HIV non-B subtype distribution: emerging trends and risk factors for imported and local infections newly diagnosed in South Australia

Monitoring HIV subtype distribution is important for understanding transmission dynamics. Subtype B has historically been dominant in Australia, but in recent years new clades have appeared. Since 2000, clade data have been collected as part of HIV surveillance in South Australia. The aim of this study was to evaluate the prevalence of and risk factors for HIV-1 non-B subtypes. The study population was composed of newly diagnosed, genotyped HIV subjects in South Australia between 2000 and 2010. We analyzed time trends and subtype patterns in this cohort; notification data were aggregated into three time periods (2000–2003, 2004–2006, and 2007–2010). Main outcome measures were number of new non-B infections by year, exposure route, and other demographic characteristics. There were 513 new HIV diagnoses; 425 had information on subtype. The majority (262/425) were in men who have sex with men (MSM), predominantly subtype B and acquired in Australia. Infections acquired in Australia decreased from 77% (2000–2003) to 64% (2007–2010) ( p = 0.007) and correspondingly the proportion of subtype B declined from 85% to 68% ( p = 0.002). Non-B infections were predominantly (83%) heterosexual contacts, mostly acquired overseas (74%). The majority (68%) of non-B patients were born outside of Australia. There was a non-significant increase from 1.6% to 4.2% in the proportion of locally transmitted non-B cases (p = 0.3). Three non-B subtypes and two circulating recombinant forms (CRFs) were identified: CRF_AE (n = 41), C (n = 36), CRF_AG (n = 13), A (n = 9), and D (n = 2). There has been a substantial increase over the past decade in diagnosed non-B infections, primarily through cases acquired overseas

Protocol for a nested case-control study design for omics investigations in the Environmental Determinants of Islet Autoimmunity cohort

Background: The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D.Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case's onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood.Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation.KEY MESSAGESThe ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored.Helena Oakey ... Lynne C. Giles ... Rebecca L. Thomson ... Pat Ashwood ... Emma J. Knight ... Simon C. Barry ... Kelly McGorm ... Jennifer J. Couper ... Megan A. S. Penno ... the ENDIA Study Group ... et al

At the coalface and the cutting edge: general practitioners’ accounts of the rewards of engaging with HIV medicine

The interviews we conducted with GPs suggest that an engagement with HIV medicine enables clinicians to develop strong and long-term relationships with and expertise about the care needs of people living with HIV ‘at the coalface’, while also feeling connected with a broader network of medical practitioners and other professionals concerned with and contributing to the ever-changing world of science: ‘the cutting edge’. The general practice HIV prescriber is being modelled here as the interface between these two worlds, offering a rewarding opportunity for general practitioners to feel intimately connected to both community needs and scientific change

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

Practice patterns for predicted difficult airway management and access to airway equipment by anaesthetists in Queensland, Australia

A postal survey was conducted to investigate difficult airway management, training and equipment availability among Fellows of the Australian and New Zealand College of Anaesthetists in Queensland. The survey aimed to determine practise patterns for predicted difficult airways and investigate equipment availability

The Royal Australian and New Zealand College of Radiologists (RANZCR) relative value unit workload model, its limitations and the evolution to a safety, quality and performance framework

The study reports on the evolution of the Australian radiologist relative value unit (RVU) model of measuring radiologist reporting workloads in teaching hospital departments, and aims to outline a way forward for the development of a broad national safety, quality and performance framework that enables value mapping, measurement and benchmarking. The Radiology International Benchmarking Project of Queensland Health provided a suitable high-level national forum where the existing Pitman-Jones RVU model was applied to contemporaneous data, and its shortcomings and potential avenues for future development were analysed. Application of the Pitman-Jones model to Queensland data and also a Victorian benchmark showed that the original recommendation of 40 000 crude RVU per full-time equivalent consultant radiologist (97-98 baseline level) has risen only moderately, to now lie around 45 000 crude RVU/full-time equivalent. Notwithstanding this, the model has a number of weaknesses and is becoming outdated, as it cannot capture newer time-consuming examinations particularly in CT. A significant re-evaluation of the value of medical imaging is required, and is now occurring. We must rethink how we measure, benchmark, display and continually improve medical imaging safety, quality and performance, throughout the imaging care cycle and beyond. It will be necessary to ensure alignment with patient needs, as well as clinical and organisational objectives. Clear recommendations for the development of an updated national reporting workload RVU system are available, and an opportunity now exists for developing a much broader national model. A more sophisticated and balanced multidimensional safety, quality and performance framework that enables measurement and benchmarking of all important elements of health-care service is needed

Cancer support services - Are they appropriate and accessible for indigenous cancer patients in Queensland, Australia?

Introduction: In Queensland, Australia, the incidence of cancer (all cancers combined) is 21% lower for Indigenous people compared with non-Indigenous people but mortality is 36% higher. Support services play an important role in helping cancer patients through their cancer journey. Indigenous cancer patients are likely to face greater unmet supportive care needs and more barriers to accessing cancer care and support. Other barriers include the higher proportion of Indigenous people who live remotely and in regional areas, a known difficulty for access to health services. This study describes the availability of cancer support services in Queensland for Indigenous patients and relevant location. Methods: Using a set criteria 121 services were selected from a pre-existing database (n=344) of cancer services. These services were invited to complete an online questionnaire. ArcGIS (www.esri.com/software/arcgis/index.html) was used to map the services' location (using postcode) against Indigenous population by local government area. Services were classified as an 'Indigenous' or 'Indigenous friendly' service using set criteria. Results: Eighty-three services (73.6%) completed the questionnaire. Mapping revealed services are located where there are relatively low percentages of Indigenous people compared with the whole population. No 'Indigenous-specific' services were identified; however, 11 services (13%) were classed 'Indigenous-friendly'. The primary support offered by these services was 'information'. Fewer referrals were received from Indigenous liaison officers compared with other health professionals. Only 8.6% of services reported frequently having contact with an Indigenous organisation; however, 44.6% of services reported that their staff participated in cultural training. Services also identified barriers to access which may exist for Indigenous clientele, including no Indigenous staff and the costs involved in accessing the service, but were unable to address these issues due to restricted staff and funding capacity. Conclusion: Further research into the best models for providing culturally appropriate cancer support services to Indigenous people is essential to ensure Indigenous patients are well supported throughout their cancer journey. Emphasis should be placed on providing support services where a high Indigenous population percentage resides to ensure support is maintained in rural and remote settings. Further efforts should be placed on relationships with Indigenous organisations and mainstream support services and encouraging referral from Indigenous liaison officers

Risk factors associated with RSV hospitalisation in the first 2 years of life, among different subgroups of children in NSW: A whole-of-population-based cohort study

Background: Data on risk factors for respiratory syncytial virus (RSV)-associated hospitalisation in Australian children may be informative for preventive measures. Methods: A whole-of-population-based study was conducted to identify comparable risk factors for RSV hospitalisation in different subgroups of children aged < 2 years in New South Wales. The cohort was divided into Indigenous children and high-risk and standard risk non-Indigenous children. Data on risk factors were obtained from the Perinatal Data Collection. RSV hospitalisations were ascertained from the Admitted Patient Data Collection. Adjusted HRs were calculated for each subgroup. Population-attributable risk associated with risk factors was estimated. Results: Four factors were associated with increased risk of RSV hospitalisation: maternal smoking during pregnancy, male sex, multiparity and birth during the first half of the RSV season. Increase in relative socioeconomic advantage was associated with decreased risk of hospitalisation. Among high and standard risk non-Indigenous children, the hazard was approximately double for children born to multiparous women compared to those born to primiparous women and among Indigenous children the hazard was approximately double among those born during the first half of the RSV season. Maternal smoking during pregnancy was associated with a 26-45% increased risk across subgroups and accounted for 17% (95% CI 9.3% to 24%) of RSV hospitalisations in Indigenous children, 5% (95% CI 2.5% to 8%) in high-risk and 6% (95% 5% to 7%) in standard risk non-Indigenous children. Discussion: Promoting avoidance of smoking during pregnancy may help in lowering the disease burden, with Indigenous children likely to benefit most

Clinical Importance of Myc Family Oncogene Aberrations in Epithelial Ovarian Cancer

Background: The Myc oncogene family has been implicated in many human malignancies and is often associated with particularly aggressive disease, suggesting Myc as an attractive prognostic marker and therapeutic target. However, for epithelial ovarian cancer (EOC), there is little consensus on the incidence and clinical relevance of Myc aberrations. Here we comprehensively investigated alterations in gene copy number, expression, and activity for Myc and evaluated their clinical significance in EOC. Methods: To address inconsistencies in the literature regarding the definition of copy number variations, we developed a novel approach using quantitative polymerase chain reaction (qPCR) coupled with a statistical algorithm to estimate objective thresholds for detecting Myc gain/amplification in large cohorts of serous (n = 150) and endometrioid (n = 80) EOC. MYC, MYCN, and MYCL1 mRNA expression and Myc activity score for each case were examined by qPCR. Kaplan-Meier and Cox-regression analyses were conducted to assess clinical significance of Myc aberrations. Results: Using a large panel of cancer cell lines (n = 34), we validated the statistical algorithm for determining clear thresholds for Myc gain/amplification. MYC was the most predominantly amplified of the Myc oncogene family members, and high MYC mRNA expression levels were associated with amplification in EOC. However, there was no association between prognosis and increased copy number or gene expression of MYC/MYCN/MYCL1 or with a pan-Myc transcriptional activity score, in EOC, although MYC amplification was associated with late stage and high grade in endometrioid EOC. Conclusion: A systematic and comprehensive analysis of Myc genes, transcripts, and activity levels using qPCR revealed that although such aberrations commonly occur in EOC, overall they have limited impact on outcome, suggesting that the biological relevance of Myc oncogene family members is limited to certain subsets of this disease