Improving communication in intensive care unit to ward transitions: Protocol for multisite national implementation of the ICU-PAUSE handoff tool

BACKGROUND: The intensive care unit (ICU)-ward transfer poses a particularly high-risk period for patients. The period after transfer has been associated with adverse events and additional work for care teams related to miscommunication or omission of information. Standardized handoff processes have been found to reduce communication errors and adverse patient events in other clinical environments but are understudied at the ICU-ward interface. We previously developed an electronic ICU-ward transfer tool, ICU-PAUSE, which embeds the key elements and diagnostic reasoning to facilitate a safe transfer of care at ICU discharge. OBJECTIVE: The aim of this study is to evaluate the implementation process of the ICU-PAUSE handoff tool across 10 academic medical centers, including the rate of adoption and acceptability, as perceived by clinical care teams. METHODS: ICU-PAUSE will be implemented in the medical ICU across 10 academic hospitals, with each site customizing the tool to their institution\u27s needs. Our mixed methods study will include a combination of a chart review, quantitative surveys, and qualitative interviews. After a 90-day implementation period, we will conduct a retrospective chart review to evaluate the rate of uptake of ICU-PAUSE. We will also conduct postimplementation surveys of providers to assess perceptions of the tool and its impact on the frequency of communication errors and adverse events during ICU-ward transfers. Lastly, we will conduct semistructured interviews of faculty stakeholders with subsequent thematic analysis with the goal of identifying benefits and barriers in implementing and using ICU-PAUSE. RESULTS: ICU-PAUSE was piloted in the medical ICU at Barnes-Jewish Hospital, the teaching hospital of Washington University School of Medicine in St. Louis, in 2019. As of July 2022, implementation of ICU-PAUSE is ongoing at 6 of 10 participating sites. Our results will be published in 2023. CONCLUSIONS: Our process of ICU-PAUSE implementation embeds each step of template design, uptake, and customization in the needs of users and key stakeholders. Here, we introduce our approach to evaluate its acceptability, usability, and impact on communication errors according to the tenets of sociotechnical theory. We anticipate that ICU-PAUSE will offer an effective handoff tool for the ICU-ward transition that can be generalized to other institutions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40918

UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis

Background &amp; aims: thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate).Methods: this was a nationwide observational cohort study conducted from August 2017 until June 2021.Results: we accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings &gt;9.6kPa (P &lt; .05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P &lt; .001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P &lt; .001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P = .121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline.Conclusion: across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.</p

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Potently neutralizing and protective human antibodies against SARS-CoV-2

The COVID-19 pandemic is a major threat to global health1 for which there are limited medical countermeasures2,3. Moreover, we currently lack a thorough understanding of mechanisms of humoral immunity4. From a larger panel of human monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein5, we identified several that exhibited potent neutralizing activity and fully blocked the receptor-binding domain of S (SRBD) from interacting with human ACE2 (hACE2). Competition-binding, structural, and functional studies allowed clustering of the mAbs into classes recognizing distinct epitopes on the SRBD as well as distinct conformational states of the S trimer. Potent neutralizing mAbs recognizing non-overlapping sites, COV2-2196 and COV2-2130, bound simultaneously to S and synergistically neutralized authentic SARS-CoV-2 virus. In two mouse models of SARS-CoV-2 infection, passive transfer of either COV2-2196 or COV2-2130 alone or a combination of both mAbs protected mice from weight loss and reduced viral burden and inflammation in the lung. In addition, passive transfer of each of two of the most potently ACE2 blocking mAbs (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on SRBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutics

Cecum Lymph Node Dendritic Cells Harbor Slow-Growing Bacteria Phenotypically Tolerant to Antibiotic Treatment

<div><p>In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%–20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.</p></div

Global impact of the first coronavirus disease 2019 (COVID-19) pandemic wave on vascular services

This online structured survey has demonstrated the global impact of the COVID-19 pandemic on vascular services. The majority of centres have documented marked reductions in operating and services provided to vascular patients. In the months during recovery from the resource restrictions imposed during the pandemic peaks, there will be a significant vascular disease burden awaiting surgeons. One of the most affected specialtie