Effect of an Electronic Health Record Decision Support Alert to Decrease Excess Cervical Cancer Screening.

OBJECTIVE: Cervical cancer screening is often conducted in excess of current screening guidelines. The objective of this study was to evaluate the effect of an electronic health record (EHR) clinical decision support alert to decrease guideline-nonadherent cervical cancer screening beyond the age limits of screening or posthysterectomy. MATERIALS AND METHODS: The proportion of guideline-nonadherent Pap tests in women younger than 21 years or older than 65 years or posthysterectomy were compared 4 months before and 3 months after implementation of an EHR clinical decision support alert warning providers that a Pap test is not indicated. Providers could cancel the Pap test or override the alert and place the order. Provider characteristics and Pap test indications were summarized by preintervention/postintervention period using descriptive statistics. The proportions of nonindicated Pap tests were compared by intervention period and provider characteristics using generalized estimating equation models. RESULTS: In women beyond the screening age limits or posthysterectomy, a total of 388 Pap tests were ordered before intervention, and 313 tests were ordered after intervention. Proportion of guideline-nonadherent tests was similar before (62%) and after intervention (63%); thus, implementation of the clinical decision support alert did not change the proportion of guideline-nonadherent Pap tests ordered (OR = 1.08, 95% CI = 0.77-1.52). It is notable that 52% of guideline-nonadherent tests were ordered by 11 providers. Even when controlling for providers who ordered more than 1 test during the study period, multivariate analysis showed that male providers were more likely to order guideline-nonadherent Pap tests (OR = 2.30, 95% CI = 1.36-3.89); no other differences by provider characteristics were observed. CONCLUSIONS: An EHR clinical decision support alert does not decrease guideline-nonadherent cervical cancer screening. These data suggest efforts to optimize clinical decision support should be focused on other aspects of cervical cancer prevention.

Impact of the COVID-19 pandemic on referral to and delivery of gynecologic oncology care.

OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on referral to and delivery of gynecologic oncology care at a National Cancer Institute-designated Comprehensive Cancer Center. METHODS: We conducted a retrospective cohort study of patients referred for evaluation by a gynecologic oncologist at Washington University in St. Louis from October 2019 - February 2020 (pre-COVID-19), and April - August 2020 (COVID-19). The primary outcome, time from referral to evaluation by a gynecologic oncologist, was compared between the two time periods. Secondary outcomes included time from initial evaluation to treatment and delays/interruptions in care due to the pandemic. Sub-group analyses were performed on patients with a cancer diagnosis to evaluate the impact of COVID-19 on treatment decision making. RESULTS: 884 patients were referred during the study period. Total referrals fell by 32% (526 to 358 patients, p < 0.001) and referrals for cancer fell by 18% (228 to 188 patients, p = 0.049). The pandemic did not impact time from referral to initial gynecologic oncology appointment overall (pre-COVID-19: 19.1 vs. COVID-19: 17.4 days, p = 0.315) or among patients with cancer (14.4 vs. 13.9 days, p = 0.662). Time from initial appointment to cancer treatment decreased by 9 days (34 days to 25 days, p = 0.001). CONCLUSION: Referrals to gynecologic oncology decreased significantly during the early months of COVID-19. Though time from referral to evaluation was not impacted by the pandemic, time to treatment initiation decreased despite institutional changes related to COVID-19.

Prognostic factors for clinical outcomes of patients with central nervous system leukemia.

Prognostic factors associated with clinical outcomes of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients with central nervous system (CNS) involvement are unknown. We retrospectively studied the characteristics and outcomes of 66 (18 pediatric and 48 adult) patients with CNS leukemia with ALL (n = 41) or AML (n = 25). The median age of patients at diagnosis of CNS leukemia was 30 (range, 1-69) years. Nearly two-third patients had CNS involvement at the initial diagnosis of leukemia. Complete remission of CNS leukemia was attained in 58 (88%) patients, and probability of overall survival at 36 months after the diagnosis of CNS leukemia was 43% for the entire cohort. We identified that achieving remission of systemic leukemia and having CNS leukemia diagnosed and treated before allogeneic transplantation were the factors associated with CNS leukemia remission. Prognostic factors associated with better overall survival in patients with CNS leukemia included pediatric age, diagnosis of CNS leukemia before receiving allogenic transplantation, achieving clearance of systemic or CNS leukemia, receiving no cranial radiation in conjunction with intrathecal chemotherapy (IT), and receiving IT consolidation after achieving remission of CNS leukemia. Our findings show that patients with CNS leukemia are at considerable risk of mortality. Awareness of modifiable prognostic factors such as avoidance of cranial radiation whenever possible and use of IT consolidation can result in improved outcomes in subset of patients with CNS leukemia.

Pancreatic stellate cell models for transcriptional studies of desmoplasia-associated genes.

BACKGROUND: Pancreatic stellate cells are emerging as key players in pathophysiopathological processes underlying the development of pancreatic disease, including pancreatitis and cancer. The cells are scarce in the pancreas making their isolation time and resource use consuming. METHODS: Therefore, with the ultimate goal of facilitating mechanistic studies, here we report the isolation, characterization, and immortalization of stellate cell lines from rat and mouse origin. RESULTS: These cell lines display morphological and molecular markers as well as non-tumorigenic characteristics similar to the frequently used hepatic counterparts. In addition, we have tested their robustness as a model for transcriptional regulatory studies. We find that these cells respond well to TGFß signaling by triggering a distinct cascade of gene expression, some genes overlap with the TGFß response of LX2 cells. These cells express several key chromatin proteins and epigenetic regulators involved in the regulation of gene expression, including co-repressors such as Sin3A (short-term repression), HP1 (long-term repression), as well as CBP/p300 (activation). Furthermore, these cells are well suited for Gal4-based transcriptional activation and repression assays. CONCLUSIONS: The cell model reported here may therefore help fuel investigations in the field of signaling, transcription, and perhaps other studies on similarly exciting cellular processes. and IAP.