bims-tyki2d 2026-02-01 papers

Issue of 2026–02–01
four papers selected by
Zoya Panahloo, UCB

Paediatr Drugs. 2026 Jan 28.

Doxecitine and Doxribtimine: First Approval.

Doxecitine and doxribtimine (KYGEVVI®) are pyrimidine nucleosides developed by UCB for the treatment of thymidine kinase 2 deficiency (TK2d). In November 2025, doxecitine and doxribtimine received its first approval in the USA for the treatment of TK2d in adult and pediatric patients with an age of symptom onset on or before 12 years. This article summarizes the milestones in the development of doxecitine and doxribtimine leading to this first approval for TK2d.

DOI: https://doi.org/10.1007/s40272-025-00734-1

J Genet Couns. 2026 Feb;35(1): e70173

Assessing patient communication preferences for reclassified variants of uncertain significance in a general genetics clinic.

Eden R Brush, Ketki Naik, Charlotte Close, Nora Nesheiwat, Sara M Berger, Alyssa Dews, Priyanka Ahimaz.

Increased detection of variants of uncertain significance (VUS) from clinical genomic testing has brought about more frequent variant reclassifications which have the potential to impact patient care and well-being. However, the lack of best practice guidelines on communicating reclassified results to patients and limited genetic counselor (GC) bandwidth has led to inconsistent disclosure practices and potential inequities in patient care. This cross-sectional study aimed to capture patient preferences for communication of VUS reclassifications. We surveyed 224 adult patients and parents/primary caregivers of pediatric patients with a VUS result from a general genetics clinic. The online survey included questions on preferred disclosure methods for VUS results downgraded to (likely) benign (dVUS) versus upgraded to (likely) pathogenic (uVUS), and perceived benefits of these methods. For dVUS, the largest group of participants preferred written disclosure (52.7%) with email being the most favored modality (71.4%). However, those with a non-English primary language and lower education preferred verbal disclosure (p = 0.015 and p = 0.005 respectively). For uVUS, the largest proportion of participants (51.3%) preferred a sequential combination of written followed by verbal disclosure, with phone call (72.3%) and email (70.5%) being the preferred verbal and written modalities, respectively. Participants favored a verbal disclosure component for uVUS more than for dVUS (p = 0.002). Perceived benefits of a written disclosure included providing documentation (71.4%) and clarity of information (70.5%) while the primary benefit of verbal disclosure was the ability to ask questions (82.7%). Overall, most patients found written disclosure sufficient for dVUS and preferred a sequential combination of written followed by verbal disclosure for uVUS, suggesting a need to process information before speaking with a clinician. This study offers patient-driven insights on optimizing communication methods for VUS reclassification disclosures, aiming to minimize GC burden and patient care disparities.

Keywords: communication modality; patient preferences; result disclosure; variant of uncertain significance; variant reclassification

DOI: https://doi.org/10.1002/jgc4.70173

Front Public Health. 2025 ;13 1728978

Measuring the health benefits of genome and exome sequencing: a systematic review of economic evaluations.

Marianna Riccio, Annalisa Rosso, Leonardo Maria Siena, Valentina Baccolini, Giuseppe Migliara, Antonio Sciurti, Claudia Isonne, Jessica Iera, Francesco Pierri, Carolina Marzuillo, Corrado De Vito, Giuseppe La Torre, Paolo Villari.

Introduction: Genome sequencing (GS) and exome sequencing (ES) technologies have gained increasing attention in health economics for evaluating their clinical and public health introduction, but their complexity challenges traditional methods. This systematic review aimed to investigate and discuss full economic evaluations (EEs) of GS and ES in relation to health outcomes, with a focus on methodological issues.
Methods: A systematic search of several databases was carried out (PROSPERO CRD42023430992). Quality was evaluated using the Quality of Health Economic Studies instrument. Key methodological features were investigated, and a narrative synthesis of the findings was performed after grouping studies by testing scope.
Results: Overall, 12 recently published cost-utility analyses (CUAs) were included, assessing the use of GS/ES for guiding targeted therapy in oncology (N = 4) or major depressive disorder (N = 1), and diagnosing rare genetic diseases (N = 7). The findings suggested that GS/ES may be cost-effective for diagnosing rare diseases and may also be cost-effective for treatment guidance under favorable conditions. Methodological rigor tended to be higher in treatment guidance studies, whereas EEs in pediatric diagnostics faced greater challenges. Utility values were largely derived from a common survey using validated multi-attribute utility instruments, and studied on proxy conditions. Variability in perspectives, target populations, and costs limited comparability. To strengthen future EEs, standardized methodologies and long-term, real-world data on clinical and non-clinical benefits are needed.
Conclusion: Traditional CUA approaches are essential to guide the implementation of new technologies, but they should be accommodated or complemented by alternative methods, innovative and comprehensive frameworks that capture the broader value of GS/ES and support their integration into clinical and public health practice.

Keywords: cost-effectiveness; cost-utility; economic evaluation; exome sequencing (ES); genome sequencing (GS); systematic review

DOI: https://doi.org/10.3389/fpubh.2025.1728978

BMC Health Serv Res. 2026 Jan 24.

From the rare to the essential: analyzing the needs of physicians and families managing rare diseases.

Irene Mussio, Patricia Triunfo, Mariana Gerstenblüth, Víctor Raggio, Patricia Cardozo, Hugo Naya, Lucia Spangenberg.

BACKGROUND: This study aims to identify the social and healthcare needs of patients with rare diseases (RD) and their physicians within a Universal Health Care System. It seeks to provide valuable insights for policymakers, patient organizations, and healthcare professionals while informing about these diseases, raising awareness, and designing strategies to improve access to quality, timely medical care, including therapies and medication at a local and regional level.
METHODS: Two semi-structured surveys were conducted between May 2023 and August 2024, targeting family members of patients with RD (N = 64) and physicians (N = 56) in Uruguay. Surveys were self-administered via email or conducted by an interviewer, and were disseminated through healthcare professionals, RD associations, and social media, using "snowball" methodology and word-of-mouth references.
RESULTS: Uruguay faces significant deficiencies in access to diagnosis and treatment for rare diseases, leading to a prolonged "diagnostic odyssey" for families and multiple barriers for physicians, ranging from lack of training to limited access to specialized tools. The low reporting rate to the National Registry of Congenital Defects and Rare Diseases and the lack of updates to the Comprehensive Health Care Plan exacerbate inequities in access to diagnosis and treatment. A key finding is inequality in access to whole-exome sequencing (WES), despite its proven effectiveness in reducing diagnostic times and improving accuracy. Its use remains restricted due to high costs and lack of universal coverage, highlighting the need for a national genomic medicine strategy and medical training in molecular diagnosis.
CONCLUSION: The survey results indicate that RDs have a significant physical, emotional, and economic impact on patients and families. The main concerns raised include diagnostic delays, partly due to difficulties accessing specific tests and treatments. The medical community also acknowledges these issues. The healthcare system needs to update its coverage to include genomic diagnostics, improve medical training, strengthen coordination, and ensure equitable treatment access. These results mimic what is seen in other countries in Latin America and the Southern Cone. They call for a comprehensive, formalized framework for diagnosis, treatment, and care of rare diseases at local and regional levels, accounting for family experiences and prioritizing family wellbeing.

Keywords: Diagnostic odyssey; Families; Physicians; Rare diseases; Semi-structured survey

DOI: https://doi.org/10.1186/s12913-025-13999-6