Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer.

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.

Can We Use Lung Function Thresholds and Respiratory Symptoms to Identify Pre-Chronic Obstructive Pulmonary Disease? A Prospective, Population-based Cohort Study.

Rationale: The term "pre-chronic obstructive pulmonary disease" ("pre-COPD") refers to individuals at high risk of developing COPD who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. Objectives: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at risk of developing COPD. Methods: The Tasmanian Longitudinal Health Study comprises a population-based cohort first studied in 1968 (at age 7 yr). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity, and static lung volumes were measured in a subgroup at age 45, and the incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Function Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden index. Measurements and Main Results: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score less than -1.264, corresponding to the lowest 10th percentile. Those below this threshold had a 36-fold increased risk of developing COPD over an 8-year follow-up period (risk ratio, 35.8; 95% confidence interval, 8.88 to 144), corresponding to a risk difference of 16.4% (95% confidence interval, 3.7 to 67.4). The sensitivity was 88%, and the specificity was 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity, and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. Conclusions: This is the first study, to our knowledge, to evaluate the discriminatory accuracy of spirometry, diffusing capacity, and static lung volume thresholds for COPD incidence in middle-aged adults. Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high risk of developing COPD in community-based settings.

Childhood infections, asthma and allergy trajectories, and chronic rhinosinusitis in middle age: A prospective cohort study across six decades.

INTRODUCTION: Evidence on the early life risk factors of adult CRS, and the history of asthma and allergies across the life course, is limited. AIM: To investigate relationships between respiratory infective/allergic conditions in childhood, and asthma and allergies across the life course and CRS in middle age. METHODS: Data were from the population-based Tasmanian Longitudinal Health Study (TAHS) cohort, first studied in 1968 when aged 6-7 years (n = 8583) and serially followed into middle age (n = 3609). Using a well-accepted epidemiological definition, participants were assigned a CRS-severity subtype at age 53: no sinusitis/CRS (reference); past doctor diagnosis only; current symptoms without doctor diagnosis; and doctor-diagnosed CRS with current symptoms. Relationships with infective/allergic respiratory illnesses at age 7, and previously published asthma-allergy trajectories from 7 to 53 years, were examined using multinominal regression. RESULTS: In middle age, 5.8% reported current CRS symptoms with 2.5% doctor-diagnosed. Childhood conditions associated with symptomatic doctor-diagnosed CRS included frequent head colds (multinomial odds ratio [mOR] = 2.04 (95% confidence interval [95% CI]: 1.24, 3.37)), frequent tonsillitis (mOR = 1.61 [95% CI: 1.00, 2.59]) and current childhood asthma (mOR = 2.23 [95% CI: 1.25, 3.98]). Life course trajectories that featured late-onset or persistent asthma and allergies were associated with all CRS subtypes in middle age; early-onset persistent asthma and allergies (mOR = 6.74, 95% CI: 2.76, 16.4); late-onset asthma allergies (mOR = 15.9, 95% CI: 8.06, 31.4), and late-onset hayfever (mOR = 3.02, 95% CI: 1.51, 6.06) were associated with symptomatic doctor-diagnosed CRS. CONCLUSION: Current asthma, frequent head colds and tonsillitis at age 7 could signal a susceptible child who is at higher risk for CRS in mid-adult life and who might benefit from closer monitoring and/or proactive management. Concurrent asthma and allergies were strongly associated and are potential treatable traits of adult CRS.

Healthcare costs attributable to diabetes in pregnancy: A cost of illness study in Tasmania, Australia.

AIMS: To estimate the direct costs during the prenatal, delivery and postpartum periods in mothers with diabetes in pregnancy, compared to those without. METHODS: This study used a population-based dataset from 2004 to 2017, including 57,090 people with diabetes and 114,179 people without diabetes in Tasmania, Australia. Based on diagnostic codes, delivery episodes with gestational diabetes mellitus (GDM) were identified and matched with delivery episodes without diabetes in pregnancy. A group of delivery episodes with pre-existing diabetes was identified for comparison. Hospitalisation, emergency department and pathology costs of these groups were calculated and adjusted to 2020-2021 Australian dollars. RESULTS: There were 2774 delivery episodes with GDM, 2774 delivery episodes without diabetes and 237 delivery episodes with pre-existing diabetes identified. Across the 24-month period, the pre-existing diabetes group required the highest costs, totalling $23,536/person. This was followed by the GDM ($13,210/person), and the no diabetes group ($11,167/person). The incremental costs of GDM over the no diabetes group were $890 (95% CI 635; 1160) in the year preceding delivery; $812 (616; 1031) within the delivery period and $341 (110; 582) in the year following delivery (p < 0.05). Within the year preceding delivery, the incremental costs in the prenatal period were $803 (579; 1058) (p < 0.05). Within the year following delivery, the incremental costs in the postpartum period were $137 (55; 238) (p < 0.05). CONCLUSIONS: Our results emphasised the importance of proper management of diabetes in pregnancy in the prenatal and postpartum periods and highlighted the significance of screening and preventative strategies for diabetes in pregnancy.

The epidemiology of acute pancreatitis in Tasmania over a 12-year period: Is this a disease of disadvantage?

BACKGROUND: The global incidence of acute pancreatitis (AP) is increasing, but little information exists about trends in Australia. This study aimed to describe incidence trends, along with clinical and socio-demographic associations, in the state of Tasmania over a recent 12-year period. METHODS: The study cohort was obtained by linking clinical and administrative datasets encompassing the whole Tasmanian population between 2007 and 2018, inclusive. Pancreatitis case definition was based on relevant ICD-10 hospitalization codes, or elevated serum lipase or amylase in pathology data. Age-standardised incidence rates were estimated, overall and stratified by sex, aetiology, and Index of Relative Socio-economic Disadvantage (IRSD). RESULTS: In the study period, 4905 public hospital AP episodes were identified in 3503 people. The age-standardised person-based incidence rate across the entire period was 54 per 100,000 per year. Incidence was inversely related to IRSD score; 71 per 100,000 per year in the most disadvantaged quartile compared to 32 in the least disadvantaged. Biliary AP incidence was higher than that of alcohol-related AP, although the greatest incidence was in "unspecified" cases. There was an increase in incidence for the whole cohort (average annual percent change 3.23 %), largely driven by the two most disadvantaged IRSD quartiles; the least disadvantaged quartile saw a slight overall decrease. CONCLUSION: This is the first Australian study providing robust evidence that AP incidence is increasing and is at the upper limit of population-based studies worldwide. This increased incidence is greatest in socio-economically disadvantaged areas, meriting further research to develop targeted, holistic management strategies.

Island medicine longitudinal cohort study: Rapid rise in chronic kidney disease in rural and remote communities.

AIM: To determine the change in incidence and prevalence of chronic kidney disease (CKD) in rural and remote communities over the last decade. METHODS: We examined the change in age-standardized incidence and prevalence in Tasmania between 2010 and 2020, using a linked dataset that included any adult with a creatinine test taken in a community laboratory during the study period (n = 581 513; 87.8% of the state's adult population). We defined CKD as two measures of eGFR <60 mL/min per 1.73 m2, at least 3 months apart. RESULTS: State-wide age-standardized prevalence of CKD increased by 28% in the decade to 2020, from 516 to 659 per 10 000 population. Prevalence in men increased 31.3% and women 24.8%. The greatest increase in age-standardized prevalence was seen in rural or remote communities with an increase of 36.6% overall, but with considerable variation by community (range + 0.4% to +88.3%). The increase in the actual number of people with CKD in the decade to 2020 was 67%, with the number of women increasing by 58% and men by 79%. CONCLUSION: The age-standardized prevalence of CKD in rural and remote regions has increased considerably over the past decade, likely compounded by limited access to primary and secondary healthcare. These findings highlight the need to ensure healthcare resources are directed to areas of greatest need.

Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils.

Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 coinfection are high. DFT1 gradually accumulates copy number variants (CNVs), and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability, and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.

Risk of subsequent keratinocyte carcinomas after a first diagnosis in Tasmania, Australia.

BACKGROUND/OBJECTIVE: A history of keratinocyte carcinoma (KC) is a risk factor for further KCs, but population-based studies quantifying the risk are lacking in Australia. We aimed to describe the risk of subsequent KCs after first KCs in the Australian state of Tasmania. METHODS: Tasmanian residents identified in the Tasmanian Cancer Registry with a first histologically confirmed basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or synchronous BCC and SCC (within 3 months) between January 1985 and December 2013 were followed up for at least 5 years for the development of a subsequent KC. Cumulative risk, incidence rates and standardised incidence ratios (SIRs) were calculated. RESULTS: Those first diagnosed with BCC-only, SCC-only or synchronous BCC and SCC had (i) 5-year cumulative risks of subsequent KCs of 32%, 29% and 51%, (ii) annualised 5-year incidence rates of 8100/100,000 person-years at risk (PYR), 7747/100,000 PYR and 16,634/100,000 PYR and (iii) SIRs of 10.6 (95% CI: 10.5-10.6), 12.5 (95% CI: 12.4-12.6) and 313.0 (95% CI: 305.2-321.1), respectively. Risk estimates increased substantially when multiple (two or more) lesions of any type were diagnosed synchronously. CONCLUSIONS: In the first Australian population-based study to describe the risk of subsequent KCs according to histological types, around one in three Tasmanians diagnosed with first KCs were diagnosed with subsequent KCs within 5 years. The risk of subsequent KCs was higher among those with a history of multiple synchronous lesions, especially if they included both BCC and SCC lesions.

Trends and associations between maternal characteristics and infant birthweight among Indigenous and non-Indigenous people in Tasmania, Australia: a population-based study.

OBJECTIVE: This study aimed to investigate the trends and associations of maternal characteristics and birthweight among Indigenous and non-Indigenous infants. STUDY DESIGN: This was a retrospective population-based study. METHODS: Fourteen years (2005-2018) of birthweight and perinatal health data of live-born singletons and their mothers obtained from the Tasmanian Data Linkage Unit were used to assess the trends and associations between maternal characteristics and infant birthweight using regression modelling. RESULTS: Compared with non-Indigenous mothers (n = 76,750), Indigenous mothers (n = 3805) had a significantly higher prevalence of risk factors during the 14-year period. Although the prevalence of prepregnancy obesity and gestational diabetes mellitus (GDM) markedly increased in both groups, the rate of increase was higher (P < 0.001) for Indigenous than non-Indigenous mothers. Smoking, alcohol consumption and illegal drug use during pregnancy reduced over the years, and there was no significant difference in the rate of reduction between the groups. Large-for-gestational-age (LGA) births increased while small-for-gestational-age (SGA) births decreased in both groups over time. In addition, high birthweight (HBW) births decreased while low birthweight (LBW) births increased. The rates of increase in LGA and LBW births and the rates of decrease in SGA and HBW births were significantly higher in Indigenous mothers compared with non-Indigenous mothers (P < 0.001 for all). The association between Indigenous ethnicity and LBW and SGA births weakened after adjusting for other confounding maternal and perinatal variables. LBW and SGA were positively associated with Indigenous ethnicity, age <18 years, smoking, alcohol consumption and illegal drug use, pre-eclampsia, underweight prepregnancy body mass index and low socio-economic status. Women with higher parity, pre-existing diabetes and prepregnancy overweight or obesity were more likely to give birth to an infant with HBW or LGA. CONCLUSIONS: The prevalence of risk factors for abnormal birthweight is higher among Tasmanian Indigenous mothers, contributing to a gap in birthweight outcomes between Indigenous and non-Indigenous infants. The dramatic increase in prepregnancy obesity and GDM in both groups highlight the importance of screening and management of GDM during pregnancy. Comprehensive programmes co-designed and co-managed in consultation with Indigenous people are needed to support healthy lifestyle choices among Indigenous women to address the barriers to individuals adopting behaviour change and to help close the health outcomes-related gap between Indigenous and non-Indigenous mothers and infants.

Incremental healthcare expenditure attributable to diabetes mellitus: A cost of illness study in Tasmania, Australia.

AIMS: To quantify the incremental direct medical costs in people with diabetes from the healthcare system perspective; and to identify trends in the incremental costs. METHODS: This was a matched retrospective cohort study based on a linked data set developed for investigating chronic kidney disease in Tasmania, Australia. Using propensity score matching, 51,324 people with diabetes were matched on age, sex and residential area with 102,648 people without diabetes. Direct medical costs (Australian dollars 2020-2021) due to hospitalisation, Emergency Department visits and pathology tests were included. The incremental costs and cost ratios between mean annual costs of people with diabetes and their controls were calculated. RESULTS: On average, people with diabetes had healthcare costs that were almost double their controls ($2427 [95% CI 2322-2543]; ratio 1.87 [95% CI 1.85-1.91]; pooled from 2007-2017). While in the first year of follow-up, the costs of a person with diabetes were $1643 (95% CI 1489-1806); ratio 1.83 (95% CI 1.76-1.92) more than their control, this increased to $2480 (95% CI 2265-2680); ratio 1.69 (95% CI 1.62-1.77) in the final year. Although the incremental costs were higher in older age groups (e.g., ≥70: $2498 [95% CI 2265-2754]; 40-49: $2117 [95% CI 1887-2384]), the cost ratios were higher in younger age groups (≥70: 1.52 [95% CI 1.48-1.56]; 40-49: 2.37 [95% CI 2.25-2.61]). CONCLUSIONS: Given the increasing burden that diabetes imposes, our findings will support policymakers in future planning for diabetes and enable targeting sub-groups with higher long-term costs for possible cost savings for the Tasmanian healthcare system.

Competing risks of death and kidney failure in a cohort of Australian adults with severe chronic kidney disease.

OBJECTIVES: To examine the competing risks of death (any cause) and of kidney failure in a cohort of Australian adults with severe chronic kidney disease. DESIGN: Population-based cohort study; analysis of linked data from the Tasmanian Chronic Kidney Disease study (CKD.TASlink), 1 January 2004 - 31 December 2017. PARTICIPANTS: All adults in Tasmania with incident stage 4 chronic kidney disease (estimated glomerular filtration rate [eGFR], 15-29 mL/min/1.73 m2 ). MAIN OUTCOME MEASURES: Death or kidney failure (defined as eGFR below 10 mL/min/1.73 m2 or initiation of dialysis or kidney transplantation) within five years of diagnosis of stage 4 chronic kidney disease. RESULTS: We included data for 6825 adults with incident stage 4 chronic kidney disease (mean age, 79.3 years; SD, 11.1 years), including 3816 women (55.9%). The risk of death increased with age - under 65 years: 0.18 (95% CI, 0.15-0.22); 65-74 years: 0.39 (95% CI, 0.36-0.42); 75-84 years, 0.56 (95% CI, 0.54-0.58); 85 years or older: 0.78 (95% CI, 0.77-0.80) - while that of kidney failure declined - under 65 years: 0.39 (95% CI, 0.35-0.43); 65-74 years: 0.12 (95% CI, 0.10-0.14); 75-84 years: 0.05 (95% CI, 0.04-0.06); 85 years or older: 0.01 (95% CI, 0.01-0.02). The risk of kidney failure was greater for people with macroalbuminuria and those whose albumin status had not recently been assessed. The risks of kidney failure and death were greater for men than women in all age groups (except similar risks of death for men and women under 65 years of age). CONCLUSIONS: For older Australians with incident stage 4 chronic kidney disease, the risk of death is higher than that of kidney failure, and the latter risk declines with age. Clinical guidelines should recognise these competing risks and include recommendations about holistic supportive care, not just on preparation for dialysis or transplantation.

Outpatient autologous stem cell transplantation in Royal Hobart Hospital, Tasmania: a single-centre, retrospective review in the Australian setting.

BACKGROUND: Several international centres have published their experiences with outpatient autologous stem cell transplantation (ASCT) as treatment of haematological malignancies. AIM: In this single-centre retrospective review, we aim to examine the outcomes of outpatient autograft and review healthcare resource utilisation in the pre-cytopenic period. METHODS: Patients undergoing ASCT in Royal Hobart Hospital, Tasmania between 2008 and 2018 had their records reviewed and key outcomes data collected based on whether they received inpatient/outpatient ASCT. An outpatient ASCT was defined as conditioning as an outpatient; patients could then be managed with an elective admission during the cytopenic period or admission only when clinically indicated. RESULTS: Of 231 ASCT performed, 135 (58%) were as outpatients: 59 used carmustine-etoposide-cytarabine-melphalan conditioning for lymphoma (BEAM-ASCT) and 76 used high-dose melphalan for myeloma and amyloidosis (MEL-ASCT). Approximately one-third of patients undergoing outpatient ASCT were admitted electively during nadir period; the majority of patients required minimal interventions prior to this time. The most common causes for unplanned hospitalisation (which occurred in 71 (80%) of the 89 planned outpatient transplants) were febrile neutropenia (39%) and mucositis (35%). Age was the only risk factor identified to increase risk of requiring unplanned hospitalisation. Use of oral antibiotic prophylaxis reduced febrile neutropenia rates among melphalan outpatient ASCT. Outpatient ASCT led to significantly reduced inpatient bed-days and overall cost (approximately A$13 000-A$16 000) compared with inpatient autografts, with no significant differences in engraftment, rates of febrile neutropenia, intensive care admissions or mortality. CONCLUSION: Outpatient autografts may save healthcare resources without compromising patient outcomes.

Association between socioeconomic status and joint replacement of the hip and knee: a population-based cohort study of older adults in Tasmania.

BACKGROUND: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. AIM: To describe the association between SES and time to THR and TKR. METHODS: One thousand and seventy-two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area-level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group; and (ii) the cohort dichotomised at the quartile 1 cut-point. RESULTS: The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2-13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR; hazard ratio (HR): 0.56; 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90; 95% CI 0.53, 1.54). However, the former became non-significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. CONCLUSIONS: The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES.

Why some do but too many don't? Barriers and enablers to physical activity in regional Tasmania - an exploratory, mixed-methods study.

BACKGROUND: The interconnectedness of physical inactivity and sedentarism, obesity, non-communicable disease (NCD) prevalence, and socio-economic costs, are well known. There is also strong research evidence regarding the mutuality between well-being outcomes and the neighbourhood environment. However, much of this evidence relates to urban contexts and there is a paucity of evidence in relation to regional communities. A better understanding of available physical activity (PA) infrastructure, its usage, and community perceptions regarding neighbourhood surroundings, could be very important in determining requirements for health improvement in regional communities. The aims of this research were to 1. Explore and evaluate the public's perception of the PA environment; and 2. Evaluate the quantity, variety, and quality of existing PA infrastructure in regional Northwest (NW) Tasmania. METHODS: A mixed methods approach guided data collection, analysis, and presentation. Quality of PA infrastructure was assessed using the Physical Activity Resource Assessment (PARA) instrument and public perception about PA environment was evaluated using the International Physical Activity Questionnaire - Environmental (IPAQ-E) module. Quantitative data were analysed using descriptive summative methods and a team-based researcher triangulation approach was utilised for qualitative data. RESULTS: Overall, a wide array of high-quality PA infrastructure (with minimal incivilities such as auditory annoyance, litter, graffiti, dog refuse, and vandalism etc.) was available. Survey respondents rated neighbourhoods positively. The overall quality of PA infrastructure, rated on a scale from 0 to 3, was assessed as high (all rated between 2 to 3) with minimal incivilities (rated between 0 and 1.5). Of note, survey respondents confirmed the availability of numerous free-to-access recreational tracks and natural amenities across the 3 local government areas (LGAs) studied. Importantly, most respondents reported minimal disruption to their routine PA practices due to the COVID-19 pandemic. CONCLUSION: This exploratory research confirmed the availability of a wide range of high-quality PA infrastructure across all three LGAs and there was an overwhelming public appreciation of this infrastructure. The challenge remains to implement place-based PA interventions that address extant barriers and further increase public awareness and utilisation of high-quality PA infrastructure.

A rare variant in EZH2 is associated with prostate cancer risk.

Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genome sequencing was performed in a large PrCa family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), was identified as segregating with disease in all but two individuals in the family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10-5 ). Transcriptome analysis was performed on prostate tumour needle biopsies available for two rare variant carriers and two wild-type cases. Although no allele-dependent differences were detected in EZH2 transcripts, a distinct differential gene expression signature was observed when comparing prostate tissue from the rare variant carriers with the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB and EGR1, which were subsequently validated by qPCR. These data provide evidence that rs78589034 is associated with increased PrCa risk in Tasmanian men and further, that this variant may be associated with perturbed EZH2 function in prostate tissue. Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including prostate, and is of significant interest as a therapeutic target.

The impact of comorbidities on health-related quality of life of people with osteoarthritis over 10 years.

OBJECTIVE: To investigate the impact of total number and patterns of comorbidities on health-related quality of life (HRQoL) and identify the most prevalent and influential comorbidity patterns in people with OA over 10 years. METHODS: Participants from the Tasmanian Older Adult Cohort aged 50-80 years, with self-reported OA and data on comorbidities and HRQoL were included. Participants were interviewed at baseline (n = 398), 2.5 (n = 304), 5 (n = 269) and 10 years (n = 191). Data on the self-reported presence of 10 chronic comorbidities were collected at baseline. HRQoL was assessed using the Assessment of Quality of Life-4-Dimensions. The long-term impacts of the number and of the nine most prevalent combinations of cardiovascular (CVD), non-OA musculoskeletal (Ms), metabolic and respiratory comorbidities on HRQoL over 10 years were analysed using linear mixed regressions. RESULTS: Compared with comorbidity-free OA participants, the health state utility (HSU) of those with 2 or ≥3 comorbidities was respectively -0.07 and -0.13 units lower over 10 years, largely driven by reduced scores for independent living, social relationships and psychological wellness. Comorbidity patterns including 'CVD+Ms' were most influential, and associated with up to 0.13 units lower HSU, mostly through negative impacts on independent living (up to -0.12), psychological wellness (up to -0.08) and social relationship (up to -0.06). CONCLUSION: Having more comorbidities negatively impacted OA patients' long-term HRQoL. OA patients with CVD and non-OA musculoskeletal conditions had the largest HSU impairment, and therefore optimal management and prevention of these conditions may yield improvements in OA patients' HRQoL.

Decommissioning and recommissioning a regional hospital in response to a COVID-19 outbreak.

CONTEXT: The COVID-19 outbreak at the North West Regional Hospital (NWRH) site in Tasmania, Australia in April 2020 was both rapid and tragic. Within 10 days of identification of the first healthcare worker infection, both hospitals had closed, and all patients were discharged or decanted to other facilities within the state. The entire hospital staff (approximately 1300 people) and their households (approximately 3000-4000 people) were furloughed for 14 days to halt the spread of infection. During the furlough period, a decommissioning, terminal clean and recommissioning process was undertaken alongside recovery and reorientation of the workforce to personal protective equipment. Within 4 days of closure, an Australian Defence Force and Australian Medical Assistance Team team opened the prioritised emergency department to provide emergency care for the local community, supported by modified diagnostic services. The decommissioning and cleaning rolled on over the ensuing month, in a predetermined priority order. As staff returned from quarantine, they recommissioned their clinical areas. The final ward, a modified medical isolation wing, reopened on day 29. ISSUE: Disaster management activities may be grouped under four main headings: prevention, preparedness, response and recovery. There are many opportunities for improvement and learning, and this article focuses on the local response and recovery, describing the process undertaken from the perspective of a small management group. Authors CC, HE, TB and MW were on the ground during the decommissioning process, then managed aspects of the cleaning and recommissioning remotely from furlough. Authors TA and TC provided specialist IPC support and developed education remotely. LESSONS LEARNED: Almost 2 months on, no new COVID-19 infections had been reported. The aim of this article is to provide a foundation for site-specific adaptation to include in pandemic escalation plans in other regional and rural settings.

The Tasmanian Atrial Fibrillation Study (TAFS): Differences in Stroke Prevention According to Sex.

Background: There are limited Australian data on sex differences in oral anticoagulant (OAC) prescribing in atrial fibrillation (AF) and ongoing debate regarding the optimal approach to stroke risk assessment and OAC prescribing in female patients with AF. Objective: The purpose of this study was to investigate sex differences in the prescribing of OACs in patients with AF stratified by stroke risk and in the rate of adverse outcomes. Methods: A retrospective analysis of patients admitted to the Royal Hobart Hospital (Tasmania, Australia) with nonvalvular AF between January 2011 and July 2015 was conducted. Rates of antithrombotic prescribing according to sex and stroke risk were assessed along with a multivariate analysis for predictors of OAC prescribing. Rates of thromboembolism, bleeding, and all-cause mortality were assessed according to sex. Results: A total of 2090 patients were included (44.7% female). Women with a CHA2DS2-VA score ≥2 were less likely to receive an OAC compared with men (56.7% vs 62.2%, P = 0.023). Female sex was an independent negative predictor of OAC prescribing (adjusted odds ratio = 0.83; 95% CI = 0.69-0.99; P = 0.041). There were no sex differences in the incidence rates of thromboembolism, bleeding, or all-cause mortality in patients newly commenced on antithrombotic therapy. Conclusion and Relevance: Female patients with a high stroke risk were less likely to receive guideline-recommended treatment. This study provides new information on prescribing trends within the Australian setting and highlights the opportunity to improve the management of female patients with AF and 1 or more additional stroke risk factors.

Regional differences in access to acute ischaemic stroke care and patient outcomes.

BACKGROUND: Advances in stroke management such as acute stroke units and thrombolysis are not uniformly distributed throughout our population, with rural areas being relatively disadvantaged. It remains unclear, however, whether such disparities have led to corresponding differences in patient outcomes. AIMS: To describe the regional differences in acute ischaemic stroke care and outcomes within the Australian state of Tasmania. METHODS: A retrospective case note audit was used to assess the care and outcomes of 395 acute ischaemic stroke patients admitted to Tasmania's four major public hospitals. Sixteen care processes were recorded, which covered time-critical treatment, allied health interventions and secondary prevention. Outcome measures were assessed using 30-day mortality and discharge destination, both of which were analysed for differences between urban and rural hospitals using logistic regression. RESULTS: No patients in rural hospitals were administered thrombolysis; these hospitals also did not have acute stroke units. With few exceptions, patients' access to the remaining care indicators was comparable between regions. After adjusting for confounders, there were no significant differences between regions in terms of 30-day mortality (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.46-2.18) or discharge destination (OR = 1.24, 95% CI 0.81-1.91). CONCLUSIONS: With the exception of acute stroke unit care and thrombolysis, acute ischaemic stroke care within Tasmania's urban and rural hospitals was broadly similar. No significant differences were found between regions in terms of patient outcomes. Future studies are encouraged to employ larger data sets, which capture a broader range of urban and rural sites and record patient outcomes at extended interval.

Epidemiology and outcomes of gastroschisis in Tasmania.

AIM: To describe the epidemiology and outcomes of gastroschisis in Tasmania. METHODS: A retrospective analysis of all pregnancies complicated by gastroschisis in Tasmania from 1996 to 2015 was undertaken (epidemiology cohort), and the presentation, surgical management and outcomes (surgery cohort) were reviewed for the period between September 1990 and July 2015. RESULTS: Gastroschisis was detected in 58 pregnancies during the 20-year epidemiology cohort period, giving an incidence of 4.4 per 10 000 live births for the 20-year period. Two of the four stillbirths occurred after 36 weeks' gestation. Of the 65 babies with gastroschisis treated at the Royal Hobart Hospital, 51 had a staged surgical repair (silo in 47, stoma formation in 4), and 14 had a primary closure. Staged repair was associated with a significantly longer duration of ventilation and stay in the neonatal intensive care unit. There were six post-natal deaths, all born in the first epoch. Death was significantly associated with the condition of the intestine at delivery (P = 0.02). There were no deaths in babies with simple gastroschisis. Complex gastroschisis was significantly associated with longer duration of total parenteral nutrition (P = 0.0002) and longer stay in hospital (P = 0.03). CONCLUSIONS: The incidence of gastroschisis in Tasmania is similar to that reported in other Australian regions and has not increased over the 20-year period of study. The high risk of stillbirth, and the significant association between mortality and the condition of the intestine at birth necessitates close fetal surveillance. Complex gastroschisis imposes a significant burden on hospital resources.