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BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, regional; OR 19.28, 95% CI 3.47-106.97, p < 0.001, linear). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.

The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of participants with different forms of S. aureus bloodstream infection. Here, we formalise the trial structure, modelling approach, and decision rules that will be used for the SNAP trial. By summarising the statistical principles governing the design, our hope is that the SNAP trial will serve as an adaptable template that can be used to improve comparative effectiveness research efficiency in other disease areas.Trial registration NCT05137119 . Registered on 30 November 2021.

Racism in emergency medicine (EM) health care research is pervasive but often underrecognized. To understand the current state of research on racism in EM health care research, we developed a consensus working group on this topic, which concluded a year of work with a consensus-building session as part of the overall Society for Academic Emergency Medicine (SAEM) consensus conference on diversity, equity, and inclusion: Developing a Research Agenda for Addressing Racism in Emergency Medicine, held on May 10, 2022. In this article, we report the development, details of preconference methods and preliminary results, and the final consensus of the Healthcare Research Working Group. Preconference work based on literature review and expert opinion identified 13 potential priority research questions that were refined through an iterative process to a list of 10. During the conference, the subgroup used consensus methodology and a consensus dollar (contingent valuation) approach to prioritize research questions. The subgroup identified three research gaps: remedies for racial bias and systematic racism, biases and heuristics in clinical care, and racism in study design, and we derived a list of six high-priority research questions for our specialty.

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%-30%. Despite this,

Fragile X Syndrome (FXS), the leading monogenic cause of intellectual disability and autism spectrum disorder, is caused by expansion of a CGG trinucleotide repeat in the 5'-UTR of the Fragile X Mental Retardation-1 (FMR1) gene. Epigenetic silencing of FMR1 results in loss of the Fragile X Mental Retardation Protein (FMRP). Although most studies to date have focused on excitatory neurons, recent evidence suggests that GABAergic inhibitory networks are also affected. To investigate human GABAergic neurogenesis, we established a method to reproducibly derive inhibitory neurons from multiple FXS and control human pluripotent stem cell (hPSC) lines. Electrophysiological analyses suggested that the developing FXS neurons had a delay in the GABA functional switch, a transition in fetal development that converts the GABAA channel's function from depolarization to hyperpolarization, with profound effects on the developing brain. To investigate the cause of this delay, we analyzed 14 400 single-cell transcriptomes from FXS and control cells at 2 stages of GABAergic neurogenesis. While control and FXS cells were similar at the earlier time point, the later-stage FXS cells retained expression of neuroblast proliferation-associated genes and had lower levels of genes associated with action potential regulation, synapses, and mitochondria compared with controls. Our analysis suggests that loss of FMRP prolongs the proliferative stage of progenitors, which may result in more neurons remaining immature during the later stages of neurogenesis. This could have profound implications for homeostatic excitatory-inhibitory circuit development in FXS, and suggests a novel direction for understanding disease mechanisms that may help to guide therapeutic interventions.

The Action-sentence Compatibility Effect (ACE) is a well-known demonstration of the role of motor activity in the comprehension of language. Participants are asked to make sensibility judgments on sentences by producing movements toward the body or away from the body. The ACE is the finding that movements are faster when the direction of the movement (e.g., toward) matches the direction of the action in the to-be-judged sentence (e.g., Art gave you the pen describes action toward you). We report on a pre-registered, multi-lab replication of one version of the ACE. The results show that none of the 18 labs involved in the study observed a reliable ACE, and that the meta-analytic estimate of the size of the ACE was essentially zero.

Introduction: The novel coronavirus (SARS-CoV-2) is the cause of COVID-19, which has had a devastating international impact. Prior reports of testing have reported low sensitivities of nasopharyngeal polymerase chain reaction (PCR), and reports of viral co-infections have varied from 0-20%. Therefore, we sought to determine the accuracy of nasopharyngeal PCR for COVID-19 and rates of viral co-infection.Methods: We conducted a retrospective chart review of all patients who received viral testing between March 1, 2020–April 28, 2020. Test results of a complete viral pathogen panel and COVID-19 testing were abstracted. We compared patients with more than one COVID-19 test for diagnostic accuracy against the gold standard of chart review.Results: We identified 1950 patients, of whom 1024 were tested for COVID-19. There were 221 repeat tests for COVID-19. Among patients with a repeat test, COVID-19 swabs had a sensitivity of 84.6% (95% confidence interval (CI), 69.5-94.4%) and a specificity of 99.5% (95%CI, 97-100%) compared to a clinical and radiographic criterion reference by chart review. We found viral co-infection rates of 2.3% in patients without COVID-19 and 6.1% in patients with COVID-19. Rates of co-infection appeared to be related to base rates of infection in the community and not a specific property of COVID-19.Conclusion: COVID-19 nasopharyngeal PCR specimens are accurate but have imperfect sensitivity. Repeat testing for high-risk patients should be considered, and presence of an alternative virus should not be used to limit testing for COVID-19 for patients where it would affect treatment or isolation.

BackgroundDesirability of outcome ranking (DOOR) is an innovative approach in clinical trials to evaluate the global benefits and risks of an intervention. We developed and validated a DOOR endpoint for Staphylococcus aureus bloodstream infection (BSI) through a survey to infectious diseases clinicians and secondary analysis of trial data.MethodsWe administered a survey of 20 cases of S. aureus BSI, asking respondents to rank outcomes by global desirability. Correlations and percentage of pairwise agreement among rankings were estimated to inform development of a DOOR endpoint, which was applied to 2 prior S. aureus BSI trials. The probability that a patient randomly assigned to experimental treatment would have a better DOOR ranking than if assigned to control was estimated. Results were also analyzed using partial credit, which is analogous to scoring an academic test, assigning 100% to the most desirable outcome, 0% to the least, and "partial credit" to intermediate ranks.ResultsForty-two recipients (97%) completed the survey. The DOOR endpoint fitting these rankings (r = 0.89; 95% confidence interval, 0.67 to 0.94) incorporated survival plus cumulative occurrence of adverse events, cure, infectious complications, and ongoing symptoms. Tailored versions of this endpoint were applied to 2 S. aureus BSI trials, and both demonstrated no benefit of the experimental treatment using DOOR and partial credit analysis.ConclusionsUsing S. aureus BSI as an exemplar, we developed a DOOR endpoint that can be used as a template for development of DOOR endpoints for other diseases. Future trials can incorporate DOOR to allow for global assessment of patient experience.

The purpose of this study was to investigate the relationship between the TVAAS growth score given by the Tennessee Department of Education and the overall Tennessee Educator Assessment Model (TEAM) observation rating for teachers in grades 3 through 8. The participating county public school system for this study is located in Northeast Tennessee. Participants were teachers in the school system teaching Math, English/Language Arts, Science, and Social Studies in grades 3 through 8 in 10 elementary schools, 6 middle schools, and 2 K-8 schools. Specifically, this research examined the relationship between the TEAM observation scores and overall TVAAS growth score given to the teacher from the Tennessee Department of Education based upon yearly-standardized test scores. Research reinforced mixed views about the validity and purpose of teacher evaluation systems and the use of Tennessee Value-Added Assessment System. Five research questions guided this study and quantitative data were analyzed using a Pearson correlation, one-way MANOVAs and a one-way ANOVA. Results indicated a moderate positive relationship between a teacher's TEAM observation score and the TVAAS growth score given by the Tennessee Department of Education.

The present study investigated the representation and processing of segmental and tonal information in visual Chinese word recognition in native and non-native Chinese readers. Two experiments using homophone judgement paradigm were conducted. When judging two Chinese characters (Experiment 1), both groups showed difficulties when the segmental but not tonal information was shared (i.e., S+T- condition), with stronger interference for non-native readers. When judging a Pinyin and a Chinese character (Experiment 2), non-native readers' S+T- disadvantage was significantly reduced. Finally, when their L1s share the Latin alphabets with Pinyin, the participants showed stronger segmental reliance compared with the native readers. These findings suggest that while both native and non-native readers rely more on segmental information in Chinese visual word recognition, this reliance is stronger among non-native readers. Furthermore, the alphabetic nature of the Pinyin orthography may help non-native readers' phonological representation and processing in a nonalphabetic writing system.

Despite increasing adoption of the direct anterior (DA) approach in total hip arthroplasty (THA), uncertainty persists regarding its outcomes beyond the 1-year mark in comparison to other approaches. We used the reverse fragility index (RFI) to evaluate the robustness of reported findings in the literature. We conducted a systematic review of randomized controlled trials (RCTs) comparing implant revision rates between DA and other approaches in THA, defined as all those different from DA. Our primary outcome was the RFI, which gauges the number of events needed for a nonsignificant result to become significant, in the revision rate between DA and other approaches. We also calculated the reverse fragility quotient by dividing the RFI by each study's sample size. Median values and interquartile ranges (IQRs) were displayed. A total of 10 RCTs with a total of 971 patients were included. The median RFI was 5 (IQR, 4 to 5), indicating the study's results would be statistically significant if the outcomes of 5 patients in 1 treatment arm were reversed. The median reverse fragility quotient was 0.049 (IQR, 0.04 to 0.057), indicating that a change of outcome in 4.9% of patients would render the revision rate significant. The median number of patients lost to follow-up was 4 (IQR, 0 to 7). Of the 10 RCTs, 6 had more patients lost to follow-up than their respective RFI values. Notable fragility was evidenced in most studies comparing DA to other approaches for THA. Surgeons should not solely rely on the P value to determine clinical significance and instead use multiple metrics. II. [ABSTRACT FROM AUTHOR]