bims-curels 2024-12-08 papers

Issue of 2024–12–08
six papers selected by
Cure Mito Foundation

Am J Med Genet A. 2024 Dec 05. e63947

SURF1 Deficiency: Expanding on Disease Phenotype and Assessing Disease Burden by Describing Clinical and Biochemical Phenotype.

Saima Kayani, Victor Daescu, Hamza Dahshi, Souad Messahel, Kasey Woleban, Berge A Minassian, Qinglan Ling, Steven J Gray.

Leigh syndrome, a severe neurological disorder is commonly caused by homozygous or bi-allelic pathogenic variants in the SURF1 gene. SURF1 deficiency leads to dysfunction of Cytochrome C Oxidase (COX) activity, which is crucial for mitochondrial oxidative phosphorylation. Understanding COX activity's correlation with disease severity is essential for developing SURF1 Leigh Syndrome biomarkers. This study assesses the disease burden in SURF1 Leigh Syndrome and evaluates COX activity as a treatment biomarker. We reviewed records and questionnaires from 17 individuals, classifying them into phenotypic and genotypic groups. We compared COX activity assays in patient fibroblasts to age-matched controls, clinical data, and neuroimaging findings. Patient COX activity was at most 50% of controls, averaging 32% (p < 0.001). Common clinical features included brainstem abnormalities (93.3%), motor regression (92.3%), bi-allelic heterozygous SURF1 variants (88.2%), and delayed growth/development (35.7%). Homozygous and heterozygous nonsense/frameshift variants showed more severe phenotypes (p = 0.008) and more MRI abnormalities (p = 0.005). Significant COX activity reduction is linked to SURF1 Leigh Syndrome, with genotype influencing disease severity. Clinical and neuroimaging correlations show potential for prognostic indicators. This study lays the groundwork for future research and clinical application of COX activity as a SURF1 Leigh Syndrome biomarker.

Keywords: Leigh syndrome; SURF1 gene; biomarkers; cytochrome C oxidase; mitochondrial disorders; neuroimaging

DOI: https://doi.org/10.1002/ajmg.a.63947

Clin Case Rep. 2024 Dec;12(12): e9591

Expanded-Access Use of Elamipretide Improves Quality of Life in Patients With Rare Mitochondrial Disorders Characterized by Ophthalmic Symptoms: A Case Series.

Sharique Ansari, Mary Kay Koenig.

This case series presents the use of elamipretide in two patients with different progressive mitochondrial disorders (chronic progressive external ophthalmoplegia [CPEO] plus and neuropathy, ataxia, and retinitis pigmentosa [NARP] syndrome) characterized by ophthalmic traits. Elamipretide was well tolerated and both patients demonstrated improvement in symptoms while on therapy.

Keywords: CPEO; Cardiolipin; Elamipretide; NARP syndrome; mitochondrial disease

DOI: https://doi.org/10.1002/ccr3.9591

J Patient Rep Outcomes. 2024 Dec 02. 8(1): 139

Reflection on a professional advisory group to inform the use of patient empowerment tools within an implementation science research project.

Katherine E Woolley, Nia J Jones, Robert Letchford, Kathleen L Withers.

Professional advisory groups, with patient and public involvement (PPI) representatives, can be used for co-production within research projects. This paper aims to document the benefits and challenges of undertaking stakeholder and participant engagement for an implementation research project within NHS (National Health Service) Wales. A patient focused research project, initiated by clinicians, on the use of patient empowerment tools within standard patient care, used a professional advisory group to identify appropriate tools to use within the research proposal. The professional advisory group was made up of therapists, NHS stakeholders, academics and PPI representatives. A hybrid-meeting style was employed to optimise participation for all members of the group. Benefits of the professional advisory group included increased engagement and ownership of the study due to co-creation, and obtaining important contextual information and lived experience. However, challenges included keeping the discussion on topic due to pre-conceived agendas, pleasing everyone in the room due to varied backgrounds, and technological issues. Future professional advisory groups should consider how to facilitate the full involvement of PPI representatives within the discussion and having a variety of resources to present the topic of discussion. Furthermore, clearly communicating what the purpose and direction of the research project is and how it fits into the wider system, should be carefully considered. Overall, it was recognised that the professional advisory group was of significant value to shape the research proposal. Due to the situational challenges faced by healthcare professional within the NHS and preconceived ideas for solutions, it is hoped that by involving stakeholders early in the process there will be greater acceptance and usability of the research findings.

Keywords: Patient activation; Patient and public involvement; Patient participation; Professional advisory group; Proposal development; Stakeholders

DOI: https://doi.org/10.1186/s41687-024-00811-y

BMC Med. 2024 12 04. 22(1): 577

Ethics practices associated with reusing health data: an assessment of patient registries.

Olmo R van den Akker, Susanne Stark, Daniel Strech.

BACKGROUND: As routinely collected patient data have become increasingly accessible over the years, more attention has been directed at the ethics of using such data for research. Patient data is often available to researchers through patient registries that typically collect data of patients with a specific condition. While ethical guidelines for using patient data are presented frequently in the literature, it is currently unknown how patient registries implement the recommendations from these guidelines in practice and how they communicate their practices. In this project, we assessed to what extent a sample of 51 patient registries provides information about a range of ethics practices.
METHODS: We searched for patient registries in the resource database of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Our ethics reporting checklist was based on three sources: the Registry Evaluation and Quality Standards Tool (REQueST), the Agency for Healthcare Research and Quality (AHRQ) guide for good registry practices, and a systematic review of the principles and norms related to health data sharing by Kalkman and colleagues. The checklist includes 26 questions about five ethics components: governance, conflicts of interest, informed consent, privacy and data protection, and use-and-access.
RESULTS: We found substantial heterogeneity in the way patient registries provide information about ethics practices. Patient registries often mentioned their governance structure and any potential conflicts of interests but typically did not describe the responsibilities and rights allocated to their funders. Information about informed consent was often provided to patients, but the available documents often lacked relevant information like the benefits and risks of participation. Privacy and data protection and use-and-access policies were typically discussed but not very concretely.
CONCLUSIONS: We conclude that registries typically provide information about key ethics practices such as governance, conflicts of interest, informed consent, privacy and data protection, and use-and-access procedures, but this information is often not as detailed as recommended in existing guidelines. The ethics reporting checklist we designed could be helpful for the ethical assessments of patient registries and other types of registries in the future as well as for self-assessment of registries aiming to improve their ethics practices.

Keywords: Conflicts of interest; Governance; Health data; Informed consent; Patient registries; Privacy and data protection; Secondary use; Use-and-access

DOI: https://doi.org/10.1186/s12916-024-03799-w

J Clin Transl Sci. 2024 ;8(1): e167

Clinical researchers' insights on key data for eligibility screening in clinical studies.

Betina Idnay, Emily R Gordon, Aubrey S Johnson, Jordan G Nestor, Karen Marder, Chunhua Weng.

Introduction: Clinical research is critical for healthcare advancement, but participant recruitment remains challenging. Clinical research professionals (CRPs; e.g., clinical research coordinator, research assistant) perform eligibility prescreening, ensuring adherence to study criteria while upholding scientific and ethical standards. This study investigates the key information CRP prioritizes during eligibility prescreening, providing insights to optimize data standardization, and recruitment approaches.
Methods: We conducted a freelisting survey targeting 150 CRPs from diverse domains (i.e., neurological disorders, rare diseases, and other diseases) where they listed essential information they look for from medical records, participant/caregiver inquiries, and discussions with principal investigators to determine a potential participant's research eligibility. We calculated the salience scores of listed items using Anthropac, followed by a two-level analytic procedure to classify and thematically categorize the data.
Results: The majority of participants were female (81%), identified as White (44%) and as non-Hispanic (64.5%). The first-level analysis universally emphasized age, medication list, and medical history across all domains. The second-level analysis illuminated domain-specific approaches in information retrieval: for instance, history of present illness was notably significant in neurological disorders during participant and principal investigator inquiries, while research participation was distinctly salient in potential participant inquiries within the rare disease domain.
Conclusion: This study unveils the intricacies of eligibility prescreening, with both universal and domain-specific methods observed. Variations in data use across domains suggest the need for tailored prescreening in clinical research. Incorporating these insights into CRP training and refining prescreening tools, combined with an ethical, participant-focused approach, can advance eligibility prescreening practices.

Keywords: Informatics; clinical research; clinical research staff; eligibility prescreening; freelisting

DOI: https://doi.org/10.1017/cts.2024.617