Academic literature on the topic 'NIMBY syndrome Victoria Melbourne'

This paper reports on the successful management of hyperphagia (exaggerated hunger) in a 14yr-old female with Prader–Willi syndrome (PWS). This child was diagnosed with PWS, (maternal uniparental disomy) at 18 months due to developmental delay, hypertonia, weight gain and extreme eating behaviour. Treatment of a supplement for appetite suppression commenced at 2 years of age. This single-case records ingestion of an Indian cactus succulent Caralluma fimbriata extract (CFE) over 12 years, resulting in anecdotal satiety, free access to food and management of weight within normal range. CFE was administered in a drink daily and dose was slowly escalated by observation for appetite suppression. Rigorous testing determined blood count, vitamins, key minerals, HbA1c, IGF-1 and function of the liver and thyroid all within normal range. The report suggests a strategy for early intervention against hyperphagia and obesity in PWS. This case was the instigator of the successful Australian PWS/CFE pilot and though anecdotal, the adolescent continues to ingest CFE followed by paediatricians at the Royal Children’s Hospital Melbourne, Victoria, Australia. Future clinical trials are worth considering, to determine an appropriate dose for individuals with PWS.

Background: Micro-dissection testicular sperm extraction (micro-TESE) for non-obstructive azoospermia (NOA) was shown to achieve the best sperm retrieval rate (SRR) compared to other techniques. However, to date there is no large series of published Australian data. Aim: To study the incidence and predicting factors of successful sperm extraction in men with NOA undergoing micro-TESE in Victoria. Method: We retrospectively analyzed the clinical data of all consecutive patients with confirmed NOA who were treated between August 2014 and April 2020 in a single medical centre in Melbourne, Victoria. None were excluded. Patients underwent micro-TESE and upon a successful sperm retrieval, sperm was either frozen for fertility preservation or used fresh for ICSI. Results: During the study period, 85 men with NOA underwent micro-TESE in our centre. The overall sperm retrieval rate (SRR) was 61.2% (52/85). All patients with a history of surgically treated cryptorchidism or childhood diseases had a successful sperm retrieval. Patients with Kleinfelter syndrome had a 75% SRR. Patients with Idiopathic NOA and patients with a history of chemotherapy had a 50% and 40% SRR, respectively. Among the different types of testicular pathology, the highest SRR was found in men with complete hyalinization (100%). Hypospermatogenesis was associated with a high SRR of 93.3%, while Sertoli-cell-only histology was associated with only 46.3% SRR. The SRR has significantly increased from 33.3% in 2015-2016 to 73.6% in 2019-2020 (p=0.003). On Multivariate logistic regression analysis, baseline FSH levels <20 IU and history of childhood disease or Klinefelter syndrome were significantly associated with successful sperm retrieval. The cumulative pregnancy rate was 23.7%. Conclusion: This first report from Australia indicates that micro-TESE is an effective method for the treatment of NOA with high SRR and pregnancy rate. Our results can help patient management and counseling.

Abnormal coagulation and fibrinolysis contributes to the respiratory distress syndrome in COVID-19. We aimed to explore the association of impaired fibrinolytic potential with disease severity and oxygen requirement in hospitalized patients. Adults admitted to hospital with confirmed COVID-19 infection between 1–31 January 2022 were included, corresponding to the first Omicron outbreak in Melbourne, Victoria. The first citrated plasma sample requested within 24 h of the patient’s presentation was obtained and analyzed by the overall hemostatic potential (OHP) assay, a spectrophotometric assay in which fibrin formation (triggered by small amounts of thrombin (OCP)) and fibrinolysis (by the addition of thrombin and tissue plasminogen activator (OHP and OFP%)) were simultaneously measured. There were 266 patients (median 72 years, 52.9% male), of which 49.6% did not require oxygen therapy. COVID-19 severity and requirement for oxygen was significantly associated with higher OCP, OHP, and lower OFP%. Vaccinated individuals compared with non-vaccinated individuals had significantly lower OHP (16.5 vs. 23.1, p = 0.015) and higher OFP (72.0% vs. 65.1%, p = 0.005), as well as significantly lower AST, ferritin, LDH, CRP, and D-dimer. A multivariate model containing OHP was constructed with the outcome of oxygen requirement, with c-statistic of 0.85 (95%CI 0.81–0.90). In this pilot study, we show a significant correlation between OHP results and requirement for oxygen supplementation in hospitalized patients during a period dominated by the Omicron variant. The results were incorporated into a multivariate model that predicted for oxygen requirement, with high discriminative ability.

Abstract Background and Aims The detection of sequence variants and copy number changes can improve diagnosis, inform prognosis and guide treatment in patients with bone marrow failure syndromes (BMFS). We aimed to establish and prospectively assess the impact of comprehensive genomic evaluation on diagnostic categorisation and clinical outcomes in patients with genomically uncharacterised BMFS. Methods Eligible patients were recruited from four participating institutions across Victoria, Australia. Inclusion criteria were (i) age >3 months (ii) clinicopathological diagnosis or suspicion of either acquired aplastic anaemia (AA), inherited BMFS, hypoplastic myelodysplastic syndrome (hMDS) or a BMFS with marrow hypoplasia/aplasia not able to be definitively categorised. Patients initially underwent 90-gene targeted sequencing (Peter MacCallum Cancer Centre PanHaem and Myeloid Amplicon next generation sequencing [NGS] panels) for rapid turnaround of accredited results for clinical decision-making. In addition, whole exome sequencing (WES), whole genome copy number analysis, NGS T-cell receptor β (TRB) repertoire assessment and longitudinal monitoring of selected mutations by digital droplet PCR (ddPCR) were performed. All patients received pre-test counselling and assessment. Genomic results were reviewed in centralised multidisciplinary case conferences including the treating clinician, molecular haematopathologists, medical scientists, clinical geneticists and genetic counsellors. Results 100 patients were enrolled. Median age was 25 years (range 3 months - 80 years); 39% were under 18 years. Detection of sequence variants or copy number abnormalities led to or confirmed a diagnosis of either an inherited or acquired BMFS in 36 patients. In 17 patients a diagnosis of an inherited BMFS was positively made by detection of pathogenic sequence variants or copy number changes in FANCA(1 patient [pt]), FANCM(1 pt), FANCI(1 pt), RAD51C(1 pt), HAX1(1 pt), SBDS(1 pt), DNAJC21(1 pt), RPS19(5 pts), RPL35A(1 pt), TERT(1 pt), TINF2(1 pt) and SAMD9L(1 pt). In five patients the clinical BMFS was considered undifferentiated without a clear candidate gene suspected on phenotypic features prior to genomic evaluation. Importantly, an established diagnosis of AA was altered to an inherited BMFS by genomic characterisation in two patients (SAMD9L, FANCA). In 19 patients pathogenic sequence variants or copy number changes were detected either leading to or confirming a diagnosis of an acquired BMFS (paroxysmal nocturnal haemoglobinuria, hMDS or AA). Pathogenic sequence variants were detected in TET2(n=5), RUNX1(n=4), ASXL1(n=3), PIGA(n=3), DNMT3A(n=3),CBL(n=2), and BCOR/IDH2/SF3B1/SRSF2/TP53/U2AF1(n=1 each). Sequencing-detected copy number abnormalities included loss of chromosome 7 (n=6), losses on chromosome 5q (n=2) and copy number loss of ETV6(n=2). Longitudinal monitoring of an acquired truncating RUNX1 mutation by ddPCR resulted in one patient undergoing allogeneic bone marrow transplant for a progressively rising allelic burden. There was a trend towards more restricted TRB diversity in patients with genomically-defined acquired BMFS versus inherited BMFS (normalised Shannon index ≤0.85, 36.4% vs 0%, p=0.09). Conclusion We have established and evaluated a model of comprehensive multimodal genomic characterisation and multidisciplinary care for 100 patients with BMFS. Our results demonstrate a significant contribution to diagnostic categorisation and patient care in this area of clinical need. Disclosures Lieschke: CSL Behring Australia: Consultancy. Tam:Janssen: Honoraria, Research Funding; Gilead: Honoraria; AbbVie: Honoraria, Research Funding; Pharmacyclics: Honoraria, Travel funding; Pharmacyclics: Honoraria; Beigene: Honoraria, Other: Travel funding; Roche: Honoraria; Beigene: Honoraria, Other: Travel funding; Gilead: Honoraria; Roche: Honoraria; AbbVie: Honoraria, Research Funding.

Abstract Introduction The CHaDOx1 nCov-19 AstraZeneca (AZ) vaccination has been associated with an antibody-mediated prothrombotic syndrome, termed "Thrombosis with Thrombocytopenia Syndrome" (TTS)[1-3]. The current diagnostic criteria for TTS are thrombosis (venous or arterial) within 4-42 days of AZ vaccine, thrombocytopenia and presence of an antibody to platelet factor 4 (PF4)[4, 5]. TTS commonly presents with cerebral venous sinus thrombosis (CVST) or splanchnic vessel thrombosis (SVT), but outside of TTS, CVST and SVT are uncommon, with an overall incidence of less than 0.5 per 100,000 [5-7]. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are also associated with TTS, however the background incidence of venous thromboembolism (VTE) is much higher, with 1-2 events per 1000 patients per year[7, 8]. Therefore, many patients will present with new VTE and a recent exposure to the AZ vaccine, requiring consideration of investigation for TTS. Recent data suggests that PF4 antibodies can be seen in up to 8% of patients without thrombosis but following AZ vaccination[9]. We hypothesised in patients with recent AZ vaccination, new VTE but with a normal platelet count, that the incidence of a PF4 antibody is similar to this background rate of PF4 positivity. If confirmed, then presence of a normal platelet count despite new VTE and recent vaccination may exclude TTS without the need for PF4 antibody testing. We present our preliminary data on the rates of PF4 antibody positivity amongst patients with VTE, recent AZ vaccination and a normal platelet count at presentation. Aim and Methods To assess the incidence of PF4 ELISA positive results in patients with confirmed VTE, recent vaccination (within 4-42 days) with the first dose of AZ vaccine, and platelet count greater than 150x10 9/L. A retrospective audit of cases referred with suspected TTS to Monash Pathology, Melbourne, Victoria, and New South Wales Health Pathology at Royal Prince Alfred Hospital and St George Hospital sites Sydney, New South Wales, Australia, for testing for anti PF4 antibodies from 1 st April to 31 st July 2021. Patient sera were tested for the Anti-PF4 antibody using the STAGO Asserachrom HPIA IgG ELISA (Asnières sur Seine, France). For patients with a positive PF4 antibody test additional testing was sought for either the presence of platelet activating antibodies with a flow cytometry-based assay or the presence of spontaneous serotonin release without heparin in the serotonin release assay. Results From April 1 st to July 31 st 350 tests were run on 332 patients. 91 patients met our criteria, of whom 51 were female and 40 male, with a median age of 73 years. Median platelet count at presentation was 226x10 9/L, and median D dimer values were 10 times the upper limit of normal. 86 patients had either DVT, PE or both, including 2 with upper limb DVT, and 5 patients had PE with concurrent arterial events (1 axillary artery thrombosis, 3 arterial strokes, 1 coronary artery thrombosis). Further details are presented in table 1. 82 patient samples tested negative for anti-PF4 antibodies by ELISA, 5 were positive, and were 4 weak positive/equivocal (see table 2 for further details). Of the positive results, 3 had functional testing available, of which 2 were negative, and 1 showed discordant results, with a positive SRA but negative flow cytometry. None of the weak positive/equivocal cases had functional testing results available. Of the negative ELISA results, 5 patients had functional testing results available, of which 4 were negative. One of these cases had positive testing by flow cytometry, but negative by SRA (case included in table 2). Conclusion In our Australian cohort of patients with their first dose of AZ vaccine and new VTE within 4-42days, but a normal platelet count (therefore not fulfilling the clinical criteria of TTS), the incidence of a positive PF4 antibody test was 9/91 (9.9%, 95% CI 3.7-15.9%) and only one had evidence of platelet activating antibodies. This observed rate is similar to that observed in healthy patients without thrombosis who received AZ vaccination as described by Thiele et. al., 2021. Further confirmation in a larger cohort of VTE patients is required, but if confirmed, then PF4 ELISA testing in patients with VTE and normal platelet count post AZ vaccine may not be required, and should give clinicians confidence to institute routine management. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract Sleep disturbances in women with and without polycystic ovary syndrome (PCOS) and their association with lifestyle factors (diet, physical activity and sitting time) Bennett C1, Mansfield DR2, Mo L2, Hodge A3, Joham A4, 5, Cain SW6, Blumfield M1, Teede H4, 5, Moran LJ4 1. Be Active Sleep and Eat (BASE) Facility, Department of Nutrition and Dietetics, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 2. Monash Lung and Sleep, Monash Health, Clayton, Victoria 3. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 4. Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria 5. Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Victoria 6. Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Clayton, Victoria Sleep disturbances are a risk factor for poorer lifestyle behaviours. While PCOS is associated with a higher prevalence of sleep disturbances, the relationship between sleep and lifestyle behaviours is unknown in PCOS. Self-reported data from the Australian Longitudinal Study on Women’s Health young cohort (31–36 years, n=6067, n=464 PCOS, n=5603 non-PCOS) were collected on PCOS, anthropometry, physical activity, sedentary behaviour, diet (74-item validated food frequency questionnaire) and sleeping behaviour (sleep quantity and adverse sleep symptoms). Multivariate regression models controlled for sleeping behaviour, BMI, age, marital status, education, income and area of residence. Women with PCOS reported greater adverse sleep symptoms, higher energy intake, diet quality (dietary guidelines index (DGI)), fibre intake and sedentary time and lower glycaemic index, compared to women without PCOS. This was not maintained for energy intake and sedentary behaviour on adjustment for confounders. For diet quality, there was an interaction between PCOS and sleep disturbances. Only for women with fewer sleep disturbances (~8 hours sleep/no adverse sleep symptoms) was PCOS associated with better diet quality (DGI higher by 3.14±0.86, p&lt;0.001), with no differences in diet quality for women with poorer sleep. Lifestyle behaviours in women with PCOS appear to be influenced by sleep quality and quantity. Nothing to disclose: CB, DM, LM, AH, AJ, SC, MB, HT, LM

BackgroundAn adverse interaction whereby opioids impair and delay the gastrointestinal absorption of oral P2Y12 inhibitors has been established, however the clinical significance of this in acute coronary syndrome (ACS) is uncertain. We sought to characterise the relationship between prehospital opioid dose and clinical outcomes in patients with ACS.MethodsPatients given opioid treatment by emergency medical services (EMS) with ACS who underwent percutaneous coronary intervention (PCI) between 1 January 2014 and 31 December 2018 were included in this retrospective cohort analysis using data linkage between the Ambulance Victoria, Victorian Cardiac Outcomes Registry and Melbourne Interventional Group databases. Patients with cardiogenic shock, out-of-hospital cardiac arrest and fibrinolysis were excluded. The primary end point was the risk-adjusted odds of 30-day major adverse cardiac events (MACE) between patients who received opioids and those that did not.Results10 531 patients were included in the primary analysis. There was no significant difference in 30-day MACE between patients receiving opioids and those who did not after adjusting for key patient and clinical factors. Among patients with ST-elevation myocardial infarction (STEMI), there were significantly more patients with thrombolysis in myocardial infarction (TIMI) 0 or 1 flow pre-PCI in a subset of patients with high opioid dose versus no opioids (56% vs 25%, p<0.001). This remained significant after adjusting for known confounders with a higher predicted probability of TIMI 0/1 flow in the high versus no opioid groups (33% vs 11%, p<0.001).ConclusionsOpioid use was not associated with 30-day MACE. There were higher rates of TIMI 0/1 flow pre-PCI in patients with STEMI prescribed opioids. Future prospective research is required to verify these findings and investigate alternative analgesia for ischaemic chest pain.