Modeling marginal features in studies of recurrent events in the presence of a terminal event.

We study models for recurrent events with special emphasis on the situation where a terminal event acts as a competing risk for the recurrent events process and where there may be gaps between periods during which subjects are at risk for the recurrent event. We focus on marginal analysis of the expected number of events and show that an Aalen-Johansen type estimator proposed by Cook and Lawless is applicable in this situation. A motivating example deals with psychiatric hospital admissions where we supplement with analyses of the marginal distribution of time to the competing event and the marginal distribution of the time spent in hospital. Pseudo-observations are used for the latter purpose.

Type I Error Probability Spending for Post-Market Drug and Vaccine Safety Surveillance With Poisson Data.

Statistical sequential hypothesis testing is meant to analyze cumulative data accruing in time. The methods can be divided in two types, group and continuous sequential approaches, and a question that arises is if one approach suppresses the other in some sense. For Poisson stochastic processes, we prove that continuous sequential analysis is uniformly better than group sequential under a comprehensive class of statistical performance measures. Hence, optimal solutions are in the class of continuous designs. This paper also offers a pioneer study that compares classical Type I error spending functions in terms of expected number of events to signal. This was done for a number of tuning parameters scenarios. The results indicate that a log-exp shape for the Type I error spending function is the best choice in most of the evaluated scenarios.

Circadian Periodicity of Ischemic Heart Disease: A Systematic Review of the Literature.

The authors performed a MEDLINE search to identify reports, published during the last 20 years, focused on circadian variation of acute myocardial infarction (AMI), and prevalence and the ratios between the number of events per hour during the morning and the other hours of the day were calculated. Despite the optimization of interventional and medical therapy of AMI since the first reports of circadian patterns in AMI occurrence, it was found that such a pattern still exists and that AMI happens most frequently in the morning hours.

The universal 2012 definition of myocardial infarction compared to the 2007 definition.

OBJECTIVES: The third Universal 2012 definition of myocardial infarction (MI) has not been compared to the Universal 2007 definition with regard to the number of cases identified, classification and mortality. DESIGN: We examined potential MI events according to the two universal definitions in 1494 patients admitted to the University hospital during the 12 months. Patients were included either because of an MI discharge diagnosis (815 patients) or due to elevated troponin I levels without an MI discharge diagnosis (679 patients). RESULTS: Applying the Universal 2012 definition resulted in 760 of the 1494 patients suffering from MI, as compared to 769 according to the Universal 2007 definition. The lower number of MI events applying the 2012 definition was mainly explained by the stricter definition of Type 4a MI. The 760 MI events were classified as Type 1 (685), 2 (27), 3 (28), 4a (13), 4b (3) and 5 (4). CONCLUSIONS: The application of the third Universal 2012 definition of MI instead of the Universal 2007 definition resulted in a 1% reduction of the total number of MIs. For a practical clinical purpose, the reduction was confined to patients with Type 4a MI. The change of definition had no impact on all-cause mortality.

Confidence interval estimation for vaccine efficacy against COVID-19.

This article focuses on the construction of a confidence interval for vaccine efficacy against contagious coronavirus disease-2019 (COVID-19) in a fixed number of events design. Five different approaches are presented, and their performance is investigated in terms of the two-sided coverage probability, non-coverage probability at the lower tail, and expected confidence interval width. Furthermore, the effect of under-sensitivity of diagnosis tests on vaccine efficacy estimation was evaluated. Except for the exact conditional method, the non-coverage probability of the remaining methods may exceed the nominal significance level, e.g., 5%, even for a large number of total confirmed COVID-19 cases. The narrower confidence interval width from the Bayesian, approximate Poisson, and mid-P methods are on the cost of increased instability of coverage probability. When the sensitivity of diagnosis test in the vaccine group is lower than that in the placebo group, the reported vaccine efficacy tends to be overly optimistic. The exact conditional method is preferable to other methods in COVID-19 vaccine efficacy trials when the total number of cases reaches 60; otherwise, mid-p method can be used to obtain a narrower interval width.

Short-Term Annoyance Due to Night-Time Road, Railway, and Air Traffic Noise: Role of the Noise Source, the Acoustical Metric, and Non-Acoustical Factors.

Field studies on traffic noise-induced annoyance have predominantly used estimated outside noise levels. We intended to complement existing knowledge with exposure-response relationships that are based on precise indoor noise measurements. Acoustic recordings inside the bedrooms of nightly road traffic and annoyance ratings in the following morning were obtained from 40 suburban residents (mean age 29.1 years ± 11.7; 26 females). We derived exposure-response functions for the probability to be "annoyed at least a little" (%LA). Further analyses compared data from the current study with those from two earlier studies on railway and aircraft noise. Annoyance increased with the number of traffic events and the equivalent sound pressure level. The inclusion of non-acoustical factors (such as assessment of road transport) improved the prediction considerably. When comparing the different traffic noise sources, %LA was higher for road than for air traffic at a given LAeq,night, but higher for road and railway than for air traffic at a given number of noise events. Acoustical as well as non-acoustical factors impact short-term annoyance induced by road, railway, and air traffic. Annoyance varies across noise sources, which may be due to differences in acoustical characteristics or in the temporal noise distribution throughout the night.

Evaluation of Ferromagnetic Steel Hardness Based on an Analysis of the Barkhausen Noise Number of Events.

Measurements are carried out of the Barkhausen noise (BN) and hardness on specimens where changes in hardness were obtained due to strain hardening (S235 and DC01 steels) and due to thermochemical treatment (AMS 6414 steel). A method is presented of processing the recorded BN signal to extract diagnostic information. The BN number of events is selected as the signal characteristic property to develop relevant correlations. A new methodology is presented for the development of correlations between the Barkhausen noise number of events and hardness. A possibility is indicated of developing correlations with a high R2 determination coefficient. The method limitations are specified.

Widespread interictal epileptic discharge more likely than focal discharges to unveil the seizure onset zone in EEG-fMRI.

OBJECTIVE: We hypothesized that the number of interictal epileptic discharges (IEDs) during scan and their spatial extent are contributing factors in obtaining appropriate activations that reveal the seizure onset zone (SOZ) in EEG-fMRI. METHODS: 157 IED types, each corresponding to one EEG scalp distribution, in 64 consecutive EEG-fMRI studies from 64 patients with refractory localization-related epilepsy were reviewed. To determine reliable activation, we used the threshold corresponding to corrected whole-brain topological false discovery rate (FDR). The location with maximum activation was compared to the presumed SOZ as defined by a comprehensive evaluation for each patient. RESULTS: The number of IEDs was significantly higher in the types with t-value above FDR than with t-value below FDR. The presumed SOZ could be delineated in 30 of the 64 patients. Among these patients, the types of IED concordant with the SOZ had significantly larger extent on scalp EEG than the IED types discordant with the SOZ. CONCLUSIONS: The number of IEDs is important factor in obtaining reliable activations in EEG-fMRI. IEDs with larger spatial extent are more likely to reveal, on maximum BOLD, accurate location of the SOZ. SIGNIFICANCE: Widespread discharges are more likely to yield a reliable activation for SOZ in EEG-fMRI.

Implications of changing definitions of myocardial infarction on number of events and all-cause mortality: the WHO 1979, ESC/ACC 2000, AHA 2003, and Universal 2007 definitions revisited.

PURPOSE: To analyse the impact of four different definitions of acute myocardial infarction (AMI) on number of events and all-cause mortality after AMI. METHODS: We retrospectively examined number of AMI events and mortality according to four different definitions of AMI, among 1494 patients admitted to Haukeland University Hospital in Norway from March 2002 to February 2003. Eligible for analysis were 815 patients with a discharge diagnosis of an AMI, and 679 patients without any AMI discharge diagnosis but with elevated cardiac troponin I level during admission. RESULTS: Applying the WHO 1979 definition resulted in 566 definite AMIs among the 1494 patients and was used as reference. According to the other definitions, there were 455 (-20%) definite AMIs by the original troponin 'rise and fall' version of the ESC/ACC 2000 definition, 729 (+29%) by the troponin 'rise or fall' interpretation of the ESC/ACC 2000 definition, 761 (+34%) by the AHA 2003 definition, and 743 (+31%) by the Universal 2007 definition (all p < 0.001). The 28-day, 1-year, 5-year, and 8-year mortality for definite AMI applying the WHO 1979 definition was 12, 19, 32, and 40%, whereas applying the Universal 2007 definition resulted in a mortality of 14, 21, 35, and 43%, respectively. CONCLUSIONS: The change of definitions of AMI during the last decades has had a significant impact on the number of AMI events and a moderate impact on the AMI mortality among hospitalized patients.

A Simulation Based Evaluation of the Asymptotic Power Formulae for Cox Models in Small Sample Cases.

Cox proportional hazards (PH) models are commonly used in medical research to investigate the associations between covariates and time to event outcomes. It is frequently noted that with less than ten events per covariate, these models produce spurious results, and therefore, should not be used. Statistical literature contains asymptotic power formulae for the Cox model which can be used to determine the number of events needed to detect an association. Here we investigate via simulations the performance of these formulae in small sample settings for Cox models with 1- or 2-covariates. Our simulations indicate that, when the number of events is small, the power estimate based on the asymptotic formulae is often inflated. The discrepancy between the asymptotic and empirical power is larger for the dichotomous covariate especially in cases where allocation of sample size to its levels is unequal. When more than one covariate is included in the same model, the discrepancy between the asymptotic power and the empirical power is even larger, especially when a high positive correlation exists between the two covariates.