Predicting multifaceted risks using machine learning in atrial fibrillation: insights from GLORIA-AF study.

Aims: Patients with atrial fibrillation (AF) have a higher risk of ischaemic stroke and death. While anticoagulants are effective at reducing these risks, they increase the risk of bleeding. Current clinical risk scores only perform modestly in predicting adverse outcomes, especially for the outcome of death. We aimed to test the multi-label gradient boosting decision tree (ML-GBDT) model in predicting risks for adverse outcomes in a prospective global AF registry. Methods and results: We studied patients from phase II/III of the Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation registry between 2011 and 2020. The outcomes were all-cause death, ischaemic stroke, and major bleeding within 1 year following the AF. We trained the ML-GBDT model and compared its discrimination with the clinical scores in predicting patient outcomes. A total of 25 656 patients were included [mean age 70.3 years (SD 10.3); 44.8% female]. Within 1 year after AF, ischaemic stroke occurred in 215 (0.8%), major bleeding in 405 (1.6%), and death in 897 (3.5%) patients. Our model achieved an optimized area under the curve in predicting death (0.785, 95% CI: 0.757-0.813) compared with the Charlson Comorbidity Index (0.747, P = 0.007), ischaemic stroke (0.691, 0.626-0.756) compared with CHA2DS2-VASc (0.613, P = 0.028), and major bleeding (0.698, 0.651-0.745) as opposed to HAS-BLED (0.607, P = 0.002), with improvement in net reclassification index (10.0, 12.5, and 23.6%, respectively). Conclusion: The ML-GBDT model outperformed clinical risk scores in predicting the risks in patients with AF. This approach could be used as a single multifaceted holistic tool to optimize patient risk assessment and mitigate adverse outcomes when managing AF.

Cross-sectional, case-control and longitudinal associations between exposure to glucagon-like peptide-1 receptor agonists and the dispensing of antidepressants.

AIM: To determine if the dispensing of glucagon-like peptide (GLP)-1 receptor agonists is associated with increased dispensing of antidepressants. MATERIALS AND METHODS: We used cross-sectional, case-control and retrospective cohort study designs to examine the association between dispensed GLP-1 receptor agonists and antidepressants between 2012 and 2022 in the 10% random sample of the Australian Pharmaceutical Benefits Scheme (PBS) data. PBS-listed GLP-1 receptor agonists, exenatide, dulaglutide and semaglutide were the exposures. Outcomes were the odds ratio [ORs; 99% confidence interval (CI)] and hazard ratio (99% CI) of being dispensed any antidepressant. Analyses were adjusted for demographic measures and the dispensing of medicines to manage cardiovascular diseases or anxiety/insomnia. Statistical tests were two-sided at the 1% level of significance. RESULTS: In total, 358 075 of 1 746 391 individuals were dispensed antidepressants, and 8495 of the 24 783 dispensed a GLP-1 receptor agonist were also dispensed an antidepressant in 2022 (OR 1.44; 99% CI 1.38-1.50); 24 103 of the 1 746 391 participants had been dispensed a GLP-1 receptor agonist between 2012 and 2021, and of these 8083 were dispensed antidepressants in 2022 (OR 1.52; 99% CI 1.46-1.59). The 2012 cohort included 1 213 316 individuals who had not been dispensed antidepressants that year. The hazard ratio of being dispensed an antidepressant between 2013 and 2022 following the dispensing of a GLP-1 receptor agonist was 1.19 (99% CI 1.12-1.27). Additional analyses restricting the time of exposure confirmed these associations for all PBS-listed GLP-1 receptor agonists. CONCLUSIONS: Individuals exposed to GLP-1 receptor agonists are at greater risk of being dispensed antidepressants. The possible impact of GLP-1 receptor agonists on the mood of consumers requires ongoing vigilance and further research.

Observational evidence linking psychotropic medicines to the dispensing of opioid agents in later life.

BACKGROUND: The use of opioid medicines is common in developed countries, particularly among older adults and those with mental health disorders. It is unclear if the association between mental disorders and opioid medicines is causal, or is due to reverse causality or confounding. METHODS: We used a 10% random sample of the Australian Pharmaceutical Benefits Scheme (years 2012-2022) to examine the cross-sectional, case-control and longitudinal association between the dispensing of antidepressants, anxiolytics, hypnotics, antipsychotics and lithium, and opioid medicines. We used logistic regression, structural equation models (SEM), and Cox regression to analyze the data. Analyses were adjusted for age (years), sex, and number of non-psychotropic medicines dispensed during the year. RESULTS: The 2022 file contained 804 334 individuals aged 50 years or over (53.1% women), of whom 181 690 (22.6%) received an opioid medicine. The adjusted odds ratio of being dispensed opioid medicines was 1.44 (99% CI = 1.42-1.46) for antidepressants, 1.97 (99% CI = 1.92-2.03) for anxiolytics, 1.55 (99% CI = 1.51-1.60) for hypnotics, 1.32 (99% CI = 1.27-1.38) for antipsychotics, and 0.60 (99% CI = 0.53-0.69) for lithium. Similar associations were noticed when we compared participants who were or not dispensed opioid medicines in 2022 for exposure to psychotropic agents between 2012 and 2021. SEM confirmed that this association was not due to reverse causality. The dispensing of antidepressants was associated with increased adjusted hazard (HR) of subsequent dispensing of opioid medicines (HR = 1.29, 99% CI = 1.27-1.30). Similar associations were observed for anxiolytics, hypnotics and antipsychotics, but not lithium. CONCLUSIONS: The dispensing of opioid medicines is higher among older individuals exposed to antidepressants, anxiolytics, hypnotics and antipsychotics than those who are not. These associations are not due to reverse causality or study design. Preventive strategies seeking to minimise the risk of inappropriate use of opioid medicines in later life should consider targeting this high-risk population.

Analysis and evaluation of explainable artificial intelligence on suicide risk assessment.

This study explores the effectiveness of Explainable Artificial Intelligence (XAI) for predicting suicide risk from medical tabular data. Given the common challenge of limited datasets in health-related Machine Learning (ML) applications, we use data augmentation in tandem with ML to enhance the identification of individuals at high risk of suicide. We use SHapley Additive exPlanations (SHAP) for XAI and traditional correlation analysis to rank feature importance, pinpointing primary factors influencing suicide risk and preventive measures. Experimental results show the Random Forest (RF) model is excelling in accuracy, F1 score, and AUC (>97% across metrics). According to SHAP, anger issues, depression, and social isolation emerge as top predictors of suicide risk, while individuals with high incomes, esteemed professions, and higher education present the lowest risk. Our findings underscore the effectiveness of ML and XAI in suicide risk assessment, offering valuable insights for psychiatrists and facilitating informed clinical decisions.

Adherence to pharmacotherapy: sine qua non for reducing cumulative risk of premature coronary disease in familial hypercholesterolemia.

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to atherosclerotic cardiovascular disease (ASCVD). The risk of ASCVD can be substantially reduced with lipid-lowering treatment (LLT). However, adherence to LLT remains a major challenge in FH patients and an under-recognized issue. We review several barriers to treatment adherence and implementation strategies for improving adherence in patients with FH. RECENT FINDINGS: Barriers that negatively affect patient adherence to treatment include the misunderstanding of perceived and actual risk of FH and the benefits of LLT, inadequate knowledge, lack of standardization of treatment, insufficient monitoring of LDL-cholesterol level, and inequalities in healthcare resources. Education of patients, carers and healthcare providers, guideline-directed treatment goals, regular monitoring, medication regimen simplification and greater access to established and new drugs are crucial enablers for improving adherence to treatment. However, given FH is present from birth, strategies for life-long adherence from childhood or young adulthood is critically important and requires further study. To be effective, strategies should be multifaceted, targeted and patient-centred involving a multidisciplinary-team with support from family, communities and peer groups. SUMMARY: FH confers a significant risk for ASCVD from a young age. Achieving better medication adherence is foundational for improving clinical outcomes and reducing the burden of atherosclerosis over a lifetime. Identification of key barriers and enablers are critical for implementing better adherence to treatment across the life-course of patients with FH.

Prospective Association Between the Dispensing of Antidepressants and of Medications to Treat Osteoporosis in Older Age.

BACKGROUND: Osteoporosis is a common condition associated with fragility fractures, especially in older individuals and women. Antidepressants have emerged as a potential risk factor, but their association with bone fragility remains uncertain because the results of past studies are difficult to generalize. We aimed to investigate the association between antidepressant exposure and subsequent treatment for osteoporosis in a nationally representative sample of Australians. METHODS: Cohort study using a 10% random sample of the Pharmaceutical Benefits Scheme (PBS) data for 2012, that included 566,707 individuals aged older than or equal to 50 years not dispensed osteoporosis medications. The effect of exposure to antidepressants during 2012 (prevalent or incident) or later (up to 2022) was examined using Cox regression models adjusted for age, sex, comorbidities and other psychotropic medications. RESULTS: Over 10 years, 73,360 (12.94%) received osteoporosis medications; 16,216 (22.10%) had been dispensed antidepressants in 2012. The hazard of osteoporosis medication dispensing was higher among those exposed to antidepressants (HR = 1.16, 99% CI = 1.14-1.18; average duration of follow up: 8.0 ± 3.1 years, range: 1-10 years). The hazard of osteoporosis medication diminished with increasing age, and the effect of antidepressants was 37%-76% more pronounced among men in the 50s and 60s. Different classes of antidepressants had a similar risk profile. CONCLUSION: The dispensing of antidepressants in older age is associated with higher hazard of subsequent dispensing of medications for osteoporosis, and this association is more marked for young older adults, particularly men. Clinicians should monitor the bone health of older individuals treated with antidepressants in order to decrease the morbidity associated with fragility fractures.

Contemporary trends in anaphylaxis burden and healthcare utilisation in Western Australia: A linked data study.

Background: Anaphylaxis is a growing public health problem in Australia. To determine the extent of the problem, we linked multiple health datasets to examine temporal trends in anaphylaxis events across the health system in Western Australia (WA). Methods: We identified an anaphylaxis cohort from 1980 to 2020 using linked datasets from ambulance, emergency departments, hospital inpatients and deaths. Age-standardised anaphylaxis event rates were calculated from 2010 to 2020. Dataset-specific rates for anaphylaxis were also examined, to show differences in health care utilisation. Annual percent change in rates (2010-2019) were estimated using age-adjusted Poisson regression models. Results: A total of 19 140 individuals (mean age 31 years; 51% female) experienced 24 239 anaphylaxis events between 2010 and 2020. From 2010 to 2019, the average annual percent increase (95% CI) in rates was 5.3% (4.8-5.8%), from 70.3 to 113.9, with rates reducing to 76.5/100 000 population in 2020. Adolescents and young adults aged 5-14 years and 15-24 years had the greatest increase of 6.9% (5.6-8.1%) and 6.8% (5.6-8.0) respectively, with those over 25 years increasing by approximately 5% per year and children 1-4 years showing the lowest annual increase of 2.6% (1.1-4.2%). The highest absolute rates were seen in under 1 year (269.7/100 000; 2019). There has been an acceleration of trends from 2015 to 2019, underpinned by large increases in 15-24 and 25-34 years. All databases, show similar increasing trends, with ambulance attendance (33.7 per 100 000), emergency presentation (89.8 per 100 000) and hospital admissions (46.2 per 100 000), for anaphylaxis highest in 2019. However, whilst ambulance and emergency presentations have grown by 8.9% (95%CI 7.9-9.8%) and 6.6% per year (95%CI 6.0-7.2%), respectively, hospitalisations appear to be steadying with only a 0.9% (95%CI 0.2-1.6%) yearly rise. Conclusion: Rates of anaphylaxis continue to increase, with WA having higher rates than previous estimates for Australia. Whilst rates are still high in infants, lower trends in children compared to older ages may indicate better prevention of allergy. Results show more people experiencing anaphylaxis now receive care in emergency and ambulance, rather than hospital. Further exploration of the patient care journey through prehospital and inpatient care is required, to understand the changing health demands of people who experience anaphylaxis.

Clinical outcomes and health care costs of transferring rural Western Australians for invasive coronary angiography, and a cost-effective alternative care model: a retrospective cross-sectional study.

OBJECTIVES: To examine the severity of coronary artery disease (CAD) in people from rural or remote Western Australia referred for invasive coronary angiography (ICA) in Perth and their subsequent management; to estimate the cost savings were computed tomography coronary angiography (CTCA) offered in rural centres as a first line investigation for people with suspected CAD. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: Adults with stable symptoms in rural and remote WA referred to Perth public tertiary hospitals for ICA evaluation during the 2019 calendar year. MAIN OUTCOME MEASURES: Severity and management of CAD (medical management or revascularisation); health care costs by care model (standard care or a proposed alternative model with local CTCA assessment). RESULTS: The mean age of the 1017 people from rural and remote WA who underwent ICA in Perth was 62 years (standard deviation, 13 years); 680 were men (66.9%), 245 were Indigenous people (24.1%). Indications for referral were non-ST elevation myocardial infarction (438, 43.1%), chest pain with normal troponin level (394, 38.7%), and other (185, 18.2%). After ICA assessment, 619 people were medically managed (60.9%) and 398 underwent revascularisation (39.1%). None of the 365 patients (35.9%) without obstructed coronaries (< 50% stenosis) underwent revascularisation; nine patients with moderate CAD (50-69% stenosis; 7%) and 389 with severe CAD (≥ 70% stenosis or occluded vessel; 75.5%) underwent revascularisation. Were CTCA used locally to determine the need for referral, 527 referrals could have been averted (53%), the ICA:revascularisation ratio would have improved from 2.6 to 1.6, and 1757 metropolitan hospital bed-days (43% reduction) and $7.3 million in health care costs (36% reduction) would have been saved. CONCLUSION: Many rural and remote Western Australians transferred for ICA in Perth have non-obstructive CAD and are medically managed. Providing CTCA as a first line investigation in rural centres could avert half of these transfers and be a cost-effective strategy for risk stratification of people with suspected CAD.

Risk of early recurrence and mortality in high-risk myocardial infarction patients: A population-based linked data study.

Background: Survival during the early period following myocardial infarction (MI) has significantly improved although there are limited data on cardiovascular recurrence during this period. Methods: We identified all emergency hospitalisations for MI from November 1, 2011 to October 31, 2016 in Western Australia from a linked hospitalisation/mortality dataset. Patients were included if they survived >3 days, had no acute kidney injury, and had ≥1 of: ≥65 years, prior MI, diabetes or peripheral arterial disease. Outcomes were major adverse cardiovascular events (MACE, a composite of CVD death, recurrent MI or stroke), cardiovascular disease (CVD) death, all-cause mortality, recurrent MI and stroke. Cumulative risks at 90-days and 1-year were estimated from Kaplan-Meier analyses and predictors of each outcome from multivariable Cox regression models. Results: There were 8024 high-risk MI patients identified (males 61.8%). Median age was 73.7 years (IQR 66.3-82.2). Half of the risk of MACE occurred in the first 90-days post-MI (6.6% vs 12.6% at 1-year) and was underpinned by risk of recurrent MI. Risk was generally higher in women than men (MACE: 6.0% males, 7.7% females, p = 0.0025; CVD mortality: 1.7% males, 3.7% females; all-cause mortality: 2.8% males, 5.6% females, p < 0.0001). Independent predictors of 90-day MACE were increasing age, heart failure history, hypertension and prior stroke. Female sex was not associated with a higher rate of any of the outcomes after multivariable adjustment. Conclusion: Half of cardiovascular events in the year following an MI occur within 90-days, demonstrating that reductions in MI burden could be achieved by further targeted intervention in the early period following an MI.

Evidence-based medication adherence among seniors in the first year after heart failure hospitalisation and subsequent long-term outcomes: a restricted cubic spline analysis of adherence-outcome relationships.

PURPOSE: Non-adherence to heart failure (HF) medications is associated with poor outcomes. We used restricted cubic splines (RCS) to assess the continuous relationship between adherence to renin-angiotensin system inhibitors (RASI) and ß-blockers and long-term outcomes in senior HF patients. METHODS: We identified a population-based cohort of 4234 patients, aged 65-84 years, 56% male, who were hospitalised for HF in Western Australia between 2003 and 2008 and survived to 1-year post-discharge (landmark date). Adherence was calculated using the proportion of days covered (PDC) in the first year post-discharge. RCS Cox proportional-hazards models were applied to determine the relationship between adherence and all-cause death and death/HF readmission at 1 and 3 years after the landmark date. RESULTS: RCS analysis showed a curvilinear adherence-outcome relationship for both RASI and ß-blockers which was linear above PDC 60%. For each 10% increase in RASI and ß-blocker adherence above this level, the adjusted hazard ratio for 1-year all-cause death fell by an average of 6.6% and 4.8% respectively (trend p < 0.05) and risk of all-cause death/HF readmission fell by 5.4% and 5.8% respectively (trend p < 0.005). Linear reductions in adjusted risk for these outcomes at PDC ≥ 60% were also seen at 3 years after landmark date (all trend p < 0.05). CONCLUSION: RCS analysis showed that for RASI and ß-blockers, there was no upper adherence level (threshold) above 60% where risk reduction did not continue to occur. Therefore, interventions should maximise adherence to these disease-modifying HF pharmacotherapies to improve long-term outcomes after hospitalised HF.

Antihypertensive Medication Adherence and the Risk of Vascular Events and Falls After Stroke: A Real-World Effectiveness Study Using Linked Registry Data.

BACKGROUND: Real-world evidence is limited on whether antihypertensive medications help avert major adverse cardiovascular events (MACE) after stroke without increasing the risk of falls. We investigated the association of adherence to antihypertensive medications on the incidence of MACE and falls requiring hospitalization after stroke. METHODS: A retrospective cohort study of adults who were newly dispensed antihypertensive medications after an acute stroke (Australian Stroke Clinical Registry 2012-2016; Queensland and Victoria). Pharmaceutical dispensing records were used to determine medication adherence according to the proportion of days covered in the first 6 months poststroke. Outcomes between 6 and 18 months postdischarge included: (i) MACE, a composite outcome of all-cause death, recurrent stroke or acute coronary syndrome; and (ii) falls requiring hospitalization. Estimates were derived using Cox models, adjusted for >30 confounders using inverse probability treatment weights. RESULTS: Among 4076 eligible participants (median age 68 years; 37% women), 55% had a proportion of days covered ≥80% within 6 months postdischarge. In the subsequent 12 months, 360 (9%) participants experienced a MACE and 337 (8%) experienced a fall requiring hospitalization. After achieving balance between groups, participants with a proportion of days covered ≥80% had a reduced risk of MACE (hazard ratio: 0.68; 95% CI: 0.54-0.84) and falls requiring hospitalization (subdistribution hazard ratio: 0.78; 95% CI: 0.62-0.98) than those with a proportion of days covered <80%. CONCLUSIONS: High adherence to antihypertensive medications within 6 months poststroke was associated with reduced risks of both MACE and falls requiring hospitalization. Patients should be encouraged to adhere to their antihypertensive medications to maximize poststroke outcomes.

Short-term DAPT after coronary stenting has similar ischemic and bleeding outcomes as long-term DAPT: a 5-year population-based cohort study.

BACKGROUND: Optimal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains controversial. AIM: We investigated the relationship between DAPT duration following PCI and long-term ischemic and bleeding outcomes under real-world conditions. METHODS: Patients aged ≥ 65 years who underwent PCI with stenting in Western Australian hospitals between 2003 and 2008 and survived 2 years were identified from linked hospital admissions data. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE) defined as a composite of all-cause death and admissions for acute coronary syndrome (ACS), coronary artery revascularization procedure, stroke, and major bleeding. Secondary outcomes were ACS admissions, all-cause death, and major bleeding admissions. Patients were followed up for 5 years from initial PCI. RESULTS: A total of 3963 patients were included in the final analysis. The mean age of the cohort was 74.5 ± 6.1 years with 67.3% males. No significant difference was seen with 6-12, 12-18, or 18-24 months DAPT, compared to 0-6 months DAPT duration for MACCE and all secondary outcomes at 3- and 5-year post-PCI. CONCLUSION: There is no significant difference in both bleeding and ischemic outcomes in long-term DAPT as compared to short-term DAPT for first- and second-generation drug-eluting stents in a real-world population.

Multivariable statistical models to predict red cell transfusion in elective surgery.

BACKGROUND: Predicting red cell transfusion may assist in identifying those most likely to benefit from patient blood management strategies. Our objective was to identify a simple statistical model to predict transfusion in elective surgery from routinely available data. MATERIALS AND METHODS: Our final multicentre cohort consisted of 42,546 patients and contained the following potential predictors of red cell transfusion known prior to admission: patient age, sex, pre-admission hemoglobin, surgical procedure, and comorbidities. Missing data were handled by multiple imputation methods. The outcome measure of interest was administration of a red cell transfusion. We used multivariable logistic regression models to predict transfusion, and evaluated the performance by applying a 10-fold cross-validation. Model accuracy was assessed by comparing the area under the receiver operating characteristics curve. After applying an optimal probability cut-off we measured model accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: 7.0% (n=2,993) of the study population received a red cell transfusion. Our most simple model predicted red cell transfusion based on admission hemoglobin and surgical procedure with a multiply imputed estimated area under the curve of 0.862 (0.856, 0.864). The estimated accuracy, sensitivity, specificity, positive predictive, and negative predictive values at the probability cut-off of 0.4 were 0.934, 0.257, 0.986, 0.573, and 0.946 respectively. DISCUSSION: A small number of variables available prior to admission can predict red cell transfusion with very good accuracy. Our model can be used to flag high-risk patients most likely to benefit from pre-operative patient blood management measures.

Overview of registries for anaphylaxis: a scoping review.

OBJECTIVE: This review aimed to describe the scope and operational features of anaphylaxis registries, and to assess their contribution to improving knowledge of anaphylaxis and care of patients who experience anaphylaxis by measuring their research output. INTRODUCTION: Structured data collection and reporting systems, such as registries, are needed to better understand the burden of anaphylaxis and to protect the growing number of patients with severe allergy. There is a need to characterize current anaphylaxis registries to identify their value in anaphylaxis surveillance, management, and research. Information synthesized in this review will provide knowledge on benefits and gaps in current registries, which may inform the implementation and global standardization of future anaphylaxis reporting systems. INCLUSION CRITERIA: This scoping review considered literature describing registries worldwide that enroll patients who have experienced anaphylaxis. Published and gray literature sources were included if they described the scope and operational features of anaphylaxis registries. METHODS: This review followed the JBI methodology for scoping reviews. Embase, MEDLINE, Scopus, and CINAHL were searched for relevant articles. Identified keywords and index terms were adapted for searches of gray literature sources, using Google advanced search functions. Only full-text studies in English were considered for inclusion. Two independent reviewers conducted title and abstract screening and those that did not meet the inclusion criteria were excluded. The full text of potentially relevant articles were retrieved; full-text screening and data extraction were also conducted by two independent reviewers. Any discrepancies were resolved through discussion or with a third reviewer. Tables and a narrative summary were used to describe and compare the scope and features (eg, inclusion criteria, patient demographics, clinical symptoms) of the identified anaphylaxis registries, and to outline their output to assess their contribution to research and clinical practice for anaphylaxis. RESULTS: A total of 77 full-text publications and eight gray literature sources were used to extract data. The literature search identified 19 anaphylaxis registries, with sites in 28 countries including Europe, the United Kingdom, Canada, the United States, Korea, and Australia. The main purposes of the identified registries were to collect clinical data for research; provide clinical support tools to improve patient care; and operate as allergen surveillance systems to protect the wider community with allergies. Differences in inclusion and health care settings exist, with 11 collecting data on anaphylaxis of any cause, two on food reactions alone, three on fatal anaphylaxis, one on perioperative anaphylaxis, and two on allergic reactions (including anaphylaxis). Five registries enroll cases in allergy centers, five in hospital settings, one in schools, and others target a combination of general practitioners, specialists in emergency departments, and other relevant hospital departments and allergy outpatient clinics. Only three registries operate under a mandatory framework. A total of 57 publications were considered research outputs from registries. All registries except two have published studies from collected data, with the greatest number of articles published from 2019 to the present. Publications mostly addressed questions regarding demographic profile, causes and cofactors, severity, fatal reactions, and gaps in management. CONCLUSIONS: This review demonstrated that anaphylaxis registries differ in their scope and operation, having been established for different purposes. Importantly, registries have contributed significantly to research, which has highlighted gaps in anaphylaxis management, provoking allergens, and informed targets for prevention for severe and fatal events. Beyond this, registries relay information about anaphylaxis to clinicians and regulatory bodies to improve patient care and protect the community. The ability to link registry data with other health datasets, standardization of data across registries, and incorporation of clinical care indicators to promote quality health care across the health system represent important targets for future systems.

Towards better reporting of the proportion of days covered method in cardiovascular medication adherence: A scoping review and new tool TEN-SPIDERS.

Although medication adherence is commonly measured in electronic datasets using the proportion of days covered (PDC), no standardized approach is used to calculate and report this measure. We conducted a scoping review to understand the approaches taken to calculate and report the PDC for cardiovascular medicines to develop improved guidance for researchers using this measure. After prespecifying methods in a registered protocol, we searched Ovid Medline, Embase, Scopus, CINAHL Plus and grey literature (1 July 2012 to 14 December 2020) for articles containing the terms "proportion of days covered" and "cardiovascular medicine", or synonyms and subject headings. Of the 523 articles identified, 316 were reviewed in full and 76 were included (93% observational studies; 47% from the USA; 2 grey literature articles). In 45 articles (59%), the PDC was measured from the first dispensing/claim date. Good adherence was defined as 80% PDC in 61 articles, 56% of which contained a rationale for selecting this threshold. The following parameters, important for deriving the PDC, were often not reported/unclear: switching (53%), early refills (45%), in-hospital supplies (45%), presupply (28%) and survival (7%). Of the 46 articles where dosing information was unavailable, 59% reported how doses were imputed. To improve the transparent and systematic reporting of the PDC, we propose the TEN-SPIDERS tool, covering the following PDC parameters: Threshold, Eligibility criteria, Numerator and denominator, Survival, Presupply, In-hospital supplies, Dosing, Early Refills, and Switching. Use of this tool will standardize reporting of the PDC to facilitate reliable comparisons of medication adherence estimates between studies.

Prior oral proton-pump inhibitor use is associated with reduced severity of aspirin-related upper gastrointestinal bleeding in older people.

Low-dose aspirin is commonly used for primary or secondary prophylaxis against cardiovascular disease in older people. However, the potential risk of upper gastrointestinal (UGI) ulceration and bleeding associated with low-dose aspirin use is often not appreciated by prescribers and older consumers. Among 133 serial patients with UGI bleeding, aspirin-users aged ≥70 years had a ninefold increased likelihood of overt UGI bleeding compared with non-users, reducing by 90% in regular proton-pump inhibitor users (adjusted odds ratio 0.10). We recommend risk-versus-benefit discussions when recommending aspirin to older people.