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Background and Purpose: Early detection of large vessel occlusion (LVO) stroke optimizes endovascular therapy and improves outcomes. Clinical stroke severity scales used for LVO identification have variable accuracy. We investigated a portable LVO-detection device (PLD), using electroencephalography and somatosensory-evoked potentials, to identify LVO stroke., Methods: We obtained PLD data in suspected patients with stroke enrolled prospectively via a convenience sample in 8 emergency departments within 24 hours of symptom onset. LVO discriminative signals were integrated into a binary classifier. The National Institutes of Health Stroke Scale was documented, and 4 prehospital stroke scales were retrospectively calculated. We compared PLD and scale performance to diagnostic neuroimaging., Results: Of 109 patients, there were 25 LVO (23%), 38 non-LVO ischemic (35%), 14 hemorrhages (13%), and 32 stroke mimics (29%). The PLD had higher sensitivity (80% [95% CI, 74-85]) and similar specificity (80% [95% CI, 77-83]) to all prehospital scales at their predetermined high probability LVO thresholds. The PLD had high discrimination for LVO ( C -statistic=0.88)., Conclusions: The PLD identifies LVO with superior accuracy compared with prehospital stroke scales in emergency department suspected stroke. Future studies need to validate the PLD's potential as an LVO triage aid in prehospital undifferentiated stroke populations.

Objective: Characterize relationships among substance misuse, depression, employment, and suicidal ideation (SI) following moderate to severe traumatic brain injury (TBI)., Design: Prospective cohort study., Setting: Inpatient rehabilitation centers with telephone follow-up; level I/II trauma centers in the United States., Participants: Individuals with moderate to severe TBI with data in both the National Trauma Data Bank and the Traumatic Brain Injury Model Systems National Database, aged 18 to 59 years, with SI data at year 1 or year 2 postinjury (N = 1377)., Main Outcome Measure: Primary outcome of SI, with secondary employment, substance misuse, and depression outcomes at years 1 and 2 postinjury., Results: Cross-lagged structural equation modeling analysis showed that year 1 unemployment and substance misuse were associated with a higher prevalence of year 1 depression. Depression was associated with concurrent SI at years 1 and 2. Older adults and women had a greater likelihood of year 1 depression. More severe overall injury (injury severity score) was associated with a greater likelihood of year 1 SI, and year 1 SI was associated with a greater likelihood of year 2 SI., Conclusions: Substance misuse, unemployment, depression, and greater extracranial injury burden independently contributed to year 1 SI; in turn, year 1 SI and year 2 depression contributed to year 2 SI. Older age and female sex were associated with year 1 depression. Understanding and mitigating these risk factors are crucial for effectively managing post-TBI SI to prevent postinjury suicide., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Individuals with traumatic brain injury (TBI) have extended inpatient hospital stays that include prolonged mechanical ventilation, increasing risk for infections, including pneumonia. Studies show the negative short-term effects of hospital-acquired pneumonia (HAP) on hospital-based outcomes; however, little is known of its long-term effects., Methods: A prospective cohort study was conducted. National Trauma Databank and Traumatic Brain Injury Model Systems were merged to derive a cohort of 3,717 adults with moderate-to-severe TBI. Exposure data were gathered from the National Trauma Databank, and outcomes were gathered from the Traumatic Brain Injury Model Systems. The primary outcome was the Glasgow Outcome Scale-Extended (GOS-E), which was collected at 1, 2, and 5 years postinjury. The GOS-E was categorized as favorable (>5) or unfavorable (≤5) outcomes. A generalized estimating equation model was fitted estimating the effects of HAP on GOS-E over the first 5 years post-TBI, adjusting for age, race, ventilation status, brain injury severity, injury severity score, thoracic Abbreviated Injury Scale score of 3 or greater, mechanism of injury, intraventricular hemorrhage, and subarachnoid hemorrhage., Results: Individuals with HAP had a 34% (odds ratio, 1.34; 95% confidence interval, 1.15-1.56) increased odds for unfavorable GOS-E over the first 5 years post-TBI compared with individuals without HAP, after adjustment for covariates. There was a significant interaction between HAP and follow-up, such that the effect of HAP on GOS-E declined over time. Sensitivity analyses that weighted for nonresponse bias and adjusted for differences across trauma facilities did not appreciably change the results. Individuals with HAP spent 10.1 days longer in acute care and 4.8 days longer in inpatient rehabilitation and had less efficient functional improvement during inpatient rehabilitation., Conclusion: Individuals with HAP during acute hospitalization have worse long-term prognosis and greater hospital resource utilization. Preventing HAP may be cost-effective and improve long-term recovery for individuals with TBI. Future studies should compare the effectiveness of different prophylaxis methods to prevent HAP., Level of Evidence: Prospective cohort study, level III.

Objective: To characterize employment stability and identify predictive factors of employment stability in working-age individuals after moderate-to-severe traumatic brain injury (TBI) that may be clinically addressed., Design: Longitudinal observational study of an inception cohort from the Traumatic Brain Injury Model Systems National Database (TBIMS-NDB) using data at years 1, 2, and 5 post-TBI., Setting: Inpatient rehabilitation centers with telephone follow-up., Participants: Individuals enrolled in the TBIMS-NDB since 2001, aged 18-59, with employment data at 2 or more follow-up interviews at years 1, 2, and 5 (N=5683)., Interventions: Not applicable., Main Outcome Measure: Employment stability, categorized using post-TBI employment data as no paid employment (53.25%), stably (27.20%), delayed (10.24%), or unstably (9.31%) employed., Results: Multinomial regression analyses identified predictive factors of employment stability, including younger age, white race, less severe injuries, preinjury employment, higher annual earnings, male sex, higher education, transportation independence postinjury, and no anxiety or depression at 1 year post-TBI., Conclusions: Employment stability serves as an important measure of productivity post-TBI. Psychosocial, clinical, environmental, and demographic factors predict employment stability post-TBI. Notable predictors include transportation independence as well as the presence of anxiety and depression at year 1 post-TBI as potentially modifiable intervention targets., (Copyright © 2018 American Congress of Rehabilitation Medicine. All rights reserved.)

In a previous study, individuals from a single Traumatic Brain Injury Model Systems and trauma center were matched using a novel probabilistic matching algorithm. The Traumatic Brain Injury Model Systems is a multicenter prospective cohort study containing more than 14,000 participants with traumatic brain injury, following them from inpatient rehabilitation to the community over the remainder of their lifetime. The National Trauma Databank is the largest aggregation of trauma data in the United States, including more than 6 million records. Linking these two databases offers a broad range of opportunities to explore research questions not otherwise possible. Our objective was to refine and validate the previous protocol at another independent center. An algorithm generation and validation data set were created, and potential matches were blocked by age, sex, and year of injury; total probabilistic weight was calculated based on of 12 common data fields. Validity metrics were calculated using a minimum probabilistic weight of 3. The positive predictive value was 98.2% and 97.4% and sensitivity was 74.1% and 76.3%, in the algorithm generation and validation set, respectively. These metrics were similar to the previous study. Future work will apply the refined probabilistic matching algorithm to the Traumatic Brain Injury Model Systems and the National Trauma Databank to generate a merged data set for clinical traumatic brain injury research use.

Objective: There is no civilian traumatic brain injury database that captures patients in all settings of the care continuum. The linkage of such databases would yield valuable insight into possible care interventions. Thus, the objective of this article is to describe the creation of an algorithm used to link the Traumatic Brain Injury Model System (TBIMS) to trauma data in state and national trauma databases., Design: The TBIMS data from a single center was randomly divided into two sets. One subset was used to generate a probabilistic linking algorithm to link the TBIMS data to the center's trauma registry. The other subset was used to validate the algorithm. Medical record numbers were obtained and used as unique identifiers to measure the quality of the linkage. Novel methods were used to maximize the positive predictive value., Results: The algorithm generation subset had 121 patients. It had a sensitivity of 88% and a positive predictive value of 99%. The validation subset consisted of 120 patients and had a sensitivity of 83% and a positive predictive value of 99%., Conclusions: The probabilistic linkage algorithm can accurately link TBIMS data across systems of trauma care. Future studies can use this database to answer meaningful research questions regarding the long-term impact of the acute trauma complex on health care utilization and recovery across the care continuum in traumatic brain injury populations.

Objective: Stroke is the leading cause of disability in the United States with most of these patients being transported by emergency medical services. These providers are the first medical point of contact and must be able to rapidly and accurately identify stroke and transport these patients to the appropriate facilities for treatment. There are many conditions that have similar presentations to stroke and can be mistakenly identified as potential strokes, thereby affecting the initial prehospital triage., Methods: A retrospective observational study examined patients with suspected strokes transported to a single comprehensive stroke center (CSC) by a helicopter emergency medical service (HEMS) agency from 2007 through 2013. Final diagnosis was extracted from the Get with the Guidelines (GWTG) database and hospital discharge diagnosis for those not included in the database. Frequencies of discharge diagnosis were calculated and then stratified into interfacility vs. scene transfers., Results: In this study 6,243 patients were transported: 3,376 patients were screened as potential strokes, of which 2,527 had a final diagnosis of stroke (2,242 ischemic stroke and 285 transient ischemic attack), 166 had intracranial hemorrhage, and 655 were stroke mimics. Stroke mimics were more common among scene transfers (223, 32%) than among interfacility transfers (432, 16%)., Conclusions: In our study approximately 20% of potential stroke patients transported via HEMS were mimics. Identifying the need for CSC resources can be an important factor in creating a prehospital triage tool to facilitate patient transport to an appropriate health care facility.

Objective: To determine whether severity of head and extracranial injuries (ECI) is associated with suicidal ideation (SI) or suicide attempt (SA) after traumatic brain injury (TBI)., Design: Factors associated with SI and SA were assessed in this inception cohort study using data collected 1, 2, and 5 years post-TBI from the National Trauma Data Bank and Traumatic Brain Injury Model Systems (TBIMS) databases., Setting: Level I trauma centers, inpatient rehabilitation centers, and the community., Participants: Participants with TBI from 15 TBIMS Centers with linked National Trauma Data Bank trauma data (N=3575)., Interventions: Not applicable., Main Outcome Measures: SI was measured via the Patient Health Questionnaire 9 (question 9). SA in the last year was assessed via interview. ECI was measured by the Injury Severity Scale (nonhead) and categorized as none, mild, moderate, or severe., Results: There were 293 (8.2%) participants who had SI without SA and 109 (3.0%) who had SA at least once in the first 5 years postinjury. Random effects logit modeling showed a higher likelihood of SI when ECI was severe (odds ratio=2.73; 95% confidence interval, 1.55-4.82; P=.001). Drug use at time of injury was also associated with SI (odds ratio=1.69; 95% confidence interval, 1.11-2.86; P=.015). Severity of ECI was not associated with SA., Conclusions: Severe ECI carried a nearly 3-fold increase in the odds of SI after TBI, but it was not related to SA. Head injury severity and less severe ECI were not associated with SI or SA. These findings warrant additional work to identify factors associated with severe ECI that make individuals more susceptible to SI after TBI., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The use of tissue-type plasminogen activator is limited to a maximum of 4.5 hours after symptom-onset. Endovascular recanalization may improve outcomes for large-vessel occlusions (LVO), but efficacy decreases with time from symptom-onset. A National Institutes of Health Stroke Scale (NIHSS) score ≥12 is predictive of LVOs and could be used to triage patients if appropriately used by prehospital providers. The NIHSS has been considered too complex and has not been validated in the prehospital setting., Methods: We reviewed all patients with ischemic stroke transported by helicopter emergency medical services (HEMS) to a single comprehensive stroke center in 2010. HEMS NIHSS were compared with in-hospital stroke team physician scores. NIHSS was categorized based on 3 clinically relevant groupings and ability to predict LVO was investigated., Results: Three-hundred five patients met inclusion criteria, 68.9% having LVO. Moderate agreement existed between HEMS and physicians (72.1%; κ=0.571). Interclass correlation was 0.879 (95% confidence interval, 0.849-0.904). Excluding patients with tissue-type plasminogen activator before HEMS transport, there were 216 patients and good agreement (82.7%; κ=0.619). Among patients presenting within 8 hours postonset and NIHSS≥12, HEMS had a sensitivity of 55.9% and positive predictive value of 83.7% in predicting LVO., Conclusions: HEMS providers can administer NIHSS with moderate to good agreement with the receiving stroke team. The use of the NIHSS in HEMS may identify patients with LVO and inform triage decisions for patients ineligible for tissue-type plasminogen activator., (© 2014 American Heart Association, Inc.)

Background: Long-term outcomes following traumatic brain injury (TBI) correlate with initial head injury severity and other acute factors. Hospital-acquired pneumonia (HAP) is a common complication in TBI. Limited information exists regarding the significance of infectious complications on long-term outcomes after TBI. We sought to characterize risks associated with HAP on outcomes 5 years after TBI., Methods: This study involved data from the merger of an institutional trauma registry and the Traumatic Brain Injury Model Systems outcome data. Individuals with severe head injuries (Abbreviated Injury Scale [AIS] score ≥ 4) who survived to rehabilitation were analyzed. Primary outcome was Glasgow Outcome Scale-Extended (GOSE) at 1, 2, and 5 years. GOSE was dichotomized into low (GOSE score < 6) and high (GOSE score ≥ 6). Logistic regression was used to determine adjusted odds of low GOSE score associated with HAP after controlling for age, sex, head and overall injury severity, cranial surgery, Glasgow Coma Scale (GCS) score, ventilation days, and other important confounders. A general estimating equation model was used to analyze all outcome observations simultaneously while controlling for within-patient correlation., Results: A total of 141 individuals met inclusion criteria, with a 30% incidence of HAP. Individuals with and without HAP had similar demographic profiles, presenting vitals, head injury severity, and prevalence of cranial surgery. Individuals with HAP had lower presenting GCS score. Logistic regression demonstrated that HAP was independently associated with low GOSE scores at follow-up (1 year: odds ratio [OR], 6.39; 95% confidence interval [CI], 1.76-23.14; p = 0.005) (2 years: OR, 7.30; 95% CI, 1.87-27.89; p = 0.004) (5-years: OR, 6.89; 95% CI, 1.42-33.39; p = 0.017). Stratifying by GCS score of 8 or lower and early intubation, HAP remained a significant independent predictor of low GOSE score in all strata. In the general estimating equation model, HAP continued to be an independent predictor of low GOSE score (OR, 4.59; 95% CI, 1.82-11.60; p = 0.001)., Conclusion: HAP is independently associated with poor outcomes in severe TBI extending 5 years after injury. This suggests that precautions should be taken to reduce the risk of HAP in individuals with severe TBI., Level of Evidence: Prognostic study, level III., Competing Interests: We have no conflicts of interest to declare

Introduction: Standardized trauma protocols (STP) have reduced morbidity and in-hospital mortality in mature trauma systems. Most hospitals in low- and middle-income countries (LMICs) have not implemented STPs, often because of financial and logistic limitations. We report the impact of an STP designed for the care of trauma patients in the emergency department (ED) at an LMIC hospital on patients with severe traumatic brain injury (STBI)., Methods: We developed an STP based on generally accepted best practices and damage control resuscitation for a level I trauma centre in Colombia. Without a pre-existing trauma registry, we adapted an administrative electronic database to capture clinical information of adult patients with TBI, a head abbreviated injury score (AIS) ≥3, and who presented ≤12h from injury. Demographics, mechanisms of injury, and injury severity were compared. Primary outcome was in-hospital mortality. Secondary outcomes were Glasgow Coma Score (GCS), length of hospital and ICU stay, and prevalence of ED interventions recommended in the STP. Logistic regression was used to control for potential confounders., Results: The pre-STP group was hospitalized between August 2010 and August 2011, the post-STP group between September 2011 and June 2012. There were 108 patients meeting inclusion criteria, 68 pre-STP implementation and 40 post-STP. The pre- and post-STP groups were similar in age (mean 37.1 vs. 38.6, p=0.644), head AIS (median 4.5 vs. 4.0, p=0.857), Injury Severity Scale (median 25 vs. 25, p=0.757), and initial GCS (median 7 vs. 7, p=0.384). Post-STP in-hospital mortality decreased (38% vs. 18%, p=0.024), and discharge GCS increased (median 10 vs. 14, p=0.034). After controlling for potential confounders, odds of in-hospital mortality post-STP compared to pre-STP were 0.248 (95%CI: 0.074-0.838, p=0.025). Hospital and ICU stay did not significantly change. The use of many ED interventions increased post-STP, including bladder catheterization (49% vs. 73%, p=0.015), hypertonic saline (38% vs. 63%, p=0.014), arterial blood gas draws (25% vs. 43%, p=0.059), and blood transfusions (3% vs. 18%, p=0.008)., Conclusions: An STP in an LMIC decreased in-hospital mortality, increased discharge GCS, and increased use of vital ED interventions for patients with STBI. An STP in an LMIC can be implemented and measured without a pre-existing trauma registry., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Standardized trauma protocols (STPs) have reduced morbidity and mortality in mature trauma systems. Most hospitals in low- and middle-income countries (LMICs) have not yet implemented such protocols, often due to financial and logistic limitations. We report preliminary findings from a trauma quality improvement (QI) initiative, using and evaluating the impact of a low-cost STP in an LMIC university hospital., Methods: We developed an STP based on generally accepted best practices and damage control resuscitation. It was designed for the resources available at the test institution. The Neiva University Hospital (NUH) is a tertiary care hospital and level I trauma center in Neiva, Colombia. As in most LMIC hospitals, there was no trauma information data system at NUH. Therefore, we adapted an administrative electronic database to capture clinically relevant information of adult patients who were hospitalized or died in the emergency department (ED) between August 2010 and June 2012 with an International Classification of Diseases, 10th revision (ICD-10) diagnoses indicating trauma (S00-Y98). Interventions that were recommended in the STP were compared in these two groups. Length of hospital stay (LOS) and mortality were also examined., Results: A total of 4,324 patients were included, of whom, 2,457 patients were in the pre-protocol period and 1,867 were in the post-protocol period. The use of several interventions increased: blood product transfusions in the ED (1.0 vs. 2.7%; p < 0.001), use of hypertonic fluids in hypotensive patients (3.2 vs. 8.9 %; p < 0.001), placement of Foley catheters (11.1 vs. 13.8%; p = 0.007), arterial blood gas draws (16.6 vs. 26.4%; p < 0.001), tetanus vaccinations (19.3 vs. 26.0%; p < 0.001), placement of multiple large bore peripheral catheters (29.5 vs. 34.7%; p < 0.001), prophylactic antibiotics (34.9 vs. 38.0%; p = 0.035), and the use of analgesics (64.5 vs. 68.0%; p = 0.016). Other interventions also trended upwards. Length of stay (LOS) decreased for both surgical and non-surgical patients (surgical 13.4 vs. 11.8 days; p = 0.017; non-surgical 4.4 vs. 3.8 days; p = 0.059). All-cause mortality of trauma patients decreased (3.9 vs. 2.9%; p = 0.088)., Conclusions: The institution of an STP at a university hospital in an LMIC has increased the use of vital interventions while decreasing overall LOS for all-cause trauma patients.

The Cre-recombination system has become an important tool for genetic manipulation of higher organisms and a model for site-specific DNA-recombination mechanisms employed by the λ-Int superfamily of recombinases. We report a novel quantitative approach for characterizing the probability of DNA-loop formation in solution using time-dependent ensemble Förster resonance energy transfer measurements of intra- and inter-molecular Cre-recombination kinetics. Our method uses an innovative technique for incorporating multiple covalent modifications at specific sites in covalently closed DNA. Because the mechanism of Cre recombinase does not conform to a simple kinetic scheme, we employ numerical methods to extract rate constants for fundamental steps that pertain to Cre-mediated loop closure. Cre recombination does not require accessory proteins, DNA supercoiling or particular metal-ion cofactors and is thus a highly flexible system for quantitatively analyzing DNA-loop formation in vitro and in vivo.