Platelet inhibitor withdrawal and outcomes after coronary artery surgery: an individual patient data meta-analysis.

OBJECTIVE: To evaluate the association between guideline-conforming as compared to shorter than recommended withdrawal period of P2Y12 receptor inhibitors prior to isolated on-pump coronary artery bypass grafting (CABG) and the incidence of severe bleeding and ischemic events. Randomized controlled trials are lacking in this field. METHODS: We searched PUBMED, Embase and other suitable databases for studies including patients on P2Y12 receptor inhibitors undergoing isolated CABG and reporting bleeding and postoperative ischemic events from 2013 to March 2024. The primary outcome was incidence of Bleeding Academic Research Consortium type 4 (BARC-4) bleeding defined as any of the following: perioperative intracranial bleeding, reoperation for bleeding, transfusion of ≥ 5 units of red blood cells, chest tube output of ≥ 2 liters. The secondary outcome were postoperative ischemic events according to the Academic Research Consortium 2 Consensus Document. Patient-level data provided by each observational trial were synthesized into a single dataset and analyzed using a two-stage IPD-MA. RESULTS: Individual data of 4,837 patients from 7 observational studies were synthesized. BARC-4 bleeding, 30-day mortality, and postoperative ischemic events occurred in 20%, 2.6%, and 5.2% of patients. After adjusting for EuroSCORE II and cardiopulmonary bypass time, guideline-conforming withdrawal was associated with decreased BARC-4 bleeding risk in patients on clopidogrel (adjusted odds ratio [OR] 0.48, 95% confidence intervals (CI) 0.28-0.81, P = 0.006) and a trend toward decreased risk in patients on ticagrelor (adjusted OR 0.48, 95% CI 0.22-1.05; P = 0.067). Guideline-conforming withdrawal was not significantly associated with 30-day mortality risk (clopidogrel: adjusted OR 0.70, 95% CI 0.30-1.61; ticagrelor: adjusted OR 0.89, 95% CI 0.37-2.18) but with decreased risk of postoperative ischemic events in patients on clopidogrel (clopidogrel: adjusted OR 0.50, 95% CI 0.30-0.82; ticagrelor: adjusted OR 0.78, 95% CI 0.45 -1.37). BARC-4 bleeding was associated with 30-day mortality risk (adjusted OR 4.76, 95% CI 2.67-8.47; P < 0.001). CONCLUSIONS: Guideline-conforming preoperative withdrawal of ticagrelor and clopidogrel was associated with a 50% reduced BARC-4 bleeding risk when corrected for EuroSCORE II and cardiopulmonary bypass time but was not associated with increased risk of 30-day mortality or postoperative ischemic events.

Sample size considerations in soft tissue biomechanics.

Biomechanical experiments help link tissue morphology with load-deformation characteristics. A tissue-dependent minimum sample number is indispensable to obtain accurate material properties. Stress-strain properties were retrieved from human dura mater and scalp skin, exemplifying two distinct soft tissues. Minimum sample sizes necessary for a stable estimation of material properties were obtained in a simulation study. One-thousand random samples were sequentially drawn for calculating the point at which a majority of the estimators settled within a corridor of stability at given tolerance levels around a 'complete' reference for the mean, median and coefficient of variation. Stable estimations of means and medians can be achieved below sample sizes of 30 at a ± 20%-tolerance within 80%-conformity for scalp skin and dura. Lower tolerance levels or higher conformity dramatically increase the required sample size. Conformity was barely ever reached for the coefficient of variation. The parameter type appears decisive for achieving conformity. STATEMENT OF SIGNIFICANCE: Biomechanical trials utilizing human tissues are needed to obtain material properties for surgical repair, tissue engineering and modeling purposes. Linking tissue mechanics with morphology helps elucidate form-function relationships, the 'morpho-mechanical link'. For material properties to be accurate, it is vital to examine a minimum number of samples. This number may vary between tissues, and the effects of intrinsic tissue characteristics on data accuracy are unclear to date. This study used data obtained from human dura and skin to compute minimum sample sizes required for estimating material properties at a stable level. It was shown that stable estimations are possible at a ± 20%-tolerance within 80%-conformity below sample sizes of 30. Higher accuracy warrants much higher sample sizes for most material properties.

Separating the impact of gradual lockdown measures on air pollutants from seasonal variability.

Analysis of near-surface measurements at several measuring points in Graz, Austria, reveals the impact of restrictive measures during the COVID-19 pandemic on the emission of atmospheric pollutants. We quantify the effects at traffic hotspots, industrial and residential areas. Using historical data collected over several years, we are able to account for meteorological and seasonal confounders. Our analysis is based on daily means as well as intraday pollution level curves. Nitrogen dioxide (NO2) has decreased drastically while the levels of particulate matter PM10 and carbon monoxide (CO) mostly exhibit little change. Traffic data shows that the decrease in traffic frequency is parallel to the decline in the levels of NO2 and NO.