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Objective: This study identified failures in emergency inter-hospital transfer, or re-triage, at high-level trauma centers receiving severely injured patients., Summary Background Data: The re-triage process averages four hours despite the fact timely re-triage within two hours mitigates injury-associated mortality. Non-trauma and low-level trauma centers reported most critical failures were in finding an accepting high-level trauma center. Critical failures at high-level trauma centers have not been assessed., Methods: This was an observational cross-sectional study at nine high-level adult trauma centers and three high-level pediatric trauma centers. Failure Modes Effects Analysis (FMEA) of the re-triage process was conducted in four phases. Phase 1 purposively sampled trauma coordinators followed by snowball sampling of clinicians, operations, and leadership to ensure representative participation. Phase 2 mapped each re-triage step. Phase 3 identified failures at each step. Phase 4 scored each failure on impact, frequency, and safeguards for detection. Standardized rubrics were used in Phase 4 to rate each failure's impact (I), frequency (F), and safeguard for detection (S) to calculate their Risk Priority Number (RPN) (I x F x S). Failures were rank ordered for criticality., Results: A total of 64 trauma coordinators, surgeons, emergency medicine physicians, nurses, operations and quality managers across twelve high-level trauma centers participated. There were 178failures identified at adult and pediatric high-level trauma centers. The most critical failures were: Insufficient trained transport staff (RPN=648); Issues transmitting imaging from sending to receiving centers (RPN=400); Incomplete exchange of clinical information(RPN=384)., Conclusions: The most critical failures were limited transportation and incomplete exchange of clinical, radiological and arrival timing information. Further investigation of these failures that includes several regions is needed to determine the reproducibility of these findings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To understand frontline ICU clinician's perceptions of end-of-life care delivery in the ICU., Design: Qualitative observational cross-sectional study., Setting: Seven ICUs across three hospitals in an integrated academic health system., Subjects: ICU clinicians (physicians [critical care, palliative care], advanced practice providers, nurses, social workers, chaplains)., Interventions: None., Measurements and Main Results: In total, 27 semi-structured interviews were conducted, recorded, and transcribed. The research team reviewed all transcripts inductively to develop a codebook. Thematic analysis was conducted through coding, category formulation, and sorting for data reduction to identify central themes. Deductive reasoning facilitated data category formulation and thematic structuring anchored on the Systems Engineering Initiative for Patient Safety model identified that work systems (people, environment, tools, tasks) lead to processes and outcomes. Four themes were barriers or facilitators to end-of-life care. First, work system barriers delayed end-of-life care communication among clinicians as well as between clinicians and families. For example, over-reliance on palliative care people in handling end-of-life discussions prevented timely end-of-life care discussions with families. Second, clinician-level variability existed in end-of-life communication tasks. For example, end-of-life care discussions varied greatly in process and outcomes depending on the clinician leading the conversation. Third, clinician-family-patient priorities or treatment goals were misaligned. Conversely, regular discussion and joint decisions facilitated higher familial confidence in end-of-life care delivery process. These detailed discussions between care teams aligned priorities and led to fewer situations where patients/families received conflicting information. Fourth, clinician moral distress occurred from providing nonbeneficial care. Interviewees reported standardized end-of-life care discussion process incorporated by the people in the work system including patient, family, and clinicians were foundational to delivering end-of-life care that reduced both patient and family suffering, as well as clinician moral distress., Conclusions: Standardized work system communication tasks may improve end-of life discussion processes between clinicians and families., Competing Interests: Dr. Janczewski received support for article research from the Agency for Healthcare Research and Quality (5F32HS027724-02). Dr. Ko’s institution received funding from the National Institutes of Health (NIH); he received support for article research from the NIH. Dr. Yang disclosed work for hire. Dr. Kruser disclosed that her spouse receives funding from AstraZeneca and Radialogica. Dr. Stey received funding from American Association for the Surgery of Trauma, American College of Surgeons, and the National Heart, Lung, and Blood Institute. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Objective: This study assessed incivility during mortality and morbidity (M&M) conference., Background: A psychologically safe environment at M&M conference enables generative discussions to improve care. Incivility and exclusion demonstrated by "shame and blame" undermine generative discussion., Methods: We used a convergent mixed-methods design to collect qualitative data through nonparticipant observations of M&M conference and quantitative data through standardized survey instruments of M&M participants. The M&M conference was attended by attending surgeons (all academic ranks), fellows, residents, medical students on surgery rotation, advanced practice providers, and administrators from the department of surgery. A standardized observation guide was developed, piloted and adapted based on expert nonparticipant feedback. The Positive and Negative Affect Schedule Short-Form (PANAS) and the Uncivil Behavior in Clinical Nursing Education (UBCNE) survey instruments were distributed to the Department of Surgery clinical faculty and categorical general surgery residents in an academic medical center., Results: We observed 11 M&M discussions of 30 cases, over 6 months with 4 different moderators. Case presentations (virtual format) included clinical scenario, decision-making, operative management, complications, and management of the complications. Discussion was free form, without a standard structure. The central theme was that limited discussion participation from attending surgeon of record, as well as absence of a systems-approach led to blame and then blame then set the stage for incivility. Among 147 eligible to participate in the survey, 54 (36.7%) responded. Assistant professors had a 2.60 higher Negative Affect score ( P =0.02), a 4.13 higher Exclusion Behavior score ( P =0.03), and a 7.6 higher UBCNE score ( P =0.04) compared with associate and full professors. Females had a 2.7 higher Negative Affect Score compared with males ( P =0.04)., Conclusion: Free-form M&M discussions led to incivility. Structuring discussion to focus upon improving care may create inclusion and more generative discussions to improve care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Illinois experienced a historic firearm violence surge in 2016 with a decline to baseline rates in 2018. This study aimed to understand this 2016 surge through the direct accounts of violence prevention community-based organisations (CBOs) in Illinois., Methods: We conducted semistructured interviews with 20 representatives from 13 CBOs from the south and west sides of greater Chicago metropolitan area. Interviews were audio recorded, coded and analysed thematically., Results: We identified lack of government-derived infrastructure and systemic poverty as the central themes of Illinois's 2016 firearm violence surge. Participants highlighted the Illinois Budget Impasse halted funding for violence prevention efforts, leading to 2016's violence. This occurred in the context of a strained relationship with the criminal justice system, where disengagement from police and mistrust in the justice system led victims and families to seek justice outside of the judicial system. Participants emphasised that systemic poverty and the obliteration of community support structures led to overwhelming desperation, which, in turn, increased risky behaviours perceived as necessary for survival. Participants disproportionately identified that this impacted the young people in their communities., Conclusions: Lack of government-derived infrastructure and systemic poverty were the central themes of the 2016 firearm violence surge. The insights gained from the 2016 surge are applicable to understanding both current and future surges. CBOs focused on violence prevention offer insights into the context and conditions fuelling surges in the epidemic of violence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: State guidelines for re-triage, or emergency inter-facility transfer, have never been characterized across the United States., Methods: All 50 states' Department of Health and/or Trauma System websites were reviewed for publicly available re-triage guidelines within their rules and regulations. Communication was made via phone or email to state agencies or trauma advisory committees to obtain or confirm the absence of guidelines where public data was unavailable. Guideline criteria were abstracted and grouped into domains of Center for Disease Control Field Triage Criteria: pattern/anatomy of injury, vital signs, special populations, and mechanisms of injury. Re-triage criteria were summarized across states using median and interquartile ranges for continuous data and frequencies for categorical data. Demographic data of states with and without re-triage guidelines were compared using the Wilcoxon rank sum test., Results: Re-triage guidelines were identified for 22 of 50 states (44%). Common anatomy of injury criteria included head trauma (91% of states with guidelines), spinal cord injury (82%), chest injury (77%), and pelvic injury (73%). Common vital signs criteria included Glasgow Coma Score (91% of states) ranging from 8 to 14, systolic blood pressure (36%) ranging from 90 to 100 mm Hg, and respiratory rate (23%) with all using 10 respirations/minute. Common special populations criteria included mechanical ventilation (73% of states), age (68%) ranging from <2 or >60 years, cardiac disease (59%), and pregnancy (55%). No significant demographic differences were found between states with versus without re-triage guidelines., Conclusion: A minority of US states have re-triage guidelines. Characterizing existing criteria can inform future guideline development., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The opioid crisis is an ongoing crisis in the United States. Postoperative patients who receive opioid prescriptions have a 3%-7% risk of developing a chronic opioid abuse problem. This study aims to describe on-target opioid prescribing and use of multimodal pain management strategies 2 y after the implementation of a multicomponent quality improvement initiative across our statewide collaborative., Methods: From July 2020 to September 2021, we prospectively collected data on opioid-prescribing and multimodal strategies for 10 targeted procedures in general, gynecologic, and orthopedic surgery at three hospitals. Prescribing was on-target if a patient was prescribed ≤50 daily morphine milligram equivalents. Multimodal strategies were defined as two or more nonopioid adjuncts used within 48 h of surgery., Results: One thousand and eleven targeted procedures were performed with prescription data available for 993 cases. The on-target prescribing rate was 79.6% (n = 790), with general surgery 92.5% (n = 285), gynecology 84.9% (n = 331), and orthopedic surgery 59.0% (n = 174). Patients who received multimodal pain approaches were associated with interventions such as patient education, transversus abdominus plane block, and prescriptions for nonopioid analgesics at discharge. There was no evidence to support a difference in the use of multimodal pain control approaches between patients whose opioid prescribing was on-target or not (73.8% versus 77.3%, P = 0.30). At the first postoperative visit, data on continued opioid use were missing in 57.3% of patients, number of pills used was missing in 93.8%, and adequate pain control was missing in 52.8%., Conclusions: On-target prescribing and multimodal strategies are common but vary by specialty. Additionally, postoperative pain control and opioid use are often not documented. To better match prescribing to patient needs, understanding patient-level and specialty-level opioid use is important., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Poor interdisciplinary care team communication has been associated with increased mortality. The study aimed to define conditions for effective interdisciplinary care team communication., Design: An observational cross-sectional qualitative study., Setting: A surgical intensive care unit in a large, urban, academic referral medical centre., Participants: A total 6 interviews and 10 focus groups from February to June 2021 (N=33) were performed. Interdisciplinary clinicians who cared for critically ill patients were interviewed. Participants included intensivist, transplant, colorectal, vascular, surgical oncology, trauma faculty surgeons (n=10); emergency medicine, surgery, gynaecology, radiology physicians-in-training (n=6), advanced practice providers (n=5), nurses (n=7), fellows (n=1) and subspecialist clinicians such as respiratory therapists, pharmacists and dieticians (n=4). Audiorecorded content of interviews and focus groups were deidentified and transcribed verbatim. The study team iteratively generated the codebook. All transcripts were independently coded by two team members., Primary Outcome: Conditions for effective interdisciplinary care team communication., Results: We identified five themes relating to conditions for effective interdisciplinary care team communication in our surgical intensive care unit setting: role definition, formal processes, informal communication pathways, hierarchical influences and psychological safety. Participants reported that clear role definition and standardised formal communication processes empowered clinicians to engage in discussions that mitigated hierarchy and facilitated psychological safety., Conclusions: Standardising communication and creating defined roles in formal processes can promote effective interdisciplinary care team communication by fostering psychological safety., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Retriage is the emergency transfer of severely injured patients from nontrauma and lower-level trauma centers to higher-level trauma centers. We identified the barriers to retriage at sending centers in a single health system., Methods: We conducted a failure modes effects and criticality analysis at 4 nontrauma centers and 5 lower-level trauma centers in a single health system. Clinicians from each center described the steps in the trauma assessment and retriage process to create a process map. We used standardized scoring to characterize each failure based on frequency, impact on retriage, and prevention safeguards. We ranked each failure using the scores to calculate a risk priority number., Results: We identified 26 steps and 93 failures. The highest-risk failure was refusal by higher-level trauma centers (receiving hospitals) to accept a patient. The most critical failures in the retriage process based on total risk, frequency, and safeguard scores were (1) refusal from a receiving higher-level trauma center to accept a patient (risk priority number = 191), (2) delay in a sending center's consultant examination of a patient in the emergency department (risk priority number = 177), and (3) delay in receiving hospital's consultant calling back (risk priority number = 177)., Conclusion: We identified (1) addressing obstacles to determining clinical indications for retriage and (2) identifying receiving level I trauma centers who would accept the patient as opportunities to increase timely retriage. Establishing clear clinical indications for retriage that sending and receiving hospitals agree on represents an opportunity for intervention that could improve the retriage of injured patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Genetically encoded Förster resonance energy transfer (FRET) sensors enable the visualization of ions, molecules, and processes in live cells. However, despite their widespread use, the molecular states that determine sensor performance are usually poorly understood, which limits efforts to improve them. We used dynamic light scattering (DLS) and time-resolved fluorescence anisotropy to uncover the sensing mechanism of ZifCV1.173, a Zn 2+ FRET sensor. We found that the dynamic range (DR) of ZifCV1.173 was dominated by the high FRET efficiency of the Zn 2+ -free state, in which the donor and acceptor fluorescent proteins were closely associated. Mutating the donor-acceptor interface revealed that the DR of ZifCV1.173 could be increased or decreased by promoting or disrupting the donor-acceptor interaction, respectively. Adapting the same mutations to a related sensor showed the same pattern of DR tuning, supporting our sensing mechanism and suggesting that DLS and time-resolved fluorescence anisotropy might be generally useful in the biophysical characterization of other FRET sensors.

Vibrational spectroscopy is a powerful tool for characterizing the complex noncovalent interactions that arise in biological systems. The nitrile stretching frequency has proven to be a particularly convenient biological probe, but the interpretation of nitrile spectroscopy is complicated by its sensitivity to local hydrogen bonding interactions. This often inhibits the straightforward interpretation of nitrile spectra by requiring knowledge of the molecular-level details of the local environment surrounding the probe. While the effect of hydrogen bonds on nitrile frequencies has been well-documented for small molecules in solution, there have been relatively few studies of these effects in a complex protein system. To address this, we introduced a nitrile probe at nine locations throughout green fluorescent protein (GFP) and compared the mean vibrational frequency of each probe to the specific hydrogen bonding geometries observed in molecular dynamics (MD) simulations. We show that a continuum of hydrogen bonding angles is found depending on the particular location of each nitrile, and that the differences in these angles account for the differences in the measured nitrile frequency. We further observed that the temperature dependence of the nitrile frequencies (measured as a frequency-temperature line slope, FTLS) was a good indicator of the hydrogen bonding interactions of the probe, even in scenarios where the nitrile was involved in complex and restricted hydrogen bonds, both from protein and from water. While constant offsets to the nitrile frequency to all hydrogen bonding environments have been applied before to interpret shifts in nitrile frequency, we show that this is insufficient in systems where the hydrogen bonds may be restricted by the surrounding medium. However, the strength of the observed correlation between nitrile frequency and hydrogen bonding angle suggests that it may be possible to disentangle electrostatic effects and effects of the orientation of hydrogen bonding on the nitrile stretching frequency. Meanwhile, the experimental measurement of the FTLS of the nitrile is an excellent tool to identify changes in the hydrogen bonding interactions for a particular probe.

Measurement of the electrostatic interactions that give rise to biological functions has been a longstanding challenge in biophysics. Advances in spectroscopic techniques over the past two decades have allowed for the direct measurement of electric fields in a wide variety of biological molecules and systems via the vibrational Stark effect (VSE). The frequency of the nitrile stretching oscillation has received much attention as an electric field reporter because of its sensitivity to electric fields and its occurrence in a relatively transparent region of the infrared spectrum. Despite these advantages and its wide use as a VSE probe, the nitrile stretching frequency is sensitive to hydrogen bonding in a way that complicates the straightforward relationship between measured frequency and environmental electric field. Here we highlight recent applications of nitrile VSE probes with an emphasis on experiments that have helped shape our understanding of the determinants of nitrile frequencies in both hydrogen bonding and nonhydrogen bonding environments.

Measurement of the magnitude, direction, and functional importance of electric fields in biomolecules has been a long-standing experimental challenge. pK a shifts of titratable residues have been the most widely implemented measurements of the local electrostatic environment around the labile proton, and experimental data sets of pK a shifts in a variety of systems have been used to test and refine computational prediction capabilities of protein electrostatic fields. A more direct and increasingly popular technique to measure electric fields in proteins is Stark effect spectroscopy, where the change in absorption energy of a chromophore relative to a reference state is related to the change in electric field felt by the chromophore. While there are merits to both of these methods and they are both reporters of local electrostatic environment, they are fundamentally different measurements, and to our knowledge there has been no direct comparison of these two approaches in a single protein. We have recently demonstrated that green fluorescent protein (GFP) is an ideal model system for measuring changes in electric fields in a protein interior caused by amino acid mutations using both electronic and vibrational Stark effect chromophores. Here we report the changes in pK a of the GFP fluorophore in response to the same mutations and show that they are in excellent agreement with Stark effect measurements. This agreement in the results of orthogonal experiments reinforces our confidence in the experimental results of both Stark effect and pK a measurements and provides an excellent target data set to benchmark diverse protein electrostatics calculations. We used this experimental data set to test the pK a prediction ability of the adaptive Poisson-Boltzmann solver (APBS) and found that a simple continuum dielectric model of the GFP interior is insufficient to accurately capture the measured pK a and Stark effect shifts. We discuss some of the limitations of this continuum-based model in this system and offer this experimentally self-consistent data set as a target benchmark for electrostatics models, which could allow for a more rigorous test of pK a prediction techniques due to the unique environment of the water-filled GFP barrel compared to traditional globular proteins.

A photoactivatable variant of superfolder green fluorescent protein (GFP) was created by replacing the threonine at position 203 with aspartic acid. Photoactivation by exposure of this mutant to UV light resulted in conversion of the fluorophore from the neutral to the negatively charged form, accompanied by a ∼95-fold increase in fluorescence under 488 nm excitation. Mass spectrometry before and after exposure to UV light revealed a change in mass of 88 Da, attributed to the double decarboxylation of Glu 222 and Asp 203. Kinetics studies and nonlinear power-dependence of the initial rate of photoconversion indicated that the double decarboxylation occurred via a multiphoton absorption process at 254 nm. In addition to providing a photoactivatable GFP with robust folding properties, a detailed mechanistic understanding of this double decarboxylation in GFP will lead to a better understanding of charge transfer in fluorescent proteins.

There is growing interest in using the nitrile vibrational oscillation as a site-specific probe of local environment to study dynamics, folding, and electrostatics in biological molecules such as proteins. Nitrile probes have been used extensively as reporters of electric field using vibrational Stark effect spectroscopy. However, the analysis of frequencies in terms of electric fields is potentially complicated by the large ground state dipole moment of the nitrile, which may irrevocably perturb the protein under investigation, and the ability of nitriles to accept hydrogen bonds, which causes frequency shifts that are not described by the Stark effect. The consequence of this is that vibrational spectroscopy of nitriles in biomolecules could be predominately sensitive to their local hydration status, not electrostatic environment, and have the potential to be particularly destabilizing to the protein. Here, we introduce green fluorescent protein (GFP) as a model system for addressing these concerns using biosynthetically incorporated p-cyanophenylalanine (pCNF) residues in the interior of GFP and measuring absorption energies of both the intrinsic GFP fluorophore and pCNF residues in response to a series of amino acid mutations. We show that observed changes in emission energy of GFP due to the mutations strongly correlate with changes in electric field experienced by both the nitrile probes and the intrinsic fluorophore. Additionally, we show that changes in electric field measured from the intrinsic fluorophore due to amino acid mutations are unperturbed by the addition of pCNF residues inserted nearby. Finally, we show that changes in electric field experienced by the vibrational probes trend monotonically with changes in field experienced by the native fluorophore even though the nitrile probe is engaged in moderate hydrogen bonding to nearby water molecules, indicated by the temperature dependence of the nitrile's absorption energy. Together these results demonstrate that even in the presence of hydrogen bonding it is possible to relate nitrile absorption frequencies to electrostatic environment by comparing highly similar environments. GFP's intrinsic linear sensitivity to electric fields makes it a convenient model system for studying electrostatics in proteins that offers lessons for proteins without this visible fluorophore.