Management Considerations for the Older Adult With Inflammatory Bowel Disease.

As the prevalence of older adults with inflammatory bowel disease (IBD) is rising, understanding the unique challenges in both diagnosis and management is becoming increasingly important. Knowledge of phenotypic differences as well as overlapping symptoms with other medical conditions is critical to obtaining a timely diagnosis of IBD in older adults. Although older adults with IBD are at higher risk for adverse events compared with younger adults with IBD, recent data have suggested that ongoing disease activity may be a significant driver of adverse clinical outcomes rather than use of current treatment modalities. Ultimately, earlier and effective treatments can improve outcomes and quality of life for older adults with IBD. However, to help improve medical decision-making, clinicians must move away from the use of chronological age alone and begin to integrate measures of biological age, such as frailty and sarcopenia, into risk stratification tools. This article reviews the management considerations for older adults with IBD and provides the rationale for incorporating measures of biological age into current practice.

Burden and risk factors for inappropriate Clostridioides Difficile infection testing among hospitalized patients.

BACKGROUND: The purpose of this study was to identify the burden and risk factors for inappropriate Clostridioides difficile infection (CDI) testing. METHODS: This was a retrospective cohort study among adults hospitalized between 2010 and 2019. Inappropriate CDI testing was defined as a formed stool specimen, an order within 7 days of a previously negative test, or an order within 24 hours of laxative administration. RESULTS: A total of 51,302 CDI orders were placed for 29,840 unique patients. 59% were appropriate and 41% were inappropriate. An additional 24% of the appropriate orders never resulted. Risk factors for inappropriate testing included orders placed by a nurse practitioner, orders placed by high-ordering providers, specific hospital units, fever, and leukocytosis. CONCLUSIONS: Nearly half of all CDI orders were inappropriate among hospitalized patients, and an additional 24% of test results never returned. Provider- and patient-level risk factors included type of provider, specific hospital units, and signs of sepsis.

Pregnant Women's Current and Intended Cannabis Use in Relation to Their Views Toward Legalization and Knowledge of Potential Harm.

OBJECTIVES: The objective of this study was to investigate pregnant women's current use of cannabis and their intended patterns of use with relation to their views on the legalization of cannabis and their knowledge of potential harms. METHODS: A voluntary, anonymous survey regarding patterns of use of cannabis and views on legalization was distributed to a convenience sample of pregnant women presenting for prenatal care at an outpatient university clinic. Chi-square and Fischer's exact tests were used for analysis using STATA. RESULTS: Of 306 surveys returned, 35% of women reported currently using cannabis at the time of diagnosis of pregnancy and 34% of those women continued to use. Seventy percent of respondents endorsed the belief that cannabis could be harmful to a pregnancy. Fifty-nine percent of respondents believed that cannabis should be legalized in some form and 10% reported that they would use cannabis more during pregnancy if it were legalized. Those who continued to use cannabis during pregnancy were less likely than those who quit to believe that cannabis use could be harmful during pregnancy (26% vs 75%, P < 0.001). The most common motivation for quitting cannabis use in pregnancy was to avoid being a bad example (74%); in comparison, only 27% of respondents listed a doctor's recommendation as a motivation to quit. CONCLUSIONS: Cannabis use during pregnancy is relatively common and persistent, despite knowledge of the potential risks of harm. Views toward legalization vary among pregnant women and may impact cannabis use during pregnancy. In a changing legal climate, there is a need for clear messaging on the effects of cannabis use during pregnancy.

Histone deacetylase inhibitor AR-42 enhances E7-specific CD8⁺ T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination.

UNLABELLED: We have previously created a potent DNA vaccine encoding calreticulin linked to the human papillomavirus (HPV) oncogenic protein E7 (CRT/E7). While treatment with the CRT/E7 DNA vaccine generates significant tumor-specific immune responses in vaccinated mice, the potency with the DNA vaccine could potentially be improved by co-administration of a histone deacetylase inhibitor (HDACi) as HDACi has been shown to increase the expression of MHC class I and II molecules. Thus, we aimed to determine whether co-administration of a novel HDACi, AR-42, with therapeutic HPV DNA vaccines could improve the activation of HPV antigen-specific CD8(+) T cells, resulting in potent therapeutic antitumor effects. To do so, HPV-16 E7-expressing murine TC-1 tumor-bearing mice were treated orally with AR-42 and/or CRT/E7 DNA vaccine via gene gun. Mice were monitored for E7-specific CD8(+) T cell immune responses and antitumor effects. TC-1 tumor-bearing mice treated with AR-42 and CRT/E7 DNA vaccine experienced longer survival, decreased tumor growth, and enhanced E7-specific immune response compared to mice treated with AR-42 or CRT/E7 DNA vaccine alone. Additionally, treatment of TC-1 cells with AR-42 increased the surface expression of MHC class I molecules and increased the susceptibility of tumor cells to the cytotoxicity of E7-specific T cells. This study indicates the ability of AR-42 to significantly enhance the potency of the CRT/E7 DNA vaccine by improving tumor-specific immune responses and antitumor effects. Both AR-42 and CRT/E7 DNA vaccines have been used in independent clinical trials; the current study serves as foundation for future clinical trials combining both treatments in cervical cancer therapy. KEY MESSAGE: AR-42, a novel HDAC inhibitor, enhances potency of therapeutic HPV DNA vaccines AR-42 treatment leads to strong E7-specific CD8+ T cell immune responses AR-42 improves tumor-specific immunity and antitumor effects elicited by HPV DNA vaccine AR-42 is more potent than clinically available HDACi in combination with HPV DNA vaccine.