Handoffs and transitions in critical care—understanding scalability: study protocol for a multicenter stepped wedge type 2 hybrid effectiveness-implementation trial

Abstract Background The implementation of evidence-based practices in critical care faces specific challenges, including intense time pressure and patient acuity. These challenges result in evidence-to-practice gaps that diminish the impact of proven-effective interventions for patients requiring intensive care unit support. Research is needed to understand and address implementation determinants in critical care settings. Methods The Handoffs and Transitions in Critical Care—Understanding Scalability (HATRICC-US) study is a Type 2 hybrid effectiveness-implementation trial of standardized operating room (OR) to intensive care unit (ICU) handoffs. This mixed methods study will use a stepped wedge design with randomized roll out to test the effectiveness of a customized protocol for structuring communication between clinicians in the OR and the ICU. The study will be conducted in twelve ICUs (10 adult, 2 pediatric) based in five United States academic health systems. Contextual inquiry incorporating implementation science, systems engineering, and human factors engineering approaches will guide both protocol customization and identification of protocol implementation determinants. Implementation mapping will be used to select appropriate implementation strategies for each setting. Human-centered design will be used to create a digital toolkit for dissemination of study findings. The primary implementation outcome will be fidelity to the customized handoff protocol (unit of analysis: handoff). The primary effectiveness outcome will be a composite measure of new-onset organ failure cases (unit of analysis: ICU). Discussion The HATRICC-US study will customize, implement, and evaluate standardized procedures for OR to ICU handoffs in a heterogenous group of United States academic medical center intensive care units. Findings from this study have the potential to improve postsurgical communication, decrease adverse clinical outcomes, and inform the implementation of other evidence-based practices in critical care settings. Trial registration ClinicalTrials.gov identifier: NCT04571749 . Date of registration: October 1, 2020

The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity

Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD); however, pathways regulating LRRK2 subcellular localization, function, and turnover are not fully defined. We performed quantitative mass spectrometry-based interactome studies to identify 48 novel LRRK2 interactors, including the microtubule-associated E3 ubiquitin ligase TRIM1 (tripartite motif family 1). TRIM1 recruits LRRK2 to the microtubule cytoskeleton for ubiquitination and proteasomal degradation by binding LRRK2911-919, a nine amino acid segment within a flexible interdomain region (LRRK2853-981), which we designate the "regulatory loop" (RL). Phosphorylation of LRRK2 Ser910/Ser935 within LRRK2 RL influences LRRK2's association with cytoplasmic 14-3-3 versus microtubule-bound TRIM1. Association with TRIM1 modulates LRRK2's interaction with Rab29 and prevents upregulation of LRRK2 kinase activity by Rab29 in an E3-ligase-dependent manner. Finally, TRIM1 rescues neurite outgrowth deficits caused by PD-driving mutant LRRK2 G2019S. Our data suggest that TRIM1 is a critical regulator of LRRK2, controlling its degradation, localization, binding partners, kinase activity, and cytotoxicity

Interocean patterns in shallow water sponge assemblage structure and function

Sponges are a major component of benthic ecosystems across the world and fulfil a number of important functional roles. However, despite their importance, there have been few attempts to compare sponge assemblage structure and ecological functions across large spatial scales. In this review, we examine commonalities and differences between shallow water (<100 m) sponges at bioregional (15 bioregions) and macroregional (tropical, Mediterranean, temperate, and polar) scales, to provide a more comprehensive understanding of sponge ecology. Patterns of sponge abundance (based on density and area occupied) were highly variable, with an average benthic cover between ~1 and 30%. Sponges were generally found to occupy more space (percentage cover) in the Mediterranean and polar macroregions, compared to temperate and tropical macroregions, although sponge densities (sponges m–2) were highest in temperate bioregions. Mean species richness standardised by sampling area was similar across all bioregions, except for a few locations that supported very high small‐scale biodiversity concentrations. Encrusting growth forms were generally the dominant sponge morphology, with the exception of the Tropical West Atlantic, where upright forms dominated. Annelids and Arthropods were the most commonly reported macrofauna associated with sponges across bioregions. With respect to reproduction, there were no patterns in gametic development (hermaphroditism versus gonochorism), although temperate, tropical, and polar macroregions had an increasingly higher percentage of viviparous species, respectively, with viviparity being the sole gamete development mechanism reported for polar sponges to date. Seasonal reproductive timing was the most common in all bioregions, but continuous timing was more common in the Mediterranean and tropical bioregions compared to polar and temperate bioregions. We found little variation across bioregions in larval size, and the dominant larval type across the globe was parenchymella. No pattens among bioregions were found in the limited information available for standardised respiration and pumping rates. Many organisms were found to predate sponges, with the abundance of sponge predators being higher in tropical systems. While there is some evidence to support a higher overall proportion of phototrophic species in the Tropical Austalian bioregion compared to the Western Atlantic, both also have large numbers of heterotrophic species. Sponges are important spatial competitors across all bioregions, most commonly being reported to interact with anthozoans and algae. Even though the available information was limited for many bioregions, our analyses demonstrate some differences in sponge traits and functions among bioregions, and among macroregions. However, we also identified similarities in sponge assemblage structure and function at global scales, likely reflecting a combination of regional‐ and local‐scale biological and physical processes affecting sponge assemblages, along with common ancestry. Finally, we used our analyses to highlight geographic bias in past sponge research, and identify gaps in our understanding of sponge ecology globally. By so doing, we identified key areas for future research on sponge ecology. We hope that our study will help sponge researchers to consider bioregion‐specific features of sponge assemblages and key sponge‐mediated ecological processes from a global perspective

Is perioperative COVID-19 really associated with worse surgical outcomes? A nationwide COVIDSurg propensity-matched analysis

BACKGROUND: Patients undergoing surgery with perioperative COVID-19 are suggested to have worse outcomes, but whether this is COVID-related or due to selection bias remains unclear. We aimed to compare the postoperative outcomes of patients with and without perioperative COVID-19. METHODS: Patients with perioperative COVID-19 diagnosed within 7 days before or 30 days after surgery between February and July 2020 from 68 US hospitals in COVIDSurg, an international multicenter database, were 1:1 propensity score matched to patients without COVID-19 undergoing similar procedures in the 2012 American College of Surgeons National Surgical Quality Improvement Program database. The matching criteria included demographics (e.g., age, sex), comorbidities (e.g., diabetes, chronic obstructive pulmonary disease, chronic kidney disease), and operation characteristics (e.g., type, urgency, complexity). The primary outcome was 30-day hospital mortality. Secondary outcomes included hospital length of stay and 13 postoperative complications (e.g., pneumonia, renal failure, surgical site infection). RESULTS: A total of 97,936 patients were included, 1,054 with and 96,882 without COVID-19. Prematching, COVID-19 patients more often underwent emergency surgery (76.1% vs. 10.3%, p &lt; 0.001). A total of 843 COVID-19 and 843 non-COVID-19 patients were successfully matched based on demographics, comorbidities, and operative characteristics. Postmatching, COVID-19 patients had a higher mortality (12.0% vs. 8.1%, p = 0.007), longer length of stay (6 [2-15] vs. 5 [1-12] days), and higher rates of acute renal failure (19.3% vs. 3.0%, p &lt; 0.001), sepsis (13.5% vs. 9.0%, p = 0.003), and septic shock (11.8% vs. 6.0%, p &lt; 0.001). They also had higher rates of thromboembolic complications such as deep vein thrombosis (4.4% vs. 1.5%, p &lt; 0.001) and pulmonary embolism (2.5% vs. 0.4%, p &lt; 0.001) but lower rates of bleeding (11.6% vs. 26.1%, p &lt; 0.001). CONCLUSION: Patients undergoing surgery with perioperative COVID-19 have higher rates of 30-day mortality and postoperative complications, especially thromboembolic, compared with similar patients without COVID-19 undergoing similar surgeries. Such information is crucial for the complex surgical decision making and counseling of these patients. (J Trauma Acute Care Surg. 2023;94: 513-524. Copyright (C) 2023 American Association for the Surgery of Trauma.)LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV

Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy: Collaborative Analysis of Cohorts of HIV-1-Infected Patients

Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART

Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA. A Prospective Multicenter Study

Objective: To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Background: Uncertainty regarding the postoperative risks of patients with SARS-CoV-2 exists. Methods: As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results: A total of 1581 patients were included; more than half of them were males (n = 822, 52.0%) and older than 50 years (n = 835, 52.8%). Most procedures (n = 1261, 79.8%) were emergent, and laparotomies (n = 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (odds ratio 2.46, 95% confidence interval [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions: Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks