Benzodiazepine and antipsychotic use among hospitalized older adults before versus after restricting visitation: March to May 2020.

BACKGROUND: Hospital visitation restrictions during the COVID-19 pandemic prompted concerns about unintended consequences for older patients, including an increased incidence of delirium and agitation. While first-line interventions for these conditions are non-pharmacologic, a lack of family support could result in increased use of benzodiazepines and antipsychotics, which are associated with poor outcomes in older adults. Little is known about the association of visitation policies with use of these medications among older adults. METHODS: We conducted a retrospective cross-sectional study among adults aged ≥65 hospitalized from March 1 through May 31, 2020 at four hospitals in the Mid-Atlantic. The dates of onset of visitation restrictions (i.e., hospital-wide guidelines barring visitors) were collected from hospital administrators. Outcomes were use of benzodiazepines and antipsychotics, assessed using patient-level electronic health record data. Using multivariable logistic regression with hospital and study-day fixed effects, the quasi-experimental study design leveraged the staggered onset of visitation restrictions across the hospitals to measure the odds of receiving each medication when visitors were versus were not allowed. RESULTS: Among 2931 patients, mean age was 76.6 years (SD, 8.3), 51.6% were female, 58.6% white, 32.5% black, and 2.6% Hispanic. Overall, 924 (31.5%) patients received a benzodiazepine and 298 (10.2%) an antipsychotic. The adjusted odds of benzodiazepine use was lower on days when visitors were versus were not allowed (adjusted odds ratio [AOR], 0.62; 95% CI, 0.39, 0.99). Antipsychotic use did not significantly differ between days when visitors were versus were not allowed (AOR, 0.98; 95% CI, 0.43, 2.21). CONCLUSIONS: Among older patients hospitalized during the first wave of the pandemic, benzodiazepine use was lower on days when visitors were allowed. These findings suggest that the presence of caregivers impacts use of potentially inappropriate medications among hospitalized older adults, supporting efforts to recognize caregivers as essential members of the care team.

Transcriptional regulation and small compound targeting of ACE2 in lung epithelial cells.

Angiotensin-converting enzyme 2 (ACE2) is the receptor of COVID-19 pathogen SARS-CoV-2, but the transcription factors (TFs) that regulate the expression of the gene encoding ACE2 (ACE2) have not been systematically dissected. In this study we evaluated TFs that control ACE2 expression, and screened for small molecule compounds that could modulate ACE2 expression to block SARS-CoV-2 from entry into lung epithelial cells. By searching the online datasets we found that 24 TFs might be ACE2 regulators with signal transducer and activator of transcription 3 (Stat3) as the most significant one. In human normal lung tissues, the expression of ACE2 was positively correlated with phosphorylated Stat3 (p-Stat3). We demonstrated that Stat3 bound ACE2 promoter, and controlled its expression in 16HBE cells stimulated with interleukin 6 (IL-6). To screen for medicinal compounds that could modulate ACE2 expression, we conducted luciferase assay using HLF cells transfected with ACE2 promoter-luciferase constructs. Among the 64 compounds tested, 6-O-angeloylplenolin (6-OAP), a sesquiterpene lactone in Chinese medicinal herb Centipeda minima (CM), represented the most potent ACE2 repressor. 6-OAP (2.5 µM) inhibited the interaction between Stat3 protein and ACE2 promoter, thus suppressed ACE2 transcription. 6-OAP (1.25-5 µM) and its parental medicinal herb CM (0.125%-0.5%) dose-dependently downregulated ACE2 in 16HBE and Beas-2B cells; similar results were observed in the lung tissues of mice following administration of 6-OAP or CM for one month. In addition, 6-OAP/CM dose-dependently reduced IL-6 production and downregulated chemokines including CXCL13 and CX3CL1 in 16HBE cells. Moreover, we found that 6-OAP/CM inhibited the entry of SARS-CoV-2 S protein pseudovirus into target cells. These results suggest that 6-OAP/CM are ACE2 inhibitors that may potentially protect lung epithelial cells from SARS-CoV-2 infection.

Subtyping CKD Patients by Consensus Clustering: The Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: CKD is a heterogeneous condition with multiple underlying causes, risk factors, and outcomes. Subtyping CKD with multidimensional patient data holds the key to precision medicine. Consensus clustering may reveal CKD subgroups with different risk profiles of adverse outcomes. METHODS: We used unsupervised consensus clustering on 72 baseline characteristics among 2696 participants in the prospective Chronic Renal Insufficiency Cohort (CRIC) study to identify novel CKD subgroups that best represent the data pattern. Calculation of the standardized difference of each parameter used the cutoff of ±0.3 to show subgroup features. CKD subgroup associations were examined with the clinical end points of kidney failure, the composite outcome of cardiovascular diseases, and death. RESULTS: The algorithm revealed three unique CKD subgroups that best represented patients' baseline characteristics. Patients with relatively favorable levels of bone density and cardiac and kidney function markers, with lower prevalence of diabetes and obesity, and who used fewer medications formed cluster 1 (n=1203). Patients with higher prevalence of diabetes and obesity and who used more medications formed cluster 2 (n=1098). Patients with less favorable levels of bone mineral density, poor cardiac and kidney function markers, and inflammation delineated cluster 3 (n=395). These three subgroups, when linked with future clinical end points, were associated with different risks of CKD progression, cardiovascular disease, and death. Furthermore, patient heterogeneity among predefined subgroups with similar baseline kidney function emerged. CONCLUSIONS: Consensus clustering synthesized the patterns of baseline clinical and laboratory measures and revealed distinct CKD subgroups, which were associated with markedly different risks of important clinical outcomes. Further examination of patient subgroups and associated biomarkers may provide next steps toward precision medicine.

Are Patients With Inflammatory Bowel Disease at an Increased Risk of Developing SARS-CoV-2 than Patients Without Inflammatory Bowel Disease? Results From a Nationwide Veterans' Affairs Cohort Study.

INTRODUCTION: The clinic course of SARS-CoV-2 among patients with inflammatory bowel disease (IBD) has been extensively studied. However, there is a paucity of data on whether patients with IBD have an increased risk of developing SARS-CoV-2 with compared with patients without IBD. METHODS: We conducted a nationwide retrospective cohort study in the US Veterans' Affairs healthcare system from January 1, 2020, to June 30, 2020. We matched each patient with IBD with 2 patients without IBD on age, sex, race, location, and comorbidities. The outcome of interest was development of SARS-CoV-2. RESULTS: Among 38,378 patients with IBD and 67,433 patients without IBD, 87 (0.23%) and 132 (0.20%) patients developed incident SARS-CoV-2 infection, respectively (P = 0.29). DISCUSSION: Patients with IBD are not at a significantly increased risk of developing SARS-CoV-2 infection when compared with patients without IBD.