Observed Event Rates Research Articles

Dynamic Risk Estimation of Adverse Events in Ambulatory LVAD Patients: A MOMENTUM 3 Analysis

BackgroundHemocompatibility-related adverse events affect patients after left ventricular assist device (LVAD) implantation but are hard to predict. ObjectivesDynamic risk modeling with a multistate model can predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory patients. MethodsThis was a secondary analysis of the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial. HeartMate 3 LVAD recipients who survived to hospital discharge and were followed for up to 2 years. A total of 145 variables were included in the multistate model with multivariate logistic regression. Model performance was assessed with the area under the curve in a holdout validation cohort. A risk stratification tool was created by dividing patients into categories of predicted risk using the final model variables and associated OR. ResultsAmong 2,056 LVAD patients, the median age was 59.4 years (20.4% women, 28.6% Black). At 2 years, the incidence of GIB, stroke, and death was 25.6%, 6.0%, and 12.3%, respectively. The multistate model included 39 total variables to predict risk of GIB (16 variables), stroke (10 variables), and death (19 variables). When ambulatory patients were classified according to their risk category, the 30-day observed event rate in the highest risk group for GIB, stroke, or death was 26.9%, 1.8%, and 4.8%, respectively. The multistate model predicted GIB, stroke, and death at any 30-day period with an area under the curve of 0.70, 0.69, and 0.86, respectively. ConclusionsThe multistate model informs 30-day risk in ambulatory LVAD recipients and allows recalculation of risk as new patient-specific data become available. The model allows for accurate risk stratification that predicts impending adverse events and may guide clinical decision making. (MOMENTUM 3 IDE Clinical Study Protocol; NCT02224755)

Long-term temporal stability of the DarkSide-50 dark matter detector

The stability of a dark matter detector on the timescale of a few years is a key requirement due to the large exposure needed to achieve a competitive sensitivity. It is especially crucial to enable the detector to potentially detect any annual event rate modulation, an expected dark matter signature. In this work, we present the performance history of the DarkSide-50 dual-phase argon time projection chamber over its almost three-year low-radioactivity argon run. In particular, we focus on the electroluminescence signal that enables sensitivity to sub-keV energy depositions. The stability of the electroluminescence yield is found to be better than 0.5%. Finally, we show the temporal evolution of the observed event rate around the sub-keV region being consistent to the background prediction.

Accuracy of Event Rate and Effect Size Estimation in Major Cardiovascular Trials

For the design of a randomized clinical trial (RCT), estimation of the expected event rate and effect size of an intervention is needed to calculate the sample size. Overestimation may lead to an underpowered trial. To evaluate the accuracy of published estimates of event rate and effect size in contemporary cardiovascular RCTs. A systematic search was conducted in MEDLINE for multicenter cardiovascular RCTs associated with MeSH (Medical Subject Headings) terms for cardiovascular diseases published in the New England Journal of Medicine, JAMA, or the Lancet between January 1, 2010, and December 31, 2019. Identified trials underwent abstract review; eligible trials then underwent full review, and those with insufficiently reported data were excluded. Data were extracted from the original publication or the study protocol, and a random-effects model was used for data pooling. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. The primary outcome was the accuracy of event rate and effect size estimation. Accuracy was determined by comparing the observed event rate in the control group and the effect size with their hypothesized values. Linear regression was used to determine the association between estimation accuracy and trial characteristics. Of the 873 RCTs identified, 374 underwent full review and 30 were subsequently excluded, resulting in 344 trials for analysis. The median observed event rate was 9.0% (IQR, 4.3% to 21.4%), which was significantly lower than the estimated event rate of 11.0% (IQR, 6.0% to 25.0%) with a median deviation of -12.3% (95% CI, -16.4% to -5.6%; P < .001). More than half of the trials (196 [61.1%]) overestimated the expected event rate. Accuracy of event rate estimation was associated with a higher likelihood of refuting the null hypothesis (0.13 [95% CI, 0.01 to 0.25]; P = .03). The median observed effect size in superiority trials was 0.91 (IQR, 0.74 to 0.99), which was significantly lower than the estimated effect size of 0.72 (IQR, 0.60 to 0.80), indicating a median overestimation of 23.1% (95% CI, 17.9% to 28.3%). A total of 216 trials (82.1%) overestimated the effect size. In this systematic review of contemporary cardiovascular RCTs, event rates of the primary end point and effect sizes of an intervention were frequently overestimated. This overestimation may have contributed to the inability to adequately test the trial hypothesis.

White Dwarfs in Dwarf Spheroidal Galaxies: A New Class of Compact-Dark-Matter Detectors.

Recent surveys have discovered a population of faint supernovae, known as Ca-rich gap transients, inferred to originate from explosive ignitions of white dwarfs. In addition to their unique spectra and luminosities, these supernovae have an unusual spatial distribution and are predominantly found at large distances from their presumed host galaxies. We show that the locations of Ca-rich gap transients are well matched to the distribution of dwarf spheroidal galaxies surrounding large galaxies, in a scenario where dark matter interactions induce thermonuclear explosions among low-mass white dwarfs that may be otherwise difficult to ignite with standard stellar or binary evolution mechanisms. A plausible candidate to explain the observed event rate are primordial black holes with masses above 10^{21} grams.

SCORE and SCORE2 in East Asian Population: A Performance Comparison

BackgroundSystematic COronary Risk Evaluation 2 (SCORE2) and SCORE2-Older Persons (OP) models have been proposed as new cardiovascular risk evaluation tools. ObjectivesThis study evaluated the performance of SCORE/SCORE-OP and SCORE2/SCORE2-OP in the East Asian population by using population-based cohort data from the National Health Insurance Service (NHIS) Health Screening Cohort of Korea. MethodsA total of 324,384 NHIS examinees from 2004 to 2005 were divided into 5 age groups: 40-49 years, 50-59 years, 60-69 years,70-79 years, and more than 80 years. The examinees had their predicted cardiovascular disease risks calculated by using SCORE, SCORE2, SCORE-OP, and SCORE2-OP models. The low-risk model was applied on the basis of the cohort’s observed event rates. The observed and predicted cardiovascular risks were compared. ResultsA total of 324,384 subjects were included (mean age 51.4 ± 7.3 years; women, 37.9% for the SCORE/SCORE2 group and mean age 73.0 ± 2.8 years; women, 47.5% for the SCORE/SCORE2-OP group). Over a median follow-up of 9 years, cardiovascular events occurred in 15.0% and 28.9% in SCORE/SCORE2 and SCORE/SCORE2-OP groups, respectively. The SCORE/SCORE-OP model underestimated cardiovascular disease risk in young men (aged 40-49 years) and women (aged 40-59 years) and overestimated it in older age groups. In contrast, SCORE2/SCORE2-OP invariably overestimated the risk in all age groups and sexes. SCORE2/SCORE2-OP showed no improvement in Harrell’s concordance index (C-index) compared with SCORE/SCORE-OP. Calibration plots favored SCORE2 over SCORE but not SCORE2-OP over SCORE-OP. ConclusionsBoth SCORE2/SCORE2-OP and SCORE/SCORE-OP overestimated cardiovascular disease risk with low performance. SCORE2/SCORE2-OP showed slight improvement over older versions, but modifications are necessary for the East Asian population.

Dramatic improvements in survival in women and men with acute myocardial infarction over 30 years: a nationwide cohort study

Abstract Background Treatment of myocardial infarction (MI) has improved over the last decades due to the implementation of early revascularization and medical therapies for secondary prevention. The impact of these treatment changes on survival in women and men has not been documented over a 30-year perspective. Purpose The aim of this study was to assess implementation of new treatment strategies and their effects on changes in long-term outcomes in all patients with MI in Sweden over 30 years. Methods In SWEDEHEART, the Swedish register for coronary heart disease, we investigated treatments and outcomes and their associations in patients admitted with MI between 1991-2021. Patients were stratified in 2-year blocks, starting with a 3-year block for 1991-1993. Primary outcome was 1-year risk of cardiovascular (CV) mortality. Effect of treatments on outcome was assessed comparing observed event rates with event rates standardized by logistic regression accounting for differences in baseline characteristics and treatment. Results A total of 433,524 cases with MI were hospitalized between 1991-2021. Between 1991-1993 and 2020-2021, treatment with reperfusion and revascularization increased from 34.7% to 77.3%; in-hospital PCI from 1.8% to 73.8 %; dual antiplatelet therapy (DAPT) from 0.0% to 73.8%; statins from 3.0% to 91.7%; beta-blockers from 66.4% to 88.3%; and renin-angiotensin-system (RAS) inhibitors from 21.6% to 81.6% (Figure 1A). During the same period, the rates of 1-year CV mortality decreased from 24.1% to 8.3%. For women, CV mortality decreased from 28.9% to 10.3% and for men from 21.7% to 7.3%. When comparing observed with standardized event rates, most of the mortality improvement was explained by the implementation of early revascularization with PCI (Figure 1B). Conclusions In this unique nationwide cohort of patients with MI over 30 years, there was a gradual implementation of revascularization and novel medical treatment. Concurrently, there was a gradual absolute reduction in 1-year risk of CV mortality with 16 percentage points, which was similar in women and men. Most of the improvement in survival was related to implementation of early revascularization strategies. Figure 1 (A) Temporal trends in treatment and (B) crude and standardized rates of cardiovascular mortality within 1 year in patients with myocardial infarction over 30 years in Sweden.

Abstract 13028: Estimating Cardiovascular Event Rates in US Veterans Using the SMART Risk Score

Background: There is limited data on racial differences in long term cardiovascular (CV) outcomes amongst U.S. veterans. Methods: Utilizing the VA Informatics and Computing Infrastructure and the Corporate Data Warehouse we compared 10-year predicted major adverse CV events [MACE, a composite of all-cause death and non-fatal myocardial infarction] in patients referred for cardiovascular consultation between 2003 and 2009 using the SMART risk score with observed rates across racial groups. The SMART risk score classified patients into low 0-9.9%, intermediate 10-19.9%, high 20-29.9%, and very high &gt;=30% risk groups. Results: 473,136 patients including white (74.7%), African American (15.5%), and other (9.8%) made the study cohort. Observed event rates were significantly higher in African Americans compared with Whites across all SMART risk groups [p&lt;0.001], and highest in the other races, inclusive of Hispanics. These results are depicted in Figure 1 . Conclusion: There is a significantly higher observed 10-year MACE rate in African American veterans compared with their white counterparts across all predicted SMART risk score groups.

Tidal disruption rate suppression by the event horizon of spinning black holes

ABSTRACT The rate of observable tidal disruption events (TDEs) by the most massive (≳ few × 107 M⊙) black holes (BHs) is suppressed due to direct capture of stars. This suppression effect depends on the space–time geometry and holds the promise of probing the spin distribution of dormant BHs at the centres of galaxies. By extending the frozen-in approximation commonly used in the Newtonian limit, we propose a general relativistic criterion for the tidal disruption of a star of given interior structure. The rate suppression factor is then calculated for different BH masses, spins, and realistic stellar populations. We find that either a high-BH spin (≳ 0.5) or a young stellar population (≲1 Gyr) allows TDEs to be observed from BHs significantly more massive than $10^8\, \mathrm{M}_{\odot }$. We call this spin-age degeneracy (SAD). This limits our utility of the TDE rate to constrain the BH spin distribution, unless additional constraints on the age of the stellar population or the mass of the disrupted star can be obtained by modelling the TDE radiation or the stellar spectral energy distribution near the galactic nuclei.

Combined Radiofrequency Ablation and Left Atrial Appendage Closure in Atrial Fibrillation and Systolic Heart Failure.

Managing patients with atrial fibrillation (AF) and comorbid heart failure (HF) with reduced (HFrEF) or mildly reduced ejection fraction (HFmrEF) is of clinical importance but a great challenge. This study aimed to evaluate the clinical benefit of the combined radiofrequency catheter ablation (RFCA) and left atrial appendage closure (LAAC) procedure in AF patients complicated with systolic HF. AF patients with HFrEF or HFmrEF who underwent the combined RFCA and LAAC procedure were prospectively enrolled in the LAACablation registry. The procedural complications and long-term outcomes were evaluated. Another cohort of AF patients with systolic HF who did not undergo either RFCA or LAAC were used for prognosis comparison. Among 802 AF patients who underwent the combined procedure, 65 patients were comorbid with systolic HF (25 with HFrEF and 40 with HFmrEF). The overall procedural complication rate was 9.2%, which was mainly attributed to acute decompensated HF (6.2%). Accompanied with markedly reduced AF burden (from median [25th, 75th percentile]: 100 [100, 100] to 0 [0, 1.2]%, p < 0.001), upward trajectories of cardiac function were observed in 51 (78.4%) patients, showing improvement in New York Heart Classification (p < 0.01), natriuretic peptide levels (from 1492 [809, 3259] to 413 [163, 880] pg/mL, p < 0.001) and left ventricular EF (from 42.6 ± 5.3 to 53.8 ± 8.2%, p < 0.001). During the 27-month follow-up period, death, thromboembolism, major bleeding, and HF rehospitalization were observed in three, one, one, and four patients, respectively. The observed event rates showed a significant reduction compared with the non-procedure AF-HF cohort (n = 138; for composite endpoint: hazard ratio: 2.509, 95% confidence interval: 1.415-4.449, p = 0.002) and with the respective rates predicted by risk scores. Combining RFCA and LAAC achieves acceptable safety and credible long-term efficacy in AF patients with systolic HF. Further randomized studies are warranted in a larger patient cohort.

Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study.

Guidelines recommend extended dual antiplatelet therapy (DAPT), including ticagrelor 60mg twice daily, in high-risk post myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischemic outcomes associated with long-term ticagrelor 60mg in routine clinical practice have not been well described. Register and claims data from US (Optum Clinformatics, IBM MarketScan, Medicare) and Europe (Sweden, Italy, UK, Germany) were extracted. Patients initiating ticagrelor 60mg≥12 months after MI, meeting eligibility criteria for PEGASUS-TIMI 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality, and of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source. 7035 patients treated with ticagrelor 60mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90mg prior to initiating ticagrelor 60mg. At 12 months from initiation of ticagrelor 60mg, the cumulative incidence (95% CI) of MI, stroke or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33). This study provides insights into the use of ticagrelor 60mg in patients with prior MI in clinical practice. Observed event rates for ischemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischemic risk in this population.Clinical Trials.gov Registration NCT04568083.

Lipoprotein(a) and the pooled cohort equations for ASCVD risk prediction: The Multi-Ethnic Study of Atherosclerosis

Background and aimsLipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) but is not included in the Pooled Cohort Equations (PCE). We aimed to assess how well the PCE predict 10-year event rates in individuals with elevated Lp(a), and whether the addition of Lp(a) improves risk prediction. MethodsWe compared observed versus PCE-predicted 10-year ASCVD event rates, stratified by Lp(a) level and ASCVD risk category using Poisson regression, and evaluated the association between Lp(a) > 50 mg/dL and ASCVD risk using Cox proportional hazards models in the Multi-Ethnic Study of Atherosclerosis (MESA). We evaluated the C-index and net reclassification improvement (NRI) with addition of Lp(a) to the PCE. ResultsThe study population included 6639 individuals (20%, n = 1325 with elevated Lp(a)). The PCE accurately predicted 10-year event rates for individuals with elevated Lp(a) with observed event rates falling within predicted limits. Elevated Lp(a) was associated with increased risk of CVD events overall (HR 1.27, 95% CI 1.00–1.60), particularly in low (HR 2.45, 95% CI 1.40–4.31), and high-risk (HR 1.41, 95% CI 1.02–1.96) individuals. Continuous NRI (95% CI) with the addition of Lp(a) to the PCE for CVD was 0.0963 (0.0158–0.1953) overall, and 0.2999 (0.0876, 0.5525) among low-risk individuals. ConclusionsThe PCE performs well for event rate prediction in individuals with elevated Lp(a). However, Lp(a) is associated with increased CVD risk, and the addition of Lp(a) to the PCE improves risk prediction, particularly among low-risk individuals. These results lend support for increasing use of Lp(a) testing for risk assessment.

Type Ia supernovae induced by primordial black holes from dark first-order phase transition

A primordial black hole (PBH) with mass 10−15≤MPBH/M⊙≤10−10 is currently beyond the sensitivity of both microlensing and black hole (BH) evaporation methods. A novel scenario has been proposed: When a PBH with mass 10−14≤MPBH/M⊙≤10−11 transits through a white dwarf (WD) made up of carbon and oxygen, Bondi-Hoyle-Lyttleton (BHL) accretion in a reactive medium creates a shock wave, which generates direct detonation ignition in the WD core and then leads to thermonuclear supernovae (SNe Ia). The aim of this study is to impose constraints on the PBH to dark matter (DM) abundance fraction, fPBH, via comparing the SN Ia event rates between PBH hypotheses and observational data. For PBH fraction less than unity, we found the observed event rate prefers PBH mass region, 7.6×10−13≤MPBH/M⊙≤6.1×10−12, under the Navarro–Frenk–White (NFW) profile. Meanwhile, the aforementioned PBH mass and abundance can be efficiently produced via a cosmological first-order phase transition (FOPT) in dark sector which associates with O(MeV) energy scale and thus gives rise to complementary signals of stochastic gravitational waves (GWs) with peak frequencies from 10−6 Hz to 10−5 Hz which can be probed by future μAres GW interferometer.

External validation of Systematic COronary Risk Evaluation 2 - Older Persons (SCORE2-OP) in the EPIC-Norfolk prospective population study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): EPIC Norfolk was supported by the Medical Research Council UK (programme grants numbers MRC G0401527, MRC G0701863, MRC G1000143) and Cancer Research UK (programme grant number CRUK 8257). Introduction The Systematic COronary Risk Evaluation 2 – Older Persons (SCORE2-OP) algorithm is developed to assess 10-year risk of fatal and non-fatal cardiovascular disease (CVD) in apparently healthy individuals aged ≥70 years. We evaluated the performance of SCORE2-OP in the European Prospective Investigation of Cancer Norfolk (EPIC-Norfolk) prospective population cohort. Purpose To validate the SCORE2-OP model in men and women aged 70-80 years without prior myocardial infarction or stroke. Methods We included individuals aged 70-80 without prior myocardial infarction or stroke. We compared SCORE2-OP (low-risk algorithm) calculated 10-year risk with 10-year observed event rates in the EPIC-Norfolk cohort. SCORE2-OP was calculated using baseline EPIC-Norfolk data (1993-1997). Cardiovascular events were defined as a composite outcome of (i) death due to ischemic heart disease, cardiac failure, cerebrovascular disease or peripheral-artery disease, (ii) non-fatal myocardial infarction or (iii) non-fatal stroke. Observed rates were adjusted for competing fatal events. We evaluated discriminative power using C-statistic and calibration by plotting predicted versus observed event rates and calculating the observed/predicted ratios. Results SCORE2-OP was evaluated in 3,712 individuals (54% women) with a median (IQR) age of 73 (72-75) years. Ten-year SCORE2-OP was 10.3% (95% confidence interval (CI) 10.2-10.4) versus observed CVD of 16.8% (95% CI 15.6-18.0), yielding a ratio of 1.6 (95% CI 1.5-1.7). Observed events consisted of 9.4% (95% CI 8.4-10.3) fatal CVD events, 10.6% (95% CI 9.6-11.5) non-fatal myocardial infarctions, 10.5% (95% CI 9.5-11.5) non-fatal strokes, adjusted for 68.9% (95% CI 67.4-70.4) competing mortality events. C-statistic was 0.60 (95% CI 0.58-0.63), with a calibration plot demonstrating underestimation of risk across sex and risk groups.(Figure). Conclusion SCORE2-OP underestimates risk in individuals aged 70-80 years, and demonstrates suboptimal discriminative ability. However some underestimation of risk is to be expected given the EPIC-Norfolk baseline between 1993-1997, a low SCORE2-OP calculated risk should not be used as a standalone argument to withhold preventive efforts in older individuals.

Carotid ultrasound and Systematic Coronary Risk Assessment 2 (SCORE2) in the prediction of cardiovascular events.

Subclinical carotid atherosclerosis adds predictive value to traditional risk factors for cardiovascular diseases (CVDs). Systematic Coronary Risk Assessment 2 (SCORE2), an algorithm composed of traditional risk factors, is state-of-the-art to estimate the 10-year risk of first-onset CVDs. We aim to investigate whether and how subclinical carotid atherosclerosis affects the performance of SCORE2. Carotid plaque presence and intima media thickness (IMT) were measured with ultrasound. SCORE2 was calculated in 4,588 non-diabetic participants aged 46-68 years. The incremental value for predicting CVD events of adding carotid plaque or IMT to SCORE2 was evaluated using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The predicted 10-year CVD risk by SCORE2 and the observed event rate were compared between participants with and without carotid plaque. Adding plaque or IMT to SCORE2 significantly improved performance for predicting CVDs. The improvement in C-statistics, IDI and NRI of adding plaque to SCORE2 for events occurring during the first 10 years were 2.20, 0.70 and 46.1%, respectively (all p < 0.0001). SCORE2 over-predicted the 10-year CVD risk in those without carotid plaque (3.93% observed versus 5.89% predicted, p < 0.0001) while under-predicted the risk in those with carotid plaque (9.69% observed versus 8.12% predicted, p = 0.043). Carotid ultrasound adds predictive performance to SCORE2 for assessment of CVD risk. Using SCORE2 without considering carotid atherosclerosis could under- or over-estimate the risk.

Cohort profile of PLUTO: a perioperative biobank focusing on prediction and early diagnosis of postoperative complications

PurposeAlthough elective surgery is generally safe, some procedures remain associated with an increased risk of complications. Improved preoperative risk stratification and earlier recognition of these complications may ameliorate postoperative recovery...

Abstract P567: Cardiovascular Health Awareness and Risk Assessment in Schoolteachers in Calcutta, India

Background: Cardiovascular disease (CVD) is the leading cause of death in India, surpassing all infectious causes. Early awareness of CVD and its risk factors and adoption of heart healthy lifestyle practices are crucial to reducing the impact of CVD in the community. Objective: To assess schoolteachers’ awareness of CVD and to compare the calculated ten-year risk of heart attack, stroke, and death by the Atherosclerotic Cardiovascular Disease (ASCVD) model to the observed event rates. Methods: We surveyed 4,150 schoolteachers out of 5,321 (78% response rate) from 400 schools in Calcutta during 2019 using a questionnaire assessing their awareness of CVD in five domains: prevalence, spectrum of CVD, its nature, risk factors, and benefits of a heart healthy lifestyle. The study population was stratified by risk tertile of their 10-year calculated ASCVD score. Results: Awareness about cardiovascular health among schoolteachers (male 41%, mean age 44 years) was low: 33 (mean score out of maximum 100), varying in different domains as shown below. Although most (86%) were at mild risk for CVD with ASCVD scores below five, nine percent had moderate risk, and five percent had high risk of CVD. There was no significant association between their risk score and their awareness of CVD health (correlation coefficient r = - 0.022, 95% confidence interval - 0.052, 0.009). Conclusions: Cardiovascular health awareness among schoolteachers in Calcutta is suboptimal, many of whom are at risk for CVD. Awareness of the disease, detection of risk factors at an early stage, and adoption of a healthy lifestyle may help reduce CVD in this community.

Impact of LIGO-Virgo black hole binaries on gravitational wave background searches

We study the impact of the black hole binary population currently probed by LIGO-Virgo on future searches for the primordial gravitational wave background. We estimate the foreground generated by the binaries using the observed event rate and a simple modeling of the black hole population. We subtract individually resolvable binaries from the foreground and utilize Fisher analysis to derive sensitivity curves for power-law signals including these astrophysical foregrounds. Even with optimistic assumptions, we find that the reach of future experiments will be severely reduced.

Clinical Outcome of Revascularization Deferral With Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A 5-Year Follow-Up Substudy From the iFR-SWEDEHEART Trial.

Background Although physiology-based assessment of coronary artery stenosis using instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) are established methods of guiding coronary revascularization, its clinical outcome in long-term deferral needs further evaluation, especially with acute coronary syndrome as a clinical presentation. The aim was to evaluate the long-term clinical outcome of deferral of revascularization based on iFR or FFR. Methods and Results This is a substudy of the iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trial, where patients deferred from revascularization from each study arm were selected. Nine hundred eight patients deferred from coronary revascularization with iFR (n=473) and FFR (n=435) were followed for 5 years. The national quality registry, SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies), was used for patient data collection and clinical follow-up. The end point was major adverse cardiac events and their individual components all-cause death, cardiovascular death, noncardiovascular death, nonfatal myocardial infarction, and unplanned revascularization. No significant difference was found in major adverse cardiac events (iFR 18.6% versus FFR 16.8%; adjusted hazard ratio, 1.08 [95% CI, 0.79-1.48]; P=0.63) or their individual components. Conclusions No differences in clinical outcomes after 5-year follow-up were noted when comparing iFR versus FFR as methods for deferral of coronary revascularization in patients presenting with stable angina pectoris and acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166736.

Predictive Accuracy of Stroke Risk Prediction Models Across Black and White Race, Sex, and Age Groups

Stroke is the fifth-highest cause of death in the US and a leading cause of serious long-term disability with particularly high risk in Black individuals. Quality risk prediction algorithms, free of bias, are key for comprehensive prevention strategies. To compare the performance of stroke-specific algorithms with pooled cohort equations developed for atherosclerotic cardiovascular disease for the prediction of new-onset stroke across different subgroups (race, sex, and age) and to determine the added value of novel machine learning techniques. Retrospective cohort study on combined and harmonized data from Black and White participants of the Framingham Offspring, Atherosclerosis Risk in Communities (ARIC), Multi-Ethnic Study for Atherosclerosis (MESA), and Reasons for Geographical and Racial Differences in Stroke (REGARDS) studies (1983-2019) conducted in the US. The 62 482 participants included at baseline were at least 45 years of age and free of stroke or transient ischemic attack. Published stroke-specific algorithms from Framingham and REGARDS (based on self-reported risk factors) as well as pooled cohort equations for atherosclerotic cardiovascular disease plus 2 newly developed machine learning algorithms. Models were designed to estimate the 10-year risk of new-onset stroke (ischemic or hemorrhagic). Discrimination concordance index (C index) and calibration ratios of expected vs observed event rates were assessed at 10 years. Analyses were conducted by race, sex, and age groups. The combined study sample included 62 482 participants (median age, 61 years, 54% women, and 29% Black individuals). Discrimination C indexes were not significantly different for the 2 stroke-specific models (Framingham stroke, 0.72; 95% CI, 0.72-073; REGARDS self-report, 0.73; 95% CI, 0.72-0.74) vs the pooled cohort equations (0.72; 95% CI, 0.71-0.73): differences 0.01 or less (P values >.05) in the combined sample. Significant differences in discrimination were observed by race: the C indexes were 0.76 for all 3 models in White vs 0.69 in Black women (all P values <.001) and between 0.71 and 0.72 in White men and between 0.64 and 0.66 in Black men (all P values ≤.001). When stratified by age, model discrimination was better for younger (<60 years) vs older (≥60 years) adults for both Black and White individuals. The ratios of observed to expected 10-year stroke rates were closest to 1 for the REGARDS self-report model (1.05; 95% CI, 1.00-1.09) and indicated risk overestimation for Framingham stroke (0.86; 95% CI, 0.82-0.89) and pooled cohort equations (0.74; 95% CI, 0.71-0.77). Performance did not significantly improve when novel machine learning algorithms were applied. In this analysis of Black and White individuals without stroke or transient ischemic attack among 4 US cohorts, existing stroke-specific risk prediction models and novel machine learning techniques did not significantly improve discriminative accuracy for new-onset stroke compared with the pooled cohort equations, and the REGARDS self-report model had the best calibration. All algorithms exhibited worse discrimination in Black individuals than in White individuals, indicating the need to expand the pool of risk factors and improve modeling techniques to address observed racial disparities and improve model performance.

FITEVT: A FORTRAN program for arrival-time analysis of nuclear-decay events

FITEVT is a FORTRAN program designed to analyze recorded arrival times of nuclear-decay events affected by dead-time. The primary goal of the program is precise and accurate determination of half-lives. Its method involves imposition of a known sufficiently long extending dead-time to the recorded event sequence, so that the original dead-time effects are completely obliterated and the remaining live-times of the survived events are known exactly. Upon completion of the analysis, the arrival-time spectrum and the live-time spectrum are predicted and compared to those constructed from the survived events. Program summaryProgram title: FITEVTLicensing provisions: MITCPC Library link to program files:https://doi.org/10.17632/scg6p9jxjk.1Programming language: FORTRAN (using double precision)Nature of problem: Accurate determination of the ideal event rate from the observed event rate in a nuclear decay can be a challenging task due to the inevitable presence of detection system's dead-time, whose nature and extent are typically unknown. Consequently, the results of nuclear half-life measurements may depend on the method used to correct for event losses due to dead-time. Therefore, there is a need for an exact method of data analysis and the means to apply it in order to ensure reproducibility, accuracy and optimized precision of the results.Solution method: FITEVT performs arrival-time analysis of the recorded events, in which a known, sufficiently large extending dead-time is imposed by means of software, so that in the resulting set of survived events the original dead-time effects are completely replaced by the effects of the imposed dead-time. As a result, the dead-time following each survived event and the remaining live-time preceding each surviving event are known exactly. This allows for application of the maximum-likelihood method of estimation, in which the half-lives as well as the other parameters of the ideal-decay-rate function can be accurately determined.Additional comments including restrictions and unusual features: In its original form the program can handle contributions from a constant event rate (i.e., a typical background) plus up to 4 different exponentially-decaying event rates. One of these 4 contributions is allowed to be negative, so that the program can be applied to the general case involving a single two-component decay chain. The employed method of analysis produces accurate results even when the product of the ideal event rate (ρ) and the extending dead-time parameter (τe) is as large as 51.2 [1]. Example used in the present paper involves simulated events having initial rate of 105 s−1, to which extending dead-time of 64 μs is imposed.Data analysis is based on maximum-likelihood principle, in which minimization of the deviance involves calculations in double precision and determination of its derivatives is based on analytical expressions. This is done in order to optimize precision and accuracy of the results as well as the program execution time.With the provided input data and a typical contemporary laptop computer, the program execution typically lasts about 5 minutes. Reducing the imposed dead-time to zero increases the number of survived events approximately by a factor of 6, but the program execution time increases by about a factor of 3.