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Background: Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods: We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. Findings: From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation: The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.

Objectives: Describe contemporary ECMO utilization patterns among patients with traumatic brain injury (TBI) and examine clinical outcomes among TBI patients requiring ECMO. Design: Retrospective cohort study. Setting: Premier Healthcare Database (PHD) between January 2016 to June 2020. Subjects: Adult patients with TBI who were mechanically ventilated and stratified by exposure to ECMO. Results: Among patients exposed to ECMO, we examined the following clinical outcomes: hospital LOS, ICU LOS, duration of mechanical ventilation, and hospital mortality. Of our initial cohort (n = 59,612), 118 patients (0.2%) were placed on ECMO during hospitalization. Most patients were placed on ECMO within the first 2 days of admission (54.3%). Factors associated with ECMO utilization included younger age (OR 0.96, 95% CI (0.95–0.97)), higher injury severity score (ISS) (OR 1.03, 95% CI (1.01–1.04)), vasopressor utilization (2.92, 95% CI (1.90–4.48)), tranexamic acid utilization (OR 1.84, 95% CI (1.12–3.04)), baseline comorbidities (OR 1.06, 95% CI (1.03–1.09)), and care in a teaching hospital (OR 3.04, 95% CI 1.31–7.05). A moderate degree (ICC = 19.5%) of variation in ECMO use was explained at the individual hospital level. Patients exposed to ECMO had longer median (IQR) hospital and ICU length of stay (LOS) [26 days (11–36) versus 9 days (4–8) and 19.5 days (8–32) versus 5 days (2–11), respectively] and a longer median (IQR) duration of mechanical ventilation [18 days (8–31) versus 3 days (2–8)]. Patients exposed to ECMO experienced a hospital mortality rate of 33.9%, compared to 21.2% of TBI patients unexposed to ECMO. Conclusions: ECMO utilization in mechanically ventilated patients with TBI is rare, with significant variation across hospitals. The impact of ECMO on healthcare utilization and hospital mortality following TBI is comparable to non-TBI conditions requiring ECMO. Further research is necessary to better understand the role of ECMO following TBI and identify patients who may benefit from this therapy.

Background Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. Methods This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors’ primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors’ primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria. Exploratory analyses included associations of ascending age groups and hormone replacement therapy home medications with postoperative AKI. Results Among 390,382 patients, 25,809 (6.6%) developed postoperative AKI (females 50 yr or younger: 2,190 of 58,585 [3.7%]; females older than 50 yr: 9,320 of 14,4047 [6.5%]; males 50 yr or younger: 3,289 of 55,503 [5.9%]; males older than 50 yr: 11,010 of 132,447 [8.3%]). When adjusted for AKI risk factors, compared to females younger than 50 yr (odds ratio, 1), the odds of AKI were higher in females older than 50 yr (odds ratio, 1.51; 95% CI, 1.43 to 1.59), males younger than 50 yr (odds ratio, 1.90; 95% CI, 1.79 to 2.01), and males older than 50 yr (odds ratio, 2.06; 95% CI, 1.96 to 2.17). Conclusions Younger females display a lower odds of postoperative AKI that gradually increases with age. These results suggest that age-related changes in women should be further studied as modifiers of postoperative AKI risk after noncardiac surgery. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Many deaths after surgery can be attributed to "failure to rescue," which may be a better surgical quality indicator than the occurrence of a postoperative complication. Acute kidney injury (AKI) is one such postoperative complication associated with high mortality. The purpose of this study is to identify perioperative risk factors associated with failure to rescue among patients who develop postoperative AKI.We identified adult patients who underwent non-cardiac surgery between 2012 and 2018 and experienced postoperative severe AKI (an increase in blood creatinine concentration of2 mg/dL above baseline or requiring hemodialysis) from the American College of Surgeons National Surgical Quality Improvement Program database. Multivariable logistic regression was used to identify risk factors for failure to rescue among patients who developed severe AKI.Among 5,765,904 patients who met inclusion criteria, 26,705 (0.46%) patients developed postoperative severe AKI, of which 6834 (25.6%) experienced failure to rescue. Risk factors with the strongest association (adjusted odds ratio1.5) with failure to rescue in patients with AKI included advanced age, higher American Society of Anesthesiologists class, presence of preoperative ascites, disseminated cancer, septic shock, and blood transfusion within 72 h of surgery start time.About one-fourth of patients who develop severe AKI after non-cardiac surgery die within 30 d of surgery. Both patient- and surgery-related risk factors are associated with this failure to rescue. Further studies are needed to identify early and effective interventions in high-risk patients who develop postoperative severe AKI to prevent the antecedent mortality.

Continuous renal replacement therapy (CRRT) is essential to the management of acute kidney injury (AKI) in critical illness. Unfortunately, large quantities of micronutrients are shown to be lost in CRRT effluent. Current literature describes serum micronutrient values in CRRT patients to be below-reference range, yet seldom compares such values to other critically ill populations unexposed to CRRT. The aim of this study was to describe and compare the prevalence of micronutrient and carnitine deficiencies in critically ill patients at high malnutrition risk exposed to CRRT to a group of patient unexposed to CRRT.A retrospective chart review was conducted at Duke University Hospital using the electronic medical record. The study group consisted of patients at high malnutrition risk requiring intensive care unit (ICU) admission from 01/01/2017-12/31/2018 with one or more of the following serum micronutrient levels checked: carnitine, copper, zinc, selenium, and vitamins B1, B6, B9, and C. Micronutrient deficiencies were defined as below the reference range and carnitine deficiencies were interpreted as an acyl to free carnitine ratio (ACFR) of0.4.106 ICU patients met inclusion criteria and 46% were exposed to CRRT. At least one micronutrient deficiency was reported in 90% of CRRT patients compared to 61% patients unexposed to CRRT (p = 0.002). A greater percentage of copper (p 0.001) and carnitine (p 0.001) deficiencies were found among patients exposed to CRRT, while more zinc deficiencies were noted among non-CRRT patients (p = 0.001).The vast majority of CRRT patients presented with micronutrient deficiencies. Clinicians should have a heightened awareness of the risk for serum copper, carnitine, and vitamin B6 deficiencies among CRRT patients. Further prospective and randomized-controlled trials are needed to better define this new category of malnutrition and test supplementation strategies to address and prevent these clinically-relevant deficiencies.

Perioperative ischemic stroke significantly increases morbidity and mortality in patients undergoing elective surgery. Mechanical thrombectomy can improve ischemic stroke outcomes, but frequency and trend of its utilization for treatment of perioperative ischemic stroke is not studied. We identified adults who underwent elective inpatient surgery from 2008 to 2018 and suffered from a perioperative ischemic stroke from the Premier Healthcare Database. The difference in mechanical thrombectomy usage before and after the updated recommendation inacute stroke guidelines was assessed in a univariate analysis using a chi-squared test. A segmented regression model was created to assess the change in rate over time.Of 6,349,668 patients with elective inpatient surgery, 12,507 (0.2%) had perioperative ischemic stroke. Mean age (and standard deviation) was 69.5 (11.7) years, and 48.8% were female. Mechanical thrombectomy was used in 1.7% patients and its use increased from 0.0% in 3rd quarter, 2008 to 4.4% in 4th quarter, 2018. Significant increase in the use of mechanical thrombectomy was seen after 3rd quarter, 2015 when its use was incorporated in acute stroke treatment guideline (1.14% before 3rd quarter, 2015 versus 3.07% after; p 0.0001). Amongst patients with perioperative ischemic stroke, patients who received mechanical thrombectomy were more likely to have their surgery performed at a teaching institute (67.3% versus 53.9%). Although a significant increase in rates of utilization of mechanical thrombectomy was observed, rates of utilization remain low, especially in non-teaching hospitals. This highlights improvements in the management of perioperative ischemic strokes and further opportunities to improve outcomes.

INTRODUCTION: Data suggest that guidelines for enteral nutrition (EN) initiation are not closely followed in clinical practice. In addition, critically ill mechanically ventilated (MV) patients have varying metabolic needs, which often increase and persist over time, requiring personalized nutrition intervention. While both over- and under-nutrition can impact patient outcomes, recent data suggest that targeted early EN delivery may reduce mortality and improve clinical outcomes. This study examined if early EN improves clinical outcomes and decreases costs in critically ill patients on MV in real-world practice. METHODS: Data from a nationwide administrative-financial database between 2018‒2020 was utilized to identify eligible adult critical care patients. Patients who received EN within 3 days after intubation (early EN) were compared to patients who started EN after 3 days of intubation (late EN). Outcomes of interest included hospital mortality, discharge disposition, hospital and intensive care unit (ICU) length of stay (LOS), MV days, and total cost. After inverse-probability-of-treatment weighting, outcomes were modeled using a nominal logistic regression model for hospital mortality and discharge disposition, a linear regression model for cost, and Cox proportional-hazards model for MV days, hospital and ICU LOS. RESULTS: A total of 27,887 adult patients with early MV were identified, of which 16,772 (60.1%) received early EN. Regression analyses showed that the early EN group had lower hospital mortality (OR=0.88, 95% CI, 0.82 to 0.94), were more likely to be discharged home (OR=1.47, 95% CI 1.38 to 1.56), had fewer MV days (HR=1.23, 95% CI, 1.11 to 1.37), shorter hospital LOS (HR=1.43, 95% CI, 1.33 to 1.54) and ICU LOS (HR=1.36, 95% CI, 1.27 to 1.46), and lower cost (-$21,226; 95% CI, -$23,605 to -$18,848) compared to the late EN group. CONCLUSION: Early EN within 3 days of MV initiation in real-world practice demonstrated improved clinical and economic outcomes. These data suggest that early EN is associated with decreased hospital mortality, increased discharge to home, and decreased hospital and ICU LOS, time on MV, and cost compared to delayed initiation of EN; highlighting the importance of early EN to optimize outcomes and support the recovery of critically ill patients on MV.

Cardiac dysfunction is common in the days after severe traumatic brain injury (TBI) and may contribute to hypotension episodes, leading to worse outcomes. Little is known about cardiac function in the minutes and hours immediately following TBI. By using fluid percussion TBI in a swine model, we aimed to characterize the immediate post injury cardiac function.Intubated, anesthetized immature (25.8 ± 1.5 kg) female swine were subjected to severe fluid percussion TBI (4.2 ± 0.2 atm). Beginning at 45 min, simulating hospital arrival, all animals were resuscitated with normal saline (NS), mannitol, and phenylephrine as needed to maintain a cerebral perfusion pressure more than 60 mm Hg and intracranial pressure (ICP) less than 20 mm Hg. Primary outcomes of cardiac function were cardiac output measured by thermodilution and transesophageal echo measurements of cardiac function recorded at prespecified time points and tested for trends over time using linear regression with spline at the time of resuscitation onset. Secondary outcomes included hemodynamic measurements, ICP, and cerebral perfusion pressure.Eighteen animals were included. Post-TBI hemodynamic changes demonstrated an early decrease in mean arterial pressure and cerebral perfusion pressure with a corresponding increase in heart rate and ICP. Immediately after injury, there was a significant decrease in both left atrial area and tissue Doppler imaging e' of the LV lateral wall. In addition, there was a simultaneous increase in LV end diastolic diameter and increase in E/e' ratio of the lateral mitral annulus. All other transesophageal echo measurements demonstrated no significant changes throughout the duration of the experiment.Traumatic brain injury is associated with cardiac dysfunction and increased mortality, however there is still a limited understanding of the hemodynamic and echocardiographic response associated with TBI. In this study we demonstrate the hemodynamic and echocardiographic changes in the early stages of TBI in swine. The authors hope that these results may help better understanding on the management of patients with severe head injury.

There were 23,854 suicides by firearms in 2017 in the US, accounting for 60% of all gun deaths. Studying firearm-related mortalities is vital for reducing preventable gun deaths. This study aims to determine the association between state-level presence of restrictive firearm laws and suicide rates with firearms.This ecological study used data from the CDC Wide-Ranging Online Data for Epidemiologic Research on decedents older than 18 years who died from intentional self-harm with firearms between 2009 and 2018. Exposures of interest were state-level restrictive firearm laws: background checks on private sales, mandatory waiting periods, and prohibited possession for domestic violence restraining orders or mental health red flags. Outcomes were rates of suicide with firearms per 100,000 persons over the 10-year period within each state. Welch's t -tests compared mean mortality rates in exposed and unexposed states.There were 208,621 deaths from intentional self-harm with firearms from 2009 to 2018. States with background checks, mandatory waiting periods, and prohibited possession were associated with lower suicide rates for all firearm types compared with states without these laws (p0.05). Only states with background checks and mandatory waiting periods were associated with lower suicide rates by handguns and large firearms (p0.05).Background checks and mandatory waiting periods correlated with fewer suicides by all firearms and specific firearm types. This reduction could be due to firearm laws directly preventing people from accessing guns or existing concurrently with other suicide prevention measures. More research should be directed to understanding how firearm laws can help reduce suicide rates.

The aim of this study was to describe the utilization patterns of brain tissue oxygen (PbtO2) monitoring following severe traumatic brain injury (TBI) and determine associations with mortality, health care use, and pulmonary toxicity. We conducted a retrospective cohort study of patients from United States trauma centers participating in the American College of Surgeons National Trauma Databank between 2008 and 2016. We examined patients with severe TBI (defined by admission Glasgow Coma Scale score ≤ 8) over the age of 18 years who survived more than 24 h from admission and required intracranial pressure (ICP) monitoring. The primary exposure was PbtO2 monitor placement. The primary outcome was hospital mortality, defined as death during the hospitalization or discharge to hospice. Secondary outcomes were examined to determine the association of PbtO2 monitoring with health care use and pulmonary toxicity and included the following: (1) intensive care unit length of stay, (2) hospital length of stay, and (3) development of acute respiratory distress syndrome (ARDS). Regression analysis was used to assess differences in outcomes between patients exposed to PbtO2 monitor placement and those without exposure by using propensity weighting to address selection bias due to the nonrandom allocation of treatment groups and patient dropout. A total of 35,501 patients underwent placement of an ICP monitor. There were 1,346 (3.8%) patients who also underwent PbtO2 monitor placement, with significant variation regarding calendar year and hospital. Patients who underwent placement of a PbtO2 monitor had a crude in-hospital mortality of 31.1%, compared with 33.5% in patients who only underwent placement of an ICP monitor (adjusted risk ratio 0.84, 95% confidence interval 0.76–0.93). The development of the ARDS was comparable between patients who underwent placement of a PbtO2 monitor and patients who only underwent placement of an ICP monitor (9.2% vs. 9.8%, adjusted risk ratio 0.89, 95% confidence interval 0.73–1.09). PbtO2 monitor utilization varied widely throughout the study period by calendar year and hospital. PbtO2 monitoring in addition to ICP monitoring, compared with ICP monitoring alone, was associated with a decreased in-hospital mortality, a longer length of stay, and a similar risk of ARDS. These findings provide further guidance for clinicians caring for patients with severe TBI while awaiting completion of further randomized controlled trials.

Traumatic brain injury (TBI) is a major global health problem and a major contributor to morbidity and mortality following multisystem trauma. Extracranial organ dysfunction is common after severe TBI and significantly impacts clinical care and outcomes following injury. Despite this, extracranial organ dysfunction remains an understudied topic compared with organ dysfunction in other critical care paradigms. In this review, we will: 1) summarize the epidemiology of extracranial multiorgan dysfunction following severe TBI; 2) examine relevant mechanisms that may be involved in the development of multi-organ dysfunction following severe TBI; and 3) discuss clinical management strategies to care for these complex patients.

To identify CT parameters useful for assessment of pulmonary hypertension (PH) in patients with severe aortic stenosis (AS).Retrospective study of 165 patients who had undergone right heart catheterization (RHC), and CTA of the thorax for preoperative aortic valve replacement (TAVR) planning. These were divided into groups based on mean pulmonary artery (PA) pressure (mPAP) of 25 mm Hg on RHC (85 cases and 80 controls). Diameters of main pulmonary artery diameter (MPAD), left pulmonary artery (LPA), right pulmonary artery (RPA), and maximal long axis and short axis diameters of the right atrium (RA) and ventricle (RV) were measured on the axial plane. Univariate and multivariate statistical analysis was utilized to identify metrics predictive of PH.MPAD, LPA, and RPA were higher in subjects with mPAP25 mm Hg (p 0.0001 for all). Thresholds of 30.5 mm for MPAD (68.4% sensitivity, 82.7% specificity), and 27.5 mm for LPA and RPA (LPA: 51.9% sensitivity, 78.8% specificity; RPA: 62.0% sensitivity, 78.8% specificity) provided the best discrimination of elevated mPAP. Compared to literature values for MPAD (28.9 mm in men and 26.9 mm in women), these thresholds provide lower sensitivity but greatly increased specificity. Inclusion of RA enlargement to MPAD increased specificity to 98.5%, while inclusion of RV enlargement increased specificity to 100%.Threshold to identify PH in patients with AS using PA enlargement is higher than previously reported range for normal. Inclusion of RA and RV enlargement improves the ability of CT to more accurately identify PH in patients with AS.

Background Bone fractures are a global public health issue; however, to date, no comprehensive study of their incidence and burden has been done. We aimed to measure the global, regional, and national incidence, prevalence, and years lived with disability (YLDs) of fractures from 1990 to 2019. Methods Using the framework of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we compared numbers and age-standardised rates of global incidence, prevalence, and YLDs of fractures across the 21 GBD regions and 204 countries and territories, by age, sex, and year, from 1990 to 2019. We report estimates with 95% uncertainty intervals (UIs). Findings Globally, in 2019, there were 178 million (95% UI 162-196) new fractures (an increase of 33.4% [30.1-37.0] since 1990), 455 million (428-484) prevalent cases of acute or long-term symptoms of a fracture (an increase of 70.1% [67.5-72.5] since 1990), and 25.8 million (17.8-35.8) YLDs (an increase of 65.3% [62.4-68.0] since 1990). The age-standardised rates of fractures in 2019 were 2296.2 incident cases (2091.1-2529.5) per 100 000 population (a decrease of 9.6% [8.1-11.1] since 1990), 5614.3 prevalent cases (5286.1-5977.5) per 100 000 population (a decrease of 6.7% [5.7-7.6] since 1990), and 319.0 YLDs (220.1-442.5) per 100 000 population (a decrease of 8.4% [7.2-9.5] since 1990). Lower leg fractures of the patella, tibia or fibula, or ankle were the most common and burdensome fracture in 2019, with an age-standardised incidence rate of 419.9 cases (345.8-512.0) per 100 000 population and an age-standardised rate of YLDs of 190.4 (125.0-276.9) per 100 000 population. In 2019, age-specific rates of fracture incidence were highest in the oldest age groups, with, for instance, 15 381.5 incident cases (11 245.3-20 651.9) per 100 000 population in those aged 95 years and older. Interpretation The global age-standardised rates of incidence, prevalence, and YLDs for fractures decreased slightly from 1990 to 2019, but the absolute counts increased substantially. Older people have a particularly high risk of fractures, and more widespread injury-prevention efforts and access to screening and treatment of osteoporosis for older individuals should help to reduce the overall burden. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

Introduction Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes. Methods We conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort. Results We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95–0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87–0.93, p p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (− 1.6, 95% CI − 2.8 to − 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26–0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients. Conclusion 4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients.

Objective To evaluate trends in the use of epidural analgesia and nonopioid and opioid analgesics for patients undergoing lobectomy from 2009 to 2018. Methods We queried the Premier database for adult patients undergoing open, video-assisted, and robotic-assisted lobectomy from 2009 to 2018. The outcome of interest was changes in the receipt of epidural analgesia and nonopioid and opioid analgesics as measured by charges on the day of surgery. We also evaluated postoperative daily opioid use. We used multivariable logistic and linear regression models to examine the association between the utilization of each analgesic modality and year. Results We identified 86,308 patients undergoing lobectomy from 2009 to 2018 within the Premier database: 35,818 (41.5%) patients had open lobectomy, 35,951 (41.7%) patients had video-assisted lobectomy, and 14,539 (16.8%) patients had robotic-assisted lobectomy. For all 3 surgical cohorts, epidural analgesia use decreased, and nonopioid analgesics use increased over time, except for intravenous nonsteroidal anti-inflammatory drugs. Use of patient-controlled analgesia decreased, while opioid consumption on the day of surgery increased and postoperative opioid consumption did not decrease over time. Conclusions In this large sample of patients undergoing lobectomy, utilization of epidural analgesia declined and use of nonopioid analgesics increased. Despite these changes, opioid consumption on day of surgery increased, and there was no significant reduction in postoperative opioid consumption. Further research is warranted to examine the association of these changes with patient outcomes.

Background Elevated perioperative heart rate potentially causes perioperative myocardial injury because of imbalance in oxygen supply and demand. However, large multicenter studies evaluating early postoperative heart rate and major adverse cardiac and cerebrovascular events (MACCEs) are lacking. Objective To assess the associations of 4 postoperative heart rate assessment methods with in-hospital MACCEs after elective coronary artery bypass grafting (CABG). Methods Using data from the eICU Collaborative Research Database in the United States from 2014 to 2015, the study evaluated postoperative heart rate measured during hospitalization within 24 hours after intensive care unit admission. Four heart rate assessment methods were evaluated: maximum heart rate, duration above heart rate 100/min, area above heart rate 100/min, and time-weighted average heart rate. The outcome was in-hospital MACCEs, defined as a composite of in-hospital death, myocardial infarction, angina, arrhythmia, heart failure, stroke, cardiac arrest, or repeat revascularization. Results Among 2585 patients, the crude rate of in-hospital MACCEs was 6.2%. In multivariable logistic regression analysis, the adjusted odds ratios (95% CI) for in-hospital MAC-CEs assessed by maximum heart rate in each heart rate category (beats per minute: >100-110, >110-120, >120-130, and >130) were 1.43 (0.95-2.15), 0.98 (0.56-1.64), 1.47 (0.76-2.69), and 1.71 (0.80-3.35), respectively. Similarly, none of the other 3 methods were associated with MACCEs. Conclusions More research is needed to assess the usefulness of heart rate measurement in patients after CABG.

Background Optimizing analgesia after cesarean delivery is a priority and requires balancing adequate pain relief with the risk of analgesics-associated adverse effects. Current recommendations are for use of a multimodal, opioid-sparing analgesic regimen that includes neuraxial morphine combined with scheduled nonsteroidal anti-inflammatory drugs (NSAIDs) and scheduled acetaminophen. Furthermore, recent studies recommend scheduled acetaminophen with as-needed opioids in lieu of acetaminophen-opioid combination drugs to reduce opioid consumption and optimize analgesia. However, the extent of utilization of this recommended regimen in the United States is unclear. We therefore performed this retrospective study to evaluate postoperative analgesic regimens utilized after cesarean delivery under neuraxial anesthesia, examine variability across institutions, evaluate changes over time in postoperative analgesic practice, and examine factors associated with the use of neuraxial morphine and of multimodal analgesia. Methods This retrospective cohort study was approved by the Duke University Institutional Review Board. Parturients who underwent cesarean delivery under neuraxial anesthesia from 2008 to 2018 were included. Data were extracted from a nationwide inpatient administrative-financial database (Premier Inc, Charlotte, NC) and included parturient characteristics, comorbidities, hospital characteristics, and charges for administered medications. The primary outcome was the postoperative analgesic regimen utilized during hospitalization, including utilization of neuraxial morphine and of multimodal analgesia for postoperative pain control. We also examined the factors associated with the use of neuraxial morphine and of the multimodal regimen incorporating neuraxial morphine, NSAIDs, and acetaminophen. Results Data from 804,752 parturients were analyzed. Of this cohort, 75.8% received neuraxial morphine, 93.2% received NSAIDs, 28.4% received acetaminophen, and 81.3% received acetaminophen-opioid combination drugs. Only 6.1% received the currently recommended regimen of neuraxial morphine with NSAIDs and acetaminophen, with this percentage increasing from 1.3% in 2008 to 15.0% in 2018. On the other hand, 58.9% received neuraxial morphine, NSAIDs, and an acetaminophen-opioid combination drug, with this regimen being utilized in 57.0% of cases in 2008 and 58.1% in 2018. The hospital in which the patient was treated accounted for 54.7% of the variation in receipt of neuraxial morphine and 41.2% in the variation in receipt of multimodal analgesia with neuraxial morphine, NSAIDs, and acetaminophen, with this variability in receipt of neuraxial morphine and of multimodal analgesia being largely independent of patient characteristics. Conclusions Relatively few parturients received the currently recommended multimodal analgesic regimen of neuraxial morphine with NSAIDs and acetaminophen after cesarean delivery. Additionally, the majority received acetaminophen-opioid combination drugs rather than plain acetaminophen. Further studies should investigate the implications for patient outcomes.

Introduction Advanced directives (ADs) provide a framework from which families may understand patient’s wishes. However, end-of-life planning may not be prioritized by everyone. This analysis aimed to determine what populations have ADs and how they affected trauma outcomes. Methods Adult trauma patients recorded in the American College of Surgeons Trauma Quality Improvement Program (TQIP) from 2013-2015 were included. The primary outcome was presence of an AD. Secondary outcomes included mortality, length of stay (LOS), mechanical ventilation, ICU admission/LOS, withdrawal of life-sustaining measures, and discharge disposition. Multivariable logistic regression models were developed for outcomes. Results 44 705 patients were included in the analyses. Advanced directives were present in 1.79% of patients. The average age for patients with ADs was 77.8 ± 10.7. African American (odds ratio (OR) .53, confidence intervals [CI] .36-.79) and Asian (OR .22, CI .05-.91) patients were less likely to have ADs. Conversely, Medicaid (OR 1.70, CI 1.06-2.73) and Medicare (OR 1.65, CI 1.25-2.17) patients were more likely to have ADs as compared to those with private insurance. The presence of ADs was associated with increased hospital mortality (OR 2.84, CI 2.19-3.70), increased transition to comfort measures (OR 2.87, CI 2.08-3.95), and shorter LOS (CO −.74, CI −1.26-.22). Patients with ADs had an increased odds of hospice care (OR 4.24, CI 3.18-5.64). Conclusion Advanced directives at admission are uncommon, particularly among African Americans and Asians. The presence of ADs was associated with increased mortality, use of mechanical ventilation, admission to the ICU, withdrawal of life-sustaining measures, and hospice. Future research should target expansion of ADs among minority populations to alleviate disparities in end-of-life treatment.

To investigate gabapentinoid utilization and association with postoperative pulmonary complications after gynecologic surgery.After Institutional Review Board approval, we performed this retrospective cohort study using the Premier Healthcare Database. We used ICD-10 and charge codes to identify adults who underwent elective gynecologic surgery from 2015 to 2018 and received either gabapentin or pregabalin on the day of surgery. Our primary outcome was a composite of pulmonary complications: respiratory failure, pneumonia, reintubation, pulmonary edema, and non-invasive or invasive ventilation. Secondary outcomes included mortality, intensive care unit admission, mechanical or non-invasive ventilation, hospital length of stay, re-admission within 30 days, opioid consumption and antiemetic use. Multivariable generalized linear mixed models were utilized to examine the associations between gabapentinoids and our outcome measures, adjusted for all covariates.Data from 253,013 patients were analyzed, with 19,121 (7.6%) receiving gabapentinoids. Gabapentinoid utilization increased from 3.9% in 2015 to 12.3% in 2018, and was associated with increased pulmonary complications (OR 1.19; 95% CI 1.03-1.38), non-invasive ventilation (odds ratio [OR] 1.53; 95% CI 1.29-1.81), duration of hospital stay (% change 1.75; 95% CI 0.92-2.59), daily antiemetic doses on day of surgery (mean difference [MD] 1.37; 95% CI 1.26-1.49) and subsequently (MD 1.61; 95% CI 1.30-1.99), and higher daily average (MD 4.59 mg; 95% CI 3.55-5.63) and total (MD 8.74 mg; 95% CI 6.83-10.62) parenteral morphine equivalents.Gabapentinoid utilization in gynecologic surgery is increasing and is associated with postoperative pulmonary complications.

Malnutrition remains a critical public health issue in the US, particularly in surgery where perioperative malnutrition is commonly underdiagnosed and undertreated. In 2016, the Global Leadership Initiative on Malnutrition (GLIM) proposed a set of consensus criteria for the diagnosis of malnutrition. Our project aims to assess the post-operative outcomes of patients meeting a modified GLIM-defined (mGLIM) malnutrition criteria undergoing emergent gastrointestinal surgery (EGS) in the NSQIP database. Current GLIM-criteria were modified with addition of admission albumin (a NSQIP-defined malnutrition variable).Adapting NSQIP data, mGLIM criteria are (1) BMI of ≤20 for age ≤ 70 and BMI ≤22 for age ≥ 71, (2) weight loss 10% within the past 6 months, (3) admission albumin ≤ 3.5, and (4) emergent bowel surgery as etiologic criteria of acute disease/injury. All patients undergoing emergent small bowel, colon, and rectal procedures were extracted from the NSQIP database and included in the study. Multivariate linear and logistic regression models controlling for relevant covariates were developed to evaluate mGLIM criteria on length of stay (LOS), mortality, and overall complication rates.We included 31,029 patients who underwent emergent bowel surgeries from years 2011-2016. Demographically, 53.6% (n = 16,622) were female, 13.0% (n = 4023) were African American, and 78.3% (n = 24,292) were Caucasian. Case composition included 71.5% colon operations, 28.0% small bowel, and 0.5% rectal cases. Overall, 1.7% (n = 517) had data necessary to qualify as malnourished as per mGLIM. Controlling for covariates, multivariate linear and logistic regression analyses show that these patients have significantly higher mortality for both colon (p 0.001, CI 1.55 | 2.61) and small bowel (p = 0.022, CI 1.08 | 2.67) procedures, longer LOS for colon (p 0.001, CI 1.93 | 4.33) operations, and higher post-operative complications for both colon (p 0.001, CI 1.61 | 2.62) and small bowel (p 0.001, CI 1.57 | 3.37) cases.This analysis shows that mGLIM criteria malnutrition is associated with poor clinical outcomes following EGS affecting LOS and mortality. Our data indicates the new mGLIM criteria can be a powerful and simple predictive score for malnutrition that can be used to predict malnutrition-related risk of poor outcomes after EGS.

Background The transition to the new ICD-10 (International Classification of Diseases, Tenth Revision) coding system in the U.S. poses challenges to the ability to consistently and accurately measure trends in comorbidities and complications. We examined the prevalence of comorbidities and postoperative medical complications before and after the transition from ICD-9 to ICD-10 among patients who underwent primary total hip or knee arthroplasty (THA or TKA). We hypothesized that the transition to ICD-10 codes was associated with discontinuity and slope change in comorbidities and medical complications. Methods The Elixhauser comorbidities and medical complications were identified using the Premier Healthcare database from fiscal year (FY)2011 to FY2018. Using multivariable segmented regression models, we examined the changes in the levels and slopes after the transition from ICD-9 to ICD-10 coding. Odds ratios (ORs) of 1 indicate decreases and increases, respectively, in levels and slopes. Results Overall, 2,006,581 patients who underwent primary THA or TKA were identified. The mean age was 65.9 ± 10.5 years, and the median length of the hospital stay was 2 days (interquartile range [IQR], 2 to 3 days). Of the comorbidities studied, congestive heart failure, hypertension, and obesity had a statistically significant but clinically small discontinuity after the transition from ICD-9 to ICD-10 coding. Of the complications, pneumonia (OR = 0.66, 95% confidence interval [CI] = 0.48 to 0.90), acute respiratory failure (OR = 1.88, 95% CI = 1.52 to 2.33), sepsis (OR = 2.54, 95% CI = 1.45 to 4.44), and urinary tract infection (OR = 1.79, 95% CI = 1.32 to 2.42) demonstrated statistically significant discontinuity. Alcohol abuse and paralysis had an increasing prevalence before the ICD transition, followed by a decreasing prevalence after the transition. In contrast, metastatic cancer, weight loss, and acquired immunodeficiency syndrome (AIDS) showed a decreasing prevalence before the ICD transition followed by an increasing prevalence after the transition. Generally, complications showed a decreasing prevalence over time. Conclusions The discontinuities after the transition from ICD-9 to ICD-10 coding were relatively small for most comorbidities. Medical complications generally showed a decreasing trend over the quarters studied. These findings support caution when conducting joint replacement studies that rely on ICD coding and include the ICD coding transition period.

BACKGROUND/OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of morbidity, mortality, and disability in the United States. While cardiopulmonary dysfunction can result in poor outcomes following severe TBI, the impact of acute kidney injury (AKI) is poorly understood. We examined the association between severe AKI with hospital mortality and healthcare utilization following isolate severe TBI. METHODS: We conducted a retrospective cohort study using the National Trauma Data Bank (NTDB) from 2007-2014. We identified a cohort of adult patients with isolated severe TBI, and described the incidence of severe AKI, corresponding to Acute Kidney Injury Network stage 3 disease or greater. We examined the association of severe AKI with the primary outcome of hospital mortality using multivariable logistic regression models. In secondary analyses, we examined the association of severe AKI with dialysis catheter placement, tracheostomy and gastrostomy utilization, and hospital length of stay. RESULTS: There were 37,851 patients who experienced isolated severe TBI during the study period. Among these patients, 787 (2.1%) experienced severe (Stage 3 or greater) AKI. In multivariable models, the development of severe AKI in the hospital was associated with in-hospital mortality (OR 2.03, 95% CI 1.64 – 2.52), need for tracheostomy (OR 2.10, 95% CI 1.52 – 2.89), PEG tube placement (OR 1.88, 95% CI 1.45 – 2.45), and increased hospital length of stay (p

Background Older adults suffering from traumatic brain injury (TBI) are subject to higher injury burden and mortality. Do Not Resuscitate (DNR) orders are used to provide care aligned with patient wishes, but they may not be equitably distributed across racial/ethnic groups. We examined racial/ethnic differences in the prevalence of DNR orders at hospital admission in older patients with severe TBI. Methods We conducted a retrospective cohort study using the National Trauma Databank (NTDB) between 2007 to 2016. We examined patients ≥ 65 years with severe TBI. For our primary aim, the exposure was race/ethnicity and outcome was the presence of a documented DNR at hospital admission. We conducted an exploratory analysis of hospital outcomes including hospital mortality, discharge to hospice, and healthcare utilization (intracranial pressure monitor placement, hospital LOS, and duration of mechanical ventilation). Results Compared to White patients, Black patients (OR 0.48, 95% CI 0.35-0.64), Hispanic patients (OR 0.54, 95% CI 0.40-0.70), and Asian patients (OR 0.63, 95% CI 0.44-0.90) had decreased odds of having a DNR order at hospital admission. Patients with DNRs had increased odds of hospital mortality (OR 2.16, 95% CI 1.94-2.42), discharge to hospice (OR 2.08, 95% CI 1.75-2.46), shorter hospital LOS (−2.07 days, 95% CI −3.07 to −1.08) and duration of mechanical ventilation (−1.09 days, 95% CI −1.52 to −0.67). There was no significant difference in the utilization of ICP monitoring (OR 0.94, 95% CI 0.78-1.12). Conclusions We found significant racial and ethnic differences in the utilization of DNR orders among older patients with severe TBI. Additionally. DNR orders at hospital admission were associated with increased in-hospital mortality, increased hospice utilization, and decreased healthcare utilization. Future studies should examine mechanisms underlying race-based differences in DNR utilization.

Current guidance recommends initiation of early enteral nutrition (early EN) within 24-36 hours of ICU admission in critically ill COVID-19 patients. Despite this recommendation, there is quite limited evidence describing the effect of early EN on outcomes in COVID-19 patients. The association between early EN (within 3 d post intubation) and clinical outcomes in adult COVID-19 patients requiring mechanical ventilation (within 2 d post ICU admission) was evaluated.We performed a nationwide observational cohort study using a nationwide administrative-financial database (Premier) in United States.Information pertaining to all COVID-19 patients admitted to ICU from 75 hospitals between April and December 2020 was analyzed.A total of 861 COVID-19 patients were included.None.Clinical outcomes were assessed via regression models to control for patient and hospital characteristics. We identified 513 COVID-19 ICU patients (59.2%) requiring mechanical ventilation who received early EN and had similar baseline characteristics to late EN group. Compared with late EN group, the early EN group had shorter ICU (hazard ratio [HR], 1.39; 95% CI, 1.15-1.68) and hospital length of stays (LOS) (HR, 1.53; 95% CI, 1.23-1.91), fewer mechanical ventilation days (HR, 1.25; 95% CI, 1.01-1.54), and lower cost (-$22,443; 95% CI, -$32,342 to -$12,534). All comparisons were statistically significant (In patients with COVID-19 requiring mechanical ventilation, early EN is associated with earlier liberation from mechanical ventilation, shorter ICU and hospital LOS, and decreased cost. Our results are among the first to support guideline recommendations for initiation of early EN in COVID-19 ICU patients. Further, our data show nearly 40% of critically ill COVID-19 patients fail to have early EN initiated, even at 3 d post initiation of mechanical ventilation. These results emphasize the need for targeted strategies promoting initiation of early EN, as this may lead to improved clinical and economic outcomes in severe COVID-19 patients.

Background Traumatic brain injury (TBI) is a major global health problem. Little research has addressed extracranial organ dysfunction following TBI, particularly myocardial injury. Using a sensitive marker of myocardial injury-high sensitivity troponin (hsTn)-we examined the incidence of early myocardial injury following TBI and explored its association with neurological outcomes following moderate-severe TBI. Methods We conducted a pilot cohort study of 133 adult (age above 17 y) subjects enrolled in the TRACK-TBI 18-center prospective cohort study. Descriptive statistics were used to examine the incidence of myocardial injury (defined as hsTn >99th percentile for a standardized reference population) across TBI severities, and to explore the association of myocardial injury with a 6-month extended Glasgow Outcome Score among patients with moderate-severe TBI. Results The mean (SD) age of the participants was 44 (17) years, and 87 (65%) were male. Twenty-six patients (20%) developed myocardial injury following TBI; myocardial injury was present in 15% of mild TBI patients and 29% of moderate-severe TBI patients (P=0.13). Median (interquartile range) hsTn values were 3.8 ng/L (2.1, 9.0), 5.8 ng/L (4.5, 34.6), and 10.2 ng/L (3.0, 34.0) in mild, moderate, and severe TBI participants, respectively (P=0.04). Overall, 11% of participants with moderate-severe TBI and myocardial injury experienced a good outcome (6-mo extended Glasgow Outcome Score≥5) at 6 months, compared with 65% in the group that did not experience myocardial injury (P=0.01). Conclusions Myocardial injury is common following TBI, with a likely dose-response relationship with TBI severity. Early myocardial injury was associated with poor 6-month clinical outcomes following moderate-severe TBI.

Herein, a case describing how point-of-care lung ultrasound was used to identify the source of progressive multiorgan failure when a chest x-ray and other routine tests failed to provide a conclusive answer is presented. The discussion after the case focuses on the following: (1) the relative strengths and weaknesses of chest x-ray versus lung ultrasound in screening for lung disease and (2) suggestions of how lung ultrasound practice can be standardized within the field of anesthesiology.

Objective: To examine racial and ethnic differences in the utilization of 3 interventions (tracheostomy placement, gastrostomy tube placement, and hospice utilization) among patients with severe acute brain injury (SABI). Design: Retrospective cohort study. Setting: Data from the National Inpatient Sample, from 2002 to 2012. Patients: Adult patients with SABI defined as a primary diagnosis of stroke, traumatic brain injury, or post-cardiac arrest who received greater than 96 hours of mechanical ventilation. Exposure: Race/ethnicity, stratified into 5 categories (white, black, Hispanic, Asian, and other). Measurements and Main Results: Data from 86 246 patients were included in the cohort, with a mean (standard deviation) age of 60 (18) years. In multivariable analysis, compared to white patients, black patients had an 20% increased risk of tracheostomy utilization (relative risk [RR]: 1.20, 95% CI: 1.16-1.24, P < .001), Hispanic patients had a 10% increased risk (RR: 1.10, 95% CI: 1.06-1.14, P < .001), Asian patients had an 8% increased risk (RR: 1.08, 95% CI: 1.01-1.16, P = .02), and other race patients had an 10% increased risk (RR: 1.10, 95% CI: 1.04-1.16, P < .001). A similar relationship was observed for gastrostomy utilization. In multivariable analysis, compared to white patients, black patients had a 25% decreased risk of hospice discharge (RR: 0.75, 95% CI: 0.67-0.85, P < .001), Hispanic patients had a 20% decreased risk (RR: 0.80, 95% CI: 0.69-0.94, P < .01), and Asian patients had a 47% decreased risk (RR: 0.53, 95% CI: 0.39-0.73, P < .001). There was no observed relationship between race/ethnicity and in-hospital mortality. Conclusions: Minority race was associated with increased utilization of tracheostomy and gastrostomy, as well as decreased hospice utilization among patients with SABI. Further research is needed to better understand the mechanisms underlying these race-based differences in critical care.

Summary Although RCTs represent the gold standard in clinical research, most clinical questions cannot be answered using this technique, because of ethical considerations, time, and cost. The goal of observational research in clinical medicine is to gain insight into the relationship between a clinical exposure and patient outcome, in the absence of evidence from RCTs. Observational research offers additional benefit when compared with data from RCTs: the conclusions are often more generalisable to a heterogenous population, which may be of greater value to everyday clinical practice. In Part 2 of this methods series, we will introduce the reader to several advanced methods for supporting the case for causality between an exposure and outcome, including: mediation analysis, natural experiments, and joint effects methods.

Introduction: Hypothermic machine perfusion (HMP) has been established as an efficacious method for preserving kidney allografts from deceased donors in clinical trials, but little data are available on the effectiveness of HMP in real-world settings. We examined factors associated with HMP use and clinical outcomes in a real-world organ procurement organization setting. Methods: We conducted a retrospective cohort study of the Lifecenter Northwest organ procurement database from 2010 to 2015, linked to the United Network of Organ Sharing outcomes database. We examined HMP utilization, and our primary outcomes were delayed graft function (DGF) and graft survival, using multivariable Poisson and Cox regression models. Results: Among 1729 deceased-donor kidneys, 797 (46%) were preserved with HMP. Higher donor age, region of procurement, and donation type were associated with HMP use. HMP was associated with a 37% decreased risk of DGF (adjusted relative risk 0.63, 95% confidence interval [CI]: 0.51–0.78), with no effect on 1-year graft survival (adjusted hazard ratio 0.83, 95% CI: 0.38–1.80). Conclusion: Variation exists in the utilization of HMP for deceased donor kidneys. HMP reduced the risk for DGF, but was not associated with improvements in long-term graft survival.

BACKGROUND Severe traumatic brain injury (TBI) can result in left ventricular dysfunction, which can lead to hypotension and secondary brain injuries. Although echocardiography is often used to examine cardiovascular function in multiple clinical settings, its use and association with outcomes following severe TBI are not known. To address this gap, we used the National Trauma Data Bank (NTDB) to describe utilization patterns of echocardiography and examine its association with mortality following severe TBI. METHODS A retrospective cohort study was conducted using a large administrative trauma registry maintained by the NTDB from 2007 to 2014. Patients >18 years with isolated severe TBI, and without concurrent severe polytrauma, were included in the study. We examined echocardiogram utilization patterns (including overall utilization, factors associated with utilization, and variation in utilization) and the association of echocardiography utilization with hospital mortality, using multivariable logistic regression models. RESULTS Among 47,808 patients, echocardiogram was utilized as part of clinical care in 2548 patients (5.3%). Clinical factors including vascular comorbidities and hemodynamic instability were associated with increased use of echocardiograms. Nearly half (46.0%, 95% confidence interval [CI], 40.3%-51.7%) of the variation in echocardiogram utilization was explained at the individual hospital level, above and beyond patient and injury factors. Exposure to an echocardiogram was associated with decreased odds of in-hospital mortality following severe TBI (adjusted odds ratio [OR] = 0.77; 95% CI, 0.69-0.87; P < .001). CONCLUSIONS Echocardiogram utilization following severe TBI is relatively low, with wide variation in use at the hospital level. The association with decreased in-hospital mortality suggests that the information derived from echocardiography may be relevant to improving patient outcomes but will require confirmation in further prospective studies.

Background Optimal administration of fluids is an important part of enhanced recovery after surgery (ERAS) protocols. We sought to examine the relationship between perioperative crystalloid volume and adverse outcomes in five common types of surgical procedures with ERAS fluid guidelines in place where large randomized controlled trials have not been conducted: breast reconstruction, bariatric, major urologic, gynoncologic, and head and neck oncologic procedures. Methods This retrospective cohort study included patients who had undergone any one of the aforementioned procedures within any facility in a large multihospital alliance (Premier, Inc, Charlotte, NC) between 2008 and 2014. We used multivariable generalized additive models to examine relationships between the total crystalloid volume (TCV) on the day of surgery and a composite adverse outcome of prolonged (>75th percentile) hospital or intensive care unit stay or in-hospital mortality. Models were constructed separately within each surgical category and adjusted for demographic, clinical, and hospital characteristics. Informed consent requirements were waived because deidentified data were used. Results We identified 83,685 patients within 312 US hospitals undergoing breast reconstruction (n = 8738), bariatric surgery (n = 8067), major urologic surgery (n = 28,654), gynoncologic surgery (n = 34,559), and head/neck oncology surgery (n = 3667). There was significant patient-independent variation in TCV. Probabilities of adverse outcomes increased at a TCV below 3 L and above 6 L for all types of surgeries except bariatric surgery, where larger volumes were associated with progressively better outcomes. Conclusions and Relevance Relationships between TCV and adverse outcomes were generally J shaped with higher volumes (>6 L) associated with increased risk. As per current ERAS guidelines, it is important to avoid excessive crystalloid volume in most surgical procedures except for bariatric surgery.

BACKGROUND Postoperative nutrition delivery is essential to surgical recovery; unfortunately, postoperative dietary intake is often poor. Recent surgical guidelines recommend use of oral nutritional supplements (ONS) to improve nutrition delivery. Our aim was to examine prevalence of coded ONS use over time and coded malnutrition rates in postoperative patients. METHODS The Premier Healthcare Database (PHD) was queried for postoperative patients found to have charges for ONS between 2008-2014. ONS use identified via charge codes. Descriptive statistics utilized to examine prevalence of malnutrition and ONS utilization. Multilevel, multivariable logistic regression models were fit to examine factors associated with ONS use. RESULTS A total of 2,823,532 surgical encounters were identified in PHD in 172 hospitals utilizing ONS charge codes. ONS-receiving patients were 72% Caucasian, 65% Medicare patients with mean age of 66 ± 16.5 years. Compared with patients not receiving ONS, ONS patients had higher van Walraven severity scores (7.3 ± 7.8 vs 2.3 ± 5.6, P < .001) with greater comorbidities. Overall coded malnutrition prevalence was 4.3%. Coded malnutrition diagnosis increased from 4.4% to 5.2% during study period. Only 15% of malnourished patients received ONS. Individual hospital practice explained much of variation in early postoperative ONS use. CONCLUSION In this large surgical population, inpatient ONS use is most common in older, Caucasian, Medicare patients with high comorbidity burden. Despite increased malnutrition during study period, observed ONS prescription rate did not increase. Our data indicate current ONS utilization in surgical patients, even coded with malnutrition, is limited and is a critical perioperative quality improvement opportunity.

Drug overdoses are a national and global epidemic. However, while overdoses are inextricably linked to social, demographic, and geographical determinants, geospatial patterns of drug-related admissions and overdoses at the neighborhood level remain poorly studied. The objective of this paper is to investigate spatial distributions of patients admitted for drug-related admissions and overdoses from a large, urban, tertiary care center using electronic health record data. Additionally, these spatial distributions were adjusted for a validated socioeconomic index called the Area Deprivation Index (ADI). We showed spatial heterogeneity in patients admitted for opioid, amphetamine, and psychostimulant-related diagnoses and overdoses. While ADI was associated with drug-related admissions, it did not correct for spatial variations and could not account alone for this spatial heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11524-020-00436-8) contains supplementary material, which is available to authorized users.

ObjectiveMultimodal analgesia has gained popularity in total hip arthroplasty (THA) and total knee arthroplasty (TKA), but large multicenter studies evaluating specific analgesic combinations are lacking.DesignA retrospective study using the Premier Healthcare Database (2009–2014).SubjectsAdults who underwent elective primary THA or TKA.MethodsWe categorized day-of-surgery analgesic exposure using eight mutually exclusive categories: acetaminophen (Ac), nonsteroidal anti-inflammatory drugs (Ns), gabapentinoids (Ga; gabapentin or pregabalin), Ac+Ns, Ac+Ga, Ns+Ga, Ac+Ns+Ga, and none of the three drugs. Multilevel models measured associations of the analgesic categories with a composite of postoperative pulmonary complications (PPCs).ResultsAmong 863,139 patients, 75.2% received at least one of the three drugs. In multilevel models, compared with none of the three drugs, Ga use was associated with increased odds of PPCs when used alone (adjusted odds ratio [aOR] = 1.35, 95% confidence interval [CI] = 1.27 to 1.44), combined with Ac (aOR = 1.16, 95% CI = 1.08 to 1.26), or combined with Ns (aOR = 1.28, 95% CI = 1.21 to 1.34). In contrast, the Ac+Ns pair was associated with decreased odds of PPCs (OR = 0.86, 95% CI = 0.83 to 0.90) and lower opioid consumption. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery.ConclusionsGabapentinoids, alone and in single combination with either acetaminophen or nonsteroidal anti-inflammatory drugs, were associated with higher PPCs, whereas the Ac+Ns pair was associated with fewer PPCs and an opioid-sparing effect. Ac+Ns+Ga was not associated with PPCs, whereas it was associated with the lowest opioid consumption on the day of surgery.

Disparities in gun violence across race are well documented. Studying these disparities is essential to reduce preventable gun deaths. This study evaluates the relationship between sociodemographic factors and firearms used in gun deaths.This retrospective cohort study of firearm mortalities from 2009 to 2018 used the Mortality Multiple Cause-of-Death Public Use Record from the National Center for Health Statistics. The primary outcome was the type of firearm used and the secondary outcome was autopsy status. Factors of interest include race, ethnicity, gender, marital status, age, education, and place of death. Factors significantly associated with outcomes in univariate analyses were included in separate multivariate logistic regression models for assaults, intentional self-harm, and accidents.A total of 276,127 firearm deaths from 2009 to 2018 were analyzed. Compared to White victims, Black victims were less likely to die from handguns (accident: odds ratio [OR] = 0.70, P 0.05; self-harm: OR = 0.84, P 0.001; assault: OR = 0.58, P 0.001) and rifles, shotguns, or large firearms (accident: OR = 0.30, P 0.001; self-harm: OR = 0.37, P 0.001; assault: OR = 0.28, P 0.001). Black decedents were more likely to undergo autopsy than White decedents (accident: OR = 2.14, P 0.001; intentional self-harm: OR = 2.02, P 0.001; assault: OR = 2.02, P 0.001). Ethnicity, gender, marital status, age, education, and other racial identities were also associated with firearms used and autopsy rates (P 0.05).Differences in firearms used and autopsy rates following gun deaths exist by race, ethnicity, gender, marital status, age, and education. Future studies should investigate the relationship between sociodemographic factors and firearms used and autopsy status following gun deaths.

Extracranial multisystem organ failure is a common sequela of severe traumatic brain injury (TBI). Risk factors for developing circulatory shock and long-term functional outcomes of this patient subset are poorly understood.To identify emergency department predictors of circulatory shock after moderate-severe TBI and examine long-term functional outcomes in patients with moderate-severe TBI who developed circulatory shock.We conducted a retrospective cohort study using the Transforming Clinical Research and Knowledge in TBI database for adult patients with moderate-severe TBI, defined as a Glasgow Coma Scale (GCS) score of13 and stratified by the development of circulatory shock within 72 hours of hospital admission (Sequential Organ Failure Assessment score ≥2). Demographic and clinical data were assessed with descriptive statistics. A forward selection regression model examined risk factors for the development of circulatory shock. Functional outcomes were examined using multivariable regression models.Of our moderate-severe TBI population (n = 407), 168 (41.2%) developed circulatory shock. Our predictive model suggested that race, computed tomography Rotterdam scores3, GCS in the emergency department, and development of hypotension in the emergency department were associated with developing circulatory shock. Those who developed shock had less favorable 6-month functional outcomes measured by the 6-month GCS-Extended (odds ratio 0.36, P = .002) and 6-month Disability Rating Scale score (Diff. in means 3.86, P = .002) and a longer length of hospital stay (Diff. in means 11.0 days, P.001).We report potential risk factors for circulatory shock after moderate-severe TBI. Our study suggests that developing circulatory shock after moderate-severe TBI is associated with poor long-term functional outcomes.

ImportanceBloodstream infections (BSIs) are a major public health problem associated with high morbidity. Little evidence exists regarding the epidemiology of BSIs and the use of appropriate empirical antimicrobial therapy.ObjectiveTo estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality.Design, Setting, and ParticipantsThis retrospective cross-sectional study used data from the Premier Healthcare database from 2016 to 2020. The analysis included 32 100 adult patients (aged ≥18 years) with BSIs from 183 US hospitals who received at least 1 new systemic antimicrobial agent within 2 days after blood samples were collected during the hospitalization. Patients with polymicrobial infections were excluded from the analysis.ExposuresAppropriate empirical therapy was defined as initiation of at least 1 new empirical antimicrobial agent to which the pathogen isolated from blood culture was susceptible either on the day of or the day after the blood sample was collected.Main Outcomes and MeasuresMultilevel logistic regression models were used to estimate the association between receipt of appropriate initial empirical antimicrobial therapy and in-hospital mortality for patients infected with gram-negative rods (GNRs), gram-positive cocci (GPC), and Candida species.ResultsAmong 32 100 patients who had BSIs and received new empirical antimicrobial agents, the mean (SD) age was 64 (16) years; 54.8% were male, 69.9% were non-Hispanic White, and in-hospital mortality was 14.3%. The most common pathogens were Escherichia coli (58.4%) and Staphylococcus aureus (31.8%). Among patients infected with S aureus, methicillin-resistant S aureus was isolated in 43.6%. The crude proportions of appropriate empirical therapy use were 94.4% for GNR, 97.0% for GPC, and 65.1% for Candida species. The proportions of appropriate therapy use for resistant organisms were 55.3% for carbapenem-resistant Enterobacterales species and 60.4% for vancomycin-resistant Enterococcus species. Compared with inappropriate empirical therapy, receipt of appropriate empirical antimicrobial therapy was associated with lower in-hospital risk of death for 3 pathogen groups (GNR: adjusted odds ratio [aOR], 0.52 [95% CI, 0.42-0.64]; GPC: aOR, 0.60 [95% CI, 0.47-0.78]; Candida species: aOR, 0.43 [95% CI, 0.21-0.87]).Conclusions and RelevanceIn this cross-sectional study of patients hospitalized with BSIs, receipt of appropriate initial empirical antimicrobial therapy was associated with lower in-hospital mortality. It is important for clinicians to carefully choose empirical antimicrobial agents to improve outcomes in patients with BSIs.

IntroductionAmong 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 analysisTheDirEct versusVIdeo LaryngosCopE(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 Ethics and disseminationThe 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 numberClinicalTrials.gov Registry (NCT05239195).

Background Gabapentinoids are commonly prescribed in perioperative multimodal analgesia protocols. Despite widespread use, the optimal dose to reduce opioid consumption while minimizing risks is unknown. We assessed dose-dependent effects of gabapentinoids on opioid consumption and postoperative pulmonary complications following total hip or knee arthroplasty (THA or TKA). We hypothesized that use of a gabapentinoid on the day of THA or TKA is associated with an increased risk of postoperative pulmonary complications in a dose-response fashion compared with the risk for patients who did not receive the drug. Methods Using the Premier Database, we identified adults who underwent elective primary THA or TKA from 2009 to 2014. The exposure was receipt of a gabapentinoid (gabapentin or pregabalin) on the day of surgery. Gabapentin dose was categorized into 5 groups: none, 1 to 350, 351 to 700, 701 to 1,050, and >1,050 mg per day. Pregabalin dose was categorized into 4 groups: none, 1 to 110, 111 to 250, and >250 mg per day. The primary outcome was a composite of postoperative pulmonary complications, defined as respiratory failure, pneumonia, reintubation, pulmonary edema, noninvasive ventilation, or invasive mechanical ventilation. Results Of 858,306 patients who underwent THA or TKA, 11.0% received gabapentin and 10.2% received pregabalin. The mean age (and standard deviation) of the patients was 65.6 ± 10.7 years, 39.6% were male, 78.2% were Caucasian, and 55.2% were covered by Medicare. In multilevel regression analysis, receipt of gabapentinoid at any dose on the day of surgery was associated with increased odds of postoperative pulmonary complications. Compared with no exposure to the drug being used by the particular group, all dose ranges of gabapentin and pregabalin were associated with greater odds of postoperative pulmonary complications (odds ratio, 95% confidence interval = 1.51, 1.40 to 1.63, for >1,050 mg of gabapentin and 1.81, 1.57 to 2.09, for >250 mg of pregabalin). We found no clinically meaningful associations between exposure to either gabapentin or pregabalin and perioperative opioid consumption or the length of the hospital stay. Conclusions Exposure to gabapentinoids at any dose on the day of THA or TKA was associated with increased odds of postoperative pulmonary complications in a dose-response fashion, with minimal effects on perioperative opioid consumption. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Both postoperative acute kidney injury (AKI) and preoperative chronic kidney disease (CKD) are associated with significantly worse outcomes following surgery. The relationship of both of these conditions with each other and with CKD progression after surgery remains poorly studied. Our objective was to assess if there was an interaction between preoperative kidney function estimated by preoperative estimated glomerular filtration rate (eGFR)/CKD stage, postoperative AKI, and eGFR/CKD progression within 1 year of surgery. Our hypothesis was that AKI severity would be associated with a faster time to eGFR/CKD stage progression within 1 year of surgery in a graded-fashion, which would be exacerbated by preoperative kidney dysfunction.This was a retrospective cohort study at Landspitali University Hospital in Iceland, which serves about 75% of the population. Participants included adults receiving their first major anesthetic between 2005 and 2018. Patients with CKD stage 5, undergoing major urologic procedures, or having missing creatinine values for follow-up of eGFR stage were excluded from analysis. The primary exposure was postoperative AKI stage within 7 days after surgery classified by the kidney disease improving global outcome (KDIGO) criteria. The primary outcome was time to progression of CKD by at least 1 eGFR/CKD stage within 1-year following surgery. Multivariable Cox proportional hazards models were used to estimate hazard of eGFR/CKD stage progression, including an interaction between AKI and preoperative CKD on eGFR/CKD stage progression.A total of 5548 patients were studied. In the multivariable model adjusting for baseline eGFR/CKD stage, when compared to patients without AKI, postoperative AKI stage 1 (hazard ratio [HR], 5.91; 95% confidence interval [CI], 4.34-8.05), stage 2 (HR, 3.86; 95% CI, 1.82-8.16), and stage 3 (HR, 3.61; 95% CI, 1.49-8.74) were all independently associated with faster time to eGFR/CKD stage progression within 1 year following surgery, though increasing AKI severity did not confer additional risk. The only significant interaction between the degree of AKI and the preexisting renal function was for stage 1 AKI, where the odds of 1-year eGFR/CKD stage progression actually decreased in patients with preoperative CKD categories 3a, 3b, and 4.KDIGO-AKI was independently associated with eGFR/CKD stage progression within the year following surgery after adjustment for baseline eGFR/CKD stage and without an interaction between worse preoperative kidney function and higher stage AKI. Our observations suggest that further studies are warranted to test whether CKD progression could be prevented by the adoption of perioperative kidney protective practices.

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

As of yet, few studies have described the prevalence or rates of assault mortalities involving Asian victims on a national level. This study aimed to describe yearly trends and regional differences in assault mortalities among Asians.This repeat cross-sectional study from 2009 to 2018 used data from the Mortality Multiple Cause-of-Death Public Use Record from the National Center for Health Statistics and the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. Total and proportion of assault mortalities involving Asians or Pacific Islanders were calculated by year. Total and rates (per 100,000 Asians or Pacific Islanders) of assault mortalities among Asians or Pacific Islanders were stratified by state and county classification where deaths occurred.In 2009, 344 assault mortalities among Asians or Pacific Islanders accounted for 2.07% of assault-related deaths. In 2018, 366 assault mortalities among Asians or Pacific Islanders accounted for 1.96% of assault-related deaths. Furthermore, there were more assault mortalities from 2009 to 2018 among Asians or Pacific Islanders in California (n = 1116) and large central metropolitan counties (n = 1707). However, the highest rates of assault mortalities were in Alaska and Mississippi (7.1 and 6.8 per 100,000, respectively) and noncore nonmetropolitan counties (2.9 per 100,000).These findings emphasize the importance of studying and addressing violence toward Asians in rural regions and Southern states. Future studies should use these results as a baseline to analyze mortality data from 2019 to 2021, when available, to examine the coronavirus disease 2019 pandemic's impact on assault mortalities among Asian.