.Copyright © 2023

Clinical Course of Four Neuromuscular Disease Patients Infected COVID-19

Introduction: Information on COVID-19 infection prevention measures and vaccines for patients with neuromuscular diseases has been sufficiently disseminated, but the details of the actual course of infected patients are rarely directly involved by neurologists. We report four cases of COVID-19 with neuromuscular diseases and were able to observe their progress. Subjects: 1 case of multiple sclerosis (MS), 1 case of chronic inflammatory demyelinating polyradiculoneuropathy / dermatitis (CIDP / DM), 1 case of limb-girdle muscular dystrophy (LGMD) and one Duchenne muscular dystrophy carrier (DMD-C) were examined. Result: MS: A 32-year-old man who was taking fingolimod, but improved by waiting at home, and he did not relapse. CIDP / DM: 54-year-old female, PSL, taking tacrolimus, using remdesivir for pneumonia. After recovery, peripheral neuropathy worsened, and steroid pulse treatment was added. LGMD: 48-year-old female Although she had pneumonia, she did not need to be ventilated and improved with only oxygen administration and favipiravir without deterioration of% VC. DMD-C: 59-year-old female, improved only by oxygen administration. The DMD (second son, 29 years old) who were cared by her was hospitalized because no one could care him. Discussion: All cases were affected prior to vaccination. Regarding CIDP, there was a case report of deterioration after illness, and this case also deteriorated and required treatment. LGMD / DMD-C did not show any deterioration in respiratory function. It is a study of a small number of cases, and it is necessary to accumulate future cases.

Benefits of Telemonitoring of Pulmonary Function-3-Month Follow-Up of Home Electronic Spirometry in Patients with Duchenne Muscular Dystrophy.

BACKGROUND: In patients with Duchenne Muscular Dystrophy (DMD), the respiratory system determines the quality and length of life; therefore, the search for easy and safe everyday monitoring of the pulmonary function is currently extremely important, particularly in the COVID-19 pandemic. The aim of the study was to evaluate the influence of a three-month home electronic spirometry (e-spirometry) monitoring of the pulmonary function and strength of respiratory muscles as well as the patients' benefits from this telemetric program. METHODS: Twenty-one boys with DMD (aged 7-22; non-ambulatory-11) received a remote electronic spirometer for home use with a special application dedicated for patients and connected with a doctor platform. Control of the hospital spirometry (forced vital capacity-FVC, forced expiratory volume in 1 second-FEV1, peak expiratory flow-PEF) and respiratory muscle strength (maximal inspiratory-MIP and expiratory pressures-MEP) before and after the three-month monitoring were performed as well telemonitoring benefit survey. RESULTS: A total of 1403 measurements were performed; 15 of the participants were able to achieve correct attempts. There were no differences between the hospital and the home spirometry results as well as between respiratory muscle strength during v1 vs. v2 visits for the whole study group (all parameters p > 0.05); the six participants achieved increased value of FVC during the study period. There was a positive correlation between ΔFVC and the number of assessments during the home spirometry (r = 0.7, p < 0.001). Differences between FVC and MIPcmH2O (r = 0.58; p = 0.01), MEPcmH2O (r = 0.75; p < 0.001) was revealed. The mean general satisfaction rating of the telemonitoring was 4.46/5 (SD 0.66) after one month and 4.91/5 (SD 0.28) after three months. The most reported benefit of the home monitoring was the improvement in breathing (38% of participants after one month, 52% after three months of telemonitoring). Forgetting about the procedures was the most common reason for irregular measurements; the participants reported also increased motivation but less time to perform tests. CONCLUSIONS: The study indicates high compliance of the home telemonitoring results with the examination in the hospital. Benefits from home spirometry were visible for all participants; the most important benefit was breathing improvement. The remote home spirometry is usable for everyday monitoring of the pulmonary function in DMD patients as well can be also treated as respiratory muscle training.

Establishment of Hong Kong Neuromuscular Disorder Patient Registry

Introduction: Neuromuscular disorders (NMDs) are a group of diseases affecting the peripheral nervous system (1). Many NMDs cause disability or even premature death (2). We aim to design and establish a robust NMD patient registry in Hong Kong. Methods: By modelling international NMD patient registries, we designed patient-professional reported questionnaires to collect the demographic, clinical c haracteristics, genetic details, family history, investigation findings and specific treatment of NMD patients. Patients were recruited through Hong Kong West Cluster (DKCH, QMH) and Kowloon Central Cluster (HKCH). We also developed self-registration online platform. p<0.05 was considered statistically significant. Findings: Since June 2019, 125 NMD patients have been enrolled in the registry with 12 participants registered online. The registry recruited 13 types of NMDs, including spinal muscular atrophy (SMA) (n=31), Duchenne muscular dystrophy (DMD) (n=19) and congenital myopathy (n=18). The age range was 7 months to 63 years old. 65.6% of those enrolled were children (<18 years old). 63.2% were male. 64.8% of the patients had genetic diagnosis. The registry has contributed to two studies. The first one is a prospective study of clinical efficiency of Nusinersen in SMA patients (n=22). 14/16 SMA patients showed improvement in at least one of motor performance (CHOP intend/RULM/HINE/HFMSE) and health-related quality of life after 1st year of treatment. The second study is the reactogenicity and immunogenicity study of the COVID-19 vaccine in DMD patients (n=4). Data will be available in October. Conclusion: Hong Kong Patient registry has contributed to ongoing and new research study to optimise medical care.

New Possibilities for Home E-monitoring of Pulmonary Function in Patients with Duchenne Muscular Dystrophy - ePULMoDMD Project

RATIONALE. Duchenne muscular dystrophy (DMD) is the most common and severe muscular dystrophy recognized in childhood. Genetically determined progressive dystrophin dysfunction in skeletal and multiple organ muscles is fatal before the age of 20 years without multi-specialized care. The most common cause of death is respiratory muscle failure. The primary task in caring for patients with DMD is the early monitoring of pulmonary functions. This has become difficult during the pandemic SARS-CoV-2 as the procedures generate aerosols, i.e. high risk of SARS-CoV-2 virus transmission. The aim of the study was to evaluate the capacity of the patients with DMD to perform longitudinal daily spirometry examinations at home. METHODS. The patients with DMD were recruited from the Rare Disease Centre, Medical University of Gdask, Poland (a member of the TREAT NMD Alliance Neuromuscular Network). Physical examination with anthropometry measurement, Vignos scale (VS), Brooke scale (BS), and Pulmonary Function Tests were measured during 3 months of monitoring. Participants used home spirometry (AioCare System, Healthup), twice every day. The adherence and correctness (separately for FEV1 and FVC) of spirometry examinations were evaluated. RESULTS. We recruited 20 boys with mean age 11.7(3.0) years (range 7-16 years) and BMI 22.3(5.5) kg/m∧2 with a median VS of 2.5 (IQR 6.5) and BS of 2 (IQR 4.0). During 3 months of monitoring 1301 spirometry examinations were performed;32% of them meet ATS/ERS criteria for FEV1 and FVC, 35% for FEV1 and 33% for FVC, however 50% of patients performed examinations with at least one maneuver with correct FVC. The mean adherence considering performance spirometry examinations twice a day was 39(26)% (range: 6%-98%). We observed a significant increase of FVC values during the monitoring period in 4/20 of patients based on linear regression model estimation. The study is still ongoing. CONCLUSIONS. The systematic pulmonary function monitoring at home in patients with restrictive diseases is an innovative project. The results showed that patients with DMD are able to monitor the lung function using a mobile spirometry system. We observed that in some cases, based on patient feedback, systematic spirometry tests were a form of pulmonary exercises and could be one of the factors that increase FVC after 3 months of monitoring. Personal spirometers could be used as a part of the therapy of patients with muscular dystrophy.

Effects of confinement in Spain during the COVID pandemic on the Duchenne muscular dystrophy pediatric population: The importance of daily physical activity

Introduction: Low-intensity aerobic training has demonstrated to be beneficial in patients with Duchenne muscular dystrophy (DMD). Aerobic exercise counteracts physical deterioration. Daily exercise (walking to and back from school, playing in the park, etc) is supposed to have a big influence on the muscular state of the patient, but its importance has never been studied before. 6MWT is a primary endpoint for DMD and a strong predictor of decline in ambulation. In Spain, because of the COVID situation, the Spanish population was confined to their home on 14th March 2020. Children could start to go for a walk from April 26th, but they didn't go back to school until September 2020. Patients and methods: DMD children visited in Hospital Sant Joan de Deu with: (1) Previous basal 6MWT (6MWT pre): June 2019;(2) 6MWT pre-confinement (6MWT basal): December 2019;(3) 6MWT post-confinement (6MWT post): June 2020. We analyzed the meters' difference between 6MWT pre and 6 MWT basal, compared with the meter's difference between 6 MWT basal and 6MWT post. Results: 28 DMD children: age: 6-17 years. Meters' difference between 6MWT pre-6MWT basal: average- 1.08, standard deviation 45.97, minimum-157, median 8.50, maximum 93. Meters' Difference between 6MWT basal-6MWT post: average- 34.62, standard deviation 48.26, minimum-124, median- 28.50, maximum 106. The differences are statistically significant (p = 0.006 Wilcoxon test). Conclusion: DMD children presented a bigger deterioration in the 6MWT after confinement. These results support the importance of avoiding a sedentary lifestyle to preserve ambulation and slow down the disease.

Mechanical ventilation in Duchenne muscular dystrophy: A pilot project in Ukraine.

BACKGROUND: Home mechanical ventilation (HMV) prolongs survival in patients with Duchenne muscular dystrophy (DMD) until ±35 years of age. This study evaluates the implementation of a HMV pilot project in children with DMD in Ukraine. METHODS: Children with DMD were invited to Kirovograd Regional Children's Clinical Hospital, Kropyvnytskyi, Ukraine, for 5 days' training with non-invasive ventilation. Donated equipment comprised second-hand Covidien PB560 ventilators from Belgium. Due to the absence of carbon dioxide pressure and pulse oximetry monitoring, indications for HMV included sleep-related symptoms, restrictive lung function test, loss of ambulation for more than 1 year, or age greater than 17 years. Master class lectures on HMV were conducted for Ukrainian doctors in conjunction with patient training. RESULTS: Twelve Ukrainian physicians took part in face-to-face master classes and 50 Ukrainian physicians participated in online master classes. Simultaneously, eight Duchenne inpatients, mean age 15.4 (SD: 1.8) years and body mass index 25.8 (SD: 4.0), were included in the study. All patients chose nasal masks and volume-pressure-assisted control mode. After 6 weeks, one patient stopped HMV, two others used HMV partially during sleep, and 5/8 used nocturnal HMV increasingly with few complaints. Follow up via phone call was organized after hospitalization. CONCLUSIONS: Implementation of HMV is feasible in DMD inpatients in Ukraine. In the short term, the Ukrainian parliament should recognize official centers for HMV, and define the funding policy of equipment for HMV, and its maintenance. Local distributors should deliver equipment for HMV and devices for monitoring carbon dioxide pressure and pulse oximetry in specialized centers for HMV.

Current care practices for patients with Duchenne muscular dystrophy in China.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has presented challenges in the care of patients with chronic diseases. We identified the challenges faced by Chinese patients with Duchenne muscular dystrophy (DMD) during the pandemic. METHODS: An online cross-sectional survey was conducted between March 27 and June 30, 2021. RESULTS: Of the 2105 valid questionnaire responses, 2,056 patients were from non-lockdown areas. In these areas, 42.8% reduced outside daily activities, 49.4% reduced rehabilitation service use, 39.7% postponed regular follow-ups, and 40.8% reported accelerated motor function decline. These figures generally increased for patients from lockdown areas-67.3% reduced outside daily activities, 44.9% reduced rehabilitation service use, 79.6% postponed regular follow-ups, and 55.1% reported accelerated motor function decline. Ambulation loss was most commonly reported in September and March before 2020; however, this trend was absent in 2020. Regarding the informed prices of disease-modifying drugs in Europe and the United States, 86.7% could afford a maximum of one-twentieth of the prices, 8.0% could afford one-tenth of the prices, and only 0.6% of the patients could afford the full prices. CONCLUSIONS: Implementation of standardized care for DMD in China is consistent with global practices, and the COVID-19 pandemic has affected the care of patients with chronic diseases worldwide, particularly in lockdown areas. Telemedicine is an effective model for providing healthcare to such patients. Healthcare workers should assist patients and establish more robust chronic disease management systems. Collaboration between governmental and non-governmental entities could address the cost of disease-modifying drugs in China and other developing countries.

Evaluating the Feasibility and Reliability of Remotely Delivering and Scoring the North Star Ambulatory Assessment in Ambulant Patients with Duchenne Muscular Dystrophy.

OBJECTIVE: The North Star Ambulatory Assessment (NSAA) is a validated 17-item functional rating scale and widely used to assess motor function in boys with Duchenne muscular dystrophy (DMD). The SARS-CoV-2 pandemic and subsequent Government 'lockdown' resulted in no face-to-face clinic visits hence the motor abilities were not monitored. The aim was to investigate whether the NSAA was feasible and reliable by video assessment. METHOD: Ten ambulant DMD boys were selected from the electronic hospital records. Two physiotherapists scored the boys' NSAA independently and the intraclass correlation coefficient was used to assess agreement. The video scores were compared to two previous NSAA in-clinic scores. RESULTS: Mean scores (SD) for clinic visit one were 22.6 (4.19) and clinic visit two 21.8 (5.3). The two physiotherapists video mean scores were 20.6 (5.66) for physiotherapist 1 and 20.6 (6.53) for physiotherapist 2. The intraclass correlation coefficient was 0.98 (95% CI 0.93-1.00) for the total NSAA and 1.00 (95% CI 1.00 to 1.00) for the rise time. The mean decline in score from clinic visit one (-12 months) to video assessment was 2.0 (2.8SD). CONCLUSION: The results from the study suggest that video NSAA is partially feasible and reliable.

COVID-19 related anxiety among parents of children suffering from Duchenne muscular dystrophy

Introduction: Duchenne (DMD) and Becker (BMD) muscular dystrophies are genetic disorders affecting skeletal, respiratory, and the cardiac muscles leading to respiratory and/or circulatory failure and death in early adulthood. Therefore, the clinical course of the disease potentially puts these patients in a high-risk group for severe and complicated course of coronavirus disease 2019 (COVID-19). Methods: We present a cross-sectional, observational study based on survey research conducted from 04th July to 6th August 2020. Parents of children with DMD or BMD were invited via online groups and forums to fill in an online questionnaire regarding demographics, medical and social information and assessment of level of anxiety. Only complete surveys were considered eligible. Statistical analysis was performed using Wizard 2beta239 (Evan Miller, Chicago, IL). All data are reported as percentage (n) or mean ± standard deviation or median (range) dependently on the data type and distribution. Appropriate tests were used and p<0.05 was considered statistically significant. Results: Sixty-three respondents, primarily female (82%), aged 39.5 ±7.8 years took part in the study. Majority of responders (51%, n=32) had two children and 35% (22) had one child, 25% (8) of responders had more than one child with BMD/DMD. Mean age of the children with dystrophy was 9.6±5.2 years. Eighty-nine percent of respondents were moderately-to-highly afraid of COVID-19-related complications in their children, 70% feared for their children lives and 72% reported concern due to healthcare system reorganisation (Figure 1). Guardians of younger children (<12 y.o.) were more concerned than the parents of older children (p=0.044). Information about protecting DMD/BMD patients against SARS-CoV-2 infection (94%) and resuming of planned hospitalizations and out-patient visits (95,3%) were indicated as factors much-to-greatly increasing guardians' sense of security. Moderate or severe level of anxiety (as assessed by General Anxiety Disorder -7 Questionnaire) was present in 20% (12) guardians. There was no difference in concern or anxiety level between DMD and BMD groups. Conclusions: COVID-19 pandemic as a new health hazard and simultaneously culprit of reorganisation in health system both resulting in increased anxiety and concern in parents, including fear of offsprings' life. Yielding adequate information by healthcare providers may ease parents' fear.

Improving Recruitment for a Newborn Screening Pilot Study with Adaptations in Response to the COVID-19 Pandemic.

Seven months after the launch of a pilot study to screen newborns for Duchenne Muscular Dystrophy (DMD) in New York State, New York City became an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. All in-person research activities were suspended at the study enrollment institutions of Northwell Health and NewYork-Presbyterian Hospitals, and study recruitment was transitioned to 100% remote. Pre-pandemic, all recruitment was in-person with research staff visiting the postpartum patients 1-2 days after delivery to obtain consent. With the onset of pandemic, the multilingual research staff shifted to calling new mothers while they were in the hospital or shortly after discharge, and consent was collected via emailed e-consent links. With return of study staff to the hospitals, a hybrid approach was implemented with in-person recruitment for babies delivered during the weekdays and remote recruitment for babies delivered on weekends and holidays, a cohort not recruited pre-pandemic. There was a drop in the proportion of eligible babies enrolled with the transition to fully remote recruitment from 64% to 38%. In addition, the proportion of babies enrolled after being approached dropped from 91% to 55%. With hybrid recruitment, the proportion of eligible babies enrolled (70%) and approached babies enrolled (84%) returned to pre-pandemic levels. Our experience adapting our study during the COVID-19 pandemic led us to develop new recruitment strategies that we continue to utilize. The lessons learned from this pilot study can serve to help other research studies adapt novel and effective recruitment methods.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular. Objectives: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. Search methods: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. Selection criteria: We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. Data collection and analysis: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). Main results: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97;64 participants;low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49;63 participants;moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67;53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93;1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04;66 participants;low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13;66 participants;low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors;both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants

Drivers of caregiver impact in Duchenne muscular dystrophy: a cohort study.

BACKGROUND: In our companion paper, we addressed the interplay between caregiver impact, out-of-pocket expenditures, and Duchenne Muscular Dystrophy (DMD) disability. We found that DMD caregiver impact could be characterized by four Latent Profile Analysis impact profiles: lowest, lower middle, upper middle, and highest impact. The impact on caregivers was often but not always worse with greater out-of-pocket expenditures. Further, while the lowest-, lower-middle, and highest-impact profiles reflected low, moderate and high disability-related caregiver burden, respectively, the upper-middle profile group was quite variable in level of disability across domains. To better understand the four caregiver-impact profiles, we examine how a comprehensive set of psychosocial factors differentiate the four profile groups. METHODS: Psychosocial factors assessed included demographic characteristics, quality of life (QOL), stress, cognitive appraisal, reserve-building, and general and COVID-specific resilience. Linear modeling examined relationships between impact profiles and psychosocial factors. We used effect size rather than p-value as the criterion for determining relevance of the broad range of characteristics examined. RESULTS: Multivariate analyses implicated stress and environmental mastery, appraisal sampling of experience, COVID-specific variables, appraisal standards of comparison, appraisal goals, demographics, appraisal combinatory algorithm, reserve-building, and resilience, in order of prominence (average eta2 = 0.29, 0.29, 0.16, 0.15, 0.09, 0.07, 0.07, 0.06, 0.05, and 0.02, respectively). On the whole, comparisons of highest-versus-lowest impact profiles revealed more and larger differences than comparisons of upper-middle versus lower-middle impact profiles. Life stress, goals, and reserve-building activities had a smaller differentiating effect in the middle groups. CONCLUSION: A more comprehensive 'story' about DMD caregiver impact involves life stress, environmental mastery, COVID-specific variables, and cognitive and behavioral factors. Implications are discussed for coaching interventions to support DMD caregivers.

Newborn screening pilot study in time of pandemic: Duchenne Muscular Dystrophy pilot project experience

Introduction: On 1st October 2019, a consented pilot study to screennewborns for Duchenne muscular dystrophy was initiated in NYS. Thepilot study is a collaboration between Parent Project MuscularDystrophy, New York State Newborn Screening (NYS NBS) program,Northwell Health Hospitals, New York-Presbyterian Hospitals, NBSTranslational Research Network (NBSTRN), American College ofMedical Genetics (ACMG), and funders. Institutional Review Board(IRB) approved the study. However, the COVID-19 pandemic led todiscussions regarding ending the pilot study unless alternativeprotocols could be established.Methods: Prior to the pandemic, patient enrollment was conductedon-site. Study coordinators at hospitals consented families in-personusing e-consents built in REDCap™ (a secure web application forbuilding and managing online surveys and databases) on hospitalapproved tablets. The specimens were then shipped to the NBSprogram where they were tested for the NBS panel and procedureswere instituted to cross-check consent forms. Duchenne results werereleased on the standard NBS report. Any baby with a borderline resulthad to have a repeat NBS specimen collected and submitted to theprogram. Any baby with a positive result would be referred and seenby a clinical genetics team, and an additional blood specimen wascollected and submitted for second-tier molecular testing. Babies withpositive molecular test results would be followed by a specialist, andfamilies would be offered carrier testing and given information aboutDuchenne and the opportunity to participate in clinical trialsDuring the pandemic, fully remote patient screening, recruitment, andreporting processeswere implemented. The remote study effortswerecomplicated by staff retention issues, technical and software/Wi-Figlitches, computer illiteracy requiring extensive instructions (a subsetof patients), lack of email access. Paper consent mailing requiredsubstantial resources.Significant resources were required at the NBS program as well.Follow-up required research staff coordinate the redraw of thesamples with the parents and pediatrician’s office and referrals weremade by telehealth or in-person visits. For molecular testing, a buccalswab sample collection kit was mailed to the families opting fortelehealth.Conclusion: Despite the challenges, development of remote studyprocedures enabled successful continuation of the pilot during thepandemic. These newprotocols could be applicable in the absence of apandemic as a complementary method to in-person recruitmentprocess and follow up, which would facilitate enrollment of patientswho would otherwise be missed. Implementation of this hybridapproach leads to optimization of patient enrollment, which couldapply to a broad spectrum of future studies and clinical trials.

Morbidity, Clinical Course and Vaccination against SARS-CoV-2 Virus in Patients with Duchenne Muscular Dystrophy: A Patient Reported Survey.

Background: Patients with Duchenne muscular dystrophy (DMD) may be at higher risk of a severe course of COVID-19. The aim of the study was to evaluate: (1) the incidence and course of COVID-19 infection in DMD patients; (2) the vaccination status of DMD patients; and (3) COVID-19 related anxiety among DMD families. Materials and Methods: The study was conducted during an online symposium for DMD patients and their families. All participants (DMD families; n = 150) were asked to fill in the online survey with questions about COVID-19 infection history, vaccination against SARS-CoV-2 and anxiety during pandemic. Results: 53 DMD patients filled in the survey. Five (9.43%) were COVID-19 positive with mild symptoms of respiratory infection and anosmia; 23 (42.6%) were vaccinated, but in almost 20% of DMD families, none of the family members was vaccinated. Respondents revealed anxiety related both to the vaccination procedure and to COVID-19 infection (complications after infection 93.6%, death 62.4% respondents). Changes in health care system organization also aroused concern among participants (85.3%). Conclusion: The course of the COVID-19 infection in DMD patients was mild. Not enough patients with DMD and their families are vaccinated. Education about the management of COVID-19 infections and the vaccination procedure for DMD patients is needed and expected.

Is It Possible to Have Home E-Monitoring of Pulmonary Function in Our Patients with Duchenne Muscular Dystrophy in the COVID-19 Pandemic?-A One Center Pilot Study.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common, progressive, irreversible muscular dystrophy. Pulmonary function is crucial for duration of life in this disease. Currently, the European Respiratory Society is focused on digital health, seeking innovations that will be realistic for digital respiratory medicine to support professionals and patients during the COVID-19 pandemic. AIMS: The aim of this study was to investigate whether it is possible to monitor pulmonary function at home using an individual electronic spirometry system in boys with Duchenne muscular dystrophy. MATERIALS AND METHODS: In this observational, prospective study, conducted from March 2021 to June 2021, twenty boys with DMD (aged 8-16) were enrolled. The patients were recruited from the Rare Disease Centre, University Clinical Centre, of Gdansk, Poland. Medical history and anthropometric data were collected, and spirometry (Jaeger, Germany) was performed in all patients at the start of the study. Each patient received an electronic individual spirometer (AioCare) and was asked to perform spirometry on their own every day, morning and evening, at home for a period of 4 weeks. The number of measurements, correctness of performing measurements, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF) were evaluated. RESULTS: Finally, 14 out of 20 boys enrolled in the study with a mean age of 12.5 years (7 non-ambulatory) applied and received a home spirometer (AioCare). A total of 283 measurements were performed by all patients at home for 4 weeks. Half of the patients were able to perform measurements correctly. There were no significant differences between mean values of FVC, FE1, PEF between home and hospital spirometry (p > 0.05) expect PEF pv% (p < 0.00046). Patients with higher FEV1 (p = 0.0387) and lower BMI (p = 0.0494) were more likely to take home spirometer measurements. The mean general satisfaction rating of home-spirometry was 4.33/5 (SD 0.78), the mean intelligibility rating was 4.83/5 (SD 0.58). Reasons for irregular measurements were: forgetting (43%), lack of motivation (29%), difficulty (14%), lack of time (14%). CONCLUSION: Home electronic monitoring of pulmonary function in patients with DMD is possible to implement in daily routines at home. This protocol should be introduced as early as possible in patients 7-8 years old with good, preserved lung function. Patients accept this form of medical care but require more education about the benefits of e-monitoring. There is a need to implement a system to remind patients of the use of electronic medical devices at home, e.g., via SMS (short message service).

Changes in motor function in Duchenne muscular dystrophy patients after travel restrictions due to COVID-19.

INTRODUCTION/AIM: This retrospective study aimed to quantify the changes in motor function in patients with Duchenne muscular dystrophy (DMD) due to the government-imposed travel restrictions associated with the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Twelve DMD patients were enrolled in this investigation (mean ± SD age: 9.8 ± 3.6 y). Their physical characteristics and motor function were evaluated approximately 3 mo before, immediately before, and approximately 3 mo after the travel restrictions were decreed. Statistical comparisons were performed of the changes in motor function before and after the travel restrictions. RESULTS: The change in range of motion (ROM) of ankle dorsiflexion was significantly decreased after the travel restrictions. Changes in body mass index and other motor function parameters were not significant. DISCUSSION: An apparent decrease in the amount of physical activity due to travel restrictions in response to COVID-19 negatively affected ankle dorsiflexion ROM but not other motor functions. A more sedentary lifestyle and lack of regular physical therapy services most likely contributed to this reduction. The use of remote rehabilitation tools with the involvement of physiotherapists may help mitigate such changes and prevent more severe physical decline.