Definition and Perception of Autonomy in Vascular Surgery Training.

BACKGROUND: There is a lack of data evaluating operative autonomy within vascular surgery. This study aims to determine where discrepancies exist in the definition of autonomy between trainees and attending faculty. METHODS: An Institutional Review Board-approved, anonymous survey was e-mailed to vascular trainees and attending faculty at all Accreditation Council for Graduate Medical Education-approved vascular surgery training programs in the United States. Data were compared using chi-square statistical analysis. RESULTS: One-hundred forty-nine responses from vascular surgery trainees (n = 89) and faculty (n = 60) were obtained. The most highly ranked preoperative skill by trainees was Case Planning, at all post-graduate year-levels. Although a majority of trainees believe this skill is expected of them, only 36.1% of attendings responded that they expect all trainee levels to perform this task. Draping/positioning was ranked as the second most important intraoperative task for all post-graduate year-levels by attendings; however, only 32.8% of attendings expect trainees to perform this. Exposure of Critical Structures was ranked as the most important intraoperative task by both trainees and attendings at the Chief and Fellow level. However, responses by both trainees and attendings showed that this is expected <70% of the time. When asked about double-scrubbing independently of other tasks, most trainees assessed double-scrubbing as inherently important to autonomy at all levels of training and within all regions. Only 44.3% of attendings responded that they expect all trainees to double-scrub. Additionally, most trainees in all regions responded that they spend <25% of cases double-scrubbed. CONCLUSIONS: These responses show a discrepancy between the skills that both trainees and attendings deem important to autonomy versus what is being expected of trainees in reality.

Studies Of Prescription Digital Therapeutics Often Lack Rigor And Inclusivity.

Little is known about the evidence to support prescription digital therapeutics, which are digital tools that rely primarily on software for diagnosis or treatment that have indications for use regulated by the Food and Drug Administration (FDA) and require a clinician's prescription. We conducted the first retrospective cross-sectional analysis of clinical studies of twenty prescription digital therapeutics authorized by the FDA and available on the market as of November 2022. Our analysis found that just two prescription digital therapeutics had been evaluated in at least one study that was randomized and blinded and that used other rigorous standards of evidence. Two-thirds of clinical studies of prescription digital therapeutics were conducted on a postmarket basis, with less rigorous standards of evidence than the standards used in premarket studies. More than half of studies did not report data on participants' race, and more than 80 percent did not report their ethnicity. More than one-third required English proficiency, and nearly half of nonpediatric studies had an upper age limit. These results suggest the need for a more rigorous and inclusive approach to clinical research supporting FDA-authorized prescription digital therapeutics. A stronger evidence base would increase confidence in these technologies' effectiveness and would enable more informed decision making about their clinical use and coverage.

Hospital Admissions Associated With Head and Neck Injuries From Olympic-style Sports and Activities Between 2010 and 2022.

The objective of this study was to evaluate which Olympic-style sports and activities are most likely to result in hospitalizations relating to head and neck injuries. This was a cross-sectional study using the National Electronic Injury Surveillance System (NEISS) database. Subjects with head and neck injuries from selected Olympic-style sports and activities between 2010 and 2022 were included. Independent variables were demographics and injury characteristics (injury location and sport). The primary outcome variable was hospitalization (yes/no). Survey-weighted descriptive, bivariate, and logistic regression statistics were computed to measure the association between demographic/injury variables and hospitalization. There were 175,995 subjects (national estimate, 5,922,584) meeting inclusion criteria. After adjusting for demographic and injury characteristics, head injuries (odds ratio [OR] = 2.17; 95% CI, 1.83-2.56; P<0.001) demonstrated higher odds of hospitalization compared with facial injuries. Injuries from cycling (OR = 2.52; 95% CI, 2.16-2.95; P<0.001), mountain biking (OR = 2.56; 95% CI, 1.80-3.65; P<0.001), and horseback riding (OR = 4.01; 95% CI, 2.76-5.83; P<0.001) demonstrated higher odds of hospitalization relative to baseball injuries. In conclusion, head and neck injuries associated with high velocity Olympic-style sports and activities such as cycling, mountain biking, and horseback riding had the highest odds of hospitalization.

Development and Characterization of an In Vitro Cell-Based Assay to Predict Potency of mRNA-LNP-Based Vaccines.

Messenger RNA (mRNA) vaccines have emerged as a flexible platform for vaccine development. The evolution of lipid nanoparticles as effective delivery vehicles for modified mRNA encoding vaccine antigens was demonstrated by the response to the COVID-19 pandemic. The ability to rapidly develop effective SARS-CoV-2 vaccines from the spike protein genome, and to then manufacture multibillions of doses per year was an extraordinary achievement and a vaccine milestone. Further development and application of this platform for additional pathogens is clearly of interest. This comes with the associated need for new analytical tools that can accurately predict the performance of these mRNA vaccine candidates and tie them to an immune response expected in humans. Described here is the development and characterization of an imaging based in vitro assay able to quantitate transgene protein expression efficiency, with utility to measure lipid nanoparticles (LNP)-encapsulated mRNA vaccine potency, efficacy, and stability. Multiple biologically relevant adherent cell lines were screened to identify a suitable cell substrate capable of providing a wide dose-response curve and dynamic range. Biologically relevant assay attributes were examined and optimized, including cell monolayer morphology, antigen expression kinetics, and assay sensitivity to LNP properties, such as polyethylene glycol-lipid (or PEG-lipid) composition, mRNA mass, and LNP size. Collectively, this study presents a strategy to quickly optimize and develop a robust cell-based potency assay for the development of future mRNA-based vaccines.

Understanding the Spike Protein in COVID-19 Vaccine in Recombinant Vesicular Stomatitis Virus (rVSV) Using Automated Capillary Western Blots.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral agent that is responsible for the coronavirus disease-2019 (COVID-19) pandemic. One of the live virus vaccine candidates Merck and Co., Inc. was developing to help combat the pandemic was V590. V590 was a live-attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV) in which the envelope VSV glycoprotein (G protein) gene was replaced with the gene for the SARS-CoV-2 spike protein (S protein), the protein responsible for viral binding and fusion to the cell membrane. To assist with product and process development, a quantitative Simple Western (SW) assay was successfully developed and phase-appropriately qualified to quantitate the concentration of S protein expressed in V590 samples. A strong correlation was established between potency and S-protein concentration, which suggested that the S-protein SW assay could be used as a proxy for virus productivity optimization with faster data turnaround time (3 h vs 3 days). In addition, unlike potency, the SW assay was able to provide a qualitative profile assessment of the forms of S protein (S protein, S1 subunit, and S multimer) to ensure appropriate levels of S protein were maintained throughout process and product development. Finally, V590 stressed stability studies suggested that time and temperature contributed to the instability of S protein demonstrated by cleavage into its subunits, S1 and S2, and aggregation into S multimer. Both of which could potentially have a deleterious effect on the vaccine immunogenicity.

Pooled screening of CAR T cells identifies diverse immune signaling domains for next-generation immunotherapies.

Chimeric antigen receptors (CARs) repurpose natural signaling components to retarget T cells to refractory cancers but have shown limited efficacy in persistent, recurrent malignancies. Here, we introduce "CAR Pooling," a multiplexed approach to rapidly identify CAR designs with clinical potential. Forty CARs with signaling domains derived from a range of immune cell lineages were evaluated in pooled assays for their ability to stimulate critical T cell effector functions during repetitive stimulation that mimics long-term tumor antigen exposure. Several domains were identified from the tumor necrosis factor (TNF) receptor family that have been primarily associated with B cells. CD40 enhanced proliferation, whereas B cell-activating factor receptor (BAFF-R) and transmembrane activator and CAML interactor (TACI) promoted cytotoxicity. These functions were enhanced relative to clinical benchmarks after prolonged antigen stimulation, and CAR T cell signaling through these domains fell into distinct states of memory, cytotoxicity, and metabolism. BAFF-R CAR T cells were enriched for a highly cytotoxic transcriptional signature previously associated with positive clinical outcomes. We also observed that replacing the 4-1BB intracellular signaling domain with the BAFF-R signaling domain in a clinically validated B cell maturation antigen (BCMA)-specific CAR resulted in enhanced activity in a xenotransplant model of multiple myeloma. Together, these results show that CAR Pooling is a general approach for rapid exploration of CAR architecture and activity to improve the efficacy of CAR T cell therapies.

Impact of COVID-19 on ready-mix concrete (RMC) industry in Ahmedabad - A case study.

India witnessed its first case of coronavirus infection (COVID-19) on January 27, 2020, in Kerala, India. Since then, the infection has spread rapidly across the country and the pandemic outbreak has affected all industries severely including the construction sector. This study aims to understand the effect of the COVID-19 pandemic on the construction sector, particularly the ready-mix concrete (RMC) industry. An attempt was made to investigate the liabilities and the losses incurred by the RMC industry in terms of income and change in the production of concrete during the coronavirus outbreak. A preliminary survey was carried out to create a database of the RMC plants located nearby the study area i.e., Ahmedabad City in the state of Gujarat, and to prepare a questionnaire using google forms. The RMC plants were visited and from the inputs of RMC officials, statistical insights were drawn. The study reveals that during the COVID-19 lockdown period there was almost a 40% loss in concrete production & 60% loss in the income generated by the ready-mix concrete industry. In addition to this, it was also found that the industry had to pay off liabilities like land rent, electricity bills, staff salaries, etc. during the time of the pandemic. This study provides the opportunity for RMC plants to identify the vital elements involved in the operation of the plant which can be affected due to such pandemic and provides guidelines to reduce the effect of any such pandemic on the plant's production & sales by ensuring the stability of all assets involved in its supply chain.

Do rural oral and maxillofacial surgeons prescribe more postoperative opioids?

PURPOSE: This study assesses rural-urban differences in opioid prescription practices among oral and maxillofacial surgeons (OMSs) who treated Medicare beneficiaries in 2017. METHODS: This cross-sectional study examines the 2017 Medicare Provider Utilization and Payment Dataset. The primary predictor variable was provider Rural-Urban Commuting Area code (rural versus urban). The primary outcome variable was mean opioid claims per Medicare beneficiary. Additional outcomes include total opioid claims volume, average Medicare beneficiaries and opioid cost per provider, mean days' supply of opioids per opioid claim, and average percentage of Medicare Part D claims represented by opioid claims. Mann-Whitney U tests compared continuous variables. A least-squares regression identified correlates of opioid claims volume. RESULTS: Rural OMSs demonstrated a higher mean opioid claims per OMS and opioid cost per provider compared to urban surgeons. Urban OMSs prescribed a greater mean days' supply of opioids per opioid claim. A larger percentage of Medicare Part D claims were represented by opioid claims for rural OMSs compared to urban OMSs. There were no differences in mean opioid claims per Medicare beneficiary. Male provider gender, female Medicare beneficiary gender, total number of beneficiaries, and a higher hierarchical condition category score were correlated with increased opioid claims per Medicare beneficiary for urban providers only. CONCLUSION: Urban and rural OMSs prescribe a similar volume of opioids per Medicare beneficiary, with rural providers prescribing higher total volumes of opioids due to larger patient panels. This work indicates that rural and urban OMSs have similar opioid prescribing practices.

An anesthesiologist-led inpatient buprenorphine initiative.

Hospitalized patients with opioid use disorder who present with acute pain are challenging to manage. Without any treatment, their mortality in the first 28 days after discharge is substantially increased. Unlike extended-release naltrexone, which requires a period of withdrawal, or methadone, which can cause prolonged corrected QT (QTc) and carries a higher risk of respiratory depression, buprenorphine provides potent analgesia with low respiratory risk. Hospitalization provides a unique opportunity for clinicians to perform buprenorphine induction, which could potentially reduce mortality without affecting analgesia. Our acute pain management service uses multimodal analgesia to maintain adequate analgesia and minimize withdrawal during buprenorphine induction in the hospital. With the assistance of narcotics addiction rehabilitation program specialists, we help link patients to outpatient buprenorphine providers and maximize the chance of successful recovery. The primary outcome of this study was to determine the percentage of patients who filled an outpatient buprenorphine prescription after undergoing inpatient induction.

Monoclonal Antibody Reagent Stability and Expiry Recommendation Combining Experimental Data with Mathematical Modeling.

Monoclonal antibodies (mAbs) are widely used as critical reagents in analytical assays. While regulatory guidelines exist for stability monitoring of biopharmaceutical antibodies, they do not apply directly to the stability of mAbs used as assay reagent. We investigated alternative approaches to real-time stability monitoring of assay reagents. We compared functional (ELISA and cell-based) and biochemical (aggregation, deamidation) assay results using temperature-stressed mAb reagents. Data from both assay groups were compared for indications of antibody degradation. Arrhenius model kinetics was used to further extrapolate stability trends. Changes detected by traditionally monitored biochemical changes were not directly predictive of assay function. Instead, monitoring of reportable results was a closer indication of changes in assay performance related to mAb degradation. Using Arrhenius kinetic modeling, we combined forced degradation of individual reagents with reportable assay results to classify reagents into risk groups with associated re-evaluation and monitoring plans. This combined approach mitigates risk by monitoring each mAb reagent individually under stressed conditions while streamlining expiry assignment through simplified Arrhenius kinetics with only limited real-time stability data.

Rural Oral and Maxillofacial Surgeon Case Mix Leads to Lower Medicare Reimbursement.

PURPOSE: A relative paucity of literature exists analyzing rural-urban differences in Medicare insurance claims by oral and maxillofacial surgeons (OMSs). The purpose of this study is to compare Medicare utilization, billing practices, and reimbursement rates between rural OMSs and their urban counterparts. METHODS: This cross-sectional study examines Medicare claims data from the 2017 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File. The primary predictor variable was the provider Rural-Urban Commuting Area Code (rural vs urban). The primary outcome variable was the total Medicare standardized payment amount per OMS. Additional variables include total number of services provided, total unique Healthcare Common Procedure Coding System codes submitted, total submitted charge amount for all services, mean beneficiary hierarchical condition category, and the total Medicare allowed/payment amount for all services. Descriptive statistics were calculated and continuous variables were compared using nonparametric Mann-Whitney U tests. RESULTS: The analysis cohort had 921 OMSs who recorded 114,169 Part B services in 2017. Urban OMSs billed more services compared to rural OMSs, saw patients with a higher average hierarchical condition category score, and submitted more claims per beneficiary. The mean reimbursement-to-charge ratio was higher among rural OMSs, although the mean payment per service was higher among urban surgeons. CONCLUSIONS: Rural OMSs bill fewer unique codes and treat less medically complex patients compared with their urban counterparts. Rural surgeons were reimbursed proportionally higher for their total submitted charges than urban surgeons; however, they were reimbursed less for each individual service provided. These differences may be attributable to the Centers for Medicare & Medicaid Services Multiple Procedure Payment Reduction policy and provider case mix.

Assessment of Risk Factors for Suicide Among US Health Care Professionals.

Importance: Burnout among health care professionals has been increasingly associated with suicide risk. An examination of possible risk factors may help in the prevention of suicide among health care professionals. Objective: To assess suicide risk factors for 3 categories of health care professionals (surgeons, nonsurgeon physicians, and dentists) compared with non-health care professionals. Design, Setting, and Participants: Data from the National Violent Death Reporting System were reviewed to identify all individuals who died by suicide in the United States between January 1, 2003, and December 31, 2016. Individuals were divided into health care professionals and non-health care professionals (general population), with the health care professionals further categorized into surgeons, nonsurgeon physicians, and dentists. The covariates of suicide decedents included demographic characteristics (age, sex, race, and marital status), medical history (mental illness, substance use, and physical health), and documented factors associated with the suicide death (job, intimate partner, financial, legal, and other problems). Data were analyzed from October 2 to December 17, 2019. Main Outcomes and Measures: In this analysis, the outcome variable was occupation, with health care professionals overall and by category compared with the general population. Multiple logistic regression analyses with backward stepwise selection were performed. Results: A total of 170 030 individuals who died by suicide between 2003 and 2016 were identified. Of those, 767 individuals (0.5%) were health care professionals (mean [SD] age, 59.6 [15.6] years; 675 men [88.0%]; 688 white [89.7%]), with the remainder of the sample (95.5%) comprising the general population (mean [SD] age, 46.8 [31.5] years; 77.7% men; 87.8% white). A total of 485 health care professionals (63.2%) were nonsurgeon physicians, 179 professionals (23.3%) were dentists, and 103 professionals (13.4%) were surgeons. Compared with the general population, risk factors for suicide among health care professionals included having Asian or Pacific Islander ancestry (odds ratio [OR], 2.80; 95% CI, 1.96-3.99; P < .001), job problems (OR, 1.79; 95% CI, 1.49-2.17; P < .001), civil legal problems (OR, 1.61; 95% CI, 1.15-2.26; P = .006), and physical health problems (OR, 1.40; 95% CI, 1.19-1.64; P < .001) and currently receiving treatment for mental illness (OR, 1.45; 95% CI, 1.24-1.69; P < .001). Compared with the general population, health care professionals had a lower risk of suicide if they had black ancestry (OR, 0.55; 95% CI, 0.36-0.84; P < .001) or were female (OR, 0.44; 95% CI, 0.35-0.55; P < .001) or unmarried (OR, 0.36; 95% CI, 0.31-0.42; P < .001). Health care professionals who died by suicide were also less likely to have problems with intimate partners (OR, 0.71; 95% CI, 0.60-0.86; P < .001) or alcohol use (OR, 0.58; 95% CI, 0.45-0.73; P < .001) compared with the general population. Surgeons had a higher risk of suicide compared with the general population if they were older, male, married, had Asian or Pacific Islander ancestry, were currently receiving treatment for mental illness, or had problems with their job or alcohol use. Compared with their nonsurgeon physician colleagues, surgeons had a higher risk of suicide if they were male, older, married, or currently receiving treatment for mental illness. Conclusions and Relevance: This study highlights risk factors for suicide among health care professionals, with additional analyses of surgeon-specific risk factors. The results may be useful in improving the detection of burnout and the development of suicide prevention interventions among health care professionals.