bims-curels 2023-05-28 papers

bims-curels

Biomed News

on Leigh syndrome

Issue of 2023–05–28
seven papers selected by
Cure Mito Foundation

Leigh syndrome mimicking neuromyelitis optica spectrum disorder (NMOSD).
Evaluation of the quality of patient involvement in a patient-led analysis of the lived experience of a rare disease.
Mitochondrial Mutations Can Alter Neuromuscular Transmission in Congenital Myasthenic Syndrome and Mitochondrial Disease.
Clinical, Genetic, and Histological Characterization of Patients with Rare Neuromuscular and Mitochondrial Diseases Presenting with Different Cardiomyopathy Phenotypes.
Patient-Guided Tours: A Patient-Centered Methodology to Understand Patient Experiences of Health Care.
Global reach of over 20 years of experience in the patient-centered Fabry Registry: Advancement of Fabry disease expertise and dissemination of real-world evidence to the Fabry community.
Practical Benefits, Challenges, and Recommendations on Social Media Recruitment: Multi-Stakeholder Interview Study.

Mult Scler. 2023 May 25. 13524585231172950

Leigh syndrome mimicking neuromyelitis optica spectrum disorder (NMOSD).

Nee Na Kim, Omar Abdel-Mannan, James Davidson, Pascale Du Pre, Rachel Kneen, Kshitij Mankad, Yael Hacohen.

  We report two children with molecularly confirmed mitochondrial disease mimicking Neuromyelitis Optica Spectrum Disorder (NMOSD). The first patient presented at the age of 15 months with acute deterioration following a pyrexial illness with clinical features localising to the brainstem and spinal cord. The second patient presented at 5 years with acute bilateral visual loss. In both cases, MOG and AQP4 antibodies were negative. Both patients died within a year of symptoms onset from respiratory failure. Arriving at an early genetic diagnosis is important for redirection of care and avoiding potentially harmful immunosuppressant therapies.

Keywords:  Neuromyelitis optica spectrum disorder; acquired demyelinating syndromes; mitochondrial diseases; neurogenetics

DOI:  https://doi.org/10.1177/13524585231172950
Res Involv Engagem. 2023 May 25. 9(1): 35

Evaluation of the quality of patient involvement in a patient-led analysis of the lived experience of a rare disease.

Dawn Lobban, Jacqui Oliver, Kelly Davio, Kenza Seddik, Veronica Porkess.

   BACKGROUND: Patients themselves are best placed to provide insights on the lived experience and to lead the analysis of such insights to bring the patient voice into peer-reviewed literature. In doing so, they can meet the authorship criteria for subsequent research publications. It is important to evaluate patient engagement to identify ways to improve future collaborations. Here, we describe the approach taken during a patient-led and patient co-authored analysis of the lived experience of generalized myasthenia gravis, which may be applicable to other indications. We also assessed the quality of patient engagement throughout the research project.
METHODS: We used self-reported experience surveys based on the Patient Focused Medicines Development Patient Engagement Quality Guidance criteria for assessing patient engagement. The surveys were adapted to focus on individual projects and assessed eight domains using a five-point Likert scale. In September 2020, we invited eight patient council members to complete a self-reported experience survey following qualitative lived experience data generation. We calculated the average experience score as a percentage of the maximum possible score. Patient authors (n = 1) and non-patient authors (n = 3) were invited to complete a similar survey in November 2021, with questions customized for relevance, to evaluate the authorship experience following publication of the research.
RESULTS: Overall, patient council members had a positive experience of taking part in this study, with an average experience score of 90% (71.6/80.0; n = 8). The patient author and non-patient authors rated their authorship experience highly, with average experience scores of 92% (78.0/85.0) and 97% (63.3/65.0), respectively. There were key aspects that contributed to the overall project success (e.g., ensuring that all participants were aligned on the project objectives at the outset and understood their roles and responsibilities). We also identified elements of the approach that could be improved in future collaborations.
CONCLUSION: In this patient-led analysis, patient council members, patient authors and non-patient authors had a positive experience of being involved in the project. We gained useful insights into elements that contributed to the project's success and ways to improve future patient-led projects on the lived experience.

Keywords:  Lived experience; Myasthenia gravis; Patient and public involvement; Patient author; Patient perspective; Qualitative research

DOI:  https://doi.org/10.1186/s40900-023-00445-2
Int J Mol Sci. 2023 May 09. pii: 8505. [Epub ahead of print]24(10):

Mitochondrial Mutations Can Alter Neuromuscular Transmission in Congenital Myasthenic Syndrome and Mitochondrial Disease.

Kaela O'Connor, Sally Spendiff, Hanns Lochmüller, Rita Horvath.

  Congenital myasthenic syndromes (CMS) are a group of rare, neuromuscular disorders that usually present in childhood or infancy. While the phenotypic presentation of these disorders is diverse, the unifying feature is a pathomechanism that disrupts neuromuscular transmission. Recently, two mitochondrial genes-SLC25A1 and TEFM-have been reported in patients with suspected CMS, prompting a discussion about the role of mitochondria at the neuromuscular junction (NMJ). Mitochondrial disease and CMS can present with similar symptoms, and potentially one in four patients with mitochondrial myopathy exhibit NMJ defects. This review highlights research indicating the prominent roles of mitochondria at both the pre- and postsynapse, demonstrating the potential for mitochondrial involvement in neuromuscular transmission defects. We propose the establishment of a novel subcategorization for CMS-mitochondrial CMS, due to unifying clinical features and the potential for mitochondrial defects to impede transmission at the pre- and postsynapse. Finally, we highlight the potential of targeting the neuromuscular transmission in mitochondrial disease to improve patient outcomes.

Keywords:  SLC25A1; TEFM; congenital myasthenic syndrome; mitochondria; mitochondrial disease; neuromuscular; neuromuscular junction

DOI:  https://doi.org/10.3390/ijms24108505
Int J Mol Sci. 2023 May 22. pii: 9108. [Epub ahead of print]24(10):

Clinical, Genetic, and Histological Characterization of Patients with Rare Neuromuscular and Mitochondrial Diseases Presenting with Different Cardiomyopathy Phenotypes.

Emanuele Monda, Michele Lioncino, Martina Caiazza, Vincenzo Simonelli, Claudia Nesti, Marta Rubino, Alessia Perna, Alfredo Mauriello, Alberta Budillon, Vincenzo Pota, Giorgia Bruno, Antonio Varone, Vincenzo Nigro, Filippo Maria Santorelli, Giuseppe Pacileo, Maria Giovanna Russo, Giulia Frisso, Simone Sampaolo, Giuseppe Limongelli.

  Cardiomyopathies are mostly determined by genetic mutations affecting either cardiac muscle cell structure or function. Nevertheless, cardiomyopathies may also be part of complex clinical phenotypes in the spectrum of neuromuscular (NMD) or mitochondrial diseases (MD). The aim of this study is to describe the clinical, molecular, and histological characteristics of a consecutive cohort of patients with cardiomyopathy associated with NMDs or MDs referred to a tertiary cardiomyopathy clinic. Consecutive patients with a definitive diagnosis of NMDs and MDs presenting with a cardiomyopathy phenotype were described. Seven patients were identified: two patients with ACAD9 deficiency (Patient 1 carried the c.1240C>T (p.Arg414Cys) homozygous variant in ACAD9; Patient 2 carried the c.1240C>T (p.Arg414Cys) and the c.1646G>A (p.Ar549Gln) variants in ACAD9); two patients with MYH7-related myopathy (Patient 3 carried the c.1325G>A (p.Arg442His) variant in MYH7; Patient 4 carried the c.1357C>T (p.Arg453Cys) variant in MYH7); one patient with desminopathy (Patient 5 carried the c.46C>T (p.Arg16Cys) variant in DES); two patients with mitochondrial myopathy (Patient 6 carried the m.3243A>G variant in MT-TL1; Patient 7 carried the c.253G>A (p.Gly85Arg) and the c.1055C>T (p.Thr352Met) variants in MTO1). All patients underwent a comprehensive cardiovascular and neuromuscular evaluation, including muscle biopsy and genetic testing. This study described the clinical phenotype of rare NMDs and MDs presenting as cardiomyopathies. A multidisciplinary evaluation, combined with genetic testing, plays a main role in the diagnosis of these rare diseases, and provides information about clinical expectations, and guides management.

Keywords:  cardiomyopathy; genetic testing; neuromuscular disease

DOI:  https://doi.org/10.3390/ijms24109108
Ann Fam Med. 2023 May-Jun;21(3):21(3): 269-273

Patient-Guided Tours: A Patient-Centered Methodology to Understand Patient Experiences of Health Care.

Sakina Walji, June Carroll.

   PURPOSE: The experience-based design approach using patient-guided tours (PGT) has been suggested as an effective way to understand the patient experience and may better allow the patient to recall thoughts and feelings. The objective of this study was to assess how patients with a disability perceive the effectiveness of PGTs for understanding their experiences of receiving primary health care.
METHODS: A qualitative study design was used. Participants were chosen by convenience sampling. The patient was asked to walk through the clinic as they would on a "typical visit" while describing their experiences. They were questioned about their experience and perception of PGTs. The tour was audiotaped and transcribed. The investigators took field notes and completed thematic content analysis.
RESULTS: Eighteen patients participated. The main findings were: (1) Touchpoints and physical cues were effective in eliciting experiences that participants stated they would not have recalled using other research methods, (2) The ability for participants to show the investigator aspects of the space that impacted their experience enabled the investigator to "see through their eyes" resulting in ease of communication and a sense of empowerment, (3) PGTs encouraged individuals to be active participants which fostered comfort and collaboration, and (4) PGTs may exclude those that are severely disabled.
CONCLUSION: This method was perceived as effective at eliciting experiences of patients with a disability. It has benefits over more traditional research methods by allowing the participant to refresh their memory at "touchpoints" and enabling them to be active participants.

Keywords:  experience-based design; patient-guided tour; patients with disabilities; qualitative research methodology; touchpoints

DOI:  https://doi.org/10.1370/afm.2971
Mol Genet Metab. 2023 Apr 29. pii: S1096-7192(23)00233-0. [Epub ahead of print]139(3): 107603

Global reach of over 20 years of experience in the patient-centered Fabry Registry: Advancement of Fabry disease expertise and dissemination of real-world evidence to the Fabry community.

Christoph Wanner, Alberto Ortiz, William R Wilcox, Robert J Hopkin, Jack Johnson, Elvira Ponce, Johan T Ebels, Julie L Batista, Manish Maski, Juan M Politei, Ana Maria Martins, Maryam Banikazemi, Aleš Linhart, Michael Mauer, João P Oliveira, Frank Weidemann, Dominique P Germain.

  Fabry disease (FD, α-galactosidase A deficiency) is a rare, progressive, complex lysosomal storage disorder affecting multiple organ systems with a diverse spectrum of clinical phenotypes, particularly among female patients. Knowledge of its clinical course was still limited in 2001 when FD-specific therapies first became available and the Fabry Registry (NCT00196742; sponsor: Sanofi) was initiated as a global observational study. The Fabry Registry has now been operational for over 20 years, overseen by expert Boards of Advisors, and has collected real-world demographic and longitudinal clinical data from more than 8000 individuals with FD. Leveraging the accumulating evidence base, multidisciplinary collaborations have resulted in the creation of 32 peer-reviewed scientific publications, which have contributed to the greatly expanded knowledge on the onset and progression of FD, its clinical management, the role of sex and genetics, the outcomes of enzyme replacement therapy with agalsidase beta, and prognostic factors. We review how the Fabry Registry has evolved from its inception to become the largest global source of real-world FD patient data, and how the generated scientific evidence has helped to better inform the medical community, individuals living with FD, patient organizations, and other stakeholders. The patient-centered Fabry Registry fosters collaborative research partnerships with the overarching goal of optimizing the clinical management of patients with FD and is well positioned to add to its past achievements.

Keywords:  Fabry disease; Registry; agalsidase beta; enzyme replacement therapy; natural history; real-world data

DOI:  https://doi.org/10.1016/j.ymgme.2023.107603
J Med Internet Res. 2023 May 22. 25 e44587

Practical Benefits, Challenges, and Recommendations on Social Media Recruitment: Multi-Stakeholder Interview Study.

Nina Goldman, Theresa Willem, Alena Buyx, Bettina M Zimmermann.

   BACKGROUND: The increasing use of social media opens new opportunities for recruiting patients for research studies. However, systematic evaluations indicate that the success of social media recruitment in terms of cost-effectiveness and representativeness depends on the type of study and its purpose.
OBJECTIVE: This study aims to explore the practical benefits and challenges of recruiting study participants with social media in the context of clinical and nonclinical studies and provide a summary of expert advice on how to conduct social media-based recruitment.
METHODS: We conducted semistructured interviews with 6 patients with hepatitis B who use social media and 30 experts from the following disciplines: (1) social media researchers or social scientists, (2) practical experts for social media recruitment, (3) legal experts, (4) ethics committee members, and (5) clinical researchers. The interview transcripts were analyzed using thematic analysis.
RESULTS: We found diverging expert opinions regarding the challenges and benefits of social media recruitment for research studies in four domains: (1) resources needed, (2) representativeness, (3) web-based community building, and (4) privacy considerations. Moreover, the interviewed experts provided practical advice on how to promote a research study via social media.
CONCLUSIONS: Even though recruitment strategies should always be sensitive to individual study contexts, a multiplatform approach (recruiting via several different social media platforms) with mixed-methods recruitment (web-based and offline recruitment channels) is the most beneficial recruitment strategy for many research studies. The different recruitment methods complement each other and may contribute to improving the reach of the study, the recruitment accrual, and the representativeness of the sample. However, it is important to assess the context- and project-specific appropriateness and usefulness of social media recruitment before designing the recruitment strategy.

Keywords:  benefits; challenges; interview; medical study; recommendations; recruitment; research study; social media; strategy

DOI:  https://doi.org/10.2196/44587