Unravelling the health and economic burden of interstitial lung diseases in adults in Australia.

BACKGROUND: Interstitial lung diseases (ILD) are a heterogenous group of over 200 disorders affecting the pulmonary interstitium. Although there have been advances in knowledge on ILDs in Australia, the characterisation of the health and economic burden of disease remained largely undetermined until recently. OBJECTIVE: The main objective of this review is to provide a synopsis of health and economic burden of ILDs in Australia, based on recently completed research. DISCUSSION: Recent research has demonstrated that idiopathic pulmonary fibrosis (IPF) is the most frequent ILD in Australia. Incidence and prevalence of IPF have demonstrated an increasing trend over the past decades. Mortality has also increased over the past decades, but has shown a slight decreasing trend recently, since the introduction of antifibrotic medication. Health-related quality of life is poor in patients with IPF, and care is estimated to cost approximately AU$299 million per year in Australia. Early diagnosis and referral to tertiary care is crucial for favourable outcomes, and general practitioners are considerably important to this as the first interface to identify patients at risk and detect early symptoms of ILDs.

Creating an interactive map visualising the geographic variations of the burden of diabetes to inform policymaking: An example from a cohort study in Tasmania, Australia.

OBJECTIVES: To visualise the geographic variations of diabetes burden and identify areas where targeted interventions are needed. METHODS: Using diagnostic criteria supported by hospital codes, 51,324 people with diabetes were identified from a population-based dataset during 2004-2017 in Tasmania, Australia. An interactive map visualising geographic distribution of diabetes prevalence, mortality rates, and healthcare costs in people with diabetes was generated. The cluster and outlier analysis was performed based on statistical area level 2 (SA2) to identify areas with high (hot spot) and low (cold spot) diabetes burden. RESULTS: There were geographic variations in diabetes burden across Tasmania, with highest age-adjusted prevalence (6.1%), excess cost ($2627), and annual costs per person ($5982) in the West and Northwest. Among 98 SA2 areas, 16 hot spots and 25 cold spots for annual costs, and 10 hot spots and 10 cold spots for diabetes prevalence were identified (p<0.05). 15/16 (94%) and 6/10 (60%) hot spots identified were in the West and Northwest. CONCLUSIONS: We have developed a method to graphically display important diabetes outcomes for different geographical areas. IMPLICATIONS FOR PUBLIC HEALTH: The method presented in our study could be applied to any other diseases, regions, and countries where appropriate data are available to identify areas where interventions are needed to improve diabetes outcomes.

Palliative care symptoms and problems in a culturally and linguistically diverse population: large retrospective cohort study.

OBJECTIVES: Migrant Australians with cancer have higher unmet needs and poorer health-related quality of life. Less is known about their palliative care experience. We aimed to assess comparative symptom distress and problem severity for culturally and linguistically diverse Australians with cancer in palliative care. METHODS: This was a retrospective, consecutive cohort study using data from the Palliative Care Outcomes Collaboration, which routinely collects standardised symptom assessments nationally at point-of-care. Adults with a cancer diagnosis who died 01/01/2016-31/12/2019 were included. The presence/absence of patient-reported symptom distress and clinician-rated problem severity were compared between people who preferred English and people who preferred another language using logistic regression models. We also compared people who preferred English and the four most common non-English languages in the dataset: Chinese, Greek, Italian and Slavic. RESULTS: A total of 53 964 people with cancer died within the study period, allowing analysis of 104 064 assessments. People preferring non-English languages were less likely to report symptoms (pain: OR=0.89 (0.84 to 0.94); all other symptoms except fatigue OR<1 and CIs did not contain 1). Except for family/carer problems (OR=1.24 (1.12 to 1.31)), linguistically diverse people were less likely to report problems. Variation was seen between non-English language groups. CONCLUSIONS: We did not find evidence of comparatively worse symptom distress or problem severity for nearly all scores for culturally and linguistically diverse Australians. Better symptom management or differential reporting may explain this. It is important to examine this further, including assessing differences within cultural and linguistic groups to ensure the delivery of high-quality palliative care.

Assessing health state utilities for people with myalgic encephalomyelitis/chronic fatigue syndrome in Australia using the EQ-5D-5L, AQoL-8D and EQ-5D-5L-psychosocial instruments.

PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition with a constellation of symptoms presenting as severe and profound fatigue of ≥ 6 months not relieved by rest. ME/CFS affects health-related quality of life (HRQoL), which can be measured using multi-attribute health state utility (HSU) instruments. The aims of this study were to quantify HSUs for people living with ME/CFS, and to identify an instrument that is preferentially sensitive for ME/CFS. METHODS: Cross-sectional national survey of people with ME/CFS using the AQoL-8D and EQ-5D-5L. Additional questions from the AQoL-8D were used as 'bolt-ons' to the EQ-5D-5L (i.e., EQ-5D-5L-Psychosocial). Disability and fatigue severity were assessed using the De Paul Symptom Questionnaire-Short Form (DSQ-SF). HSUs were generated using Australian tariffs. Mean HSUs were stratified for sociodemographic and clinical factors. Bland-Altman plots were used to compare the three HSU instruments. RESULTS: For the 198 participants, mean HSUs (95% confidence intervals) were EQ-5D-5L: 0.46 (0.42-0.50); AQoL-8D: 0.43 (0.41-0.45); EQ-5D-5L-Psychosocial: 0.44 (0.42-0.46). HSUs were substantially lower than population norms: EQ-5D-5L: 0.89; AQoL-8D: 0.77. As disability and fatigue severity increased, HSUs decreased in all three instruments. Bland-Altman plots revealed interchangeability between the AQoL-8D and EQ-5D-5LPsychosocial. Floor and ceiling effects of 13.5% and 2.5% respectively were observed for the EQ-5D-5L instrument only. CONCLUSIONS: ME/CFS has a profound impact on HRQoL. The AQoL-8D and EQ-5D-5L-Psychosocial can be used interchangeably: the latter represents a reduced participant burden.

The economic burden of myalgic encephalomyelitis/chronic fatigue syndrome in Australia.

Objective This study aimed to estimate costs of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to patients, government and Australian society. Methods Australian ME/CFS patients and their carers were recruited using convenience sampling. Patients completed an online retrospective cost diary, providing ME/CFS-related direct medical, non-medical and indirect costs. Informal care costs were collected directly from carers. Data from the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule were linked to participant survey data. Annual per patient and total societal costs were estimated, broken down by category and presented in 2021 AUD. Factors associated with higher costs were investigated using generalised linear models. Results One hundred and seventy five patients (mean age 49 years s.d. 14, 79.4% female) completed the cost diary. Estimated total annual societal costs of ME/CFS in Australia ranged between $1.38 and $10.09 billion, with average annual total costs of $63 400/patient. Three-quarters of these costs were due to indirect costs ($46 731). Disability severity was the key factor associated with higher costs, particularly for indirect costs (being 2.27-fold higher for severe disability than no/mild disability). Conclusions ME/CFS poses a significant economic burden in Australia, owing mainly to high indirect and informal care costs.

Surveillance for liver cancer in primary care: A systematic review of the evidence.

BACKGROUND AND OBJECTIVES: In Australia, mortality rates for hepatocellular carcinoma (HCC) are rising. Targeted surveillance is recommended to increase early diagnosis. The aim of this study was to synthesise evidence regarding HCC surveillance in primary care and identify barriers and facilitators to surveillance. METHOD: A systematic review was performed, with searches conducted in five biomedical databases, the Centre for Reviews and Dissemination website and the grey literature. Study quality was assessed using the National Institute for Heath and Care Excellence (NICE) quality appraisal checklists. RESULTS: In all, 32 studies, focusing on viral hepatitis and cirrhosis patients, were included in the review. HCC surveillance rates were lower for patients managed by primary care providers (PCPs) than for those managed by gastroenterologists/hepatologists. HCC surveillance rates increased when additional support was provided to PCPs (eg reminder systems, nurse follow-up). Key barriers were a lack of awareness of HCC risks and surveillance recommendations, as well as competing priorities PCPs must address when working with patients with multimorbidity. DISCUSSION: HCC surveillance programs in primary care should be accompanied by additional support for PCPs and strategies to increase awareness of clinical recommendations.

Long-term exposure to low concentrations of air pollution and decline in lung function in people with idiopathic pulmonary fibrosis: Evidence from Australia.

BACKGROUND AND OBJECTIVE: Little is known about the association between ambient air pollution and idiopathic pulmonary fibrosis (IPF) in areas with lower levels of exposure. We aimed to investigate the impact of air pollution on lung function and rapid progression of IPF in Australia. METHODS: Participants were recruited from the Australian IPF Registry (n = 570). The impact of air pollution on changes in lung function was assessed using linear mixed models and Cox regression was used to investigate the association with rapid progression. RESULTS: Median (25th-75th percentiles) annual fine particulate matter (<2.5 µm, PM2.5 ) and nitrogen dioxide (NO2 ) were 6.8 (5.7, 7.9) µg/m3 and 6.7 (4.9, 8.2) ppb, respectively. Compared to living more than 100 m from a major road, living within 100 m was associated with a 1.3% predicted/year (95% confidence interval [CI] -2.4 to -0.3) faster annual decline in diffusing capacity of the lungs for carbon monoxide (DLco). Each interquartile range (IQR) of 2.2 µg/m3 increase in PM2.5 was associated with a 0.9% predicted/year (95% CI -1.6 to -0.3) faster annual decline in DLco, while there was no association observed with NO2 . There was also no association between air pollution and rapid progression of IPF. CONCLUSION: Living near a major road and increased PM2.5 were both associated with an increased rate of annual decline in DLco. This study adds to the evidence supporting the negative effects of air pollution on lung function decline in people with IPF living at low-level concentrations of exposure.

Risk of hospital admission or emergency department presentation due to diabetes complications: a retrospective cohort study in Tasmania, Australia.

Objective To estimate the risk of an emergency department (ED)/inpatient visit due to complications in people with diabetes and compare them to their non-diabetes counterparts. Methods This matched retrospective cohort study used a linked dataset in Tasmania, Australia for the 2004-17 period. People with diabetes (n = 45 378) were matched on age, sex and geographical regions with people without diabetes (n = 90 756) based on propensity score matching. The risk of an ED/inpatient visit related to each complication was estimated using negative binomial regression. Results In people with diabetes, the combined ED and admission rates per 10 000 person-years were considerable, especially for macrovascular complications (ranging from 31.8 (lower extremity amputation) to 205.2 (heart failure)). The adjusted incidence rate ratios of ED/inpatient visits were: retinopathy 59.1 (confidence interval 25.8, 135.7), lower extremity amputation 11.1 (8.8, 14.1), foot ulcer/gangrene 9.5 (8.1, 11.2), nephropathy 7.4 (5.4, 10.1), dialysis 6.5 (3.8, 10.9), transplant 6.3 (2.2, 17.8), vitreous haemorrhage 6.0 (3.7, 9.8), fatal myocardial infarction 3.4 (2.3, 5.1), kidney failure 3.3 (2.3, 4.5), heart failure 2.9 (2.7, 3.1), angina pectoris 2.1 (2.0, 2.3), ischaemic heart disease 2.1 (1.9, 2.3), neuropathy 1.9 (1.7, 2.0), non-fatal myocardial infarction 1.7 (1.6, 1.8), blindness/low vision 1.4 (0.8, 2.5), non-fatal stroke 1.4 (1.3, 1.6), fatal stroke 1.3 (0.9, 2.1) and transient ischaemic attack 1.1 (1.0, 1.2). Conclusions Our results demonstrated the high demand on hospital services due to diabetes complications (especially macrovascular complications) and highlighted the importance of preventing and properly managing microvascular complications. These findings will support future resource allocation to reduce the increasing burden of diabetes in Australia.

Hepatocellular carcinoma surveillance based on the Australian Consensus Guidelines: a health economic modelling study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fastest increasing cause of cancer death in Australia. A recent Australian consensus guidelines recommended HCC surveillance for cirrhotic patients and non-cirrhotic chronic hepatitis B (CHB) patients at gender and age specific cut-offs. A cost-effectiveness model was then developed to assess surveillance strategies in Australia. METHODS: A microsimulation model was used to evaluate three strategies: biannual ultrasound, biannual ultrasound with alpha-fetoprotein (AFP) and no formal surveillance for patients having one of the conditions: non-cirrhotic CHB, compensated cirrhosis or decompensated cirrhosis. One-way and probabilistic sensitivity analyses as well as scenario and threshold analyses were conducted to account for uncertainties: including exclusive surveillance of CHB, compensated cirrhosis or decompensated cirrhosis populations; impact of obesity on ultrasound sensitivity; real-world adherence rate; and different cohort's ranges of ages. RESULTS: Sixty HCC surveillance scenarios were considered for the baseline population. The ultrasound + AFP strategy was the most cost-effective with incremental cost-effectiveness ratios (ICER) compared to no surveillance falling below the willingness-to-pay threshold of A$50,000 per quality-adjusted life year (QALY) at all age ranges. Ultrasound alone was also cost-effective, but the strategy was dominated by ultrasound + AFP. Surveillance was cost-effective in the compensated and decompensated cirrhosis populations alone (ICERs < $30,000), but not cost-effective in the CHB population (ICERs > $100,000). Obesity could decrease the diagnostic performance of ultrasound, which in turn, reduce the cost-effectiveness of ultrasound ± AFP, but the strategies remained cost-effective. CONCLUSIONS: HCC surveillance based on Australian recommendations using biannual ultrasound ± AFP was cost-effective.

The influence of immortal time bias in observational studies examining associations of antifibrotic therapy with survival in idiopathic pulmonary fibrosis: A simulation study.

Background: Immortal time bias (ITB) has been overlooked in idiopathic pulmonary fibrosis (IPF). We aimed to identify the presence of ITB in observational studies examining associations between antifibrotic therapy and survival in patients with IPF and illustrate how ITB may affect effect size estimates of those associations. Methods: Immortal time bias was identified in observational studies using the ITB Study Assessment Checklist. We used a simulation study to illustrate how ITB may affect effect size estimates of antifibrotic therapy on survival in patients with IPF based on four statistical techniques including time-fixed, exclusion, time-dependent and landmark methods. Results: Of the 16 included IPF studies, ITB was detected in 14 studies, while there were insufficient data for assessment in two others. Our simulation study showed that use of time-fixed [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.47-0.64] and exclusion methods (HR 0.79, 95% CI 0.67-0.92) overestimated the effectiveness of antifibrotic therapy on survival in simulated subjects with IPF, in comparison of the time-dependent method (HR 0.93, 95% CI 0.79-1.09). The influence of ITB was mitigated using the 1 year landmark method (HR 0.69, 95% CI 0.58-0.81), compared to the time-fixed method. Conclusion: The effectiveness of antifibrotic therapy on survival in IPF can be overestimated in observational studies, if ITB is mishandled. This study adds to the evidence for addressing the influence of ITB in IPF and provides several recommendations to minimize ITB. Identifying the presence of ITB should be routinely considered in future IPF studies, with the time-dependent method being an optimal approach to minimize ITB.

Mapping EQ5D utilities from forced vital capacity and diffusing capacity in fibrotic interstitial lung disease.

OBJECTIVES: Fibrotic interstitial lung disease (ILD) includes a large group of conditions that lead to scarring of the lungs. The lack of available 5-level EuroQol 5D (EQ5D) data has limited the ability to conduct economic evaluations in ILD. The purpose of this study was to develop and validate a mapping algorithm that predicts EQ5D utilities from commonly collected pulmonary function measurements (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]) in fibrotic ILDs. METHODS: EQ5D utility and pulmonary function measurements from the Canadian Registry for Pulmonary Fibrosis were included. Ordinary least squares (OLS), beta regression, two-part, and tobit models were used to map EQ5D utilities from FVC or DLCO. Model performance was assessed by comparing the predicted and observed utilities. Subgroup analyses were also conducted to test how well models performed across different patient characteristics. The models were then externally validated in the Australian Idiopathic Pulmonary Fibrosis Registry. RESULTS: The OLS model performed as well as other more complex models (root mean squared error: 0.17 for FVC and 0.16 for DLCO). As with the other models, the OLS algorithm performed well across the different subgroups (except for EQ5D utilities < 0.5) and in the external validation cohort. CONCLUSION: We developed a mapping algorithm that predicts EQ5D utilities from FVC and DLCO, with the intent that this algorithm can be applied to clinical trial populations and real-world cohorts that have not prioritized collection of health-related utilities. The mapping algorithm can be used in future economic evaluations of potential ILD therapies.

The relative contribution of co-morbidities to health-related quality of life of people with idiopathic pulmonary fibrosis using the Assessment of Quality of Life-8-Dimension multi-attribute utility instrument.

PURPOSE: Little is known about the impact of co-morbidities on health-related quality of life (HRQoL) for people with idiopathic pulmonary fibrosis (IPF). We aimed to investigate the relative contribution of co-morbidities to HRQoL of people with IPF. METHODS: N = 157 participants were recruited from the Australian IPF Registry (AIPFR). Health state utilities (HSUs), and the super-dimensions of physical and psychosocial scores were measured using the Assessment of Quality of Life-8-Dimensions (AQoL-8D). The impact of co-morbidities on HRQoL was investigated using linear regression and general dominance analyses. RESULTS: A higher number of co-morbidities was associated with lower HSUs (p trend = 0.002). Co-morbidities explained 9.1% of the variance of HSUs, 16.0% of physical super-dimensional scores, and 4.2% of psychosocial super-dimensional scores. Arthritis was associated with a significant reduction on HSUs (ß = - 0.09, 95% confidence interval [CI] - 0.16 to - 0.02), largely driven by reduced scores on the physical super-dimension (ß = - 0.13, 95% CI - 0.20 to - 0.06). Heart diseases were associated with a significant reduction on HSUs (ß = - 0.09, 95% CI - 0.16 to - 0.02), driven by reduced scores on physical (ß = - 0.09, 95% CI - 0.16 to - 0.02) and psychosocial (ß = -0.10, 95% CI - 0.17 to - 0.02) super-dimensions. CONCLUSIONS: Co-morbidities significantly impact HRQoL of people with IPF, with markedly negative impacts on their HSUs and physical health. A more holistic approach to the care of people with IPF is important as better management of these co-morbidities could lead to improved HRQoL in people with IPF.

The economic burden of idiopathic pulmonary fibrosis in Australia: a cost of illness study.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease found mostly in elderly persons, characterized by a high symptom burden and frequent encounters with health services. This study aimed to quantify the economic burden of IPF in Australia with a focus on resource utilization and associated direct costs. METHODS: Participants were recruited from the Australian IPF Registry (AIPFR) between August 2018 and December 2019. Data on resource utilization and costs were collected via cost diaries and linked administrative data. Clinical data were collected from the AIPFR. A "bottom up" costing methodology was utilized, and the costing was performed from a partial societal perspective focusing primarily on direct medical and non-medical costs. Costs were standardized to 2021 Australian dollars ($). RESULTS: The average annual total direct costs per person with IPF was $31,655 (95% confidence interval (95% CI): $27,723-$35,757). Extrapolating costs based on prevalence estimates, the total annual costs in Australia are projected to be $299 million (95% CI: $262 million-$338 million). Costs were mainly driven by antifibrotic medication, hospital admissions and medications for comorbidities. Disease severity, comorbidities and antifibrotic medication all had varying impacts on resource utilization and costs. CONCLUSION: This cost-of-illness study provides the first comprehensive assessment of IPF-related direct costs in Australia, identifies the key cost drivers and provides a framework for future health economic analyses. Additionally, it provided insight into the major cost drivers which include antifibrotic medication, hospital admissions and medications related to comorbidities. Our findings emphasize the importance of the appropriate management of comorbidities in the care of people with IPF as this was one of the main reasons for hospitalizations.

Assessment of health-related quality of life in Australian patients with idiopathic pulmonary fibrosis: a comparison of the EQ-5D-5L and the AQoL-8D.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating chronic lung disease with a high symptom burden, which has a substantial impact on health-related quality of life (HRQoL). Our study aimed to assess the suitability of the EuroQol five-dimension (EQ-5D-5L) and the Assessment of Quality of Life- eight-dimension (AQoL-8D) questionnaires in measuring HRQoL as health state utility values (HSUVs) in an Australian IPF cohort. METHODS: Data for estimation of health state utility values (HSUVs) were collected from participants of the Australian IPF Registry (AIPFR) using self-administered surveys which included the EQ-5D-5L and the AQoL-8D. Data on lung function and disease specific HRQoL instruments were collected from the AIPFR. Performance of the two instruments was evaluated based on questionnaire practicality, agreement between the two instruments and test performance (internal and construct validity). RESULTS: Overall completion rates for the EQ-5D-5L and AQoL-8D were 96% and 85%, respectively. Mean (median) HSUVs were 0.65 (0.70) and 0.69 (0.72) for the EQ-5D-5L and AQoL-8D, respectively. There was reasonable agreement between the two instruments based on the Bland-Altman plot mean difference (-0.04) and intraclass correlation coefficient (0.84), however there were some fundamental differences. A larger range of values was observed with the EQ-5D-5L (-0.57-1.00 vs 0.16-1.00). The EQ-5D-5L had a greater divergent sensitivity and efficacy in relation to assessing HSUVs between clinical groupings. The AQoL-8D ,however, had a higher sensitivity to measure psychosocial aspects of HRQoL in IPF. CONCLUSION: The EQ-5D-5L demonstrated superior performance when compared to AQoL-8D in persons with IPF. This may be attributable to the high symptom burden which is physically debilitating to which the EQ-5D-5L may be more sensitive.

Costs of major complications in people with and without diabetes in Tasmania, Australia.

Objective We set out to estimate healthcare costs of diabetes complications in the year of first occurrence and the second year, and to quantify the incremental costs of diabetes versus non-diabetes related to each complication. Methods In this cohort study, people with diabetes (n = 45 378) and their age/sex propensity score matched controls (n = 90 756) were identified from a linked dataset in Tasmania, Australia between 2004 and 2017. Direct costs (including hospital, emergency room visits and pathology costs) were calculated from the healthcare system perspective and expressed in 2020 Australian dollars. The average-per-patient costs and the incremental costs in people with diabetes were calculated for each complication. Results First-year costs when the complications occurred were: dialysis $78 152 (95% CI 71 095, 85 858), lower extremity amputations $63 575 (58 290, 68 688), kidney transplant $48 487 (33 862, 68 283), non-fatal myocardial infarction $30 827 (29 558, 32 197), foot ulcer/gangrene $29 803 (27 183, 32 675), ischaemic heart disease $29 160 (26 962, 31 457), non-fatal stroke $27 782 (26 285, 29 354), heart failure $27 379 (25 968, 28 966), kidney failure $24 904 (19 799, 32 557), angina pectoris $18 430 (17 147, 19 791), neuropathy $15 637 (14 265, 17 108), nephropathy $15 133 (12 285, 18 595), retinopathy $14 775 (11 798, 19 199), transient ischaemic attack $13 905 (12 529, 15 536), vitreous hemorrhage $13 405 (10 241, 17 321), and blindness/low vision $12 941 (8164, 19 080). The second-year costs ranged from 16% (ischaemic heart disease) to 74% (dialysis) of first-year costs. Complication costs were 109-275% higher than in people without diabetes. Conclusions Diabetes complications are costly, and the costs are higher in people with diabetes than without diabetes. Our results can be used to populate diabetes simulation models and will support policy analyses to reduce the burden of diabetes.

Survival of primary liver cancer for people from culturally and linguistically diverse backgrounds in Australia.

BACKGROUND: Survival for Primary Liver Cancer (PLC) has been investigated in Australia, but limited work has been conducted on the burden for people with different socioeconomic status, region of residence, causes of PLC, and culturally and linguistically diverse (CALD) backgrounds. This study aimed to cover this gap in the literature by investigating PLC survival with the aforementioned factors. METHODS: This study linked four administrative datasets: Victorian Cancer Registry, Admitted Episodes Dataset, Emergency Minimum Dataset, and Death Index. The cohort was all cases with a PLC notification within the Victorian Cancer Registry between 01/01/2008 and 01/01/2016. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test was used to compare the difference in survival between subgroups. The Cox proportional hazard model was used to explore factors associated with PLC survival. RESULTS: The 1-, 3- and 5-year survival rates were 50.0%, 28.1% and 20.6%, respectively, with a median survival of 12.0 months (95% confidence interval (CI): 11.0 - 12.9 months). Higher survival was associated with younger age, hepatocellular carcinoma, and higher socio-economic status. People born in Asian, African, and American regions had higher survival than those born in Australia and New Zealand. Cases with viral hepatitis as an identified aetiology had higher survival than those whose PLC was related to alcohol consumption (hazard ratio=1.52, 95% CI: 1.19 - 1.96), diabetes and fatty liver disease (hazard ratio=1.35, 95% CI: 1.08 - 1.68). CONCLUSION: Survival outcomes for people diagnosed with PLC were still poor and affected by many factors. Asian and African cases had better survival than Australian and New Zealand patients as PLC in Asian and African cases was mostly caused by viral hepatitis. Metropolitan areas were associated with a higher survival than rural areas, not only due to accessibility to surveillance and healthcare services but also because the majority of overseas-born patients reside in metropolitan areas.

Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS).

BACKGROUND: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis. METHODS: We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0-3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses. DISCUSSION: This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018.

Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in Australian primary care patients: only part of the story?

BACKGROUND: ME/CFS is a disorder characterized by recurrent fatigue and intolerance to exertion which manifests as profound post-exertional malaise. Prevalence studies internationally have reported highly variable results due to the 20 + diagnostic criteria. For Australia, the prevalence of ME/CFS based on current case definitions is unknown. OBJECTIVES: To report prevalence of ME/CFS in patients aged ≥ 13 years attending Australian primary care settings for years 2015-2019, and provide context for patterns of primary care attendance by people living with ME/CFS. METHODOLOGY: Conducted in partnership with the Patient Advisory Group, this study adopted a mixed methods approach. De-identified primary care data from the national MedicineInsight program were analyzed. The cohort were regularly attending patients, i.e. 3 visits in the preceding 2 years. Crude prevalence rates were calculated for years 2015-2019, by sex, 10-year age groups, remoteness and socioeconomic status. Rates are presented per 100,000population (95% confidence intervals (CI)). Qualitative data was collected through focus groups and in-depth 1:1 interview. RESULTS: Qualitative evidence identified barriers to reaching diagnosis, and limited interactions with primary care due to a lack of available treatments/interventions, stigma and disbelief in ME/CFS as a condition. In each year of interest, crude prevalence in the primary care setting ranged between 94.9/100,000 (95% CI: 91.5-98.5) and 103.9/100,000 population (95%CI: 100.3-107.7), equating to between 20,140 and 22,050 people living with ME/CFS in Australia in 2020. Higher rates were observed for age groups 50-59 years and 40-49 years. Rates were substantially higher in females (130.0-141.4/100,000) compared to males (50.9-57.5/100,000). In the context of the qualitative evidence, our prevalence rates likely represent an underestimate of the true prevalence of ME/CFS in the Australian primary care setting. CONCLUSION: ME/CFS affects a substantial number of Australians. Whilst this study provides prevalence estimates for the Australian primary care setting, the qualitative evidence highlights the limitations of these. Future research should focus on using robust case ascertainment criteria in a community setting. Quantification of the burden of disease can be used to inform health policy and planning, for this understudied condition.

A Comprehensive Systematic Review of Data Linkage Publications on Diabetes in Australia.

Aims: Our study aimed to identify the common themes, knowledge gaps and to evaluate the quality of data linkage research on diabetes in Australia. Methods: This systematic review was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (the PRISMA Statement). Six biomedical databases and the Australian Population Health Research Network (PHRN) website were searched. A narrative synthesis was conducted to comprehensively identify the common themes and knowledge gaps. The guidelines for studies involving data linkage were used to appraise methodological quality of included studies. Results: After screening and hand-searching, 118 studies were included in the final analysis. Data linkage publications confirmed negative health outcomes in people with diabetes, reported risk factors for diabetes and its complications, and found an inverse association between primary care use and hospitalization. Linked data were used to validate data sources and diabetes instruments. There were limited publications investigating healthcare expenditure and adverse drug reactions (ADRs) in people with diabetes. Regarding methodological assessment, important information about the linkage performed was under-reported in included studies. Conclusions: In the future, more up to date data linkage research addressing costs of diabetes and its complications in a contemporary Australian setting, as well as research assessing ADRs of recently approved antidiabetic medications, are required.

Hospitalisation costs of primary liver cancer in Australia: evidence from a data-linkage study.

Objective This study aimed to estimate the public hospital costs associated with primary liver cancer (PLC) in the first and second years following the cancer diagnosis. Methods This study linked administrative datasets of patients diagnosed with PLC in Victoria, Australia, from January 2008 to December 2015. The health system perspective was adopted to estimate the direct healthcare costs associated with PLC, based on inpatient and emergency costs. Costs were estimated for the first 12 months and 12-24 months after the PLC diagnosis and expressed in 2017 Australian dollars (A$). The cost estimated was then extrapolated nationally. The linear mixed model with a Box-Cox transformation of the costs was used to explore the relationship between costs and patients' sociodemographic and clinical characteristics. Results For the first 12 months, the total and annual per-patient cost was A$211.4 million and A$63 664, respectively. Costs for the subsequent year were A$49.7 million and A$46 751, respectively. Regarding the cost extrapolation to Australia, the total cost was A$137 million for the first 12 months after notification and A$42.6 million for the period from 12 to 24 months. Higher costs per episode of care were mostly associated with older age, hepatocellular carcinoma type of PLC, metropolitan hospitals, and Asian birth region. Conclusion This study showed the public hospital admission and emergency costs associated with PLC and the substantial economic burden this cancer has placed on the Australian health system.