bims-curels Biomed News
on Leigh syndrome
Issue of 2023‒10‒22
twelve papers selected by
Cure Mito Foundation

  1. Endocr Metab Immune Disord Drug Targets. 2023 Oct 18.
      INTRODUCTION: Metabolic myopathies (MM) are a heterogeneous group of genetic disorders affecting metabolic pathways involved in energy production during rest, exercise and physiologic stress (fever, fasting, …). Impairments in the pathways of glycolysis/ glycogenolysis, fatty acid transport/oxidation or in the mitochondrial respiratory chain present primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic or in the set of clinical manifestations for which a high level of suspicion is important.METHODS: Retrospective descriptive study of the clinical, biochemical, and molecular features of patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central from 2009 to 2022.
    RESULTS: Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7 McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1 Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase deficiency. Ages varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were asymptomatic (1 Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise 12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight (35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients, the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by muscle biopsy.
    CONCLUSION: MM are a heterogeneous set of disorders, but a careful history may guide the differential diagnosis among biochemical pathways and other etiologies. Nowadays, molecular testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic options, such as enzyme replacement therapy, restricted diets, emergency regime and cofactors. All patients benefit from adequate lifestyle modifications, individualized exercise prescription, nutritional intervention, and genetic counselling.
    Keywords:  fatty acid; fatty acid oxidation disorders; glycogenosis; metabolic myopathies; mitochondrial diseases; rhabdomyolysis
  2. OTA Int. 2023 Dec;6(4): e287
      Objectives: Patient engagement in the design and implementation of clinical trials is necessary to ensure that the research is relevant and responsive to patients. The PREP-IT trials, which include 2 pragmatic trials that evaluate different surgical preparation solutions in orthopaedic trauma patients, followed the patient-centered outcomes research (PCOR) methodology throughout the design, implementation, and conduct. We conducted a substudy within the PREP-IT trials to explore participants' experiences with trial participation.Methods: At the final follow-up visit (12 months after their fracture), patients participating in the PREP-IT trials were invited to participate in the substudy. After providing informed consent, participants completed a questionnaire that asked about their experience and satisfaction with participating in the PREP-IT trials. Descriptive statistics are used to report the findings.
    Results: Four hundred two participants participated in the substudy. Most participants (394 [98%]) reported a positive experience, and 376 (94%) participants felt their contributions were appreciated. The primary reasons for participation were helping future patients with fracture (279 [69%]) and to contribute to science (223 [56%]). Two hundred seventeen (46%) participants indicated that their decision to participate was influenced by the minimal time commitment.
    Conclusions: Most participants reported a positive experience with participating in the PREP-IT trials. Altruism was the largest motivator for participating in this research. Approximately half of the participants indicated that the pragmatic, low-participant burden design of the trial influenced their decision to participate. Meaningful patient engagement, a pragmatic, and low-burden protocol led to high levels of participant satisfaction.
    Keywords:  PREP-IT; orthopaedic trauma; patient engagement; patient-centered outcomes research; randomized controlled trials
  3. Biosystems. 2023 Oct 12. pii: S0303-2647(23)00213-7. [Epub ahead of print] 105038
      Metabolic Control Theory (MCT) and Metabolic Control Analysis (MCA) are the two sides, theoretical and experimental, of the measurement of the sensitivity of metabolic networks in the vicinity of a steady state. We will describe the birth and the development of this theory from the first analyses of linear pathways up to a global mathematical theory applicable to any metabolic network. We will describe how the theory, given the global nature of mitochondrial oxidative phosphorylation, solved the problem of what controls mitochondrial ATP synthesis and then how it led to a better understanding of the differential tissue expression of human mitochondrial pathologies and of the heteroplasmy of mitochondrial DNA, leading to the concept of the threshold effect.
    Keywords:  Metabolic control analysis; Metabolic control theory; Mitochondrial diseases; Oxidative phoshorylation
  4. Am J Med Genet A. 2023 Oct 20.
      Rare diseases (RDs) are defined as diseases that affect a low number of the population. Prenatal diagnoses of RDs can add a lot of unique stress for parents. For example, parents who have prenatal diagnoses experience not only grief of expectation, but are forced to become patient advocates with incomplete information as their child is not yet born, and in many cases parents experience a lot of uncertainty. This typically involves seeking support groups and finding pre- and postnatal specialists all which come with mental and financial cost. Here we discuss the importance of targeted patient resources for parents to help alleviate some of their stress. Patient advocacy organizations can be incredibly useful for parents to navigate the complex healthcare system and help mitigate feelings of isolation, especially when parents can talk to others in a similar situation. We collaborated with a patient organization to create a prenatal parent support guide to address how parental needs such as mental well-being and practicing self-care can be met. We hope that resources such as these can help empower those with a pregnancy affected with a RD diagnosis.
    Keywords:  patient advocacy; rare diseases; vascular anomaly; vascular malformation
  5. BMJ Evid Based Med. 2023 Oct 19. pii: bmjebm-2023-112646. [Epub ahead of print]
    Keywords:  Medical Oncology; Patient Care
  6. Health Expect. 2023 Oct 18.
      Although the implementation of person-centred care (PCC) has gained momentum in healthcare systems, it is not always obvious why it is an important objective in clinical settings and educational institutions that train future healthcare professionals. Various conceptions about PCC have flourished, such as that it only works in certain healthcare contexts, it is the same as the patient making all their own healthcare decisions, it is too demanding for most patients, the word 'patient' may no longer be used, the care provided is already person-centred, and that there is simply not enough time and resources to achieve it. This viewpoint paper aims to problematize these conceptions and may be used for didactical and reflective exercises that support the transition towards more person-centred healthcare. PATIENT OR PUBLIC CONTRIBUTION: The Person Council for patients and carers at the University of Gothenburg provided focus group input on and validated the occurrence of the conceptions discussed in the present paper. The person council consists of a group of persons with many years of personal experiences of health care, either as patients and/or relatives/carers. One member of the person council who is also a designer and artist created the illustration for the article.
    Keywords:  conceptions; implementation; person-centred care
  7. JMIR Hum Factors. 2023 Oct 17. 10 e50357
      BACKGROUND: The digitalization of health care has many potential benefits, but it may also negatively impact health care professionals' well-being. Burnout can, in part, result from inefficient work processes related to the suboptimal implementation and use of health information technologies. Although strategies to reduce stress and mitigate clinician burnout typically involve individual-based interventions, emerging evidence suggests that improving the experience of using health information technologies can have a notable impact.OBJECTIVE: The aim of this systematic review was to collect evidence of the benefits and challenges associated with the use of digital tools in hospital settings with a particular focus on the experiences of health care professionals using these tools.
    METHODS: We conducted a systematic literature review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to explore the experience of health care professionals with digital tools in hospital settings. Using a rigorous selection process to ensure the methodological quality and validity of the study results, we included qualitative studies with distinct data that described the experiences of physicians and nurses. A panel of 3 independent researchers performed iterative data analysis and identified thematic constructs.
    RESULTS: Of the 1175 unique primary studies, we identified 17 (1.45%) publications that focused on health care professionals' experiences with various digital tools in their day-to-day practice. Of the 17 studies, 10 (59%) focused on clinical decision support tools, followed by 6 (35%) studies focusing on electronic health records and 1 (6%) on a remote patient-monitoring tool. We propose a theoretical framework for understanding the complex interplay between the use of digital tools, experience, and outcomes. We identified 6 constructs that encompass the positive and negative experiences of health care professionals when using digital tools, along with moderators and outcomes. Positive experiences included feeling confident, responsible, and satisfied, whereas negative experiences included frustration, feeling overwhelmed, and feeling frightened. Positive moderators that may reinforce the use of digital tools included sufficient training and adequate workflow integration, whereas negative moderators comprised unfavorable social structures and the lack of training. Positive outcomes included improved patient care and increased workflow efficiency, whereas negative outcomes included increased workload, increased safety risks, and issues with information quality.
    CONCLUSIONS: Although positive and negative outcomes and moderators that may affect the use of digital tools were commonly reported, the experiences of health care professionals, such as their thoughts and emotions, were less frequently discussed. On the basis of this finding, this study highlights the need for further research specifically targeting experiences as an important mediator of clinician well-being. It also emphasizes the importance of considering differences in the nature of specific tools as well as the profession and role of individual users.
    Keywords:  burnout; clinical decision support; electronic health record; electronic medical records; health care professionals; health information technology; qualitative research
  8. Cancer Discov. 2023 Oct 20. OF1
      The developed single-cell method MERCI predicts mitochondrial trafficking between tumor and T cells.
  9. Clin Exp Immunol. 2023 Oct 20. pii: uxad112. [Epub ahead of print]
      Cladribine tablets are a treatment for multiple sclerosis with effects on lymphocytes, yet its mode of action has not been fully established. Here, we analyzed the effects of cladribine on mitochondrial DNA integrity in lymphocytes. We treated cultured human T-cell lines (CCRF-CEM and Jurkat) with varying concentrations of cladribine to mimic the slow cell depletion observed in treated patients. The CCRF-CEM was more susceptible to cladribine than Jurkat cells. In both cells mitochondrial protein synthesis, mitochondrial DNA copy number and mitochondrial cytochrome-c oxidase-I mRNA mutagenesis was not affected by cladribine, while caspase-3 cleavage was detected in Jurkat cells at 100 nM concentration. Cladribine treatment at concentrations up to 10 nM in CCRF-CEM and 100 nM in Jurkat cells did not induce significant increase in mitochondrial DNA mutations. Peripheral blood mononuclear cells from 8 multiple sclerosis patients and 4 controls were cultured with or without an effective dose of cladribine (5 nM). However, we did not find any differences in mitochondrial DNA somatic mutations in lymphocyte subpopulations (CD4+, CD8+ and CD19+) between treated vs. non-treated cells. The overall mutation rate was similar in patients and controls. When different lymphocyte subpopulations were compared, greater mitochondrial DNA mutation levels were detected in CD8+ (p=0.014) and CD4+ (p=0.038) as compared to CD19+ cells, these differences were independent of cladribine treatment. We conclude that T-cells have more detectable mitochondrial DNA mutations than B-cells, and cladribine has no detectable mutagenic effect on lymphocyte mitochondrial genome nor does it impair mitochondrial function in human T-cell lines.
    Keywords:  cladribine; lymphocytes; mitochondrial DNA; multiple sclerosis
  10. Int J Technol Assess Health Care. 2023 Oct 16. 39(1): e62
      OBJECTIVES: The objective was to identify and describe the published guidance and current academic discourse of ethical issues and standards related to the use of Social Media Research for generating patient insights for the use by health technology assessment (HTA) or health policy decisions.METHODS: A scoping review of the literature was conducted in PubMed and Embase and identified 935 potential references published between January 2017 and June 2021. After title and abstract screening by three reviewers, 40 publications were included, the relevant information was extracted and data were collected in a mind map, which was then used to structure the output of the review.
    RESULTS: Social Media Research may reveal new insights of relevance to HTA or health policies into patient needs, patient experiences, or patient behaviors. However, the research approaches, methods, data use, interpretation, and communication may expose those who post the data in social media channels to risks and potential harms relating to privacy, anonymity/confidentiality, authenticity, context, and rapidly changing technologies.
    CONCLUSIONS: An actively engaged approach to ensuring ethical innocuousness is recommended that carefully follows best practices throughout planning, conduct, and communication of the research. Throughout the process and as a follow-up, there should be a discourse with the ethical experts to maximally protect the current and future users of social media, to support their trust in the research, and to advance the knowledge in parallel to the advancement of the media themselves, the technologies, and the research tools.
    Keywords:  ethics; health technology assessment; privacy; social media listening; social media research
  11. Qual Health Res. 2023 Oct 16. 10497323231201027
      This autoethnographic research utilizes reflexivity as a method to explore my self-experience of Lyme disease while holding co-occurring identities as a researcher, health professional, and mother. Awareness of self is central in psychotherapy so that therapists do not adversely impact their clients. This is similar for researchers who are ethically required to acknowledge and reduce any potential risk(s) of harm to their participants. In this study, I describe and systematically analyze my experiences as a patient with symptom-persistent Lyme disease, contextualized through co-occurring identities as a mother, a regulated (mental) health professional, and a scholar investigating the embodied experience of being a Lyme disease patient in the Canadian context. The central research question guiding this study is: "What are my experiences with symptom-persistent Lyme disease?" The results of this study suggest reflexivity is an important practice in both health research and healthcare. Relationships with health professionals have a significant impact on patients' healthcare experiences, and engaging in reflexive practice may improve the responsivity of healthcare professionals toward patients' needs and embodied experiences and serve as a check on pre-existing power relations in healthcare. Further, this research contributes to the current academic knowledge on symptom-persistent Lyme disease by offering a reflexive representation of my experiences as a researcher who is also a health professional and a patient within the Canadian healthcare system. Representations of patients' experiences are critical in advancing health research and ensuring equitable care for patients. Autoethnography offers important insights into patients' disease experiences.
    Keywords:  Lyme disease; chronic illness; healthcare; reflexive transdisciplinary