Comparative Costs to Medicare and Medicare Beneficiaries of Alternative AF Stroke Risk Reduction Strategies.

Background: As healthcare costs are increasingly being shifted from payers to patients, it is important to understand the economic consequences of therapeutic strategies to both payers and patients. Objective: To determine the relative costs to Medicare and Medicare beneficiaries (patients) of warfarin, non-vitamin K oral anticoagulants (NOACs), and left atrial appendage closure (LAAC) for stroke risk reduction in nonvalvular atrial fibrillation. Methods: An economic model was developed to assess costs at 5 and 10 years. For warfarin and NOACs, inputs were derived from published meta-analyses; for LAAC with the Watchman device, inputs were derived from pooled 5-year PROTECT AF and PREVAIL trial results. The model captured therapy costs vs clinical event costs, including procedural complications and follow-up clinical outcomes. Costs were based on 2023 Medicare reimbursement and copayment rates. Results: At 10 years, overall LAAC costs ($48,337) were lower than those of NOACs ($81,198) and warfarin ($52,359). Overall LAAC costs were lower than those of NOACs by year 5 and warfarin by year 9. At 5 years, patient LAAC costs were lowest at $4,764, compared to $7,146 and $6,453 for NOACs and warfarin, respectively. LAAC patient costs were lower than those of NOACs by year 3 and warfarin by year 4. Clinical events comprised 96% of overall warfarin costs vs 48% for LAAC and 40% for NOACs. Conclusion: LAAC yielded the lowest overall and patient costs. Warfarin costs were largely driven by clinical events, which may represent an unplanned financial burden for patients. These considerations should be incorporated into shared decision-making discussions about stroke prophylaxis strategies.

Phytoplankton optical fingerprint libraries for development of phytoplankton ocean color satellite products.

Phytoplankton respond to physical and hydrographic forcing on time and space scales up to and including those relevant to climate change. Quantifying changes in phytoplankton communities over these scales is essential for predicting ocean food resources, occurrences of harmful algal blooms, and carbon and other elemental cycles, among other predictions. However, one of the best tools for quantifying phytoplankton communities across relevant time and space scales, ocean color sensors, is constrained by its own spectral capabilities and availability of adequately vetted and relevant optical models. To address this later shortcoming, greater than fifty strains of phytoplankton, from a range of taxonomic lineages, geographic locations, and time in culture, alone and in mixtures, were grown to exponential and/or stationary phase for determination of hyperspectral UV-VIS absorption coefficients, multi-angle and multi-spectral backscatter coefficients, volume scattering functions, particle size distributions, pigment content, and fluorescence. The aim of this publication is to share these measurements to expedite their utilization in the development of new optical models for the next generation of ocean color satellites.

Measuring undergraduates' understanding of the culture of scientific research as an outcome variable in research on CUREs.

Researchers who work on course-based undergraduate research experiences (CUREs) and issues related to science, technology, engineering, and math (STEM) retention have begun exploring changes in student thinking about what it means to be a scientist. To support this effort, we developed rubrics to score answers to three open-response prompts: What does it mean to think like a scientist? What does it mean to do science? and Did you do real research in your coursename labs? The rubric development process was iterative and was based on input from the literature, experienced researchers, and early-career undergraduates. A post hoc analysis showed that the rubric elements map to 27 of 31 statements in the Culture of Scientific Research (CSR) framework, suggesting that scored responses to the three prompts can assess how well students understand what being a science professional entails. Scores on responses from over 400 students who were starting an introductory biology course for majors furnish baseline data from the rubrics and suggest that (i) undergraduates at this level have, as expected, a novice-level understanding of CSR, and (ii) level of understanding in novice students does not vary as a function of demography or academic preparation. Researchers and instructors are encouraged to add CSR to their list of learning objectives for CUREs and consider assessing it using the rubrics provided here.

Good neighbors? Does aggregation of nests in an Arctic-breeding shorebird influence daily survival rates?

Our current understanding of the factors that influence where birds nest is incomplete, yet such information is important for accurate demographic assessments. To address questions related to spatial distributions of shorebird nests and to evaluate factors that may affect nest distribution in these species, during 2017 and 2019, we studied a small population of semipalmated sandpiper Calidris pusilla breeding in the Central Canadian Arctic, near the Karrak Lake Research Station, in Nunavut. The spatial distribution of semipalmated sandpiper nests at this site suggested loose aggregation, with median nearest neighbor distances of 73.8 m and 92.0 m in 2017 and 2019, respectively, while no nests were detected on mainland areas in the vicinity. Evidence for the influence of nesting distribution on the daily survival rate of nests, however, was mixed. Neither nearest neighbor distance nor local nest density had a significant effect on daily nest survival in 2017, but in 2019, the best approximating model included an effect of local nest density, which indicated that nests in areas of high density had reduced survival rates. Contrary to other studies assessing settlement and nest site selection in semipalmated sandpipers, the spatial distribution of nests in this population demonstrates aggregation in an otherwise territorial species, but suggests that aggregated nesting can impose a cost on nest survival under certain conditions.

Interaction of COVID-19 With Common Cardiovascular Disorders.

The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain groups appeared to be at higher risk for severe illness once infected. One such group that immediately came to the forefront and garnered international attention was patients with preexisting cardiovascular disease. Here, we examine the available literature describing the interaction of COVID-19 with a myriad of cardiovascular conditions and diseases, paying particular attention to patients diagnosed with arrythmias, heart failure, and coronary artery disease. We further discuss the association of acute COVID-19 with de novo cardiovascular disease, including myocardial infarction due to coronary thrombosis, myocarditis, and new onset arrhythmias. We will evaluate various biochemical theories to explain these findings, including possible mechanisms of direct myocardial injury caused by the severe acute respiratory syndrome coronavirus-2 virus at the cellular level. Finally, we will discuss the strategies employed by numerous groups and governing bodies within the cardiovascular disease community to address the unprecedented challenges posed to the care of our most vulnerable patients, including heart transplant recipients, end-stage heart failure patients, and patients suffering from acute coronary syndromes, during the early days and height of the COVID-19 pandemic.

Cardiac tamponade-mediated generalized coronary vasospasm presenting as an inferior ST-segment elevation myocardial infarction: a case report.

Background: Coronary vasospasm is a rare cause of ST-segment elevation myocardial infarction (STEMI) and can be precipitated by numerous inciting factors including endogenous catecholamines. Differentiating coronary vasospasm from an acute atherothrombotic event is diagnostically challenging and requires a careful clinical history combined with electrocardiographic and angiographic abnormalities to make the diagnosis and guide therapy. Case Summary: We report a case of cardiogenic shock secondary to cardiac tamponade leading to an endogenous catecholamine surge resulting in profound arterial vasospasm and STEMI. The patient presented with chest pain and inferior ST segment elevations prompting emergent coronary angiography, demonstrating subtotal occlusion of the right coronary artery, severe proximal left anterior descending coronary artery stenosis, and diffusely stenosed aortoiliac vessels. Emergent transthoracic echocardiogram revealed a large pericardial effusion and hemodynamics consistent with cardiac tamponade. Pericardiocentesis resulted in dramatic hemodynamic improvement with immediate normalization of ST segments. Repeat coronary angiography performed one day later showed no angiographically significant coronary or peripheral arterial stenosis. Discussion: This is the first reported case of simultaneous coronary and peripheral arterial vasospasm presenting as inferior STEMI caused by endogenous catecholamines from cardiac tamponade. Several clues suggest coronary vasospasm including the discordant electrocardiography (ECG) and coronary angiographic findings as well as diffusely stenosed aortoiliac vessels. Diffuse vasospasm was confirmed when repeat angiography performed after pericardiocentesis demonstrated angiographic resolution of coronary and peripheral arterial stenosis. Though rare, circulating endogenous catecholamines resulting in diffuse coronary vasospasm may present as STEMI and should be considered based on the clinical history, ECG findings, and coronary angiography.

A CURE on the Evolution of Antibiotic Resistance in Escherichia coli Improves Student Conceptual Understanding.

We developed labs on the evolution of antibiotic resistance to assess the costs and benefits of replacing traditional laboratory exercises in an introductory biology course for majors with a course-based undergraduate research experience (CURE). To assess whether participating in the CURE imposed a cost in terms of exam performance, we implemented a quasi-experiment in which four lab sections in the same term of the same course did the CURE labs, while all other students did traditional labs. To assess whether participating in the CURE impacted other aspects of student learning, we implemented a second quasi-experiment in which all students either did traditional labs over a two-quarter sequence or did CURE labs over a two-quarter sequence. Data from the first experiment showed minimal impact on CURE students' exam scores, while data from the second experiment showed that CURE students demonstrated a better understanding of the culture of scientific research and a more expert-like understanding of evolution by natural selection. We did not find disproportionate costs or benefits for CURE students from groups that are minoritized in science, technology, engineering, and mathematics.

Assessing how well students understand the molecular basis of evolution by natural selection.

Researchers have called for undergraduate courses to update teaching frameworks based on the Modern Synthesis with insights from molecular biology, by stressing the molecular underpinnings of variation and adaptation. To support this goal, we developed a modified version of the widely used Assessing Conceptual Reasoning of Natural Selection (ACORNS) instrument. The expanded tool, called the E-ACORNS, is explicitly designed to test student understanding of the connections among genotypes, phenotypes, and fitness. E-ACORNS comprises a slight modification to the ACORNS open-response prompts and a new scoring rubric. The rubric is based on five core concepts in evolution by natural selection, with each concept broken into elements at the novice, intermediate, and expert-level understanding. Initial tests of the E-ACORNS showed that (1) upper-level undergraduates can score responses reliably and quickly, and (2) students who were just starting an introductory biology series for majors do not yet grasp the molecular basis of phenotypic variation and its connection to fitness.

Writing and Using Learning Objectives.

Learning objectives (LOs) are used to communicate the purpose of instruction. Done well, they convey the expectations that the instructor-and by extension, the academic field-has in terms of what students should know and be able to do after completing a course of study. As a result, they help students better understand course activities and increase student performance on assessments. LOs also serve as the foundation of course design, as they help structure classroom practices and define the focus of assessments. Understanding the research can improve and refine instructor and student use of LOs. This essay describes an online, evidence-based teaching guide published by CBE-Life Sciences Education (LSE) at http://lse.ascb.org/learning-objectives. The guide contains condensed summaries of key research findings organized by recommendations for writing and using LOs, summaries of and links to research articles and other resources, and actionable advice in the form of a checklist for instructors. In addition to describing key features of the guide, we also identify areas that warrant further empirical studies.

Potential Reduction in Adverse Events and Cost with Novel Anticoagulants among Patients with Acute Limb Ischemia.

Background: Acute limb ischemia (ALI) is associated with significant morbidity and mortality. Novel anticoagulants reduce adverse events among patients with peripheral artery disease, though the potential effect of these therapies is unclear in patients with ALI. The present study thus sought to evaluate the potential clinical benefit of universal application of novel anticoagulants to a high-risk population of patients with ALI. Methods: In this retrospective cohort study, we identified patients diagnosed with ALI in the Veterans Affairs Healthcare System between 2015 and 2016. We then calculated the incidence of adverse cardiovascular events (death/stroke/myocardial infarction/amputation/repeat intervention) as if they were treated with rivaroxaban using published data. Further, we calculated the cost to treat a Veteran diagnosed with one of these outcomes, and the potential savings had patients been universally treated with novel anticoagulants. Results: We identified 286 patients that presented with lower extremity ALI and were not treated with anticoagulation. Potential treatment of these patients with rivaroxaban resulted in significantly fewer adverse events, with an 11.9% reduction in cases at 21 months (95% CI: 5.5-17.8%) and a 13.4% reduction in cases at 47 months (95% CI: 5.6-20.5%). This corresponded to significant decreases in healthcare spending for patients with ALI who were treated with rivaroxaban. Conclusions: Among patients with ALI, treatment with rivaroxaban could result in a significant reduction in adverse cardiovascular events. The reduction in events would in turn lead to significant decreases in healthcare spending for this population.

Aminolevulinic Acid 20% Solution Combined With Photodynamic Therapy for Treatment of Actinic Keratoses: A Review.

Actinic keratoses (AK) are lesions with potential to transform into nonmelanoma skin cancers. Numerous methods are available for treatment of AK. Here, we review clinical trial data on the use of photodynamic treatment combined with the sensitizing agent aminolevulinic acid 20% solution (ALA-PDT) for AK management. Although treatment guidelines for AK vary in their specific recommendations, efficacy of ALA-PDT is considered comparable or better relative to other FDA-approved treatments for AK. It is generally well tolerated and has a very acceptable long-term safety profile. ALA-PDT is typically recommended for patients who have multiple AKs and is associated with improved cosmetic outcomes compared with cryotherapy. Patients who undergo treatment with ALA-PDT should receive thorough education regarding the risks and benefits of treatment, the treatment regimen and the importance of adhering to it, how to manage local reactions, and signs and symptoms that warrant further evaluation. J Drugs Dermatol. 2021;20(11):1239-1244. doi:10.36849/JDD.6166.

Publisher Correction: Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Active learning narrows achievement gaps for underrepresented students in undergraduate science, technology, engineering, and math.

We tested the hypothesis that underrepresented students in active-learning classrooms experience narrower achievement gaps than underrepresented students in traditional lecturing classrooms, averaged across all science, technology, engineering, and mathematics (STEM) fields and courses. We conducted a comprehensive search for both published and unpublished studies that compared the performance of underrepresented students to their overrepresented classmates in active-learning and traditional-lecturing treatments. This search resulted in data on student examination scores from 15 studies (9,238 total students) and data on student failure rates from 26 studies (44,606 total students). Bayesian regression analyses showed that on average, active learning reduced achievement gaps in examination scores by 33% and narrowed gaps in passing rates by 45%. The reported proportion of time that students spend on in-class activities was important, as only classes that implemented high-intensity active learning narrowed achievement gaps. Sensitivity analyses showed that the conclusions are robust to sampling bias and other issues. To explain the extensive variation in efficacy observed among studies, we propose the heads-and-hearts hypothesis, which holds that meaningful reductions in achievement gaps only occur when course designs combine deliberate practice with inclusive teaching. Our results support calls to replace traditional lecturing with evidence-based, active-learning course designs across the STEM disciplines and suggest that innovations in instructional strategies can increase equity in higher education.

Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment.

Altered metabolism in pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) contributes to the pathology of pulmonary hypertension (PH), but changes in substrate uptake and how substrates are utilized have not been fully characterized. We hypothesized stable isotope metabolomics would identify increased glucose, glutamine and fatty acid uptake and utilization in human PASMCs and PAECs from PH versus control specimens, and that TGF-ß treatment would phenocopy these metabolic changes. We used 13C-labeled glucose, glutamine or a long-chain fatty acid mixture added to cell culture media, and mass spectrometry-based metabolomics to detect and quantify 13C-labeled metabolites. We found PH PASMCs had increased glucose uptake and utilization by glycolysis and the pentose shunt, but no changes in glutamine or fatty acid uptake or utilization. Diseased PAECs had increased proximate glycolysis pathway intermediates, less pentose shunt flux, increased anaplerosis from glutamine, and decreased fatty acid ß-oxidation. TGF-ß treatment increased glycolysis in PASMCs, but did not recapitulate the PAEC disease phenotype. In TGF-ß-treated PASMCs, glucose, glutamine and fatty acids all contributed carbons to the TCA cycle. In conclusion, PASMCs and PAECs collected from PH subjects have significant changes in metabolite uptake and utilization, partially recapitulated by TGF-ß treatment.

Financial and resource costs of transvenous lead extraction in a high-volume lead extraction centre.

OBJECTIVES: Transvenous lead extraction (TLE) poses a significant economic and resource burden on healthcare systems; however, limited data exist on its true cost. We therefore estimate real-world healthcare reimbursement costs of TLE to the UK healthcare system at a single extraction centre. METHODS: Consecutive admissions entailing TLE at a high-volume UK centre between April 2013 and March 2018 were prospectively recorded in a computer registry. In the hospital's National Health Service (NHS) clinical coding/reimbursement database, 447 cases were identified. Mean reimbursement cost (n=445) and length of stay (n=447) were calculated. Ordinary least squares regressions estimated the relationship between cost (bed days) and clinical factors. RESULTS: Mean reimbursement cost per admission was £17 399.09±£13 966.49. Total reimbursement for all TLE admissions was £7 777 393.51. Mean length of stay was 16.3±15.16 days with a total of 7199 bed days. Implantable cardioverter-defibrillator and cardiac resynchronisation therapy defibrillator devices incurred higher reimbursement costs (70.5% and 68.7% higher, respectively, both p<0.001). Heart failure and prior valve surgery also incurred significantly higher reimbursement costs. Prior valve surgery and heart failure were associated with 8.3 (p=0.017) and 5.5 (p=0.021) additional days in hospital, respectively. CONCLUSIONS: Financial costs to the NHS from TLE are substantial. Consideration should therefore be given to cost/resource-sparing potential of leadless/extravascular cardiac devices that negate the need for TLE particularly in patients with prior valve surgery and/or heart failure. Additionally, use of antibiotic envelopes and other interventions that reduce infection risk in patients receiving transvenous leads should be considered.

Composition and Drivers of Gut Microbial Communities in Arctic-Breeding Shorebirds.

Gut microbiota can have important effects on host health, but explanatory factors and pathways that determine gut microbial composition can differ among host lineages. In mammals, host phylogeny is one of the main drivers of gut microbiota, a result of vertical transfer of microbiota during birth. In birds, it is less clear what the drivers might be, but both phylogeny and environmental factors may play a role. We investigated host and environmental factors that underlie variation in gut microbiota composition in eight species of migratory shorebirds. We characterized bacterial communities from 375 fecal samples collected from adults of eight shorebird species captured at a network of nine breeding sites in the Arctic and sub-Arctic ecoregions of North America, by sequencing the V4 region of the bacterial 16S ribosomal RNA gene. Firmicutes (55.4%), Proteobacteria (13.8%), Fusobacteria (10.2%), and Bacteroidetes (8.1%) dominated the gut microbiota of adult shorebirds. Breeding location was the main driver of variation in gut microbiota of breeding shorebirds (R 2 = 11.6%), followed by shorebird host species (R 2 = 1.8%), and sampling year (R 2 = 0.9%), but most variation remained unexplained. Site variation resulted from differences in the core bacterial taxa, whereas rare, low-abundance bacteria drove host species variation. Our study is the first to highlight a greater importance of local environment than phylogeny as a driver of gut microbiota composition in wild, migratory birds under natural conditions.

Can Test Anxiety Interventions Alleviate a Gender Gap in an Undergraduate STEM Course?

Gender gaps in exam scores or final grades are common in introductory college science and engineering classrooms, with women underperforming relative to men with the same admission test scores or college grade point averages. After failing to close a historically documented gender gap in a large introductory biology course using interventions targeted at training a growth mindset, we implemented interventions designed to reduce student test anxiety. We combined evidence-based exercises based on expressive writing and on reappraising physiological arousal. We also used a valid measure to quantify test anxiety at the start and end of the course. This instrument measures an individual's self-declared or perceived test anxiety-also called trait anxiety-but not the immediate or "state" anxiety experienced during an actual exam. Consistent with previous reports in the literature, we found that women in this population declared much higher test anxiety than men and that students who declared higher test anxiety had lower exam scores than students who declared lower test anxiety. Although the test anxiety interventions had no impact on the level of self-declared trait anxiety, they did significantly increase student exam performance. The treatment benefits occurred in both men and women. These data suggest that 1) a combination of interventions based on expressive writing and reappraising physiological arousal can be a relatively easy manner to boost exam performance in a large-enrollment science, technology, engineering, and mathematics (STEM) course and encourage emotion regulation; 2) women are more willing than men to declare that they are anxious about exams, but men and women may actually experience the same level of anxiety during the exam itself; and 3) women are underperforming in STEM courses for reasons other than gender-based differences in mindset or test anxiety.

Th2 CD4+ T Cells Are Necessary and Sufficient for Schistosoma-Pulmonary Hypertension.

Background Inflammation underlies many forms of pulmonary hypertension (PH), including that resulting from Schistosoma infection, a major cause of PH worldwide. Schistosomiasis-associated PH is proximately triggered by embolization of parasite eggs into the lungs, resulting in localized type 2 inflammation. However, the role of CD4+ T cells in this disease is not well defined. Methods and Results We used a mouse model of schistosomiasis-associated PH, induced by intraperitoneal egg sensitization followed by intravenous egg challenge, with outcomes including right ventricle systolic pressure measured by cardiac catheterization, and cell density and phenotype assessed by flow cytometry. We identified that embolization of Schistosoma eggs into lungs of egg-sensitized mice increased the perivascular density of T-helper 2 (Th2) CD4+ T cells by recruitment of cells from the circulation and triggered type 2 inflammation. Parabiosis confirmed that egg embolization is required for localized type 2 immunity. We found Th2 CD4+ T cells were necessary for Schistosoma-induced PH, given that deletion of CD4+ T cells or inhibiting their Th2 function protected against type 2 inflammation and PH following Schistosoma exposure. We also observed that adoptive transfer of Schistosoma-sensitized CD4+ Th2 cells was sufficient to drive type 2 inflammation and PH. Conclusions Th2 CD4+ T cells are a necessary and sufficient component for the type 2 inflammation-induced PH following Schistosoma exposure.

True Grit: Passion and persistence make an innovative course design work.

Our first two experiments on adapting a high-structure course model to an essentially open-enrollment university produced negative or null results. Our third experiment, however, proved more successful: performance improved for all students, and a large achievement gap that impacted underrepresented minority students under traditional lecturing closed. Although the successful design included preclass preparation videos, intensive active learning in class, and weekly practice exams, student self-report data indicated that total study time decreased. Faculty who have the grit to experiment and persevere in making evidence-driven changes to their teaching can reduce the inequalities induced by economic and educational disadvantage.