King Edward Memorial Hospital

Multi-omics in combination with advanced computational methodologies synthesizes diverse omics data to provide deeper insights into molecular interactions and offers transformative potential for unravelling phenomenon behind disease complexities, improving diagnostics, disease prevention, and personalized treatments. This integrative strategy enables our understanding of gene-environment relationships, chronic disease progression, and the intricate molecular pathways involved in health. Effective multi-omics analyses require robust data sharing, accessibility, interoperability, and governance, which are critical for linking genomic elements to phenotypic traits. The Global Alliance for Genomics and Health advocates for responsible data-sharing practices, by promoting key principles such as transparency and equity. By emphasizing a collaborative approach to data utilization, our proposed framework seeks to advance improved disease prevention and treatment strategies. Multi-disciplinary collaboration, encompassing researchers, clinicians, policy makers, and patient representatives, is pivotal for driving innovation and addressing rare disease diagnostics. The success of multi-omics applications hinges on the establishment of comprehensive datasets, understanding the functional implications of multi-omic variation, adherence to findable, accessible, interoperable, reusable (FAIR) and Collective Benefit, Authority to Control, Responsibility, and Ethics (CARE) principles, and the strengthening of global genomic commons, benefiting scientific research, drug development, and broader health initiatives. Our review highlights essential components of multi-omics integration, underscoring its potential to transform the landscape of precision medicine and improved patient outcomes worldwide.

MECP2 duplication syndrome (MDS) is an ultrarare, X-linked neurodevelopmental disorder that is poorly understood in terms of its natural history and phenotypic variability. There is limited information on how individuals with MDS acquire, retain or lose fundamental functional skills (gross motor, purposeful hand function and communication) - that of which this study aimed to better characterise in the largest case series to date.For 160 individuals with MDS (median age 9.06 y, range: 0.57-51.63 y; 84% male), we report that phenotypic penetrance in females can, in some, result in a similar functional skill deficits to males. However, a higher proportion of females acquired gross motor and fine motor skills compared to males. Use of words was the most common parent-reported skill regression (34/90 [38%]) followed by fine motor/hand function (26/90 [29%]), independent walking (25/90 [28%]) and feeding (25/90 [28%]). Additionally, lower proportions of functional ability were present in those with seizures compared to those without. A general trend was also observed for decreasing functional skills with increasing age. Additionally, those with a larger duplication length (1 + Mb) were less likely to be able to acquire independent walking compared with those with less than a 1 + Mb duplication (p < 0.001).This is the first study to comprehensively map the developmental trajectory of functional skills in MDS and provides a seminal baseline for better characterising the natural history of this disorder. Further investigations are required to understand the importance of interventional therapy on the retainment of functional skills.

Endometriosis and adenomyosis are prevalent chronic inflammatory conditions that significantly impact reproductive-age women, leading to debilitating symptoms such as pelvic pain, dysmenorrhea and infertility. Endometriosis is characterized by ectopic endometrial tissue outside the uterus, while adenomyosis involves endometrial deposits within the myometrium, often causing overlapping symptoms. Accurate diagnosis is essential for effective management, yet challenges persist due to variability in lesion location and presentation. Imaging plays a crucial role in the diagnosis, staging, and management of these conditions. While transvaginal ultrasound (TVUS) remains a reliable first-line tool with high specificity, magnetic resonance imaging (MRI) offers superior sensitivity, particularly for endometriomas and deep endometriosis. Both modalities have their limitations but are complementary in preoperative assessment and treatment planning. Emerging imaging protocols, classification systems, and advancements such as dynamic TVUS and improved MRI techniques are discussed. Despite significant progress, the lack of a universally accepted classification system and standardized imaging protocols highlights the need for further research. Advancing diagnostic accuracy and treatment strategies through imaging holds promise for improving patient outcomes. This article reviews the pathophysiology, staging and subtypes of endometriosis and adenomyosis. Recent society guidelines are addressed and readers are provided with updates on imaging technologies with insights into future directions.

Introduction Gestational trophoblastic neoplasia (GTN) is a rare, malignant form of gestational trophoblastic disease (GTD), and international guidelines recommend centralisation of care for best outcomes. The Western Australian Trophoblastic Centre (WATC) was established in 2023 aiming to provide centralised, person‐centred care coordinated by a specialist nurse within a multidisciplinary team. This project aimed to describe the patient population and evaluate lived experience and satisfaction in this new model of care. Methods An observational descriptive study utilised a review of service data to describe the profile of service users and a cross‐sectional survey to collect quantitative and qualitative evaluation data. Data underwent descriptive statistical and content analysis. Results The review determined 172 people accessed the WATC from January 2023 to April 2024. The majority were treated for a partial mole (50%) or a complete mole (38%). Sixty‐six service users responded to the survey. Descriptive analysis revealed an extremely high level of service satisfaction across all areas of care. The few reports of dissatisfaction related to awareness of psychological and external services and support for family member needs. Survey participants expressed mixed preference for face‐to‐face and telephone appointments. Within open‐ended responses, participants commonly expressed satisfaction with empathetic and supportive care delivered by the specialist nurse, information provision and having access to a contact person through the service. Suggestions for improvement were associated with practical issues, such as parking and logistical challenges in attending appointments, and communication. Conclusions Satisfaction with this centralised service model for the management of GTD was extremely high, emphasising the person‐centred approach coordinated by a specialist nurse. This evaluation validates service continuation in its current form and supports wider implementation of similar models in other centres for people accessing care for GTD management.

BackgroundRare disease clinical trials face unique challenges, resulting in low enrollment and limited retention. Digital health technologies (DHTs), when applied through a patient-centric lens, offer promising solutions to these challenges by enhancing data collection efficiency, improving patient engagement, and supporting long-term health care.MethodsThis study investigates DHT application in clinical studies across the ten most-studied rare diseases and was registered with PROSPERO (registration number: CRD420251088025). Up to June 26 2024, a total of 262 studies were identified through ClinicalTrials.gov, the International Clinical Trials Registry Platform, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science. DHT applications were classified into patient recruitment, digital treatment, data monitoring and collection, outcome assessment, remote follow-up, and long-term care management based on scenarios and functionalities.ResultsAmong all DHT applications, data monitoring and collection was the most prevalent (31.3%), serving primarily to enable continuous tracking of physiological parameters relevant to specific rare disease conditions. Digital treatment is featured in 57 studies (21.8%), most commonly as digital physiotherapy. A notable increase in DHT adoption is observed from 2017–2020 to 2021–2024 across nearly all ten diseases. Between 2021 and 2024, cystic fibrosis shows the highest proportion of DHT-enabled trials relative to all studies conducted for that disease (29.7%).ConclusionsOur findings reveal a growing trend toward digital integration in rare disease trials to support decentralized, scalable, and patient-centered research models. We propose a “4A” conceptual framework—Accessibility, Agility, Awareness, and Adaptability to accelerate therapeutic development and expand access to care for these underserved rare disease populations.

Background and AimsTruncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv.MethodsAn international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM.ResultsA total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23).ConclusionsDisease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

Birthing in a hospital with on-site surgical facilities (co-located care) is considered preferable for neonates with surgical conditions. However, it may not always be feasible. Whether transfer of surgical neonates from birth hospital to a surgical facility affects the outcomes of this cohort is unclear. We conducted a systematic review to investigate the association of birth location/transfer with all-cause mortality and disability among neonates with congenital/acquired surgical conditions. Data Sources from PubMed, Embase, CINAHL, and Web of Science were searched till December 2024. Studies from high-income countries (HICs) comparing infants transferred to a surgical center for surgery versus infants born and operated in a co-located care facility were included. Random effects model was used for meta-analysis. The quality of studies and certainty of evidence were assessed using Newcastle-Ottawa Scale and the GRADE framework respectively. The primary outcomes of interest were all-cause mortality and neurodevelopmental impairment at latest follow up. A total of 61 studies from 20 HICs were included. Compared to co-located care, transfer for surgery did not increase the odds of risk-adjusted and crude mortality in neonates with congenital diaphragmatic hernia [adjusted odds ratio (aOR):0.86 (0.49 to 1.49), 5 studies, 8366 infants; crude OR:0.68 (0.51 to 0.91, i.e., decreased mortality), 22 studies, 12970 infants], critical congenital heart disease [aOR:0.79 (0.42 to 1.48), 3 studies, 13485 infants; OR:1.04 (0.66 to 1.64), 10 studies, 14447 infants], surgical necrotizing enterocolitis [aOR:0.99 (0.61 to 1.61), 4 studies, 5891 infants; OR:1.03 (0.64 to 1.65), 5 studies, 5915 infants], gastroschisis [aOR:1.07 (0.68 to 1.68), 2 studies, 5294 infants; OR:0.80 (0.48 to 1.35), 11 studies, 8708 infants], tracheo-oesophageal fistula [aOR:0.97 (0.39 to 2.39), 1 study, 937 infants; OR:0.62 (0.37 to 1.04), 4 studies, 4050 infants], congenital or perinatal intestinal conditions [OR:2.69 (0.26 to 28.34), 4 studies, 1799 infants]. Neurodevelopmental outcomes between the groups were comparable in the three studies that reported this outcome. Whilst many included studies were of good quality, certainty of evidence was very low due to their observational design and heterogeneity. In conclusion, transfer of neonates from the birth hospital to another facility for surgical intervention was not associated with increased risk of mortality or disability. The evidence from this comprehensive meta-analysis would be useful for clinicians, parents and health policy makers. Systematic review registration: PROSPERO CRD 42024565651.