Interactive Media-Based Approach for an Exception From Informed Consent Trial Involving Patients With Trauma.

Importance: Exception From Informed Consent (EFIC) research requires community consultation (CC) and public disclosure (PD). Traditional methods of conducting CC and PD are slow, expensive, and labor intensive. Objective: To describe the feasibility and reach of a novel interactive, media-based approach to CC and PD and to identify the similarities and differences between trial sites in website views, survey responses, online community forum attendance, and opt-out requests. Design, Setting, and Participants: This survey study analyzed the CC and PD campaigns conducted for the TAP trial (Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival), an EFIC trial of the early administration of prothrombin complex concentrate in patients with trauma. The CC and PD campaigns consisted of social media advertisements, linked websites, community surveys, and online community forums. These activities were coordinated from a central site and approved by a central institutional review board. This study focused on the first 52 of 91 TAP trial sites (level I trauma centers) in the US to have completed their CC and PD campaigns. Community members in the catchment areas of the participating trauma centers were targeted. Data analysis was conducted between October 2023 and February 2024. Exposure: Social media advertisements, surveys, and online community meetings conducted as part of the CC and PD campaign for the TAP trial. Main Outcomes and Measures: Social media campaign reach and engagement, web page views, survey results, online community forum attendance, and opt-out requests. Results: Fifty-two trial sites were approved for participant enrollment. Social media advertisements were displayed 92 million times, reaching 11.8 million individuals. The median (IQR) number of people reached in each location was 210 317 (172 068-276 968). Site-specific websites were viewed 144 197 times (median [IQR] viewings per site, 2984 [1267-4038]). A total of 17 206 fully or partly completed surveys were received, and survey respondents had a median (IQR) age of 40.1 (15-65) years and included 10 444 females (60.7%). Overall, 60.6% survey respondents said they would want to be entered into the trial even if they could not give consent, 87.7% agreed that emergency care research was necessary, and 88.0% agreed that the TAP trial should be conducted in their community. Online community forums were attended by a median (IQR) number of 38 (20-63) people. Four opt-out requests were received. Conclusions and Relevance: The interactive media-based approach to CC and PD for the ongoing TAP trial showed the feasibility and benefits of executing an efficient, coordinated, centrally run series of locally branded and geographically targeted CC and PD campaigns for a large EFIC study.

Diagnostic performance of the ABC score in the PROPPR trial.

INTRODUCTION: The Assessment of Blood Consumption (ABC) score is used to predict massive transfusions (MT). However, its diagnostic performance has not been widely examined, especially when used as an objective tool to enroll patients in multi-center clinical trials. The purpose of this study was to evaluate the performance of the ABC score in enrolling patients in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial. We hypothesized the ABC score would have a similar diagnostic performance to predict the need for massive transfusion as previous studies. METHODS: This is a retrospective analysis of the PROPPR trial. Patients were enrolled either on the basis of an ABC score ≥2, or by Physician Gestalt, when the ABC score was <2. We calculated the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios of the ABC score (≥2) for predicting MT (>10 units of red blood cells/24 h or transfusion of >3 units of red blood cells within the first hour). RESULTS: Of the 680 patients, 438 patients (64 %) had an ABC score of ≥2 and 242 (36 %) had an ABC score of <2. An ABC score of ≥2 had 66.8 % sensitivity and 37.0 % specificity for predicting the need for MT, with a PPV of 88.2 % and NPV of 13.1 %. Similarly, an ABC≥2 had 65.6 % sensitivity and 44.6 % specificity for predicting the need for >3 units RBCs in 1 hour, with a PPV of 89.5 % and NPV of 15.3 %. CONCLUSION: The ABC score had lower performance than previously reported for predicting MT, when applied to PROPPR trial patients. The performance for predicting the need for a 3-unit red blood cell transfusion (or more) in the first hour was slightly higher. LEVEL OF EVIDENCE: Level III, Prognostic.

Feasibility of using an automated call service to collect quality of life and functional outcome data in trauma patients.

Objectives: Following up trauma patients after discharge, to evaluate their subsequent quality of life and functional outcomes, is notoriously difficult, time consuming, and expensive. Automated systems are a conceptually attractive solution. We prospectively assessed the feasibility of using a series of automated phone calls administered by Emmi Patient Engagement to survey trauma patients after discharge. Methods: Recruitment into the study was incorporated into the patient discharge process by nursing staff. For this pilot, we included trauma patients discharging home and who were able to answer phone calls. A script was created to evaluate the Extended Glasgow Outcome Scale and the EuroQol EQ-5D to assess functional status and quality of life, respectively. Call attempts were made at 6 weeks, 3 months, 6 months, and 1 year after discharge. Results: A total of 110 patients initially agreed to participate. 368 attempted patient encounters (calls or attempted calls) took place, with 104 (28.3%) patients answering a least one question in the study. 21 unique patients (19.1% of those enrolled) completed 27 surveys. Conclusions: Automated, scripted phone calls to survey patients after discharge are not a feasible way of collecting functional and quality of life data. Level of evidence: Level II/prospective.

Outcomes of patients enrolled in a prospective and randomized trial on basis of gestalt assessment or ABC score.

BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial rapidly enrolled patients based on an Assessment of Blood Consumption (ABC) ≥ 2 score, or physician gestalt (PG) when ABC score was <2. The objective of this study was to describe what patients were enrolled by the two methods and whether patient outcomes differed based on these enrollments. We hypothesized that there would be no differences in outcomes based on whether patients were enrolled via ABC score or PG. METHODS: Patients were enrolled with an ABC ≥ 2 or by PG when ABC was <2 by the attending trauma surgeon. We compared 1-hour, 3-hour, 6-hour, 12-hour, 18-hour, and 24-hour mortality, 30-day mortality, time to hemostasis, emergent surgical or interventional radiology procedure and the proportion of patients who required either >10 units of blood in 24 hours or >3 units in 1 hour. RESULTS: Of 680 patients, 438 (64%) were enrolled on the basis of an ABC score ≥2 and 242 (36% by PG when the ABC score was <2). Patients enrolled by PG were older (median, 44; interquartile range [IQR], 28-59; p < 0.001), more likely to be White (70.3% vs. 60.3%, p = 0.014), and more likely to have been injured by blunt mechanisms (77.3% vs. 37.2%, p < 0.001). They were also less hypotensive and less tachycardic than patients enrolled by ABC score (both p < 0.001). The groups had similar Injury Severity Scores in the ABC ≥ 2 and PG groups (26 and 27, respectively) and were equally represented (49.1% and 50.8%, respectively) in the 1:1:1 treatment arm. There were no significant differences between the ABC score and PG groups for mortality at any point. Time to hemostasis (108 for patients enrolled on basis of Gestalt, vs. 100 minutes for patients enrolled on basis of ABC score), and the proportion of patients requiring a massive transfusion (>10 units/24 hours) (44.2% vs. 47.3%), or meeting the critical administration threshold (>3 unit/1 hour) (84.7% vs. 89.5%) were similar ( p = 0.071). CONCLUSION: Early identification of trauma patients likely to require a massive transfusion is important for clinical care, resource use, and selection of patients for clinical trials. Patients enrolled in the PROPPR trial based on PG when the ABC score was <2 represented 36% of the patients and had identical outcomes to those enrolled on the basis of an ABC score of ≥2. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Incidence, Risk Factors, and Outcomes Associated With Recurrent Neonatal Acute Kidney Injury in the AWAKEN Study.

Importance: The incidence and associated outcomes of recurrent acute kidney injury (rAKI) in neonates remain largely unknown. Objective: To determine the incidence, risk factors, and clinical outcomes associated with rAKI in critically ill neonates. Design, Setting, and Participants: This cohort study was a secondary analysis of the multicenter, international Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates retrospective study. Comparisons were made among neonates with no AKI, a single AKI episode (sAKI), and rAKI. All neonates younger than 14 days who were admitted between January 1 and March 31, 2014, to 24 participating level II to IV neonatal intensive care units and received intravenous fluids for at least 48 hours were considered for inclusion. Neonates with congenital heart disease requiring surgery within the first week of life, lethal chromosomal anomalies, death within 48 hours of admission, or severe congenital kidney abnormalities were excluded. Data were analyzed from May 23, 2022, to December 8, 2023. Exposure: Recurrent AKI using the neonatal Kidney Disease: Improving Global Outcomes criteria. Determination of each rAKI required a complete return to the baseline serum creatinine level that defined the prior AKI episode. Main Outcomes and Measures: Incidence and risk factors of rAKI and associations of rAKI with length of stay (LOS; ie, birth to hospital discharge) and mortality. Results: The study cohort (n = 2162) included 1233 male neonates (57.0%). Gestational age distribution was less than 29 weeks for 276 neonates (12.8%), 29 to less than 36 weeks for 958 (44.3%), and 36 weeks or older for 928 (42.9%). Of 605 neonates with AKI, 133 (22.0%) developed rAKI with risk factors including younger gestational age, lower birthweight, and higher stage of initial AKI. Infants with rAKI experienced longer median LOS (no AKI, 17 [IQR, 8-34] days; sAKI, 18 [IQR, 9-45] days; rAKI, 60 [IQR, 25-109] days; P < .001). Time-varying Cox proportional hazards regression models suggest rAKI is independently associated with a lower hazard of discharge (adjusted hazard ratio, 0.7 [95% CI, 0.6-0.9]; P = .01) when compared with sAKI, but mortality did not differ between groups (adjusted hazard ratio, 1.4 [95% CI, 0.6-3.0]; P = .44). Conclusions and Relevance: In this cohort study, neonatal rAKI was independently associated with longer LOS when compared with sAKI, suggesting that rAKI in neonates may be an important clinical distinction warranting further study and careful monitoring after an initial AKI episode.

Socio-demographic and comorbid risk factors for poor prognosis in patients hospitalized with community-acquired bacterial pneumonia in southeastern US.

BACKGROUND: How socio-demographic characteristics and comorbidities affect bacterial community-acquired pneumonia (CAP) prognosis during/after hospitalization is important in disease management. OBJECTIVES: To identify predictors of medical intensive care unit (MICU) admission, length of hospital stay (LOS), in-hospital mortality, and bacterial CAP readmission in patients hospitalized with bacterial CAP. METHODS: ICD-9/10 codes were used to query electronic medical records to identify a cohort of patients hospitalized for bacterial CAP at a tertiary hospital in Southeastern US between 01/01/2013-12/31/2019. Adjusted accelerated failure time and modified Poisson regression models were used to examine predictors of MICU admission, LOS, in-hospital mortality, and 1-year readmission. RESULTS: There were 1956 adults hospitalized with bacterial CAP. Median (interquartile range) LOS was 11 days (6-23), and there were 26 % (513) MICU admission, 14 % (266) in-hospital mortality, and 6 % (117) 1-year readmission with recurrent CAP. MICU admission was associated with heart failure (RR 1.38; 95 % CI 1.17-1.62) and obesity (RR 1.26; 95 % CI 1.04-1.52). Longer LOS was associated with heart failure (adjusted time ratio[TR] 1.27;95 %CI 1.12-1.43), stroke (TR 1.90;95 %CI 1.54,2.35), type 2 diabetes (TR 1.20;95 %CI 1.07-1.36), obesity (TR 1.50;95 %CI 1.31-1.72), Black race (TR 1.17;95 %CI 1.04-1.31), and males (TR 1.24;95 %CI 1.10-1.39). In-hospital mortality was associated with stroke (RR 1.45;95 %CI 1.03-2.04) and age ≥65 years (RR 1.34;95 %CI 1.06-1.68). 1-year readmission was associated with COPD (RR 1.55;95 %CI 1.05-2.27) and underweight BMI (RR 1.74;95 %CI 1.04-2.90). CONCLUSIONS: Comorbidities and socio-demographic characteristics have varying impacts on bacterial CAP in-hospital prognosis and readmission. More studies are warranted to confirm these findings to develop comprehensive care plans and inform public health interventions.

Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates: A Secondary Analysis of the PENUT Randomized Clinical Trial.

Importance: Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI. Objective: To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes. Design, Setting, and Participants: This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022. Exposure: Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]). Main Outcomes and Measures: The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models. Results: A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64). Conclusions and Relevance: In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance. Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.

Pain in Trauma Patients: Measurement and Predisposing Factors.

INTRODUCTION: Acute pain is common after injury. This study intended to evaluate the feasibility of quantifying pain experience over an entire admission using "area under the pain curve" and to identify factors associated with increased pain. METHODS: This retrospective single-center study included all trauma patients admitted from 2013 to 2020. Maximum pain scores were extracted for each day. Pain was defined as area under the curve (AUC) of maximum pain scores/day plotted against time. Injury patterns were analyzed by dichotomizing Abbreviated Injury Scale (AIS) scores (AIS < 3 versus AIS ≥ 3) for each body region. Urinary drug screen results were collected from admission data. A general linear model was used to determine which injury patterns, mechanisms, and age groups were predictive of increased AUC in all patients together and separate by operative and nonoperative groups. RESULTS: We identified 21,640 patients, of which 70% were male and 83% had suffered blunt injury. Overall injury severity was associated with increased pain experience. Serious head injury, younger age, and older age (compared to 45-49 y) were associated with decreased pain. Spinal injuries, thoraco-abdominal injuries, and combined thoracic and lower extremity injuries were predictive of increased pain. Compared to patients with no positive test for illicit substances or documentation of prehospital narcotic medications, the pain experience was greater for both, those who had been administered a narcotic in the prehospital setting and those who tested positive for illicit substances. CONCLUSIONS: This study extends the concept of total pain experience using AUC methodology. Our results demonstrate associations between increased pain and certain patterns of injury, ages, and presence of drugs on admission. Measuring total pain experience could assist in comparing pain-management strategies. Future research should focus on validating pain experience against quality-of-life measurements.

A decomposition of the effects of the COVID-19 pandemic on changes in the motor vehicle collision related mortality in Alabama.

BACKGROUND/OBJECTIVE: Motor vehicle collisions are the leading cause of unintentional injury death in Alabama and at various points during the COVID-19 pandemic there were documented increases in the following risk driving behaviors: speeding, driving under the influence, and seat belt citations. Thus, the objective was to characterize the overall motor vehicle collision (MVC)-related mortality rate in Alabama and the contribution of each component over the first two years of the pandemic compared to before the pandemic by three different road classes: urban arterials, rural arterials, and all other road classes. METHODS: MVC data were derived from the Alabama eCrash database, an electronic crash reporting system used by police officers across the state. Data on vehicle miles traveled each year were collected from the U.S. Department of Transportation's Federal Highway Administration estimates of traffic volume trends. MVC-related mortality in Alabama was the primary outcome and year of MVC was the exposure. The novel decomposition method broke down population mortality rate into four parts: deaths per MVC injury, injury per MVC, MVC per vehicle miles traveled (VMT), and VMT per population. Poisson models with scaled deviance were used to estimate rate ratios of each component. Relative contribution (RC) of each component was calculated by taking the absolute value of the component's beta coefficient and dividing by the sum of the absolute values of all components' beta coefficients. Models were stratified by road class. RESULTS: Across all road classes combined, there were no significant changes to the overall MVC-related mortality rate (per population) and its components when comparing 2020-2022 to 2017-2019; this was due to the increased case fatality rate (CFR) being offset by decreases in the VMT rate and MVC injury rate. In 2020, among rural arterials a non-significant increased mortality rate was offset by a decreased VMT rate (RR 0.91, 95% CI 0.84-0.98, RC 19.2%) and MVC injury rate (RR: 0.89, 95% CI: 0.82-0.97, RC: 22.2%) when compared to 2017-2019. For non-arterials, a non-significant decreased MVC mortality rate was observed in 2020 when compared to 2017-2019 (RR 0.86, 95% CI 0.71-1.03). When considering 2021-2022 versus 2020, the only significant component for any road class was a decreased MVC injury rate for non-arterials (RR: 0.90,95% CI: 0.89-0.93) but this was offset by an increased MVC rate and CFR, resulting in no significant change to the mortality rate (per population). CONCLUSIONS: In a state with one of the highest MVC-related mortality rates in the country, despite decreases in VMTs per population and injuries per MVC, the MVC mortality rate per population did not change during the pandemic due in part to the contributions of an increase in the case fatality rate. Future research should determine whether the increase in CFR was associated with risky driving behaviors during the pandemic.

An ecological study regarding the association between paraquat exposure and end stage renal disease.

BACKGROUND: Persons who experience paraquat poisoning rapidly develop damage to a variety of organ systems including acute kidney injury (AKI), the occurrence of which is associated with an increased risk of death. However, little is known about the effects of chronic paraquat exposure on renal function and the onset of chronic renal disease. The objective of the current study is to assess the association between paraquat exposure and the incidence of end stage renal disease (ESRD) in the United States. METHODS: Data on the incidence of ESRD for the period 2010 through 2017 and kilograms of paraquat use per square mile for each county in the conterminous United States was obtained from the United States Renal Data System (USRDS) and the National Water Quality Assessment (NAWQA) Program, respectively. Negative binomial regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association between quartiles of paraquat exposure and the incidence of ESRD. RESULTS: The incidence of ESRD increased with increasing paraquat density. Based on a 20-year exposure lag, those in the highest paraquat density quartile had a 21% higher rate of ESRD compared to the lowest quartile whereas for a 15-year lag the increase was 26%. Adjusted associations were attenuated though still followed an increasing linear trend across quintiles. CONCLUSIONS: The results of this study are consistent with a large number of studies documenting a high incidence of AKI and a small number of studies chronic renal disease following acute and chronic paraquat exposure, respectively. While the pathophysiological mechanisms underlying kidney injury following paraquat poisoning are well understood, more research is necessary to understand the natural history of chronic kidney disease due to chronic paraquat exposure.

Clinical risk factors for admission with Pseudomonas and multidrug-resistant Pseudomonas community-acquired pneumonia.

BACKGROUND: Microbial etiology for community-acquired pneumonia (CAP) is evolving with pathogens known for high CAP mortality e.g., Pseudomonas species. Chronic obstructive pulmonary disease (COPD) patients are at risk for hospitalization for CAP. Understanding regional patterns and risk factors for multidrug-resistant (MDR) Pseudomonas acquisition has implications for antimicrobial stewardship. OBJECTIVES: To evaluate the regional epidemiology of MDR Pseudomonas CAP and its association with COPD. METHODS: We queried the electronic medical records of the University of Alabama at Birmingham Healthcare System to identify patients hospitalized for CAP with Pseudomonas positive respiratory samples between 01/01/2013-12/31/2019. Log binomial regression models were used to examine associations between COPD diagnosis and risk of Pseudomonas/MDR Pseudomonas CAP. RESULTS: Cohort consisted of 913 culture positive CAP cases aged 59-year (IQR:48-68), 61% (560) male, 60% (547) white, 65% (580) current/past smokers, and 42% (384) COPD. Prevalence of Pseudomonas CAP in culture positive CAP was 18% (167), MDR Pseudomonas CAP in Pseudomonas CAP was 22% (36), and yearly incidence of MDR Pseudomonas CAP was stable (p = 0.169). COPD was associated with Pseudomonas CAP (RR 1.39; 95% CI 1.01, 1.91; p = 0.041) but not with MDR Pseudomonas CAP (0.71; 95% CI 0.35, 1.45; p = 0.349). Stroke (RR 2.64; 95% CI 1.51, 4.61; p = 0.0006) and use of supplemental oxygen (RR 2.31; 95% CI 1.30, 4.12; p = 0.005) were associated with MDR Pseudomonas CAP. CONCLUSION: Incidence of MDR Pseudomonas CAP was stable over time. COPD was associated with Pseudomonas CAP but not with MDR Pseudomonas CAP. Larger cohort studies are needed to confirm findings.

Over-transfusion with blood for suspected hemorrhagic shock is not associated with worse clinical outcomes.

BACKGROUND: We evaluated patient outcomes after early, small volume red blood cell (RBC) transfusion in the setting of presumed hemorrhagic shock. We hypothesized that transfusion with even small amounts of blood would be associated with more complications. STUDY DESIGN AND METHODS: Retrospective review of trauma patients admitted to a Level 1 trauma center between 2016-2021. Patients predicted to require massive transfusion who survived ≥72 h were categorized according to units of RBCs transfused in the first 24 h. A Cox regression model stratified by dichotomized ISS and adjusted for SBP <90 mm Hg and pulse >120 bpm on arrival was used to estimate hazard ratios (HRs) for outcomes of interest. RESULTS: A total of 3121 (24%) received RBC transfusion within the first 24 h. Massive transfusion protocol (MTP) was activated in 38% (1188/3121): 17% received no RBCs, 27.4% 1-3 units, 32.4% 4-9 units, and 22.7% ≥10 units. Mean ISS increased with each category of RBC transfusion. There was no difference in the risk of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), infection, cardiac arrest, venous thromboembolism or stroke for patients receiving 1-3 units compared to the non-transfused group or 4-9 units group (p > 0.05). Compared to those receiving ≥10 units, the 1-3 units group had a significantly lower risk of AKI, ARDS, and cardiac arrest. DISCUSSION: Early empiric RBC transfusion for presumed hemorrhagic shock may subject patients to potential over-transfusion and end-organ damage. Among patients meeting clinical triggers for MTP, 1-3 units of allogeneic RBCs is not associated with worse outcomes.

Endotheliopathy is Associated with a 24-hour Fibrinolysis Phenotype Described by Low TEG Lysis and High D-Dimer after Trauma: a Secondary Analysis of the PROPPR Study.

Objectives: Determine associations between biomarkers of endotheliopathy, 24-hour fibrinolysis phenotypes and clinical outcomes after trauma. Background: The vascular endothelium is a critical regulator of hemostasis and organ function. The relationship between markers of endotheliopathy and fibrinolysis following trauma has not been evaluated. Methods: We performed a secondary analysis of prospectively collected biomarker data in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized controlled trial. We stratified subjects by 24-hour thromboelastography (TEG) percent clot lysis (LY30) and plasma D-dimer (DD) levels and evaluated differences in endotheliopathy biomarkers and clinical outcomes between subjects with one of four 24-hour fibrinolysis phenotypes: LY30 0.9-2.9% (LY30norm), LY30 >2.9% (LY30high), LY30 <0.9% and low DD (LY30low+DDlow), and LY30 <0.9% and high DD (LY30low+DDhigh). Results: The analysis included 168 subjects with LY30norm, 32 with LY30high, 147 with LY30low+DDlow and 124 with LY30low+DDhigh. LY30low+DDhigh subjects had greater injury severity and a higher incidence of severe head injury, multiorgan failure (MOF), and mortality than the other phenotypes. All endotheliopathy biomarkers were significantly higher in the LY30low+DDhigh phenotype. Adjusting for injury severity, mechanism and head trauma, 24-hour angiopoietin-2 and soluble thrombomodulin were independently associated with the LY30low+DDhigh phenotype. Both endothelial biomarkers were discriminating for MOF. Subjects with thrombomodulin level >9.5 ng/mL and angiopoietin-2 level >3.6 ng/mL accounted for 64% of subjects who developed MOF. Conclusions: In a multicenter trauma cohort, subjects with a fibrinolysis phenotype characterized by low TEG lysis and elevated DD 24 hours after injury have significantly worse endotheliopathy and clinical outcomes. Our findings support mechanistic evaluations of the role of the endothelium in fibrinolysis dysregulation that may drive late-stage organ injury.

Balancing enrollment and mortality in hemorrhage control trials: A secondary analysis of the PROPPR trial.

BACKGROUND: Designing clinical trials on hemorrhage control requires carefully balancing the need for high enrollment numbers with the need of focusing on the sickest patients. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial enrolled patients within 2 hours of arrival to the emergency department for a trial of injured patients at risk for massive transfusion. We conducted a secondary analysis to determine how time-to-randomization affected patient outcomes and the balance between enrollment and mortality. METHODS: Patients from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were compared based on 30-minute time to randomization intervals. Outcomes included 24-hour and 30-day mortality, time to hemostasis, adverse events, and operative procedures. Additional analyses were conducted based on treatment arm allocation, mechanism of injury, and variation in start time (arrival vs. randomization). RESULTS: Randomization within 30 minutes of arrival was associated with higher injury severity (median Injury Severity Score, 29 vs. 26 overall; p < 0.01), lower systolic blood pressure (median, 91 vs. 102 mm Hg overall; p < 0.01), and increased penetrating mechanism (50% vs. 47% overall; p < 0.01). Faster time-to-randomization was associated with increased 24-hour (20% for 0- to 30 minute entry, 9% for 31-minute to 60-minute entry, 10% for 61-minute to 90-minute entry, 0% for 91-minute to 120-minute entry; p < 0.01) and 30-day mortality (p < 0.01). There were no significant associations between time-to-randomization and adverse event occurrence, operative interventions, or time to hemostasis. CONCLUSION: Increasing time to randomization in this large multicenter randomized trial was associated with increased survival. Fastest randomization (within 0-30 minutes) was associated with highest 24-hour and 30-day mortality, but only 57% of patients were enrolled within this timeframe. Only 3% of patients were enrolled within the last 30-minute window (91-120 minutes), with none of them dying within the first 24 hours. For a more optimal balance between enrollment and mortality, investigators should consider shortening the time to randomization when planning future clinical trials of hemorrhage control interventions. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level II.

Racial and rural-urban disparities in cardiovascular risk factors among patients with head and neck cancer in a clinical cohort.

BACKGROUND: Evidence on distribution of cardiovascular disease (CVD) risk factors in patients with head and neck squamous cell carcinoma (HNSCC) is limited. We assessed disparities in prevalence and incidence of CVD risk factors in patients with HNSCC. METHODS: Electronic health records (EHR) data on 2262 patients with HNSCC diagnosed between 2012 and 2018 at a NCI-designated cancer center were included. Prevalence of CVD risk factors at baseline and incidence at 1-year post HNSCC diagnosis were assessed using logistic and robust Poisson regression, respectively. RESULTS: At baseline, 31.72% white patients with HNSCC had dyslipidemia, compared to 24.29% blacks (p < 0.008); diabetes was more prevalent in blacks (p < 0.027). Odds of ≥1 prevalent CVD clinical risk factor at baseline was lower in blacks (OR, 95%CI: 0.71, 0.54-0.93) and in rural patients (OR, 95%CI: 0.70, 0.58-0.85). At 1 year, risk of incident diabetes was higher in rural patients (RR, 95%CI: 1.63, 1.21-2.19). CONCLUSIONS: Demographic disparities were observed in distribution of CVD risk factors in patients with HNSCC.

Institutional Adherence to Current Mohs Surgery Appropriate Use Criteria With Reasons for Nonadherence and Recommendations for Future Versions.

BACKGROUND: The appropriate use criteria (AUC) were established to optimize the use of Mohs micrographic surgery (MMS) and confer the highest possible clinical benefit to the patient. OBJECTIVE: We documented our adherence to AUC and review reasons for nonadherence regarding lesions classified as inappropriate, in the hopes of informing future versions of the AUC. MATERIALS AND METHODS: A retrospective review of 1,000 consecutive patients who underwent MMS at a single institution. A total of 1,318 biopsy-proven nonmelanoma skin cancers were treated with MMS, and each skin cancer that underwent MMS was classified as appropriate, uncertain, or inappropriate based on the AUC. RESULTS: Data were collected on 1,318 lesions with 1,237 (93.9%) categorized as appropriate, 59 (4.5%) uncertain, and 22 (1.7%) not appropriate. The primary variables that determined appropriateness were type of cancer (p = .001), size (p < .001), and area of body (p < .001). CONCLUSION: Institutional adherence to AUC was high, with 93.9% of treated tumors classified as appropriate, 4.5% as uncertain and 1.7% as inappropriate. By far the most commonly reported reason for performing MMS on an inappropriate lesion in our review was the treatment of adjacent lesions in 1 session.

Imaging analysis of ischemic strokes due to blunt cerebrovascular injury.

BACKGROUND: The timing of stroke onset among patients with blunt cerebrovascular injury (BCVI) is not well understood. All blunt trauma patients at our institution undergo a screening computed tomographic angiography (CTA) of the neck. Most patients with CTA evidence of BCVI are treated with aspirin, and all patients with clinical evidence of stroke are treated with aspirin and undergo magnetic resonance imaging (MRI) of the brain. We conducted a retrospective review to determine the incidence of stroke upon admission and following admission. METHODS: All neck CTAs and head MRIs obtained in blunt trauma patients were reviewed from August 2017 to August 2019. All CTAs that were interpreted as showing BCVI were individually reviewed to confirm the diagnosis of BCVI. Stroke was defined as brain MRI evidence of new ischemic lesions, and each MRI was reviewed to identify the brain territory affected. We extracted the time to aspirin administration and the timing of stroke onset from patients' electronic health records. RESULTS: Of the 6,849 blunt trauma patients, 479 (7.0%) had BCVIs. Twenty-four patients (5.0%) with BCVI had a stroke on admission. Twelve (2.6%) of the remaining 455 patients subsequently had a stroke during their hospitalization. The incidence of stroke among patients with BCVI was 7.5%; 2.6% were potentially preventable. Only 5 of the 12 patients received aspirin before the onset of stroke symptoms. All 36 patients with BCVI and stroke had thromboembolic lesions in the territory supplied by an injured vessel. CONCLUSION: With universal screening, CTA evidence of BCVI is common among blunt trauma patients. Although acute stroke is also relatively common in this population, two thirds of strokes are already evident on admission. One third of BCVI-related strokes occur after admission and often relatively early, necessitating rapid commencement of preventative treatment. Further studies are required to demonstrate the value of antithrombotic administration in preventing stroke in BCVI patients. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.

Understanding the geography of trauma: Combining spatial analysis and funnel plots to create comprehensive spatial injury profiles.

BACKGROUND: Understanding geographic patterns of injury is essential to operating an effective trauma system and targeting injury prevention. Choropleth maps are helpful in showing spatial relationships but are unable to provide estimates of spread or degrees of confidence. Funnel plots overcome this issue and are a recommended graphical aid for comparisons that allow quantification of precision. The purpose of this project was to demonstrate the complementary roles of choropleth maps and funnel plots in providing a thorough representation of geographic trauma data. METHODS: This is a retrospective analysis of emergency medical service transport data of adult patients in Alabama from July 2015 to June 2020. Choropleth maps of case volume and observed-to-expected ratios of incidence were created using US Census Bureau data. Funnel plots were created to relate incidence rate to county population. Subgroup analyses included patients with critical physiology, penetrating, blunt, and burn injuries. RESULTS: We identified 65,247 trauma incidents during the study period. The overall statewide incidence rate was 133 per 10,000 persons. The highest number of incidents occurred in the most populous counties (Jefferson, 10,768; Mobile, 5,642). Choropleth maps for overall incidence and subgroups highlighted that spatial distribution of overall case volume and observed-to-expected ratios are not always congruent. Funnel plots identified possible and probable outliers, and revealed skewed or otherwise unique patterns among injury subgroups. CONCLUSION: This study demonstrates the complementarity of choropleth maps and funnel plots in describing trauma patterns. Comprehensive geospatial analyses may help guide a data-driven approach to trauma system optimization and injury prevention. Combining maps of case counts, incidence, and funnel plots helps to not only identify geographic trends in data but also quantify outliers and display how far results fall outside the expected range. The combination of these tools provides a more comprehensive geospatial analysis than either tool could provide on its own. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.

Traditional risk factors and cancer-related factors associated with cardiovascular disease risk in head and neck cancer patients.

Background: Risk of incident cardiovascular disease (CVD) in head and neck squamous cell carcinoma (HNSCC) patients is under-reported. We assessed the association of HNSCC-related factors and traditional risk factors with 1- and 5-year CVD risk in HNSCC patients without prevalent CVD at cancer diagnosis. Methods: A clinical cohort of 1,829 HNSCC patients diagnosed between 2012 and 2018, at a National Cancer Institute (NCI)-designated cancer center was included. Information on HNSCC-related factors [HNSCC anatomical subsite, stage at diagnosis, treatment, and tumor human papillomavirus (HPV) status] were extracted from the tumor registry. Data on traditional risk factors (hypertension, dyslipidemia, diabetes, tobacco smoking status, and obesity) were extracted from the electronic health records system (EHR) at baseline (HNSCC diagnosis). A composite of ischemic heart disease, heart failure, and ischemic stroke was the outcome of interest in time to event analysis. Hazard ratio (HR) (95% CI) were reported with death as a competing risk. Results: In patients diagnosed with HNSCC, 10.61% developed incident CVD events by 1-year post cancer diagnosis. One-year CVD risk was lower in patients using antihypertensive medications at baseline, compared to patients without baseline hypertension [HR (95% CI): 0.41 (0.24-0.61)]. One-year CVD risk was high in patients receiving HNSCC surgery. Patients receiving radiation therapy had a higher 5-year CVD risk than surgery patients [HR (95% CI): 2.17 (1.31-3.04)]. Patients using antihypertensive medications had a lower 5-year CVD risk than patients without baseline hypertension [HR (95% CI): 0.45 (0.22-0.75)]. Older age and diabetes were associated with increased 1- and 5-year CVD risk. HPV-negative patients were older (p 0.006) and had a higher 5-year cumulative incidence of CVD (p 0.013) than HPV-positive patients. Conclusion: Traditional risk factors and cancer-related factors are associated with CVD risk in HNSCC patients. Future research should investigate the role of antihypertensive medications in reducing CVD risk in HNSCC patients.