Estimating the impact of bias in causal epidemiological studies: the case of health outcomes following assisted reproduction.

Researchers interested in causal questions must deal with two sources of error: random error (random deviation from the true mean value of a distribution), and bias (systematic deviance from the true mean value due to extraneous factors). For some causal questions, randomization is not feasible, and observational studies are necessary. Bias poses a substantial threat to the validity of observational research and can have important consequences for health policy developed from the findings. The current piece describes bias and its sources, outlines proposed methods to estimate its impacts in an observational study, and demonstrates how these methods may be used to inform debate on the causal relationship between medically assisted reproduction (MAR) and health outcomes, using cancer as an example. In doing so, we aim to enlighten researchers who work with observational data, especially regarding the health effects of MAR and infertility, on the pitfalls of bias, and how to address them. We hope that, in combination with the provided example, we can convince readers that estimating the impact of bias in causal epidemiologic research is not only important but necessary to inform the development of robust health policy and clinical practice recommendations.

Predicting Adverse Outcomes Following Catheter Ablation Treatment for Atrial Flutter/Fibrillation.

BACKGROUND & AIM: To develop prognostic survival models for predicting adverse outcomes after catheter ablation treatment for non-valvular atrial fibrillation (AF) and/or atrial flutter (AFL). METHODS: We used a linked dataset including hospital administrative data, prescription medicine claims, emergency department presentations, and death registrations of patients in New South Wales, Australia. The cohort included patients who received catheter ablation for AF and/or AFL. Traditional and deep survival models were trained to predict major bleeding events and a composite of heart failure, stroke, cardiac arrest, and death. RESULTS: Out of a total of 3,285 patients in the cohort, 177 (5.3%) experienced the composite outcome-heart failure, stroke, cardiac arrest, death-and 167 (5.1%) experienced major bleeding events after catheter ablation treatment. Models predicting the composite outcome had high-risk discrimination accuracy, with the best model having a concordance index >0.79 at the evaluated time horizons. Models for predicting major bleeding events had poor risk discrimination performance, with all models having a concordance index <0.66. The most impactful features for the models predicting higher risk were comorbidities indicative of poor health, older age, and therapies commonly used in sicker patients to treat heart failure and AF and AFL. DISCUSSION: Diagnosis and medication history did not contain sufficient information for precise risk prediction of experiencing major bleeding events. Predicting the composite outcome yielded promising results, but future research is needed to validate the usefulness of these models in clinical practice. CONCLUSIONS: Machine learning models for predicting the composite outcome have the potential to enable clinicians to identify and manage high-risk patients following catheter ablation for AF and AFL proactively.

Six-minute walk test distance at time of hospital discharge is strongly and independently associated with all-cause mortality following cardiac surgery.

We investigated the impact of distance covered in the six-minute walk test (6mWT) before being discharged from the hospital after cardiac surgery on the risk of all-cause mortality. Our study included 1127 patients who underwent cardiac surgery and then took part in a standardised physiotherapist-supervised inpatient rehabilitation programme during 2007-2017. The percentage of the predicted 6mWT distance, and the lower limit of normal distance was calculated based on individual patients' age, sex, and body mass index. We used Cox regression with adjustment for confounders to determine multivariable-adjusted hazard ratios (HRs) for mortality. Over a median follow-up period of 6.4 (IQR: 3.5-9.2) years, 15% (n = 169) patients died. We observed a strong and independent inverse association between 6mWT distance and mortality, with every 10 m increase in distance associated to a 4% reduction in mortality (HR: 0.96, 95% CI 0.94-0.98, P < 0.001). Those in the top tertile for predicted 6mWT performance had a 49% reduced risk of mortality (HR: 0.51, 95% CI 0.33-0.79) compared to those in the bottom tertile. Patients who met or exceeded the minimum normal 6mWT distance had 36% lower mortality risk (HR: 0.64, 95% CI 0.45-0.92) compared to those who did not meet this benchmark. Subgroup analysis showed that combined CABG and valve surgery patients walked less in the 6mWT compared to those undergoing isolated CABG or valve surgeries, with a significant association between 6mWT and mortality observed in the isolated procedure groups only. In conclusion, the longer the distance covered in the 6mWT before leaving the hospital, the lower the risk of mortality.

In-hospital outcomes by insurance type among patients undergoing percutaneous coronary interventions for acute myocardial infarction in New South Wales public hospitals.

BACKGROUND: International evidence suggests patients receiving cardiac interventions experience differential outcomes by their insurance status. We investigated outcomes of in-hospital care according to insurance status among patients admitted in public hospitals with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a cohort study within the Australian universal health care system with supplemental private insurance. Using linked hospital and mortality data, we included patients aged 18 + years admitted to New South Wales public hospitals with AMI and undergoing their first PCI from 2017-2020. We measured hospital-acquired complications (HACs), length of stay (LOS) and in-hospital mortality among propensity score-matched private and publicly funded patients. Matching was based on socio-demographic, clinical, admission and hospital-related factors. RESULTS: Of 18,237 inpatients, 30.0% were privately funded. In the propensity-matched cohort (n = 10,630), private patients had lower rates of in-hospital mortality than public patients (odds ratio: 0.59, 95% CI: 0.45-0.77; approximately 11 deaths avoided per 1,000 people undergoing PCI procedures). Mortality differences were mostly driven by STEMI patients and those from major cities. There were no significant differences in rates of HACs or average LOS in private, compared to public, patients. CONCLUSION: Our findings suggest patients undergoing PCI in Australian public hospitals with private health insurance experience lower in-hospital mortality compared with their publicly insured counterparts, but in-hospital complications are not related to patient health insurance status. Our findings are likely due to unmeasured confounding of broader patient selection, socioeconomic differences and pathways of care (e.g. access to emergency and ambulatory care; delays in treatment) that should be investigated to improve equity in health outcomes.

Real-world evidence on the association between cardiac implantable electronic device infection and all-cause mortality.

AIMS: An infection following cardiac implantable electronic device (CIED) procedure is a serious complication, but its association with all-cause mortality is inconsistent across observational studies. To quantify the association between CIED infection and all-cause mortality in a large, contemporary cohort from New South Wales, Australia. METHODS AND RESULTS: This retrospective cohort study used linked hospital and mortality data and included all patients aged >18 years who underwent a CIED procedure between July 2017 and September 2022. Cardiac implantable electronic device infection was defined by the presence of relevant diagnosis codes. Cox regression to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the association of CIED infection with mortality, at 1-year, and at the end of follow-up, with CIED infection included as a time-dependent variable, and other potential risk factors for mortality included as fixed covariates. We followed 37,750 patients with CIED procedures {36% female, mean age [standard deviation (SD)] 75.8 [12.7] years}, and 487 (1.3%) CIED infections were identified. We observed 5771 (15.3%) deaths during an average follow-up of 25.2 (SD 16.8) months. Compared with no infection group, patients with CIED infection had a higher Kaplan-Meier mortality rate (19.4 vs. 6.8%) and adjusted hazard of mortality (aHR 2.73, 95% CI 2.10-3.54) at 12 months post-procedure. These differences were attenuated but still remained significant at the end of follow-up (aHR 1.83, 95% CI 1.52-2.19). CONCLUSION: In a complete, state-wide cohort of CIED patients, infection was associated with higher risks of both short-term and long-term mortality.

Have We Been Underestimating Modifiable Dementia Risk? An Alternative Approach for Calculating the Combined Population Attributable Fraction for Modifiable Dementia Risk Factors.

Estimating the fraction of dementia cases in a population attributable to a risk factor or combination of risk factors (the population attributable fraction (PAF)) informs the design and choice of dementia risk-reduction activities. It is directly relevant to dementia prevention policy and practice. Current methods employed widely in the dementia literature to combine PAFs for multiple dementia risk factors assume a multiplicative relationship between factors and rely on subjective criteria to develop weightings for risk factors. In this paper we present an alternative approach to calculating the PAF based on sums of individual risk. It incorporates individual risk factor interrelationships and enables a range of assumptions about the way in which multiple risk factors will combine to affect dementia risk. Applying this method to global data demonstrates that the previous estimate of 40% is potentially too conservative an estimate of modifiable dementia risk and would necessitate subadditive interaction between risk factors. We calculate a plausible conservative estimate of 55.7% (95% confidence interval: 55.2, 56.1) based on additive risk factor interaction.

Factors Associated with Participation in a Multidomain Web-Based Dementia Prevention Trial: Evidence from Maintain Your Brain (MYB).

BACKGROUND: The Maintain Your Brain (MYB) trial aims to prevent cognitive decline and dementia through multidomain, web-based risk-reduction. To facilitate translation, it is important to understand drivers of participation. OBJECTIVE: To describe characteristics associated with participation in MYB. METHODS: This was an observational ancillary study of MYB, a randomized controlled trial nested within the 45 and Up Study in New South Wales, Australia. We linked 45 and Up Study survey and MYB participation data. The study cohort comprised 45 and Up Study participants, aged 55-77 years at 1 January 2018, who were invited to participate in MYB. 45 and Up Study participant characteristics and subsequent MYB consent and participation were examined. RESULTS: Of 98,836 invited, 13,882 (14%) consented to participate and 6,190 participated (6%). Adjusting for age and sex, a wide range of factors were related to participation. Higher educational attainment had the strongest relationship with increased MYB participation (university versus school non-completion; AdjOR = 5.15; 95% CI:4.70-5.64) and lower self-rated quality of life with reduced participation (Poor versus Excellent: AdjOR = 0.19; 95% CI:0.11-0.32). A family history of Alzheimer's disease was related to increased participation but most other dementia risk factors such as diabetes, obesity, stroke, high blood pressure, and current smoking were associated with reduced participation. CONCLUSION: Higher socio-economic status, particularly educational attainment, is strongly associated with engagement in online dementia prevention research. Increasing population awareness of dementia risk factors, and better understanding the participation barriers in at-risk groups, is necessary to ensure online interventions are optimally designed to promote maximum participation.

Editor's Choice - Comparison of Outcomes for Major Contemporary Endograft Devices Used for Endovascular Repair of Intact Abdominal Aortic Aneurysms.

OBJECTIVE: To compare rates of mortality, rupture, and secondary intervention following endovascular repair (EVAR) of intact abdominal aortic aneurysms (AAA) using contemporary endograft devices from three major manufacturers. METHODS: This was a retrospective cohort study using linked clinical registry (Australasian Vascular Audit) and all payer administrative data. Patients undergoing EVAR for intact AAA between 2010 and 2019 in New South Wales, Australia were identified. Rates of all cause death, secondary rupture, and secondary intervention (subsequent aneurysm repair; other secondary aortic intervention) were compared for patients treated with Cook, Medtronic, and Gore standard devices. Inverse probability of treatment weighted proportional hazards and competing risk regression were used to adjust for patient, clinical, and aneurysm characteristics, using Cook as the referent device. RESULTS: This study identified 2 874 eligible EVAR patients, with a median follow up of 4.1 (maximum 9.5) years. Mortality rates were similar for patients receiving different devices (ranging between 7.0 and 7.3 per 100 person years). There was no statistically significant difference between devices in secondary rupture rates, which ranged between 0.4 and 0.5 per 100 person years. Patients receiving Medtronic and Gore devices tended to have higher crude rates of subsequent aneurysm repair (1.5 per 100 person years) than patients receiving Cook devices (0.8 per 100 person years). This finding remained in the adjusted analysis, but was only statistically significant for Medtronic devices (HR 1.57, 95% CI 1.02 - 2.47; HR 1.73, 95% CI 0.94 - 3.18, respectively). CONCLUSION: Major endograft devices have similar overall long term safety profiles. However, there may be differences in rates of secondary intervention for some devices. This may reflect endograft durability, or patient selection for different devices based on aneurysm anatomy. Continuous comparative assessments are needed to guide evidence for treatment decisions across the range of available devices.

Comparison of long-term outcomes of bioprosthetic and mechanical aortic valve replacement in patients younger than 65 years.

OBJECTIVES: The objectives of this study were to compare rates of mortality and reoperations for patients aged younger than 65 years who underwent surgical aortic valve replacement (AVR). AVR with a bioprosthetic valve (BV) is increasing among younger patients, however evidence to inform the choice between BV or mechanical valve is limited. METHODS: We performed a retrospective cohort study using linked hospital and mortality data from Australia, for 3969 AVR patients between 2003 and 2018. We compared outcomes for valves in inverse probability of treatment-weighted cohorts, stratified according to age (18-54 years; 55-64 years). We used weighted Cox regression models to estimate hazard ratios (HRs) and weighted cumulative incidence function for subdistribution hazards, for follow-up intervals: 0 to 10 and >10 to 15 years. RESULTS: Among patients aged 55 to 64 years, there was no difference in mortality at 0 to 10 years. However, at >10 to 15 years, mortality was higher among BV recipients (HR, 1.56; 95% CI, 1.01-2.42). There was no difference among patients aged 18 to 54 years. Reoperation rates for patients aged 55 to 64 years did not differ according to valve type at 0 to 10 years, but were higher for BV than mechanical valve at >10 to 15 years (HR, 2.87; 95% CI, 1.69-4.86). For patients aged 18 to 54 years, reoperation rates were consistently higher for BV at both time intervals (HR, 2.54 [95% CI, 1.03-6.25] and HR, 4.48 [95% CI, 2.15-9.32], respectively). CONCLUSIONS: Patients aged 55 to 64 years who received a BV had a higher risk of mortality beyond 10 years. Rates of reoperations were higher among patients implanted with a BV in the entire cohort. Further investigation of long-term outcomes among patients with a BV is necessary. Continuous long-term monitoring of BV technologies will ensure evidence-based decision-making and regulation.

Long-Term Outcomes Following Elective Repair of Intact Abdominal Aortic Aneurysms: A Comparison Between Open Surgical and Endovascular Repair Using Linked Administrative and Clinical Registry Data.

OBJECTIVE: Compare long-term mortality, secondary intervention and secondary rupture following elective endovascular aneurysm repair (EVAR) and open surgical repair (OSR). BACKGROUND: EVAR has surpassed OSR as the most common procedure used to repair abdominal aortic aneurysm (AAA), but evidence regarding long-term outcomes is inconclusive. METHODS: We included patients in linked clinical registry and administrative data undergoing EVAR or OSR for intact AAA between January 2010 and June 2019. We used an inverse probability of treatment-weighted survival analysis to compare all-cause mortality, cause-specific mortality, secondary interventions and secondary rupture, and evaluate the impact of secondary interventions and secondary rupture on all-cause mortality. RESULTS: The study included 3460 EVAR and 427 OSR patients. Compared to OSR, the EVAR all-cause mortality rate was lower in the first 30 days [adjusted hazard ratio (HR) = 0.22, 95% confidence interval (CI) 0.140.33], but higher between 1 and 4 years (HR = 1.29, 95% CI 1.12-1.48) and after 4years (HR = 1.41, 95% CI 1.23-1.63). Secondary intervention rates were higher over the first 30 days (HR = 2.26, 95% CI 1.11-4.59), but lower between 1 and 4years (HR = 0.59, 95% CI 0.48-0.74). Secondary aortic intervention rates were higher across the entire follow-up period (HR = 2.52, 95% CI 2.06-3.07). Secondary rupture rates did not differ significantly (HR = 1.06, 95% CI 0.73-1.55). All-cause mortality beyond 1 year remained significantly higher for EVAR after adjusting for any secondary interventions, or secendary rupture. CONCLUSIONS: EVAR has an early survival benefit compared to OSR. However, elevated long-term mortality and higher rates of secondary aortic interventions and subsequent aneurysm repair suggest that EVAR may be a less durable method of aortic aneurysm exclusion.

Interaction effects of multimorbidity and frailty on adverse health outcomes in elderly hospitalised patients.

We quantified the interaction of multimorbidity and frailty and their impact on adverse health outcomes in the hospital setting. Using aretrospective cohort study of persons aged ≥ 75 years, admitted to hospital during 2010-2012 in New South Wales, Australia, and linked with mortality data, we constructed multimorbidity, frailty risk and outcomes: prolonged length of stay (LOS), 30-day mortality and 30-day unplanned readmissions. Relative risks (RR) of outcomes were obtained using Poisson models with random intercept for hospital. Among 257,535 elderly inpatients, 33.6% had multimorbidity and elevated frailty risk, 14.7% had multimorbidity only, 19.9% had elevated frailty risk only and 31.8% had neither. Additive interactions were present for all outcomes, with a further multiplicative interaction for mortality and LOS. Mortality risk was 4.2 (95% CI 4.1-4.4), prolonged LOS 3.3 (95% CI 3.3-3.4) and readmission 1.8 (95% CI 1.7-1.9) times higher in patients with both factors present compared with patients with neither. In conclusion, multimorbidity and frailty coexist in older hospitalized patients and interact to increase the risk of adverse outcomes beyond the sum of their individual effects. Their joint effect should be considered in health outcomes research and when administering hospital resources.

An Observational Study of Clinical and Health System Factors Associated With Catheter Ablation and Early Ablation Treatment for Atrial Fibrillation in Australia.

OBJECTIVE: To investigate clinical and health system factors associated with receiving catheter ablation (CA) and earlier ablation for non-valvular atrial fibrillation (AF). METHODS: We used hospital administrative data linked with death registrations in New South Wales, Australia for patients with a primary diagnosis of AF between 2009 and 2017. Outcome measures included receipt of CA versus not receiving CA during follow-up (using Cox regression) and receipt of early ablation (using logistic regression). RESULTS: Cardioversion during index admission (hazard ratio [HR] 1.96; 95% CI 1.75-2.19), year of index admission (HR 1.07; 95% CI 1.05-1.10), private patient status (HR 2.65; 95% CI 2.35-2.97), and living in more advantaged areas (HR 1.18; 95% CI 1.13-1.22) were associated with a higher likelihood of receiving CA. A history of congestive heart failure, hypertension, diabetes, and myocardial infarction were associated with a lower likelihood of receiving CA. Private patient status (odds ratio [OR] 2.04; 95% CI 1.59-2.61), cardioversion during index admission (OR 1.25; 95% CI 1.0-1.57), and history of diabetes (OR 1.6; 95% CI 1.06-2.41) were associated with receiving early ablation. CONCLUSIONS: Beyond clinical factors, private patients are more likely to receive CA and earlier ablation than their public counterparts. Whether the earlier access to ablation procedures in private patients is leading to differences in outcomes among patients with atrial fibrillation remains to be explored.

Post-Discharge Antithrombotic Therapy Following Transcatheter Aortic Valve Implantation in Australian Patients.

BACKGROUND: Guidelines recommend antithrombotic therapy for patients following transcatheter aortic valve implantation (TAVI) to reduce the risk of ischaemic events and bioprosthetic valve thrombosis. OBJECTIVE: To describe antithrombotic dispensing within 30 days of discharge for Australian patients receiving TAVI. METHODS: We performed a state-wide retrospective cohort study using linked hospital and medicines dispensing data from January 2013 to December 2018 for all patients receiving TAVI in New South Wales, Australia. We identified patients dispensed oral anticoagulants (vitamin K antagonists [warfarin], direct oral anticoagulants [DOACs]) or clopidogrel within 30 days of discharge. We examined demographic and clinical predictors of antithrombotic dispensing. RESULTS: Our cohort comprised 1,217 patients who underwent TAVI; median age was 84 years and 707 (58.1%) were male. Of these, 808 patients (66.4%) had an antithrombotic dispensed within 30 days of hospital discharge. One-third (33.7%) of these patients were dispensed an anticoagulant (16.1% warfarin; 17.6% DOACs) and two-thirds (66.3%) were dispensed clopidogrel. Patients undergoing TAVI were more likely to be dispensed an antithrombotic medicine within 30-days of hospital discharge if they had been dispensed antithrombotic medicines (RR 1.07; 95% CI 1.03-1.11) or angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers (RR 1.04; 95% CI 1.00-1.07) in the 6 months prior to admission. Patients with a history of haemorrhage were less likely to be dispensed an antithrombotic medicine within 30 days of hospital discharge (RR 0.93; 95% CI 0.89-0.98). CONCLUSIONS: We observed gaps in best evidence pharmacotherapy for patients post-TAVI, with almost one third of patients not receiving antithrombotic medicines post-discharge. Further research is needed to quantify the impact of emerging clinical guidelines recommending single antiplatelet therapy, on adherence to best-practice care.

Population-wide contribution of medically assisted reproductive technologies to overall births in Australia: temporal trends and parental characteristics.

STUDY QUESTION: In a country with supportive funding for medically assisted reproduction (MAR) technologies, what is the proportion of MAR births over-time? SUMMARY ANSWER: In 2017, 6.7% of births were conceived by MAR (4.8% ART and 1.9% ovulation induction (OI)/IUI) with a 55% increase in ART births and a stable contribution from OI/IUI births over the past decade. WHAT IS KNOWN ALREADY: There is considerable global variation in utilization rates of ART despite a similar infertility prevalence worldwide. While the overall contribution of ART to national births is known in many countries because of ART registries, very little is known about the contribution of OI/IUI treatment or the socio-demographic characteristics of the parents. Australia provides supportive public funding for all forms of MAR with no restrictions based on male or female age, and thus provides a unique setting to investigate the contribution of MAR to national births as well as the socio-demographic characteristics of parents across the different types of MAR births. STUDY DESIGN, SIZE, DURATION: This is a novel population-based birth cohort study of 898 084 births using linked ART registry data and administrative data including birth registrations, medical services, pharmaceuticals, hospital admissions and deaths. Birth (a live or still birth of at least one baby of ≥400 g birthweight or ≥20 weeks' gestation) was the unit of analysis in this study. Multiple births were considered as one birth in our analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included a total of 898 084 births (606 488 mothers) in New South Wales and the Australian Capital Territory, Australia 2009-2017. We calculated the prevalence of all categories of MAR-conceived births over the study period. Generalized estimating equations were used to examine the association between parental characteristics (parent's age, parity, socio-economic status, maternal country of birth, remoteness of mother's dwelling, pre-existing medical conditions, smoking, etc.) and ART and OI/IUI births relative to naturally conceived births. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of MAR births increased from 5.1% of all births in 2009 to 6.7% in 2017, representing a 30% increase over the decade. The proportion of OI/IUI births remained stable at around 2% of all births, representing 32% of all MAR births. Over the study period, ART births conceived by frozen embryo-transfer increased nearly 3-fold. OI/IUI births conceived using clomiphene citrate decreased by 39%, while OI/IUI births conceived using letrozole increased 56-fold. Overall, there was a 55% increase over the study period in the number of ART-conceived births, rising to 56% of births to mothers aged 40 years and older. In 2017, almost one in six births (17.6%) to mothers aged 40 years and over were conceived using ART treatment. Conversely, the proportion of OI/IUI births was similar across different mother's age groups and remained stable over the study period. ART children, but not OI/IUI children, were more likely to have parents who were socio-economically advantaged compared to naturally conceived children. For example, compared to naturally conceived births, ART births were 16% less likely to be born to mothers who live in the disadvantaged neighbourhoods after accounting for other covariates (adjusted relative risk (aRR): 0.84 [95% CI: 0.81-0.88]). ART- or OI/IUI-conceived children were 25% less likely to be born to immigrant mothers than births after natural conception (aRR: 0.75 [0.74-0.77]). LIMITATIONS, REASONS FOR CAUTION: The social inequalities that we observed between the parents of children born using ART and naturally conceived children may not directly reflect disparities in accessing fertility care for individuals seeking treatment. WIDER IMPLICATIONS OF THE FINDINGS: With the ubiquitous decline in fertility rates around the world and the increasing trend to delay childbearing, this population-based study enhances our understanding of the contribution of different types of MARs to population profiles among births in high-income countries. The parental socio-demographic characteristics of MAR-conceived children differ significantly from naturally conceived children and this highlights the importance of accounting for such differences in studies investigating the health and development of MAR-conceived children. STUDY FUNDING/COMPETING INTEREST(S): This study was funded through Australian National Health and Medical Research Council (NHMRC) grant: APP1127437. G.M.C. is an employee of The University of New South Wales (UNSW) and Director of the National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW. The NPESU manages the Australian and New Zealand Assisted Reproduction Database with funding support from the Fertility Society of Australia and New Zealand. C.V. is an employee of The University of New South Wales (UNSW), Director of Clinical Research of IVFAustralia, Member of the Board of the Fertility Society of Australia and New Zealand, and Member of Research Committee of School of Women's and Children's Health, UNSW. C.V. reports grants from Australian National Health and Medical Research Council (NHMRC), and Merck KGaA. C.V. reports consulting fees, and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript, writing or educational events or attending meeting or travel from Merck, Merck Sparpe & Dohme, Ferring, Gedon-Richter and Besins outside this submitted work. C.V. reported stock or stock options from Virtus Health Limited outside this submitted work. R.J.N. is an employee of The University of Adelaide, and Chair DSMC for natural therapies trial of The University of Hong Kong. R.J.N. reports grants from NHMRC. R.J.N. reports lecture fees and support for attending or travelling for lecture from Merck Serono which is outside this submitted work. L.R.J. is an employee of The UNSW and Foundation Director of the Centre for Big Data Research in Health at UNSW Sydney. L.R.J. reports grants from NHMRC. The other co-authors have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Evidence-practice gaps in P2Y12 inhibitor use after hospitalisation for acute myocardial infarction: findings from a new population-level data linkage in Australia.

BACKGROUND: P2Y12 inhibitor therapy is recommended for 12 months in patients hospitalised for acute myocardial infarction (AMI) unless the bleeding risk is high. AIMS: To describe real-world use of P2Y12 inhibitor therapy following AMI hospitalisation. METHODS: We used population-level linked hospital data to identify all patients discharged from a public hospital with a primary diagnosis of AMI between July 2011 and June 2013 in New South Wales and Victoria, Australia. We used dispensing claims to examine dispensing of a P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) within 30 days of discharge and multilevel models to identify predictors of post-discharge dispensing and persistence of therapy to 1 year. RESULTS: We identified 31 848 patients hospitalised for AMI, of whom 56.8% were dispensed a P2Y12 inhibitor within 30 days of discharge. The proportion of patients with post-discharge dispensing varied between hospitals (interquartile range: 25.0-56.5%), and significant between-hospital variation remained after adjusting for patient characteristics. Patient factors associated with the lowest likelihood of post-discharge dispensing were: having undergone coronary artery bypass grafting (odds ratio (OR): 0.17; 95% confidence intervals (CI): 0.15-0.20); having oral anticoagulants dispensed 180 days before or 30 days after discharge (OR: 0.39, 95% CI: 0.35-0.44); major bleeding (OR: 0.68, 95% CI: 0.61-0.76); or being aged ≥85 years (OR: 0.68, 95% CI: 0.62-0.75). A total of 26.8% of patients who were dispensed a P2Y12 inhibitor post-discharge discontinued therapy within 1 year. CONCLUSION: Post-hospitalisation use of P2Y12 inhibitor therapy in AMI patients is low and varies substantially by hospital of discharge. Our findings suggest strategies addressing both health system (hospital and physician) and patient factors are needed to close this evidence-practice gap.

Rates of Low-Value Service in Australian Public Hospitals and the Association With Patient Insurance Status.

Importance: Low-value services have limited or no benefit to patients. Rates of low-value service in public hospitals may vary by patient insurance status, given that there may be different financial incentives for treatment of privately insured patients. Objective: To assess the variation in rates of 5 low-value services performed in Australian public hospitals according to patient funding status (ie, private or public). Design, Setting, and Participants: This retrospective cross-sectional study analyzed New South Wales public hospital data from January 2013 to June 2018. Patients included in the sample were over age 18 years and eligible to receive low-value services based on diagnoses and concomitant procedures. Data analysis was conducted from June to December 2020. Main Outcomes and Measures: Hospital-specific rates of low-value knee arthroscopic debridement, vertebroplasty for osteoporotic spinal fractures, hyperbaric oxygen therapy, oophorectomy with hysterectomy, and laparoscopic uterine nerve ablation for chronic pelvic pain were measured. For each measure, rates within each public hospital were compared by patient funding status descriptively and using multilevel models. Results: A total of 219 862 inpatients were included in analysis from 58 public hospitals across the 5 measures. A total of 38 365 (22 904 [59.7%] women; 12 448 [32.4%] aged 71-80 years) were eligible for knee arthroscopic debridement for osteoarthritis; 2520 (1924 [76.3%] women; 662 [26.3%] aged 71-80 years), vertebroplasty for osteoporotic spinal fractures; 162 285 (82 046 [50.6%] women; 28 255 [17.4%] aged 61-70 years), hyperbaric oxygen therapy; 15 916 (7126 [44.8%] aged 41-50 years), oophorectomy with hysterectomy; and 776 (327 [42.1%] aged 18-30 years), uterine nerve ablation for chronic pelvic pain. Overall rates of low-value services varied considerably between measures, with the lowest rate for hyperbaric oxygen therapy (0.3 procedures per 1000 inpatients [47 of 158 220 eligible inpatients]) and the highest for vertebroplasty (30.8 procedures per 1000 eligible patients [77 of 2501 eligible inpatients]). There was significant variation in rates between hospitals, with a few outlying hospitals (ie, <10), particularly for knee arthroscopy (range from 1.8 to 21.0 per 1000 eligible patients) and vertebroplasty (range from 13.1 to 70.4 per 1000 eligible patients), with higher numerical rates of low-value services among patients with private insurance than for those without. However, there was no association overall between patient insurance status and low-value services. Overall differences in rates among those with and without private insurance by individual procedure type were not statistically significant. Conclusions and Relevance: There was significant variation in rates of low-value services in public hospitals. While there was no overall association between private insurance and rate of low-value services, private insurance may be associated with low-value service rates in some hospitals. Further exploration of factors specific to local hospitals and practices are needed to reduce this unnecessary care.

Use of health and aged care services in Australia following hospital admission for myocardial infarction, stroke or heart failure.

BACKGROUND: Cardiovascular diseases (CVD), including myocardial infarction (MI), stroke and heart failure (HF) are the leading cause of death amongst the older population worldwide. The aim of this study is to investigate trajectories of use of health and aged care services after hospital admission for MI, stroke or HF among community-dwelling people not previously receiving aged care services. METHODS: The study population comprised people aged 65+ years from the 45 and Up Study with linked records for hospital stays, aged care services and deaths for the period 2006-14. Among those with an index hospital admission for MI, stroke or HF, we developed Sankey plots to describe and visualize sequences and trajectories of service use (none, re-hospitalization, community care, residential care, death) in the 12 months following discharge. We used Cox proportional hazards models to estimate hazard ratios (HRs), for commencing community care and entering residential care (and the other outcomes) within 3, 6 and 12 months, compared to a matched group without MI, stroke or HF. RESULTS: Two thousand six hundred thirty-nine, two thousand five hundred and two thousand eight hundred seventy-three people had an index hospitalization for MI, stroke and HF, respectively. Within 3 months of hospital discharge, 16, 32 and 29%, respectively, commenced community care (multivariable-adjusted HRs: 1.26 (95%CI:1.18-1.35), 1.53 (95%CI:1.44-1.64) and 1.39 (95%CI:1.32-1.48)); and 7, 18 and 14%, respectively, entered residential care (HRs: 1.25 (95%CI:1.12-1.41), 2.65 (95%CI:2.42-2.91) and 1.50 (95%CI:1.37-1.65)). Likewise, 26, 15 and 28%, respectively, were rehospitalized within 3 months following discharge (multivariable-adjusted HRs: 4.78 (95%CI:4.31-5.32), 3.26 (95%CI:2.91-3.65) and 4.94 (95%CI:4.47-5.46)). CONCLUSIONS: Older people hospitalized for major CVD may be vulnerable to transition-related risks and have poor health trajectories, thus emphasizing the value of preventing such events and care strategies targeted towards this at-risk group.

How Much Is a Human Life Worth? A Systematic Review.

OBJECTIVES: To systematically review studies eliciting monetary value of a statistical life (VSL) estimates within, and across, different sectors and other contexts; compare the reported estimates; and critically review the elicitation methods used. METHODS: In June 2019, we searched the following databases to identify methodological and empirical studies: Cochrane Library, Compendex, Embase, Environment Complete, Informit, ProQuest, PubMed, Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reporting and a modified Consolidated Health Economic Evaluation Reporting Standards checklist to assess the quality of included studies. RESULTS: We identified 1455 studies, of which we included 120 in the systematic review. A stated-preference approach was used in 76 articles, with 51%, 41%, and 8% being contingent valuation studies, discrete-choice experiments, or both, respectively. A revealed-preference approach was used in 43 articles, of which 74% were based on compensating-wage differentials. The human capital approach was used in only 1 article. We assessed most publications (87%) as being of high quality. Estimates for VSL varied substantially by context (sector, developed/developing country, socio-economic status, etc), with the median of midpoint purchasing power parity-adjusted estimates of 2019 US$5.7 million ($6.8 million, $8.7 million, and $5.3 million for health, labor market, and transportation safety sectors, respectively). CONCLUSIONS: The large variation observed in published VSLs depends mainly on the context rather than the method used. We found higher median values for labor markets and developed countries. It is important that health economists and policymakers use context-specific VSL estimates. Methodological innovation and standardization are needed to maximize comparability of VSL estimates within, and across, sectors and methods.