Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. METHODS: We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. RESULTS: A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10(-5)). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. CONCLUSIONS: Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation

Challenges of nurse delivery of psychological interventions for long-term conditions in primary care: a qualitative exploration of the case of chronic fatigue syndrome/myalgic encephalitis

Background The evidence-base for a range of psychosocial and behavioural interventions in managing patients with long term conditions (LTCs) is now well-established. With increasing numbers of such patients with such conditions being managed in primary care, and a shortage of specialists in psychology and behavioural management to deliver interventions, such therapeutic interventions are increasingly being delivered by general nurses with limited training in psychological interventions. It is unknown what issues this raises for the nurses or their patients. The purpose of the study was to examine the challenges faced by non-specialist nurses when delivering psychological interventions for a long term condition (Chronic Fatigue Syndrome /Myalgic Encephalomyelitis; CFS/ME) within a primary care setting. Methods A qualitative study nested within a randomised controlled trial [ISRCTN 74156610] explored the experiences and acceptability of two different psychological interventions (pragmatic rehabilitation and supportive listening) from the perspectives of nurses, their supervisors and patients. Exploring data from each perspective provides triangulation, and therefore increased trustworthiness, of the analysis. Semi-structured in-depth interviews were conducted with 46 patients, three nurse therapists and three supervisors and an iterative approach was used to develop conceptual categories from the dataset. Results Analyses reveal four sets of challenges that were common to both interventions: i) Being a novice therapist; ii) engaging patients in the therapeutic model; iii) dealing with emotions and iv) complexity of primary care. Each challenge had the potential to cause tension between therapist and patient. A number of strategies were developed by participants to manage the tensions. Conclusion Tensions exist for nurses when attempting to deliver psychological therapy for patients with CFS/ME in a primary care trial which would need to be addressed before implementing within routine clinical practice. Similar tensions may be found for other long term conditions. These have implications for developing therapeutic alliance and highlight the need for regular supervision