Westmead Hospital Research Articles

An evaluation of the use of a “short moment of intensive training” (SMIT) in delivering trauma-nursing education

Abstract Background In 2021, Westmead Hospital opened a 13-bed trauma ward, drawing the nursing workforce from various surgical specialties and generating an urgent need for trauma-nursing education. The SMIT (short moment of intensive training) method was developed to deliver targeted, flexible, priority focused and customised education. Aim The primary aim of the study was to demonstrate that specific education on chest trauma using the SMIT method improved nurses’ knowledge and confidence in caring for patients who have experienced trauma. Methods Nurses who met the recruitment criteria completed a pre-SMIT chest-trauma knowledge assessment and trauma-nursing confidence assessment. The SMITs, comprising five sessions, were conducted by the trained instructors. On completion of each session, the instructor recorded the duration of the session, and the nurses completed the “Participant Feedback of SMIT” tool. Once a nurse had completed all five SMITs, they completed the post-SMIT knowledge and confidence assessments. Results A sample size of 13 nurses participated in the study; 14 nurses were recruited, and one excluded. A statistically significant difference was found between the post-SMIT and pre-SMIT knowledge tests (p = 0.003), and post-SMIT and pre-SMIT confidence tests (p = 0.000). No difference was found in the amount of time needed to complete the knowledge test post-SMIT (p = 0.434). Instructor feedback included the time-consuming nature of one-to-one teaching, and the need to conduct sessions close together to minimise the need to revise previous content. Conclusions The SMIT teaching method was beneficial for our novice cohort of trauma nurses to increase their knowledge and confidence in treating patients with chest trauma. Recommendations for future research include additional trauma topics, and application of SMITs to other clinical settings. Keywords: Trauma Nurse Education, nursing confidence, critical thinking, chest trauma, trauma ward education, opportunistic learning, teachable moment.

Burosumab in adults with X-linked hypophosphatemia: real-world experience from a retrospective study in Sydney

Abstract X-linked hypophosphatemia (XLH) is a chronic disabling hereditary musculoskeletal disorder associated with inactivating PHEX mutations and elevated circulating FGF-23 concentrations. In a placebo-controlled trial of adults with XLH, burosumab (anti-FGF-23 antibody) demonstrated durable improvements in phosphate concentrations, and self-reported stiffness and physical limitation. However, real-world data regarding burosumab efficacy and tolerability in adults with XLH is lacking. A retrospective audit was performed of patients (age ≥ 18-years) who commenced four-weekly subcutaneous burosumab for XLH at Royal North Shore and Westmead Hospitals, Sydney, between January 2021 and June 2024. Patients were managed per standard clinical care and burosumab dose adjusted as necessary according to manufacturer instructions. Electronic medical records were reviewed to collate data regarding patient demographics, XLH-related complications and prior treatment, burosumab dosage and side effects, and pre- and post-burosumab biochemistry and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores. Of thirteen adults with XLH, all had hypophosphatemia before commencing burosumab (mean 0.64 ± 0.08 mmol/L). Mean WOMAC scores demonstrated baseline impairments in stiffness, pain and physical limitation. Burosumab was administered for median 15 months during follow-up (median dose 70 mg). Hypophosphatemia resolved in all patients within three months of burosumab (mean 1.03 ± 0.38 mmol/L). Two patients developed hyperphosphatemia two weeks after commencing burosumab requiring dose reduction. One patient ceased burosumab in the setting of hypercalcaemia and constipation secondary to pre-existing tertiary hyperparathyroidism. Adverse events were mild, including transient musculoskeletal discomfort (n = 4), restless legs (n = 2), injection site reaction (n = 2) and headache (n = 1). Repeat WOMAC within 12 months of commencing burosumab (n = 9) demonstrated clinically meaningful improvements in stiffness (-33.3 ± 12.5, P<.001) and physical function (-14.3 ± 16.2, P=.029). This study reports real-world outcomes of adults with XLH treated with burosumab. Clinical experience from two centres in Sydney support trial findings that burosumab is well-tolerated and associated with improved serum phosphate concentrations and self-reported stiffness and physical function.

Patient and carer transition outcomes and experiences at the Westmead Centre for Adolescent and Young Adult Health, Westmead, Australia: protocol for a longitudinal cohort study

IntroductionThe Westmead Centre for Adolescent and Young Adult Health is a purpose-built facility supporting integrated care for young patients with a variety of long-term health conditions transitioning from paediatric services...

A study protocol for live and deceased donor uterus transplantation as a treatment for women with uterine factor infertility.

Uterus transplantation (UTx) is an emerging treatment option for women with uterine factor infertility (UFI) or the absence of a functional uterus. This is the study protocol for the first human UTx clinical trial in Australia. This protocol outlines the approved training program used to plan, diagnose, screen, and treat patients who may be eligible for UTx using living and deceased donors. This multi-site clinical research study includes three tertiary hospital sites within New South Wales (NSW), Australia - Prince of Wales, Royal Hospital for Women and Westmead Hospitals. Our UTx protocol is based on that used by our collaborative partner, the inaugural UTx team in Gothenburg, Sweden. The Swedish UTx team provides ongoing preceptorship for the Australian UTx team. Ethics approval for six UTx procedures using living or deceased donors (Western Sydney Local Health District Human Research Ethics Committee: 2019/ETH138038) was granted in 2020. Results from surgeries and live births will be published. Data will be prospectively entered into the registry of the International Society of Uterus Transplantation (ISUTx), a sub-section of The Transplantation Society (TTS). ACTRN12622000917730. A multidisciplinary research team has been formed between three tertiary hospitals in Sydney - The Royal Hospital for Women, Prince of Wales and Westmead Hospitals; and with the Swedish UTx, University of Gothenburg. The Swedish team pioneered animal and human UTx studies since 1998, including publishing the first live birth after UTx. (1) This Australian trial commenced in January 2023. Uterus transplantation gives women with UFI the opportunity to be gestational and genetic mothers. It is a complex procedure for both the donor and recipient, with medical and surgical risks. An extensive multidisciplinary approach is required to optimise patient safety and graft outcomes. This protocol outlines our Australian UTx team strategy for screening, recruitment, surgical approach, and clinical management of UTx recipients and donors.

Abstract 2533: In-depth multi-omic profiling of immune cells in cancer patients developing immune-related adverse events

Abstract Background: The clinical efficacy of immune-checkpoint inhibitors is complicated by the risk for immune-related adverse events (irAEs) that can involve any organ systems. To date, (1) we cannot predict irAE risk reliably at patient level and (2) irAEs remain a diagnosis of exclusion as there are no specific clinical or biological markers. The goal of this study was to elucidate intricate transcriptomic and proteomic signatures of immune cells in patients evolving irAEs. Methods: This pilot trial was conducted as part of a prospective multicenter cohort study (NCT04631731). The study cohort consisted of n=71 patients who were treated with ICIs across Blacktown and Westmead Hospitals, NSW, Australia. Peripheral blood mononuclear cells (PBMCs) were collected from both pre-treatment and after 6-8 weeks post-ICI commencement. Samples were further utilized for RNA sequencing, flow cytometry and Chromium 3’ gene expression analysis (10x Genomics). Results: The median age was 67 years old with the 78% (n=56) of Caucasian origin. The predominant number of patients were treated with dual ICIs. N=21 patients experienced irAEs. Firstly, a differential analysis established a set of genes which were significantly (FDR<0.01) dysregulated between patients with (group A) and without irAEs (group B) and were mostly related to cell cycle and regulation. Notably, phospholipase D signaling pathway was exclusively upregulated in group A and is known to be linked to B cell expansion. Secondly, a cell enrichment analysis within the group A revealed a significant increase of CD4+ and CD8+ T central memory (Tcm) cells upon the toxicity onset as compared to baseline stage. Thirdly, the flow cytometry data established that group A had (1) higher expression of CD27 on CD4+ T cells, a member of Traf-linked tumor necrosis factor receptor family essential for T cells’ maturation and (2) lower expression of inhibitory receptor LAG3 (CD223) which is crucial for maintaining homeostasis of immune system through suppression of T cell proliferation. Finally, we sequenced CD45+ cells from n=4 patients from group A and n=4 from group B at both pre- and post-treatment stages. The unsupervised clustering established 17 different clusters in our single cell dataset with cluster 11 was unique only to patients from group A. The differential analysis established that a set of n=62 genes was significantly upregulated (p<0.05) in cluster 11. Functional annotation established that B cell activation and proliferation pathways were enriched by those genes further stressing B cells’ role in irAEs development. Conclusions: Our real-world cohort study established significant molecular and cellular differences between patients with and without irAEs. Further research in larger cohorts is imperative to validate the established findings and to elucidate the precise mechanisms contributing to the development of irAEs. Citation Format: Dmitrii Shek, Bo Gao, Joey Lai, Brian Gloss, Adnan Nagrial, Ines Pires da Silva, Matteo S. Carlino, Scott A. Read, Golo Ahlenstiel. In-depth multi-omic profiling of immune cells in cancer patients developing immune-related adverse events [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2533.

Drug survival of biologics in psoriasis: An Australian multicentre retrospective study.

Drug survival, which refers to the time from treatment initiation to discontinuation, provides a surrogate measure of the effectiveness of a biologic in a real-world setting (J Invest Dermatol, 2015, 135, 1). The aim of this study was to determine the drug survival of biologics that are currently available in Australia. We also analysed the treatment efficacy of these biologics and reasons for discontinuation. Retrospective data from outpatient Dermatology biologic clinics in Westmead Hospital and Royal Prince Alfred Hospital (Sydney, Australia) from April 2006 to December 2020 were collected. Kaplan-Meier analysis was used to calculate drug survival. A total of 306 patients who underwent 566 treatment courses were analysed. Guselkumab was observed to have the longest drug survival, with cumulative drug survival rates of 94.2% ± 4.0 at 1- and 5-years. This was followed by ixekizumab which had a 1-year survival rate of 87.2% ± 4.5 and 5-year survival rate of 59.4% ± 9.5. Ixekizumab and guselkumab were also noted to have superior treatment efficacy compared with other biologics, with PASI-75 rates of 94.9% and 93.8%, respectively. The most common reasons for treatment discontinuation were a lack of initial efficacy to treatment and a loss of efficacy over time despite an initial response, respectively. To our knowledge, this is the first Australian study to report on outcomes of multiple new biologics that are currently in use for the treatment of chronic plaque psoriasis. Overall, this study provides insight into patterns of care from a local experience that may help guide the management of moderate-to-severe psoriasis.

Results of selective decontamination with oral neomycin and metronidazole for major colorectal surgery in Australia: A cohort study

ObjectiveThe role of selective decontamination with oral antibiotics (OABs) and mechanical bowel preparation (MBP) prior to elective colorectal surgery is still widely debated. The objective of this study was to compare the outcomes of selective decontamination with neomycin, metronidazole and MBP compared to those of decontamination with MBP alone or with no preparation. MethodsSelective decontamination with neomycin and metronidazole combined with bowel preparation was introduced prior to elective colorectal surgery as part of an enhanced recovery after surgery program at Westmead Hospital, a major Australian tertiary referral hospital, between June 2017 and January 2023. Comparisons between short-term outcomes of OAB + MBP and MBP/no preparation were made using prospectively collected data on length of stay (LOS), readmission, mortality within 30 days, anastomotic leakage (AL), surgical site infection (SSI), urinary tract infection, deep venous thrombosis and/or pulmonary embolism, pneumonia, and ileus. Follow-up was limited to hospital stays and subsequent presentations within the health district within thirty days of surgery. The Mann–Whitney U test was used to analyse continuous data, and the chi-square test was used for categorical data. Univariate and multivariate regression modelling was performed to identify risk factors associated with an increased likelihood of SSI and AL. ResultsPatients with oral neomycin and metronidazole combined with bowel preparation had reduced superficial SSI (2.7% vs. 7.6%, p = 0.043) and overall complications (32.7% vs. 44.6%, p = 0.020), particularly Clavien–Dindo 1 complications (7.3% vs. 16.5%, p = 0.009). However, the differences in AL (2.7% vs. 4.5%, p = 0.369) and organ/space SSI (1.3% vs. 3.7%, p = 0.327) were not statistically significant. The median LOS (6 d vs. 6 d, p = 0.370) was not different between the groups. ConclusionSelective decontamination with neomycin and metronidazole reduces the risk of SSIs and overall complications. There was a trend to toward a lower AL, but this difference was not statistically significant.

Enhanced recovery after elective spinal surgery: an Australian pilot study.

The principles of enhanced recovery after surgery (ERAS) aim to reduce the physiological stress of surgery which in turn improve clinical and health economic outcomes. There is ample evidence in literature supporting ERAS methodologies in other surgical specialties, but its adoption in spinal surgery, especially in Australia remains in infancy. The aim of this project is to describe the early experience with an evidence-based ERAS pathway for simple spine surgery, a first of its kind in Australia. An ERAS protocol was designed using an evidenced-based review of the literature. The authors then conducted a prospective cohort analysis looking at outcome of patients undergoing elective spinal (lumbar and cervical) decompression surgery under ERAS principles by a single surgeon on the Westmead Hospital Campus between March 2021 to May 2023. Primary outcomes were patient length of stay (LOS), patient reported pain and disability scores and complications (including readmissions within 30 days and re-operation within 6 months). Secondary outcomes included predictors of failure for same-day discharge. A total of 52 patients underwent spinal decompression surgeries under the ERAS protocol. Overall 43 out of 52 patients (83.7%) were successfully discharged on the same day as their surgery. Patient reported outcomes were improved at 6 weeks and 6 months confirming durability of intervention. The rates of complications were similar to literature reported rates for simple lumbar or cervical decompression procedures and there were no readmissions within 30 days or re-operations within 6 months of surgery. Being of non-English speaking background [odds ratio (OR) =6.08, P=0.04] and from home alone (OR =10.25, P=0.03) were predictors of failure of same day discharge in this small cohort. Implementation of ERAS protocols for simple spinal decompression surgeries is feasible and produces durable improved patient outcomes while reducing LOS in hospitals. Patient social factors can be predictive of lack of compliance.

Clinical features associated with epilepsy occurrence, resolution, and drug resistance in children with cerebral palsy: A population-based study.

To investigate clinicoradiological features associated with epilepsy, its resolution, and drug resistance in children with cerebral palsy (CP). Data were gathered from the New South Wales/Australian Capital Territory CP Register, encompassing children with CP born between 2003 and 2015 (n = 1916). Clinical features and the severity of impairments were compared among three groups: children with current epilepsy (n = 604), those with resolved epilepsy by age 5 years (n = 109), and those without epilepsy (n = 1203). Additionally, a subset of the registry cohort attending Children's Hospital Westmead (n = 256) was analysed to compare epilepsy and treatment characteristics between drug-responsive (n = 83) and drug-resistant groups (n = 147) using logistic regression and hierarchical cluster analysis. Manual Ability Classification System levels IV and V, intellectual impairment, and vision impairment were found to be associated with epilepsy in children with CP on multivariable analysis (p < 0.01). Moderate to severe intellectual impairment and bilateral spastic CP were independent positive and negative predictors of epilepsy persistence at the age of 5 years respectively (p < 0.05). Microcephaly and multiple seizure types were predictors of drug-resistant epilepsy (area under the receiver operating characteristic curve of 0.83; 95% confidence interval 0.77-0.9). Children with a known genetic cause (14%) and CP epilepsy surgery group (4.3%) formed specific clinical subgroups in CP epilepsy. Our study highlights important clinical associations of epilepsy, its resolution, and treatment response in children with CP, providing valuable knowledge to aid in counselling families and identifying distinct prognostic groups for effective medical surveillance and optimal treatment. Severe motor and non-motor impairments in cerebral palsy (CP) increase epilepsy risk. Epilepsy more likely resolves in bilateral spastic and milder CP impairments. Epilepsy in CP often manifests at an early age with multiple seizure types and high drug resistance. Children with a known genetic cause and CP epilepsy surgery group represent distinct clinical subgroups.

Predicting cardiac and pregnancy outcomes in women with adult congenital heart disease using the Anatomic and Physiological (AP) Classification System: How much does physiology matter?

BackgroundPregnancy in women with congenital heart disease (CHD) is associated with an increased risk of adverse maternal and fetal events. Despite the physiological impact of CHD on pregnancy, current risk stratification scores primarily consider anatomical lesions. We assessed the performance of the novel American Heart Association Anatomic and Physiological (AP) classification system in predicting adverse maternal cardiac, obstetric and fetal events, and compared it with established risk models. MethodsThis retrospective cohort study enrolled pregnant women with CHD managed by the Westmead Hospital high-risk pregnancy team. Preconception risk stratification scores (AP classification, mWHO classification, CARPREG II and ZAHARA scores) were retrospectively assigned to each pregnancy by an adult CHD cardiologist and compared with the primary outcome measures, which were maternal cardiac, obstetric and fetal complications. ResultsWe analysed 176 pregnancies in 120 women with CHD. Maternal cardiac risk significantly increased between AP class 2 and 3 (p = 0.001). Within class 3, higher physiological status correlated with maternal cardiac events (p < 0.001). Increasing AP severity correlated with lower fetal birthweight percentiles (p = 0.003). The AP classification was similar to mWHO at predicting maternal cardiac outcomes (AUC 0.787 vs 0.777, p < 0.001), but the CARPREG II (AUC 0.852, p < 0.001) and ZAHARA scores (AUC 0.864, p < 0.001) had higher discriminatory ability within our cohort. ConclusionThe AP classification system shows non-inferior preconception maternal cardiac risk prediction compared to current validated scores. Consideration of physiological status has additive predictive value in the most complex patients (Stage III). Prospective, multicenter studies are required for further validation for preconception risk estimation.

Follow-up assessment of sleep-related symptoms in patients aftertreatment forcancer: responses to continuous positive airway pressure treatment for co-morbid obstructive sleep apnoea.

To assess changes in sleep-related symptoms in patients withbreastcancer, endometrial cancer and melanoma previously examined for sleep-related symptoms and the presence of PSG (polysomnography)-determined OSA, ≥ 3years post-treatment; and to evaluate how CPAP treatment affects sleep-related symptoms in patients previously diagnosed with OSA. Patients initially recruited from breast cancer, endometrial cancer, and melanoma follow-up clinics at Westmead Hospital (Sydney, Australia) participated in this questionnaire-based study. Demographic and change in cancer status data were collected at follow-up. Patients completed the Pittsburgh Sleep Quality Index [poor sleep quality, PSQITOTAL ≥ 5au], Insomnia Severity Index, Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire; with ΔPSQITOTAL ≥ 3au indicating a clinically meaningful change in sleep quality over follow-up. PSG-determined OSA was confirmed using the apnoea-hypopnoea index. CPAP compliance was determinedvia self-report (CPAP compliant, CPAP; not compliant, non-CPAP). Logistic regression models determined if changes in cancer status, AHI, cancer subgroup or CPAP treatment was predictive of ΔPSQITOTAL ≥ 3 auand p < 0.05 indicated statistical significance. The 60 patients recruited had breast cancer (n = 22), endometrial cancer (n = 15), and melanoma (n = 23).Cancer subgroups were similarly aged, and all had median follow-up PSQITOTAL scores ≥ 5au; breast cancer patients scoring the highest (p < 0.05). TheCPAPgroup had significantly reduced PSQITOTAL scores (p = 0.02)at follow-up, unlike thenon-CPAP group. Cancer subgroups had similar median ISITOTAL, ESSTOTAL and FOSQ-10TOTAL scoresat follow-up, regardless of CPAP treatment. There were no significant predictors of ΔPSQITOTAL ≥ 3 au at follow-up. Sleep-related symptoms persist in patients withcancer ≥ 3years aftertreatment, although these symptoms improve with CPAP. Future studies should evaluate how CPAP affects survival outcomes in cancer patients with comorbid OSA.

Spine Surgery and Home Again: The Nurse's Role in the Patient Journey

Abstract Enhanced recovery after surgery (ERAS) programs – also referred to as fast-track programs - are multidisciplinary, evidence-based perioperative pathways, designed to achieve early recovery for patients undergoing major surgery (Ali et al., 2018). ERAS utilises strategies to optimise the patient's condition for surgery and recovery. In particular, the aim is to achieve an earlier discharge from hospital for the patient and a more rapid resumption of normal activities after surgery, without an increase in complications or readmissions (Dietz et al., 2019). An essential element of ERAS programs is multidisciplinary collaboration between surgical, anaesthetic, nursing and allied health teams. While elements of ERAS may vary between surgical units and hospitals, there are many common features in the preoperative, intraoperative and postoperative phases. Minimally invasive spine surgery techniques and instrumentation have evolved rapidly over the past decade, and there is now a worldwide interest in ERAS programs for spine surgeries, including lumbar and cervical decompression and fusion procedures (Li et al., 2021). Nurses have a pivotal role in the successful implementation and sustainability of ERAS protocols because of their specialised knowledge and skill, and their constant presence throughout the patient care pathway (Wainwright et al., 2022). This publication presents learnings from the implementation of an ERAS program for minimally invasive spine surgery at Westmead Hospital, NSW.

Somatostatin receptor expression and clinical outcome of multilineage pituitary tumours expressing PIT1 and SF1.

The application of transcription factor immunohistochemistry to pituitary neuroendocrine tumour (PitNET) assessment has allowed identification of tumours that do not conform to a single lineage. Multilineage pituitary transcription factor 1 (PIT1) and steroidogenic factor 1 (SF1) PitNETs are a rare and relatively newly described tumour subtype. These tumours express both transcription factors and may also express combinations of hormones corresponding to both lineages. Histological and clinical characteristics can vary, and overall clinical behaviour and prognosis is not known. We describe the clinical outcomes and somatostatin receptor status (SSTR) of a series of nine cases identified from our cohort of pituitary tumours at Westmead Hospital. Eight PitNETs (88.9%) expressed growth hormone and caused acromegaly at presentation. Of the seven macrotumours that caused acromegaly, one had cavernous sinus invasion. The Ki-67 labeling index score ranged from 0.6% to 3.6%. About 88% of tumours that secreted excess growth hormone exhibited strong immunostaining for SSTR 2 and all tumours displayed weak immunoreactivity for SSTR5. In 62.5% of patients with acromegaly, cure was achieved after surgical resection. Somatostatin receptor ligands resulted in clinical remission in cases where medical treatment was initiated. There was no new tumour recurrence or regrowth over an overall mean follow-up period of 62.5 months.

The Long-Term Outcome of Abdominal Wall Defects Exomphalos &amp; Gastroschisis Retrospective Single Centre Study Children Hospital at Westmead, Sydney, Australia

Objective: To examine the natural history and detailed outcome of diagnosed cases of abdominal wall defects that admitted to The Children`s Hospital at Westmead. Methods: This was A retrospective single centre study of all cases of abdominal wall defects admitted between the 1st of October 1998 and the 1st of January 2007 to The Children`s Hospital at Westmead. The study had been conducted through a retrospective review of the neonatal, pediatric surgery records and subsequent follow-up information of all cases of Omphalocele and Gastroschisis diagnosed. Results: Ninety cases with anterior abdominal wall defects were admitted. Majority of the cases were born at Westmead Hospital. There were 25 neonates with Gastroschisis (27 females, 28 males), and 35 neonates with Exomphalos (15 females, 20 males). Eighty-one neonates had prenatal ultrasound diagnosis. Some neonates had associated congenital anomalies which results in five deaths (4 Exomphalos, 1 Gastroschisis). Post operative complications were common and the postoperative hospital stay was often lengthy. Twenty-five patients out of the ninety (15 Gastroschisis, 10 exomphalos) required further operations which were related to their primary diagnosis of Gastroschisis or Exomphalos, mostly for abdominal wall hernias. Conclusions: Long-term outcome was favourable in majority of cases with abdominal wall defects and mortality substantially happened in neonates with associated anomalies. Reoperations were necessary in those patients who had postoperative hernias.

Cardiac "hypertrophy" phenotyping: differentiating aetiologies with increased left ventricular wall thickness on echocardiography.

Differentiating phenotypes of cardiac "hypertrophy" characterised by increased wall thickness on echocardiography is essential for management and prognostication. Transthoracic echocardiography is the most commonly used screening test for this purpose. We sought to identify echocardiographic markers that distinguish infiltrative and storage disorders that present with increased left ventricular (LV) wall thickness, namely, cardiac amyloidosis (CA) and Anderson-Fabry disease (AFD), from hypertensive heart disease (HHT). Patients were retrospectively recruited from Westmead Hospital, Sydney, and Princess Alexandra Hospital, Brisbane. LV structural, systolic, and diastolic function parameters, as well as global (LVGLS) and segmental longitudinal strains, were assessed. Previously reported echocardiographic parameters including relative apical sparing ratio (RAS), LV ejection fraction-to-strain ratio (EFSR), mass-to-strain ratio (MSR) and amyloidosis index (AMYLI) score (relative wall thickness × E/e') were evaluated. A total of 209 patients {120 CA [58 transthyretin amyloidosis (ATTR) and 62 light-chain (AL) amyloidosis], 31 AFD and 58 HHT patients; mean age 64.1 ± 13.7 years, 75% male} comprised the study cohort. Echocardiographic measurements differed across the three groups, The LV mass index was higher in both CA {median 126.6 [interquartile range (IQR) 106.4-157.9 g/m2]} and AFD [median 134 (IQR 108.8-152.2 g/m2)] vs. HHT [median 92.7 (IQR 79.6-102.3 g/m2), p < 0.05]. LVGLS was lowest in CA [median 12.29 (IQR 10.33-15.56%)] followed by AFD [median 16.92 (IQR 14.14-18.78%)] then HHT [median 18.56 (IQR 17.51-19.97%), p < 0.05]. Diastolic function measurements including average e' and E/e' were most impaired in CA and least impaired in AFD. Indexed left atrial volume was highest in CA. EFSR and MSR differentiated secondary (CA + AFD) from HHT [receiver operating curve-area under the curve (ROC-AUC) of 0.80 and 0.91, respectively]. RAS and AMYLI score differentiated CA from AFD (ROC-AUC of 0.79 and 0.80, respectively). A linear discriminant analysis with stepwise variable selection using linear combinations of LV mass index, average e', LVGLS and basal strain correctly classified 79% of all cases. Simple echocardiographic parameters differentiate between different "hypertrophic" cardiac phenotypes. These have potential utility as a screening tool to guide further confirmatory testing.

The Potential for a Chat-Based Artificial Intelligence Model to Facilitate Educational Messaging on Hypertension.

HomeHypertensionAhead of PrintPotential for a Chat-Based Artificial Intelligence Model to Facilitate Educational Messaging on Hypertension No AccessResearch ArticleRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialNo AccessResearch ArticleRequest AccessPotential for a Chat-Based Artificial Intelligence Model to Facilitate Educational Messaging on Hypertension Edel O’Hagan, Daniel McIntyre and Liliana Laranjo Edel O’HaganEdel O’Hagan Correspondence to: Edel O’Hagan, The University of Sydney, Westmead Applied Research Centre, Faculty of Medicine and Health, Westmead Hospital, Westmead, NSW, 2145, Australia. Email E-mail Address: [email protected] Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Australia. Search for more papers by this author , Daniel McIntyreDaniel McIntyre https://orcid.org/0000-0003-4854-4050 Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Australia. Search for more papers by this author and Liliana LaranjoLiliana Laranjo Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, Australia. Search for more papers by this author Originally published16 Jun 2023https://doi.org/10.1161/HYPERTENSIONAHA.123.21395Hypertension. 2023;0FootnotesFor Sources of Funding and Disclosures, see page XXX.Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/HYPERTENSIONAHA.123.21395.Correspondence to: Edel O’Hagan, The University of Sydney, Westmead Applied Research Centre, Faculty of Medicine and Health, Westmead Hospital, Westmead, NSW, 2145, Australia. Email edel.[email protected]edu.au Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.123.21395PMID: 37325936 Originally publishedJune 16, 2023 KeywordslifestylehypertensionintelligencefeedbackhealthPDF download Advertisement SubjectsHigh Blood PressureHypertension

Efficacy and safety of CNM-Au8 in amyotrophic lateral sclerosis (RESCUE-ALS study): a phase 2, randomised, double-blind, placebo-controlled trial and open label extension.

CNM-Au8® is a catalytically-active gold nanocrystal neuroprotective agent that enhances intracellular energy metabolism and reduces oxidative stress. The phase 2, randomised, double-blind, placebo-controlled trial and open label extension RESCUE-ALS trial evaluated the efficacy and safety of CNM-Au8 for treatment of amyotrophic lateral sclerosis (ALS). RESCUE-ALS and its long-term open label extension (OLE) were conducted at two multidisciplinary ALS clinics located in Sydney, Australia: (i) the Brain and Mind Centre and (ii) Westmead Hospital. The double-blind portion of RESCUE-ALS was conducted from January 16, 2020 (baseline visit, first-patient first-visit (FPFV)) through July 13, 2021 (double-blind period, last-patient last-visit (LPLV)). Participants (N=45) were randomised 1:1 to receive 30mg of CNM-Au8 or matching placebo daily over 36 weeks in addition to background standard of care, riluzole. The primary outcome was mean percent change in summed motor unit number index (MUNIX), a sensitive neurophysiological biomarker of lower motor neuron function. Change in total (or summated) MUNIX score and change in forced vital capacity (FVC) were secondary outcome measures. ALS disease progression events, ALS Functional Rating Scale (ALSFRS-R) change, change in quality of life (ALSSQOL-SF) were assessed as exploratory outcome measures. Long-term survival evaluated vital status of original active versus placebo randomisation for all participants through at least 12 months following last-patient last-visit (LPLV) of the double-blind period. RESCUE-ALS and the open label study are registered in clinicaltrials.gov with registration numbers NCT04098406 and NCT05299658, respectively. In the intention-to-treat (ITT) population, there was no significant difference in the summated MUNIX score percent change (LS mean difference: 7.7%, 95% CI:-11.9 to 27.3%, p=0.43), total MUNIX score change (18.8, 95% CI:-56.4 to 94.0), or FVC change (LS mean difference: 3.6, 95% CI:-12.4 to 19.7) between the active and placebo treated groups at week 36. In contrast, survival analyses through 12-month LPLV demonstrated a 60% reduction in all-cause mortality with CNM-Au8 treatment [hazard ratio=0.408 (95% Wald CI: 0.166 to 1.001, log-rank p=0.0429). 36 participants entered the open label extension (OLE), and those initially randomised to CNM-Au8 exhibited a slower rate of disease progression, as measured by time to the occurrence of death, tracheostomy, initiation of non-invasive ventilatory support, or gastrostomy tube placement. CNM-Au8 was well-tolerated, and no safety signals were observed. CNM-Au8, in combination with riluzole, was well-tolerated in ALS with no identified safety signals. While the primary and secondary outcomes of this trial were not significant, the clinically meaningful exploratory results support further investigation of CNM-Au8 in ALS. The RESCUE-ALS was substantially funded by a grant from FightMND. Additional funding was provided by Clene Australia Pty Ltd.

Scenario-Based Collaboration: Identifying the Role of the NSW Biocontainment Centre in the Response to High Consequence Infectious Diseases

Introduction:The New South Wales (NSW) Biocontainment Centre (NBC) is the first high-level isolation unit in Australia. This state-wide referral facility, located at Westmead Hospital, Sydney, will provide care for patients with high-consequence infectious diseases (HCIDs), including viral hemorrhagic fevers (VHF). In preparation, a tabletop exercise with key stakeholders was held to introduce and socialize the NBC’s capacity to support NSW’s preparedness for the management of a patient with HCID.Method:Invitations were provided to key stakeholders within Westmead Hospital (facility executive, emergency and ICU services, security, switchboard); NSW Preparedness and Response Branch; retrieval services; peripheral hospitals; pediatric hospital network; and NSW Public health units (state and district).The scenario presented was an unwell patient with suspected VHF arriving at a peripheral hospital emergency department.Discussion during the four-hour long exercise was facilitated with directed questions and injects, and was recorded. Recommendations and key learnings from the exercise and debrief provided opportunities to enhance current response assumptions.Results:Forty-five people participated both face-to-face and virtually. Participant discussion showed increasing appreciation of patient presentations to any part of the NSW health system and available assistance. Recommendations included: enhanced access to NBC support with a direct “1-800 number”, coordination for communication, treatment, and transport, and if required, deployment of an NBC team to peripheral sites. Areas for future collaborative work were identified.Conclusion:This exercise successfully achieved collaboration of key stakeholders to develop an updated, comprehensive and robust plan for management of HCID patients within NSW, regardless of their presentation site. It has created an opportunity to brainstorm and optimize how the NBC can interact with other agencies to maximize the NSW HCID response.

The first Australian uterus transplantation procedure: A result of a long-term Australian-Swedish research collaboration.

The aim is to report the results of Australia's first uterus transplantation (UTx). Following long-standing collaboration between the Swedish and Australian teams, Human Research Ethics approval was obtained to perform six UTx procedures in a collaborative multi-site research study (Western Sydney Local District Health 2019/ETH13038), including Royal Hospital for Women, Prince of Wales Hospital, and Westmead Hospital in New Souh Wales. Surgeries were approved in both the live donor (LD) and deceased donor models in collaboration with the inaugural Swedish UTx team. This is the first UTx procedure to occur in Australia, involving a mother donating her uterus to her daughter. The total operative time for the donor was 9 h 54 min. Concurrently, recipient surgery was synchronised to minimise graft ischaemic time, and the total operative time for the recipient was 6 h 12 min. Surgery was by laparotomy in the LD and recipient. The total warm ischaemic time of the graft was 1 h 53 min, and the cold ischaemic time was 2 h 17 min (total ischaemic time 4 h 10 min). The patient's first menstruation occurred 33 days after the UTx procedure. Twenty-five years of Swedish and Australian collaboration has led to Australia's first successfully performed UTx surgery at The Royal Hospital for Women, Sydney, Australia.

Isolated anti-Ro52 identifies a severe subset of Sjögren's syndrome patients.

Serum autoantibodies targeting the SSA/Ro proteins are a key component of the classification criteria for the diagnosis of Sjögren's syndrome (SS). Most patients' serum reacts with both Ro60 and Ro52 proteins. Here we compare the molecular and clinical characteristics of patients diagnosed with SS with anti-Ro52 in the presence or absence of anti-Ro60/La autoantibodies. A cross-sectional study was performed. Patients in the SS biobank at Westmead Hospital (Sydney, Australia) that were positive for anti-Ro52 were included and stratified based on the absence (isolated) or presence (combined) of anti-Ro60/La, measured by line immunoassay. We examined clinical associations and the serological and molecular characteristics of anti-Ro52 using ELISA and mass spectrometry in serological groups. A total of 123 SS patients were included for study. SS patients with isolated anti-Ro52 (12%) identified a severe serological subset characterised by higher disease activity, vasculitis, pulmonary involvement, rheumatoid factor (RhF) and cryoglobulinaemia. Serum antibodies reacting with Ro52 in the isolated anti-Ro52 subset displayed less isotype switching, less immunoglobulin variable region subfamily usage and a lower degree of somatic hypermutation than the combined anti-Ro52 subset. In our cohort of SS patients, isolated anti-Ro52 represents a severe subset of SS, and is associated with the presence of cryoglobulinaemia. We therefore provide clinical relevance to the stratification of SS patients by their sero-reactivities. It is possible that the autoantibody patterns may be immunological epiphenomena of the underlying disease process, and further work is required to unearth the mechanisms of the differential clinical phenotypes.