Dempsey, Timothy

Objective: The specialty of critical care in the United States currently lacks a single, broad, unified database. We conducted a scoping review of existing established national ICU databases, describing national and international patterns of critical care delivery. Data Sources: A systematic literature search was undertaken using MEDLINE, Embase, and Web of Science search engines. Study Selection: Projects describing national critical care delivery (including any subspecialty) published in any language were included. Titles, abstracts, and full-text manuscripts were reviewed in duplicate for inclusion. Data Extraction: National database characteristics were collected, including the number and subspecialty of ICUs, the inaugural year, data entry methodology, the number of episodes of care included, and captured clinical data elements. Data Synthesis: Of 24,003 abstracts screened, 185 manuscripts were eligible for inclusion. Thirty countries were identified as having established national ICU registries: Argentina, Australia/New Zealand, Austria, Belgium, Brazil, Canada, Denmark, Ecuador, Finland, Germany, Iceland, India, Ireland, Italy, Japan, Kenya, Malaysia, Mexico, Nepal, Netherlands, Norway, Pakistan, Paraguay, Spain, Sri Lanka, Sweden, Switzerland, United Kingdom, United States and Uruguay. Data entry commonly incorporates a combination of automated data abstraction from electronic healthcare systems and manual data entry, followed by independent validation. Frequently recorded variables include patient demographics; admission vital signs and laboratory data; comorbidities; admission source and diagnoses; ICU diagnoses, treatments, and complications; illness severity scores; and clinically relevant outcomes including discharge disposition, functional status, lengths of stay, and mortality. Conclusions: Insights and experience gained from the study of mature national ICU registries may be used to guide an equivalent U.S. multidisciplinary program aimed at benchmarking, needs assessment, quality improvement, and research facilitation

Objectives Evaluate the associations between patients taking ACE inhibitors and angiotensin receptor blockers (ARBs) and their clinical outcomes after an acute viral respiratory illness (AVRI) due to COVID-19. Design Retrospective cohort. Setting The USA; 2017–2018 influenza season, 2018–2019 influenza season, and 2019–2020 influenza/COVID-19 season. Participants People with hypertension (HTN) taking an ACEi, ARB or other HTN medications, and experiencing AVRI. Main outcome measures Change in hospital admission, intensive care unit (ICU) or coronary care unit (CCU), acute respiratory distress (ARD), ARD syndrome (ARDS) and all-cause mortality, comparing COVID-19 to pre-COVID-19 influenza seasons. Results The cohort included 1 059 474 episodes of AVRI (653 797 filled an ACEi or ARB, and 405 677 other HTN medications). 58.6% were women and 72.9% with age ≥65. The ACEi/ARB cohort saw a larger increase in risk in the COVID-19 influenza season than the other HTN medication cohort for four out of five outcomes, with an additional 1.5 percentage point (pp) increase in risk of an inpatient stay (95% CI 1.2 to 1.9 pp) and of ICU/CCU use (95% CI 0.3 to 2.7 pp) as well as a 0.7 pp (0.1 to 1.2 pp) additional increase in risk of ARD and 0.9 pp (0.4 to 1.3 pp) additional increase in risk of ARDS. There was no statistically significant difference in the absolute risk of death (−0.2 pp, 95% CI −0.4 to 0.1 pp). However, the relative risk of death in 2019/2020 versus 2017/2018 for the ACEi/ARB group was larger (1.40 (1.36 to 1.44)) than for the other HTN medication cohort (1.24 (1.21 to 1.28)). Conclusions People with AVRI using ACEi/ARBs for HTN had a greater increase in poor outcomes during the COVID-19 pandemic than those using other medications to treat HTN. The small absolute magnitude of the differences likely does not support changes in clinical practice.

Objectives Evaluate associations between ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs) and clinical outcomes in acute viral respiratory illness (AVRI). Design Retrospective cohort analysis of claims data. Setting The USA; 2018–2019 influenza season. Participants Main cohort: people with hypertension (HTN) taking an ACEi, ARB or other HTN medications, and experiencing AVRI. Falsification cohort: parallel cohort receiving elective knee or hip replacement. Main outcome measures Main cohort: hospital admission, intensive care unit, acute respiratory distress (ARD), ARD syndrome and all-cause mortality. Falsification cohort: complications after surgery and all-cause mortality. Results The main cohort included 236 843 episodes of AVRI contributed by 202 629 unique individuals. Most episodes were in women (58.9%), 81.4% in people with Medicare Advantage and 40.3% in people aged 75+ years. Odds of mortality were lower in the ACEi (0.78 (0.74 to 0.83)) and ARB (0.64 (0.61 to 0.68)) cohorts compared with other HTN medications. On all other outcomes, people taking ARBs (but not ACEis) had a >10% reduction in odds of inpatient stays compared with other HTN medications. In the falsification analysis (N=103 353), both ACEis (0.89 (0.80 to 0.98)) and ARBs (0.82 (0.74 to 0.91)) were associated with decreased odds of complications compared with other HTN medications; ARBs (0.64 (0.47 to 0.87)) but not ACEis (0.79 (0.60 to 1.05)) were associated with lower odds of death compared with other HTN medications. Conclusions Outpatient use of ARBs was associated with better outcomes with AVRI compared with other medications for HTN. ACEis were associated with reduced risk of death, but with minimal or no reduction in risk of other complications. A falsification analysis conducted to provide context on the possible causal implications of these findings did not provide a clear answer. Further analysis using observational data will benefit from additional approaches to assess causal relationships between these drugs and outcomes in AVRI.

Abstract Rationale In October 2014, the antifibrotic medications pirfenidone and nintedanib became the first medications approved by the U.S. Food and Drug Administration for use in patients with idiopathic pulmonary fibrosis (IPF). Since approval, there has been no nonregistry analysis of the real-world adoption of these medications in everyday clinical practice. Objectives To evaluate the adoption, persistence, and out-of-pocket (OOP) costs of pirfenidone and nintedanib since their approval in the United States in 2014. Methods A retrospective cohort analysis was performed by identifying privately insured and Medicare Advantage beneficiaries with IPF. We then split the patients into three cohorts: those who were untreated and those who filled a prescription for either pirfenidone or nintedanib between October 1, 2014, and July 31, 2019. The primary outcome was adoption of the medications. Secondary outcomes included medication persistence and prescription drug costs. Results A total of 10,996 patients with IPF were identified in the data set. A minority of patients (26.4%) with IPF identified in the cohort had started either medication since approval in 2014, with the adoption of both medications being comparable at around 13.2%. Those receiving the medications were younger (72 vs. 73.9 yr; P < 0.0001) and healthier (3.9 vs. 4.9 comorbidities; P < 0.0001) than those not receiving treatment. Men were significantly more likely to receive treatment than woman (30.0% vs. 21.9%; P < 0.0001). Among treated patients, 42.8% discontinued the medications during the study period. Patients’ OOP expenses per month were high for both drugs (mean, $397.51 for nintedanib; mean, $394.49 for pirfenidone). Conclusions The adoption of both the antifibrotic medications in the United States in everyday practice has been low since approval and may be associated with the high OOP cost.