Methods: A multidisciplinary group of experts from six ASEAN member states convened for two face-to-face meetings to discuss barriers and possible recommendations for optimizing NCD management, focused on cardiovascular diseases and mental disorders, in the region. Multiple approaches, ie, analysis of insights from the meetings and a review of existing literature on NCD programs in the ASEAN region were followed. The proposed recommendations were also based on selected successful interventions in ASEAN member states, thus providing actionable strategies.
Results: The gaps identified in NCD management for cardiovascular diseases and mental disorders in the ASEAN region were classified into gaps relating to policies and to clinical and public health practice. The proposed solutions addressing policy gaps include fostering multisectoral public-private partnerships, employing "whole-of-government" and "whole-of-society" approaches and promoting "health-in-all policies approach" to manage issues with financing, accessibility, efficiency and quality of health services. Whereas proposed solutions to bridge clinical and public health practice gaps entail strengthening primary care services, building the capacity of trained healthcare workers and employing collaborative care for holistic management of patients.
Conclusion: The scale of premature and preventable deaths from NCDs in the ASEAN region remains a serious public health concern and requires a "whole-of-system approach". The interventions proposed in this paper build on regional collaborations and knowledge sharing to help develop a concerted and targeted response to NCDs.
OBJECTIVE: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.
METHODS: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.
RESULTS: Prenatal features included hypokinesia or akinesia and growth restriction. Six pregnancies were terminated. Nine infants were born at or near term with severe-to-profound weakness and required resuscitation. Seven died following withdrawal of life support. Two surviving children require ongoing respiratory support. Most cohort members had at least 1 disease-causing variant predicted to result in some near-normal-length titin expression. The exceptions, from 2 unrelated families, had homozygous truncating variants predicted to induce complete nonsense mediated decay. However, subsequent analyses suggested that the causative variant in each family had an additional previously unrecognized impact on splicing likely to result in some near-normal-length titin expression. This impact was confirmed by minigene assay for 1 variant.
INTERPRETATION: This study confirms the clinical variability of congenital titinopathy. Severely affected individuals succumb prenatally/during infancy, whereas others survive into adulthood. It is likely that this variability is because of differences in the amount and/or length of expressed titin. If confirmed, analysis of titin expression could facilitate clinical prediction and increasing expression might be an effective treatment strategy. Our findings also further-support the hypothesis that some near-normal-length titin expression is essential to early prenatal survival. Sometimes expression of normal/near-normal-length titin is due to disease-causing variants having an additional impact on splicing. ANN NEUROL 2025;97:611-628.