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.

The quality of life impact of the COVID-19 pandemic and lockdowns for people living with multiple sclerosis (MS): evidence from the Australian MS Longitudinal Study.

PURPOSE: People living with multiple sclerosis (PwMS) in metropolitan Victoria, Australia, experienced a 112-day, COVID-19-related lockdown in mid-2020. Contemporaneously, Australian PwMS elsewhere experienced minimal restrictions, resulting in a natural experiment. This study investigated the relationships between lockdowns, COVID-19-related adversity, and health-related quality of life (HRQoL). It also generated health state utilities (HSU) representative of changes in HRQoL. METHODS: Data were extracted from Australian MS Longitudinal Study surveys, which included the Assessment of Quality of Life-Eight Dimensions (AQoL-8D) instrument and a COVID-19 questionnaire. This COVID-19 questionnaire required participants to rank their COVID-19-related adversity across seven health dimensions. Ordered probits were used to identify variables contributing to adversity. Linear and logit regressions were applied to determine the impact of adversity on HRQoL, defined using AQoL-8D HSUs. Qualitative data were examined thematically. RESULTS: N = 1666 PwMS (average age 58.5; 79.8% female; consistent with the clinical presentation of MS) entered the study, with n = 367 (22.0%) exposed to the 112-day lockdown. Lockdown exposure and disability severity were strongly associated with higher adversity rankings (p < 0.01). Higher adversity rankings were associated with lower HSUs. Participants reporting major adversity, across measured health dimensions, had a mean HSU 0.161 (p < 0.01) lower than participants reporting no adversity and were more likely (OR: 2.716, p < 0.01) to report a clinically significant HSU reduction. Themes in qualitative data supported quantitative findings. CONCLUSIONS: We found that COVID-19-related adversity reduced the HRQoL of PwMS. Our HSU estimates can be used in health economic models to evaluate lockdown cost-effectiveness for people with complex and chronic (mainly neurological) diseases.

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.

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.

Exploring the cost-effectiveness of EBV vaccination to prevent multiple sclerosis in an Australian setting.

BACKGROUND: Increasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination to prevent MS in an Australian setting. METHODS: A five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: From societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=-$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=-$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios. CONCLUSIONS: MS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective.

The disease-modifying therapy utilisation and cost trend for multiple sclerosis in Australia between 2013 and 2022.

BACKGROUND: The MS disease-modifying therapies (DMTs) prescribing landscape in Australia have changed over time. OBJECTIVES: This study evaluated the utilisation and cost trends of MS-related DMTs in Australia over 10 years and investigated differences between States/Territories. METHODS: The prescription and costs of 16 DMTs were extracted from the Pharmaceutical Benefits Scheme for 2013-2022. Descriptive approaches analysed the total number of people prescribed DMTs and total DMT costs per 10,000 population, proportions of prescriptions/costs by DMT groups and the number of people prescribed each individual DMT and costs of each DMT over the 10-year period. All estimates were for Australia and each State/Territory individually. RESULTS: The number of people prescribed DMT and costs per 10,000 population had substantial growth between 2013 and 2022: 125%/164% for Australia, and 94%-251%/129%-373% for individual States/Territories. Higher efficacy group accounted for 54% of total people prescribed DMTs in 2013 and 75% in 2022. Fingolimod was the most popular DMT until 2020, then was dominated by ocrelizumab. The trends of individual DMT prescriptions and costs differed between states particularly in Western Australia (WA), Tasmania and Northern Territory (NT). CONCLUSION: DMT prescriptions and costs continuously increased over the last decade, particularly for higher efficacy DMTs, and their trends differed between States/Territories.

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.

Using qualitative free-text data to investigate the lived experience of the COVID-19 pandemic for a large cohort of Australians with different multiple sclerosis related disability levels.

BACKGROUND: No large-scale qualitative studies have investigated the lived experience of people living with multiple sclerosis (PwMS) during the pandemic according to their disability level. We used qualitative research methods to investigate the lived experience of a large cohort of Australians living with differing multiple sclerosis (MS)-related disability levels during the COVID-19 pandemic. We also provided useful contextualisation to existing quantitative work. METHODS: This was a retrospective survey-based mixed-methods cohort study. A quality-of-life study was conducted within the Australian MS Longitudinal Study during the pandemic. Disability severity was calculated using the Patient Determined Disease Steps. Qualitative free-text data regarding COVID-19 impacts was collected/analysed for word frequency and also thematically (inductively/deductively using sophisticated grounded theory) using NVivo software. We also triangulated word frequency with emerging themes. RESULTS: N=509 PwMS participated providing n=22 530 words of COVID-19-specific data. Disability severity could be calculated for n=501 PwMS. The word 'working' was important for PwMS with no disability, and 'support' and 'isolation' for higher disability levels. For PwMS with milder disability, thematic analysis established that multitasking increased stress levels, particularly if working from home (WFH) and home-schooling children. If not multitasking, WFH was beneficial for managing fatigue. PwMS with severe disability raised increased social isolation as a concern including prepandemic isolation. CONCLUSIONS: We found negative impacts of multitasking and social isolation for PwMS during the pandemic. WFH was identified as beneficial for some. We recommend targeted resourcing decisions for PwMS in future pandemics including child-care relief and interventions to reduce social isolation and suggest that these could be incorporated into some form of advanced care planning. As the nature of work changes postpandemic, we also recommend a detailed investigation of WFH for PwMS including providing tailored employment assistance.

Calibration of the IQVIA Core Diabetes Model to the stroke outcomes from the SUSTAIN 6 cardiovascular outcomes trial of once-weekly semaglutide.

AIMS: In the SUSTAIN 6 cardiovascular outcomes trial, once-weekly semaglutide was associated with a statistically significant reduction in major adverse cardiovascular events compared with placebo. To date, no studies have assessed how accurately existing diabetes models predict the outcomes observed in SUSTAIN 6. The aims of this analysis were to investigate the performance of the IQVIA Core Diabetes Model when used to predict the SUSTAIN 6 trial outcomes, to calibrate the model such that projected outcomes reflected observed outcomes, and to examine the impact of calibration on the cost-effectiveness of once-weekly semaglutide from a UK healthcare payer perspective. METHODS: The IQVIA Core Diabetes Model was calibrated to ensure that the projected non-fatal stroke event rates reflected the non-fatal stroke event rates observed in SUSTAIN 6 over a two-year time horizon. Cost-effectiveness analyses of once-weekly semaglutide versus placebo plus standard of care were conducted over a lifetime horizon using the uncalibrated and calibrated models to assess the impact on cost-effectiveness outcomes. RESULTS: To replicate the non-fatal stroke event rate in SUSTAIN 6, calibration of the model through the application of relative risks for stroke of 1.07 and 1.65 with once-weekly semaglutide and placebo, respectively, was required. In the long-term cost-effectiveness analysis, the uncalibrated model projected an incremental cost-effectiveness ratio for once-weekly semaglutide versus placebo plus standard of care of GBP 22,262 per quality-adjusted life year (QALY) gained, which fell to GBP 17,594 per QALY gained when the calibrated model was used. CONCLUSIONS: The requirement for calibration to replicate the outcomes observed in SUSTAIN 6 suggests that the reductions in risk of cardiovascular complications observed with once-weekly semaglutide cannot be solely explained by differences in conventional risk factors. Accurate estimation of the risk of diabetes-related complications using methods such as calibration is important to ensure accurate cost-effectiveness analyses are conducted.

trips4health: a single-blinded randomised controlled trial incentivising adult public transport use for physical activity gain.

BACKGROUND: Public transport users tend to accumulate more physical activity than non-users; however, whether physical activity is increased by financially incentivising public transport use is unknown. The trips4health study aimed to determine the impact of an incentive-based public transport intervention on physical activity. METHODS: A single-blinded randomised control trial of a 16-week incentive-based intervention involved Australian adults who were infrequent bus users (≥ 18 years; used bus ≤ 2 times/week) split equally into intervention and control groups. The intervention group were sent weekly motivational text messages and awarded smartcard bus credit when targets were met. The intervention group and control group received physical activity guidelines. Accelerometer-measured steps/day (primary outcome), self-reported transport-related physical activity (walking and cycling for transport) and total physical activity (min/week and MET-min/week) outcomes were assessed at baseline and follow-up. RESULTS: Due to the COVID pandemic, the trial was abandoned prior to target sample size achievement and completion of all assessments (N = 110). Steps/day declined in both groups, but by less in the intervention group [-557.9 steps (-7.9%) vs.-1018.3 steps/week (-13.8%)]. In the intervention group, transport-related physical activity increased [80.0 min/week (133.3%); 264.0 MET-min/week (133.3%)] while total physical activity levels saw little change [35.0 min/week (5.5%); 25.5 MET-min/week (1.0%)]. Control group transport-related physical activity decreased [-20.0 min/week (-27.6%); -41.3 MET-min/week (-17.3%)], but total physical activity increased [260.0 min/week (54.5%); 734.3 MET-min/week (37.4%)]. CONCLUSION: This study found evidence that financial incentive-based intervention to increase public transport use is effective in increasing transport-related physical activity These results warrant future examination of physical activity incentives programs in a fully powered study with longer-term follow-up. TRIAL REGISTRATION: This trial was registered with the Australian and New Zealand Clinical Trials Registry August 14th, 2019: ACTRN12619001136190; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377914&isReview=true.

Estimating the disutility of relapse in relapsing-remitting and secondary progressive multiple sclerosis using the EQ-5D-5L, AQoL-8D, EQ-5D-5L-psychosocial, and SF-6D: implications for health economic evaluation models.

BACKGROUND AND AIMS: Relapses are an important clinical feature of multiple sclerosis (MS) that result in temporary negative changes in quality of life (QoL), measured by health state utilities (HSUs) (disutilities). We aimed to quantify disutilities of relapse in relapsing remitting MS (RRMS), secondary progressive MS (SPMS), and relapse onset MS [ROMS (including both RRMS and SPMS)] and examine these values by disability severity using four multi-attribute utility instruments (MAUIs). METHODS: We estimated (crude and adjusted and stratified by disability severity) disutilities (representing the mean difference in HSUs of 'relapse' and 'no relapse' groups as well as 'unsure' and 'no relapse' groups) in RRMS (n = 1056), SPMS (n = 239), and ROMS (n = 1295) cohorts from the Australian MS Longitudinal Study's 2020 QoL survey, using the EQ-5D-5L, AQoL-8D, EQ-5D-5L-Psychosocial, and SF-6D MAUIs. RESULTS: Adjusted mean overall disutilities of relapse in RMSS/SPMS/ROMS were - 0.101/- 0.149/- 0.129 (EQ-5D-5L), - 0.092/- 0.167/- 0.113 (AQoL-8D), - 0.080/- 0.139/- 0.097 (EQ-5D-5L-Psychosocial), and - 0.116/- 0.161/- 0.130 (SF-6D), approximately 1.5 times higher in SPMS than in RRMS, in all MAUI. All estimates were statistically significant and/or clinically meaningful. Adjusted disutilities of RRMS and ROMS demonstrated a U-shaped relationship between relapse disutilities and disability severity. Relapse disutilities were higher in 'severe' disability than 'mild' and 'moderate' in the SPMS cohort. CONCLUSION: MS-related relapses are associated with substantial utility decrements. As the type and severity of MS influence disutility of relapse, the use of disability severity and MS-type-specific disutility inputs is recommended in future health economic evaluations of MS. Our study supports relapse management and prevention as major mechanisms to improve QoL in people with MS.

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.

Cardiovascular and health cost impacts of cuff blood pressure underestimation and overestimation of invasive aortic systolic blood pressure.

OBJECTIVE: Hypertension management is directed by cuff blood pressure (BP), but this may be inaccurate, potentially influencing cardiovascular disease (CVD) events and health costs. This study aimed to determine the impact on CVD events and related costs of the differences between cuff and invasive SBP. METHODS: Microsimulations based on Markov modelling over one year were used to determine the differences in the number of CVD events (myocardial infarction or coronary death, stroke, atrial fibrillation or heart failure) predicted by Framingham risk and total CVD health costs based on cuff SBP compared with invasive (aortic) SBP. Modelling was based on international consortium data from 1678 participants undergoing cardiac catheterization and 30 separate studies. Cuff underestimation and overestimation were defined as cuff SBP less than invasive SBP and cuff SBP greater than invasive SBP, respectively. RESULTS: The proportion of people with cuff SBP underestimation versus overestimation progressively increased as SBP increased. This reached a maximum ratio of 16 : 1 in people with hypertension grades II and III. Both the number of CVD events missed (predominantly stroke, coronary death and myocardial infarction) and associated health costs increased stepwise across levels of SBP control, as cuff SBP underestimation increased. The maximum number of CVD events potentially missed (11.8/1000 patients) and highest costs ($241 300 USD/1000 patients) were seen in people with hypertension grades II and III and with at least 15 mmHg of cuff SBP underestimation. CONCLUSION: Cuff SBP underestimation can result in potentially preventable CVD events being missed and major increases in health costs. These issues could be remedied with improved cuff SBP accuracy.

A prospective study of the impact of COVID-19-related restrictions on activities and mobility upon physical activity, travel behaviour and attitudes.

Background and aims: Public health measures adopted to contain the spread of COVID-19 included restrictions on activities and mobility as people were asked to stay at home and schools moved to online learning. This may have increased risk of non-communicable disease by limiting recreational and transport-related physical activity. Building on an existing study, we assessed changes in self-reported and device-measured physical activity and travel behaviour before, during and after the peak of local COVID-19 outbreak and restrictions (March-July 2020). We examined beliefs in effectiveness of strategies to increase active and public transport after restrictions were reduced. Methods: A longitudinal study of adult infrequent bus users (average ≤ 2 trips per week; n = 70; 67% women) in Hobart, Australia. One-week assessment periods at four separate timepoints (before, during, 0-3 months after, and 3-6 months after the peak restrictions period) involved wearing an accelerometer, daily transport diaries, online surveys and tracking bus smartcard boardings. Results: Physical activity (especially among older participants), bus use and private motor vehicle use declined significantly during or 0-3 months after the peak restrictions period and returned to pre-restrictions levels by 3-6 months after the peak restrictions period, except bus use which remained significantly lower. Retrospective surveys overstated declines in bus use and active transport and self-reports understated declines in physical activity. Social distancing and improving service efficiency and frequency were seen as effective strategies for increasing bus use after restrictions but belief in effectiveness of distancing decreased over time. Conclusions: When restrictions on mobility are increased, supportive health promotion measures are needed to prevent declines in physical activity, particularly for older adults. Public transport systems need capacity to implement temporary distancing measures to prevent communicable disease transmission. Providing convenient, flexible, and efficient options for public transport may help to replenish public transport use after restrictions are reduced.

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.

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 effect of high versus low cognitive load on the development of nociceptive hypersensitivity: The roles of sympathetic arousal, sex and pain-related fear.

BACKGROUND: According to limited-capacity theories of attention, less attentional resources remain available when engaging in a high- versus a low-demanding cognitive task. This may reduce the perceived intensity and the evoked cortical responses of concomitant nociceptive stimuli. Whether and how the competition for limited attentional resources between a cognitive task and pain impacts the development of long-lasting hypersensitivity is unclear. METHODS: Eighty-four healthy participants were randomized into a low or high cognitive load group. Low-frequency electrical stimulation (LFS) of the skin was used to induce secondary hypersensitivity. We hypothesized that performing the high-load task during LFS would reduce the development of hypersensitivity. We examined whether painfulness, nonpain-related sympathetic arousal, or sex related to hypersensitivity, by assessing intensity and unpleasantness of mechanical pinprick stimulation. During task execution, we recorded steady-state evoked potentials evoked by LFS and skin conductance level for sympathetic arousal. Afterwards, participants reported task difficulty and LFS-related fear. For the primary outcomes, we used mixed analysis of variances. RESULTS: The results confirmed the difference in cognitive load. Although LFS successfully induced hypersensitivity, the high-load task did not reduce its development. Next, the steady-state evoked potentials did not differ between groups. Hypersensitivity correlated positively with pain-related fear and negatively with skin conductance level before LFS, despite the lack of group differences in skin conductance level. We did not find any sex differences in hypersensitivity. CONCLUSIONS: These results do not confirm that high cognitive load or sex modulate hypersensitivity, but show associations with pain-related fear and non-pain-related sympathetic arousal. SIGNIFICANCE: Previous research has mainly focused on cognitive load effects on the perception of acute painful stimuli. Yet this study extends our understanding by investigating cognitive load effects on the development of long-lasting secondary hypersensitivity, a common aspect in numerous persistent pain conditions. As cognitive tasks are presented during a painful procedure inducing secondary hypersensitivity, we test the long-lasting effects of cognitive load. Additionally, we used psychophysiological measurements to explored potential underlying mechanisms involving limited attentional resources and sympathetic arousal.

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.