Background: Non-adherence to lipid-lowering therapy (LLT) affects up to half of patients and contributes substantially to preventable cardiovascular morbidity and mortality. Existing measures, such as the proportion of days covered, provide cross-sectional summaries but fail to capture the dynamic patterns of adherence over time. Although group-based trajectory modelling identifies distinct longitudinal adherence patterns, no approach currently predicts trajectory membership prospectively while incorporating patient-reported barriers. We developed BRIDGE, a barrier-informed Bayesian model to predict adherence trajectories and identify their underlying drivers. Methods: BRIDGE incorporates patient-reported barriers as structured prior information within a Bayesian framework for adherence-trajectory prediction. The model was designed not only to estimate which patients are likely to follow different adherence trajectories, but also to generate clinically interpretable probability estimates that help explain why those trajectories may arise and what modifiable factors may be most relevant for intervention. Results: BRIDGE achieved a macro AUROC of 0.809 (95% CI 0.806 to 0.813), comparable to random forest (0.815 (95% CI 0.812 to 0.819)) and XGBoost (0.821 (95% CI 0.818 to 0.824)), two widely used machine-learning benchmarks for structured clinical prediction. Calibration was superior to random forest (Brier score 0.530 vs 0.545; ), and performance was stable across six independent training runs (AUROC SD = 0.003). Incorporating barrier-informed priors improved accuracy by 3.5% and calibration by 5.5% compared to flat priors, showing that incorporation of patient-reported barriers added value beyond electronic medical record data alone. Four clinically distinct adherence trajectories were identified: gradual decline associated with treatment deprioritisation amid polypharmacy (10.4%), early discontinuation linked to asymptomatic risk dismissal (40.5%), rapid decline associated with intolerance (28.8%), and persistent adherence (20.2%). Counterfactual analysis identified trajectory-specific intervention levers. Conclusions: BRIDGE provides accurate and well-calibrated prediction of adherence trajectories while offering clinically actionable insights into their underlying drivers. By integrating patient-reported barriers with routine clinical data, the model supports targeted, mechanism-informed interventions at the point of prescribing to improve adherence to cardioprotective therapies. Funding MRFF CVD Mission Grant 2017451 ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding by MRFF CVD Mission Grant 2017451 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was obtained under Monash University Human Research Ethics Committee (MUHREC) project number 40627. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data underlying this article will be shared on reasonable request to the corresponding author and subject to approval by stakeholders.

Abstract Objective First seizure events are common and may exert an immediate and profound impact on people's lives. Less understood are their long‐term consequences. This prospective, longitudinal study aimed to measure and compare psychosocial and health‐related work productivity trajectories following first seizure events of various etiologies. Methods Adults with first seizure events were recruited from five epilepsy centers in Australia and the US between 2020 and 2023. Participants completed questionnaires covering health‐related quality of life (HRQOL; EQ‐5D‐5L, QOLIE‐31), anxiety and depressive symptomatology (HADS), and productivity (WPAI) within 6 weeks of their first seizure event, and 6‐ and 12 months later. Results One hundred ninety‐six participants (median age 42 years, 55.6% male) met inclusion criteria. 101 (51.5%) had newly‐diagnosed epilepsy, 46 (23.4%) had acute symptomatic seizures, and 49 (25.0%) had syncope (seizure mimic). Compared to baseline, at 12‐month follow‐up, the acute symptomatic seizure group showed significant improvement in EQ‐5D‐5L utility (p = 0.001). The newly diagnosed epilepsy and acute symptomatic seizure groups both demonstrated improved QOLIE‐31 scores over 12 months (acute symptomatic seizure p = 0.025; newly diagnosed epilepsy p < 0.001). The newly diagnosed epilepsy group showed significant reductions in absenteeism (p < 0.001), presenteeism (p < 0.001), overall work impairment (p < 0.001), and activity impairment (p = 0.002). The acute symptomatic seizure group had a significant reduction in informal care needs (p < 0.001). Anxiety and depressive symptomatology remained unchanged across all groups. Significance HRQOL improved for people with acute symptomatic seizures and newly diagnosed epilepsy over time, but anxiety and depressive symptomatology remained unchanged. Future studies may explore interventions to improve screening and treatment of anxiety and depression for people following first seizure events. Plain Language Summary This study investigated changes in quality of life, anxiety and depressive symptomatology, and health‐related work productivity over a 12‐month period for adults with first seizure events. Participants reported improvements in quality of life, reduced sick days, increased productivity at work, and less need for informal care. Concerningly, there was no change in their anxiety and depressive symptoms. The findings of this study may prompt first seizure clinicians to regularly screen patients for anxiety and depressive disorders, and treat these appropriately.

Background: Heart failure is common in hospitalised adults, who often have high rates of polypharmacy. Two-thirds of readmissions are for non-cardiovascular reasons, where medications and comorbidities are likely to be contributors. The aim of this study was to quantify the proportion of non-cardiovascular readmissions and examine the factors associated with non-cardiovascular readmissions among multimorbid adults with heart failure. Methods: We conducted a retrospective cohort study of multimorbid adults aged ≥ 45 years with heart failure who were discharged from four metropolitan hospitals between August 2016 and June 2023. Non-cardiovascular polypharmacy was defined as the use of five or more non-cardiovascular medications as extracted from the electronic medical record at discharge from the hospitals. Non-cardiovascular readmissions were defined as those with a non-cardiovascular condition as the principal diagnosis. The proportion of patients with one or more non-cardiovascular readmissions, cardiovascular readmissions, or deaths by 12 months was calculated. Logistic regression was used to determine the factors associated with the occurrence of a non-cardiovascular readmission over 12 months. Results: In total, 4912 patients were included in the study, with 56% (n = 2734) having non-cardiovascular polypharmacy. The proportion of patients with one or more non-cardiovascular readmissions was 32% at 12 months post-discharge. Nineteen percent of patients had one or more cardiovascular readmissions, while a further 28% had died by 12 months. Non-cardiovascular polypharmacy was associated with a 48% increase in the odds (OR 1.48 95% CI 1.28-1.72) of having a non-cardiovascular readmission within 12 months. Conclusions: Non-cardiovascular readmissions occurred more frequently than cardiovascular readmissions in adults with heart failure. Non-cardiovascular polypharmacy was associated with a 48% increase in the odds of having a non-cardiovascular readmission, potentially through medication-related harm or as a surrogate of comorbidity burden. Future studies should explore holistic approaches to the management of multimorbid adults with heart failure, including optimisation of comorbidities and non-cardiovascular medications.

Cutting edge cancer therapies are increasingly brought to market at high prices, creating a tension between getting new therapies to patients as quickly as possible, and doing so in a cost-effective manner. The earlier cancer therapies are granted market authorisation, the less mature data on efficacy, safety, and quality of life are. The resulting uncertainty can complicate health technology assessments (HTAs) and therefore delay reimbursement decisions, which the vast majority of patients rely on to gain access to expensive new medicines. This narrative review summarises recent innovations in cancer therapies from a health economic perspective in Australia. We describe how such therapies are financed on the Pharmaceutical Benefits Scheme and the challenges they bring to HTA, such as their increased reliance on surrogate endpoints, extrapolation of immature survival data, and high budget impact. We discuss current methods the field has developed to overcome these problems, including managed entry agreements, coverage with evidence development, early health economic modelling, and the use of real-world evidence. These strategies aim to balance innovation and affordability, ensuring that patients can access life-extending therapies while maintaining the sustainability of Australia’s healthcare system.

AIMS:To quantify the productivity burden of cardiovascular disease (CVD) in type 2 diabetes and the potential benefits of improved CVD risk factor control. METHODS AND RESULTS:We designed models to quantify the productivity burden (using the productivity-adjusted life-year; PALY) of CVD in Australians with type 2 diabetes aged 40-69 years from 2023-2032. PALYs were ascribed a financial value equivalent to gross domestic product (GDP) per full-time worker (AU$204 167 (€124 542)). The base-case model was designed to quantify the productivity burden of CVD in the target population. Then, other hypothetical scenarios were simulated to estimate the potential productivity gains resulting from improved control of risk factors. These scenarios included reductions in systolic blood pressure (SBP), number of smokers, total cholesterol, and incidence of type 2 diabetes. All future costs and outcomes were discounted at an annual rate of 5%. In the base-case (i.e. current projections), the estimated total PALYs lost due to CVD in type 2 diabetes were 1.21 million [95%CI (1.10-1.29 million)], contributing to an AU$258.93 (€157.94) billion [95%CI (AU$258.73-261.69 (€157.83-159.63) billion)] lost in the country's GDP. If there were reductions in SBP, number of smokers, total cholesterol, and incidence of type 2 diabetes, there would be gains of 7,889, 28,971, 7,117, and 320 124 PALYs, respectively. These improvements would also lead to economic gains of AU$1.72 (€1.05) billion, AU$6.21 (€3.79) billion, AU$1.55 billion (€947.33 million), and AU$68.34 (€41.69) billion, respectively. CONCLUSION:Targeted 'early lifestyle' strategies that can prevent CVD in Australians with type 2 diabetes are likely to positively impact Australian health and work productivity.

In patients with myocardial infarction (MI), the level of sphingolipids, such as ceramide (Cer), is elevated and is associated with an increased risk of progression towards heart failure (HF). Dihydroceramide desaturase 1 (DES1) catalyses the conversion of dihydroceramide (dhCer) into Cer in the de novo sphingolipid pathway. While pharmacological inhibition of DES1 has shown therapeutic benefits in metabolic disease and cancer models, its role in cardiac remodelling remains unclear. This study aimed to determine whether pharmacological inhibition of DES1 using the novel compound, CIN038, attenuates cardiac remodelling following ischemia-reperfusion (I/R) injury. Three-month-old male C57Bl/6 mice underwent I/R or sham surgery (n = 8) and were treated with vehicle or CIN038 (50 mg/kg/day, i.p.) for 28 days. Cardiac function, molecular changes, and lipid profiles in circulation and liver were assessed at the endpoint. CIN038 reduced infarct size and cardiac myocyte hypertrophy compared to the I/R + vehicle group. Profibrotic signalling was reduced in the infarcted hearts, as evidenced by reduced expression of Col1a1, Col3a1, and Tgfb mRNA and decreased levels of α-SMA and TGFβ1 protein expression. Inflammatory signalling was attenuated with reduced ERK and NFkB phosphorylation and suppression of Il-6-STAT axis. Despite these structural and molecular improvements, no changes were observed in cardiac function. Lipidomic analysis revealed selective alterations in circulating and hepatic lipid species, including plasmalogen phosphatidylethanolamines and ether-linked triglycerides, suggesting modulation of lipid metabolism. Collectively, these findings indicate that CIN038 attenuates post-ischemic cardiac remodelling by suppressing inflammatory and profibrotic signalling, highlighting DES1 as a potential therapeutic target following MI.

To understand the application of productivity-adjusted life years (PALYs) as an outcome measure across various disease contexts. We conducted a scoping review of studies published between 2018 and April 2025 that utilised PALYs to illustrate their potential applications and identify methodological approaches that have been applied. Using a citation-based search, we selected studies that applied PALYs to quantify societal health burdens in specific diseases or contexts. Extracted data included health conditions, country, timeframe, model type, outcomes, productivity index components, gross domestic product and sensitivity analysis. Findings were summarised through narrative synthesis. A total of 41 studies conducted between 2018 and 2025 were reviewed, including chronic diseases such as diabetes and cardiovascular diseases, as well as environmental factors. Conditions such as breast cancer, leukaemia, kidney disease, mental health, knee osteoarthritis, epilepsy and sleep apnoea had the lowest productivity indices. Most of these studies originated from high-income countries (n = 27), followed by upper-middle-income (n = 10), and lower-middle-income (n = 4) settings. Life table models were the most common methodological approach adopted (n = 26), followed by dynamic models (n = 10). Studies focused on disease prevention (n = 21) outnumbered those addressing disease management (n = 18). Most studies accounted for both absenteeism and presenteeism (n = 30). Estimates of productivity loss per person using gross domestic product ranged from US1137 to AU217,983 annually. PALYs have been utilised in diverse diseases and contexts, highlighting their utility in measuring societal health impacts. However, adding unpaid and informal work makes burden estimates more accurate. The increasing emphasis on prevention indicates a strategic change in health policy and economic assessment.

Abstract Background The ability to predict failure of infliximab (IFX) in acute severe ulcerative colitis (ASUC) is crucial to identify patients who may benefit from dose-escalation, sequential rescue or early colectomy. Methods PREDICT-UC (NCT02770040) was a randomised controlled trial that compared IFX dosing strategies in ASUC.1 Clinical factors and biomarkers were collected daily between day 0 to 3 post-IFX and assessed on their ability to predict IFX failure (Lichtiger score ≥10 on day 14) and 3-month colectomy. Stepwise logistic regression was used to develop a Risk of IFX Failure (RIF) index, which was calibrated against the observed risk of IFX failure. The RIF index represents the predicted probability of IFX failure and takes on values between 0 and 1. Internal validation was performed using bootstrap validation. Results Of 138 patients, 46 received a first IFX dose of 10mg/kg and 92 received 5mg/kg; 39 (28%) experienced IFX failure and 17 (12%) required colectomy by 3 months. There was no difference in lymphocyte count (LC, ×109/L) on day 0 (prior to IFX) in patients who failed or responded to IFX (median [IQR] 1.1 [0.9–1.6] vs 1.3 [0.9–1.8], P=0.47). LC rose by day 3 in both groups, though to a lesser degree in patients who failed IFX (median [IQR] 1.9 [1.4–2.8]) compared to responders (3.3 [2.1–4.9]; P=0.004), and lower in patients requiring colectomy (median [IQR] 1.4 [1.1–1.9] vs 3.0 [2.0–4.8]; P<0.001). A lower day 3 LC was predictive of IFX failure (AUC 0.71, 95% CI 0.60–0.81) and colectomy (AUC 0.83, 95% CI 0.74–0.92). A higher CRP was predictive of both IFX failure and colectomy at all time-points from days 0 to 3 (day 3 CRP AUC 0.68, P=0.003 and 0.70, P=0.019 respectively). A lower day 3 albumin predicted IFX failure (AUC 0.63, P=0.039) while a lower day 2 albumin predicted colectomy (AUC 0.66, P=0.042). The final RIF index comprised day 3 stool frequency, rectal bleeding score, CRP and LC. The RIF index had a naïve AUC of 0.80 and an optimism-adjusted AUC of 0.73 (95% CI 0.65–0.80) for predicting IFX failure, and a naïve AUC of 0.90 and an optimism-adjusted AUC of 0.88 (95% CI 0.81–0.94) for predicting colectomy. A RIF index threshold of ≥0.15 had an 85% sensitivity and 90% negative predictive value (NPV) for IFX failure and a 94% sensitivity and 98% NPV for colectomy, while a threshold of ≥0.50 had a 92% specificity and 69% positive predictive value (PPV) for IFX failure, and an 88% specificity and 42% PPV for colectomy. Conclusion Lymphocytosis by day 3 is a novel predictor of response to IFX rescue in ASUC. The RIF index is a simple on-treatment risk index that predicts IFX failure and colectomy, and may be used to inform IFX dose-optimisation or switch to alternate therapies. References 1Choy MC, Li Wai Suen CFD, Con D, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol 2024; 9(11): 981-96.

AIMS:Approximately 1 in 11 people are intolerant to statins. There have been no studies evaluating the cost-effectiveness of early intervention for primary prevention of cardiovascular disease (CVD) with three non-statin drugs [ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i; inclisiran and evolocumab), and bempedoic acid]. We aimed to evaluate the cost-effectiveness of these therapies when initiated at age 40 years. METHODS AND RESULTS:We used a published microsimulation model populated with 108 statin-intolerant individuals. The model simulated the ageing of individuals from 40 to 85 years. We calculated the incremental cost-effectiveness ratio when non-statin lipid-lowering strategies were initiated at age 40 years compared to no intervention until a cardiovascular event. Incremental cost-effectiveness ratios were compared to Australian and UK cost-effectiveness thresholds of 28 000 AUD and 25 000 GBP per quality adjusted life year gained, respectively. We adopted each countries national healthcare system perspective (2022 AUD/GBP) and discounted health economic results by 5% annually for Australia and 3.5% annually for the UK. At current prices in Australia, ezetimibe was cost-effective in 34/108 (31.4%) individuals simulated; bempedoic acid in 17/108 (15.7%); bempedoic acid and ezetimibe in combination in 14/108 (13.0%); while inclisiran and evolocumab were not cost-effective in any individuals. Corresponding numbers for the UK were 98/108 (90.7%); 5/108 (4.6%); 11/108 (10.2%); 0/108 (0.0%); and 0/108 (0.0%). Cost-effectiveness of bempedoic acid was predominantly among individuals with an LDL-C of at least 4.0 mmol/L and systolic blood pressure of at least 140 mmHg in Australia and 5.0 mmol/L and 160 mmHg in the UK, respectively. CONCLUSION:Ezetimibe and bempedoic acid, both alone and in combination, are cost-effective for long-term primary prevention of CVD in a range of people with statin intolerance, depending on their baseline risk of CVD.

AIM:We sought to investigate the use of lipid-lowering therapy (LLT) and the attainment of low-density lipoprotein cholesterol (LDL-C) goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Australian general practices. The study aimed to investigate the discrepancies between guideline recommendations and clinical practice. METHOD:This retrospective study used electronic data from Australian general practitioners, extracted from IQVIA's "general practice electronic medical record" data set, covering the period from January 2010 to June 2022. Descriptive statistics examined the relationships between demographics, clinical characteristics, treatment patterns, adherence to LLT, and the achievement of guideline-recommended LDL-C goals, with data stratified by gender, age, and LDL-C levels. RESULTS:Of 13,644 patients with ASCVD identified, 64% of the patients with ASCVD were men, and the overall mean age was 70 years (±13.5 standard deviation). Only 51.9% of patients had a recorded LDL-C test at their most recent general practice physician visit. Of those tested, 60.5% and 50.6% had increased LDL-C levels >1.8 mmol/L and >2.0 mmol/L, respectively. Statin therapy was prescribed to n=11,100 (81.3%) of patients during the study period, but this fell to n=8,918 (65.4%) by the last consult. Of those on treatment at their last review, statin monotherapy was the most common (n=7,861, 57.6%), with a low use of combination therapies (n=1,004, 7.36%). At 1 year, 80.1% of patients on statin monotherapy were adherent (proportion of days covered ≥0.8), but this fell to 47.9% at 5 years. The use of non-high-intensity statins were associated with the highest persistence, being 47.5% adherent at 5 years. There were no significant differences in persistence between females and males nor across age categories <44, 44-65, and>65 years old. CONCLUSIONS:The study highlights gaps in the management of ASCVD in Australian general practice, including the lack of monitoring of LDL-C levels, under-prescription of proven LLT, and increasingly poor adherence and persistence with LLT over time.

BACKGROUND:Low-density lipoprotein cholesterol (LDL-C) control remains suboptimal, with limited evidence on how adherence to lipid-modifying agents (LMAs) varies by atherosclerotic cardiovascular disease (ASCVD) risk. OBJECTIVE:To examine the relationship between LDL-C levels, adherence to LMAs, and ASCVD risk. METHODS:Adults (n = 4,262) prescribed LMAs between 2013 and 2023 (median age 60 years, 49% male) were categorized into low (<5%), borderline (5% to <7.5%), intermediate (7.5% to <20%), and high (≥20%) 10-year ASCVD risk groups. Adherence was defined as having ≥1 prescription of LMA every 6 months, with adherence trajectories identified over 5 years using group-based trajectory analysis: gradual decline, rapid decline, and early discontinuation. RESULTS:Average LDL-C decreased from 3.6 ± 1.1 mmol/L (139.2 ± 42.5 mg/dL) to 2.7 ± 1.1 mmol/L (104.4 ± 42.5 mg/dL) across all risk groups, with only 23% achieving <1.8 mmol/L (69.6 mg/dL) and 18% achieving ≥50% reduction. LDL-C was highest in the early discontinuation trajectory, across all ASCVD risk groups, averaging 2.9 mmol/L (112.1 mg/dL) in the low ASCVD risk group (42%), 2.8 mmol/L (108.3 mg/dL) in the borderline (13%), 2.5 mmol/L (96.7 mg/dL) in the intermediate (33%), and 2.3 mmol/L (88.9 mg/dL) in the high-risk group (11%). Higher LDL-C was associated with younger age, being male, non-smoking status, absence of diabetes, untreated blood pressure, early LMA discontinuation, higher total cholesterol ratio, and lower high-density lipoprotein cholesterol. CONCLUSION:Long-term adherence to LMAs remains a challenge, particularly in low-risk. Target achievement was poor, highlighting gaps in therapeutic optimization, patient engagement, and monitoring.

AIMS:This study aimed to identify distinct trajectories of lipid-modifying medication (LMM) persistence over time and to explore characteristics associated with each pattern. METHODS:Using primary care data from IQVIA, we conducted a retrospective cohort study of adults prescribed LMMs between January 2015 and December 2017, with 5 years of follow-up. Persistence was defined as ≥1 prescription every 6 months. Group-based trajectory modelling identified medication persistence patterns; characteristics were compared using 1-way ANOVA and chi-squared tests. RESULTS:Among 51 504 individuals (mean age 62 years, 53% male), 4 distinct trajectories were identified: persistent use (PU, 20%), gradual decline (10%), rapid decline (29%) and early discontinuation (41%). Compared to those who discontinued early, individuals in the rapid decline, gradual decline and PU groups were older by 1.18 (95% confidence interval: 0.82-1.55), 2.61 (2.08-3.13) and 3.71 (3.30-4.12) years, respectively. Persistent users were more likely to have cardiovascular risk factors: a higher proportion of smokers (44.4 vs. 39.6%), elevated systolic blood pressure (≥140 mmHg: 36.9 vs. 32.9%) and reduced renal function (estimated glomerular filtration rate >45 mL/min/m2: 14.4 vs. 11.7%) compared to those who discontinued LMMs early. In contrast, the early discontinuation group had a greater proportion of metropolitan residents (76.1 vs. 69.2%) and individuals with elevated total cholesterol ratios (>4: 60.8 vs. 53.8%) than the PU group. CONCLUSIONS:Distinct profiles across trajectories highlight the need for tailored interventions to improve long-term medication use, particularly among younger, healthier individuals and those residing in metropolitan areas.

Importance:Long-term back problems impact an individual's ability to participate in the workforce productively, potentially resulting in financial stress and furthering inequities. Estimates of future productivity losses could inform advocacy and policy making. Objective:To estimate the productivity losses of long-term back problems in working-age Australians (aged 15-64 years) over the next 10 years (2024-2033). Design, Setting, and Participants:This modeling study used a dynamic population-level model to simulate the population of working Australians with long-term back problems. Age- and sex-specific prevalence and workforce participation data were obtained from the 2022 National Health Survey. Excess all-cause mortality, absenteeism, and presenteeism data due to long-term back problems were derived from published sources. Main Outcomes and Measures:Primary outcomes were years of life lost, full-time equivalent workers lost, and productivity losses due to long-term back problems. Productivity losses were estimated as productivity-adjusted life-years and associated costs to Australia's gross domestic product (GDP). Results:In 2024, 2 950 538 Australians had long-term back problems, which was projected to increase to 3 258 612 million by 2033. Long-term back problems resulted in an estimated loss of 3 394 255 productivity-adjusted life-years over the 10-year period, equating to a loss of more than 638 billion Australian dollars in Australia's GDP. Reducing the relative prevalence and incidence of long-term back problems by 10% was estimated to result in a gain of 41.4 billion Australian dollars in GDP over the 10-year period. Conclusions and Relevance:In this modeling study estimating future productivity losses from long-term back problems, substantial economic gains could be achieved from reducing the prevalence and impact of the condition. This model highlights the need to assess the effectiveness of interventions on work-related outcomes.

BACKGROUND AND OBJECTIVES:This paper describes the overall number of prescriptions and unique medicines dispensed and costs borne by a cohort of patients treated with lipid-lowering therapy and report on associations with age, concessional status and comorbidity. METHOD:This was a 12-month cross-sectional study using the 10% random sample of the Australian Pharmaceutical Benefits Scheme (PBS) dispensing data for 2019. RESULTS:A high number of prescriptions and unique medicines dispensed was associated with older age, concessional status and comorbidity. Around one-quarter of patients aged 61-80 years were dispensed ≥57 prescriptions, ≥10 unique medicines and seven or more unique long-term medicines during the year. PBS status was the strongest predictor of cost borne, with one-quarter of general beneficiaries paying $760 or more. DISCUSSION:This cohort commonly has related comorbidities resulting in multiple prescribed medicines, frequent dispensing and out-of-pocket costs. General practitioners are likely aware of patients' overall health and circumstances and can assist with periodic medicine review and the use of combination or extended-release preparations when available. Improved knowledge of the PBS safety net would be beneficial. Recent changes to the PBS will effect some reduction in dispensing frequency and cost borne by patients, but these changes could be extended.

INTRODUCTION:There are many non-operative factors (patient specific and management strategies) that are ubiquitous across all surgeries, which may influence perioperative pain. Recognition of these factors and their association with pain and analgesia requirements could provide avenues for improved perioperative care. METHODS:All consecutive surgical patients admitted to six Australian tertiary hospitals (2017-2024) were included. The primary outcome was postoperative pain score (0 = no pain to 10 = unbearable pain). Additional outcomes included "Pain Crisis", quantity of postoperative and discharge analgesia. Pain scores were calculated using the median scores in the 5 days postoperatively. Postoperative analgesia was quantified by total morphine milligram equivalents (MME) in the 5 days postoperatively and discharge analgesia as MME provided on the discharge prescription. Multivariable binary logistic and linear regression models, with backward elimination, were employed with clinical characteristics and non-operative management factors included as predictors. RESULTS:A total of 37,278 patients were included. Of these, 92% were unplanned emergency procedures. Psychological factors, such as depression and anxiety, significantly influenced perioperative pain and opioid use. An increase in socio-economic status was associated with less postoperative analgesia but more discharge analgesia. Older patients generally experienced less pain and required fewer opioids. Contrastingly, increased frailty correlated with higher opioid usage. Patients speaking English as a primary language reported more postoperative pain, without higher opioid use. Patients who did not identify as a First Nations Australian received 30% more opioids on discharge, despite no relationship with pain. DISCUSSION/CONCLUSION:An integrated, anticipatory, patient-centric approach to perioperative pain and analgesia that considers not only the surgical factors but also the individual's psychological and socio-economic context is required.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) has a 22%-74% 28-day mortality rate and 30%-40% 30-day readmission rate. We investigated the acceptability and feasibility of a multimodal community intervention for ACLF. METHODS: A single-arm nonrandomized pilot study of consecutive participants with ACLF was conducted in a tertiary health service. Participants received weekly medical and nursing reviews, dietetics, physiotherapy, pharmacy, social work, addiction medicine, and neuropsychiatry, where indicated. A digital platform included remote weight monitoring and online surveys. The primary outcome was acceptability/ feasibility. Secondary outcomes included safety, mortality, readmission, liver disease severity, and costs. RESULTS: Fiftynine patients were enrolled with median age 51 years (inter- quartile range (IQR): 45-59); majority alcohol etiology (74%),and median Model for End-Stage Liver Disease Sodium score 16 (IQR: 12-21). LivR Well was acceptable with low attrition (8 of 59), adherence to the program including home visits (mean 8.4 +/- 4.2) and consultations (mean 2.4 +/- 1.5) per patient. This was supported by positive feedback and themes identified through a qualitative subanalysis. Feasibility was demonstrated by recruitment rate of 4.94 patients/month and 86% completion. Mortality was lower than expected at 3%, 30- day readmission rate was 15%, and median Model for End- Stage Liver Disease Sodium score reduced to 15 (P = .01). Median 6-month costs reduced from $30,454 (IQR: $21,953-$65,657) to $17,657 ($4249-$42,876) (P = .009). The total 6-month health-care cost was $1,868,859 (95% confi- dence interval 1,081,821-2,655,897) compared to $2,518,227 (95% confidence interval 1,959,610-3,076,844). CONCLUSION: LivR Well was acceptable, feasible, and safe with low shortterm mortality and readmission rates. Health-care costs were reduced by 26% driven by a 40% reduction in 30-day readmission. Further evaluation includes a randomized controlled trial of LivR Well compared to standard care.