Mechanisms by which the cystic fibrosis transmembrane conductance regulator may influence SARS-CoV-2 infection and COVID-19 disease severity.

Patients with cystic fibrosis (CF) exhibit pronounced respiratory damage and were initially considered among those at highest risk for serious harm from SARS-CoV-2 infection. Numerous clinical studies have subsequently reported that individuals with CF in North America and Europe-while susceptible to severe COVID-19-are often spared from the highest levels of virus-associated mortality. To understand features that might influence COVID-19 among patients with cystic fibrosis, we studied relationships between SARS-CoV-2 and the gene responsible for CF (i.e., the cystic fibrosis transmembrane conductance regulator, CFTR). In contrast to previous reports, we found no association between CFTR carrier status (mutation heterozygosity) and more severe COVID-19 clinical outcomes. We did observe an unexpected trend toward higher mortality among control individuals compared with silent carriers of the common F508del CFTR variant-a finding that will require further study. We next performed experiments to test the influence of homozygous CFTR deficiency on viral propagation and showed that SARS-CoV-2 production in primary airway cells was not altered by the absence of functional CFTR using two independent protocols. On the contrary, experiments performed in vitro strongly indicated that virus proliferation depended on features of the mucosal fluid layer known to be disrupted by absent CFTR in patients with CF, including both low pH and increased viscosity. These results point to the acidic, viscous, and mucus-obstructed airways in patients with cystic fibrosis as unfavorable for the establishment of coronaviral infection. Our findings provide new and important information concerning relationships between the CF clinical phenotype and severity of COVID-19.

Maximizing Adherence and Minimizing Time to Antibiotics: A Multidisciplinary Institutional Trauma Bay Protocol for Single Antibiotic Prophylaxis in Open Fractures.

OBJECTIVES: To determine if a multidisciplinary institutional protocol can optimize the time to antibiotic (Abx) administration for open fractures (openFx) and improve compliance with the administration of Abx prophylaxis during trauma activation. DESIGN: Retrospective pre-post study design. SETTING: Single Level II Trauma Center. PATIENT SELECTION CRITERIA: All patients who triggered a trauma activation with suspected openFx and were treated according to the institutional single antibiotic regimen were eligible for inclusion. Patients were excluded if fractures did not involve the appendicular skeleton. Patients treated before implementation of a standardized institutional protocol where premixed IV bags of antibiotics were stocked in automated dispensing systems within ED trauma bays (January 2021-October 2022) were defined as the "pre" group and those treated following implementation the "post" group. OUTCOME MEASURES AND COMPARISONS: The primary outcome was time from trauma bay arrival to antibiotic aministration, measured in minutes, with comparisons made between preprotocol and postprotocol implementation. Secondary outcomes for comparison included rates (%) of time to Abx <60 minutes, allergic reactions, acute kidney injury, ototoxicity, surgical site infection, multi-drug-resistant organisms identified in blood or biopsy cultures in cases requiring reoperation, and Clostridium difficile infection in the gastrointestinal system, confirmed by stool test results, within 30 days. RESULTS: Twenty-four patients (mean age 39.5 ± 16.3 years) met the criteria after protocol implementation compared with 72 patients (mean age 34.3 ± 14.8 years) before implementation. Implementation of the institutional protocol resulted in a significant reduction in the time to Abx administration for openFx from 87.9 ± 104.6 minutes to 22.2 ± 12.8 minutes in the postprotocol group ( P < 0.001). In addition, only 53% in the preprotocol group received Abx within 60 minutes compared with 96% in postprotocol group ( P < 0.001). Post hoc power analysis revealed that the study was powered at 92% (effect size = 0.72) to detect a significant difference between the preprotocol and postprotocol groups. CONCLUSION: This study provides evidence that a multidisciplinary institutional protocol for the administration of Abx prophylaxis can be an effective strategy for optimizing the time to Abx administration in cases of suspected openFx. This protocol may be implemented in other trauma centers to optimize time to Abx administration for openFx. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Impact of an Educational Intervention on Hospital Pharmacists' Knowledge and Application of Substance Withdrawal Management.

Background: Patients with substance use disorders are often encountered in an acute care setting and withdrawal management is important. Available literature reveals inadequate acute management of substance withdrawal due to lack of experience and knowledge of medications. Methods: A quality improvement project was implemented to improve hospital pharmacists' knowledge, application, and practice of inpatient opioid and alcohol withdrawal management through provision of didactic and case-based education and implementation of practice based prospective drug utilization review (PDUR). Pharmacists' knowledge of the management of alcohol and opioid withdrawal was assessed by a 10-item survey pre-and post-intervention. Results: Twenty-one pharmacists completed the education and pre- and post-surveys. Scores for the 21 pharmacists improved significantly, with pre- and post-intervention scores of 7.33 ± 1.98 and 8.86 ± 0.91, respectively (P = .0035). Most pharmacists completed their required PDUR submission, and several pharmacist interventions were made and accepted post-education. Pharmacists indicated that the education increased their confidence and enabled them to learn new information that could be directly applied to their pharmacy practice. Conclusion: Providing education and requiring a PDUR improved pharmacists' knowledge, application, and practice of inpatient opioid and alcohol withdrawal management. Re-education or expanded education may be warranted to further increase pharmacists' competence.