In this retrospective study, we compared the cause of death among hospitalized patients who died with a diagnosis of COVID-19 across two periods of the pandemic two years apart: an early period (admissions June to October 2020), when the population was immunologically naïve, and a later period (admissions April to October 2022), when an estimated 96% of the population had immunity from prior infection, vaccination, or both. Two investigators independently reviewed the medical records of 100 in-hospital deaths (50 per period) and classified each death as COVID-19 related, uncertain, or not COVID-19 related, using logistic regression to compare the two periods. Deaths during the early period were more likely to reflect a direct consequence of COVID-19 infection than deaths in the later period (adjusted odds ratio 0.25 for the later vs. early period; 95% CI 0.10 to 0.64; p = 0.004). This difference was largely attenuated when vaccination status was added to the model, suggesting a protective effect of vaccination against COVID-19 related mortality.

Background Many previous studies have investigated the prognostic value of body mass index (BMI) for GBM outcomes with varying results. We present a comprehensive literature review and meta-analysis investigating BMI as a prognostic value in GBM. Methods A systematic review of literature on adult patients with GBM published between 1999 and 2023 was conducted within OVID Medline, Pubmed, and Scopus. Non-English studies, unpublished studies, prior studies in series, and studies without BMI or survival data were excluded from our analysis. Random-effects meta-analyses were conducted on hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS). Risk of bias was assessed using the Newcastle Ottawa Scale. Results 29 articles were identified, and 14 studies were included after full text review. 9 studies were included in analysis of OS for overweight versus normal weight with pooled HR of 1.02 and extremely high heterogeneity (I2 = 81 %). 7 studies contributed data for OS for obese versus normal weight with pooled HR of 0.98 and high heterogeneity (I2 = 81 %). Subgroup analysis of overweight versus normal weight and obese versus normal weight yielded conflicting results. 5 studies contributed data for PFS with HR of 1.17 and again demonstrated high heterogeneity (I2 = 76 %). Conclusions Pooled results from all studies demonstrated very high heterogeneity and inconsistent results on subgroup analysis. Limitations included the small number of studies available, the poor quality of reported results, and differences in adjustment of HR between studies. No conclusion regarding the association between BMI and GBM survival can be drawn at this time.

The coronavirus disease of 2019 (COVID-19) pandemic exacerbated barriers to care for people living with human immunodeficiency virus (HIV) (PLWH). The quick uptake of telemedicine in the outpatient setting provided promise for care continuity. In this study, we compared appointment and laboratory no-show rates in an urban outpatient HIV clinic during three time periods: (1) Pre-COVID-19: 9/15/2019–3/14/2020 (predominately in-person), (2) “Early” COVID-19: 3/15/2020-9/14/2020 (predominately telemedicine), and (3) “Later” COVID-19: 9/15/2020-3/14/2021 (mixed in-person/telemedicine). Multivariable logistic regression models evaluated the two study hypotheses: (i) equivalence of Period 2 with Period 1 and of Period 3 with Period 1 and (ii) improved outcomes with telemedicine over in-person visits. No-show rates were 1

<p>PDF file - 47K, Analysis of Change in PHM Variables</p>

Context: Multi-cancer early detection (MCED) tests are being developed for use in cancer screening. There is a dearth of information on primary care provider perceptions about MCED test use. Objective: To assess primary care provider perceptions related to MCED test use. Study Design and Analysis: Single group pilot study. Setting or Dataset: Four primary care practices in a large urban health system. Population Studied: Thirty-seven primary care providers. Intervention/Instrument: Self-administered online survey. Outcome Measures: Provider perceived competence in MCED test use, as the average of 4 items measured on a 5-point Likert scale (1 = Strongly Disagree to 5 = Strongly Agree; alpha = 0.81); the influence of various concerns on provider receptivity to MCED test use, as the average of 11 items measured on a 5-point scale (1 = No influence to 5 = Overwhelming influence; alpha = 0.83); and the likelihood of ordering MCED testing in the future. Results: Twenty-seven (73%) providers (22 physicians and 5 nurse practitioners) completed the survey. Background characteristics were: < 60 years of age (69%), female (50%), and white (62%). Twenty one (76%) respondents were aware that MCED tests are being developed. The mean (standard deviation) score for perceived competence in managing MCED testing was 4.0 (0.6). The mean (standard deviation) score for the influence of concerns about MCED test use was 3.4 (0.7); with 70% of providers reporting a lot or an overwhelming level of concern about patient insurance coverage. Twenty-two (81%) providers indicated they were likely to order MCED testing in the future. Conclusion: Most providers were aware that MCED tests are being developed and felt capable of managing MCED testing in clinical care. Provider concerns indicate some reticence about offering MCED testing at this time, but most providers were open to MCED testing in the future. In anticipation of MCED test availability for cancer screening, research is needed to identify factors that are likely to affect provider support for and use of such testing in clinical practice.

e13607 Background: Randomized clinical trials of multi-cancer early detection (MCED) tests are being planned, and primary care providers (PCPs) are likely to encounter patients who are considering participation. Little information has been reported about provider support for patient participation in such trials. Methods: We surveyed PCPs from 4 practices in a large health system to learn about their views on patient participation in a hypothetical MCED test trial. The PCPs received a link to view a patient-oriented infographic that described a trial in which participants would undergo serial blood draws for MCED testing and would be randomly assigned either to standard care or to receive MCED test results and follow-up, as needed. After viewing the infographic, respondents were asked to complete a brief survey that included statements related to factors that would affect their receptivity to patient participation in the trial, using a 5-point Likert type response scale that ranged from 1 = Strongly Disagree to 5 = Strongly Agree. The survey also included a single item that asked respondents if they would support patient participation in the trial and provided an opportunity to report the main reason for their answer. Finally, the survey contained a background characteristics section. We computed frequency distributions of survey responses. Results: Twenty-seven of 37 (73%) invited primary care providers completed the survey. About half of the respondents were women and two thirds were white; 81% were physicians while 19% were nurse practitioners, 54% were in practice for less than 20 years, all were board certified, and 74% had a hospital affiliation. Receptivity scores regarding a future MCED trial were high, with a mean of 3.8 and standard deviation of 0.6. Overall, 25 providers (93%) reported that they would support patient participation in an MCED test trial. The most commonly reported reasons for supporting patient participation were the belief that early cancer detection is important and the belief that research to develop new cancer screening tests is needed. The most commonly cited reasons for not supporting participation were concern about managing patients diagnosed with cancer in the trial and worry that trial participants would require too many practice resources. Conclusions: The overwhelming majority of respondents supported patient participation in an MCED test trial, but many were concerned about trial impact on their capacity to meet patient needs. Further research is needed in a larger study to validate these results and learn more about factors likely to influence PCP support for patient participation in MCED test trials and actual participation.

"Decision Preferences in Shared Decision-Making for Lung Cancer Screening among White and African American Individuals." Annals of the American Thoracic Society, 20(5), pp. 756–758

PDF file - 62KB, Supplementary information regarding the modeling and estimation of access and navigation effects.

Despite the widespread availability of effective vaccines, new cases of infection with severe acute respiratory syndrome coronavirus-2, the cause of coronavirus disease 2019 (COVID-19), remain a concern in the settings of vaccine hesitancy and vaccine breakthrough. In this randomized, controlled, phase 2 trial, we hypothesized that high-dose ascorbic acid delivered intravenously to achieve pharmacologic concentrations may target the high viral phase of COVID-19 and thus improve early clinical outcomes. Sixty-six patients admitted with COVID-19 and requiring supplemental oxygen were randomized to receive either escalating doses of intravenous ascorbic acid plus standard of care or standard of care alone. The demographic and clinical characteristics were well-balanced between the two study arms. The primary outcome evaluated in this study was clinical improvement at 72 h after randomization. While the primary outcome was not achieved, point estimates for the composite outcome and its individual components of decreased use of supplemental oxygen, decreased use of bronchodilators, and the time to discharge were all favorable for the treatment arm. Possible favorable effects of ascorbic acid were most apparent during the first 72 h of hospitalization, although these effects disappeared over the course of the entire hospitalization. Future larger trials of intravenous ascorbic acid should be based on our current understanding of COVID-19 with a focus on the potential early benefits of ascorbic in hospitalized patients.

Current guidelines recommend annual lung cancer screening (LCS), but rates are low. The current study evaluated strategies to increase LCS. This study was a randomized controlled trial designed to evaluate the effects of patient outreach and shared decision making (SDM) about LCS among patients in four primary care practices. Patients 50 to 80 years of age and at high risk for lung cancer were randomized to Outreach Contact plus Decision Counseling (OC-DC, n = 314), Outreach Contact alone (OC, n = 314), or usual care (UC, n = 1748). LCS was significantly higher in the combined OC/OC-DC group versus UC controls (5.5% vs. 1.8%; hazard ratio, HR = 3.28; 95% confidence interval, CI: 1.98 to 5.41; p = 0.001). LCS was higher in the OC-DC group than in the OC group, although not significantly so (7% vs. 4%, respectively; HR = 1.75; 95% CI: 0.86 to 3.55; p = 0.123). LCS referral/scheduling was also significantly higher in the OC/OC-DC group compared to controls (11% v. 5%; odds ratio, OR = 2.02; p = 0.001). We observed a similar trend for appointment keeping, but the effect was not statistically significant (86% v. 76%; OR = 1.93; p = 0.351). Outreach contacts significantly increased LCS among primary care patients. Research is needed to assess the additional value of SDM on screening uptake.

428 Background: Pancreatic adenocarcinoma is the fourth most common cause of cancer-related death in the US. The location of the primary lesion has long been thought to influence survival due to differences in time to presentation and ability to undergo cancer directed surgery. We hypothesized that patients with tumors arising in the body or tail (distal) would have poorer survival than patients who presented with lesions in the head of the pancreas (proximal) and that this difference would be true regardless of stage at diagnosis due in part to other factors such as intrinsic differences in the biology of these tumor types. A retrospective chart review at a single center with a high volume of pancreatic cancer directed surgery was carried out to address this question. Methods: Institution database was queried to identify patients with the ICD9 diagnosis of pancreatic adenocarcinoma of the head, body, and tail between 2014-2017; the inclusion criteria were 18 years or older, biopsy proven adenocarcinoma and a single mass in the pancreas at presentation. A total of 907 entries were screened with 324 patients being analyzed (236 proximal and 88 distal). CDC National Death Index registry and obituary reports were utilized to determine official dates of death. Results: Overall median survival was statistically higher in the proximal group than the distal group 16.0 vs 11.2 months (p=0.015). However, there was no significant difference in survival by stage of the proximal group over the distal group with stage I/II in the proximal group surviving 21 months versus distal 25.7 months, p=0.436; stage III, proximal surviving 11.7 months versus distal 18.0 months, p=0.393; stage IV, proximal surviving 6.5 months versus distal 4.9 months, p=0.675. The distal group was more likely to be metastatic on diagnosis (59% versus 18%) and was less likely to undergo surgery (34% vs 50%). In the surgical group, there was similar survival of 24.6 months in the proximal group versus 19.4 distal (p=0.795). Conclusions: Patients in the proximal group had a higher overall survival than the distal group as expected. Overall, however, when broken down by stage or surgery, the difference in survival between the proximal and distal groups was minimal with Hazard Ratio 0.96 (95%, CI=0.7, 1.30). Therefore, early stage diagnosis or surgery strongly account for the survival benefit in the proximal population rather than other factors like an intrinsic difference in the nature of the tumors themselves.

This study investigated predictors of overall and test-specific colorectal cancer screening (CRCS). Stool blood test (SBT) and/or colonoscopy screening were offered to primary care patients in two randomized controlled trials which assessed the impact of behavioral interventions on screening. Data were obtained through surveys and electronic medical records. Among 1942 participants, 646 (33%) screened. Exposure to interventions was associated with higher overall CRCS by twofold to threefold; older age, African American race, being married, and having a higher screening decision stage were also associated with higher overall CRCS (odds ratios = 1.30, 1.31, 1.34, and 5.59, respectively). Intervention, older age, female gender, and being married were associated with higher SBT adherence, while preference for colonoscopy was associated with lower SBT adherence. Intervention and higher decision stage were associated with higher colonoscopy adherence, while preference for SBT was associated with lower colonoscopy adherence. Among older individuals, African Americans had higher overall CRCS than whites, but this was not true among younger individuals (interaction p = .041). The higher screening adherence of African Americans over whites was due to stronger screening with a non-preferred test, i.e., higher SBT adherence only among individuals who preferred colonoscopy and higher colonoscopy adherence only among individuals who preferred SBT. Intervention exposure, sociodemographic background, and screening decision stage predicted overall CRCS adherence. Gender and test preference also affected test-specific screening adherence. Interactions involving race and test preference suggest that it is important to provide both colonoscopy and SBT screening options to patients, particularly African Americans.

Background: Hispanic adults in the United States have low colorectal cancer (CRC) screening rates and are more likely than non-Hispanic adults to be diagnosed with advanced-stage CRC. We evaluated the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) of a novel multilevel decision support and navigation intervention (DSNI) designed to increase CRC screening among Hispanic primary care patients. Methods: The trial enrolled 400 consented participants from a health system sampling frame of 2,720 Hispanic patients eligible for CRC screening in five primary care practices. We randomized 203 patients to receive a mailed standard intervention (SI Group) that included informational material, a fecal immunochemical test kit, a reminder versus 197 patients who received the SI plus a telephone screening DSNI (DSNI Group). We assessed DSNI effects using health system and study administrative data. Results: 1) Reach: DSNI delivery reached 84% of participants. 2) Effectiveness: The DSNI group produced a screening rate that was significantly greater (p < .001) than in the SI group (78% and 43%, respectively). 3) Adoption: All participating primary care practices and patients remained in the study. 4) Implementation: DSNI delivery required an average of 4.1 decision support and navigation call attempts with the total call effort averaging 35 minutes. 5) Maintenance: Health system leaders have acknowledged DSNI benefits and are actively engaged in determining how to sustain DSNI implementation. Conclusion: The DSNI achieved high levels of reach, effectiveness, adoption, and implementation with a modest investment of resources. The project team is addressing the challenge of DSNI maintenance in the health system. Further work is needed to determine intervention effectiveness in other health systems and in the general patient population. Trial Registration: ClinicalTrials.gov identifier : NCT02272244

Abstract Herpesvirus-based immunotherapies are emerging as exciting new possibilities for vaccines and cancer treatment. We have been exploring the use of a cytomegalovirus (CMV)-based cancer therapy to promote productive tumor-specific immunity and modify the tumor microenvironment. We previously showed that intratumoral (IT) infections with murine (M)CMV led to significant delays in the growth of B16 melanomas that were, surprisingly, independent of vaccine antigens encoded in the viral backbone. Although MCMV could infect B16 cells directly in vitro, tumor-associated macrophages (TAMs) were a primary target for viral infection in vivo. To test the mechanistic role of TAMs, we depleted monocytic phagocytes with clodronate. Loss of these myeloid cells completely prevented MCMV from delaying tumor growth. Macrophages are well-known targets of MCMV infection and in vitro studies demonstrated that MCMV infection of M2-polarized macrophages resulted in repolarization to an M1-like phenotype. In vivo, MCMV infection also increased expression of several inflammatory cytokines in the tumor. In a natural infection, MCMV uses the chemokine MCK-2 to recruit monocytes to the site of infection. Strikingly, MCMV deficient in MCK-2 was ineffective at delaying tumor growth. Further studies demonstrated that MCK-2 was necessary for MCMV to induce macrophage accumulation in the tumor and infiltration into the center of lesions. Finally, we found that repeated IT injections of MCMV caused more marked tumor growth delay and resulted in increased tumor clearance. Together, our results show that MCMV promotes tumor growth delay by modulation of the TAM compartment through recruitment of new macrophages via viral MCK-2 and infection of TAMs to promote an M1-like state within the tumor. Citation Format: Nicole A. Wilski, Christina Del Casale, Vitali Alexeev, Constantine Daskalakis, Timothy J. Purwin, Andrew E. Aplin, Christopher M. Snyder. Cytomegalovirus infection of melanoma delays tumor growth by recruiting and altering monocytic phagocytes in the tumor [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A74.

Background and purpose: We conducted a phase I trial of alisertib, an oral aurora kinase inhibitor, with fractionated stereotactic re-irradiation therapy (FSRT) for patients with recurrent high grade glioma (HGG). Materials and methods: Adult patients with recurrent HGG were enrolled from Feb 2015 to Feb 2017. Patients were treated with concurrent FSRT and alisertib followed by maintenance alisertib. Concurrent alisertib dose was escalated from 20 mg to 50 mg twice daily (BID). Results: 17 patients were enrolled. Median follow-up was 11 months. Median FSRT dose was 35 Gy. There were 6, 6, 3, and 2 patients enrolled in 20 mg, 30 mg, 40 mg, and 50 mg cohort, respectively. Only one DLT was observed. One patient in the 20 mg cohort had severe headache (Grade 3) resolved with steroids. There was no non-hematological grade 3 or higher toxicity. There were two Grade 4 late toxicities (one with grade 4 neutropenia and leukopenia, one with pulmonary embolism). One patient developed radiation necrosis (Grade 3). Sixteen patients finished concurrent treatment and received maintenance therapy (median cycles was 3, range 1-9). OS for all cohorts at 6 months was 88.2% with median survival time of 11.1 months. PFS at 6 months was 35.3% with median time to progression of 4.9 months. The trial stopped early due to closure of alisertib program with only 2 of 3 planned patients enrolled in the 50 mg cohort. Conclusion: Re-irradiation with FSRT combined with alisertib is safe and well tolerated for HGG with doses up to 40 mg BID. Although no DLT observed in the 50 mg cohort, this cohort was not fully enrolled and MTD was not reached. Clinical outcomes appear comparable to historical results. (NCT02186509) (C) 2018 Elsevier B.V. All rights reserved.

INTRODUCTION: Direct access colonoscopy (DAC) pathways facilitate access to colon cancer screening. However, the absence of a pre-procedure office visit may increase the risk for inadequate colon cleansing, particularly in patients (pts) already at high risk for this. The aim of this pilot study was to establish non-inferiority of preparation (prep) adequacy for high-risk patients receiving high-dose (HD) purgative versus average-risk patients receiving standard-dose (SD) prep. METHODS: This was a retrospective single academic center study. HD assignment for DAC was based on any of the following criteria: chronic constipation (<3 BM/week), medications (narcotics, tricyclics, or calcium channel blockers), diabetes mellitus (DM) on medication, stroke, BMI >35, or prior inadequate prep. All pts received a PEG based prep. HD was defined as >2L PEG-ELS/vitamin C (MoviPrep®), >4L of PEG-ELS, or >2L PEG 3350-sports drink. Prep adequacy (BBPS of ≥2 per segment) was compared between the HD and SD groups, with a 12% relative margin of non-inferiority (relative risk = 0.88). Assuming an overall 85% adequacy rate, 140 patients per group would give the study 80% power. Secondary outcomes were comparison of inadequate prep risk factors between study groups. RESULTS: We identified 1,522 pts who received DAC over 11 months. 156 pts were excluded due to no electronic prep order or non-PEG prep use. These interim analyses are based on all 59 HD pts and a subset of 140 of the 1307 SD pts. The adequacy rates were 92% for HD (54/59) versus 99% for SD (139/140), failing to establish non-inferiority ( P -value = 0.17). Predictably, HD pts were more likely than SD pts to have prior inadequate preparation (19% vs. 0%), to be obese (68% vs. 39%), to have chronic constipation (15% vs. 6%), to have DM on medication (32% vs. 16%), and to be using narcotics (10% vs. 5%) or tricyclics (5% vs. 1%). CONCLUSION: Despite miss-assignment of many pts high risk for inadequate prep to SD, we found high rates of adequate cleansing in all DAC pts. Improper prep assignment and retrospective design allowing examination of only electronic (and not telephone) orders likely contributed to fewer pts than expected in the HD arm. This interim analysis does not establish non-inferiority of the HD prep for pts high risk for prep failure. Future efforts will focus on analyzing and correcting the cause for pt miss-assignment and prospectively evaluating prep adequacy in these two groups.

Inpatient (inpt) colonoscopy is performed almost exclusively to evaluate symptoms or signs. Effective bowel preparation is crucial but is frequently inadequate in inpts. We previously compared 4L PEG-ELS PM to split dose 2L PEG-ELS with vitamin C (PEG-Asc) (MoviPrep®) for inpt colonoscopy and found no significant difference with respect to adequacy (67%-72%). This study evaluated whether a formulary change from standard dose to high dose PEG-Asc improved preparation adequacy.

Introduction: Management of pediatric pain from medical procedures is of great importance for improving both patient care and experience. In this study, we investigated methods of managing acute pain in infants and children by studying the correlation between the number of attempts to complete painful procedures, given different comfort measures. Methods: The study is a retrospective review of 74,276 procedures performed at two pediatric hospitals in an integrated academic children's health system between 2013 and 2016. We compared three comfort measures most frequently offered: positions of comfort (POC), distraction (DIST), and pharmacological (PHARM). These methods were compared in the setting of four procedures: peripheral intravenous (PIV) catheter insertion, gastrointestinal tube placement, incision procedures, and bladder catheterization. We used the number of attempts needed to complete a procedure as a measure of efficacy minimizing distressing experience in an acutely painful setting (single attempt vs repeat attempts). Results: Among younger children, DIST appears superior to the other two methods; it performs significantly better for three of the four procedures (PIV catheterization, incision wound, and urinary catheterization) among infants aged <1 year and for PIV catheterization among toddlers aged 1-3 years. For older children, POC tends to perform slightly better than the other two methods, although it is significantly better only for PIV catheterization among adolescents aged 13-21 years and urinary catheterization among children aged 9-12 years. Conclusion: Results from this study may be used to determine appropriate comfort measures for painful procedures in pediatric setting.