SCAI/HRS technical review on transcatheter left atrial appendage occlusion.

Background: Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of stroke due to thrombus formation in the left atrial appendage, where over 90% of thrombi originate. While oral anticoagulation (OAC) is the standard therapy for stroke prevention, many patients cannot tolerate long-term OAC due to bleeding risks. Percutaneous left atrial appendage occlusion (LAAO) has emerged as an alternative strategy.

Embedding research into the organisational structure of smaller rural hospitals: building research culture and capacity and understanding perceived rural health workforce benefit.

Background: Rural hospitals in Australia have not been afforded the same opportunities for research activity as their metropolitan counterparts. Equitable access to career and research opportunities has been identified as a potential strategy to enhance workforce satisfaction and retention in rural areas. Smaller rural hospitals show potential in being key settings for research; but minimal investment has translated into a lack of action and knowledge.

Discordance between a deep learning model and clinical-grade variant pathogenicity classification in a rare disease cohort.

Genetic testing is essential for diagnosing and managing clinical conditions, particularly rare Mendelian diseases. Although efforts to identify rare phenotype-associated variants have focused on protein-truncating variants, interpreting missense variants remains challenging. Deep learning algorithms excel in various biomedical tasks, yet distinguishing pathogenic from benign missense variants remains elusive.

Establishment of a Research Unit in Colac, a Medium Rural Town: An Update on Progress and Guidance for Rural Health Service Research Strategy Development.

Background: Rural health services have not had the same opporunities for research as metropolitan health services. Despite increasing awareness of the importance of placed-based research led by rural health services, there are few examples in the literature on how this can be done.

Aims: In this AJRH Practice Insight we aim to provide an update on the establishment and progress of the Colac Area Health (CAH) research unit.

A Novel Tool to Communicate the Needs of Survivors of Trauma to Health Professionals: A Mixed Methods Pilot Study.

Aim(s): To explore the acceptability and feasibility of using a trauma-informed communication tool to convey client needs to health professionals; and to understand the barriers and enablers for clients using the tool.

Design: Mixed methods design pilot study conducted by nurses from a regional community health service in Victoria, Australia, of purposively sampled clients who have a history of sexual assault and/or family violence and clinicians from a primary care service.

Methods: The investigators developed a pocket-sized communication card to convey clients' history of trauma and the clients' emotional and physical needs to health care providers.

Epigenomic newborn screening for conditions with intellectual disability and autistic features in Australian newborns.

This study describes a protocol to assess a novel workflow called Epi-Genomic Newborn Screening (EpiGNs) on 100,000 infants from the state of Victoria, Australia. The workflow uses a first-tier screening approach called methylation-specific quantitative melt analysis (MS-QMA), followed by second and third tier testing including targeted methylation and copy number variation analyzes with droplet digital PCR, EpiTYPER system and low-coverage whole genome sequencing. EpiGNs utilizes only two 3.

Rural healthcare workforce preparation, response, and work during the COVID-19 pandemic in Australia: Lessons learned from in-depth interviews with rural health service leaders.

Background: Low population density, geographic spread, limited infrastructure and higher costs are unique challenges in the delivery of healthcare in rural areas. During the COVID-19 pandemic, emergency powers adopted globally to slow the spread of transmission of the virus included population-wide lockdowns and restrictions upon movement, testing, contact tracing and vaccination programs. The aim of this research was to document the experiences of rural health service leaders as they prepared for the emergency pandemic response, and to derive from this the lessons learned for workforce preparedness to inform recommendations for future policy and emergency planning.

Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.

Purpose: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively.

Methods: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID.

Results: The ES diagnostic yield was 42 of 74 (57%).

Diet-Related Disease Prevention in a Rural Australian Setting: Understanding Barriers, Enablers, and the Role of Rural Health Services in Supporting Changes in Local Rural Food Environments.

Bold and comprehensive action is needed to prevent diet-related diseases in rural areas, which includes improving food environments to enable healthier dietary practices. Rural health services are integral to the health of rural populations, yet their role in community disease prevention is not swell understood. This study sought to understand health service, local government, and food outlet stakeholders' perspectives on (1) the drivers of unhealthy retail environments in a rural setting; (2) the role of rural health services in supporting changes in local food environments; and to (3) identify characteristics of potential interventions.

Polyposis found on index colonoscopy in a 56-year-old female - variant in juvenile polyposis syndrome: A case report.

Background: Juvenile polyposis syndrome (JPS) is a rare hereditary polyposis disease frequently associated with an autosomal-dominant variant of the or gene. It often manifests with symptoms in children and adolescents and is infrequently diagnosed in asymptomatic adults. Establishing the diagnosis is important as patients with JPS have a high risk of developing gastrointestinal cancer and require genetic counselling and close routine follow-up.

Substrate Imaging Before Catheter Ablation of Ventricular Tachycardia: Risk Prediction for Acute Hemodynamic Decompensation.

Background: The PAINESD (Pulmonary disease, Age, Ischemic cardiomyopathy, NYHA functional class, Ejection fraction, Storm, Diabetes mellitus) risk score has been validated as a predictor of periprocedural acute hemodynamic decompensation (AHD) in patients undergoing ventricular tachycardia (VT) ablation. Whether the addition of total scar volume (TSV) determined by preprocedure computed tomography imaging provides additional risk stratification has not been previously investigated.

Objectives: The purpose of this study was to evaluate the impact of TSV on the risk of AHD and its adjunctive benefit to the PAINESD score newly modified as Pulmonary disease, Age, Ischemic cardiomyopathy, NYHA class, Ejection fraction, Storm, Scar volume, Diabetes mellitus (PAINES2D) based on the addition of scar volumes.

Clinical and imaging modality factors impacting radiological interpretation of breast screening in young women with neurofibromatosis type 1.

Young women with Neurofibromatosis type 1 (NF1) have a high risk of developing breast cancer and poorer survival following breast cancer diagnosis. International guidelines recommend commencing breast screening between 30 and 35 years; however, the optimal screening modality is unestablished, and previous reports suggest that breast imaging may be complicated by the presence of intramammary and cutaneous neurofibromas (cNFs). The aim of this study was to explore potential barriers to implementation of breast screening for young women with NF1.

Identifying primary and secondary MLH1 epimutation carriers displaying low-level constitutional MLH1 methylation using droplet digital PCR and genome-wide DNA methylation profiling of colorectal cancers.

Background: MLH1 epimutation is characterised by constitutional monoallelic MLH1 promoter hypermethylation, which can cause colorectal cancer (CRC). Tumour molecular profiles of MLH1 epimutation CRCs were used to classify germline MLH1 promoter variants of uncertain significance and MLH1 methylated early-onset CRCs (EOCRCs). Genome-wide DNA methylation and somatic mutational profiles of tumours from two germline MLH1: c.

PRDM1 DNA-binding zinc finger domain is required for normal limb development and is disrupted in split hand/foot malformation.

Split hand/foot malformation (SHFM) is a rare limb abnormality with clefting of the fingers and/or toes. For many individuals, the genetic etiology is unknown. Through whole-exome and targeted sequencing, we detected three novel variants in a gene encoding a transcription factor, PRDM1, that arose de novo in families with SHFM or segregated with the phenotype.

Australian Genomics: Outcomes of a 5-year national program to accelerate the integration of genomics in healthcare.

Australian Genomics is a national collaborative partnership of more than 100 organizations piloting a whole-of-system approach to integrating genomics into healthcare, based on federation principles. In the first five years of operation, Australian Genomics has evaluated the outcomes of genomic testing in more than 5,200 individuals across 19 rare disease and cancer flagship studies. Comprehensive analyses of the health economic, policy, ethical, legal, implementation and workforce implications of incorporating genomics in the Australian context have informed evidence-based change in policy and practice, resulting in national government funding and equity of access for a range of genomic tests.

Further delineation of dosage-sensitive K/L mediated Xq28 duplication syndrome includes incomplete penetrance.

The low copy tandem repeat area at Xq28 is prone to recurrent copy number gains, including the K/L mediated duplications of 300 kb size (herein described as the K/L mediated Xq28 duplication syndrome). We describe five families, including nine males with K/L mediated Xq28 duplications, some with regions of greater copy number variation (CNV). We summarise findings in 25 affected males reported to date.

Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome.

Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.

Agreement between parents' and clinical researchers' ratings of behavioral problems in children with fragile X syndrome and chromosome 15 imprinting disorders.

Background: Despite the increasing number of clinical trials involving children with neurodevelopmental disorders, appropriate and objective outcome measures for behavioral symptoms are still required.

Aim: This study assessed the agreement between parents' and clinical researchers' ratings of behavioral problem severity in children with fragile X syndrome (FXS) and chromosome 15 imprinting disorders.

Methods And Procedures: The cohort comprised 123 children (64% males), aged 3-17 years, with FXS (n = 79), Prader-Willi (PWS; n = 19), Angelman (AS; n = 15), and Chromosome 15q duplication (n = 10) syndromes.