bims-curels Biomed News
on Leigh syndrome
Issue of 2023–06–25
thirteen papers selected by
Cure Mito Foundation
  1. Metabolic inflexibility and unusual catabolism in Leigh-like syndrome due to m.10191T>C.
  2. Ethical Considerations in Clinical Trials for Rare Genetic Diseases: The Case of Huntington's Disease.
  3. A comprehensive study of the rare diseases and conditions targeted by orphan drug designations and approvals over the forty years of the Orphan Drug Act.
  4. Who Is Responsible for Promoting Equity in Rare Disease Research?
  5. Rare Disease, Advocacy, and Caregiver Burnout.
  6. The evolution of the mitochondrial disease diagnostic odyssey.
  7. Patient and research groups team up to push government for clinical trial transparency.
  8. Emerging healthcare interventions: Patient-Centered Outcomes Research Institute's programmatic initiative.
  9. Reliance on Advocacy is the Symptom Not the Disease.
  10. Frequency-based rare diagnoses as a novel and accessible approach for studying rare diseases in large datasets: a cross-sectional study.
  11. Benchmarking Patient Engagement Capabilities and Preparedness of Drug Development Sponsors.
  12. "Because it is a rare disease…it needs to be brought to attention that there are things out of the norm": a qualitative study of patient and physician experiences of Wilson disease diagnosis and management in the US.
  13. Do Hospitals Satisfy Our Healthcare Information Needs for Rare Diseases?: Comparison of Healthcare Information Provided by Hospitals with Information Needs of Family Caregivers.
  1. Clin Nutr ESPEN. 2023 08;pii: S2405-4577(23)00131-6. [Epub ahead of print]56 149-151
    Metabolic inflexibility and unusual catabolism in Leigh-like syndrome due to m.10191T>C.
    Shaundra M Newstead, Josef Finsterer.
       BACKGROUND AND AIMS: Hypercatabolism is a well-known feature of mitochondrial diseases but some patients may present with hypometabolism, as the following case.
    METHODS: Case report using standard investigation methods.
    RESULTS: The patient is a 32 years-old female with a Leigh-like syndrome due to the mtDNA variant m.10191 T > C in MT-ND3. Leigh-like syndrome is characterized by symmetric basal ganglia or brainstem lesions plus involvement of organs other than the brain. The patient presented with hypometabolism, which did not respond to ketogenic diet but responded to fasting. The patient showed a Warburg-like effect, which resulted in reliance on glucose due to the exclusion of oxidative phosphorylation with an extremely low VO2max. The patient only entered substantial ketosis when all gluconeogenic substrates were removed. Prolonged survival in the index patient may have possibly resulted from this previously unreported protective mechanism to reduce oxidative stress. The unusual Warburg-like phenomenon was interpreted as a possible mechanism of patients with a mitochondrial disease to survive into adulthood.
    CONCLUSIONS: This case shows that mitochondrial disease can manifest with hypometabolism and that an unusual Warburg-like effect may be responsible in some patients with mitochondrial disease to survive into adulthood.
    Keywords:  Ketogenic diet; Leigh-like syndrome; Mitochondrial disease; Respiratory chain; Warburg effect
    DOI:  https://doi.org/10.1016/j.clnesp.2023.05.007
  2. Am J Bioeth. 2023 07;23(7): 94-96
    Ethical Considerations in Clinical Trials for Rare Genetic Diseases: The Case of Huntington's Disease.
    Adys Mendizabal, Nora L Jones.
      
    DOI:  https://doi.org/10.1080/15265161.2023.2207511
  3. Orphanet J Rare Dis. 2023 Jun 23. 18(1): 163
    A comprehensive study of the rare diseases and conditions targeted by orphan drug designations and approvals over the forty years of the Orphan Drug Act.
    Lewis J Fermaglich, Kathleen L Miller.
       BACKGROUND: Rare diseases affect more than 30 million Americans. The passage of the Orphan Drug Act (ODA) in the United States in 1983 represented a launching point for a rare disease drug development revolution for these patients. Financial incentives provided by the ODA through its Orphan Drug Designation Program, in addition to remarkable scientific advances over the past 40 years, have led to hundreds of drug approvals for rare diseases. Our research examines the rare diseases that have been targeted by orphan drug designations and subsequent approvals since the law was enacted.
    METHODS: Using an internal FDA database, we classified and analyzed all orphan drug designations and approvals from 1983 to 2022 by disease and therapeutic area.
    RESULTS: Over the 40 years of the ODA, 6,340 orphan drug designations were granted, representing drug development for 1,079 rare diseases. Additionally, 882 of those designations resulted in at least one FDA approval for use in 392 rare diseases. Much of this development has been concentrated in oncology as seven of the top ten most designated and approved diseases were rare cancers.
    CONCLUSIONS: Researchers have estimated that there may be 7000-10,000 rare diseases that have been identified and described. Based on our study, we can conclude that around 5% of rare diseases have an FDA-approved drug and up to 15% of rare diseases have at least one drug that has been developed and shown promise in their treatment, diagnosis or prevention. Funding of basic and translational science for rare disease drug development should continue in order to bring therapies to the millions of affected patients who remain without treatment options.
    DOI:  https://doi.org/10.1186/s13023-023-02790-7
  4. Am J Bioeth. 2023 07;23(7): 83-85
    Who Is Responsible for Promoting Equity in Rare Disease Research?
    Matthew S McCoy.
      
    DOI:  https://doi.org/10.1080/15265161.2023.2207512
  5. Am J Bioeth. 2023 07;23(7): 91-94
    Rare Disease, Advocacy, and Caregiver Burnout.
    Gretchen Agans.
      
    DOI:  https://doi.org/10.1080/15265161.2023.2207509
  6. Orphanet J Rare Dis. 2023 Jun 22. 18(1): 157
    The evolution of the mitochondrial disease diagnostic odyssey.
    John L P Thompson, Amel Karaa, Hung Pham, Philip Yeske, Jeffrey Krischer, Yi Xiao, Yuelin Long, Amanda Kramer, David Dimmock, Amy Holbert, Cliff Gorski, Kristin M Engelstad, Richard Buchsbaum, Xiomara Q Rosales, Michio Hirano.
       BACKGROUND: Mitochondrial diseases often require multiple years and clinicians to diagnose. We lack knowledge of the stages of this diagnostic odyssey, and factors that affect it. Our goals are to report the results of the 2018 Odyssey2 (OD2) survey of patients with a medical diagnosis of mitochondrial disease; and to propose steps to reduce the odyssey going forward, and procedures to evaluate them.
    METHODS: Data are from the NIH-funded NAMDC-RDCRN-UMDF OD2 survey (N = 215). The main outcomes are Time from symptom Onset to mitochondrial disease Diagnosis (TOD) and Number of Doctors Seen during this diagnostic process (NDOCS).
    RESULTS: Expert recoding increased analyzable responses by 34% for final mitochondrial diagnosis and 39% for prior non-mitochondrial diagnosis. Only one of 122 patients who initially saw a primary care physician (PCP) received a mitochondrial diagnosis, compared to 26 of 86 (30%) who initially saw a specialist (p < 0.001). Mean TOD overall was 9.9 ± 13.0 years, and mean NDOCS 6.7 ± 5.2. Mitochondrial diagnosis brings extensive benefits through treatment changes and increased membership in and support of advocacy groups.
    CONCLUSIONS: Because TOD is long and NDOCS high, there is great potential for shortening the mitochondrial odyssey. Although prompt patient contact with primary mitochondrial disease specialists, or early implementation of appropriate tests, may shorten the diagnostic odyssey, specific proposals for improvement require testing and confirmation with adequately complete, unbiased data across all its stages, and appropriate methods. Electronic Health Record (EHRs) may help by accessing diagnostic codes early, but their reliability and diagnostic utility have not been established for this group of diseases.
    DOI:  https://doi.org/10.1186/s13023-023-02754-x
  7. BMJ. 2023 06 19. 381 1392
    Patient and research groups team up to push government for clinical trial transparency.
    Elisabeth Mahase.
      
    DOI:  https://doi.org/10.1136/bmj.p1392
  8. Int J Technol Assess Health Care. 2023 Jun 20. 39(1): e36
    Emerging healthcare interventions: Patient-Centered Outcomes Research Institute's programmatic initiative.
    Gowri Raman, Meghana Vijaysimha, Emma Kopleff, Kelly Dunham, Greg Martin, Jean Slutsky, William Lawrence.
      The Patient-Centered Outcomes Research Institute (PCORI) is a nonprofit, nongovernmental organization established by the U.S. Congress to fund comparative clinical effectiveness research focusing on patient-centered outcomes through the engagement of stakeholders. Evaluation of emerging healthcare innovations is one of PCORI's five National Priorities for Health. One such initiative is PCORI's Emerging Technologies and Therapeutics Reports program, established to provide timely overviews of evidence on new drugs and other healthcare technologies. This article provides an overview of completed and ongoing Emerging Technologies and Therapeutics Reports including lessons learned to date. In addition to systematic searches, systematic selection of studies, and transparent reporting of the available evidence, informed by a select number of stakeholders (i.e., key informants), these reports focus on contextual factors shaping the diffusion of emerging technologies that are often not reported in the medical literature. This article also compares processes and methodologies of health technology assessments (HTAs) from a selected number of national and international publicly funded agencies with a goal toward potential future enhancement of PCORI's Emerging Technologies and Therapeutics Reports program. HTAs vary considerably in terms of funding, types of assessments, the role of manufacturers, stakeholder engagement, timeline to complete from the start to the finish of a draft report publication, and communication of uncertainty for informed decision making. Future Emerging Technologies and Therapeutics Reports may focus on rapid reports to support a more expedient development of evidence. Future research could explore the role of contextual factors identified in these reports on targeted evidence generation.
    Keywords:  PCORI; emerging technology; emerging therapeutics; health technology assessments; stakeholder engagement
    DOI:  https://doi.org/10.1017/S0266462323000284
  9. Am J Bioeth. 2023 07;23(7): 86-88
    Reliance on Advocacy is the Symptom Not the Disease.
    Lynette Hammond Gerido.
      
    DOI:  https://doi.org/10.1080/15265161.2023.2207540
  10. BMC Med Res Methodol. 2023 Jun 17. 23(1): 143
    Frequency-based rare diagnoses as a novel and accessible approach for studying rare diseases in large datasets: a cross-sectional study.
    Thomas S Tröster, Viktor von Wyl, Patrick E Beeler, Holger Dressel.
       BACKGROUND: Up to 8% of the general population have a rare disease, however, for lack of ICD-10 codes for many rare diseases, this population cannot be generically identified in large medical datasets. We aimed to explore frequency-based rare diagnoses (FB-RDx) as a novel method exploring rare diseases by comparing characteristics and outcomes of inpatient populations with FB-RDx to those with rare diseases based on a previously published reference list.
    METHODS: Retrospective, cross-sectional, nationwide, multicenter study including 830,114 adult inpatients. We used the national inpatient cohort dataset of the year 2018 provided by the Swiss Federal Statistical Office, which routinely collects data from all inpatients treated in any Swiss hospital. Exposure: FB-RDx, according to 10% of inpatients with the least frequent diagnoses (i.e.1.decile) vs. those with more frequent diagnoses (deciles 2-10). Results were compared to patients having 1 of 628 ICD-10 coded rare diseases.
    PRIMARY OUTCOME: In-hospital death.
    SECONDARY OUTCOMES: 30-day readmission, admission to intensive care unit (ICU), length of stay, and ICU length of stay. Multivariable regression analyzed associations of FB-RDx and rare diseases with these outcomes.
    RESULTS: 464,968 (56%) of patients were female, median age was 59 years (IQR: 40-74). Compared with patients in deciles 2-10, patients in the 1. were at increased risk of in-hospital death (OR 1.44; 95% CI: 1.38, 1.50), 30-day readmission (OR 1.29; 95% CI 1.25, 1.34), ICU admission (OR 1.50; 95% CI 1.46, 1.54), increased length of stay (Exp(B) 1.03; 95% CI 1.03, 1.04) and ICU length of stay (1.15; 95% CI 1.12, 1.18). ICD-10 based rare diseases groups showed similar results: in-hospital death (OR 1.82; 95% CI 1.75, 1.89), 30-day readmission (OR 1.37; 95% CI 1.32, 1.42), ICU admission (OR 1.40; 95% CI 1.36, 1.44) and increased length of stay (OR 1.07; 95% CI 1.07, 1.08) and ICU length of stay (OR 1.19; 95% CI 1.16, 1.22).
    CONCLUSION(S): This study suggests that FB-RDx may not only act as a surrogate for rare diseases but may also help to identify patients with rare disease more comprehensively. FB-RDx associate with in-hospital death, 30-day readmission, intensive care unit admission, and increased length of stay and intensive care unit length of stay, as has been reported for rare diseases.
    Keywords:  Rare disease [MAJR]; Rare diseases/epidemiology [MeSH Terms]; Rare diseases/mortality [MeSH Terms]; Rare diseases/statistics and numerical data [MeSH Terms]
    DOI:  https://doi.org/10.1186/s12874-023-01972-y
  11. Ther Innov Regul Sci. 2023 Jun 19.
    Benchmarking Patient Engagement Capabilities and Preparedness of Drug Development Sponsors.
    Jennifer Y Kim, Maria Paula Bautista Acelas, Courtney A Granville, Kenneth Getz.
      Consistent implementation and measurement of patient engagement initiatives across the industry have remained aspirational and elusive despite strong interest in adopting patient-centric approaches. One factor contributing to this inertia stems from a lack of standardized implementation of patient engagement activities, which varies widely from company to company, making it difficult to track and measure. Further, empirical evidence mapping the impact of patient engagement capabilities on clinical research outcomes has remained sparse. To address this gap, the Drug Information Association (DIA) and Tufts Center for the Study of Drug Development (Tufts CSDD) at the Tufts University School of Medicine developed and administered an assessment tool that companies can use to not only evaluate their organization's patient engagement capabilities and implementation preparedness but can also measure the impact of such activities on trial outcomes. Results showed that while most organizations are providing logistical support to increase patient engagement in the form of travel stipends, accommodation, and financial incentives, most are not implementing more involved forms of patient engagement such as gathering patient input through patient input panels or patient steering committees. This paper discusses the process for designing and administering this assessment tool, the results of the assessment, and future implications.
    Keywords:  Clinical research; Impact; Patient engagement; Patient engagement capabilities
    DOI:  https://doi.org/10.1007/s43441-023-00545-x
  12. Orphanet J Rare Dis. 2023 Jun 22. 18(1): 158
    "Because it is a rare disease…it needs to be brought to attention that there are things out of the norm": a qualitative study of patient and physician experiences of Wilson disease diagnosis and management in the US.
    Karen M Bailey, Navdeep Sahota, Uyen To, Peter Hedera.
       BACKGROUND: Wilson disease (WD) is a genetic disorder of copper metabolism that leads to copper accumulation in various organs, primarily the liver and brain, resulting in heterogenous hepatic, neurologic, and psychiatric symptoms. Diagnosis can occur at any age, requiring lifelong treatment, which can involve liver transplantation. This qualitative study aims to understand the wider patient and physician experience of the diagnosis and management of WD in the US.
    METHODS: Primary data were collected from 1:1 semi structured interviews with US-based patients and physicians and thematically analyzed with NVivo.
    RESULTS: Twelve WD patients and 7 specialist WD physicians (hepatologists and neurologists) were interviewed. Analysis of the interviews revealed 18 themes, which were organized into 5 overarching categories: (1) Diagnosis journey, (2) Multidisciplinary approach, (3) Medication, (4) The role of insurance, and (5) Education, awareness, and support. Patients who presented with psychiatric or neurological symptoms reported longer diagnostic journeys (range 1 to 16 years) than those presenting with hepatic symptoms or through genetic screening (range 2 weeks to 3 years). All were also affected by geographical proximity to WD specialists and access to comprehensive insurance. Exploratory testing was often burdensome for patients, but receipt of a definitive diagnosis led to relief for some. Physicians emphasized the importance of multidisciplinary teams beyond hepatology, neurology, and psychiatry and recommended a combination of chelation, zinc, and a low-copper diet; however, only half the patients in this sample were on a chelator, and some struggled to access prescription zinc due to insurance issues. Caregivers often advocated for and supported adolescents with their medication and dietary regimen. Patients and physicians recommended more education and awareness for the healthcare community.
    CONCLUSIONS: WD requires the coordination of care and medication among several specialists due to its complex nature, but many patients do not have access to multiple specialties due to geographical or insurance barriers. Because some patients cannot be treated in Centers of Excellence, easy access to reliable and up-to-date information is important to empower physicians, patients, and their caregivers in managing the condition, along with general community outreach programs.
    Keywords:  Interviews; Patient-reported; Qualitative; Treatment experience; Wilson disease
    DOI:  https://doi.org/10.1186/s13023-023-02778-3
  13. Health Commun. 2023 Jun 20. 1-10
    Do Hospitals Satisfy Our Healthcare Information Needs for Rare Diseases?: Comparison of Healthcare Information Provided by Hospitals with Information Needs of Family Caregivers.
    Ting Wang, Brady Lund, Mirah Dow.
      This study uses a cross-sectional online survey approach to investigate the gap between healthcare information provided by hospitals and family caregivers' information needs and the relationship between demographic factors and information satisfaction. The results indicate that family caregivers have diverse healthcare information needs for daily care, but the information provided by hospitals could not satisfy these information needs most of the time. Family caregivers' information satisfaction was unrelated to various demographic factors, such as age, race, education level, and annual household income. Family caregivers who were male and spent less time searching for rare disease related information and whose children received a rare disease clinical diagnosis and spent more days in hospitals after birth expressed higher information satisfaction. Based on the findings, this study recommends strengthening continuing education of physicians about rare diseases to increase diagnosis and conducting information literacy assessments of family caregivers to better meet their information needs about daily care.
    DOI:  https://doi.org/10.1080/10410236.2023.2228010
This page is being maintained by Thomas Krichel. It was last updated on 2024‒11‒22 at 4:14.