Washington University Research Articles

Economic Analysis of On-Street Parking with Urban Delivery

The surge in online shopping has dramatically increased the demand for short-term curb access for package pickups and deliveries, leading to heightened competition for limited curb space. This paper addresses the problem of how the unique parking demand of deliverers, particularly their parking duration for delivery attempts linked to parking space availability, affects the dynamics of urban curb parking systems. We develop continuum models of a curb parking system and perform analytical analyses to understand the dynamics and steady-state properties of the system under the influence of increased urban deliveries. We conduct comparative statics to examine how various curb management measures, such as pricing, parking duration caps, and dedicated delivery bays, influence the equilibrium conditions, followed by comparisons of the theoretical capacity of these measures. We further demonstrate the working mechanism of delivery bays and their role in forestalling specific failures within a hybrid system with both general parkers and deliverers. Finally, we investigate curb management strategies in nonstationary operational contexts and prescribe the optimal strategies therein. Our findings offer valuable insights into the unique properties that deliverers introduce to curb parking dynamics, highlighting the need for a strategic reevaluation of current management practices. We find that pricing strategies for metered parking to general parkers prove to be more efficient and flexible compared with other interventions. Notably, our analysis suggests that when curb parking pricing is optimally calibrated, the necessity for dedicated delivery bays diminishes. Furthermore, we reveal that optimal curb management strategies could diverge in response to surges in demand, depending on whether the increase sources from general parkers or deliverers. To be effective, the sizing of delivery bays must align with the underlying causes of parking scarcity. History: This paper has been accepted for the Transportation Science Special Section on ISTTT25 Conference. Funding: This work was supported by the George Washington University [University Facilitating Fund]. Supplemental Material: The online appendices are available at https://doi.org/10.1287/trsc.2024.0569 .

Predicting Out-of-Hospital Cardiac Arrest in the General Population Using Electronic Health Records.

The majority of out-of-hospital cardiac arrests (OHCAs) occur among individuals in the general population, for whom there is no established strategy to identify risk. In this study, we assess the use of electronic health record (EHR) data to identify OHCA in the general population and define salient factors contributing to OHCA risk. The analytical cohort included 2366 individuals with OHCA and 23 660 age- and sex-matched controls receiving health care at the University of Washington. Comorbidities, electrocardiographic measures, vital signs, and medication prescription were abstracted from the EHR. The primary outcome was OHCA. Secondary outcomes included shockable and nonshockable OHCA. Model performance including area under the receiver operating characteristic curve and positive predictive value were assessed and adjusted for observed rate of OHCA across the health system. There were significant differences in demographic characteristics, vital signs, electrocardiographic measures, comorbidities, and medication distribution between individuals with OHCA and controls. In external validation, discrimination in machine learning models (area under the receiver operating characteristic curve 0.80-0.85) was superior to a baseline model with conventional cardiovascular risk factors (area under the receiver operating characteristic curve 0.66). At a specificity threshold of 99%, correcting for baseline OHCA incidence across the health system, positive predictive value was 2.5% to 3.1% in machine learning models compared with 0.8% for the baseline model. Longer corrected QT interval, substance abuse disorder, fluid and electrolyte disorder, alcohol abuse, and higher heart rate were identified as salient predictors of OHCA risk across all machine learning models. Established cardiovascular risk factors retained predictive importance for shockable OHCA, but demographic characteristics (minority race, single marital status) and noncardiovascular comorbidities (substance abuse disorder) also contributed to risk prediction. For nonshockable OHCA, a range of salient predictors, including comorbidities, habits, vital signs, demographic characteristics, and electrocardiographic measures, were identified. In a population-based case-control study, machine learning models incorporating readily available EHR data showed reasonable discrimination and risk enrichment for OHCA in the general population. Salient factors associated with OCHA risk were myriad across the cardiovascular and noncardiovascular spectrum. Public health and tailored strategies for OHCA prediction and prevention will require incorporation of this complexity.

Judge rules in favor of former employee

Case name: Buck‐Yael v. Washington University, No. 4:23CV492 (E.D. Mo. 03/28/24).

Ramucirumab in combination with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma: a single-centre, phase 1/2 trial

VEGF, a key mediator of angiogenesis and resistance to immunotherapy, is overexpressed in head and neck squamous cell carcinoma (HNSCC). We aimed to determine the recommended phase 2 dose of ramucirumab, a selective VEGFR2 inhibitor, given with pembrolizumab and the objective response rate of this combination as first-line treatment for recurrent or metastatic HNSCC. In this single-centre, phase 1/2 trial, which was done at Washington University (St Louis, MO, USA), eligible patients were aged 18 years or older with incurable recurrent or metastatic HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. Patients in phase 2 were required to have had no previous systemic therapy for recurrent or metastatic disease. In a dose de-escalation phase 1 design, patients received ramucirumab (starting dose 10 mg/kg given intravenously) and pembrolizumab (200 mg intravenously) on day 1 of each 21-day cycle. The recommended phase 2 dose of ramucirumab was defined as the highest dose at which one or fewer of three patients had dose-limiting toxicity during cycle one (primary endpoint of phase 1). In a Simon's two-stage phase 2 design, patients received the recommended phase 2 dose of ramucirumab and pembrolizumab. Tumour response (primary endpoint of phase 2) was assessed by Response Evaluation Criteria in Solid Tumours (version 1.1). We hypothesised that there would be an objective response rate of 32% or higher (null ≤13%). Eight or more responses among 33 evaluable patients (those with at least one response assessment) was evidence for activity (80% power; one-sided α=0·05). Analyses were done per protocol. The trial is registered with ClinicalTrials.gov, NCT03650764, and is closed to enrolment. Between June 18, 2019, and Feb 11, 2021, three patients enrolled and were treated in phase 1 and 37 patients in phase 2. Median age of all patients was 64 years (IQR 59-72). 36 (90%) of 40 patients were men and four (10%) were women, and 36 (90%) patients were White, three (8%) were Black or African American, and one (3%) was Asian. In phase 1, no dose-limiting toxicity event occurred. The recommended phase 2 dose of ramucirumab was 10 mg/kg. Median follow-up for patients on phase 2 was 14·8 months (IQR 4·9-31·0). In phase 2, 18 (55%; 95% CI 38-70) of 33 evaluable patients had an objective response, including confirmed complete response in 11 patients, confirmed partial response in six patients, and unconfirmed partial response in one patient. The most common grade 3 or worse adverse events were dysphagia (14 [38%] of 37 patients), lung infection (11 [30%]), lymphocyte count decrease (ten [27%]), hypophosphataemia (nine [24%]), and hypertension (eight [22%]). No treatment-related deaths were recorded. Ramucirumab and pembrolizumab were safe to administer to patients with recurrent or metastatic HNSCC, and the objective response rate with this combination as first-line treatment for recurrent or metastatic HNSCC was favourable. Further studies of ramucirumab and pembrolizumab in patients with recurrent or metastatic HNSCC are warranted. Lilly and the Joseph Sanchez Foundation.

Frontline assessors’ opinions about grading committees in a medicine clerkship

BackgroundCollective decision-making by grading committees has been proposed as a strategy to improve the fairness and consistency of grading and summative assessment compared to individual evaluations. In the 2020–2021 academic year, Washington University School of Medicine in St. Louis (WUSM) instituted grading committees in the assessment of third-year medical students on core clerkships, including the Internal Medicine clerkship. We explored how frontline assessors perceive the role of grading committees in the Internal Medicine core clerkship at WUSM and sought to identify challenges that could be addressed in assessor development initiatives.MethodsWe conducted four semi-structured focus group interviews with resident (n = 6) and faculty (n = 17) volunteers from inpatient and outpatient Internal Medicine clerkship rotations. Transcripts were analyzed using thematic analysis.ResultsParticipants felt that the transition to a grading committee had benefits and drawbacks for both assessors and students. Grading committees were thought to improve grading fairness and reduce pressure on assessors. However, some participants perceived a loss of responsibility in students’ grading. Furthermore, assessors recognized persistent challenges in communicating students’ performance via assessment forms and misunderstandings about the new grading process. Interviewees identified a need for more training in formal assessment; however, there was no universally preferred training modality.ConclusionsFrontline assessors view the switch from individual graders to a grading committee as beneficial due to a perceived reduction of bias and improvement in grading fairness; however, they report ongoing challenges in the utilization of assessment tools and incomplete understanding of the grading and assessment process.

Adherence to cancer screening for patients with Li-Fraumeni syndrome: A report on our experience at Fred Hutchinson Cancer Center.

e22553 Background: Li-Fraumeni syndrome (LFS) is a high-risk cancer predisposition syndrome where patients are at risk of developing multiple primary cancers, synchronous, and metachronous cancers in their lifetimes. Patients with LFS often serve as their own advocates to request and receive appropriate cancer screening as few clinicians have experience in caring for them and few clinics are adequately staffed to provide complex cancer screening coordination. Methods: Fred Hutchinson Cancer Center (Fred Hutch) is a large academic cancer care center associated with the University of Washington. In July 2020, Fred Hutch's clinical cancer genetic service launched a high-risk surveillance clinic for patients with hereditary cancer syndromes requiring services from multiple specialties. Our clinic has since helped patients with LFS receive coordinated cancer screening. Here we report on adherence to the Toronto protocol by reviewing patient demographic, cancer history and family history, and genetic records. Furthermore, we report on the number of visits, types of screening, and cancer diagnoses patients with LFS received since enrolling in the high-risk clinic. Results: A total of 112 patients with LFS were seen in the high-risk surveillance clinic between July 2020 and December 2023. Of these patients’ paths reviewed so far, 73 patients established with the clinic and received blood work and/or MRI imaging scans, and 42 were seen in at least one follow up visit. 2 patients with LFS were diagnosed with one or more new cancer diagnosis since enrollment, both have completed treatment, and both are without evidence of disease as of February 2024. Conclusions: The high-risk surveillance clinic was promptly utilized by patients with LFS for coordination of their complex cancer screening needs and to guide their next steps when triaging symptoms and concerns. While the clinic addresses a gap in cancer screening coordination, patients with LFS need wrap around care close to where they live which is difficult to accomplish in the Pacific Northwest.

Evaluating global research trends in special needs dentistry: A systematic bibliometrix analysis.

Special needs dentistry (SND) is a vast and fragmented field of study. This comprehensive bibliometric analysis aimed to evaluate the scope of SND, including the existing knowledge base, distribution structure, quantitative relationships, and research trends. A systematic search was conducted on March 10, 2022, using the Web of Science Core Collection database, covering the period from 1985 to 2021, focusing on studies reporting on special needs populations in a dentally relevant context. Records were title-screened and analyzed for key bibliometric indicators. Among 48,374 articles, 13,869 underwent bibliometric analysis. Peak SND research occurred during 1985-1997. United States led in productivity, trailed by Brazil and Japan. University of Sao Paulo excelled in Brazil, University of Washington and University of North Carolina in the United States. The Journal of Dental Research was the most productive source of research and also had the highest number of citations, followed by Community Dentistry and Oral Epidemiology. Keyword analysis revealed that "elderly", "caries", and "epidemiology" were the most commonly used author keywords. This study represents the first bibliometric analysis of SND literature. It emphasizes the need for increased collaboration between institutions and authors. Furthermore, it suggests focusing on research input from non-dental disciplines and populations with rarer intellectual or developmental conditions.

Lessons learned in migrating from one commercial genetics decision-support tool to another: Assessment of data integrity and utilization readiness.

e23232 Background: Rapid advancements in health information technology have greatly influenced how clinicians engage with patient health data. In the context of clinical genetics, the electronic health record (EHR) often contains a wide array of data to identify patients at elevated risk for hereditary cancer syndromes. However, these data often exist in multiple forms and disparate locations, which in the presence of numerous commercial EHR solutions, results in significant variations in how institutions codify genetic data. Furthermore, within an institution, there is often internal pressure to migrate from one support tool to another, necessitating a focus on data integrity during such a transition. Methods: Fred Hutchinson Cancer Center (Fred Hutch) is a large academic cancer care center associated with the University of Washington. Between July and December 2023, the Fred Hutch Clinical Cancer Genetics and Genetic Counseling Service migrated their family history database from commercial pedigree software, Progeny, to another commercial pedigree and decision-support tool, CancerIQ. Following completion of the data migration on more than 13,000 patient records, study team planned to review a total of 500 randomly selected patient charts in both support tools. Each chart was reviewed to determine: (1) the presence of genetic intake information, (2) the presence and results of genetic testing, if available, and (3) whether the patient met National Comprehensive Cancer Network (NCCN) criteria for testing. A chart was noted to be concordant between the two support tools if there was agreement in all three of the above. Results: So far, a total of 240 patient charts were reviewed between the two support tools. Of these, 226 (94.2%) were noted to be fully concordant. Of the 14 charts that were noted to be discordant, the distribution of the discordant data was: 5 charts differed on whether genetic testing had been ordered, 5 charts differed on the results of the testing (often omitting one or more variants), and 4 differed on whether the patient met NCCN criteria for testing. Conclusions: At our institution, there was high data integrity following migration from one commercial and pedigree-generating software solution to another. While these results can ease clinician concerns following such support tools transitions, it also highlights areas for improvement in how family and patient genetic data is recorded.

Racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer.

1017 Background: Despite well-documented disparities in survival between patients (pts) with Black and White racial backgrounds, there are limited data on racial equity of targeted treatment use for pts with estrogen receptor positive, HER2 negative (ER+/HER2-) metastatic breast cancer (MBC). We evaluated differences in circulating tumor DNA (ctDNA) genomic alterations in Black and White pts with ER+/HER2- MBC. Methods: This retrospective cohort study analyzed a database of 1327 pts with MBC who were treated at Washington University in St. Louis, Massachusetts General Hospital, and Northwestern University and had ctDNA testing through the commercially available Guardant360 assay. Progesterone receptor (PR) status of the ER+/HER2- pts was identified to categorize pts as ER+/PR+/HER2- (N=60 Black, N=435 White) and ER+/PR-/HER2- (N=24 Black, N=237 White). Pts were evaluated by self-reported race and use of PIK3CA, CDK4/6, and mTOR inhibitors, either through clinical trial enrollment or after FDA approval. A multivariate logistic analysis was performed to determine genomic and prognostic differences by race. Overall survival (OS) from time of first ctDNA testing was determined by subgroup. Results: Black pts with PIK3CA single nucleotide variants (SNVs) were significantly less likely to receive targeted therapy than White pts (5.9%, 1/17 pts vs. 28.8%, 45/156 pts, Fisher’s exact test p=0.045), while there was no difference in use of CDK4/6 or mTOR inhibitors. None of the Black pts with PIK3CA mutations were enrolled in clinical trials vs. 11.5% of White pts. Black pts with ER+/PR+/HER2- tumors were more likely to have CCND1 copy number variation (cnv) (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1-5.4, p=0.030) when compared with White pts. Black pts with PR- tumors were more likely to have de novo metastatic disease (OR 3.4, 95% CI 1.1-10.8, p=0.034) and GATA3SNV (OR 3.5, 95% CI 1.04-11.6, p=0.044). KRAS cnv was more common in White PR- pts (HR 2.9, CI 1.02-8.3, p=0.045). There were significant differences in OS between Black and White pts with ER+/PR+/HER2- tumors (median OS of 25 vs. 32 months, respectively) and for Black and White pts with ER+/PR-/HER2- MBC, (median OS of 9.1 vs. 21 months, respectively, log-rank test p=0.00093). Conclusions: To our knowledge, this is the largest clinicogenomic dataset comparing genomic alterations and targeted treatment use by race in MBC. We identified significant disparities in the use of PI3K inhibitors for Black pts while other drugs that do not require genomic profiling were similarly utilized. OS and clinical trial enrollment disparities are consistent with prior findings and must continue to be addressed. Further research is needed to validate these findings, elucidate the factors contributing to these disparities, and explore interventions to improve racial disparities in use of precision medicine therapies and enrollment in clinical trials.

Effects of preoperative breast MRI on surgical management in women aged 40 years and younger with breast cancer.

e13656 Background: Evaluating the use of preoperative breast MRI on the management of breast cancer can help guide surgical decision making for young female patients newly diagnosed with breast cancer. Methods: A retrospective chart review of the George Washington University database between January 2015 and December 2020 identified 125 women age 40 or younger diagnosed with breast cancer. Of the 125 women, 23 were excluded from the study as they were lost to follow up due to care transfers. The management impact of pre-operative MRI was examined and variables collected include age, race, family history, genetic predisposition, breast density, method of detection, initial imaging findings, initial biopsy results, preoperative MRI findings, additional biopsies, additional biopsy results, and surgery type. Results: Patient ages ranged from 22 to 40 (mean 34.5), 69 (67.6%) had a family history of breast cancer, 81 (79.4%) had dense breasts (30 extremely dense and 51 heterogeneously dense), and 82 (80.4%) had the cancer detected due to clinical symptoms with the remaining during surveillance due to high risk. Of all women included, 55 (53.9%) had additional findings on MRI warranting biopsy of which 25 (45.5%) were biopsy proven cancer. 39 (39.4%) patients had lumpectomy and 59 (59.6%) had mastectomy. 1 (0.01%) patient did not undergo surgery due to widespread metastasis. The use of preoperative MRI identified additional carcinoma in 25 (24.5%) out of 102 patients. 24 (96%) in the ipsilateral breast, and 1 (4%) in the contralateral breast. Conclusions: Overall, this data indicates that the use of preoperative MRI for the treatment of breast cancer in young patients increases the detection of occult breast cancer prior to definitive therapy in 24.5% of patients, critically important information for optimal management. We recommend that all young women with newly diagnosed breast cancer undergo pre-operative MRI to further optimize patient care.

Comparing FGFR-3 and TS-HDS Seropositive Small Fiber Neuropathy: Unique Patient Features, Symptoms, Laboratory, and Nerve Conduction Study Findings.

Small fiber neuropathy presents a significant diagnostic and therapeutic challenge. To solve this challenge, efforts have been made to identify autoantibodies associated with this condition. Previous literature has often considered tri-sulfated heparin disaccharide (TS-HDS) and fibroblast growth factor receptor 3 (FGFR3) as a singular seropositive group and/or focused primarily on symptomatic associations. One hundred seventy-two small fiber neuropathy patients with a Washington University Sensory Neuropathy panel were selected for TS-HDS seropositivity, FGFR-3 seropositivity, and seronegative controls. Data were collected to on the demographic, symptomatic, and laboratory profiles of each subgroup. Percent female (P = 0.0043), frequency of neuropathic pain symptoms (P = 0.0074), and erythrocyte sedimentation rate (P = 0.0293), vitamin D (P < 0.0001), and vitamin B12 (P = 0.0033) differed between the groups. Skin biopsy was more frequently normal within both the FGFR-3 and the TS-HDS cohort (P = 0.0253). TS-HDS and FGFR-3 display a distinct phenotype from both controls and one another. Immunoglobulin M (IgM) against FGFR-3 and IgM against TS-HDS may be individually valuable markers for the development of distinct clinical phenotypes.

Integration of Clinical Trial Development in Hematology-Oncology Fellowship Training.

Several barriers to physicians becoming clinical investigators exist, including inexperience, lack of available mentors, and inconsistent instructive approaches with varying degrees of participation during training. These barriers cause fewer hematology-oncology fellows to pursue academic careers. A consensus is needed on structuring education in clinical investigation paired with active participation in development of a clinical trial guided by a mentor with the goal of increasing fellow interest in clinical research and pursuit of careers in academic medicine. The clinical trial development (CTD) program was initiated at Washington University School of Medicine in St. Louis in 2002 as a hands-on learning experience for hematology and oncology fellows in the design, implementation, and publication of clinical trials. Each fellow was required to identify a mentor and propose at least 1 prospective investigator-initiated clinical trial. At the time of data abstraction in July 2023, 118 fellows had participated in the CTD program and initiated protocols in a variety of areas according to their interests. Fellows were included in data abstraction if their fellowship began in 2002 through 2021; the program is ongoing, and the most recent class will graduate in 2024. Disease types were evenly distributed between solid tumor oncology (60 [51%]) or classic and malignant hematology (58 [49%]). Ninety-three fellows (79%) obtained institutional review board approval, and 60 (65%) published their results. Among graduating fellows, 67 (66%) secured an academic faculty appointment. Fellows with institutional review board-approved projects had significantly higher odds of obtaining an academic faculty appointment (odds ratio, 4.96; 95% confidence interval, 1.54, 15.98; P = .007).Next StepsNext steps will be to further evaluate the effect of the mentorship network on early career productivity of trainees that graduate and the feasibility of extending the program to another institution.

Predicting post-surgical functional status in high-grade glioma with resting state fMRI and machine learning

PurposeHigh-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care.MethodsAdult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of resting state network connectivity (FC), tumor location, and tumor volume were used to train a random forest classifier to predict functional outcomes based on Karnofsky Performance Status (KPS < 70, KPS ≥ 70).ResultsThe models achieved a nested cross-validation accuracy of 94.1% and an AUC of 0.97 in classifying KPS. The strongest predictors identified by the model included FC between somatomotor, visual, auditory, and reward networks. Based on location, the relation of the tumor to dorsal attention, cingulo-opercular, and basal ganglia networks were strong predictors of KPS. Age was also a strong predictor. However, tumor volume was only a moderate predictor.ConclusionThe current work demonstrates the ability of machine learning to classify postoperative functional outcomes in HGG patients prior to surgery accurately. Our results suggest that both FC and the tumor’s location in relation to specific networks can serve as reliable predictors of functional outcomes, leading to personalized therapeutic approaches tailored to individual patients.

In Place of a Missing Place

This essay reflects on works chosen from the Sonnenfeld Collection at the Katzen Gallery at American University in Washington, DC—it originally accompanied an exhibition at that gallery in early 2021—to comment on the observations of several generations of Israeli artists on the land and its meaning for the culture and politics of Israel’s coming into existence and evolution during the first 70 years of its existence. Beginning with a pair of photographs of pioneers in the land in the fifteen years before statehood—and conceptually re-purposed by a contemporary Israeli artist in 2008—and moving through decade after decade of engagement with the landscape of Israel in both figurative and abstract modes, with and without humans present within these contexts, veering from brightly colored to virtually colorless images, including paintings and photographs, the essay traces a distance between earlier assertions of presence and the gradual emergence of questions regarding presence, absence, and identity. Israel, in its internal development, is both visually and thus verbally interwoven with the issue of its external relationship with its immediate neighbors and to the shifts between what comprises “internal” and “external”—”this” and “other”—as the context has metamorphosized from the 1930s to the 1950s to 1967 to 1993 to 2000 and to the present.

Knowledge mapping of chronic insomnia: a bibliometric analysis (2000-2023).

Recently, significant scientific research breakthroughs have been witnessed in the treatment of chronic insomnia. However, it seems that there is currently no bibliometric analysis of this. Therefore, we hope to comprehensively review and analyze the scholarly system and research focus in the field of chronic insomnia treatment through bibliometric methods. Between 2000 and 2023, we explored various papers in relation to the treatment of chronic insomnia in the Web of Science Core Collection(WOSCC) database. Subsequently, the collected papers were subjected to bibliometric analysis utilizing CiteSpace, VOSviewer, and the "bibliometric" package in R language. With China and the United States(USA) among them, a total of 2937 papers were published across 49 countries. Publications related to the treatment of chronic insomnia were increasing year by year. The Laval University, Washington University, Pittsburgh University, and Stanford University were key research institutions. The journal Sleep was widely popular in the field and was also one of the most cited journals. These papers came from 148 authors, with Morin, Charles M., Roth, Thomas, Espie, Colin A., Harvey, Allison G., and Buysse, Daniel J. publishing the most papers and Morin, cm being co-cited the most. The treatment process of chronic insomnia can be divided into three main stages: drug intervention, diseases related to chronic insomnia, and cognitive behavioral therapy and mental health. Keywords such as "children and adolescents", "novel coronavirus pneumonia" (COVID-19), "mental health" and "heart failure" have become the focus of current research. We carried out a detailed bibliometric review of the development trends and research results of chronic insomnia research through this study for the first time. The information it provides reveals recent research hotspots and cutting-edge issues, providing valuable reference materials for researchers focusing on the treatment of chronic insomnia.

Acupuncture knowledge, attitudes, beliefs and health service needs after traumatic brain injury: a cross-sectional survey.

Acupuncture is a promising treatment for common symptoms after traumatic brain injury (TBI). Our objectives were to explore knowledge, attitudes and beliefs about acupuncture, identify health service needs and assess the perceived feasibility of weekly acupuncture visits among individuals with TBI. We surveyed adults 18 years of age and older with TBI who received care at the University of Washington. Respondents were asked to complete 143 questions regarding acupuncture knowledge, attitudes and beliefs, injury-related symptoms and comorbidities, and to describe their interest in weekly acupuncture. Respondents (n = 136) reported a high degree of knowledge about acupuncture as a component of Traditional Chinese Medicine, needle use and safety, but were less knowledgeable regarding that the fact that most conditions require multiple acupuncture treatments to achieve optimal therapeutic benefit. Respondents were comfortable talking with healthcare providers about acupuncture (63.4%), open to acupuncture concurrent with conventional treatments (80.6%) and identified lack of insurance coverage as a barrier (50.8%). Beliefs varied, but respondents were generally receptive to using acupuncture as therapy. Unsurprisingly, respondents with a history of acupuncture (n = 60) had more acupuncture knowledge than those without such a history (n = 66) and were more likely to pursue acupuncture without insurance (60%), for serious health conditions (63.3%) or alongside conventional medical therapy (85.0%). Half of all respondents expressed interest in participating in weekly acupuncture for up to 12 months and would expect almost a 50% improvement in symptoms by participating. Adults with TBI were receptive and interested in participating in weekly acupuncture to address health concerns. These results provide support for exploring the integration of acupuncture into the care of individuals with TBI.

Research highlights challenges facing nonprofit grant managers

A new study from REI Systems, in partnership with the National Grants Management Association and the Trachtenberg School of Public Policy and Public Administration at George Washington University, shows that nonprofit grant managers are struggling with cumbersome software systems and a lack of personnel as they conduct their duties, whether that's awarding and shepherding grantmaker funding to grantees, or managing and reporting on the funds on behalf of nonprofit grantees.

Is the Risk of Intrahepatic Cholestasis Increased with Supplemental Progesterone?

This study aimed to evaluate the relationship between supplemental progesterone use during pregnancy and the development of intrahepatic cholestasis of pregnancy (ICP). A retrospective, matched case-control study was conducted among a population of women who delivered at George Washington University Hospital (GW) between 2012 and 2022. Women diagnosed with ICP (cases) were identified using International Statistical Classification of Diseases (ICD) codes, and data were collected via chart abstraction. Descriptive data included patient demographics, pregnancy characteristics, and medical history. Laboratory values related to ICP were collected. Cases were matched on a 1:3 ratio by maternal age, body mass index, and gravidarum to women who delivered at GW during the same month and did not carry a diagnosis of ICP (controls). A univariate logistic regression model was created to assess the use of supplemental progesterone between groups, adjusting for the use of assisted reproductive technology in the current pregnancy, and a history of liver disease. One hundred and twenty women who delivered during the study period were confirmed to have a diagnosis of ICP. Cases were matched with 360 controls and measures compared between the two groups. Cases were significantly more likely to have a history of liver disease (5.9 vs. 1.7%, p = 0.0021), multiple gestation (10.0 vs. 3.3%, p < 0.0001), a history of ICP in a previous pregnancy (10.0 vs. 0%, p < 0.0001), and to have delivered at an earlier gestational age (mean 37.1 vs. 38.6 weeks, p < 0.0001) as compared with controls. No differences were seen in the odds of supplemental progesterone use in both unadjusted and adjusted models (OR = 1.14, 95% CI: 0.30-4.34; adjusted Odds Ratio [aOR] = 0.98 [0.24-3.94]). Contrary to recent evidence, no association was seen with the use of supplemental progesterone. It is possible that the associated risk with supplemental progesterone is dependent on medication formulation or route of administration. · Supplemental progesterone use in pregnancy may increase the risk of developing ICP.. · Previous investigations of progesterone and ICP have demonstrated mixed results.. · The association may be dependent on the route of administration and formulation of progesterone..

Abstract GS03-07: Protocol-defined biomarker analysis in the PALLAS (AFT-05) adjuvant trial: Genomic subtype derived from RNA sequencing of HR+/HER2- early breast cancer

Abstract Background. The phase 3 PALLAS trial (NCT02513394) compared two years of the CDK4/6 inhibitor palbociclib with endocrine therapy of provider choice, versus endocrine therapy alone, as adjuvant treatment for patients with Stage II-III hormone receptor-positive HER2-negative (HR+/HER2-) breast cancer. Genomic subtype (PAM50 intrinsic subtype) measured from whole-transcriptome RNA sequencing data was defined in the protocol of the PALLAS trial as the primary biomarker for analysis of prediction and prognosis. Clinical data have been previously presented (Gnant et al, JCO 2022), and the trial now has 5-year median follow-up. Methods. As part of trial eligibility, all participants in PALLAS provided a tumor tissue block prior to randomization (surgical if primary resection, core biopsy if neoadjuvant treatment) for translational analyses (TRANS-PALLAS). The biorepository and laboratory were blinded to identity and processed samples in random order, to minimize bias. Nucleic acids were extracted from samples with sufficient tumor tissue and cellularity (&amp;gt;25 mm2 with ≥20% cancer nuclei). The Genome Sequencing Center at Washington University St. Louis performed whole-transcriptome RNA sequencing. Libraries were prepared from 1 µg DNase-1 treated total RNA, if total RNA DV200 &amp;gt;28 (Agilent Bioanalyzer), using an unbiased library protocol of RNA HyperPrep kit with RiboErase (HMR) (Kapa Biosystems, Wilmington, MA). 100 bp paired-end sequencing was performed on NovaSeq 6000 using S4 Reagent Kit (Illumina, San Diego, CA), with 48 libraries pooled per lane. Intrinsic subtype was determined using Bioclassifier package (Research PAM50 script, Parker et al.) only for the analysis population of primary breast cancer samples that had not been exposed to prior neoadjuvant therapy. Invasive disease-free survival (IDFS) will be visualized using Kaplan-Meier plots, with log-rank test between groups. Cox models of proportional hazards will be developed to evaluate prognosis adjusted for known clinical covariates, or for predictive interactions. The pre-defined level of significance is a two-sided 0.05. Results. From the total study population of 5796 enrolled patients, 4655 tissue blocks had sufficient tumor content to process for RNA, with 3931 yielding sufficient RNA for sequencing, and 2669/4655 (57.3%) submitted tissue blocks had DV200 ≥28 and were successfully sequenced. Clinical unblinding revealed 2370 unique patients (1182 in the palbociclib treatment arm and 1188 in the control arm) with intrinsic subtype defined from their untreated primary tumor: 1555 (65.6%) luminal A, 287 (12.1%) luminal B, 167 (7.0%) HER2-enriched, 310 (13.1%) basal-like, 51 (2.2%) normal-like. We will report the results for association of molecular subtype, proliferation score, and Risk of Recurrence (ROR) scores with invasive disease-free survival (IDFS) by treatment arm at the meeting. Conclusions. The TRANS-PALLAS cohort represents one of the largest biorepositories of HR+/HER2- early breast cancer reflecting contemporary systemic management in the framework of a prospectively randomized global trial. Required tumor block submission in this phase 3 trial yielded data from unbiased whole-transcriptome RNA sequencing of the primary tumor prior to treatment from 41% of the PALLAS participants. The proportion of luminal A cancers was unexpectedly high (66%), indicating a lower-risk distribution of cancers in this population. The planned analyses of prediction and prognosis are ongoing and those results will be presented at the time of the meeting. Support: AFT, ABCSG, Pfizer, ECOG-ACRIN, NSABP Foundation, GBG, BIG; Clinicaltrials.gov Identifier: NCT02513394; https://acknowledgments.alliancefound.org Citation Format: Daniel Stover, Dominik Hlauschek, Erica Mayer, W. Fraser Symmans, Mark Watson, Iros Barozzi, Martin Filipits, Karla Ballman, Meritxell Bellet- Ezquerra, Justin Balko, Gabor Rubovszky, Nicholas Zdenkowski, Adam Brufsky, Guenther Steger, Claudine Isaacs, Sibylle Loibl, Fernando Henao, Meredith Regan, Yuan Liu, Christian Fesl, Patrick O'Brien, Angela DeMichele, Michael Gnant, Otto Metzger. Protocol-defined biomarker analysis in the PALLAS (AFT-05) adjuvant trial: Genomic subtype derived from RNA sequencing of HR+/HER2- early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS03-07.

Abstract PO5-20-02: Secondary BRain metastases prevention after Isolated intracranial progression on trastuzumab/pertuzumab or T-DM1 in pts with aDvanced human epidermal Growth factor receptor 2+ brEast cancer with addition of Tucatinib (BRIDGET)

Abstract Background: Despite treatment with trastuzumab-based therapy, up to half of patients with HER2+ advanced/metastatic breast cancer (MBC) will develop brain metastases (BrM). First-line therapy for advanced HER2+ MBC remains a taxane, trastuzumab, pertuzumab (TP) which demonstrates poor brain permeability. Isolated brain relapse with stable or absent extracranial disease remains a clinical problem in both the adjuvant (Untch et al., ESMO 2019 Congress) and metastatic settings (Noteware et al., Breast Cancer Res Treat. 2023). Current guidelines recommend continuing current systemic therapy in the setting of first isolated brain relapse following local therapy. Tucatinib, a brain-penetrable HER2-targeting tyrosine kinase inhibitor, when added to trastuzumab and capecitabine improves intracranial progression free survival (PFS) and overall survival (OS) in patients with stable or active HER2+ BrMs. We hypothesize that adding tucatinib to TP or T-DM1 in patients with HER2+ MBC with isolated brain relapse or progression could delay or prevent the development of further intracranial lesions and improve OS. Methods: BRIDGET (NCT05323955) is a single arm, phase II, multicenter study of tucatinib added to TP or T-DM1 after local therapy in patients with isolated brain relapse or progression. A total of 48 patients at 9 U.S. sites as part of the Hoosier Cancer Research Network (HCRN) with metastatic HER2+ breast cancer will be enrolled after 1st or 2nd BrM relapse or progression within 8 weeks of local therapy. Patients must currently be receiving standard of care treatment with TP or T-DM1 in the metastatic setting, or adjuvant trastuzumab-based or T-DM1 therapy with isolated brain recurrence. Extracranial disease must be stable per RECISTv1.1 or absent. Patients may not have leptomeningeal disease or untreated brain lesions over 5 mm. Patients will receive continuous tucatinib added to their current therapy (TP or T-DM1). The primary objective is intracranial PFS compared to a historical control (H0: PFS &amp;lt; 5 months (mos), HA: PFS &amp;gt; 8 mos) of the HER2CLIMB clinical trial where patients could continue on trial with isolated brain progression. In these patients, median time from brain progression to second progression or death was 7.6 mos (95% CI, 3.9 to 11.3 mos) in the tucatinib arm versus 3.1 mos (95% CI, 1.2 to 4.1 mos) in the control arm (Lin et al., J Clin Onc 2020). Secondary endpoints include PFS by RECISTv1.1, PFS of extracranial disease, locally treated versus new distant intracranial metastasis PFS, site of first progression (brain versus non-brain), OS, and toxicity in patients with BrM. Collection of correlative specimens including archival tissue, cerebrospinal fluid (optional), whole blood for ctDNA are planned. Patient-reported outcomes surveyed utilizing the FACT-BR and FACIT-Fatigue questionnaires are also included for future analyses. As of 7/06/23, accrual is 5 patients of the anticipated 48 patients overall, across 5 sites (Duke University, Dana Farber Cancer Institute, Ohio State University, Providence Portland Medical Center, and Washington University in St. Louis) currently open. An additional 4 sites are pending opening. Those interested in this trial can reach out to the study Principal Investigators, Carey Anders, MD (carey.anders@duke.edu) or Sarah Sammons, MD (sarahl_sammons@dfci.harvard.edu). Citation Format: Sarah Sammons, Amanda Van Swearingen, Laura Noteware, Nusayba Bagegni, Kelly Moulton, Stevie Threatt, Denise Jaggers, Shannon Shea, Eric Lipp, Erin Riley, Sin-Ho Jung, Gloria Broadwater, Masey Ross, Kimberly Strickland, Sasha Beyer, Alison Conlin, Aki Morikawa, Rashmi Murthy, Carey Anders. Secondary BRain metastases prevention after Isolated intracranial progression on trastuzumab/pertuzumab or T-DM1 in pts with aDvanced human epidermal Growth factor receptor 2+ brEast cancer with addition of Tucatinib (BRIDGET) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-02.