Race, Ethnicity, and Delayed Time to COVID-19 Testing Among US Health Care Workers.

Importance: Access to COVID-19 testing is critical to reducing transmission and supporting early treatment decisions; when made accessible, the timeliness of testing may also be an important metric in mitigating community spread of the infection. While disparities in transmission and outcomes of COVID-19 have been well documented, the extent of timeliness of testing and the association with demographic factors is unclear. Objectives: To evaluate demographic factors associated with delayed COVID-19 testing among health care personnel (HCP) during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study used data from the Preventing Emerging Infections Through Vaccine Effectiveness Testing study, a multicenter, test-negative, case-control vaccine effectiveness study that enrolled HCP who had COVID-19 symptoms and testing between December 2020 and April 2022. Data analysis was conducted from March 2022 to Junne 2023. Exposure: Displaying COVID-19-like symptoms and polymerase chain reaction testing occurring from the first day symptoms occurred up to 14 days after symptoms occurred. Main Outcomes and Measures: Variables of interest included patient demographics (sex, age, and clinical comorbidities) and COVID-19 characteristics (vaccination status and COVID-19 wave). The primary outcome was time from symptom onset to COVID-19 testing, which was defined as early testing (≤2 days) or delayed testing (≥3 days). Associations of demographic characteristics with delayed testing were measured while adjusting for clinical comorbidities, COVID-19 characteristics, and test site using multivariable modeling to estimate relative risks and 95% CIs. Results: A total of 5551 HCP (4859 female [82.9%]; 1954 aged 25-34 years [35.2%]; 4233 non-Hispanic White [76.3%], 370 non-Hispanic Black [6.7%], and 324 non-Hispanic Asian [5.8%]) were included in the final analysis. Overall, 2060 participants (37.1%) reported delayed testing and 3491 (62.9%) reported early testing. Compared with non-Hispanic White HCP, delayed testing was higher among non-Hispanic Black HCP (adjusted risk ratio, 1.18; 95%CI, 1.10-1.27) and for non-Hispanic HCP of other races (adjusted risk ratio, 1.17; 95% CI, 1.03-1.33). Sex and age were not associated with delayed testing. Compared with clinical HCP with graduate degrees, all other professional and educational groups had significantly delayed testing. Conclusions and Relevance: In this cross-sectional study of HCP, compared with non-Hispanic White HCP and clinical HCP with graduate degrees, non-Hispanic Black HCP, non-Hispanic HCP of other races, and HCP all other professional and education backgrounds were more likely to have delayed COVID-19 testing. These findings suggest that time to testing may serve as a valuable metric in evaluating sociodemographic disparities in the response to COVID-19 and future health mitigation strategies.

Differences in Prevalence of Transfusion Protocols between Critically Ill Neurologic and Non-Neurologic Patient Populations.

This study describes the prevalence of blood transfusion protocols in ICUs caring for neurologically vs. non-neurologically injured patients across a sample of US ICUs. This prospective, observational multi-center cohort study is a subgroup analysis of the USCIITG-CIOS, comprising 69 ICUs across the US (25 medical, 24 surgical, 20 mixed ICUs). Sixty-four ICUs were in teaching hospitals. A total of 6179 patients were enrolled, with 1266 (20.4%) having central nervous system (CNS) primary diagnoses. We evaluated whether CNS versus non-CNS diagnosis was associated with care in ICUs with restrictive transfusion protocols (RTPs) or massive transfusion protocols (MTPs) and whether CNS versus non-CNS diagnosis was associated with receiving blood products or colloids during the initial 24 h of care. Protocol utilization in CNS vs. non-CNS patients was as follows: RTPs-36.9% vs. 42.9% (p < 0.001); MTPs-48.3% vs. 47.4% (p = 0.57). Blood product transfusions in the first 24 h of ICU care (comparing CNS vs. non-CNS patients) were as follows: packed red blood cells-4.3% vs. 14.6% (p < 0.001); fresh frozen plasma-2.9% vs. 5.1% (p < 0.001); colloid blood products-3.2% vs. 9.2% (p < 0.001). In this cohort, we found differences in ICU utilization of RTPs, but not MTPs, when comparing where critically ill patients with neurologic versus non-neurologic primary diagnoses received ICU care.

Racial and ethnic disparities in emergency department restraint use: A multicenter retrospective analysis.

BACKGROUND: Research regarding disparities in physical restraint use in the emergency department (ED) is limited. We evaluated the role of race, ethnicity, and preferred language on the application of physical restraint among ED patients held under a Massachusetts section 12(a) order for mandatory psychiatric evaluation. METHODS: We identified all ED patient encounters with a section 12(a) order across a large integrated 11-hospital health system from January 2018 through December 2019. Information on age, race, ethnicity, preferred language, insurance, mental illness, substance use, history of homelessness, and in-network primary care provider was obtained from the electronic health record. We evaluated for differences in physical restraint use between subgroups via a mixed-effect logistic regression with random-intercept model. RESULTS: We identified 32,054 encounters involving a section 12(a) order. Physical restraints were used in 2,458 (7.7%) encounters. Factors associated with physical restraint included male sex (adjusted odds ratio [aOR] = 1.44, 95% confidence interval [CI] = 1.28 to 1.63), Black/African American race (aOR = 1.22, 95% CI = 1.01 to 1.48), Hispanic ethnicity (aOR = 1.45, 95% CI = 1.22 to 1.73), Medicaid insurance (aOR = 1.21, 95% CI = 1.05 to 1.39), and a diagnosis of bipolar disorder or psychotic disorder (aOR = 1.51, 95% CI = 1.31 to 1.74). Across all age groups, patients who were 25 to 34 years of age were at highest risk of restraint (aOR = 2.01, 95% CI = 1.69 to 2.39). Patients with a primary care provider within our network (aOR = 0.81, 95% CI = 0.72 to 0.92) were at lower risk of restraint. No associations were found between restraint use and language, history of alcohol or substance use, or homelessness. CONCLUSION: Black/African American and Hispanic patients under an involuntary mandatory emergency psychiatric evaluation hold order experience higher rates of physical restraint in the ED. Factors contributing to racial disparities in the use of physical restraint, including the potential role of structural racism and other forms of bias, merits further investigation.

Disability Rating Scale in the First Few Weeks After a Severe Traumatic Brain Injury as a Predictor of 6-Month Functional Outcome.

BACKGROUND: An early acute marker of long-term neurological outcome would be useful to help guide clinical decision making and therapeutic effectiveness after severe traumatic brain injury (TBI). We investigated the utility of the Disability Rating Scale (DRS) as early as 1 wk after TBI as a predictor of favorable 6-mo Glasgow Outcome Scale extended (GOS-E). OBJECTIVE: To determine the predictability of a favorable 6-mo GOS-E using the DRS measured during weeks 1 to 4 of injury. METHODS: The study is a sub analysis of patients enrolled in the Epo Severe TBI Trial (n = 200) to train and validate L1-regularized logistic regression models. DRS was collected at weeks 1 to 4 and GOS-E at 6 mo. RESULTS: The average area under the receiver operating characteristic curve was 0.82 for the model with baseline demographic and injury severity variables and week 1 DRS and increased to 0.88 when including weekly DRS until week 4. CONCLUSION: This study suggests that week 1 to 4 DRS may be predictors of favorable 6-mo outcome in severe TBI patients and thus useful both for clinical prognostication as well as surrogate endpoints for adaptive clinical trials.

External Validation of the qSOFA Score in Emergency Department Patients With Pneumonia.

BACKGROUND: Pneumonia is the leading cause of sepsis. In 2016, the 3rd International Consensus Conference for Sepsis released the Quick Sepsis-Related Organ Failure Assessment (qSOFA) to identify risk for poor outcomes in sepsis. OBJECTIVE: We sought to externally validate qSOFA in emergency department (ED) patients with pneumonia and compare the accuracy of qSOFA to systemic inflammatory response syndrome score (SIRS), Confusion, Respiratory Rate and Blood Pressure (CRB), Confusion, Respiratory Rate, Blood Pressure and Age (CRB-65), and DS CRB-65, which is based on the CRB-65 score and includes two additional items-presence of underlying comorbid disease and blood oxygen saturation. METHODS: A subgroup analysis of U.S. Critical Illness and Injury Trials Group (USCIITG-Lung Injury Prevention Study [LIPS]; ClinicalTrials.gov ID: NCT00889772) prospective cohort. The primary outcome was in-hospital mortality. Secondary outcomes were measures of intensive care unit (ICU) utilization. Sensitivity, specificity, and area under the curve (AUC) were reported. RESULTS: From March to August 2009, 5584 patients were enrolled; 713 met inclusion criteria. Median age was 61 years (interquartile range 49-75 years). SIRS criteria had the highest sensitivity for death (89%) and lowest specificity (25%), while CRB had the highest specificity (88%) and lowest sensitivity (31%), followed by qSOFA (80% and 53%, respectively). This trend was maintained for the secondary outcomes. There was no significant difference in the AUC for death using qSOFA (AUC 0.75; 95% confidence interval [CI] 0.66-0.84), SIRS (AUC 0.70; 95% CI 0.61-0.78), CRB (AUC 0.71; 95% CI 0.62-0.80), CRB-65 (AUC 0.71; 95% CI 0.63-0.80), and DS CRB-65 (AUC 0.73; 95% CI 0.64-0.82). CONCLUSIONS: In this multicenter observational study of ED patients hospitalized with pneumonia, we found no significant differences between qSOFA and SIRS for predicting in-hospital death. In addition, several popular pneumonia-specific severity scores performed nearly identically to qSOFA score in predicting death and ICU utilization. Validation is needed in a larger sample.

Intravenous Bone Marrow Mononuclear Cells for Acute Ischemic Stroke: Safety, Feasibility, and Effect Size from a Phase I Clinical Trial.

Cellular therapy is a promising investigational modality to enhance poststroke recovery. We conducted a single-arm, phase I clinical trial to determine the safety and feasibility of intravenous (IV) administration of autologous bone marrow mononuclear cells (MNCs) after acute ischemic stroke (AIS). Patients with moderate severity of AIS underwent bone marrow harvest followed by IV reinfusion of MNCs within 24-72 hours of onset. A target dose of 10 million cells per kilogram was chosen based on preclinical data. Patients were followed up daily during hospitalization and at 1, 3, 6, 12, and 24 months for incidence of adverse events using laboratory, clinical (12 months), and radiological (24 months) parameters. The trial was powered to detect severe adverse events (SAEs) with incidences of at least 10% and planned to enroll 30 patients. Primary outcomes were study-related SAEs and the proportion of patients successfully completing study intervention. A propensity score-based matched control group was used for the estimation of effect size (ES) for day-90 modified Rankin score (mRS). There were no study-related SAEs and, based on a futility analysis, enrolment was stopped after 25 patients. All patients successfully completed study intervention and most received the target dose. Secondary analysis estimated the ES to be a reduction of 1 point (95% confidence interval: 0.33-1.67) in median day-90 mRS for treated patients as compared with the matched control group. Bone marrow harvest and infusion of MNCs is safe and feasible in patients with AIS. The estimated ES is helpful in designing future randomized controlled trials. Stem Cells 2019;37:1481-1491.

Glasgow Outcome Scale Measures and Impact on Analysis and Results of a Randomized Clinical Trial of Severe Traumatic Brain Injury.

The original unstructured Glasgow Outcome Scale (uGOS) and the newer structured interviews GOS and the Extended GOS (GOS-E) have been used widely as outcomes in severe traumatic brain injury (TBI) trials. We compared outcome categories (ranging from dead [D] to good recovery [GR]) for each measure in a randomized trial of transfusion threshold and the implications of measure choice and analysis methods for the results of the trial. We planned to explore patient symptomology possibly driving any discrepancies between the patient's uGOS and GOS scores. Category correspondence between uGOS and GOS scores occurred in 160 (88.4%) of the 181 analyzed cases. The GOS-E and GOS instruments incorporated more behavioral/cognitive/social and other components, leading to a worse outcome in some cases than for the uGOS. Choice of outcome measure and analysis led to incongruous conclusions. Dichotomizing uGOS into favorable outcome (GR and moderate disability [MD] categories) versus unfavorable (severe disability [SD], vegetative state [VS], and D categories), we observed a significant effect of transfusion threshold (odds ratio [OR] = 0.51, p = 0.03; adjusted OR = 0.40, p = 0.02). For the same dichotomization of GOS and GOS-E, the effect was not statistically significant but the ORs were similar (ORs between 0.57 and 0.68, p > 0.15 for all). An effect was not detected using ordinal logistic regression or sliding dichotomy method for all three measures. Differences in categorizations of subjects between moderate and severe disability among the scales impacted conclusions of the trial. In future studies, particular attention should be given to implementing GOS measures and describing the methodology for how outcomes were ascertained.

IMPACT probability of poor outcome and plasma cytokine concentrations are associated with multiple organ dysfunction syndrome following traumatic brain injury.

OBJECTIVE: Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS. METHODS: The authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI. RESULTS: Two hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94-42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)-6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20-1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01-1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24-2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18-19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06-1.40, p = 0.006). CONCLUSIONS: Admission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.

EAST Multicenter Trial on targeted temperature management for hanging-induced cardiac arrest.

BACKGROUND: We sought to determine the outcome of suicidal hanging and the impact of targeted temperature management (TTM) on hanging-induced cardiac arrest (CA) through an Eastern Association for the Surgery of Trauma (EAST) multicenter retrospective study. METHODS: We analyzed hanging patient data and TTM variables from January 1992 to December 2015. Cerebral performance category score of 1 or 2 was considered good neurologic outcome, while cerebral performance category score of 3 or 4 was considered poor outcome. Classification and Regression Trees recursive partitioning was used to develop multivariate predictive models for survival and neurologic outcome. RESULTS: A total of 692 hanging patients from 17 centers were analyzed for this study. Their overall survival rate was 77%, and the CA survival rate was 28.6%. The CA patients had significantly higher severity of illness and worse outcome than the non-CA patients. Of the 175 CA patients who survived to hospital admission, 81 patients (46.3%) received post-CA TTM. The unadjusted survival of TTM CA patients (24.7% vs 39.4%, p < 0.05) and good neurologic outcome (19.8% vs 37.2%, p < 0.05) were worse than non-TTM CA patients. However, when subgroup analyses were performed between those with an admission Glasgow Coma Scale score of 3 to 8, the differences between TTM and non-TTM CA survival (23.8% vs 30.0%, p = 0.37) and good neurologic outcome (18.8% vs 28.7%, p = 0.14) were not significant. Targeted temperature management implementation and post-CA management varied between the participating centers. Classification and Regression Trees models identified variables predictive of favorable and poor outcome for hanging and TTM patients with excellent accuracy. CONCLUSION: Cardiac arrest hanging patients had worse outcome than non-CA patients. Targeted temperature management CA patients had worse unadjusted survival and neurologic outcome than non-TTM patients. These findings may be explained by their higher severity of illness, variable TTM implementation, and differences in post-CA management. Future prospective studies are necessary to ascertain the effect of TTM on hanging outcome and to validate our Classification and Regression Trees models. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.

Smartphone transmission of electrocardiography images to reduce time of cardiac catheterization laboratory activation.

BACKGROUND: This retrospective study evaluated the use of a smartphone application to facilitate communication between the emergency physician (EP) and the interventional cardiologist in order to minimize the time to cardiac catheterization laboratory (CCL) activation and time to percutaneous coronary intervention (PCI). METHODS: We retrospectively collected pertinent time-points in the management of patients diagnosed with STEMI in the emergency department and their outcome. The primary outcome was the reduction in the time from ECG interpretation to CCL activation after the implementation of a smartphone application. A total of 84 patients were enrolled. Patients' electrocardiography (ECG) were described by traditional verbal communication via telephone (group 1, n = 40) and by additional smartphone transmission of ECG images to an interventional cardiologist (group 2, n = 44). Relevant time-points were recorded for analysis. RESULTS: The time from ECG interpretation to CCL activation was reduced from 28.3 ± 4.1 in group 1 to 17.6 ± 2.3 min in group 2 (p = 0.03). Similarly, the time from ECG interpretation to balloon inflation time (D2B) decreased from 93.1 to 73.4 min (p = 0.025). Comparing group 2 with group 1, the door to balloon (D2B) time improved to 90.4 ± 9.8 from 119.3 ± 16.3 min (p = 0.23), the proportion of patients with a D2B time less than 90 min increased to 70.5% from 52.5% (p = 0.09), and the mortality rate decreased to 2.2% from 12.5% (p = 0.07). CONCLUSION: The additional use of a smartphone application to transmit ECG information to interventional cardiologists by EPs facilitated communication and reduced the decision time to CCL activation and percutaneous intervention.

Comorbidity, Pain, Utilization, and Psychosocial Outcomes in Older versus Younger Sickle Cell Adults: The PiSCES Project.

Background. Patients with SCD now usually live well into adulthood. Whereas transitions into adulthood are now often studied, little is published about aging beyond the transition period. We therefore studied age-associated SCD differences in utilization, pain, and psychosocial variables. Methods. Subjects were 232 adults in the Pain in Sickle Cell Epidemiology Study (PiSCES). Data included demographics, comorbidity, and psychosocial measures. SCD-related pain and health care utilization were recorded in diaries. We compared 3 age groups: 16-25 (transition), 26-36 (younger adults), and 37-64 (older adults) years. Results. Compared to the 2 adult groups, the transition group reported fewer physical challenges via comorbidities, somatic complaints, and pain frequency, though pain intensity did not differ on crisis or noncrisis pain days. The transition group utilized opioids less often, made fewer ambulatory visits, and had better quality of life, but these differences disappeared after adjusting for pain and comorbidities. However, the transition group reported more use of behavioral coping strategies. Conclusion. We found fewer biological challenges, visits, and better quality of life, in transition-aged versus older adults with SCD, but more behavioral coping. Further study is required to determine whether age-appropriate health care, behavioral, or other interventions could improve age-specific life challenges of patients with SCD.

Association of pre-hospital theophylline use and mortality in chronic obstructive pulmonary disease patients with sepsis.

BACKGROUND: Although theophylline has been shown to have anti-inflammatory effects, the therapeutic use of theophylline before sepsis is unknown. The aim of our study was to determine the effect of theophylline on COPD patients presenting with sepsis. METHODS: This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients with COPD who were hospitalized for sepsis between 2000 and 2011 were divided into theophylline users and non-users. The primary outcome was 30-day mortality. The secondary outcome was in-hospital death, intensive care unit admission, and need for mechanical ventilation. Cox proportional hazard model and conditional logistic regression were used to calculate the risk between groups. RESULTS: A propensity score-matched cohort of 51,801 theophylline users and 51,801 non-users was included. Compared with non-users, the 30-day (HR 0.931, 95% CI 0.910-0.953), 180-day (HR 0.930, 95% CI 0.914-0.946), 365-day (HR 0.944, 95% CI 0.929-0.960) and overall mortality (HR 0.965, 95% CI 0.952-0.979) were all significantly lower in theophylline users. Additionally, the theophylline users also had lower risk of in-hospital death (OR 0.895, 95% CI 0.873-0.918) and need for mechanical ventilation (OR 0.972, 95% CI 0.949-0.997). CONCLUSIONS: Theophylline use is associated with a lower risk of sepsis-related mortality in COPD patients. Pre-hospital theophylline use may be protective to COPD patients with sepsis.

Early risk factors and the role of fluid administration in developing acute respiratory distress syndrome in septic patients.

BACKGROUND: Sepsis is a major risk factor for acute respiratory distress syndrome (ARDS). However, there remains a paucity of literature examining risk factors for ARDS in septic patients early in their course. This study examined the role of early fluid administration and identified other risk factors within the first 6 h of hospital presentation associated with developing ARDS in septic patients. METHODS: This was a secondary analysis of septic adult patients presenting to the Emergency Department or being admitted for high-risk elective surgery from the multicenter observational cohort study, US Critical Injury and Illness trial Group-Lung Injury Prevention Study 1 (USCIITG-LIPS 1, NCT00889772). Multivariable logistic regression was performed to identify potential early risk factors for ARDS. Stratified analysis by shock status was performed to examine the association between early fluid administration and ARDS. RESULTS: Of the 5584 patients in the original study cohort, 2534 (45.4%) met our criteria for sepsis. One hundred and fifty-six (6.2%) of these patients developed ARDS during the hospital stay. In multivariable analyses, Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR 1.10, 95% CI 1.07-1.13), age (OR 0.97, 95% CI 0.96-0.98), total fluid infused in the first 6 h (in liters) (OR 1.15, 95% CI 1.03-1.29), shock (OR 2.57, 95% CI 1.62-4.08), pneumonia as a site of infection (OR 2.31, 95% CI 1.59-3.36), pancreatitis (OR 3.86, 95% CI 1.33-11.24), and acute abdomen (OR 3.77, 95% CI 1.37-10.41) were associated with developing ARDS. In the stratified analysis, total fluid infused in the first 6 h (in liters) (OR 1.05, 95% CI 0.87-1.28) was not associated with the development of ARDS in the shock group, while there was an association in the non-shock group (OR 1.21, 95% CI 1.05-1.38). CONCLUSIONS: In septic patients, the following risk factors identified within the first 6 h of hospital presentation were associated with ARDS: APACHE II score, presence of shock, pulmonary source of infection, pancreatitis, and presence of an acute abdomen. In septic patients without shock, the amount of fluid infused during the first 6 h of hospital presentation was associated with developing ARDS.

Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells.

Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5-8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×106 cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re-infusion occurred within 48 hours after injury. Patients were monitored for harvest-related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging-based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging-based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow-up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest that correlated with functional outcomes. Key inflammatory cytokines were downregulated. Treatment of severe, adult traumatic brain injury using an intravenously delivered autologous bone marrow mononuclear cell infusion is safe and logistically feasible. There appears to be a treatment signal as evidenced by central nervous system structural preservation, consistent with previous pediatric trial data. Inflammatory biomarkers are downregulated after cell infusion. Stem Cells 2016 Video Highlight: https://youtu.be/UiCCPIe-IaQ Stem Cells 2017;35:1065-1079.

Association of weekend effect with early mortality in severe sepsis patients over time.

BACKGROUND: The aim of this study is to investigate the "weekend effect" and early mortality of patients with severe sepsis. METHODS: Using the Taiwanese National Healthcare Insurance Research Database, all patients who were hospitalized for the first time with an episode of severe sepsis between January 2000 and December 2011 were identified and the short-term mortality of patients admitted on weekdays was compared to those admitted on weekends. The primary endpoint was 7-day mortality. The secondary endpoints were 14 and 28-day mortality. RESULTS: A total of 398,043 patients were identified to have had the diagnosis of severe sepsis. Compared with patients admitted on weekends, patients admitted on weekdays had a lower 7-day mortality rate (adjusted odds ratio [OR] 0.89, 95% confidential interval [CI] 0.87-0.91), 14-day mortality rate (adjusted OR 0.92, 95% CI 0.90-0.93), and 28-day mortality rate (adjusted OR 0.97, 95% CI 0.95-0.98). This "weekend effect" was maintained every year throughout the 11-year study period. CONCLUSIONS: Patients with severe sepsis are more likely to die in the hospital if they were admitted on weekends than if they were admitted on weekdays.

Adult Status Epilepticus: A Review of the Prehospital and Emergency Department Management.

Seizures are a common presentation in the prehospital and emergency department setting and status epilepticus represents an emergency neurologic condition. The classification and various types of seizures are numerous. The objectives of this narrative literature review focuses on adult patients with a presentation of status epilepticus in the prehospital and emergency department setting. In summary, benzodiazepines remain the primary first line therapeutic agent in the management of status epilepticus, however, there are new agents that may be appropriate for the management of status epilepticus as second- and third-line pharmacological agents.

The incidence of ARDS and associated mortality in severe TBI using the Berlin definition.

BACKGROUND: The incidence of adult respiratory distress syndrome (ARDS) in severe traumatic brain injury (TBI) is poorly reported. Recently, a new definition for ARDS was proposed, the Berlin definition. The percentage of patients represented by TBI in the Berlin criteria study is limited. This study describes the incidence and associated mortality of ARDS in TBI patients. METHODS: The study was an analysis of the safety of erythropoietin administration and transfusion threshold on the incidence of ARDS in severe TBI patients. Three reviewers independently assessed all patients enrolled in the study for acute lung injury/ARDS using the Berlin and the American-European Consensus Conference (AECC) definitions. A Cox proportional hazards model was used to assess the relationship between ARDS and mortality and 6-month Glasgow Outcome Scale (GOS) score. RESULTS: Two hundred patients were enrolled in the study. Of the patients, 21% (41 of 200) and 26% (52 of 200) developed ARDS using the AECC and Berlin definitions, respectively, with a median time of 3 days (interquartile range, 3) after injury. ARDS by either definition was associated with increased mortality (p = 0.04) but not with differences in functional outcome as measured by the GOS score at 6 months. Adjusted analysis using the Berlin criteria showed an increased mortality associated with ADS (p = 0.01). CONCLUSION: Severe TBI is associated with an incidence of ARDS ranging from 20% to 25%. The incidence is comparable between the Berlin and AECC definitions. ARDS is associated with increased mortality in severe TBI patients, but further studies are needed to validate these findings. LEVEL OF EVIDENCE: Epidemiologic study, level II.

Daily home opioid use in adults with sickle cell disease: The PiSCES project.

BACKGROUND: Although opioid prescribing in sickle cell disease (SCD) can be controversial, little is published about patterns of opioid use. OBJECTIVE: To report on home opioid use among adults with SCD. DESIGN: Cohort study. PARTICIPANTS: Adults with SCD (n=219) who completed daily pain diaries for up to 6 months and had at least one home pain day. MAIN MEASURES: Use of long-acting or short-acting opioids, other analgesics, or adjuvants; the proportion of home days, home pain days, and home crisis days with opioid use; these two outcomes according to patient characteristics. KEY RESULTS: Patients used opioids on 12,311 (78 percent) of 15,778 home pain days. Eighty-five patients (38.8 percent) used long-acting opioids with or without short-acting opioids and 103 (47.0 percent) used only short-acting opioids. Twenty-one (9.6 percent) patients used only non-opioid analgesics and 10 (4.6 percent) used no analgesics. Both pain intensity and pain frequency were higher among opioid users (analysis of variance [ANOVA], p<0.0001). Opioid users used hydroxyurea more often than nonusers, even when controlling for mean pain on pain days. Among all patients, significant relationships were found between any opioid use and somatic symptom burden, SCD stress, negative coping, and physical and mental quality of life (QOL); the relationship with SCD stress and physical QOL remained when controlled for mean pain. Among opioid users, similar associations were found between frequency of opioid use and some disease-related and psychosocial variables. CONCLUSIONS: In this adult SCD sample, opioids were used by the majority of patients. Pain was the overwhelming characteristic associated with use, but disease-related and psychosocial variables were also associated.