Publications

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality despite efforts to improve standard interventions. As CRC patients can benefit from immunotherapeutic strategies that incite effector T cell action, cancer vaccines represent a safe and promising therapeutic approach to elicit protective and durable immune responses against components of the tumor microenvironment (TME). In this study, we investigate the pre-clinical potential of a Listeria monocytogenes (Lm)-based vaccine targeting the CRC-associated vasculature. CRC survival and progression are reliant on functioning blood vessels to effectively mediate various metabolic processes and oxygenate underlying tissues. We, therefore, advance the strategy of initiating immunity in syngeneic mouse models against the endogenous pericyte antigen RGS5, which is a critical mediator of pathological vascularization. Overall, Lm-based vaccination safely induced potent anti-tumor effects that consisted of recruiting functional Type-1-associated T cells into the TME and reducing tumor blood vessel content. This study underscores the promising clinical potential of targeting RGS5 against vascularized tumors like CRC.

BACKGROUND: Atrial fibrillation is a common cause of stroke among older adults and is often first detected during hospitalization, given frequent use of cardiac telemetry.

METHODS: In a 20% national sample of Medicare fee-for-service beneficiaries, we identified patients aged 65-or-older newly diagnosed with atrial fibrillation while hospitalized in 2016. Our primary outcome was an oral anticoagulant claim within 7-days of discharge. Multivariable logistic regression analyses assessed relationships between anticoagulation initiation and thromboembolic and bleeding risk scores while controlling for demographics, frailty, comorbidities, and hospitalization characteristics.

RESULTS: Among 38,379 older adults newly diagnosed with atrial fibrillation while hospitalized (mean age 78.2 [SD 8.4]; 51.8% female; 83.3% white), 36,633 (95.4%) had an indication for anticoagulation and 24.6% (9011) of those initiated an oral anticoagulant following discharge. Higher CHA2 DS2 -VASc score was associated with a small increase in oral anticoagulant initiation (predicted probability 20.5% [95% CI, 18.7%-22.3%] for scores <2 and 24.9% [CI, 24.4%-25.4%] for ≥4). Elevated HAS-BLED score was associated with a small decrease in probability of anticoagulant initiation (25.4% [CI, 24.4%-26.4%] for score <2 and 23.1% [CI, 22.5%-23.8%] for ≥3). Frailty was associated with decreased likelihood of oral anticoagulant initiation (24.7% [CI, 23.2%-26.2%] for non-frail and 18.1% [CI, 16.6%-19.6%] for moderately-severely frail). Anticoagulant initiation varied by primary reason for hospitalization, with predicted probability highest among patients with a primary diagnosis of atrial fibrillation (46.1% [CI, 45.0%-47.3%]) and lowest among those with non-cardiovascular conditions (13.8% [CI, 13.3%-14.3%]) and bleeds (3.6% [CI, 2.4%-4.8%]).

CONCLUSIONS: Oral anticoagulant initiation is uncommon among older adults newly diagnosed with atrial fibrillation during hospitalization, even among patients hospitalized primarily for atrial fibrillation and patients with high thromboembolic risk. Clinicians should discuss risks and benefits of oral anticoagulants with all inpatients found to have atrial fibrillation.

IMPORTANCE: Use of telehealth has increased substantially in recent years. However, little is known about whether the likelihood of completing recommended tests and specialty referrals-termed diagnostic loop closure-is associated with visit modality.

OBJECTIVES: To examine the prevalence of diagnostic loop closure for tests and referrals ordered at telehealth visits vs in-person visits and identify associated factors.

DESIGN, SETTING, AND PARTICIPANTS: In a retrospective cohort study, all patient visits from March 1, 2020, to December 31, 2021, at 1 large urban hospital-based primary care practice and 1 affiliated community health center in Boston, Massachusetts, were evaluated.

MAIN MEASURES: Prevalence of diagnostic loop closure for (1) colonoscopy referrals (screening and diagnostic), (2) dermatology referrals for suspicious skin lesions, and (3) cardiac stress tests.

RESULTS: The study included test and referral orders for 4133 patients (mean [SD] age, 59.3 [11.7] years; 2163 [52.3%] women; 203 [4.9%] Asian, 1146 [27.7%] Black, 2362 [57.1%] White, and 422 [10.2%] unknown or other race). A total of 1151 of the 4133 orders (27.8%) were placed during a telehealth visit. Of the telehealth orders, 42.6% were completed within the designated time frame vs 58.4% of those ordered during in-person visits and 57.4% of those ordered without a visit. In an adjusted analysis, patients with telehealth visits were less likely to close the loop for all test types compared with those with in-person visits (odds ratio, 0.55; 95% CI, 0.47-0.64).

CONCLUSIONS: The findings of this study suggest that rates of loop closure were low for all test types across all visit modalities but worse for telehealth. Failure to close diagnostic loops presents a patient safety challenge in primary care that may be of particular concern during telehealth encounters.

OBJECTIVES: Pregnancy provides a critical opportunity to engage individuals with opioid use disorder in care. However, before the COVID-19 pandemic, there were multiple barriers to accessing buprenorphine/naloxone during pregnancy. Care disruptions during the pandemic may have further exacerbated these existing barriers. To quantify these changes, we examined trends in the number of individuals filling buprenorphine/naloxone prescriptions during the COVID-19 pandemic.

METHODS: We estimated an interrupted time series model using linked national pharmacy claims and medical claims data from prepandemic (May 2019 to February 2020) to the pandemic period (April 2020 to December 2020). We estimated changes in the growth rate in the monthly number of individuals filling buprenorphine/naloxone prescriptions in the 6 months preceding a delivery claim, per 100,000 pregnancies, during the COVID-19 pandemic.

RESULTS: We identified 2947 pregnant individuals filling buprenorphine/naloxone prescriptions. Before the pandemic, there was positive growth in the monthly number of individuals filling buprenorphine/naloxone prescriptions (4.83%; 95% confidence interval [CI], 3.82-5.84%). During the pandemic, this monthly growth rate declined for both individuals on commercial insurance and individuals on Medicaid (all payers: -5.53% [95% CI, -6.65% to -4.41%]; Medicaid: -7.66% [95% CI, -10.14% to -5.18%]; Commercial: -3.59% [95% CI, -5.32% to -1.87%]).

CONCLUSION: The number of pregnant individuals filling buprenorphine/naloxone prescriptions was increasing, but this growth has been lost during the pandemic.

Despite the availability of various treatment options, colorectal cancer (CRC) remains a significant contributor to cancer-related mortality. Current standard-of-care interventions, including surgery, chemotherapy, and targeted agents like immune checkpoint blockade and anti-angiogenic therapies, have improved short-term patient outcomes depending on disease stage, but survival rates with metastasis remain low. A promising strategy to enhance the clinical experience with CRC involves the use of dendritic cell (DC) vaccines that incite immunity against tumor-derived blood vessels, which are necessary for CRC growth and progression. In this report, we target tumor-derived pericytes expressing DLK1 with a clinically-relevant alpha type-1 polarized DC vaccine (αDC1) in a syngeneic mouse model of colorectal cancer. Our pre-clinical data demonstrate the αDC1 vaccine's ability to induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity and ablating the tumor vasculature. This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious αDC1-based strategies for patients with CRC.

IMPORTANCE: Underrepresentation of women and racial and ethnic minority individuals among reviewers and funded investigators in health research has been widely reported. It is unknown whether such underrepresentation exists in the Veterans Health Administration (VHA).

OBJECTIVE: To describe gender and racial and ethnic makeup of VHA Health Services Research and Development (HSR&D) study sections and funding awardees and to explore the associations between gender and racial and ethnic makeup of study sections and awardees who were women and racial and ethnic minority individuals.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study at the VHA evaluated study section members and funding awardees from 5 review cycles from March 13, 2018, through March 6, 2020, identified via the HSR&D and National Institutes of Health websites.

MAIN OUTCOMES AND MEASURES: Univariable and multivariable logistic regression models were used to determine the likelihood of an awardee being a woman or a racial or ethnic minority individual based on the gender and racial and ethnic makeup of study sections, respectively. Separate models were conducted for investigator-initiated research proposals only.

RESULTS: Thirty-six study sections comprised 664 reviewers, including 381 women (57.4%) and 81 racial and ethnic minority individuals (12.2%). Of the 146 funded proposals, 77 (52.7%) were awarded to women and 25 (17.1%) to racial and ethnic minority investigators; 29 (19.9%) were reviewed by study sections with no racial and ethnic minority reviewers. The odds of a woman awardee were more than 5 times greater for proposals reviewed by study sections comprising the highest proportion of women (fourth quartile; >58.3%) than the lowest proportion of women (first quartile; ≤50.0%) (adjusted odds ratio [aOR], 5.24 [95% CI, 1.70-16.13]). Similarly, the odds of a racial or ethnic minority awardee were 3 times greater for proposals reviewed by study sections in the top 50th percentile for proportion of racial and ethnic minority individuals (>7.3%) than the bottom 50th percentile (aOR, 3.08 [95% CI, 1.18-8.09]). Secondary analyses limited to investigator-initiated research proposals identified similar associations.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of VHA HSR&D-funded research, racial and ethnic minority individuals were underrepresented among investigators and reviewers. More women and racial and ethnic minority reviewers on study sections were associated with women and racial and ethnic minority individuals awarded funding.

BACKGROUND: Anecdotal evidence suggests that gender inequity persists in academic pharmacy. To date, there are limited published data about the perception of gender inequity in academic pharmacy.

OBJECTIVE: The objective of this project was to determine themes associated with gender inequity perceptions in social and administrative science faculty from 2 national pharmacy organizations.

METHODS: A gender equity task force comprising 13 members from Social and Administrative Sciences (SAS) sections of the American Pharmacists Association and the American Association of Colleges of Pharmacy was formed. The task force designed a semistructured interview guide comprising questions about demographics and core areas where inequities likely exist. When the survey invitation was sent to faculty members of the SAS sections via Qualtrics, faculty indicated whether they were willing to be interviewed. Interviews were conducted by 2 members of the task force via video conferencing application. The interviews were transcribed. Topic coding involving general categorization by theme followed by refinement to delineate subcategories was used. Coding was conducted independently by 3 coders followed by consensus when discrepancies were identified.

RESULTS: A total of 21 faculty participated in the interviews. Respondents were primarily female (71%), were white (90%), had Doctor of Philosophy as their terminal degree (71%), and were in nontenure track positions (57%). Most respondents (90%) experienced gender inequity. A total of 52% reported experiencing gender inequity at all ranks from graduate student to full professor. Four major themes were identified: microaggression (57%), workload (86%), respect (76%), and opportunities (38%). Workload, respect, and opportunities included multiple subthemes.

CONCLUSION: Faculty respondents perceive gender inequities in multiple areas of their work. Greater inequity perceptions were present in areas of workload and respect. The task force offers multiple recommendations to address these inequities.