Implementing the National Heart, Lung, and Blood Institute's Strategic Vision in the Division of Cardiovascular Sciences-2022 Update.

Spurred by the 2016 release of the National Heart, Lung, and Blood Institute's Strategic Vision, the Division of Cardiovascular Sciences developed its Strategic Vision Implementation Plan-a blueprint for reigniting the decline in cardiovascular disease (CVD) mortality rates, improving health equity, and accelerating translation of scientific discoveries into better cardiovascular health (CVH). The 6 scientific focus areas of the Strategic Vision Implementation Plan reflect the multifactorial nature of CVD and include (1) addressing social determinants of CVH and health inequities, (2) enhancing resilience, (3) promoting CVH and preventing CVD across the lifespan, (4) eliminating hypertension-related CVD, (5) reducing the burden of heart failure, and (6) preventing vascular dementia. This article presents an update of strategic vision implementation activities within Division of Cardiovascular Sciences. Overarching and cross-cutting themes include training the scientific workforce and engaging the extramural scientific community to stimulate transformative research in cardiovascular sciences. In partnership with other NIH Institutes, Federal agencies, industry, and the extramural research community, Division of Cardiovascular Sciences strategic vision implementation has stimulated development of numerous workshops and research funding opportunities. Strategic Vision Implementation Plan activities highlight innovative intervention modalities, interdisciplinary systems approaches to CVD reduction, a life course framework for CVH promotion and CVD prevention, and multi-pronged research strategies for combatting COVID-19. As new knowledge, technologies, and areas of scientific research emerge, Division of Cardiovascular Sciences will continue its thoughtful approach to strategic vision implementation, remaining poised to seize emerging opportunities and catalyze breakthroughs in cardiovascular sciences.

Exposure-response relationships of etrolizumab in patients with moderately-to-severely active ulcerative colitis.

Etrolizumab is an IgG1-humanized monoclonal anti-ß7 integrin antibody. Phase III trials with induction and/or maintenance phases were conducted in patients with moderately-to-severely active ulcerative colitis (UC) who were either previously treated with tumor necrosis factor (TNF) inhibitors (HICKORY) or were TNF inhibitor naïve (HIBISCUS I/II, LAUREL, and GARDENIA). A total of eight exposure-response analyses were conducted for two clinical outcomes (remission and endoscopic improvement) at the end of induction for studies HIBISCUS I/II (combined) and HICKORY and at the end of maintenance for studies HICKORY and LAUREL. Trough concentration at week 4 (Ctrough,wk4 ) of induction was selected as the exposure metric. Exposure-response (ER) modeling was conducted using logistic regression. A full covariate model was used to examine the impact of covariates on clinical outcomes. Linear models with a single intercept for placebo and active treatments adequately described the data for all eight analyses. The etrolizumab exposure-response slope was significant (p < 0.05) for seven of the eight analyses. Baseline Mayo Clinic Score (MCS) was the only statistically significant covariate that impacted induction remission and endoscopic improvement. No statistically significant covariate was identified to impact maintenance outcomes except for baseline fecal calprotectin on endoscopic improvement for LAUREL study. A statistically significant positive ER relationship was identified for most of the clinical outcomes tested, reflecting a better treatment effect in patients with UC with higher etrolizumab Ctrough,wk4 of induction. Baseline MCS was the only other significant covariate impacting induction efficacy. Besides Ctrough,wk4 of induction, no consistent covariate was identified to impact maintenance efficacy.

Analysis of Safety, Medical Resource Utilization, and Treatment Costs by Drug Class for Management of Inflammatory Bowel Disease in the United States Based on Insurance Claims Data.

INTRODUCTION: Conventional pharmaceutical interventions for inflammatory bowel disease (IBD) provide limited disease/symptom control and are associated with an increased risk of adverse events (AEs). These limitations increase patient morbidity, medical resource utilization (MRU), and costs. METHODS: The IQVIA™ Real-World Data Adjudicated Claims-US database was leveraged to identify adult patients (> 18 years) with Crohn's disease (Crohn's) or ulcerative colitis (UC), who were new and chronic users (≥ 60 days) of oral corticosteroids (OCS), immunosuppressants (IS), anti-tumor necrosis factor agents (anti-TNF) or combinations thereof. Using aminosalicylate-treated patients as a reference, we compared AE incidence, MRU, and medical costs across drug classes. RESULTS: The analysis included 30,676 patients (Crohn's: n = 14,528; UC: n  = 16,148). OCS monotherapy was the strongest predictor of any AE occurring [Crohn's: hazard ratio 1.62 (1.51-1.73); UC: hazard ratio 1.57 (1.49-1.66)]. A similar pattern was observed for severe infection and bone-related conditions. Patients with UC or Crohn's receiving OCS or IS plus OCS were more likely to have emergency department visits, IBD-related hospitalizations/visits/procedures, and gastrointestinal surgery than were patients receiving other therapies. Annualized total medical costs (pharmacy plus hospital service costs) were greatest for anti-TNF plus IS or anti-TNF therapy in both Crohn's and UC. Annualized medical service costs (excluding IBD drug costs) were highest for patients initiating OCS-containing therapies [Crohn's: OCS, $27,041 (24,882-29,200) and OCS plus IS, $23,332 (19,889-26,775); UC: OCS, $19,659 (17,977-21,340)]. CONCLUSION: Although biologic therapies have higher pharmacy costs, treatment decisions should consider the increased AE risks and long-term MRU costs associated with chronic use of OCS-containing therapies. FUNDING: This study was funded by F. Hoffmann-La Roche Ltd. The journal's Rapid Service Fee and Open Access publication were paid for by ApotheCom on behalf of Genentech, a member of the Roche group who funded the study.

Disseminated histoplasmosis in a liver transplant recipient.

A 61-yr-old liver transplant recipient presented with abdominal cramping and nonbloody diarrhea resulting in orthostasis. Multiple ulcerations throughout the colon were seen during endoscopy, and biopsies from the ulcer edges revealed histoplasmosis. Treatment with a course of itraconazole improved the diarrhea. The patient later presented with pericarditis and symptomatic pleural effusions, the latter of which was confirmed to be a result of disseminated histoplasmosis. Treatment with amphotericin B led to resolution. Histoplasmosis should be considered in liver transplant patients with diarrhea and large ulcers in the colon. The presence of disseminated histoplasmosis should be ruled out once colonic histoplasmosis has been diagnosed.