A natural history study in Limb Girdle Muscular Dystrophy 2I : magnetic resonance imaging, spectroscopy and physical outcome measures

M.D.Limb Girdle Muscular Dystrophy 2I (LGMD2I) is caused by mutations in the fukutin related protein gene (FKRP). It is an important and frequent cause of LGMD, particularly in Northern Europe, and can range from a severe muscular dystrophy in childhood, very similar to Duchenne muscular dystrophy, to a much milder adult disease. Respiratory involvement and cardiomyopathy are common. This thesis aims to assess the natural history of a particular subset of this rare condition across four main European centres. Thirty eight ambulant LGMD2I patients from Newcastle, London, Paris and Copenhagen were recruited. The age range was 18-64 years and disease duration, 0-49 years. Magnetic resonance imaging (MRI) and Magnetic resonance spectroscopy (MRS) have both been performed. T1-weighted images were used to assess fat infiltration patterns using a qualitative radiological score and a quantitative 3-point Dixon technique, applied over two time points, and was performed to track the progression of fat infiltration. MRI fat infiltration has been correlated with muscle strength and function longitudinally. In the Newcastle upon Tyne cohort, cardiac MRI was also studied assessing the cardiac involvement in this condition. Chapter 1 presents an overview of muscular dystrophy and the current knowledge in LGMD2I and chapter 2 includes a literature review of both skeletal muscle and cardiac imaging. Chapter 3 focuses on the methodology of the study, including the patient demographics, physical assessment tools and MRI and MRS specifics. Chapters 4 -9 contain the results section; including physical and functional assessments, both cross-sectional and longitudinal, the cross sectional and longitudinal MRI results, skeletal MRS, cardiac MRI data and the FKRP registry respectively. Discussion of the results is found at the end of each chapter. Chapter 10 concludes with areas for future research

Bostonia: v. 63, no. 3

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

A pilot study of a single intermittent arm cycling exercise programme on people affected by Facioscapulohumeral dystrophy (FSHD)

For patients affected by Facioscapulohumeral dystrophy (FSHD), alternate methods for increasing physical activity engagement that may benefit shoulder function and wider health are needed. Arm cycling has been proposed as a potential method for achieving this although dosage parameters and evidence is limited. The aim of this study was to conduct a pilot study evaluating the effect of a single intermittent arm cycling exercise programme on people affected by FSHD. People with confirmed genetic diagnosis of FSHD between the ages 18–60 years were recruited to attend a single session for the exercise intervention (5 exercise efforts lasting 2 minutes each with 30 seconds of rest between each effort). Prior to exercise, measures of shoulder function (Oxford shoulder score), strength and range of movement were recorded. During the exercise participants were video recorded to quantify range of movement and extract movement profile features. Participants comments were recorded and followed up four days later to check for adverse events. Fifteen participants, (6F:9M) were recruited with median (IQR) Oxford Shoulder Scores of 25 (18 to 39). All participants successfully completed the exercise intervention with only transient symptoms consistent with exercise being reported and achieving a median (IQR) rate of perceived exertion scores of 13 (12 to 13). Movement profile data was available for 12 out of 15 participants and suggests that exercise intensity did not compromise movement. An association between strength and shoulder function (R2 = 0.5147), Rate of perceived exertion (RPE) of the final effort against shoulder function and strength (R2 = 0.2344 and 0.1743 respectively) was identified. Participant comments were positive regarding the exercise intervention. Our study demonstrates that an intermittent arm cycling programme is feasible for people affected by FSHD. Further work is needed to evaluate physiological responses to exercise across variations in programme variables and equipment set up in a larger sample of people affected by FSHD.Funder: The Orthopaedic Institute Limited; Grant(s): RPG16

A Recurrent Pathogenic Variant in TPM2 Reveals Further Phenotypic and Genetic Heterogeneity in Multiple Pterygium Syndrome-Related Disorders.

Multiple pterygium syndrome (MPS) disorders are a phenotypically and genetically heterogeneous group of conditions characterised by multiple joint contractures (arthrogryposis), pterygia (joint webbing) and other developmental defects. MPS is most frequently inherited in an autosomal recessive fashion but X-linked and autosomal dominant forms also occur. Advances in genomic technologies have identified many genetic causes of MPS-related disorders and genetic diagnosis requires large targeted next generation sequencing gene panels or genome-wide sequencing approaches. Using the Illumina TruSightOne clinical exome assay we identified a recurrent heterozygous missense substitution in TPM2 (encoding beta tropomyosin) in three unrelated individuals. This was confirmed to have arisen as a de novo event in the two patients with parental samples. TPM2 mutations have previously been described in association with a variety of dominantly inherited neuromuscular phenotypes including nemaline myopathy, congenital fibre-type disproportion, distal arthrogryposis and trismus pseudocamptodactyly, and in a patient with autosomal recessive Escobar syndrome and a nemaline myopathy. The three cases reported here had overlapping but variable features. Our findings expand the range of TMP2-related phenotypes and indicate that de novo TMP2 mutations should be considered in isolated cases of MPS-related conditions. This article is protected by copyright. All rights reserved

'Everyday Advocates’ for Inclusive Care?:Perspectives on Enhancing the Provision of Long-Term Care Services for Older Lesbian, Gay and Bisexual Adults in Wales

This paper centres on a neglected area of social work with older people—the social inclusion of older lesbian, gay and bisexual (LGB) adults in long-term care environments. The translation of equality law into the delivery of adult care services is a challenging endeavour for organisations, even more so in the morally contested terrain of sexual well-being. In this paper, we report findings from a mixed-methods study into the provision of long-term care for older adults who identify as LGB. Herein we present findings from a survey of care workers and managers (n = 121) and from focus groups with equality and LGB stakeholder representatives (n = 20) in Wales. Focusing on the current knowledge and understanding of staff, we suggest that affirmative beliefs and practices with sexual minorities are evident amongst care workers and managers; however, the inclusion of LGB residents needs to be advanced systemically at structural, cultural and individual levels of provision. There is a need for enhancing awareness of the legacy of enduring discrimination for older LGB people, for cultural acceptance in care environments of older people's sexual desires and relationships, and for a more explicit implementation of equality legislation. Social workers in adult care can advance this agenda

A pilot study of a single intermittent arm cycling exercise programme on people affected by Facioscapulohumeral dystrophy (FSHD)

From PLOS via Jisc Publications RouterHistory: received 2021-07-28, collection 2022, accepted 2022-05-06, epub 2022-06-24Publication status: PublishedFunder: The Orthopaedic Institute Limited; Grant(s): RPG162For patients affected by Facioscapulohumeral dystrophy (FSHD), alternate methods for increasing physical activity engagement that may benefit shoulder function and wider health are needed. Arm cycling has been proposed as a potential method for achieving this although dosage parameters and evidence is limited. The aim of this study was to conduct a pilot study evaluating the effect of a single intermittent arm cycling exercise programme on people affected by FSHD. People with confirmed genetic diagnosis of FSHD between the ages 18–60 years were recruited to attend a single session for the exercise intervention (5 exercise efforts lasting 2 minutes each with 30 seconds of rest between each effort). Prior to exercise, measures of shoulder function (Oxford shoulder score), strength and range of movement were recorded. During the exercise participants were video recorded to quantify range of movement and extract movement profile features. Participants comments were recorded and followed up four days later to check for adverse events. Fifteen participants, (6F:9M) were recruited with median (IQR) Oxford Shoulder Scores of 25 (18 to 39). All participants successfully completed the exercise intervention with only transient symptoms consistent with exercise being reported and achieving a median (IQR) rate of perceived exertion scores of 13 (12 to 13). Movement profile data was available for 12 out of 15 participants and suggests that exercise intensity did not compromise movement. An association between strength and shoulder function (R2 = 0.5147), Rate of perceived exertion (RPE) of the final effort against shoulder function and strength (R2 = 0.2344 and 0.1743 respectively) was identified. Participant comments were positive regarding the exercise intervention. Our study demonstrates that an intermittent arm cycling programme is feasible for people affected by FSHD. Further work is needed to evaluate physiological responses to exercise across variations in programme variables and equipment set up in a larger sample of people affected by FSHD

Upper limb rehabilitation in facioscapulohumeral dystrophy (FSHD): a patients perspective

Purpose: The study aims to identify exercise programmes used by Facioscapulohumeral dystrophy (FSHD) patients in the community, along with barriers and perceptions. Methods: A web based survey, distributed to patients on the UK FSHD registry, and focus groups were conducted. Thematic analysis was conducted on answers to survey questions supported by focus group notes, from seven FSHD patients. Results: A response rate of 43.6% was achieved with 232 out of 532 patients completing the survey. Only 44.4% engaged with exercises targeting the upper body. The themes from the data were: 1) Understanding of disease mechanism shaping exercise choice 2) Lack of understanding about the condition and how exercise interacts with it 3) Support from professionals 4) Barriers to exercise and 5) Thoughts about future research. Conclusion: Exercise selection was variable amongst FSHD patients. Lack of information, pain, fatigue, availability and access to facilities, cost and time were identified as barriers to exercise. Participants (92.2%) agreed additional research into upper limb exercises is needed and felt a 3-month arm cycling intervention with monthly clinical visits and MRI imaging would be appropriate. Further research is needed to develop evidence based exercise interventions and guidance for upper limb exercise prescription in FSHD.</jats:p

Upper Limb Rehabilitation in Facioscapulohumeral Muscular Dystrophy: A Patients' Perspective.

ObjectiveTo identify (1) what exercise modalities people living with facioscapulohumeral muscular dystrophy (FSHD) are undertaking in the community as a part of their ongoing rehabilitation and (2) what future research projects would gain the support of people with FSHD.DesignAn online questionnaire composed of open and closed questions. Conventional content analysis was used for open questions, and quantitative analysis was used for closed questions.SettingOnline questionnaire distributed to a United Kingdom FSHD registry.ParticipantsA total of 232 patients on the United Kingdom FSHD registry (N=232).InterventionsNone.Main outcome measuresNone.ResultsA response rate of 43.6% was achieved with 232 of 532 patients completing the survey. Despite 85.8% (n=199) of patients experiencing shoulder instability that affects daily living, only 44.4% (n=103) engaged with exercises targeting the upper body. The themes from the data were understanding of disease mechanism shaping exercise choice, lack of understanding about the condition and the benefit of exercise, support from professionals, barriers to exercise, and thoughts about future research. Participants (92.2%, n=214) agreed additional research into upper limb exercises is needed and felt a 3-month arm cycling intervention with monthly clinical visits and magnetic resonance imaging would be appropriate.ConclusionsExercise selection was variable among patients with FSHD, and lack of information, pain, fatigue, availability and access to facilities, cost, and time were identified as barriers to exercise. This may account for the limited engagement with upper limb rehabilitation despite the high percentage of shoulder instability in patients with FSHD. Further research is needed to develop evidence-based exercise interventions, and guidance for upper limb exercise prescription in FSHD, and patients are supportive of this

Does Media Affect Learning: Where Are We Now?

It is time to extinguish the argument as to whether or not the media of 1983 could, should or would affect learning outcomes. The technological advances that have occurred in the 20 years since Clark sparked the debate and Kozma fanned the flames have made the question irrelevant. High-speed, portable, reasonably priced computers, the Internet, and the World Wide Web have changed the face of how, when, and where learning occurs. The media of 2004 does affect learning. The question is no longer if; the question is how

Risdiplam in Spinal Muscular Atrophy: Safety Profile and Use Through The Early Access to Medicine Scheme for the Paediatric Cohort in Great Britain

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by mutations in Survival motor neuron 1 (SMN1) gene, leading to reduction in survival motor neuron protein (SMN), key for motor neuron survival and function in the brainstem and spinal cord. Risdiplam is an orally administered SMN2-splicing modifier which increases production of functional SMN protein. Risdiplam was offered in the UK under early access to medicines scheme (EAMS) to SMA type 1 and 2 patients aged 2 months and older, not suitable for authorised treatments from September 2020 to December 2021. OBJECTIVE: To describe the largest paediatric European real-world set of data on patients' characteristics and short-term safety for risdiplam in Great Britain through EAMS. METHODS: We collated data from SMA REACH UK a national clinical and research network for all patients enrolled onto EAMS and assessed all submitted adverse events. RESULTS: Of the 92 patients; 78% were Type 2 SMA, mean age 10.9 years, range 0-17 years. 56 were treatment naïve, 33 previously treated; of these 25 had received nusinersen, 3 previous treatment unknown. Sixty adverse events (AEs) were reported occurring in 34 patients. The commonest were respiratory tract infections and gastrointestinal disturbance. Four life-threatening events were reported with 2 deaths and permanent cessation of risdiplam in 3 patients.Overall, 38/60 AEs were considered unrelated to risdiplam, 10/60 related to risdiplam and for 12/60 causality not specified. CONCLUSIONS: This study found a safety profile similar to clinical trials with no new safety concerns identified. With the restricted eligibility of onasemnogene abeparvovec and complications of nusinersen administration, EAMS allowed access or continued treatment to naïve patients or patients no longer suitable for approved medications. Collection of longitudinal data for this complex population is needed, to provide greater insights into risdiplam's role in addressing patients' needs into the future