BACKGROUND:The use of validated risk stratification tools for the workup of suspected pulmonary embolism (PE) is a recommendation of the American Society of Hematology and the American College of Emergency Physicians. METHODS:We designed and implemented electronic clinical pretest probability (PTP) tools for use in emergency departments (ED). Overall, 38 EDs (tertiary and regional EDs) in the United States were involved across three health systems. PTP use was analyzed between September 12, 2022 and January 11, 2023 in 270,247 ED visits. PTP use was examined in terms of the percentage of visits for which patients underwent computed tomography pulmonary angiography (CTPA). Each site chose the 3-tier Wells' score for implementation and Site 2 designed a combined Wells', pulmonary embolism rule-out criteria (PERC), and YEARS score. RESULTS:At Site 3, forced use resulted in documented PTP scores in 49-53% of ordered CTPAs. At Sites 1 and 2, where PTP scores were optional, documented PTP scores occurred in 2-3% and 1-3% of CTPA orders, respectively. At Site 1, the use of PTP increased slightly over the study period, with signs that PE yield on imaging was also increasing (3.4-5.9%). At Site 2, PE yield on imaging was 9-10%, and it remained similar, with similar use of PTP tools over the study period. PE yield (6-8%) on imaging also remained similar throughout the study at Site 3. CONCLUSIONS:Guideline-endorsed PTP scores for PE at three independent health systems in the United States did not increase PE yield on imaging. Novel implementation strategies involving interdisciplinary teams are urgently needed.

Guidelines for diagnosing pulmonary embolism (PE) start with a risk assessment using a pretest probability (PTP) tool, followed by D-dimer testing or computed tomography pulmonary angiography (CTPA) depending on risk. The project aimed to develop an electronic clinical quality measure (eCQM) to encourage broader use of a validated PTP scoring tool in emergency departments (EDs) to more accurately diagnose PE and to reduce unnecessary CTPAs. To identify a value set to accurately identify CTPA and abnormal D-dimer tests using standard classification systems and clinical vocabularies (ie, Current Procedural Terminology [CPT], Logical Observation Identifiers Names and Codes [LOINC], systematized nomenclature of medicine clinical terms [SNOMED CT]) across 3 academic United States health care systems. A comprehensive value set to identify CTPAs was selected, which contained 31 codes. Additionally, each health care system had unique, site-specific codes to more granularly identify CTPAs. Three health care systems representing 38 EDs from across the country submitted data from all ED encounters between September 12, 2022, and January 11, 2023. Imaging types were reviewed from each of the CPT codes and LOINC. The project evaluated whether a D-dimer was obtained using CPT and LOINC and whether the D-dimer result was elevated using SNOMED CT. The number of ED encounters, PTP use, and diagnosis of PE using different codes were determined. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value for selected codes were calculated. Over a 4-month study period, 270,214 encounters were included from 38 EDs. 11,794 ED encounters with CTPAs during the study period, using the site-specific codes were identified. The comprehensive value set had a PPV of 63.4%. Restricting the CTPA value set to CPT code 71275 or LOINC 88322-3 improved the PPV to 82% with 100% sensitivity and 99% specificity. The restricted value set captured the highest proportion of relevant site-specific codes. D-dimer values were identified using LOINC codes 48065-7 and 91556-1 at Site 1 and 48067-3 at Site 2. SNOMED CT codes were not used at any site to identify elevated D-dimer results. Different D-dimer tests with different normal ranges were used at each site, and only one site provided an abnormal flag for D-dimer results. Heterogeneity in the use of nationally standardized codes for labs and imaging tests limits the ability to measure and compare quality across health care organizations for CTPA and D-dimer results. Restricting the identification of CTPA to CPT Code 71275 or LOINC 88322-3 resulted in high sensitivity and specificity, but false positives remain. Additionally, coding for an abnormal D-dimer test result is not standardized across institutions. Therefore, the currently available value sets cannot be used to develop eCQMs whose aim is to evaluate whether CTPA is ordered appropriately based on the PTP risk level and laboratory testing.

Background: The risk of venous thromboembolism (VTE) increases during pregnancy and continues to rise throughout pregnancy with maximum risk in the postpartum period. The guidelines that stratify patients into VTE risk categories are conflicting. Aims: (1) Evaluate the incidence of postpartum VTE (VTE within 3 months of delivery) over 1 year. (2) Determine the number of patients that would have received VTE prophylaxis based on different society recommendations. (3) Determine the number of patients with VTE that would possibly been prevented with different society recommendations. Methods: Characteristics of 3190 patients who underwent delivery at our medical center were investigated for incidence and risk factors for VTE. Data was collected using the International Classification of Diseases codes and by chart review. Descriptive statistics were calculated. Results: The incidence of postpartum VTE in our patient cohort (n=3190) was 0.25% (8/3190). Most patients were aged ≥30 (66.6%), white (61%) and had BMI >30 (61.1%). The number of patients who had previous history of cancer, lupus, inflammatory bowel disease and sickle cell disease were 77 (2.4%), 12 (0.4%), 25 (0.8%), and 2 (0.1%), respectively. Sixteen (0.5%) patients had a history of provoked VTE, and 76 (2.4%) patients had a family history of VTE. The proportion of patients who had cesarean delivery, postpartum hemorrhage, pre-eclampsia, and multiple gestation pregnancy were 571 (17.9%), 340 (10.7%), 295 (9.2%), and 40 (1.3%), respectively. 46 (1.4%) patients had prolonged hospitalization of >3 days, who were deemed to have decreased mobility, which is an important risk factor for VTE. Mechanical prophylaxis was used postpartum in 465 patients (14.4%), low molecular weight heparin in 55 patients (1.7%), and other anticoagulation in 20 patients (0.6%). Two of the patients with a VTE event within 90 days postpartum received prophylaxis in our cohort. The percentage of patients who would have received pharmacologic VTE prophylaxis based on Royal College of Obstetricians and Gynecologists (RCOG) risk factors criteria, Society of Obstetricians and Gynaecologists of Canada (SOGC), and 'Eubanks’ risk scoring criteria was 61.3% (n=1954), 33.8% (n=1077), and 15% (n=513), respectively. RCOG predicted 7 of the 8 VTE events compared to only 2 of the VTE events predicted by Eubanks. Sensitivity of RCOG was high at 87.5% whereas specificity of Eubanks was high at 0.84. SOGC predicted 4 of the VTE events with a specificity of 0.67 and sensitivity of 0.50. Conclusion: The number of postpartum patients recommended to receive peripartum anticoagulation varies widely depending on the risk scoring tool employed. Optimized risk stratification for peripartum VTE prophylaxis is needed.

Importance:Accurate prediction of surgical case duration is critical for operating room (OR) management, as inefficient scheduling can lead to reduced patient and surgeon satisfaction while incurring considerable financial costs. Objective:To evaluate the feasibility and accuracy of large language models (LLMs) in predicting surgical case length using unstructured clinical data compared to existing estimation methods. Design, Setting, and Participants:This was a retrospective study analyzing elective surgical cases performed between January 2017 and December 2023 at a single academic medical center and affiliated community hospital ORs. Analysis included 125 493 eligible surgical cases, with 1950 used for LLM fine-tuning and 2500 for evaluation. An additional 500 cases from a community site were used for external validation. Cases were randomly sampled using strata to ensure representation across surgical specialties. Exposures:Eleven LLMs, including base models (GPT-4, GPT-3.5, Mistral, Llama-3, Phi-3) and 2 fine-tuned variants (GPT-4 fine-tuned, GPT-3.5 fine-tuned), were used to predict surgical case length based on clinical notes. Main Outcomes and Measures:The primary outcome was average error between predicted and actual surgical case length (wheels-in to wheels-out time). The secondary outcome was prediction accuracy, defined as predicted length within 20% of actual duration. Results:Fine-tuned GPT-4 achieved the best performance with a mean absolute error (MAE) of 47.64 minutes (95% CI, 45.71-49.56) and R2 of 0.61, matching the performance of current OR scheduling (MAE, 49.34 minutes; 95% CI, 47.60-51.09; R2, 0.63; P = .10). Both GPT-4 fine-tuned and GPT-3.5 fine-tuned significantly outperformed current scheduling methods in accuracy (46.12% and 46.08% vs 40.92%, respectively; P < .001). GPT-4 fine-tuned outperformed all other models during external validation with similar performance metrics (MAE, 48.66 minutes; 95% CI, 45.31-52.00; accuracy, 46.0%). Base models demonstrated variable performance, with GPT-4 showing the highest performance among non-fine-tuned models (MAE, 59.20 minutes; 95% CI, 56.88 - 61.52). Conclusion and Relevance:The findings in this study suggest that fine-tuned LLMs can predict surgical case length with accuracy comparable to or exceeding current institutional scheduling methods. This indicates potential for LLMs to enhance operating room efficiency through improved case length prediction using existing clinical documentation.

Although several systematic reviews found that ambulatory diabetes mellitus (DM) interventions involving pharmacists generally yielded better outcomes than the ones that did not, existing studies have limitations in rigor and study design. To examine the intention-to-treat effects of the Ambulatory Diabetes Outreach Program (ADOP) on participants’ A1c values and healthcare utilization over a 52-month follow-up period. Difference-in-differences with staggered adoption. Specifically, we employed the Callaway and Sant’Anna’s “group-time average treatment effect” estimator using not-yet treated as controls adjusting for patient’s age, BMI, sex, race, comorbidity, payor, and socio-economic status. All patients with at least one ADOP treatment encounter from July 2017 to October 2021, regardless of program completion or length of exposure to the program. ADOP, a collaborative population health program led by pharmacists and nurse specialists to provide individualized type 2 DM management and education within a large and diverse health system. Patients’ A1c values and healthcare utilization, including inpatient admission, inpatient days, and numbers of visits to the emergency department, urgent care, and primary care in recent 6 months. ADOP participation was associated with an overall average reduction of 1.04 percentage points (95

Supplementary Figure 6. Kaplan-Meier curve analysis examining MPS1 expression (red- high expression, black- low expression) and overall survival association in 1115 breast (A) and 1405 lung (B) cancer patients using univariate analysis using KM-Plotter (www.kmplot.com).

Supplementary Figure 1: Inhibition of MPS1 activity compromises the viability of GBM tumor cells.

INTRODUCTION:Evidence suggests that inpatients who develop delirium experience worse outcomes. Although there is reason to believe that COVID-positive patients may be at a higher risk for developing delirium, little is known about the association between COVID-19 and delirium among hospitalized patients outside the intensive care unit (ICU). This study aimed to examine (1) the independent association between COVID-19 infection and the development of delirium among all non-ICU patients and (2) the risk factors associated with developing delirium among patients admitted with COVID-19, with a special focus on presenting symptoms.METHODS:Using electronic health record (EHR) data of adults admitted to any general medical unit at a large academic medical center from July 2020 through February 2021, we used a cross-sectional multivariable logistic regression to estimate the associations, while adjusting for patients' sociodemographic, clinical characteristics, delirium-free length of stay, as well as time fixed effects.RESULTS:Multivariable regression estimates applied to 20 509 patients hospitalized during the study period indicate that COVID-19-positive patients had 72% higher relative risk (odds ratio 1.72; 95% CI, 1.31 - 2.26; P < 0.001) of developing delirium than the COVID-19-negative patients. However, among the subset of patients admitted with COVID-19, having any COVID-19-specific symptoms was not associated with elevated odds of developing delirium compared to those who were asymptomatic, after controlling for potential confounders.CONCLUSIONS:COVID-19 positivity was associated with higher odds of developing delirium among patients during their non-ICU hospitalization. These findings may be helpful in targeting the use of delirium prevention strategies among non-ICU patients.

BACKGROUND:The Medicare Annual Wellness Visit is a preventive visit that is largely underutilized, a problem further compounded by the COVID-19 pandemic.METHODS:We implemented a digital outreach intervention to improve Annual Wellness Visit scheduling in our health system. Using a bulk outreach functionality in the electronic medical record, we sent a message to patients due for an Annual Wellness Visit and analyzed the efficacy of this message on scheduling rates while also assessing its impact by race.RESULTS:Patients who read the message were 40% more likely to schedule an Annual Wellness Visit (OR 1.42; 95% CI, 1.34 - 1.50) compared to those who did not read the message.DISCUSSION:After this intervention, Annual Wellness Visit scheduling rates increased by 50% for White patients and 325% for Black patients versus prepandemic rates in 2019.

Supplementary Figure 5. To assay nonhomologous end joining (NHEJ), U251 DR-GFP cells were transfected with pCBAScel vector and harvested at 48 hours after indicated treatments. Genomic DNA was harvested for PCR amplification using DR-GFP primers, followed by I-Scel+Bcgl enzyme digestion and PCR products were subjected to gel electrophoresis.

Supplementary Figure 3. Western blot analysis of pDNAPK and DNAPK from 2.5 uM NMS-P715 treated and irradiated (4 Gy) U251 cells.

Supplementary Figure 2. Molecular profiling reveals changes in genes associated with DNA replication, recombination and repair.

Introduction: Use of validated risk stratification tools for work up of suspected pulmonary embolism (PE) is an endorsed recommendation of the American Society of Hematology and the American College of Emergency Physicians. Due to variations in clinical practice, electronic health record (EHR) systems, and medical provider trainings, the use, documentation, and implementation of these tools vary widely. Current processes do not allow for electronic capture and quality reporting at most institutions. Methods: We sought to design and implement clinical pre-test probability (PTP) tools at three large healthcare institutions for use in emergency departments (ED). At each site, a hematologist partnered with ED physician leadership and local information technology experts to design and implement PTP tools in clinical workflows. Overall, 38 EDs (high volume tertiary EDs and smaller regional EDs) located in the United States along the East Coast and Midwest regions were involved. A major goal of implementation was integration into clinical workflow and automatic documentation. After design and implementation, awareness and education of the new EHR tool was distributed electronically to ED providers. After implementation, use of PTP tools was analyzed between September 12, 2022 and January 11, 2023. PTP use was examined as percent of visits for which patients underwent CT pulmonary angiography (CTPA). Results: Each institution chose the 3 tier Wells' Score for implementation while one site designed an integrated Wells'/PERC or YEARS score calculator. Two sites implemented the tool as an optional flowsheet and one site implemented the tool as mandatory parameters within the orders for PE imaging studies. The mandatory tool could be bypassed with prespecified selections or if a D-dimer existed within 48 hours . Complete details of the site-specific implementation are shown in Table 1. Over the 4-month evaluation timeframe, there was a total of 270,214 ED encounters. Uptake and utilization of the PTP tools are shown in Table 2. Use of PTP was highest at the site with forced PTP documentation which ranged from 49-53% of ordered CTPAs, compared to Site 2 where use was 2-3%, and Site 1 where use ranged from 1-3%. At Site 1, use of PTP increased slightly over the study period with signs that PE yield on imaging was increasing as well (3.4% to 5.9%). At Site 2, PE yield on imaging was overall high (9-10%), and remained similar with similar use of PTP tools over the study period. Use of PTP and PE yield (6-8%) on imaging also remained similar throughout the study at Site 3. Conclusion: Forced use of PTP within the orders for CTPA led to the highest use of PTP (Site 3) but this did not result in meaningfully higher PE yield on CTPA compared to the other sites. PE yield at each site was at or above the 5% yield for PE on CTPA which has been previously reported. Given that PTP uptake was relatively stable over the measurement period at Site 2 and 3, this indicates the process had mostly stabilized and that other strategies are needed to improve uptake of PTP, reduce utilization of CTPA, and further increase yield on CTPA. Increasing PTP use and rising PE yield at Site 1 demonstrated ongoing potential for improvements past this study timeframe.

Despite the widespread adoption of early warning systems (EWSs), it is uncertain if their implementation improves patient outcomes. The authors report a pre-post quasi-experimental evaluation of a commercially available EWS on patient outcomes at a 700-bed academic medical center. The EWS risk scores were visible in the electronic medical record by bedside clinicians. The EWS risk scores were also monitored remotely 24/7 by critical care trained nurses who actively contacted bedside nurses when a patient’s risk levels increased. The primary outcome was inpatient mortality. Secondary outcomes were rapid response team calls and activation of cardiopulmonary arrest (code-4) response teams. The study team conducted a regression discontinuity analysis adjusting for age, gender, insurance, severity of illness, risk of mortality, and hospital occupancy at admission. The analysis included 53,229 hospitalizations. Adjusted analysis showed no significant change in inpatient mortality, rapid response team call, or code-4 activations after implementing the EWS. This study confirms the continued uncertainty in the effectiveness of EWSs and the need for further rigorous examinations of EWSs.

Supplementary Figure 4. To assay homologous recombination (HR), U251 DR-GFP cells were transfected with pCBAScel vector and harvested at 48 hours after indicated treatments. GFP+ve cells representing HR repair events were determined by flow cytometry and PCR based assays.

Objective: Use the RE-AIM framework to examine the implementation of a patient contextual data (PCD) Tool designed to share patients' needs, values, and preferences with care teams ahead of clinical encounters.Materials & Methods: Observational study that follows initial PCD Tool scaling across primary care at a Midwestern academic health network. Program invitations, enrollment, patient submissions, and clinician views were tracked over a 1-year study period. Logistic regression modeled the likelihood of using the PCD Tool, accounting for patient covariates.Results: Of 58,874 patients who could be contacted by email, 9,183 (15.6%) became PCD Tool users. Overall, 76% of primary care providers had patients who used the PCD Tool. Older age, female gender, non-minority race, patient portal activation, and Medicare coverage were significantly associated with increased likelihood of use. Number of office visits, medical issues, and behavioral health conditions also associated with use. Primary care staff viewed 18.7% of available PCD Tool summaries, 1.1% to 57.6% per clinic. Discussion: The intervention mainly reached non-minority patients and patients who used more health services. Given the requirement for an email address on file, some patients may have been underrepresented. Overall, patient reach and adoption and clinician adoption, implementation, and maintenance of this Tool were modest but stable, consistent with a non-directive approach to fostering adoption by introducing the Tool in the absence of clear expectations for use.Conclusion: Healthcare organizations must implement effective methods to increase the reach, adoption, implementation, and maintenance of PCD tools across all patient populations. Assisting people, particularly racial minorities, with PCD Tool registration and actively supporting clinician use are critical steps in implementing technology that facilitates care.

Background: Elevated body mass index (BMI) is a risk factor for adverse outcomes following total hip arthroplasty (THA). It is unknown if preoperative weight loss to a BMI <40 kg/m(2) is associated with reduced risk of adverse outcomes. Methods: We retrospectively reviewed elective, primary THA performed at an academic center from 2015 to 2019. Patients were split into groups based on their BMI trajectory prior to THA: BMI consistently <40 ("BMI <40"); BMI >40 at the time of surgery ("BMI >40"); and BMI >40 within 2 years preopera-tively, but <40 at the time of surgery ("Weight Loss"). Length of stay (LOS), 30-day readmissions, and complications as defined by Centers for Medicare and Medicaid Services were compared between groups using parsimonious regression models and Fisher's exact testing. Adjusted analyses controlled for sex, age, and American Society of Anesthesiologists class. Results: In total, 1589 patients were included (BMI <40: 1387, BMI >40: 96, Weight Loss: 106). The rate of complications in each group was 3.5%, 6.3%, and 8.5% and the rate of 30-day readmissions was 3.0%, 4.2%, and 7.5%, respectively. Compared to the BMI <40 group, the weight loss group had a significantly higher risk of 30-day readmission (odds ratio [OR] 2.70, 95% confidence interval [CI] 1.19-6.17, P = .02), higher risk of any complication (OR 2.47, 95% CI 1.09-5.59, P = .03), higher risk of mechanical complications (OR 3.07, 95% CI 1.14-8.25, P = .03), and longer median LOS (16% increase, P = .002). The BMI >40 group had increased median LOS (10% increase, P = .03), but no difference in readmission or complications (P > .05) compared to BMI <40. Conclusion: Weight loss from BMI >40 to BMI <40 prior to THA was associated with increased risk of readmission and complications compared to BMI <40, whereas BMI >40 was not. Level of evidence: Level III -Retrospective Cohort Study. (c) 2021 Elsevier Inc. All rights reserved.