Development of respiratory care guidelines for Duchenne muscular dystrophy in the UK: key recommendations for clinical practice.

Significant inconsistencies in respiratory care provision for Duchenne muscular dystrophy (DMD) are reported across different specialist neuromuscular centres in the UK. The absence of robust clinical evidence and expert consensus is a barrier to the implementation of care recommendations in public healthcare systems as is the need to increase awareness of key aspects of care for those living with DMD. Here, we provide evidenced-based and/or consensus-based best practice for the respiratory care of children and adults living with DMD in the UK, both as part of routine care and in an emergency. METHODOLOGY: Initiated by an expert working group of UK-based respiratory physicians (including British Thoracic Society (BTS) representatives), neuromuscular clinicians, physiotherapist and patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK respiratory teams and neuromuscular services, consensus was achieved on these best practice recommendations for respiratory care in DMD. RESULT: The resulting recommendations are presented in the form of a flow chart for assessment and monitoring, with additional guidance and a separate chart setting out key considerations for emergency management. The recommendations have been endorsed by the BTS. CONCLUSIONS: These guidelines provide practical, reasoned recommendations for all those managing day-to-day and acute respiratory care in children and adults with DMD. The hope is that this will support patients and healthcare professionals in accessing high standards of care across the UK.

Functional abilities, respiratory and cardiac function in a large cohort of adults with Duchenne muscular dystrophy treated with glucocorticoids.

BACKGROUND AND PURPOSE: The transition to adult services, and subsequent glucocorticoid management, is critical in adults with Duchenne muscular dystrophy. This study aims (1) to describe treatment, functional abilities, respiratory and cardiac status during transition to adulthood and adult stages; and (2) to explore the association between glucocorticoid treatment after loss of ambulation (LOA) and late-stage clinical outcomes. METHODS: This was a retrospective single-centre study on individuals with Duchenne muscular dystrophy (≥16 years old) between 1986 and 2022. Logistic regression, Cox proportional hazards models and survival analyses were conducted utilizing data from clinical records. RESULTS: In all, 112 individuals were included. Mean age was 23.4 ± 5.2 years and mean follow-up was 18.5 ± 5.5 years. At last assessment, 47.2% were on glucocorticoids; the mean dose of prednisone was 0.38 ± 0.13 mg/kg/day and of deflazacort 0.43 ± 0.16 mg/kg/day. At age 16 years, motor function limitations included using a manual wheelchair (89.7%), standing (87.9%), transferring from a wheelchair (86.2%) and turning in bed (53.4%); 77.5% had a peak cough flow <270 L/min, 53.3% a forced vital capacity percentage of predicted <50% and 40.3% a left ventricular ejection fraction <50%. Glucocorticoids after LOA reduced the risk and delayed the time to difficulties balancing in the wheelchair, loss of hand to mouth function, forced vital capacity percentage of predicted <30% and forced vital capacity <1 L and were associated with lower frequency of left ventricular ejection fraction <50%, without differences between prednisone and deflazacort. Glucocorticoid dose did not differ by functional, respiratory or cardiac status. CONCLUSION: Glucocorticoids after LOA preserve late-stage functional abilities, respiratory and cardiac function. It is suggested using functional abilities, respiratory and cardiac status at transition stages for adult services planning.

Using the consolidated Framework for Implementation Research to integrate innovation recipients' perspectives into the implementation of a digital version of the spinal cord injury health maintenance tool: a qualitative analysis.

BACKGROUND: Despite advances in managing secondary health complications after spinal cord injury (SCI), challenges remain in developing targeted community health strategies. In response, the SCI Health Maintenance Tool (SCI-HMT) was developed between 2018 and 2023 in NSW, Australia to support people with SCI and their general practitioners (GPs) to promote better community self-management. Successful implementation of innovations such as the SCI-HMT are determined by a range of contextual factors, including the perspectives of the innovation recipients for whom the innovation is intended to benefit, who are rarely included in the implementation process. During the digitizing of the booklet version of the SCI-HMT into a website and App, we used the Consolidated Framework for Implementation Research (CFIR) as a tool to guide collection and analysis of qualitative data from a range of innovation recipients to promote equity and to inform actionable findings designed to improve the implementation of the SCI-HMT. METHODS: Data from twenty-three innovation recipients in the development phase of the SCI-HMT were coded to the five CFIR domains to inform a semi-structured interview guide. This interview guide was used to prospectively explore the barriers and facilitators to planned implementation of the digital SCI-HMT with six health professionals and four people with SCI. A team including researchers and innovation recipients then interpreted these data to produce a reflective statement matched to each domain. Each reflective statement prefaced an actionable finding, defined as alterations that can be made to a program to improve its adoption into practice. RESULTS: Five reflective statements synthesizing all participant data and linked to an actionable finding to improve the implementation plan were created. Using the CFIR to guide our research emphasized how partnership is the key theme connecting all implementation facilitators, for example ensuring that the tone, scope, content and presentation of the SCI-HMT balanced the needs of innovation recipients alongside the provision of evidence-based clinical information. CONCLUSIONS: Understanding recipient perspectives is an essential contextual factor to consider when developing implementation strategies for healthcare innovations. The revised CFIR provided an effective, systematic method to understand, integrate and value recipient perspectives in the development of an implementation strategy for the SCI-HMT. TRIAL REGISTRATION: N/A.

Emery-Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure.

BACKGROUND AND AIMS: Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants. METHODS: Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidences in male and female variant-carriers were determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared with consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC). RESULTS: Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers [mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively]. Nine (23.7%) males developed MVA and five (13.2%) developed ESHF during a median (inter-quartile range) follow-up of 65.0 (24.3-109.5) months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median (inter-quartile range) age of 58.6 (53.2-60.4) years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank P = .49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank P = .09). CONCLUSIONS: Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.

Recommendation to update the British Society for Cutaneous Allergy corticosteroid series.

BACKGROUND: Patch testing is an important investigation when dermatitis is unresponsive to, or worsened by, topical corticosteroid treatment. There is a balance to be struck between testing too many allergens, which is expensive, time consuming and risks causing sensitization, and testing too few, which risks missing the diagnosis. The current British Society for Cutaneous Allergy (BSCA) corticosteroid series comprises eight allergens and was last updated in February 2007. AIM: To review and update the BSCA corticosteroid series. METHODS: We retrospectively analysed data from 16 patch test centres in the UK and Ireland for all patients who were patch tested to a corticosteroid series between August 2017 and July 2019. We recorded the allergens tested, the number and percentage tested to a corticosteroid series and the number of positive results for each allergen. We identified the allergens that test positive in ≥ 0.1% of selectively tested patients. RESULTS: Overall, 3531 patients were tested to a corticosteroid series in the 16 centres. The number of allergens tested ranged from 7 to 18 (mean 10). The proportion of patch test patients who were tested to a corticosteroid series ranged from 1% to 99%. Six allergens in the 2017 BSCA series tested positive in ≥ 0.1% of patients. Nine allergens not in the BSCA corticosteroid series tested positive in ≥ 0.1% of patients. CONCLUSION: This audit demonstrates the importance of regular review of recommended series and the significant variations in practice. The new BSCA corticosteroid series that we recommend contains 13 haptens, with the addition of the patient's own steroid creams as appropriate.

Disrupted mana and systemic abdication: Maori qualitative experiences accessing healthcare in the 12 years post-injury.

BACKGROUND: Maori have been found to experience marked health inequities compared to non-Maori, including for injury. Accessing healthcare services post-injury can improve outcomes; however, longer-term experiences of healthcare access for injured Maori are unknown. This paper reports on data from the longitudinal Prospective Outcomes of Injury Study - 10 year follow up (POIS-10) Maori study in Aotearoa/New Zealand (NZ), to qualitatively understand Maori experiences of accessing injury-related healthcare services long-term. METHODS: Follow-up telephone interviews were conducted with 305 POIS-10 Maori participants, who were injured and recruited 12-years earlier, experiencing a range of injury types and severities. Free text responses about trouble accessing injury-related health services were thematically analysed. RESULTS: Sixty-one participants (20%) reported trouble accessing injury-related health services and provided free text responses. Three related themes describing participants' experiences were connected by the overarching concept that participants were engaging with a system that was not operating in a way it was intended to work: 1) Competing responsibilities and commitments encapsulates practical barriers to accessing services, such as a lack of time and having to prioritise other responsibilities such as work or whanau (family); 2) Disrupted mana refers to the feelings of personal disempowerment through, for example, receiving limited support, care or information tailored to participants' circumstances and is a consequence of patients contending with the practical barriers to accessing services; and 3) Systemic abdication highlights systemic barriers including conflicting information regarding diagnoses and treatment plans, and healthcare provider distrust of participants. CONCLUSIONS: Twelve years post-injury, a considerable proportion of Maori reported experiencing barriers to accessing healthcare services. To restore a sense of manaakitanga and improve Maori access to healthcare, Maori-specific supports are required and systemic barriers must be addressed and removed.

Benefits and limitations of the transfer online of Irish College of General Practitioners (ICGP) continuing medical education (CME) small group learning (SGL) during COVID-19: a national Delphi study.

INTRODUCTION: In Ireland, continuing medical education (CME) small group learning (SGL) has been shown to be an effective way of delivering CME, particularly for rural general practitioners (GPs). This study sought to determine the benefits and limitations of the relocation of this education from face to face to online learning during COVID-19. METHODS: A Delphi survey method was used to obtain a consensus opinion from a group of GPs recruited via email through their respective CME tutors, and who had consented to participate. The first round gathered demographic details and asked doctors to report the benefits and/or limitations of learning online in their established Irish College of General Practitioners (ICGP) small groups. RESULTS: A total of 88 GPs from 10 different geographical areas participated. Response rates in rounds one, two and three were 72%, 62.5% and 64%, respectively. The study group was 40% male; 70% were in practice ≥15 years, 20% practiced rurally, and 20% were single-handed. Attending established CME-SGL groups allowed GPs to discuss the practical application of rapidly changing guidelines both in COVID-19 and non-COVID-19 care. They could discuss new local services and compare their practice with others during a time of change; this helped them feel less isolated. They reported that online meetings were less social; moreover, the informal learning that occurs before and after meetings did not take place. CONCLUSION: GPs in established CME-SGL groups benefited from online learning as they could discuss how to adapt to rapidly changing guidelines while feeling supported and less isolated. They report that face to face meetings offer more opportunities for informal learning.

Cardiac and pulmonary findings in dysferlinopathy: A 3-year, longitudinal study.

INTRODUCTION/AIMS: There is debate about whether and to what extent either respiratory or cardiac dysfunction occurs in patients with dysferlinopathy. This study aimed to establish definitively whether dysfunction in either system is part of the dysferlinopathy phenotype. METHODS: As part of the Jain Foundation's International Clinical Outcome Study (COS) for dysferlinopathy, objective measures of respiratory and cardiac function were collected twice, with a 3-y interval between tests, in 188 genetically confirmed patients aged 11-86 y (53% female). Measures included forced vital capacity (FVC), electrocardiogram (ECG), and echocardiogram (echo). RESULTS: Mean FVC was 90% predicted at baseline, decreasing to 88% at year 3. FVC was less than 80% predicted in 44 patients (24%) at baseline and 48 patients (30%) by year 3, including ambulant participants. ECGs showed P-wave abnormalities indicative of delayed trans-atrial conduction in 58% of patients at baseline, representing a risk for developing atrial flutter or fibrillation. The prevalence of impaired left ventricular function or hypertrophy was comparable to that in the general population. DISCUSSION: These results demonstrate clinically significant respiratory impairment and abnormal atrial conduction in some patients with dysferlinopathy. Therefore, we recommend that annual or biannual follow-up should include FVC measurement, enquiry about arrhythmia symptoms and peripheral pulse palpation to assess cardiac rhythm. However, periodic specialist cardiac review is probably not warranted unless prompted by symptoms or abnormal pulse findings.

Occupational allergic contact dermatitis to Piperamido Nitrotoluene in pharmaceutical workers: A case series.

BACKGROUND: Imatinib mesylate is a first-generation tyrosine kinase inhibitor. Piperamido Nitrotoluene, also known as F5, is an intermediate used in the manufacturing of imatinib. We present a case series of allergic contact dermatitis to F5 in pharmaceutical workers. METHODS: Four male pharmaceutical workers were referred between 2007 and 2021 with new dermatitis predominantly affecting the periorbital region. All were involved in the production of imatinib and particularly exposed to F5. Following medical history and examination, they underwent patch testing to standard series and F5 diluted in white soft paraffin (WSP). RESULTS: All patients tested positive confirming a diagnosis of contact allergy to F5. The first case tested positive to F5 diluted to 1% in WSP, the second to F5 diluted to 10% in WSP and the third and fourth to F5 diluted to 1% and 10% in WSP. In all four cases, dermatitis resolved when they were removed from exposure to F5. CONCLUSIONS: To the best of our knowledge, these are the first cases of allergic contact dermatitis to F5 confirmed by patch testing in the literature. In February 2016, a generic formulation of imatinib entered the market. Globalized production of imatinib may result in further cases presenting to dermatology departments worldwide.

Effects of cardiac medications on ventricular function in patients with Duchenne muscular dystrophy-related cardiomyopathy.

INTRODUCTION/AIMS: The DMD Care Considerations Working Group Guidelines 2010 recommended treating cardiac dystrophinopathy with angiotensin-converting enzyme-inhibitor (ACEi) and beta-blocker (BB) therapy to prevent the progressive decline in left ventricular function expected from earlier, natural history studies. The aim of this research was to audit change in measures of left ventricular function over 8 years to 4 years before and 4 years after deploying an ACEi/BB combination systematically at a dedicated "cardiology-muscle" clinic. METHODS: This is an institutionally registered, retrospective, case-file-based audit of serial echocardiographic measures of left ventricular fractional shortening accumulated over the period 1995 to 2015. RESULTS: Data from 104 genetically confirmed Duchenne muscular dystrophy (DMD) patients, aged 22.2 ± 5.3 years at data censure, were included. Mean age at first detection of left ventricular dysfunction was 15.1 ± 4.2 years, but older in those on maintenance steroid therapy (16.8 ± 4.2 vs 14.5 ± 4.1 years; P = .04). Group mean fractional shortening fell by 1.5%/year over the 4 years before therapy, but this decreased to 0.9%/year over the first 4 years after starting therapy. Analysis of limited left ventricular ejection fraction measures showed similar but nonsignificant changes. Neither age at detection of left ventricular dysfunction nor fractional shortening percent at time of therapy initiation affected the beneficial response. DISCUSSION: The results support the international DMD recommendations of the time. This combination of cardiac medications helps stabilize heart function. For the best long-term effects, therapy needs to be initiated no later than on first detection left ventricular impairment.

Novel agents for atopic dermatitis in patients over 50 years of age: A case series.

Lan et al recently highlighted the under-representation of older adults in clinical trials of systemic therapies for atopic dermatitis (AD). Late-onset AD is increasingly recognized in older adults. Spontaneous remission is uncommon with this phenotype. Existing drug treatments such as corticosteroids, methotrexate, ciclosporin, and azathioprine are complicated by adverse effects including increased malignancy risk, immunosuppression in the context of immunosenescence, and drug interactions in the setting of polypharmacy. A case series is presented of seven patients over 50 years of age with AD who were prescribed dupilumab or tofacitinib or upadacitinib for at least 6 months. All patients were clear or almost clear (investigator global assessment score 0/1) after 1 month of therapy. No significant adverse events were seen. This case series provides preliminary evidence about the safety and efficacy of these novel drugs for AD in older adults. Further studies with higher numbers of participants are needed to obtain real-world evidence for these drugs in older adults, given the limited data in clinical trials.

Development of a Programme Theory for Early Intervention Vocational Rehabilitation: A Realist Literature Review.

Purpose Little is currently known about how early intervention vocational rehabilitation (EIVR) works for people with newly acquired neurological conditions such as traumatic brain injury, acquired brain injury and spinal cord injury. This study aims, from a realist framework, to identify relevant literature and develop an initial programme theory to understand how EIVR might work for people experiencing acquired neurological disability. Realist reviews are ideally placed to address the identified knowledge gap as they assist in gaining a deeper understanding of how the intervention works, for whom it works best, and the contexts that promote the activation of desired outcomes. Methods We used a seven-step iterative process to synthesise literature using a realist approach. The steps included: development of initial programme theory, literature search, article selection, extracting and data organising, synthesis of evidence and programme theory refinement. We performed a literature search using the following databases: Cinahl, Embase, EMcare, Medline, PsychInfo and Scopus. Articles were selected if they contributed to the knowledge describing what is EIVR and how it works in newly acquired neurological conditions. Data were extracted and synthesised to develop a programme theory for EIVR. Results Following screening of 448 references, 37 documents were eligible for data extraction. We developed a refined programme theory of EIVR consisting of three contexts (prioritisation of exploring work options, return to work discussed as an option, and workplace support), nine mechanisms (ensuring rehabilitation teams' culture, fostering hope, exploring options, optimising self-efficacy, maintaining worker identity, staying connected, setting goals, engaging employer, and flexing roles) and three outcomes (confidence in ability to work, psychological adjustment, and engagement in solution focussed options). Conclusions This appears to be the first paper to explore how EIVR works, for whom and in what situations. We have produced a programme theory that may provide an initial understanding of EIVR following acquired neurological conditions.

How does small group continuing medical education (CME) impact on practice for rural GPs and their patients, a mixed-methods study.

Studies which report outcomes of continuing medical education (CME) interventions for rural general practitioners (GPs) are limited. This mixed methods study recruited GPs from four CME small group learning (SGL) tutor groups based in different rural locations in the Republic of Ireland. A two-hour teaching module on deprescribing in older patients was devised and implemented. Assessment of educational outcomes was via questionnaires, prescribing audits and qualitative focus groups. All GPs (n = 43) in these CME-SGL groups agreed to participate, 27 of whom (63%) self-identified as being in rural practice. Rural GPs were more likely to be male (56%), in practice for longer (19 years), and attending CME for longer (13 years). The questionnaires indicated learning outcomes were achieved knowledge increased immediately after the education, and was maintained 6 months later. Twenty-four GPs completed audits involving 191 patients. Of these, 152 (79.6%) were de-prescribed medication. In the qualitative focus groups, GPs reported sharing experiences with their peers during CME-SGL helped them to improve patient care and ensured that clinical practice is more consistent across the group. For rural GPs, CME-SGL involving discussion of cases and the practical implementation of guidelines, associated with audit, can lead to changes in patient care.

Interventions for preventing and treating cardiac complications in Duchenne and Becker muscular dystrophy and X-linked dilated cardiomyopathy.

BACKGROUND: The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further. OBJECTIVES: To assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months. SEARCH METHODS: On 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies. SELECTION CRITERIA: We considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria. MAIN RESULTS: We included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.The randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).A study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) -0.60% CI -6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).A study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD -0.20%, 95% CI -3.07 to 2.67, N = 21), and for ejection fraction the mean change was -1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD -2.30%, 95% CI -9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between the treatment and placebo groups (low-certainty evidence).A multicentre controlled study added eplerenone or placebo to 42 patients with DMD with early cardiomyopathy but preserved left ventricular function already established on ACEI or ARB therapy. Results showed that eplerenone slowed the rate of decline of magnetic resonance (MR)-assessed left ventricular circumferential strain at 12 months (eplerenone group median 1.0%, interquartile range (IQR) 0.3 to -2.2; placebo group median 2.2%, IQR 1.3 to -3.1%; P = 0.020). The median decline in LVEF over the same period was also less in the eplerenone group (-1.8%, IQR -2.9 to 6.0) than in the placebo group (-3.7%, IQR -10.8 to 1.0; P = 0.032). We downgraded the certainty of evidence to very low for study limitations and serious imprecision. Serious adverse events were reported in two patients given placebo but none in the treatment group (very low-certainty evidence).A randomised placebo-controlled study of subcutaneous growth hormone in 16 participants with DMD or BMD showed an increase in left ventricular mass after three months' treatment but no significant improvement in cardiac function. The evidence was of very low certainty due to imprecision, indirectness, and study limitations. There were no clinically significant adverse events (very low-certainty evidence).Some studies were at risk of bias, and all were small. Therefore, although there is some evidence from non-randomised data to support the prophylactic use of perindopril for cardioprotection ahead of detectable cardiomyopathy, and for lisinopril or losartan plus eplerenone once cardiomyopathy is detectable, this must be considered of very low certainty. Findings from non-randomised studies, some of which have been long term, have led to the use of these drugs in daily clinical practice. AUTHORS' CONCLUSIONS: Based on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.

Cardiac involvement in female carriers of duchenne or becker muscular dystrophy.

INTRODUCTION: The significance of abnormal cardiac measures in asymptomatic females who harbor dystrophin gene mutations is controversial. METHODS: Echo-measures of ventricular function were compared with published norms in a cross-sectional study of 130 (age, 39 ± 15.7 years) "carriers" of Duchenne or Becker muscular dystrophy (DMD/BMD). Correlations between cardiomyopathy (CM) and mutation, creatine kinase (CK) levels, age, and muscle symptoms were investigated. RESULTS: Depending on definition, CM prevalence was 3-33%. Ejection fraction (Simpson method) was < 55% in 9 (13%) and < 40% in 2 (2.9%). Eleven (8.5%) had wall motion abnormalities. Left ventricular end-systolic dimensions were increased in 7 (5.7%) and end-diastolic in 17 (13.9%). CM did not correlate with mutation type, DMD or BMD phenotype, CK level, muscle symptoms, or age. CONCLUSIONS: Occult CM can be found by screening in DMD/BMD carriers. Its lack of age-correlation suggests that not all abnormalities progress. Optimum screening schedules require a better understanding of progressive CM. Muscle Nerve 55: 810-818, 2017.

Atrial arrhythmia after transcatheter closure of secundum atrial septal defects in patients ≥40 years of age.

AIM: Data on arrhythmia outcome following device closure of atrial septal defect (ASD) are lacking. This study provides medium-term follow-up data on atrial arrhythmias in patients who were ≥40 years of age at the time of transcatheter ASD closure. METHODS AND RESULTS: It is a retrospective review. Mean age of the 159 patients was 57 years. Median follow-up was 3.6 years (range 6 months-10.9 years). Patients were classified, according to arrhythmia status prior to ASD closure, into Group I, no history of atrial arrhythmia (n = 119, mean age 55.5 years); Group II, paroxysmal atrial arrhythmia (n = 18, mean age 55.7 years); and Group III, persistent atrial fibrillation (n = 22, mean age 65.7 years). Group III patients were significantly older, had larger left atrial size, and had higher mean pulmonary arterial pressure than Group I and II patients (P < 0.001). Prior to closure, radiofrequency ablation was carried out in 12/18 (66%) of Group II and 3/22 (14%) of Group III. After device closure, 7 patients (6%) of Group I developed new atrial fibrillation. Fifty per cent (9/18) of Group II but only 9% (2/22) of Group III were in sinus rhythm on follow-up. CONCLUSION: Device closure alone in patients with persistent atrial arrhythmia is not likely to restore sinus rhythm in the medium term. New atrial arrhythmia occurred in 6% of patients who were in sinus rhythm prior to device closure. At least 50% of the patients with paroxysmal atrial arrhythmia continue to have significant atrial arrhythmia following device closure, and the role of ablation prior to closure in patients with a history of arrhythmia requires refinement.

Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults.

AIMS: To provide insight into the mechanism of sudden adult death syndrome (SADS) and to give new clinical guidelines for the cardiac management of patients with the most common mitochondrial DNA mutation, m.3243A>G. These studies were initiated after two young, asymptomatic adults harbouring the m.3243A>G mutation died suddenly and unexpectedly. The m.3243A>G mutation is present in ∼1 in 400 of the population, although the recognized incidence of mitochondrial DNA (mtDNA) disease is ∼1 in 5000. METHODS AND RESULTS: Pathological studies including histochemistry and molecular genetic analyses performed on various post-mortem samples including cardiac tissues (atrium and ventricles) showed marked respiratory chain deficiency and high levels of the m.3243A>G mutation. Systematic review of cause of death in our m.3243A>G patient cohort showed the person-time incidence rate of sudden adult death is 2.4 per 1000 person-years. A further six cases of sudden death among extended family members have been identified from interrogation of family pedigrees. CONCLUSION: Our findings suggest that SADS is an important cause of death in patients with m.3243A>G and likely to be due to widespread respiratory chain deficiency in cardiac muscle. The involvement of asymptomatic relatives highlights the importance of family tracing in patients with m.3243A>G and the need for specific cardiac arrhythmia surveillance in the management of this common genetic disease. In addition, these findings have prompted the derivation of cardiac guidelines specific to patients with m.3243A>G-related mitochondrial disease. Finally, due to the prevalence of this mtDNA point mutation, we recommend inclusion of testing for m.3243A>G mutations in the genetic autopsy of all unexplained cases of SADS.