Baricitinib in hospitalised patients with COVID-19: A meta-analysis of randomised controlled trials.

Background: To date, only dexamethasone and tocilizumab have been shown to reduce mortality in patients with COVID-19. Baricitinib is a Janus kinase 1/2 inhibitor with known anti-inflammatory and anti-viral properties. We performed a meta-analysis of RCTs assessing the role of baricitinib in hospitalised patients with COVID-19. Methods: Electronic databases such as MEDLINE, EMBASE, and Cochrane Central were searched up until March 31, 2022, for RCTs evaluating the efficacy of baricitinib in hospitalised patients with COVID-19. The outcomes assessed were 28-day mortality, progression to invasive mechanical ventilation (IMV) or ECMO, progression to respiratory failure needing positive pressure ventilation, IMV or death, duration of hospitalisation and time to discharge. The meta-analysis was registered in the PROSPERO database (CRD42022314579). Findings: Four studies (with 10,815 patients) were included in the analysis. Pooled analysis using random-effects model showed a statistically significant reduction in 28-day mortality (OR 0.69, 95% CI 0.50-0.94; p=0.04, I2=65%) and composite outcome of progression to severe disease needing positive pressure ventilation, IMV or death (OR 0.89, 95% CI 0.80-0.99, p= 0.03, I2=0%). There was a favorable trend towards reduced progression to IMV or ECMO (OR 0.76, 95% CI 0.58-1.01; p=0.06, I2=49%) in the baricitinib arm compared to standard therapy, even though it was not statistically significant. Statistical significance was achieved for all outcomes with fixed-effects model analysis. Interpretation: In hospitalised patients with COVID-19, baricitinib was associated with reduced 28-day mortality although there was not a statistically significant reduction in progression to IMV or ECMO. Baricitinib used in conjunction with standard of care treatments is associated with improved mortality in hospitalised patients with COVID-19 disease. Funding: None.

The impact of errors on healthcare professionals in the critical care setting.

PURPOSE: Medical errors occur at high rates in intensive care units (ICUs) and have great consequences. The impact of errors on healthcare professionals is rarely discussed. We hypothesized that issues regarding blame and guilt following errors in the ICU exist and may be dependent on type of practitioner, level of experience, and error type. MATERIALS AND METHODS: An online survey was conducted of members of a large critical care medical society addressing three clinical scenarios of procedural, diagnostic and treatment errors. RESULTS: Nine hundred one practitioners responded. In all scenarios, negative feeling after medical errors occurred in all practitioners regardless of experience or field. Surgeons and anesthesiologists showed higher negative responses after procedural errors while internal medicine and emergency medicine practitioners had higher negative responses after diagnostic errors. Survey respondents identified multiple ways to address these adverse feelings, including debriefing with the medical team (68%), talking with colleagues (68%) and discussing with patients and families (36%). CONCLUSIONS: In critical care, blame and guilt after medical errors are common and affect all providers. Critical care practitioners have identified methods which may help mitigate adverse feeling after medical errors, including debriefing and talking with colleagues. Hospitals may benefit from developing these types of strategies after medical errors.

Arterial Catheter Use in the ICU: A National Survey of Antiseptic Technique and Perceived Infectious Risk.

OBJECTIVES: Recent studies have shown that the occurrence rate of bloodstream infections associated with arterial catheters is 0.9-3.4/1,000 catheter-days, which is comparable to that of central venous catheters. In 2011, the Centers for Disease Control and Prevention published new guidelines recommending the use of limited barrier precautions during arterial catheter insertion, consisting of sterile gloves, a surgical cap, a surgical mask, and a small sterile drape. The goal of this study was to assess the attitudes and current infection prevention practices used by clinicians during insertion of arterial catheters in ICUs in the United States. DESIGN: An anonymous, 22-question web-based survey of infection prevention practices during arterial catheter insertion. SETTING: Clinician members of the Society of Critical Care Medicine. SUBJECTS: Eleven thousand three hundred sixty-one physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who elect to receive e-mails from the Society of Critical Care Medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 1,265 responses (11% response rate), with 1,029 eligible participants after exclusions were applied. Only 44% of participants reported using the Centers for Disease Control and Prevention-recommended barrier precautions during arterial catheter insertion, and only 15% reported using full barrier precautions. The mean and median estimates of the incidence density of bloodstream infections associated with arterial catheters were 0.3/1,000 catheter-days and 0.1/1,000 catheter-days, respectively. Thirty-nine percent of participants reported that they would support mandatory use of full barrier precautions during arterial catheter insertion. CONCLUSIONS: Barrier precautions are used inconsistently by critical care clinicians during arterial catheter insertion in the ICU setting. Less than half of clinicians surveyed were in compliance with current Centers for Disease Control and Prevention guidelines. Clinicians significantly underestimated the infectious risk posed by arterial catheters, and support for mandatory use of full barrier precautions was low. Further studies are warranted to determine the optimal preventive strategies for reducing bloodstream infections associated with arterial catheters.

Central line placement in patients with and without prophylactic plasma.

Central line placement (CLP) is a common life-saving intervention in critically ill patients, and patients with coagulation abnormalities as identified by an abnormal international normalized ratio (INR) may receive prophylactic plasma transfusion before the procedure despite previously published data that such a practice is not efficacious. Over a 14-month period, 287 CLPs were performed in the intensive care unit. The use of plasma preprocedure in patients with an elevated INR was generally discouraged but left to the discretion of the operator. A total of 100 lines were placed in patients with a preprocedure INR greater than 1.5, 27 of whom received prophylactic fresh frozen plasma. Only 1 case of bleeding was observed in a patient with an INR of 3.9, who received fresh frozen plasma preprocedure (0/73 vs 1/27; P = .6). The occurrence of bleeding was very low overall with CLP (0.3%; 95% confidence interval, 0%-2%), and no benefit of prophylactic plasma was observed.

Natriuretic peptides differentially attenuate thrombin-induced barrier dysfunction in pulmonary microvascular endothelial cells.

Previous studies have described a protective effect of atrial natriuretic peptide (ANP) against agonist-induced permeability in endothelial cells derived from various vascular beds. In the current study, we assessed the effects of the three natriuretic peptides on thrombin-induced barrier dysfunction in rat lung microvascular endothelial cells (LMVEC). Both ANP and brain natriuretic peptide (BNP) attenuated the effect of thrombin on increased endothelial monolayer permeability and significantly enhanced the rate of barrier restoration. C-type natriuretic peptide (CNP) had no effect on the degree of thrombin-induced monolayer permeability, but did enhance the restoration of the endothelial barrier, similar to ANP and BNP. In contrast, the non-guanylyl cyclase-linked natriuretic peptide receptor specific ligand, cyclic-atrial natriuretic factor (c-ANF), delayed the rate of barrier restoration following exposure to thrombin. All three natriuretic peptides promoted cGMP production in the endothelial cells; however, 8-bromo-cGMP alone did not significantly affect thrombin modulation of endothelial barrier function. ANP and BNP, but not CNP or c-ANF, blunted thrombin-induced RhoA GTPase activation. We conclude that ANP and BNP protect against thrombin-induced barrier dysfunction in the pulmonary microcirculation by a cGMP-independent mechanism, possibly by attenuation of RhoA activation.