One of the goals of a pilot study is to identify unforeseen problems, such as ambiguous inclusion or exclusion criteria or misinterpretations of questionnaire items. Although sample size calculation methods for pilot studies have been proposed, none of them are directed at the goal of problem detection. In this article, we present a simple formula to calculate the sample size needed to be able to identify, with a chosen level of confidence, problems that may arise with a given probability. If a problem exists with 5% probability in a potential study participant, the problem will almost certainly be identified (with 95% confidence) in a pilot study including 59 participants.

Background— The transition from persistent to permanent atrial fibrillation (AF) is associated with increased complexity of fibrillatory conduction. We have investigated the spatial distribution of fibrillation waves and structural alterations in the atrial free walls in a goat model of AF. Methods and Results— AF was maintained for 3 weeks (short term [ST], persistent AF) or 6 months (long term [LT], permanent AF). Fibrillation patterns were assessed with epicardial mapping. The origin of fibrillation waves and sites of conduction abnormalities were more homogeneously distributed in LT than in ST goats. Histologically, the total area fraction occupied by fibrous tissue and the degree of perimysial fibrosis (separation between myocyte bundles) were not significantly different between groups. However, endomysial fibrosis (distance between myocytes within bundles) was significantly larger in LT goats, particularly in the outer millimeter of the atria. By contrast, myocyte diameters were larger in LT goats throughout the atrial walls. High-resolution optical mapping showed that epicardial wavefront expansion was slower and more anisotropic in LT than in ST goats. Finally, a mathematical model of a simplified atrial architecture confirmed the potential impact of epicardial endomysial fibrosis on AF complexity. Conclusions— Altered propagation after 6 months of AF is consistent with homogeneous structural remodeling in the outer millimeter of the atria. Loss of continuity of the epicardial layer because of endomysial fibrosis may reduce its synchronizing effect, thereby increasing the complexity of fibrillatory conduction pathways. The exact distribution of fibrosis may be more important for the occurrence of conduction disturbances than the overall quantity.

Introduction and hypothesisThis study aimed to determine the relationship of recurrent cystocele with avulsion of puborectalis muscle and other risk factors.MethodsIn this prospective observational cohort study, 245 women undergoing anterior colporrhaphy were invited for a 2-year follow-up visit consisting of a questionnaire, physical examination, and translabial 3D ultrasonography. Women with and without recurrent cystocele were compared to identify recurrence risk factors.ResultsOf the 245 women, 156 agreed to the follow-up visit (63.7%). Objective recurrence rate was 80 of 156 (51.3%). Seventeen of the 156 (10.9%) reported subjective recurrence. Risk factors for anatomical recurrence were complete avulsion of puborectalis muscle (OR, 2.4; 95% CI, 1.3, 4.7), advanced preoperative stage (OR, 2.0; 95% CI, 1.0, 4.1), family history of prolapse (OR, 2.4; 95% CI, 1.2, 4.9), and sacrospinous fixation (OR, 6.5; 95% CI, 2.0, 21.2).ConclusionsRisk factors for anatomical cystocele recurrence after anterior colporrhaphy were complete avulsion of puborectalis muscle, advanced preoperative stage, family history of prolapse, and sacrospinous fixation.

It has been proven challenging to conduct traditional efficacy trials for Ebola virus (EBOV) vaccines. In the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model. We here propose to infer the protective effect of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen with an 8-week interval in humans by immunobridging. Immunogenicity and protective efficacy data were obtained for Ad26.ZEBOV and MVA-BN-Filo vaccine regimens using a fully lethal EBOV Kikwit challenge model in cynomolgus monkeys (nonhuman primates [NHP]). The association between EBOV neutralizing antibodies, glycoprotein (GP)-binding antibodies, and GP-reactive T cells and survival in NHP was assessed by logistic regression analysis. Binding antibodies against the EBOV surface GP were identified as the immune parameter with the strongest correlation to survival post EBOV challenge, and used to infer the predicted protective effect of the vaccine in humans using published data from phase I studies. The human vaccine-elicited EBOV GP-binding antibody levels are in a range associated with significant protection against mortality in NHP. Based on this immunobridging analysis, the EBOV GP-specific-binding antibody levels elicited by the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in humans will likely provide protection against EBOV disease.

No abstract