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BACKGROUND: In 2018, a set of entrustable professional activities (EPAs) and procedural skills assessments were developed for anesthesiology training, but they did not assess all the Accreditation Council for Graduate Medical Education (ACGME) milestones. The aims of this study were to (1) remap the 2018 EPA and procedural skills assessments to the revised ACGME Anesthesiology Milestones 2.0, (2) develop new assessments that combined with the original assessments to create a system of assessment that addresses all level 1 to 4 milestones, and (3) provide evidence for the validity of the assessments. METHODS: Using a modified Delphi process, a panel of anesthesiology education experts remapped the original assessments developed in 2018 to the Anesthesiology Milestones 2.0 and developed new assessments to create a system that assessed all level 1 through 4 milestones. Following a 24-month pilot at 7 institutions, the number of EPA and procedural skill assessments and mean scores were computed at the end of the academic year. Milestone achievement and subcompetency data for assessments from a single institution were compared to scores assigned by the institution’s clinical competency committee (CCC). RESULTS: New assessment development, 2 months of testing and feedback, and revisions resulted in 5 new EPAs, 11 nontechnical skills assessments (NTSAs), and 6 objective structured clinical examinations (OSCEs). Combined with the original 20 EPAs and procedural skills assessments, the new system of assessment addresses 99% of level 1 to 4 Anesthesiology Milestones 2.0. During the 24-month pilot, aggregate mean EPA and procedural skill scores significantly increased with year in training. System subcompetency scores correlated significantly with 15 of 23 (65.2%) corresponding CCC scores at a single institution, but 8 correlations (36.4%) were <30.0, illustrating poor correlation. CONCLUSIONS: A panel of experts developed a set of EPAs, procedural skill assessment, NTSAs, and OSCEs to form a programmatic system of assessment for anesthesiology residency training in the United States. The method used to develop and pilot test the assessments, the progression of assessment scores with time in training, and the correlation of assessment scores with CCC scoring of milestone achievement provide evidence for the validity of the assessments.

Abstract Disclosure: B. Clarke: Advisory Board Member; Self; Ascendis Pharma, Takeda, Entera-Bio, Extend-Bio, Amolyt. Consulting Fee; Self; Ascendis Pharma, Takeda, Entera-Bio, Extend-Bio, Amolyt. Grant Recipient; Self; Ascendis Pharma, Takeda. Research Investigator; Self; Ascendis Pharma, Takeda. Other; Self; Ascendis Pharma, Takeda, Entera-Bio, Extend-Bio, Amolyt. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Alexion Pharmaceuticals, Inc., Ascendis Pharma, Takeda, Ultragenyx. Consulting Fee; Self; Amgen Inc, Alexion Pharmaceuticals, Inc., Amolyt, Ascendis Pharma, Ultragenyx. Grant Recipient; Self; Amolyt. Research Investigator; Self; Radius Health, Inc, Takeda, Ultragenyx, Amolyt, Ascendis Pharma, Chugai. Speaker; Self; Amgen Inc. Other; Self; Amgen Inc, Alexion Pharmaceuticals, Inc., Ascendis Pharma, Takeda, Ultragenyx. M.R. Rubin: Research Investigator; Self; Chugai Pharma. P.E. Schwarz: Stock Owner; Self; Novo Nordisk, Genmab. T.J. Vokes: Consulting Fee; Self; Takeda, Ascendis Pharma. Research Investigator; Self; Ascendis Pharma, Radius Health, Inc. D.M. Shoback: Research Investigator; Self; Bone Health Tech. C. Gagnon: Advisory Board Member; Self; Novo Nordisk. Grant Recipient; Self; Shire, Takeda, Ascendis Pharma. Research Investigator; Self; Novo Nordisk. Other; Self; Amgen Inc. A. Palermo: Consulting Fee; Self; Theramex, Bruno, Farmaceutici, Amgen Inc. Grant Recipient; Self; Amgen Inc. Research Investigator; Self; Amgen Inc, Shire, Ascendis Pharma. Speaker; Self; UCB, Amgen Inc. L.G. Abbott: Advisory Board Member; Self; Ascendis. Research Investigator; Self; Takeda, Shire, Ascendis Pharma. Speaker; Self; Abbott Laboratories, Clarus. Other; Self; Ascendis. L.C. Hofbauer: Advisory Board Member; Self; Amgen Inc, UCB. Other; Self; Amgen Inc, UCB. L. Kohlmeier: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc., Ascendis Pharma. Research Investigator; Self; Ascendis Pharma. Speaker; Self; Amgen Inc, Radius Health, Inc, Alexion Pharmaceuticals, Inc., Ascendis Pharma. Other; Self; Amgen Inc, Radius Health, Inc, Alexion Pharmaceuticals, Inc., Ascendis Pharma, MediMaps. F. Cetani: None. S. Phil: Employee; Self; Ascendis Pharma. X. An: Employee; Self; Ascendis Pharma. A.R. Smith: Employee; Self; Ascendis Pharma. B. Lai: Employee; Self; Ascendis Pharma. J. Le: Employee; Self; Ascendis Pharma. J. Ukena: Employee; Self; Ascendis Pharma. C. Sibley: Employee; Self; Ascendis Pharma. A. Shu: Employee; Self; Ascendis Pharma. L. Rejnmark: Advisory Board Member; Self; Takeda, Amolyt. Research Investigator; Self; Takeda, Kyowa Kirin International, Ascendis Pharma, Calcilytix Therapeutics. Other; Self; Calcilytix Therapeutics. Objective: Evaluate the long-term efficacy and safety of TransCon PTH as a potential hormone replacement therapy for hypoparathyroidism. Methods: PaTHway is a phase 3 trial of TransCon PTH with a placebo (PBO)-controlled 26-week blinded period and a 156-week open-label extension (OLE) period. Results through Week 52 (26 weeks blinded + 26 weeks OLE) are reported. Three-component efficacy endpoint: normal serum calcium (8.3-10.6 mg/dL) and independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D). Other endpoints: Hypoparathyroidism Patient Experience Scale (HPES); 36-Item Short Form Survey (SF-36); bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA); bone turnover markers (BTM) procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTx). Safety was assessed by 24-hour urine calcium and reported treatment-emergent adverse events (TEAEs). Results: Of the 82 participants given study drug, 79 completed blinded treatment and entered the OLE, and 78 (59 TransCon PTH/TransCon PTH, 19 PBO/TransCon PTH) completed Week 52. Overall at Week 52, 81% (63/78) met the efficacy endpoint, 95% (74/78) achieved independence from conventional therapy, and none required active vitamin D. Mean albumin-adjusted serum calcium was within the normal range at all time points in the OLE (8.9 mg/dL at Week 52). Mean Week 52 HPES scores showed sustained improvement from baseline in disease-related symptoms and the impact of hypoparathyroidism on physical functioning and daily life. Mean Week 52 SF-36 physical functioning scores also remained above baseline. In the TransCon PTH/TransCon PTH group, mean BMD corrected Z-scores trended toward norms from baseline to Weeks 26 and 52:1.5, 0.7, 0.7 at the lumbar spine (L1-L4); 0.8, 0.3, 0.3 at femoral neck; 0.9, 0.5, 0.4 at total hip; and 0.3, 0.3, 0.3 at distal 1/3 radius; P1NP peaked at Week 26 and CTx at Week 12. Smaller incremental changes were seen in BMD and BTM from Weeks 26 to 52 than baseline to Week 26. In the PBO/TransCon PTH group, changes in BMD and BTM from Week 26 to 52 resembled those in the TransCon PTH/TransCon PTH group from baseline to Week 26. Mean 24-hour urine calcium excretion decreased from 376 mg/day at baseline to 195 mg/day at Week 52. Most TEAEs were mild or moderate and none led to discontinuation of the study drug or trial. Conclusions: At Week 52 of the PaTHway trial, TransCon PTH showed a similar sustained efficacy, safety, and tolerability profile to that of Week 26, demonstrating its potential as a hormone replacement therapy for adults with hypoparathyroidism. Indices of skeletal dynamics trended toward age- and sex-matched norms in the TransCon/TransCon PTH group. TransCon PTH treatment in the PBO/TransCon PTH group showed rapid improvement in all outcomes in the first 26 weeks of the OLE consistent with the pattern in the TransCon PTH group during the blinded period. Presentation: Saturday, June 17, 2023

Abstract Prior to the 1970s, blending food and liquids and putting them through an enteral access device (EAD) was the most common form of enteral nutrition (EN). However, in the 1970s, blenderized tube feedings (BTFs) became less popular due to the emergence of modern commercial enteral formulas (CEFs). Recently, a cultural shift toward consuming a natural diet, consisting of whole foods, has led to a resurgence in the use of BTF. The increasing use of BTF in a variety of patient care settings identifies a need for practice recommendations that provide guidance for nutrition professionals and patients. Members of the American Society for Parental and Enteral Nutrition (ASPEN) Enteral Nutrition Committee identified salient clinical questions concerning BTF, conducted a comprehensive literature search, and subsequently developed practice recommendations pertaining to the use of BTF. This paper was approved by the ASPEN 2022–2023 Board of Directors.

Abstract Background Published data on the risk of venous thromboembolism (VTE) with coronavirus disease 2019 (COVID-19) vaccines are scarce and inconclusive, leading to an unmet need for further studies. Methods A retrospective, multicentered study of adult patients vaccinated for one of the three approved COVID-19 vaccines in the United States of America and a pre-COVID-19 cohort of patients vaccinated for influenza at two institutions: Mayo Clinic Enterprise sites and the Medical College of Wisconsin, looking at rate of VTE over 90 days. VTE was identified by applying validated natural language processing algorithms to relevant imaging studies. Kaplan–Meier curves were used to evaluate rate of VTE and Cox proportional hazard models for incident VTE after vaccinations. Sensitivity analyses were performed for age, sex, outpatient versus inpatient status, and type of COVID-19 vaccine. Results A total of 911,381 study subjects received COVID-19 vaccine (mean age: 56.8 [standard deviation, SD: 18.3] years, 55.3% females) and 442,612 received influenza vaccine (mean age: 56.5 [SD: 18.3] years, 58.7% females). VTE occurred within 90 days in 1,498 (0.11%) of the total 1,353,993 vaccinations: 882 (0.10%) in the COVID-19 and 616 (0.14%) in the influenza vaccination cohort. After adjusting for confounding variables, there was no difference in VTE event rate after COVID-19 vaccination compared with influenza vaccination (adjusted hazard ratio: 0.95 [95% confidence interval: 0.85–1.05]). No significant difference in VTE rates was observed between the two cohorts on sensitivity analyses. Conclusion In this large cohort of COVID-19-vaccinated patients, risk of VTE at 90 days was low and no different than a pre-COVID-19 cohort of influenza-vaccinated patients.

Abstract Background Warfarin monitoring may be done at the point-of-care (POC) at home, in a clinic environment, or be performed using plasma specimens in a central laboratory. With a goal of standardizing International Normalization Ratio (INR) measurements and improving data integrity by enabling electronic transmission of results from any location, we evaluated two POC INR devices against an internal plasma INR reference method. Methods We conducted a multicenter study to test the accuracy of two commercially available point of care devices: Coag-Sense PT2 Meter (Coagusense, Inc., Fremont, CA) and CoaguChek XS Pro or XS Plus (Roche Diagnostics, Indianapolis, IN) compared with plasma INR values among warfarin treated patients. Bias and linear regression analysis were assessed for device-plasma INR comparisons. Warfarin dosing decisions were assessed for each device compared to an internal plasma INR reference method (Instrumentation Laboratories ACLTOP 500, 550, 750 analyzers (Werfen Diagnostics, Bedford MA) in one of three CLIA-certified laboratories. The thromboplastin used at our institution for INR measures is HemosIL RecombiPlasTin 2G (R2G) reagent (Werfen Diagnostics, Bedford MA) which has an International Sensitivity Index (ISI) of 1.0. Results Two hundred ninety-nine warfarin patients treated across three Mayo Clinic sites agreed to participate in the study. Common anticoagulant indications were atrial fibrillation (63.9%), venous thromboembolism (21.7%) and heart valve prosthesis (15.4%) with a 2.0–3.0 INR target range for 93.6% of patients. For the CoaguChek devices, 81.3% of values fell within 0.2 INR units of plasma INR referent and 95.3% within 0.4 units. The correlation between CoaguChek whole blood and plasma INR was excellent (R2 = 0.93). For the Coag-Sense device, 34.1% of values fell within 0.2 INR units and 60.2% within 0.4 INR units of plasma INR values, with a slightly weaker correlation between Coag-Sense whole blood and plasma INR (R2 = 0.83; P &lt; 0.0001). Mean (± standard deviation) deviation from plasma INR was 0.04 ± 0.2 for CoaguChek compared to 0.4 ± 0.3 for Coag-Sense (P &lt; 0.0001). The difference between POC devices was largely attributed to systematic negative bias between Coag-Sense and ACL TOP plasma INR values. Using the plasma INR as the reference method for dosing decision making, appropriate dosing recommendations would have occurred for 97.7% of CoaguChek and 81.6% of Coag-Sense results. Conclusion Compared to our institution's plasma reference method, INR values obtained from the CoaguChek devices (XS Pro and XS Plus) exhibited less systematic bias compared to the Coag-Sense values. This translates to greater percentage of concordant management decisions between POC and laboratory plasma INR methods when the CoaguChek device is used.

BACKGROUND The long-term efficacy and safety of hyaluronic acid fillers injected into the neck have yet to be analyzed in a prospective trial in the United States. OBJECTIVE Analyze the long-term efficacy and safety of a hyaluronic acid filler for static horizontal neck rhytids. MATERIALS AND METHODS Twenty-six subjects were enrolled in the study. Six subjects were randomized to receive saline and 20 subjects were randomized to receive HARR. All subjects were randomized to use a cannula on 1 side and needle on the other with optional retreatment on day 30 and optional crossover treatment with different assignment on day 60. The subjects were graded using the Transverse Neck Line Scale, Canfield photography, and the Global Aesthetic Improvement Scale on day 360. RESULTS A significant improvement from baseline on day 360 was achieved on the Transverse Neck Line Scale according to the blind evaluator, subjects, and investigator without any delayed-onset or prolonged side effects. There was no significant difference in the average improvement from the short-term analysis on day 60 to the long-term analysis on day 360. CONCLUSION HARR achieved significant long-term improvement in static horizontal neck rhytids without any long-term side effects.

PURPOSE The Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) is a phase II platform trial that uses response adaptive randomization and genomic profiling to efficiently identify novel therapies for phase III testing. Three initial experimental arms (abemaciclib [a cyclin-dependent kinase [CDK]4/6 inhibitor], neratinib [an epidermal growth factor receptor [EGFR]/human epidermal growth factor receptor 2 inhibitor], and CC-115 [a deoxyribonucleic acid–dependent protein kinase/mammalian target of rapamycin inhibitor]) were simultaneously evaluated against a common control arm. We report the results for each arm and examine the feasibility and conduct of the adaptive platform design. PATIENTS AND METHODS Patients with newly diagnosed O 6 -methylguanine–DNA methyltransferase-unmethylated glioblastoma were eligible if they had tumor genotyping to identify prespecified biomarker subpopulations of dominant glioblastoma signaling pathways (EGFR, phosphatidylinositol 3-kinase, and CDK). Initial random assignment was 1:1:1:1 between control (radiation therapy and temozolomide) and the experimental arms. Subsequent Bayesian adaptive randomization was incorporated on the basis of biomarker-specific progression-free survival (PFS) data. The primary end point was overall survival (OS), and one-sided P values are reported. The trial is registered with ClinicalTrials.gov (identifier: NCT02977780 ). RESULTS Two hundred thirty-seven patients were treated (71 control; 73 abemaciclib; 81 neratinib; 12 CC-115) in years 2017-2021. Abemaciclib and neratinib were well tolerated, but CC-115 was associated with ≥ grade 3 treatment-related toxicity in 58% of patients. PFS was significantly longer with abemaciclib (hazard ratio [HR], 0.72; 95% CI, 0.49 to 1.06; one-sided P = .046) and neratinib (HR, 0.72; 95% CI, 0.50 to 1.02; one-sided P = .033) relative to the control arm but there was no PFS benefit with CC-115 (one-sided P = .523). None of the experimental therapies demonstrated a significant OS benefit ( P > .05). CONCLUSION The INSIGhT design enabled efficient simultaneous testing of three experimental agents using a shared control arm and adaptive randomization. Two investigational arms had superior PFS compared with the control arm, but none demonstrated an OS benefit. The INSIGhT design may promote improved and more efficient therapeutic discovery in glioblastoma. New arms have been added to the trial.

ImportanceLip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.ObjectiveTo analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence ReviewThe incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.FindingsIn 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and RelevanceIn this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

AbstractBackgroundThe PI3K/AKT pathway, extensively studied in cancer, is vital for regulating cell metabolism, differentiation, and proliferation. Pathogenic variants in the PIK3R1 gene, which encodes three regulatory units of class IA PI3Ks, have been found in affected tissue of individuals with vascular lesions. These variants predominantly occur in the iSH2 domain, disrupting inhibitory contacts with the catalytic unit and leading to PI3K activation. Germline variants in this gene are also linked to an immunological condition called Activated PI3K delta syndrome type 2 (APDS2).MethodsThis is a case report and literature review. Clinical data were retrieved from medical records.ResultsA male patient presented with extensive vascular malformation covering over 90% of his body, along with complete 2–3 toe syndactyly, suggesting a vascular malformation syndrome called PROS. Low levels of IgA and IgG were detected. The patient achieved his developmental milestones and had above‐average weight, height, and head circumference. Exome sequencing of skin and blood DNA revealed a de novo variant in PIK3R1 (c.1746‐2A>G, p.?) in 9% of the patient's blood cells and 25% of cultured fibroblasts. Initially, classified as a variant of uncertain significance, this variant was later confirmed to be the cause.ConclusionsThis is the first intronic SNV in a canonical splice site within iSH2 described, highlighting the importance of iSH2 in the regulation of the PI3K/AKT pathway and its involvement in the development of vascular overgrowth and antibody deficiency.