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We performed a prospective, open-label, randomised controlled trial comparing the air-Q(®) against the LMA-ProSeal™ in adults undergoing general anaesthesia. One hundred subjects (American Society of Anesthesiologists physical status 1-3) presenting for elective, outpatient surgery were randomly assigned to 52 air-Q(®) and 48 ProSeal devices. The primary study endpoint was airway seal pressure. Oropharyngolaryngeal morbidity was assessed secondarily. Mean (SD) airway seal pressures for the air-Q(®) and ProSeal were 30 (7) cmH (2) O and 30 (6) cmH(2) O, respectively (p = 0.47). Postoperative sore throat was more common with the air-Q(®) (46% vs 38%, p = 0.03) as was pain on swallowing (30% vs 5%, p = 0.01). In conclusion, the air-Q(®) performs well as a primary airway during the maintenance of general anaesthesia with an airway seal pressure similar to that of the ProSeal, but with a higher incidence of postoperative oropharyngolaryngeal complaints. [ABSTRACT FROM AUTHOR]

The second-generation air-Q intubating laryngeal airway is a newer commercially available supraglottic airway device. In this retrospective review, we describe our initial clinical experience of 70 insertions. The ease and number of insertion attempts, airway leak pressure, device positioning, duration of use, success of fibreoptic-aided intubation and oropharyngeal morbidity were recorded. The intubating laryngeal airway was successfully inserted in all 770 patients and functioned adequately as a primary airway in all 57 patients in which it was used. The median airway leak pressure was 25 and 30 cmH2O for the single-use and reusable devices (P = 0.001), respectively. Fibreoptic-aided intubation using the intubating laryngeal airway as a conduit was successful in 12/13 (92%) cases. One in four (26%) patients complained of mild sore throat postoperatively before discharge. In our series, the intubating laryngeal airway performed adequately as a primary airway during anaesthesia with respect to ease of insertion, adequacy of airway maintenance, and as a conduit for intubation in both anticipated and unanticipated difficult airways. Further investigation is warranted regarding the role of the intubating laryngeal airway as a conduit for both blind and fibreoptic-aided intubation. In addition, the incidence of postoperative throat complaints deserves further scrutiny. [ABSTRACT FROM AUTHOR]

The LMA-Supreme is a single-use disposable laryngeal mask that combines features of several laryngeal mask airways in one device. The primary aim of our study was to compare ease of use and operator preference for fibreoptic-aided intubation through the LMA-Supreme using an Aintree Intubating Catheter or Arndt Airway Exchange Catheter Set. Twenty participants experienced in fibreoptic-aided intubation performed a total of 40 intubations on an AirSim airway manikin through a #4 LMA-Supreme. Intubation using the Arndt Airway Exchange Catheter Set was easier than with the Aintree Intubating Catheter. Half of the participants preferred Aintree Intubating Catheter-assisted intubation, citing fewer steps and faster performance as the reasons. All 20 (100%) Arndt Airway Exchange Catheter Set-assisted intubations and 18/20 (90%) of Aintree Intubating Catheter-assisted intubations were successful. Aintree Intubating Catheter and Arndt Airway Exchange Catheter Set-assisted intubations can be performed quickly, successfully and with minimal difficulty through the LMA-Supreme by experienced operators. While the Arndt Airway Exchange Catheter may be easier the Aintree Intubating Catheter is faster. [ABSTRACT FROM AUTHOR]

Purpose: Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA)., Methods: An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician-researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements., Results: The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care., Conclusion: Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: In-hospital cardiac arrest (IHCA) is a significant public health burden. Rates of return of spontaneous circulation (ROSC) have been improving, but the best way to care for patients after the initial resuscitation remains poorly understood, and improvements in survival to discharge are stagnant. Existing North American cardiac arrest databases lack comprehensive data on the post-resuscitation period, and we do not know current post-IHCA practice patterns. To address this gap, we developed the Discover In-Hospital Cardiac Arrest (Discover IHCA) study, which will thoroughly evaluate current post-IHCA care practices across a diverse cohort., Objectives: Our study collects granular data on post-IHCA treatment practices, focusing on temperature control and prognostication, with the objective of describing variation in current post-IHCA practice., Design, Setting, and Participants: This is a multicenter, prospectively collected, observational cohort study of patients who have suffered IHCA and have been successfully resuscitated (achieved ROSC). There are 24 enrolling hospital systems (23 in the United States) with 69 individual enrolling hospitals (39 in the United States). We developed a standardized data dictionary, and data collection began in October 2023, with a projected 1000 total enrollments. Discover IHCA is endorsed by the Society of Critical Care Medicine., Interventions, Outcomes, and Analysis: The study collects data on patient characteristics including pre-arrest frailty, arrest characteristics, and detailed information on post-arrest practices and outcomes. Data collection on post-IHCA practice was structured around current American Heart Association and European Resuscitation Council guidelines. Among other data elements, the study captures post-arrest temperature control interventions and post-arrest prognostication methods. Analysis will evaluate variations in practice and their association with mortality and neurologic function., Conclusions: We expect this study, Discover IHCA, to identify variability in practice and outcomes following IHCA, and be a vital resource for future investigations into best-practice for managing patients after IHCA., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: Post-marketing surveillance of sotrovimab's effect during implementation in the Canadian population is limited., Methods: The study used a propensity score-matched retrospective cohort design. Follow-up began between the periods of December 15, 2021 and April 30 2022. The study assessed any severe outcome defined as all-cause hospital admission or mortality within 30 days of a confirmed COVID-19-positive test. Covariate-adjusted odds ratios between sotrovimab treatment and the severe outcome was conducted using logistic regression., Results: There were 22,289 individuals meeting the treatment criteria for sotrovimab. There were 1603 treated and 6299 untreated individuals included in the analysis. The outcome occurrence in the study was 5.49% (treated) and 4.21% (untreated), with a median time from diagnosis to treatment of 1.00 days (interquartile range 2.00 days). In the propensity-matched cohort, sotrovimab was not associated with lower odds of a severe outcome (odds ratio 1.20, 95% confidence interval 0.91-1.58), adjusting for confounding variables., Conclusions: After adjusting for confounding variables, sotrovimab treatment was not associated with lower odds of a severe outcome within 30-days of COVID-19-positive date., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: A recent randomized trial found that using a bougie did not increase the incidence of successful intubation on first attempt in critically ill adults. The average effect of treatment in a trial population, however, may differ from effects for individuals. Objective: We hypothesized that application of a machine learning model to data from a clinical trial could estimate the effect of treatment (bougie vs. stylet) for individual patients based on their baseline characteristics ("individualized treatment effects"). Methods: This was a secondary analysis of the BOUGIE (Bougie or Stylet in Patients Undergoing Intubation Emergently) trial. A causal forest algorithm was used to model differences in outcome probabilities by randomized group assignment (bougie vs. stylet) for each patient in the first half of the trial (training cohort). This model was used to predict individualized treatment effects for each patient in the second half (validation cohort). Measurements and Main Results: Of 1,102 patients in the BOUGIE trial, 558 (50.6%) were the training cohort, and 544 (49.4%) were the validation cohort. In the validation cohort, individualized treatment effects predicted by the model significantly modified the effect of trial group assignment on the primary outcome ( P value for interaction = 0.02; adjusted qini coefficient, 2.46). The most important model variables were difficult airway characteristics, body mass index, and Acute Physiology and Chronic Health Evaluation II score. Conclusions: In this hypothesis-generating secondary analysis of a randomized trial with no average treatment effect and no treatment effect in any prespecified subgroups, a causal forest machine learning algorithm identified patients who appeared to benefit from the use of a bougie over a stylet and from the use of a stylet over a bougie using complex interactions between baseline patient and operator characteristics.

Introduction: Among critically ill patients undergoing orotracheal intubation in the emergency department (ED) or intensive care unit (ICU), failure to visualise the vocal cords and intubate the trachea on the first attempt is associated with an increased risk of complications. Two types of laryngoscopes are commonly available: direct laryngoscopes and video laryngoscopes. For critically ill adults undergoing emergency tracheal intubation, it remains uncertain whether the use of a video laryngoscope increases the incidence of successful intubation on the first attempt compared with the use of a direct laryngoscope., Methods and Analysis: The D ir E ct versus VI deo Laryngos C op E (DEVICE) trial is a prospective, multicentre, non-blinded, randomised trial being conducted in 7 EDs and 10 ICUs in the USA. The trial plans to enrol up to 2000 critically ill adults undergoing orotracheal intubation with a laryngoscope. Eligible patients are randomised 1:1 to the use of a video laryngoscope or a direct laryngoscope for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is the incidence of severe complications between induction and 2 min after intubation, defined as the occurrence of one or more of the following: severe hypoxaemia (lowest oxygen saturation <80%); severe hypotension (systolic blood pressure <65 mm Hg or new or increased vasopressor administration); cardiac arrest or death. Enrolment began on 19 March 2022 and is expected to be completed in 2023., Ethics and Dissemination: The trial protocol was approved with waiver of informed consent by the single institutional review board at Vanderbilt University Medical Center and the Human Research Protection Office of the Department of Defense. The results will be presented at scientific conferences and submitted for publication in a peer-reviewed journal., Trial Registration Number: ClinicalTrials.gov Registry (NCT05239195)., Competing Interests: Competing interests: MWS was supported by the National Heart, Lung and Blood Institute (K23HL143053). JDC was supported by the National Heart, Lung and Blood Institute (K23HL153584-01). JPG received support from the CHEST Foundation for instruction and travel. TWR was supported in part by the National Institutes of Health and received consulting payments from Cumberland Pharmaceuticals and Cytovale, and served on a data safety and monitoring board for Sanofi., (© 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.)

Objectives: To determine if there was excess mortality in Alberta, Canada during the coronavirus disease 2019 (COVID-19) pandemic, to confirm if excess mortality affected all age groups equally, and to determine what proportions of excess deaths were directly related to COVID-19 and non-pharmaceutical drug poisoning., Methods: Weekly all-cause data used to estimate excess mortality were modelled against the pre-pandemic period (January 2015-February 2020). Age-adjusted weekly mortality rates for March 2020 to December 2021 were compared with the preceding 5 years., Results: From March 2020 to December 2021, there was an 11% excess mortality rate, corresponding to an average of 265 monthly excess deaths (maximum >30%). COVID-19-related deaths ( n =3202) accounted for 54.9% of total excess deaths ( n =5833) that occurred in the 22-month period. The increase in all-cause excess deaths was proportionately higher, and with significantly greater numbers, in younger age groups. Significant increases in monthly drug poisoning deaths occurred from March 2020 to April 2021, with a total of 1819 deaths. Eight hundred and 25 excess drug poisoning deaths, representing 25.4% of total all-cause excess deaths, occurred, mainly among those aged 25-60 years. Overall, 54.9% of all excess deaths were directly related to COVID-19 and 25.4% were related to drug poisoning., Conclusions: There was a significant increase in all-cause mortality during the COVID-19 pandemic. Although older adults are more likely to die of COVID-19, a massive increase in non-COVID-19-related mortality was observed among younger people. These factors should be considered in public policy decisions on epidemic/pandemic management., (© 2022 The Author(s).)

Importance: Hypotension is common during tracheal intubation of critically ill adults and increases the risk of cardiac arrest and death. Whether administering an intravenous fluid bolus to critically ill adults undergoing tracheal intubation prevents severe hypotension, cardiac arrest, or death remains uncertain., Objective: To determine the effect of fluid bolus administration on the incidence of severe hypotension, cardiac arrest, and death., Design, Setting, and Participants: This randomized clinical trial enrolled 1067 critically ill adults undergoing tracheal intubation with sedation and positive pressure ventilation at 11 intensive care units in the US between February 1, 2019, and May 24, 2021. The date of final follow-up was June 21, 2021., Interventions: Patients were randomly assigned to receive either a 500-mL intravenous fluid bolus (n = 538) or no fluid bolus (n = 527)., Main Outcomes and Measures: The primary outcome was cardiovascular collapse (defined as new or increased receipt of vasopressors or a systolic blood pressure <65 mm Hg between induction of anesthesia and 2 minutes after tracheal intubation, or cardiac arrest or death between induction of anesthesia and 1 hour after tracheal intubation). The secondary outcome was the incidence of death prior to day 28, which was censored at hospital discharge., Results: Among 1067 patients randomized, 1065 (99.8%) completed the trial and were included in the primary analysis (median age, 62 years [IQR, 51-70 years]; 42.1% were women). Cardiovascular collapse occurred in 113 patients (21.0%) in the fluid bolus group and in 96 patients (18.2%) in the no fluid bolus group (absolute difference, 2.8% [95% CI, -2.2% to 7.7%]; P = .25). New or increased receipt of vasopressors occurred in 20.6% of patients in the fluid bolus group compared with 17.6% of patients in the no fluid bolus group, a systolic blood pressure of less than 65 mm Hg occurred in 3.9% vs 4.2%, respectively, cardiac arrest occurred in 1.7% vs 1.5%, and death occurred in 0.7% vs 0.6%. Death prior to day 28 (censored at hospital discharge) occurred in 218 patients (40.5%) in the fluid bolus group compared with 223 patients (42.3%) in the no fluid bolus group (absolute difference, -1.8% [95% CI, -7.9% to 4.3%]; P = .55)., Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, administration of an intravenous fluid bolus compared with no fluid bolus did not significantly decrease the incidence of cardiovascular collapse., Trial Registration: ClinicalTrials.gov Identifier: NCT03787732.

Background: Hypoxemia is common during tracheal intubation in intensive care units. To prevent hypoxemia during intubation, 2 methods of delivering oxygen between induction and laryngoscopy have been proposed: bag-mask ventilation and supplemental oxygen delivered by nasal cannula without ventilation (apneic oxygenation). Whether one of these approaches is more effective for preventing hypoxemia during intubation of critically ill patients is unknown. Methods: We performed a secondary analysis of data from 138 patients enrolled in 2, consecutive randomized trials of airway management in an academic intensive care unit. A total of 61 patients were randomized to receive bag-mask ventilation in a trial comparing bag-mask ventilation to none, and 77 patients were randomized to receive 100% oxygen at 15 L/min by nasal cannula in a trial comparing apneic oxygenation to none. Using multivariable linear regression accounting for age, body mass index, severity of illness, and oxygen saturation at induction, we compared patients assigned to bag-mask ventilation with those assigned to apneic oxygenation regarding lowest oxygen saturations from induction to 2 min after intubation. Results: Patients assigned to bag-mask ventilation and apneic oxygenation were similar at baseline. The median lowest oxygen saturation was 96% (interquartile range [IQR] 89%-100%) in the bag-mask ventilation group and 92% (IQR 84%-99%) in the apneic oxygenation group. After adjustment for prespecified confounders, bag-mask ventilation was associated with a higher lowest oxygen saturation compared to apneic oxygenation (mean difference, 4.2%; 95% confidence interval, 0.7%-7.8%; P  = .02). The incidence of severe hypoxemia (oxygen saturation<80%) was 6.6% in the bag-mask ventilation group and 15.6% in the apneic oxygenation group (adjusted odds ratio, 0.33; P  = .09). Conclusions: This secondary analysis of patients assigned to bag-mask ventilation and apneic oxygenation during 2 clinical trials suggests that bag-mask ventilation is associated with higher oxygen saturation during intubation compared to apneic oxygenation.

Importance: For critically ill adults undergoing emergency tracheal intubation, failure to intubate the trachea on the first attempt occurs in up to 20% of cases and is associated with severe hypoxemia and cardiac arrest. Whether using a tracheal tube introducer ("bougie") increases the likelihood of successful intubation compared with using an endotracheal tube with stylet remains uncertain., Objective: To determine the effect of use of a bougie vs an endotracheal tube with stylet on successful intubation on the first attempt., Design, Setting, and Participants: The Bougie or Stylet in Patients Undergoing Intubation Emergently (BOUGIE) trial was a multicenter, randomized clinical trial among 1102 critically ill adults undergoing tracheal intubation in 7 emergency departments and 8 intensive care units in the US between April 29, 2019, and February 14, 2021; the date of final follow-up was March 14, 2021., Interventions: Patients were randomly assigned to use of a bougie (n = 556) or use of an endotracheal tube with stylet (n = 546)., Main Outcomes and Measures: The primary outcome was successful intubation on the first attempt. The secondary outcome was the incidence of severe hypoxemia, defined as a peripheral oxygen saturation less than 80%., Results: Among 1106 patients randomized, 1102 (99.6%) completed the trial and were included in the primary analysis (median age, 58 years; 41.0% women). Successful intubation on the first attempt occurred in 447 patients (80.4%) in the bougie group and 453 patients (83.0%) in the stylet group (absolute risk difference, -2.6 percentage points [95% CI, -7.3 to 2.2]; P = .27). A total of 58 patients (11.0%) in the bougie group experienced severe hypoxemia, compared with 46 patients (8.8%) in the stylet group (absolute risk difference, 2.2 percentage points [95% CI, -1.6 to 6.0]). Esophageal intubation occurred in 4 patients (0.7%) in the bougie group and 5 patients (0.9%) in the stylet group, pneumothorax was present after intubation in 14 patients (2.5%) in the bougie group and 15 patients (2.7%) in the stylet group, and injury to oral, glottic, or thoracic structures occurred in 0 patients in the bougie group and 3 patients (0.5%) in the stylet group., Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, use of a bougie did not significantly increase the incidence of successful intubation on the first attempt compared with use of an endotracheal tube with stylet., Trial Registration: ClinicalTrials.gov Identifier: NCT03928925

Frequent screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic populations using antigen-based point-of-care tests (APOCTs) is occurring globally with limited clinical performance data. The positive predictive value (PPV) of two APOCTs used in the asymptomatic screening of SARS-CoV-2 among health care workers (HCWs) at continuing care (CC) sites across AB, Canada, was evaluated. Between 22 February and 2 May 2021, CC sites implemented SARS-CoV-2 voluntary screening of their asymptomatic HCWs. On-site testing with Abbott Panbio or BD Veritor occurred on a weekly or twice-weekly basis. Positive APOCTs were confirmed with a real-time reverse transcriptase PCR (rRT-PCR) reference method. A total of 71,847 APOCTs (17,689 Veritor and 54,158 Panbio) were performed among 369 CC sites. Eighty-seven (0.12%) APOCTs were positive, of which 39 (0.05%) were confirmed as true positives using rRT-PCR. Use of the Veritor and Panbio resulted in 76.6% and 30.0% false-positive detection, respectively ( P < 0.001). This corresponded to PPVs of 23.4 and 70.0% for the Veritor and Panbio, respectively. Frequent screening of SARS-CoV-2 among asymptomatic HCWs in CC, using APOCTs, resulted in a very low detection rate and a high rate of detection of false positives. Careful assessment of the risks versus benefits of APOCT programs and the prevalence of infection in this population needs to be thoroughly considered before implementation.

Background: Pain assessment in brain-injured patients in the intensive care unit (ICU) is challenging and existing scales may not be representative of behavioral reactions expressed by this specific group. This study aimed to validate the French-Canadian and English revised versions of the Critical-Care Pain Observation Tool (CPOT-Neuro) for brain-injured ICU patients., Methods: A prospective cohort study was conducted in three Canadian and one American sites. Patients with a traumatic or a non-traumatic brain injury were assessed with the CPOT-Neuro by trained raters (i.e., research staff and ICU nurses) before, during, and after nociceptive procedures (i.e., turning and other) and non-nociceptive procedures (i.e., non-invasive blood pressure, soft touch). Patients who were conscious and delirium-free were asked to provide their self-report of pain intensity (0-10). A first data set was completed for all participants (n = 226), and a second data set (n = 87) was obtained when a change in the level of consciousness (LOC) was observed after study enrollment. Three LOC groups were included: (a) unconscious (Glasgow Coma Scale or GCS 4-8); (b) altered LOC (GCS 9-12); and (c) conscious (GCS 13-15)., Results: Higher CPOT-Neuro scores were found during nociceptive procedures compared to rest and non-nociceptive procedures in both data sets (p < 0.001). CPOT-Neuro scores were not different across LOC groups. Moderate correlations between CPOT-Neuro and self-reported pain intensity scores were found at rest and during nociceptive procedures (Spearman rho > 0.40 and > 0.60, respectively). CPOT-Neuro cut-off scores ≥ 2 and ≥ 3 were found to adequately classify mild to severe self-reported pain ≥ 1 and moderate to severe self-reported pain ≥ 5, respectively. Interrater reliability of raters' CPOT-Neuro scores was supported with intraclass correlation coefficients > 0.69., Conclusions: The CPOT-Neuro was found to be valid in this multi-site sample of brain-injured ICU patients at various LOC. Implementation studies are necessary to evaluate the tool's performance in clinical practice.

Background: Pain from rib fractures is associated with significant pulmonary morbidity. Epidural and paravertebral blocks (EPVBs) have been recommended as part of a multimodal approach to rib fracture pain, but their utility is often challenging in the trauma intensive care unit (ICU). The serratus anterior plane block (SAPB) has potential as an alternative approach for chest wall analgesia., Methods: This retrospective study compared critically injured adults sustaining multiple rib fractures who had SAPB (n=14) to EPVB (n=25). Patients were matched by age, body mass index, American Society of Anesthesiology Physical Status, whether the patient required intubation, number of rib fractures and injury severity score. Outcome measures included hospital length of stay, ICU length of stay, preblock and post block rapid shallow breathing index (RSBI) in intubated patients, pain scores and morphine equivalent doses administered 24-hour preblock and post-block in non-intubated patients, and mortality., Results: There were no demographic differences between the two groups after matching. Nearly all of the patients who received either SAPB or EPVB demonstrated a reduction in RSBI or pain scores. The preblock RSBI was higher in the serratus anterior plane block group, but there was no difference between any of the other outcome measures., Discussion: This retrospective study of our institutional data suggests no difference in efficacy between the serratus anterior plane block and neuraxial block for traumatic rib fracture pain in critically ill patients, but the sample size was too small to show statistical equivalence. Serratus anterior plane block is technically easier to perform with fewer theoretical contraindications compared with traditional neuraxial block. Further study with prospective comparative trials is warranted., Level of Evidence: Retrospective matched cohort; Level IV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology, but how proteins localize differentially to these structures within a shared cytoplasm remains unclear. Here, we show that the actin-binding domains of accessory proteins can be sensitive to filament conformational changes. Using a combination of live cell imaging and in vitro single molecule binding measurements, we show that tandem calponin homology domains (CH1-CH2) can be mutated to preferentially bind actin networks at the front or rear of motile cells. We demonstrate that the binding kinetics of CH1-CH2 domain mutants varies as actin filament conformation is altered by perturbations that include stabilizing drugs and other binding proteins. These findings suggest that conformational changes of actin filaments in cells could help to direct accessory binding proteins to different actin cytoskeletal structures through a biophysical feedback loop.

Endotracheal intubation (EI) is a potentially lifesaving but high-risk procedure in critically ill patients. While the ACGME mandates that trainees in pulmonary and critical care medicine (PCCM) achieve competence in this procedure, there is wide variation in EI training across the USA. One study suggests that 40% of the US PCCM trainees feel they would not be proficient in EI upon graduation. This article presents a review of the EI training literature; the recommendations of a national group of PCCM, anesthesiology, emergency medicine, and pediatric experts; and a call for further research, collaboration, and consensus guidelines.

Introduction: Cardiovascular collapse is a common complication during tracheal intubation of critically ill adults. Whether administration of an intravenous fluid bolus prevents cardiovascular collapse during tracheal intubation remains uncertain. A prior randomised trial found fluid bolus administration to be ineffective overall but suggested potential benefit for patients receiving positive pressure ventilation during tracheal intubation., Methods and Analysis: The PREventing cardiovascular collaPse with Administration of fluid REsuscitation during Induction and Intubation (PREPARE II) trial is a prospective, multi-centre, non-blinded randomised trial being conducted in 13 academic intensive care units in the USA. The trial will randomise 1065 critically ill adults undergoing tracheal intubation with planned use of positive pressure ventilation (non-invasive ventilation or bag-mask ventilation) between induction and laryngoscopy to receive 500 mL of intravenous crystalloid or no intravenous fluid bolus. The primary outcome is cardiovascular collapse, defined as any of: systolic blood pressure <65 mm Hg, new or increased vasopressor administration between induction and 2 min after intubation, or cardiac arrest or death between induction and 1 hour after intubation. The primary analysis will be an unadjusted, intention-to-treat comparison of the primary outcome between patients randomised to fluid bolus administration and patients randomised to no fluid bolus administration using a χ 2 test. The sole secondary outcome is 28-day in-hospital mortality. Enrolment began on 1 February 2019 and is expected to conclude in June 2020., Ethics and Dissemination: The trial was approved by either the central institutional review board at Vanderbilt University Medical Center or the local institutional review board at each trial site. Results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences., Trial Registration Number: NCT03787732., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Macrophage phagocytosis can be triggered by diverse receptor-ligand interactions to clear pathogens and dead cells from a host. Many ways of assaying phagocytosis exist that utilize a variety of phagocytic targets with different combinations of receptor-ligand interactions, making comparisons difficult. To study how phagocytosis is affected by specific changes to the target surface, we developed an in vitro assay based on reconstituted membrane-coated target particles to which known molecules can be added. The targets are made by coating glass beads with supported lipid bilayers followed by coupling proteins and other ligands of interest. Composition of the lipid bilayer can be varied to bind and orient specific proteins, incorporate signaling and reporter lipids, and control bilayer fluidity. To quantify phagocytosis, the reconstituted target particles are incubated with macrophages in vitro for a defined period of time, imaged with fluorescence microscopy and analyzed with software that measures the amount of target particle fluorescence within each macrophage. A multi-well plate format can be used for multi-parameter studies (e.g., to investigate how phagocytosis is affected by specific receptor-ligand interactions, ligand density, lipid charge, membrane fluidity and other molecular details). As an example, we demonstrate that antibody-dependent phagocytosis is more efficient for targets with fluid membranes than non-fluid membranes. The assay protocol takes approximately 6 h and requires basic molecular biology, mammalian cell culture and fluorescence microscopy skills. This assay can also be used with other phagocytic and non-phagocytic cells to study the individual or collective roles of receptors and ligands in immune effector function.

Objective: The development of these updated clinical practice guidelines (CPGs) was commissioned by the American Association of Clinical Endocrinologists (AACE), The Obesity Society (TOS), American Society for Metabolic and Bariatric Surgery (ASMBS), Obesity Medicine Association (OMA), and American Society of Anesthesiologists (ASA) Boards of Directors in adherence with the AACE 2017 protocol for standardized production of CPGs, algorithms, and checklists., Methods: Each recommendation was evaluated and updated based on new evidence from 2013 to the present and subjective factors provided by experts., Results: New or updated topics in this CPG include: contextualization in an adiposity-based chronic disease complications-centric model, nuance-based and algorithm/checklist-assisted clinical decision-making about procedure selection, novel bariatric procedures, enhanced recovery after bariatric surgery protocols, and logistical concerns (including cost factors) in the current health care arena. There are 85 numbered recommendations that have updated supporting evidence, of which 61 are revised and 12 are new. Noting that there can be multiple recommendation statements within a single numbered recommendation, there are 31 (13%) Grade A, 42 (17%) Grade B, 72 (29%) Grade C, and 101 (41%) Grade D recommendations. There are 858 citations, of which 81 (9.4%) are evidence level (EL) 1 (highest), 562 (65.5%) are EL 2, 72 (8.4%) are EL 3, and 143 (16.7%) are EL 4 (lowest)., Conclusions: Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity. Clinical decision-making should be evidence based within the context of a chronic disease. A team approach to perioperative care is mandatory, with special attention to nutritional and metabolic issues., (By mutual agreement among the authors and editors of their respective journals, this work is being published jointly in Surgery for Obesity and Related Diseases, Obesity, and Endocrine Practice. © AACE 2019.)

Objective: The development of these updated clinical practice guidelines (CPG) was commissioned by the American Association of Clinical Endocrinologists, The Obesity Society, the American Society of Metabolic and Bariatric Surgery, the Obesity Medicine Association, and the American Society of Anesthesiologists boards of directors in adherence to the American Association of Clinical Endocrinologists 2017 protocol for standardized production of CPG, algorithms, and checklists., Methods: Each recommendation was evaluated and updated based on new evidence from 2013 to the present and subjective factors provided by experts., Results: New or updated topics in this CPG include contextualization in an adiposity-based, chronic disease complications-centric model, nuance-based, and algorithm/checklist-assisted clinical decision-making about procedure selection, novel bariatric procedures, enhanced recovery after bariatric surgery protocols, and logistical concerns (including cost factors) in the current healthcare arena. There are 85 numbered recommendations that have updated supporting evidence, of which 61 are revised and 12 are new. Noting that there can be multiple recommendation statements within a single numbered recommendation, there are 31 (13%) Grade A, 42 (17%) Grade B, 72 (29%) Grade C, and 101 (41%) Grade D recommendations. There are 858 citations, of which 81 (9.4%) are evidence level (EL) 1 (highest), 562 (65.5%) are EL 2, 72 (8.4%) are EL 3, and 143 (16.7%) are EL 4 (lowest)., Conclusions: Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity. Clinical decision-making should be evidence-based within the context of a chronic disease. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues., Competing Interests: Disclosures Chair of the Task Force: Jeffrey I. Mechanick, M.D., M.A.C.E.: Abbott Nutrition, honoraria for lectures and program development. Co-Chairs of the Task Force: Caroline Apovian, M.D.: Orexigen, GI Dynamics, Takeda, Nutrisystem, Zafgen, Sanofi-Aventis, Novo Nordisk, Scientific Intake, Xeno Biosciences, Rhythm Pharmaceuticals, Eisai, EnteroMedica, Bariatrix Nutrition, consultant; Gelesis and Science-Smart LLC, stock options; Aspire Bariatrics, Myos, the Vela Foundation, the Dr. Robert C. and Veronica Atkins Foundation, Coherence Lab, Energesis, Gelesis, Orexigen, GI Dynamics, Takeda, Novo Nordisk, PCORI, research grant support. Stacy Brethauer, M.D., Medtronic, speaker. W. Timothy Garvey, M.D., F.A.C.E., Merck, Novo Nordisk, American Medical Group Association, BOYDSense, Sanofi, Gilead, Amgen, Abbott Nutrition, National Diabetes and Obesity Research Institute, diaTribe Foundation, consultant; IONIS, Novartis, Bristol-Myers-Squibb, Pfizer, Merck, Lilly, stock; Sanofi, Novo Nordisk, Pfizer, research grant support. Aaron M. Joffe, D.O., F.C.C.M., American Society of Anesthesiologists, speaker. Robert F. Kushner, M.D., Novo Nordisk, Retrofit, Weight Watchers, consultant. Richard Lindquist, M.D., F.A.A.S.P., Seca scales, Metagenics/Bariatric Advantage, Livongo/Retrofit, consultant; Novo Nordisk Orexigen, speaker. Rachel Pessah-Pollack, M.D., F.A.C.E., Boehringer Ingelheim, Eli Lilly, Radius, consultant and advisor. Richard D. Urman, M.B.A., M.D., C.P.E., 3M, Sandoz, consulting fees; Merck, Medtronic, research grant support. Julie Kim, M.D. and Jennifer Seger, M.D., report no potential conflicts of interest. Task Force Members: Shanu Kothari, M.D., F.A.C.S., F.A.S.M.B.S., Ethicon, Lexington Medical, consultant; Gore Medical, speaker. Michael V. Seger, M.D., F.A.C.S., F.A.S.M.B.S., Obalon Therapeutics, consultant and speaker. Christopher D. Still, D.O., F.A.C.N., F.A.C.P., Novo Nordisk, speaker; Ethicon-Endosurgery, research grant support. M. Kathleen Figaro, M.S., M.D., F.A.C.E., Novo Nordisk, Boehringer Ingelheim, speaker. Stephanie Adams, Ph.D., John B. Cleek, M.D., Karen Flanders, M.S.N., C.N.P., C.B.N. Jayleen Grams, M.D., Ph.D., Daniel L. Hurley, M.D., F.A.C.E., and Riccardo Correa, M.D., F.A.C.E., report no potential conflicts of interest. Reviewers: Michael A. Bush, M.D., F.A.C.E., Eli Lilly, Novo Nordisk, Sanofi, Boehringer Ingleheim, Janssen, AstraZeneca, speaker. Dace L. Trence, M.D., F.A.C.E., Medtronic, Sanofi, stock ownership. Scott Isaacs, M.D., F.A.C.P., F.A.C.E. and Ann M. Rogers, M.D., F.A.C.S., report no potential conflicts of interest. Note: Reference sources are followed by an evidence level [EL] rating of 1, 2, 3, or 4., (Copyright © 2019. Published by Elsevier Inc.)

This is an updated, comprehensive review of the psychometric properties of behavioral pain assessment tools for use with noncommunicative, critically ill adults. Articles were searched in 5 health databases. A total of 106 articles were analyzed, including 54 recently published papers. Nine behavioral pain assessment tools developed for noncommunicative critically ill adults and 4 tools developed for other non-communicative populations were included. The scale development process, reliability, validity, feasibility, and clinical utility were analyzed using a 0 to 20 scoring system, and quality of evidence was also evaluated. The Behavioral Pain Scale, the Behavioral Pain Scale-Nonintubated, and the Critical-Care Pain Observation Tool remain the tools with the strongest psychometric properties, with validation testing having been conducted in multiple countries and various languages. Other tools may be good alternatives, but additional research on them is necessary., (©2019 American Association of Critical-Care Nurses.)

Objective: The development of these updated clinical practice guidelines (CPGs) was commissioned by the American Association of Clinical Endocrinologists (AACE), The Obesity Society, American Society of Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists Boards of Directors in adherence with the AACE 2017 protocol for standardized production of CPGs, algorithms, and checklists. Methods: Each recommendation was evaluated and updated based on new evidence from 2013 to the present and subjective factors provided by experts. Results: New or updated topics in this CPG include: contextualization in an adiposity-based chronic disease complications-centric model, nuance-based and algorithm/checklist-assisted clinical decision-making about procedure selection, novel bariatric procedures, enhanced recovery after bariatric surgery protocols, and logistical concerns (including cost factors) in the current health-care arena. There are 85 numbered recommendations that have updated supporting evidence, of which 61 are revised and 12 are new. Noting that there can be multiple recommendation statements within a single numbered recommendation, there are 31 (13%) Grade A, 42 (17%) Grade B, 72 (29%) Grade C, and 101 (41%) Grade D recommendations. There are 858 citations, of which 81 (9.4%) are evidence level (EL) 1 (highest), 562 (65.5%) are EL 2, 72 (8.4%) are EL 3, and 143 (16.7%) are EL 4 (lowest). Conclusion: Bariatric procedures remain a safe and effective intervention for higher-risk patients with obesity. Clinical decision-making should be evidence based within the context of a chronic disease. A team approach to perioperative care is mandatory, with special attention to nutritional and metabolic issues. A1C = hemoglobin A1c; AACE = American Association of Clinical Endocrinologists; ABCD = adiposity-based chronic disease; ACE = American College of Endocrinology; ADA = American Diabetes Association; AHI = Apnea-Hypopnea Index; ASA = American Society of Anesthesiologists; ASMBS = American Society of Metabolic and Bariatric Surgery; BMI = body mass index; BPD = biliopancreatic diversion; BPD/DS = biliopancreatic diversion with duodenal switch; CI = confidence interval; CPAP = continuous positive airway pressure; CPG = clinical practice guideline; CRP = C-reactive protein; CT = computed tomography; CVD = cardiovascular disease; DBCD = dysglycemia-based chronic disease; DS = duodenal switch; DVT = deep venous thrombosis; DXA = dual-energy X-ray absorptiometry; EFA = essential fatty acid; EL = evidence level; EN = enteral nutrition; ERABS = enhanced recovery after bariatric surgery; FDA = U.S. Food and Drug Administration; G4G = Guidelines for Guidelines; GERD = gastroesophageal reflux disease; GI = gastrointestinal; HCP = health-care professional(s); HTN = hypertension; ICU = intensive care unit; IGB = intragastric balloon(s); IV = intravenous; LAGB = laparoscopic adjustable gastric band; LAGBP = laparoscopic adjustable gastric banded plication; LGP = laparoscopic greater curvature (gastric) plication; LRYGB = laparoscopic Roux-en-Y gastric bypass; LSG = laparoscopic sleeve gastrectomy; MetS = metabolic syndrome; NAFLD = nonalcoholic fatty liver disease; NASH = nonalcoholic steatohepatitis; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; OAGB = one-anastomosis gastric bypass; OMA = Obesity Medicine Association; OR = odds ratio; ORC = obesity-related complication(s); OSA = obstructive sleep apnea; PE = pulmonary embolism; PN = parenteral nutrition; PRM = pulmonary recruitment maneuver; RCT = randomized controlled trial; RD = registered dietician; RDA = recommended daily allowance; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; SIBO = small intestinal bacterial overgrowth; TOS = The Obesity Society; TSH = thyroid-stimulating hormone; T1D = type 1 diabetes; T2D = type 2 diabetes; VTE = venous thromboembolism; WE = Wernicke encephalopathy; WHO = World Health Organization.

Background: Tracheal intubation is common in the care of critically ill adults and is frequently complicated by hypotension, cardiac arrest, or death. We aimed to evaluate administration of an intravenous fluid bolus to prevent cardiovascular collapse during intubation of critically ill adults., Methods: We did a pragmatic, multicentre, unblinded, randomised trial in nine sites (eight ICUs and one emergency department) around the USA. Critically ill adults (≥18 years) undergoing tracheal intubation were randomly assigned (1:1, block sizes of 2, 4, and 6, stratified by study site) to either an intravenous infusion of 500 mL of crystalloid solution or no fluid bolus. The primary outcome, assessed in the intention-to-treat population, was cardiovascular collapse, defined as a new systolic blood pressure <65 mm Hg; new or increased vasopressor receipt between induction and 2 min after tracheal intubation; or cardiac arrest or death within 1 h of tracheal intubation. Adverse events were assessed in the as-treated population. This trial, which is now complete, is registered with ClinicalTrials.gov, number NCT03026777., Findings: Patients were enrolled from Feb 6, 2017, to Jan 9, 2018, when the data and safety monitoring board stopped the trial on the basis of futility. By trial termination, 337 (63%) of 537 screened adults had been randomly assigned. Cardiovascular collapse occurred in 33 (20%) of 168 patients in the fluid bolus group compared with 31 (18%) of 169 patients in the no fluid bolus group (absolute difference 1·3% [95% CI -7·1% to 9·7%]; p=0·76). The individual components of the cardiovascular collapse composite outcome did not differ between groups (new systolic blood pressure <65 mm Hg 11 [7%] in the bolus group vs ten [6%] in the no-bolus group, new or increased vasopressor 32 [19%] vs 31 [18%], cardiac arrest within 1 h seven [4%] vs two [1%], death within 1 h of intubation two [1%] vs one [1%]). In-hospital mortality was not significantly different in the fluid bolus group (48 [29%]) compared with no fluid bolus (59 [35%])., Interpretation: Administration of an intravenous fluid bolus did not decrease the overall incidence of cardiovascular collapse during tracheal intubation of critically ill adults compared with no fluid bolus in this trial., Funding: US National Institutes of Health., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic bacterial organism resistant to first line antibiotics. Acquisition of MRSA is often classified as either healthcare-associated or community-acquired. It has been shown that both healthcare-associated and community-acquired infections contribute to the spread of MRSA within healthcare facilities. The objective of this study was to estimate the incremental inpatient cost and length of stay for individuals colonized or infected with MRSA. Common analytical methods were compared to ensure the quality of the estimate generated. This study was performed at Alberta Ministry of Health (Edmonton, Alberta), with access to clinical MRSA data collected at two Edmonton hospitals, and ministerial administrative data holdings., Methods: A retrospective cohort study of patients with MRSA was identified using a provincial infection prevention and control database. A coarsened exact matching algorithm, and two regression models (semilogarithmic ordinary least squares model and log linked generalized linear model) were evaluated. A MRSA-free cohort from the same facilities and care units was identified for the matched method; all records were used for the regression models. Records span from January 1, 2011 to December 31, 2015, for individuals 18 or older at discharge., Results: Of the models evaluated, the generalized linear model was found to perform the best. Based on this model, the incremental inpatient costs associated with hospital-acquired cases were the most costly at $31,686 (14,169 - 60,158) and $47,016 (23,125 - 86,332) for colonization and infection, respectively. Community-acquired MRSA cases also represent a significant burden, with incremental inpatient costs of $7397 (2924 - 13,180) and $14,847 (8445 - 23,207) for colonization and infection, respectively. All costs are adjusted to 2016 Canadian dollars. Incremental length of stay followed a similar pattern, where hospital-acquired infections had the longest incremental stays of 35.2 (16.3-69.5) days and community-acquired colonization had the shortest incremental stays of 3.0 (0.6-6.3) days., Conclusions: MRSA, and in particular, hospital-acquired MRSA, places a significant but preventable cost burden on the Alberta healthcare system. Estimates of cost and length of stay varied by the method of analysis and source of infection, highlighting the importance of selecting the most appropriate method.

Background: Difficult or failed intubation is a major contributor to morbidity for patients and liability for anesthesiologists. Updated difficult airway management guidelines and incorporation of new airway devices into practice may have affected patient outcomes. The authors therefore compared recent malpractice claims related to difficult tracheal intubation to older claims using the Anesthesia Closed Claims Project database., Methods: Claims with difficult tracheal intubation as the primary damaging event occurring in the years 2000 to 2012 (n = 102) were compared to difficult tracheal intubation claims from 1993 to 1999 (n = 93). Difficult intubation claims from 2000 to 2012 were evaluated for preoperative predictors and appropriateness of airway management., Results: Patients in 2000 to 2012 difficult intubation claims were sicker (78% American Society of Anesthesiologists [ASA] Physical Status III to V; n = 78 of 102) and had more emergency procedures (37%; n = 37 of 102) compared to patients in 1993 to 1999 claims (47% ASA Physical Status III to V; n = 36 of 93; P < 0.001 and 22% emergency; n = 19 of 93; P = 0.025). More difficult tracheal intubation events occurred in nonperioperative locations in 2000 to 2012 than 1993 to 1999 (23%; n = 23 of 102 vs. 10%; n = 10 of 93; P = 0.035). Outcomes differed between time periods (P < 0.001), with a higher proportion of death in 2000 to 2012 claims (73%; n = 74 of 102 vs. 42%; n = 39 of 93 in 1993 to 1999 claims; P < 0.001 adjusted for multiple testing). In 2000 to 2012 claims, preoperative predictors of difficult tracheal intubation were present in 76% (78 of 102). In the 97 claims with sufficient information for assessment, inappropriate airway management occurred in 73% (71 of 97; κ = 0.44 to 0.66). A "can't intubate, can't oxygenate" emergency occurred in 80 claims with delayed surgical airway in more than one third (39%; n = 31 of 80)., Conclusions: Outcomes remained poor in recent malpractice claims related to difficult tracheal intubation. Inadequate airway planning and judgment errors were contributors to patient harm. Our results emphasize the need to improve both practitioner skills and systems response when difficult or failed tracheal intubation is encountered.

Rationale: "Target trial emulation" has been proposed as an observational method to answer comparative effectiveness questions, but it has rarely been attempted concurrently with a randomized clinical trial (RCT). Objectives: We tested the hypothesis that blinded analysts applying target trial emulation to existing observational data could predict the results of an RCT. Methods: PreVent (Preventing Hypoxemia with Manual Ventilation during Endotracheal Intubation) was a multicenter RCT examining the effects of positive-pressure ventilation during tracheal intubation on oxygen saturation and severe hypoxemia. Analysts unaware of PreVent's results used patient-level data from three previous trials evaluating airway management interventions to emulate PreVent's eligibility criteria, randomization procedure, and statistical analysis. After PreVent's release, results of this blinded observational analysis were compared with those of the RCT. Difference-in-differences estimates for comparison of treatment effects between the observational analysis and the PreVent trial are reported on the absolute scale. Results: Using observational data, we were able to emulate PreVent's randomization procedure to produce balanced groups for comparison. The lowest oxygen saturation during intubation was higher in the positive-pressure ventilation group than the no positive-pressure ventilation group in the observational analysis ( n  = 360; mean difference = 1.8%; 95% confidence interval [CI] = -1.0 to 4.6) and in the PreVent trial ( n  = 401; mean difference = 3.9%; 95% CI = 1.4 to 6.4), though the observational analysis could not exclude no difference. Difference-in-differences estimates comparing treatment effects showed reasonable agreement for lowest oxygen saturation between the observational analysis and the PreVent trial (mean difference = -2.1%; 95% CI = -5.9 to 1.7). Positive-pressure ventilation resulted in lower rates of severe hypoxemia in both the observational analysis (risk ratio = 0.60; 95% CI = 0.38 to 0.93) and in the PreVent trial (risk ratio = 0.48; 95% CI = 0.30 to 0.77). The absolute reduction in the incidence of severe hypoxemia with positive-pressure ventilation was similar in the observational analysis (9.4%) and the PreVent trial (12.0%), though the difference between these estimates had wide CIs (mean difference = 2.5%; 95% CI = -8.0 to 13.6%). Conclusions: Applying target trial emulation methods to existing observational data for the evaluation of a novel intervention produced results similar to those of a randomized trial. These findings support the use of target trial emulation for comparative effectiveness research.

Purpose: In hospital-based studies, patients intubated by physicians while in an inclined position compared to supine position had a higher rate of first pass success and lower rate of peri-intubation complications. We evaluated the impact of patient positioning on prehospital endotracheal intubation in an EMS system with rapid sequence induction capability. We hypothesized that patients in the inclined position would have a higher first-pass success rate., Methods: Prehospital endotracheal intubation cases performed by paramedics between 2012 and 2017 were prospectively collected in airway registries maintained by a metropolitan EMS system. We included all adult (age ≥ 18 years) non-traumatic, non-arrest patients who received any attempt at intubation. Patients were categorized according to initial positioning: supine or inclined. The primary outcome measure was first pass success with secondary outcomes of laryngoscopic view and challenges to intubation., Results: Of the 13,353 patients with endotracheal intubation attempted by paramedics during the study period, 4879 were included for analysis. Of these, 1924 (39.4%) were intubated in the inclined position. First pass success was 86.3% among the inclined group versus 82.5% for the supine group (difference 3.8%, 95% CI: 1.5%-6.1%). First attempt laryngeal grade I view was 62.9% in the inclined group versus 57.1% for the supine group (difference 5.8%, 2.0-9.6). Challenges to intubation were more frequent in the supine group (42.3% versus 38.8%, difference 3.5%, 0.6-6.3)., Conclusion: Inclined positioning was associated with a better grade view and higher rate of first pass success. The technique should be considered as a viable approach for prehospital airway management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In the intensive care unit (ICU), extubation failure has been associated with greater resource utilization and worsened clinical outcomes. Most recently, nighttime extubation (NTE) has been reported as a risk factor for increased ICU and hospital mortality. We hypothesized that, in a large, urban, university-affiliated hospital with multidisciplinary assessment for extubation, rigorously protocolized extubation algorithms, and expert airway managers available at all times of day for assessment of high-risk extubations, NTE would not confer additional risk of adverse clinical outcomes., Methods: This was a retrospective cohort study of mechanically ventilated adults at a single university-affiliated hospital. NTE was defined as occurring between 7:00 PM and 6:59 AM the following day. All data were extracted from the institution's electronic medical record. Multivariable regression analyses were used to assess associations between NTE and reintubation, ICU and hospital length of stay (LOS), and mortality with adjustments for demographic and clinical covariates defined a priori. Palliative, unplanned, and routine postoperative extubations were excluded in sensitivity analyses., Results: Of 2241 patients, 204 of 2241 (9.1%) underwent NTE. The rates of reintubation (NTE 6.9% versus daytime extubation [DTE] 12.4%; adjusted odds ratio [95% confidence interval {CI}], 0.78 [0.43-1.41]; P = .41) and in-hospital mortality (NTE 3.4% versus DTE 5.9%; adjusted odds ratio [95% CI], 0.72 [0.28-1.84]; P = .49) were not found to differ. NTE, compared to DTE, was associated with shorter duration of mechanical ventilation (median [interquartile range], 1 [0-1] days vs 2 [1-4] days; adjusted ratio of geometric means [RGMs] [95% CI], 0.64 [0.54-0.70]; P < .001), ICU (2 [1-5] days vs 4 [2-10] days; adjusted RGMs [95% CI], 0.65 [0.57-0.75]; P < .001), and hospital LOS (6 [3-18] days vs 13 [6-25] days; adjusted RGMs [95% CI], 0.64 [0.56-0.74]; P < .001). These results were unchanged in sensitivity analyses., Conclusions: Patients who underwent NTE were not at increased risk of reintubation or in-hospital mortality. In addition, NTE was associated with a shortened duration of mechanical ventilation and hospital LOS. In health care systems with similar critical care delivery models, NTE may coincide with reduced resource utilization in appropriately selected patients.

Background: Erysipelothrix rhusiopathiae is a zoonotic pathogen that causes erysipeloid and is most frequently associated with exposure to domestic swine. Infection of native and prosthetic joints is a rarely reported manifestation., Case Presentation: We describe a case of E. rhusiopathiae prosthetic joint infection in a woman with a history of exposure to wild animals in the Canadian Arctic. Patient management involved a 1-stage surgical revision exchange with an antibiotic impregnated cement spacer and 6 weeks of intravenous penicillin G followed by 6 weeks of oral amoxicillin. Ten previously reported cases of E. rhusiopathiae joint infection are reviewed. Recent increases in mortality due to infection with this organism among host animal populations in the Canadian Arctic have generated concern regarding a potential increase in human infections. However, whole genome sequencing (WGS) of the organism was unable to identify a zoonotic origin for this case., Conclusions: Consideration should be given to E. rhusiopathiae as a cause of joint infections if the appropriate epidemiologic and host risk factors exist. Expanded use of WGS in other potential animal hosts and environmental sources may provide important epidemiologic information in determining the source of human infections.

Background: Hypoxemia is the most common complication during tracheal intubation of critically ill adults and may increase the risk of cardiac arrest and death. Whether positive-pressure ventilation with a bag-mask device (bag-mask ventilation) during tracheal intubation of critically ill adults prevents hypoxemia without increasing the risk of aspiration remains controversial., Methods: In a multicenter, randomized trial conducted in seven intensive care units in the United States, we randomly assigned adults undergoing tracheal intubation to receive either ventilation with a bag-mask device or no ventilation between induction and laryngoscopy. The primary outcome was the lowest oxygen saturation observed during the interval between induction and 2 minutes after tracheal intubation. The secondary outcome was the incidence of severe hypoxemia, defined as an oxygen saturation of less than 80%., Results: Among the 401 patients enrolled, the median lowest oxygen saturation was 96% (interquartile range, 87 to 99) in the bag-mask ventilation group and 93% (interquartile range, 81 to 99) in the no-ventilation group (P = 0.01). A total of 21 patients (10.9%) in the bag-mask ventilation group had severe hypoxemia, as compared with 45 patients (22.8%) in the no-ventilation group (relative risk, 0.48; 95% confidence interval [CI], 0.30 to 0.77). Operator-reported aspiration occurred during 2.5% of intubations in the bag-mask ventilation group and during 4.0% in the no-ventilation group (P = 0.41). The incidence of new opacity on chest radiography in the 48 hours after tracheal intubation was 16.4% and 14.8%, respectively (P = 0.73)., Conclusions: Among critically ill adults undergoing tracheal intubation, patients receiving bag-mask ventilation had higher oxygen saturations and a lower incidence of severe hypoxemia than those receiving no ventilation. (Funded by Vanderbilt Institute for Clinical and Translational Research and others; PreVent ClinicalTrials.gov number, NCT03026322.)., (Copyright © 2019 Massachusetts Medical Society.)

Rationale: Hypoxemia is a common complication during tracheal intubation of critically ill adults and is a frequently used endpoint in airway management research. Identifying patients likely to experience low oxygen saturations during tracheal intubation may be useful for clinical practice and clinical trials., Objectives: To identify risk factors for lower oxygen saturations and severe hypoxemia during tracheal intubation of critically ill adults and develop prediction models for lowest oxygen saturation and hypoxemia., Methods: Using data on 433 intubations from two randomized trials, we developed linear and logistic regression models to identify preprocedural risk factors for lower arterial oxygen saturations and severe hypoxemia between induction and 2 minutes after intubation. Penalized regression was used to develop prediction models for lowest oxygen saturation after induction and severe hypoxemia. A simplified six-point score was derived to predict severe hypoxemia., Results: Among the 433 intubations, 426 had complete data and were included in the model. The mean (standard deviation) lowest oxygen saturation was 88% (14%); median (interquartile range) was 93% (83-98%). Independent predictors of severe hypoxemia included hypoxemic respiratory failure as the indication for intubation (odds ratio [OR], 2.70; 95% confidence interval [CI], 1.58-4.60), lower oxygen saturation at induction (OR, 0.92 per 1% increase; 95% CI, 0.89-0.96 per 1% increase), younger age (OR, 0.97 per 1-year increase; 95% CI, 0.95-0.99 per 1-year increase), higher body mass index (OR, 1.03 per 1 kg/m 2 ; 95% CI, 1.00-1.06 per 1 kg/m 2 ), race (OR, 4.58 for white vs. black; 95% CI, 1.97-10.67; OR, 4.47 for other vs. black; 95% CI, 1.19-16.84), and operator with fewer than 100 prior intubations (OR, 2.83; 95% CI, 1.37-5.85). A six-point score using the identified risk factors predicted severe hypoxemia with an area under the receiver operating curve of 0.714 (95% CI, 0.653 to 0.778)., Conclusions: Lowest oxygen saturation and severe hypoxemia during tracheal intubation in the intensive care unit can be accurately predicted using routinely available preprocedure clinical data, with saturation at induction and hypoxemic respiratory failure being the strongest predictors. A simple bedside score may identify patients at risk for hypoxemia during intubation to help target preventative interventions and facilitate enrichment in clinical trials.

Objective: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU., Design: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017., Methods: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified., Results: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation., Conclusions: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Introduction: Hypoxaemia is the most common complication during endotracheal intubation of critically ill adults, and it increases the risk of cardiac arrest and death. Manual ventilation between induction and intubation has been hypothesised to decrease the incidence of hypoxaemia, but efficacy and safety data are lacking., Methods and Analysis: The Preventing Hypoxemia with Manual Ventilation during Endotracheal Intubation trial is a prospective, multicentre, non-blinded randomised clinical trial being conducted in seven intensive care units in the USA. A total of 400 critically ill adults undergoing endotracheal intubation will be randomised 1:1 to receive prophylactic manual ventilation between induction and endotracheal intubation using a bag-valve-mask device or no prophylactic ventilation. The primary outcome is the lowest arterial oxygen saturation between induction and 2 min after successful endotracheal intubation, which will be analysed as an unadjusted, intention-to-treat comparison of patients randomised to prophylactic ventilation versus patients randomised to no prophylactic ventilation. The secondary outcome is the incidence of severe hypoxaemia, defined as any arterial oxygen saturation of less than 80% between induction and 2 min after endotracheal intubation. Enrolment began on 2 February 2017 and is expected to be complete in May 2018., Ethics and Dissemination: The trial was approved by the institutional review boards or designees of all participating centres. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences., Trial Registration Number: NCT03026322; Pre-results., Competing Interests: Competing interests: All authors completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors declared no potential conflicts of interest with the current work. TWR reported serving on an advisory board for Avisa Pharma, LLC, and as the Director of Medical Affairs for Cumberland Pharmaceuticals., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Airway management in the presence of acute cervical spine injury (CSI) is challenging. Because it limits cervical spine motion during tracheal intubation and allows for neurological examination after the procedure, awake fiberoptic bronchoscopy (FOB) has traditionally been recommended. However, with the widespread availability of video laryngoscopy (VL), its use has declined dramatically. Our aim was to describe the frequency of airway management techniques used in patients with CSI at our level I trauma center and report the incidence of neurological injury attributable to airway management., Methods: Adults presenting to the operating room with CSI without a tracheal tube in situ between September 2010 and June 2017 were included. All patients were intubated in the presence of manual-in-line stabilization, a hard cervical collar, or surgical traction. Worsening neurological status was defined as new motor or sensory deficits on postoperative examination., Results: Two hundred fifty-two patients were included, of which 76 (30.2%) had preexisting neurological deficits. VL was the most frequent initial airway management technique used (49.6%). Asleep FOB was commonly performed alone (30.6%) or in conjunction with VL (13.5%). Awake FOB was rarely performed (2.3%), as was direct laryngoscopy (2.8%). All techniques were associated with high first-attempt success rates, and no cases of neurological injury attributable to airway management technique were identified., Conclusions: Among patients with acute CSI at a high-volume academic trauma center, VL was the most commonly used initial intubation technique. Awake FOB and direct laryngoscopy were performed infrequently. No cases of neurological deterioration secondary to airway management occurred with any method. Assuming care is taken to limit neck movement, providers should use the intubation technique with which they have the most comfort and skill.

Macrophages protect the body from damage and disease by targeting antibody-opsonized cells for phagocytosis. Though antibodies can be raised against antigens with diverse structures, shapes, and sizes, it is unclear why some are more effective at triggering immune responses than others. Here, we define an antigen height threshold that regulates phagocytosis of both engineered and cancer-specific antigens by macrophages. Using a reconstituted model of antibody-opsonized target cells, we find that phagocytosis is dramatically impaired for antigens that position antibodies >10 nm from the target surface. Decreasing antigen height drives segregation of antibody-bound Fc receptors from the inhibitory phosphatase CD45 in an integrin-independent manner, triggering Fc receptor phosphorylation and promoting phagocytosis. Our work shows that close contact between macrophage and target is a requirement for efficient phagocytosis, suggesting that therapeutic antibodies should target short antigens in order to trigger Fc receptor activation through size-dependent physical segregation., (Copyright © 2018 Elsevier Inc. All rights reserved.)