Looking for opportunities to co-enroll: The DISCOVERY study experience

BackgroundConducting high-quality stroke trials is complex and costly. Often these trials compete for the attention of researchers and the availability of patients. Enrolling patients in more than one study concurrently has the potential to accelerate recruitment into individual studies. DISCOVERY is a multicenter, inception cohort study of cognitive impairment and dementia following ischemic or hemorrhagic stroke. At the request of site investigators, a DISCOVERY committee reviews individual studies for approval of possible concurrent co-enrollment into DISCOVERY. The purpose of this report is to summarize the characteristics and outcomes of studies reviewed by committee for possible co-enrollment.MethodsThis analysis covers studies reviewed from 07/01/2020 to 04/26/2022 by the Site Management Committee (SMC) of the DISCOVERY Recruitment and Retention Core. Characterization of each study included study type, number and length of follow-up visits, and whether there were protocol-required blood draws, brain imaging studies, or cognitive tests. Studies were scored for patient burden and scientific overlap with Discovery. The primary outcome was SMC approval to co-enroll.Results59 studies were reviewed, and 69.5% (n = 41, 21 clinical trials; 20 observational studies) were found by the SMC to be appropriate for co-enrollment. Higher patient burden and greater scientific overlap with DISCOVERY reduced the rates of approval for co-enrollment.ConclusionA large number of diverse stroke studies are being run concurrently across the DISCOVERY study network, however, about two-thirds of the studies were considered appropriate for consideration of co-enrollment. Future studies should study how co-enrollment might improve trial network efficiency.     

Elastic properties of Thiel‐embalmed human ankle tendon and ligament

Thiel embalming is recommended as an alternative to formalin‐based embalming because it preserves tissue elasticity, color, and flexibility in the long term, with low infection and toxicity risk. The degree to which Thiel embalming preserves elasticity has so far been assessed mainly by subjective scoring, with little quantitative verification. The aim of this study is to quantify the effect of Thiel embalming on the elastic properties of human ankle tendons and ligament. Biomechanical tensile tests were carried out on six Thiel‐embalmed samples each of the peroneus longus, peroneus brevis, and calcaneal tendons, and the calcaneofibular ligament, with strain rates of 0.25%s^?1, 2%s^?1, and 8%s^?1. The stress?strain relationship was calculated from the force‐extension response with cross‐sectional area and gauge length. Young's modulus was determined from the stress?strain curve. The results showed that the tendon and ligament elasticity were lower after Thiel embalming than the literature values for fresh nonembalmed tendons and ligament. The biomechanical tensile test showed that the measured elasticity of Thiel‐embalmed tendons and ligaments increased with the strain rate. The Thiel embalming method is useful for preserving human ankle tendons and ligaments for anatomy and surgery teaching and research, but users need to be aware of its softening effects. The method retains the mechanical strain rate effect on tendons and ligament. Clin. Anat. 28:917–924, 2015. © 2015 Wiley Periodicals, Inc.     

The Value of Electrocardiographic Abnormalities in the Prognosis of Pulmonary Embolism: A Consensus Paper

Electrocardiographic (ECG) abnormalities in the setting of acute pulmonary embolism (PE) are being increasingly characterized and mounting evidence suggests that ECG plays a valuable role in prognostication for PE. We review the historical 21‐point ECG prognostic score for the severity of PE and examine the updated evidence surrounding the utility of ECG abnormalities in prognostication for severity of acute PE. We performed a literature search of MEDLINE, EMBASE, and PubMed up to February 2015. Article titles and abstracts were screened, and articles were included if they were observational studies that used a surface 12‐lead ECG as the instrument for measurement, a diagnosis of PE was confirmed by imaging, arteriography or autopsy, and analysis of prognostic outcomes was performed. Thirty‐six articles met our inclusion criteria. We review the prognostic value of ECG abnormalities included in the 21‐point ECG score, including new evidence that has arisen since the time of its publication. We also discuss the potential prognostic value of several ECG abnormalities with newly identified prognostic value in the setting of acute PE.     

Concomitant ablation of atrial fibrillation in rheumatic mitral valve surgery

Objective

Efficacy of atrial fibrillation ablation in rheumatic mitral valve disease has been regarded inferior to that in nonrheumatic diseases. This study aimed to evaluate net clinical benefits by the addition of concomitant atrial fibrillation ablation in rheumatic mitral valve surgery.

Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese

Background and aims

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

Measures for evaluation of prognostic improvement under multivariate normality for nested and nonnested models

When comparing performances of two risk prediction models, several metrics exist to quantify prognostic improvement, including the change in the area under the Receiver Operating Characteristic curve, the Integrated Discrimination Improvement, the Net Reclassification Index at event rate, the change in Standardized Net Benefit, the change in Brier score, and the change in scaled Brier score. We explore the behavior and interrelationships between these metrics under multivariate normality in nested and nonnested model comparisons. We demonstrate that, within the framework of linear discriminant analysis, all six statistics are functions of squared Mahalanobis distance, a robust metric that properly measures discrimination by quantifying the separation between the risk scores of events and nonevents. These relationships are important for overall interpretability and clinical usefulness. Through simulation, we demonstrate that the performance of the theoretical estimators under normality is comparable or superior to empirical estimation methods typically used by investigators. In particular, the theoretical estimators for the Net Reclassification Index and the change in Standardized Net Benefit exhibit less variability in their estimates as compared to their empirically estimated counterparts. Finally, we explore how these metrics behave with potentially nonnormal data by applying these methods in a practical example based on the sex-specific cardiovascular disease risk models from the Framingham Heart Study. Our findings aim to give greater insight into the behavior of these measures and the connections existing among them and to provide additional estimation methods with less variability for the Net Reclassification Index and the change in Standardized Net Benefit.