Guideline Concordance of Aspirin Use for Primary Prevention in Adult Outpatients.

Recent guidelines have recommended a reduced role for primary prevention aspirin use, which is associated with increased bleeding risk. This study seeks to characterize guideline-discordant aspirin use among adults in a community care setting. As part of a quality improvement initiative, patients at one internal medicine and one family medicine clinic affiliated with an academic hospital were sent an electronic survey. Patients were included if they were at least 40 years old, had a primary care provider at the specified sites, and were seen in the last year. Patients were excluded if they had an indication for aspirin other than primary prevention. Responses were collected from February 15 to March 16, 2022. Analyses were performed to identify predictors of primary prevention aspirin use and predictors of guideline-discordant aspirin; aspirin users and non-users were compared using Fisher's exact test, independent samples t-tests, and multivariable logistic regression. Of 1460 patients sent a survey, 668 (45.8%) responded. Of respondents, 132 (24.1%) reported aspirin use that was confirmed to be for primary prevention. Overall, 46.2-58.3% of primary prevention aspirin users were potentially taking aspirin contrary to guideline recommendations. Predictors of discordant aspirin use included a history of diabetes mellitus and medication initiation by a primary care provider. In conclusion, primary prevention aspirin use may be overutilized and discordant with recent guideline recommendations for about half of patients, suggesting a need for aspirin de-implementation. These efforts may be best focused at the primary care level.

Two for One: Tuberculid and Leukocytoclastic Vasculitis in an Adolescent.

A 13-year-old girl with fevers, abdominal pain, and vomiting for 4 days presented with a full body pruritic rash that began in the axilla and spread rapidly to the rest of the body. She was recently diagnosed with tuberculosis and had been on rifampin, isoniazid, pyrazinamide and ethambutol (RIPE) therapy for 1 month to treat this infection, raising concern for a severe drug reaction. On exam, there were pink to hemorrhagic crusted papules diffusely on the body; two skin biopsies from the right ankle and right arm showed leukocytoclastic vasculitis and tuberculid pathologies, respectively. Tuberculids are a cutaneous form of tuberculosis that represent a hypersensitivity reaction to Mycobacterium tuberculosis or its antigens. These rashes can mimic other common diseases, and this case highlights the importance of obtaining histopathology early in the disease course for accurate and prompt diagnosis.

Guidelines for the effective and ethical sampling of herbaria.

The use of herbaria for science and conservation is enabling greatly enhanced scopes and scales of discovery, exploration and protection of biodiversity. The availability of digital, open-access herbarium data is, perhaps counter-intuitively, expanding the use of physical collections by researchers who use digital collections to find specimens and then sample physical collections for multiomics investigations, including genomics, transcriptomics, metabolomics, proteomics and microbiomics. These investigations are leading to new scientific insights and supporting the development of conservation actions, but they come with a substantial cost: the partial or complete destruction of often irreplaceable specimens, which constitute a global heritage that should be permanently safeguarded for future reference. Here we provide a set of recommended best practices for the sustainable, equitable and ethical sampling of herbarium specimens. Our recommendations are intended for two complementary and partially overlapping audiences-users and stewards-who together build, use and protect herbarium collections.

Factors associated with venous thromboembolism pharmacoprophylaxis initiation in hospitalized medical patients: the Medical Inpatients Thrombosis and Hemostasis study.

BACKGROUND: Although guidelines recommend risk assessment for hospital-acquired venous thromboembolism (HA-VTE) to inform prophylaxis decisions, studies demonstrate inappropriate utilization of pharmacoprophylaxis in hospitalized medical patients. Predictors of pharmacoprophylaxis initiation in medical inpatients remain largely unknown. OBJECTIVES: To determine factors associated with HA-VTE pharmacoprophylaxis initiation in adults hospitalized on medical services. METHODS: We performed a cohort study using electronic health record data from adult patients hospitalized on medical services at 4 academic medical centers between 2016 and 2019. Main measures were candidate predictors of HA-VTE pharmacoprophylaxis initiation, including known HA-VTE risk factors, predicted HA-VTE risk, and bleeding diagnoses present on admission. RESULTS: Among 111 550 admissions not on intermediate or full-dose anticoagulation, 48 520 (43.5%) received HA-VTE pharmacoprophylaxis on the day of or the day after admission. After adjustment for age, sex, race/ethnicity, and study site, the strongest clinical predictors of HA-VTE pharmacoprophylaxis initiation were malnutrition and chronic obstructive pulmonary disease. Thrombocytopenia and history of gastrointestinal bleeding were associated with decreased odds of HA-VTE pharmacoprophylaxis initiation. Patients in the highest 2 tertiles of predicted HA-VTE risk were less likely to receive HA-VTE pharmacoprophylaxis than patients in the lowest (first) tertile (OR, 0.84; 95% CI, 0.81-0.86 for the second tertile; OR, 0.95; 95% CI, 0.92-0.98 for the third tertile). CONCLUSION: Among patients not already receiving anticoagulants, HA-VTE pharmacoprophylaxis initiation during the first 2 hospital days was lower in patients with a higher predicted HA-VTE risk and those with risk factors for bleeding. Reasons for not initiating pharmacoprophylaxis in those with a higher predicted HA-VTE risk could not be assessed.

A cost analysis of medications prescribed by vascular surgeons.

OBJECTIVE: Various pharmaceutical cost options have been developed by multiple companies such as GoodRx, Amazon Pharmacy, Mark Cuban Cost Plus Drugs (CPD), Health Warehouse, and local retail pharmacies) to curb the cost of prescription medications prices that patients are having to bear. Vascular surgeons provide long-term continuity of care to patients with vascular disease who often require long-term medical management. This study sought to compare the different pharmaceutical options available for the most prescribed medications by vascular surgeons to their patients and to understand which of them are the most cost-effective. METHODS: The Medicare Part D catalog and vascular surgical literature were evaluated to identify which medications are most prescribed by vascular surgeons. The average price per tablet being paid by patients was identified using the Agency for Healthcare and Research database. The prices per tablet for each of the above pharmaceutical companies were found using online catalogs or coupons. The prices were then compared using analysis of variance and t-tests. RESULTS: All four pharmaceutical cost options provide medication cost savings to patients compared with retail pharmacy costs. Analysis of variance showed that there were statistically significant differences among the different pharmaceutical cost options (F 15.44>2.36; P < .001). Mark Cuban CPD provided the most significant cost advantage over the other pharmaceutical options (P < .01). On a national scale, medications prescribed by vascular surgeons through Mark Cuban CPD could provide a 52% cost reduction to patients with vascular disease with a potential annual savings of over $3 billion dollars for the selected medications. CONCLUSIONS: CPD shows a strong potential for cost savings for patients commonly prescribed medications by vascular surgeons. As a specialty that provides long-term care and establishes long-term relationships with its patients, vascular surgeons have the unique ability to impact their overall health in a meaningful way by limiting the financial burdens associated with vascular-based medication acquisition and utilization.

Effects of Dietary Nitrate Supplementation on High-Intensity Cycling Sprint Performance in Recreationally Active Adults: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis investigated the influence of dietary nitrate supplementation on performance metrics during cycling sprint exercise according to the PRISMA guidelines. Searches were conducted on MEDLINE, PubMed, ScienceDirect, Scopus, and SPORTDiscus databases up to September 2023. Inclusion criteria were healthy recreationally active men and women who consumed nitrate-rich and nitrate-deficient beetroot juice to assess performance outcomes of mean power, peak power, time-to-peak power, and minimum power during 30-s cycling sprints. Risk of bias was assessed using the Cochrane Risk of Bias 2 and TESTEX tools and funnel plots. A random effects model was performed on six studies and showed that dietary nitrate had significant effects on time-to-peak power (SMD: -0.66, 95% CI: -1.127 to -0.192, p = 0.006) but not on mean power, peak power, or minimum power. Subgroup analysis revealed that an acute low nitrate dose improved time-to-peak power (SMD: -0.977, 95% CI: -1.524 to -0.430, p < 0.001) but not after a multiday moderate nitrate dose (SMD: -0.177, 95% CI: -0.619 to -0.264, p = 0.431). These data suggest that acute nitrate supplementation can benefit time-to-peak power during 30-s cycling sprints, but due to the limited availability of data and heterogeneity in methodology, these results should be interpreted with caution. There was insufficient data on women to analyze sex-based differences. Future studies are required to provide insight on how supplementation regimen and population impact the effects of dietary nitrate for enhancing cycling sprint performance.

Meeting Report: 2023 Muscular Dystrophy Association Summit on 'Safety and Challenges in Gene Therapy of Neuromuscular Diseases'.

 This meeting report summarizes the presentations and discussions held at the summit on Challenges in Gene Therapy hosted by the Muscular Dystrophy Association (MDA) in 2023. Topics covered include safety issues, mitigation strategies and practical considerations pertaining to the clinical translation of gene therapies for neuromuscular disease. The listing of actionable recommendations will assist in overall efforts in the field to achieve safe and efficacious translation of gene therapies for neuromuscular disease patients.

Outpatient remdesivir treatment program for hospitalized patients with coronavirus disease-2019: Patient perceptions, process and economic impact.

BACKGROUND: Remdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In a prior work, patients who continued remdesivir in an outpatient setting experienced better 28-day clinical outcomes. Here, we assessed patients' perspectives and the economic impact of this outpatient practice. METHODS: Hospitalized patients who received remdesivir for COVID-19 at Mayo Clinic, Rochester, from 11/6/2020 to 11/5/2021 and were dismissed to continue remdesivir in the outpatient setting were surveyed. The cost of care was compared between those who remained hospitalized versus those who were dismissed. RESULTS: 93 (19.8 %) among 470 eligible patients responded to the electronic survey. Responders were older than non-responders. The majority (70.5 %) had symptoms resolved by the time of the survey. Ten (11.4 %) patients had persistent symptoms attributed to long COVID-19. The majority were satisfied with the quality of care (82.3 %) and overall experience (76.0 %) in the infusion clinic. After adjusting for gender, comorbidity score, and WHO severity scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p < .01). An estimate of 1,077 hospital bed-days were made available to other patients as a result of this transition to outpatient. CONCLUSION: An outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital beds for other patients needing critical services.

Outcomes of direct oral anticoagulants with aspirin vs warfarin with aspirin: a registry-based cohort study.

Background: For patients anticoagulated with direct oral anticoagulants (DOACs) or warfarin and on aspirin (ASA) for nonvalvular atrial fibrillation and/or venous thromboembolism, it is unclear if bleeding outcomes differ. Objectives: To assess bleeding rates for ASA with DOACs vs warfarin and one another. Methods: Registry-based cohort study of patients followed by a 6-center quality improvement collaborative in Michigan using data from 2009 to 2022. The study included adults on ASA with warfarin or DOACs for atrial fibrillation and/or venous thromboembolism without a recent myocardial infarction or heart valve replacement. Results: After propensity matching by anticoagulant class, we compared 2 groups of 1467 patients followed for a median of 18.0 months. Any bleeding and nonmajor bleeding was increased with DOACs + ASA compared with warfarin + ASA (32.2 vs 27.8 and 27.1 vs 22.9 events/100 patient-years; relative risks [RRs], 1.1 and 1.2; 95% CIs, 1.1-1.2 and 1.1-1.3, respectively). After matching by drug, patients on apixaban + ASA vs warfarin + ASA had more bleeding (31.2 vs 27.8 events/100 patient-years; RR, 1.1; 95% CI, 1.0-1.2) and nonmajor bleeding but less major bleeding (3.8 vs 4.7 events/100 patient-years; RR, 0.8; 95% CI, 0.6-1.0) and emergency room visits for bleeding. Patients on rivaroxaban + ASA vs warfarin + ASA had more bleeding (39.3 vs 26.3 events/100 patient-years, RR, 1.5; 95% CI, 1.3-1.6), nonmajor bleeding, and thrombosis. Patients on apixaban + ASA vs rivaroxaban + ASA had significantly less bleeding (22.5 vs 39.3/100 patient-years; RR, 0.6; 95% CI, 0.5-0.7), nonmajor bleeding, major bleeding (2.1 vs 5.5 events/100 patient-years; RR, 0.4; 95% CI, 0.2-0.6), emergency room visits for bleeding, and thrombotic events. Conclusion: Patients on DOAC + ASA without a recent myocardial infarction or heart valve replacement had more nonmajor bleeding but otherwise similar outcomes compared with warfarin + ASA. Patients treated with rivaroxaban + ASA experienced more adverse clinical events compared with warfarin + ASA or apixaban + ASA.

Noninvasive Ventilation for Preoxygenation during Emergency Intubation.

BACKGROUND: Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain. METHODS: In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. RESULTS: Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.).

Neutrophil glucose flux as a therapeutic target in antiphospholipid syndrome.

Neutrophil hyperactivity and neutrophil extracellular trap release (NETosis) appear to play important roles in the pathogenesis of the thromboinflammatory autoimmune disease known as antiphospholipid syndrome (APS). The understanding of neutrophil metabolism has advanced tremendously in the past decade, and accumulating evidence suggests that a variety of metabolic pathways guide neutrophil activities in health and disease. Our previous work characterizing the transcriptome of APS neutrophils revealed that genes related to glycolysis, glycogenolysis, and the pentose phosphate pathway (PPP) were significantly upregulated. Here, we found that neutrophils from patients with APS used glycolysis more avidly than neutrophils from people in the healthy control group, especially when the neutrophils were from patients with APS with a history of microvascular disease. In vitro, inhibiting either glycolysis or the PPP tempered phorbol myristate acetate- and APS IgG-induced NETosis, but not NETosis triggered by a calcium ionophore. In mice, inhibiting either glycolysis or the PPP reduced neutrophil reactive oxygen species production and suppressed APS IgG-induced NETosis ex vivo. When APS-associated thrombosis was evaluated in mice, inhibiting either glycolysis or the PPP markedly suppressed thrombosis and circulating NET remnants. In summary, these data identify a potential role for restraining neutrophil glucose flux in the treatment of APS.

Medical Nutrition Education for Health, Not Harm: BMI, Weight Stigma, Eating Disorders, and Social Determinants of Health.

Effective nutrition training is fundamental to medical education. Current training is inadequate and can cause harm to students and patients alike; it leaves physicians unprepared to counsel on nutrition, places undue focus on weight and body mass index (BMI), can exacerbate anti-obesity bias, and increase risk for development of eating disorders, while neglecting social determinants of health and communication skills. Physicians and educators hold positions of influence in society; what we say and how we say it matters. We propose actionable approaches to improve nutrition education to minimize harm and pursue evidence-based, effective, and equitable healthcare.

Bubble reachers and uncivil discourse in polarized online public sphere.

Early optimism saw possibilities for social media to renew democratic discourse, marked by hopes for individuals from diverse backgrounds to find opportunities to learn from and interact with others different from themselves. This optimism quickly waned as social media seemed to breed ideological homophily marked by "filter bubbles" or "echo chambers." A typical response to the sense of fragmentation has been to encourage exposure to more cross-partisan sources of information. But do outlets that reach across partisan lines in fact generate more civil discourse? And does the civility of discourse hosted by such outlets vary depending on the political context in which they operate? To answer these questions, we identified bubble reachers, users who distribute content that reaches other users with diverse political opinions in recent presidential elections in Brazil, where populism has deep roots in the political culture, and Canada, where the political culture is comparatively moderate. Given that background, this research studies unexplored properties of content shared by bubble reachers, specifically the quality of conversations and comments it generates. We examine how ideologically neutral bubble reachers differ from ideologically partisan accounts in the level of uncivil discourse they provoke, and explore how this varies in the context of the two countries considered. Our results suggest that while ideologically neutral bubble reachers support less uncivil discourse in Canada, the opposite relationship holds in Brazil. Even non-political content by ideologically neutral bubble reachers elicits a considerable amount of uncivil discourse in Brazil. This indicates that bubble reaching and incivility are moderated by the national political context. Our results complicate the simple hypothesis of a universal impact of neutral bubble reachers across contexts.

Neonatal Mouse Bone Marrow Isolation and Preparation of Bone Marrow-Derived Macrophages.

Various techniques for isolating bone marrow from adult mice have been well established. However, isolating bone marrow from neonatal mice is challenging and time-consuming, yet for some models, it is translationally relevant and necessary. This protocol describes an efficient and straightforward method for preparing bone marrow cells from 7-9-day-old pups. These cells can then be further isolated or differentiated into specific cell types of interest. Macrophages are crucial immune cells that play a major role in inflammation and infection. During development, neonatal macrophages contribute significantly to tissue remodeling. Moreover, the phenotype and functions of neonatal macrophages differ from those of their adult counterparts. This protocol also outlines the differentiation of neonatal macrophages from the isolated bone marrow cells in the presence of L929-conditioned medium. Surface markers for differentiated neonatal macrophages were assessed using flow cytometric analysis. To demonstrate functionality, the phagocytic efficiency was also tested using pH-sensitive dye-conjugated Escherichia coli.

Comparing Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prediction of Extraprostatic Extension of Prostate Cancer and Surgical Guidance: A Prospective Nonrandomized Clinical Trial.

PURPOSE: Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach. MATERIALS AND METHODS: We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities. RESULTS: The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone (P = .01). CONCLUSIONS: PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations. CLINICALTRIALS.GOV IDENTIFIER: NCT04936334.

Evaluating post-rhinoplasty nasal obstruction treatment: The efficacy of VivAer radiofrequency ablation.

PURPOSE: Nasal obstruction is a prevalent issue affecting up to one-third of adults, often requiring surgical intervention. Low-temperature radiofrequency (RF) treatment, specifically VivAer, has emerged as a promising alternative, especially for the treatment of nasal valve collapse (NVC). However, its efficacy in patients with a history of rhinoplasty or nasal valve repair remains unexplored. METHODS: A single-center retrospective chart review was conducted on 37 patients with a history of rhinoplasty or nasal valve repair who underwent VivAer RF treatment. Treatment outcomes were assessed using the Nasal Obstruction Symptom Evaluation (NOSE) scale. The primary outcome was defined as a decrease in NOSE score by at least one severity category or a 20 % reduction in total NOSE score. RESULTS: The study found a statistically significant average reduction in NOSE score of 22.4 points or 36.6 %. Among patients with a positive treatment response (21 patients or 56.8 %), the average NOSE score reduction was 34.7 points or 55.6 %. Repeat RF treatment in non-responders resulted in a 50 % response rate. No significant difference was observed in treatment outcomes based on the type of prior rhinoplasty or NVC. CONCLUSIONS: Temperature-controlled RF treatment with VivAer can effectively alleviate nasal obstruction in patients with a history of rhinoplasty or nasal valve repair, offering a viable alternative to revision surgery. The study also highlights the potential benefit of repeat RF treatment in non-responders. Further research, including randomized controlled trials, is needed to validate these promising results and expand the treatment options for this complex patient population.

A Cross-Sectional Survey Study of Cannabis Use for Fibromyalgia Symptom Management.

OBJECTIVE: To assess the use of cannabis as a symptom management strategy for patients with fibromyalgia. PATIENTS AND METHODS: An electronic, cross-sectional survey was conducted among patients diagnosed with fibromyalgia and treated in Integrative Medicine & Health at Mayo Clinic, Rochester, Minnesota. The survey was constructed with the Symptom Management Theory tool and was sent anonymously via web-based software to patients with a diagnosis of fibromyalgia. RESULTS: Of 5234 patients with fibromyalgia sent the online survey, 1336 (25.5%) responded and met the inclusion criteria. Survey respondents had a median age of 48 (Q1-Q3: 37.5-58.0) years, and most identified as female. Nearly half of respondents (49.5%, n=661) reported cannabis use since their fibromyalgia diagnosis. The most common symptoms for which respondents reported using cannabis were pain (98.9%, n=654); fatigue (96.2%; n=636); stress, anxiety, or depression (93.9%; n=621); and insomnia (93.6%; n=619). Improvement in pain symptoms with cannabis use was reported by 82.0% (n=536). Most cannabis-using respondents reported that cannabis also improved symptoms of stress, anxiety, and depression and of insomnia. CONCLUSION: Considering that cannabis is a popular choice among patients for managing fibromyalgia symptoms, clinicians should have adequate knowledge of cannabis when discussing therapeutic options for fibromyalgia with their patients.