Citations

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Background and Purpose After cochlear implantation, metallic artifact can obscure nearby structures on CT images, which is problematic in patients with facial nerve stimulation (FNS). This study evaluated the usefulness of co-registered pre- and post-operative examinations to evaluate the cochlear implant and adjacent structures. Materials and Methods A retrospective review was completed of consecutive patients that underwent CT imaging of the temporal bone before and after placement of a cochlear implant. Two blinded neuroradiologists independently reviewed all available examinations. All examinations were assessed for the presence or absence of dehiscence of the osseous ridge between the cochlea and facial nerve canal (FNC). Pre-operative and fused pre- and post-operative examinations were compared in their ability to visualize the osseous ridge using a 5-point Likert scale (ranging from 1 = unfused images were substantially superior to 5 = fused images were substantially superior). The electrode closest to the FNC were noted. Results Of 34 included patients, 13 (38.2%) were female and 21 (61.8%) were male; average age was 72.2. Seven patients (20.6%) had frank dehiscence between the cochlea and FNC. Fused images were superior to the post-operative study alone for assessing the integrity of the osseous partition between the cochlea and FNC and for reducing artifact from the electrode array (average Likert scores for both reviewers were 4.4 and 4.7). There was good agreement between reviewers in noting electrode closest to the FNC (concordance correlation coefficient=0.82). Conclusions Following cochlear implantation, co-registered pre- and post-operative CT images are superior to conventional images in assessing the anatomic relationship between the cochlea and FNC.

Background: Bibliometric citation analyses have been widely used in medicine to help researchers gain foundational knowledge about a topic and identify subtopics of popular interest for further investigations. There is a lack of similar research in collegiate athletics. Purpose: To identify the 100 most-cited research publications related to collegiate athletics. Study Design: Cross-sectional study. Methods: The Clarivate Analytics Web of Knowledge database was used to generate a list of articles relating to collegiate athletics on January 24, 2022. Articles were filtered by the total number of citations, and the 100 most-cited articles were selected. For each article, we identified and analyzed the following: author name, publication year, country of origin, journal name, article type, main research topic area, competitive level, sex of study population, and level of evidence. Results: Of the top 100 most-cited articles, 63 were related to medicine. In total, 96% of articles were published in the United States, and 80% were published in the year 2000 or later. Of the top 100 articles, 85 were observational; only 5 were experimental. The sport most represented was soccer, followed by football, baseball, and basketball. Of the top 100 articles, 21 were published in a single journal, the American Journal of Sports Medicine. Ten authors published ≥5 of the top 100 most-cited studies. Conclusion: The majority of top 100 articles were published in the United States after 1999 and primarily focused on medicine-related topics. Soccer was studied by more articles than football, baseball, and basketball. An author’s prestige may have influenced the likelihood of citation. The top 100 most-cited studies provide researchers, medical students, residents, and fellows with a foundational list of the most important and influential academic contributions to the literature on collegiate athletics.

AbstractWith a view to finding new applications of biomedical system dynamics, this article expands upon on our talk at the 2021 International System Dynamics Conference on the occasion of receiving the J. W. Forrester Award for the article, “Personalized ESA doses for anemia management in hemodialysis patients with end‐stage renal disease” (System Dynamics Review 2018, 34(1–2): 121–153). We summarize the evolution of a project which took place in a clinical setting between 2008 and 2015 that led to the award‐winning article. We present concepts from receptor theory that informed the first system dynamics application of biophysical system dynamics to the successful diagnosis, prescription, administration, and improvement of individualized patient care. We expand upon these ideas to present a generalized structure, DART (Dynamic Approach to Receptor Theory). It can be used to simulate the physiological effects of any agent, be it an exogenous pharmacological agent, an endogenous enzyme or hormone, or a toxin of some sort. We suggest including within the pharmacological technical literature easily acquired but frequently omitted critical parameter values and rate constants. These would enable researchers to perform transient analyses of biophysical phenomena in addition to static equilibrium analyses typically performed. With the availability of this data, we suggest that the fundamental tools of system dynamics might be used to reconceptualize the 100‐year‐old field of “occupation theory” (today, receptor theory) to deliver high‐resolution insights into physiological dynamics and the preventive, prescriptive, and palliative interventions they might require. It is our hope that these ideas could pave the way forward to novel, groundbreaking applications in biomedical system dynamics. © 2022 System Dynamics Society.

Background TAILOR‐PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype‐guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss‐of‐function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex‐specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional‐hazards models. Among 5276 randomized patients, loss‐of‐function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P =0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P =0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value ( P int =0.59) or BARC bleeding ( P int =0.47) nor for sex and genotype (MACE P int =0.15, and BARC bleeding P int =0.60). Conclusions CYP2C19 loss‐of‐function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype‐guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01742117.

Neurodevelopmental disorders are associated with metabolic pathway imbalances; however, most metabolic measurements are made peripherally, leaving central metabolic disturbances under-investigated. Cerebrospinal fluid obtained intraoperatively from children with autism spectrum disorder (ASD, n = 34), developmental delays (DD, n = 20), and those without known DD/ASD (n = 34) was analyzed using large-scale targeted mass spectrometry. Eighteen also had epilepsy (EPI). Metabolites significantly related to ASD, DD and EPI were identified by linear models and entered into metabolite–metabolite network pathway analysis. Common disrupted pathways were analyzed for each group of interest. Central metabolites most involved in metabolic pathways were L-cysteine, adenine, and dodecanoic acid for ASD; nicotinamide adenine dinucleotide phosphate, L-aspartic acid, and glycine for EPI; and adenosine triphosphate, L-glutamine, ornithine, L-arginine, L-lysine, citrulline, and L-homoserine for DD. Amino acid and energy metabolism pathways were most disrupted in all disorders, but the source of the disruption was different for each disorder. Disruption in vitamin and one-carbon metabolism was associated with DD and EPI, lipid pathway disruption was associated with EPI and redox metabolism disruption was related to ASD. Two microbiome metabolites were also detected in the CSF: shikimic and cis-cis-muconic acid. Overall, this study provides increased insight into unique metabolic disruptions in distinct but overlapping neurodevelopmental disorders.

Abstract The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.

Purpose The purpose of this study is to examine the effects of scribe use on physicians, nurses, and patients in an orthopaedic sports medicine clinic. Methods Surveys containing validated outcome measures relating to physician well‐being and workplace satisfaction, among other variables, were used to assess the influence of medical scribes on clinic function. These surveys were collected for 8 months from all patients, nurses, and orthopaedic surgeons working in one orthopaedic sports medicine clinic. Time during a half‐day clinic (i.e., 20 or more patients) was documented by surgeons after the last patient was seen. Results The average time spent per half day of clinic was 104 minutes on nonscribe days and 25 minutes on scribe days. Additionally, the time spent documenting encounters per half day of clinic was 87 minutes on average without scribes and 26 minutes on average with scribes. The average surgeon single assessment numeric evaluation (SANE) score was 48.1 without scribes, and 89.3 with scribes. The overall assessment of the clinic by nurses was 73.4 out of 100 on average without scribes and 87.7 out of 100 on average with scribes. Patients did not report a significant change in rating of overall experience (4.7/5.0 with scribes and 4.8/5.0 without scribes, ( P = .27) or wait time between scheduled appointment time and surgeon arrival (15.1 minutes with scribes and 18.1 minutes without scribes; P = .12). Conclusions We found the use of scribes in a high‐volume orthopaedic sports medicine clinic to have a favorable impact on physicians, nurses, and trainees. The use of a scribe also significantly reduced the time required by surgeons for documentation during clinic and at the end of each clinic day. Patients also reported no significant difference in patient clinic experience scores. Clinical Relevance Orthopaedic surgeons spend a substantial amount of time on paperwork. The results of this study could provide information on whether the use of a scribe helps to reduce administrative burden on orthopedic surgeons.