bims-tyki2d 2026-05-03 papers

Issue of 2026–05–03
six papers selected by
Zoya Panahloo, UCB

J Community Genet. 2026 Apr 26. pii: 52. [Epub ahead of print]17(3):

Transforming clinical trials in rare genetic diseases through telemedicine.

Marco Crimi, Sebastiano Bianca.

Keywords: Artificial Intelligence; Clinical trials; EHealth; Rare genetic diseases; Remote Monitoring; Telemedicine

DOI: https://doi.org/10.1007/s12687-026-00887-7

J Korean Med Sci. 2026 Apr 27. 41(16): e125

Evaluation of Team-Based Genetic Counseling Services in Korea.

In Hee Choi, Su Min Ji, Seo Yeon Yang, Gu-Hwan Kim, Jinhee Lee, Sunyoung Choi, Beom Hee Lee.

BACKGROUND: Despite growing interest in genetic counseling services in South Korea, limited studies have evaluated their effectiveness. Ongoing discussions in South Korea are examining the integration of team-based genetic counseling services into the Korean healthcare system. This study aimed to provide evidence for the integration of genetic counseling services into the healthcare system by evaluating genetic counseling outcomes and satisfaction after services were jointly provided by a medical geneticist and certified genetic counselors.
METHODS: From February to June 2023, we conducted a survey using the Korean version of the Genetic Counseling Outcome Scale (K-GCOS) and the Genetic Counseling Satisfaction Scale (GCSS) among 102 patients with genetic disorders and their families who received genetic counseling services provided by the genetics team.
RESULTS: The average time spent on genetic counseling was 43.9 minutes per patient, with preparation time of 59.9 minutes. The satisfaction scores for the genetic counseling services were overall high, specifically for the following items: "My genetic counselor helped me to identify what I needed to know to make decisions about what would happen to me (86.3%)," "The genetic counseling session was valuable to me (85.3%)," and "The genetic counseling session was about the right length of time I needed (83.3%)." Patients who received genetic counseling within 6 months of diagnosis had significantly higher K-GCOS scores than those who received counseling after 6 months (102.88 vs. 95.00, t = 2.607, P = 0.011), indicating that earlier counseling is more effective following a diagnosis. No significant difference was observed between the two groups in terms of the GCSS (t = 0.983, P = 0.328). Additionally, a significant positive correlation was observed between GCSS and K-GCOS (r = 0.204, P = 0.040), indicating that genetic counseling can not only provide information but also offer psychological support to patients.
CONCLUSION: This study proposes a healthcare system in which a genetics team works collaboratively to provide genetic counseling. It also offers evidence for effectively integrating genetic counselors into the Korean healthcare system by evaluating the outcomes and satisfaction associated with team-based genetic counseling services.

Keywords: Clinical Genetics Service; Empowerment; Genetic Counseling Satisfaction; Genetic Counselor; Healthcare System

DOI: https://doi.org/10.3346/jkms.2026.41.e125

Front Sports Act Living. 2026 ;8 1710264

Effects of exercise training on skeletal muscle function in patients with mitochondrial myopathy: a systematic review.

Qiliang Wan, Yi Ding, Wenduo Liu, Kun Yang.

Background: Mitochondrial myopathy (MM) is a group of rare, progressive muscle disorders characterized by impaired oxidative phosphorylation due to mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) mutations, leading to exercise intolerance, muscle weakness, and metabolic dysfunction. Although exercise is increasingly recognized for its capacity to enhance mitochondrial function and muscle performance, the specific effects of different exercise prescriptions (in terms of modality, intensity, and duration) on MM and their phenotype-specific outcomes remain heterogeneous. This study systematically investigates how various exercise types influence mitochondrial function, muscle performance, and clinical outcomes across MM subtypes.
Methods: Databases including PubMed, Web of Science, Embase, and Scopus were searched from 1990 to September 2025. Clinical trials involving exercise interventions in MM patients were included, with outcomes covering exercise capacity, muscle function, mitochondrial markers, and metabolic indices. Risk of bias was assessed using Revised Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I V2), and methodological quality was appraised with the Mixed Methods Appraisal Tool (MMAT).
Results: Fifteen studies (1 randomized controlled trial and 14 non-randomized trials) including a total of 157 MM patients (sample size per study: 4-20) were analyzed. Moderate-intensity aerobic and resistance exercise consistently improved maximal oxygen uptake (VO2 max), maximal workload (W max), muscle strength, and mitochondrial enzyme activity, with no consistent group-level increases observed in creatine kinase (CK) levels or mtDNA mutation burden. Aerobic training enhanced oxidative capacity, phosphocreatine (PCr) recovery, and antioxidant defense, while resistance training improved muscle strength, satellite cell activation, and reduced cytochrome c oxidase (COX)-deficient fibers. Combined regimens yielded additive benefits. Most interventions lasted 8-14 weeks, 3-5 sessions per week. Phenotype-specific responses were evident: patients with large-scale deletions or m.3243A>G mutations showed favorable adaptation, whereas other point mutations or microdeletions displayed variable or adverse responses.
Conclusion: Moderate-intensity, phenotype-specific exercise prescriptions, especially those integrating both aerobic and resistance components, may enhance mitochondrial and muscular function in patients with mitochondrial myopathy while reducing the likelihood of adverse effects. However, larger controlled trials are needed to confirm long-term efficacy and to clarify potential risk profiles.
Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251145502, PROSPERO CRD420251145502.

Keywords: exercise intervention; exercise recommendations; mitochondrial function; mitochondrial myopathy; pathological mechanisms

DOI: https://doi.org/10.3389/fspor.2026.1710264

Clin Transl Sci. 2026 May;19(5): e70550

The Placebo Effect in Rare Disease Clinical Trials: Measurement, Impact, and Statistical Approaches for Patient-as-Own-Control Designs.

Marshall L Summar, Janet Woodcock.

A frequently cited concern regarding patient-as-own-control trial designs in rare disease is the potential for placebo and related effects to inflate apparent treatment efficacy. Whether this concern is disqualifying or manageable has not been systematically evaluated. We reviewed meta-analyses quantifying placebo effect magnitude by endpoint type, reporter modality, and trial duration and evaluated statistical methods available for post-trial placebo adjustment in own-control designs. Placebo effects depend heavily on endpoint type. For objective endpoints (enzyme activity, serum biomarkers, imaging volumetrics)-which constitute the majority of primary endpoints in approved rare disease therapies-placebo effects are consistently small and in most meta-analyses statistically indistinguishable from zero (standardized mean difference [SMD] < 0.10). For subjective endpoints (patient-reported pain, caregiver-rated function), effects are larger (SMD 0.20-0.50) but well-characterized and correctable. Placebo effects peak early and decay over weeks, providing a temporal signature distinguishable from sustained pharmacological effects. Multiple complementary analytical methods-including temporal trajectory modeling, objective-subjective concordance analysis, Bayesian informative priors, extended run-in observation designs, and blinded outcome assessment-are available to quantify and manage placebo contributions. Importantly, the randomized controlled trial's structural advantage in canceling placebo is itself degraded in small samples, where asymmetric allocation of placebo responders can distort between-arm comparisons. The placebo objection to own-control designs is manageable rather than disqualifying. For objective endpoints, correction is minimal. For subjective endpoints, a rich analytical toolkit supports credible decomposition of drug and placebo components. These findings support the broader adoption of own-control designs in rare disease clinical trials.

DOI: https://doi.org/10.1111/cts.70550

J Genet Couns. 2026 Jun;35(3): e70209

Parent/caregiver needs during pediatric genome-wide sequencing: A scoping literature review.

Priyanka Murali, Joon-Ho Yu.

The integration of genome-wide sequencing (GWS) including whole-exome and whole-genome sequencing, has transformed pediatric diagnostics, yet the needs of parents and caregivers during this process remain insufficiently explored. This scoping review aims to synthesize current knowledge on parental and caregiver needs across the GWS process in pediatric settings to inform better clinical practices and support systems. A scoping review was conducted following PRISMA guidelines. Electronic databases including PubMed, PsycINFO, CINAHL, Embase, and Web of Science were searched, yielding 684 articles, with 57 meeting the inclusion criteria. Data extraction focused on study characteristics, clinical settings, and identified parental needs categorized into pre-test, interim, and post-test periods. Conventional content analysis was used to inductively code and identify categories of needs. Parental needs were categorized into two main themes: (1) informational needs, encompassing tailored communication, understanding prognosis, logistics, and evolving information; and (2) emotional support, emphasizing the importance of initial provider interactions and support from healthcare providers and peer groups. Informational and emotional needs were interrelated, impacting parents' overall experiences. The review highlighted significant gaps during the interim waiting period, with needs largely focused on pre- and post-test periods. Parents navigating the pediatric GWS process require comprehensive informational and emotional support. Effective communication before testing and empathetic follow-up contribute to positive experiences. Addressing gaps at different times throughout the process and fostering continuous provider and peer support can enhance the integration of GWS in pediatric care, improving family-centered outcomes.

Keywords: caregivers; exome sequencing; genome sequencing; parents; pediatric genetics

DOI: https://doi.org/10.1002/jgc4.70209

BMC Med. 2026 Apr 30.

Rational use of expensive medicines in the Netherlands: strategies to improve effectiveness and reduce burden on patients and society - a narrative review.

Bart M F Penninx, Sander W Tas, Lonneke Timmers, Nicole C A J van de Kar, Atse Huisman, Denise van den Berg, Zoé L E van Kempen, Carla E M Hollak.

BACKGROUND: While new expensive medicines often offer substantial benefits to patients, they can carry inherent drawbacks such as uncertainty regarding efficacy translating into effectiveness, safety and rational use, as well as a substantial financial burden on society and/or patients. Rational use of medicines aims to maximize effectiveness whilst minimizing side effects, patient burden, and societal costs. In the Netherlands, initiatives aiming to improve the rational use of expensive medicines are being carried out with increasing frequency and in a programmatic manner. This review identified the strategies used, and includes a structured approach for their application during the medicine's use in clinical practice.
MAIN BODY: Rational use initiatives, driven by clinicians and pharmacists, and funded by the Dutch Ministry of Health and the Dutch health insurers were evaluated for strategies that aim to improve the rational use of expensive medicines. In addition, a non-systematic narrative review was carried out through searches in Google, Google Scholar, Pubmed, the Artificial Intelligence (AI)- tools Global Campus and Evidence Hunt to identify additional strategies. Identified strategies were categorized by assessing whether they aimed to address the efficacy-effectiveness gap or to reduce the side effects and societal burden of expensive medicines. Thirteen strategies to improve rational use were identified. Two strategies were identified that aim to address the efficacy-effectiveness gap: optimize patient selection and generating evidence on clinical endpoints. 11 additional strategies that aim to reduce side effects or societal burden were identified: dose reduction, personalized dose optimization, interval lengthening, shortening of the treatment duration, biosimilar/generic drug use, non-medical drug switching, reduction of additional non-medication costs, reduction of drug wastage, switching the route of administration, boosting (improve drug exposure and/or reduce the dose by influencing pharmacokinetic parameters through co-interventions), and optimization of medication adherence.
CONCLUSIONS: Rational use of expensive medications is essential as part of a drug's life cycle and can benefit patients as well as society. The framework and strategies described in this overview provide guidance for the future rational use of expensive medicines, both for those already in use and for those newly introduced.

Keywords: Access; Efficacy-effectiveness gap; Expensive medicines; Rational use; Societal burden

DOI: https://doi.org/10.1186/s12916-026-04897-7