Identifying Clinical Research Priorities in Adult Pulmonary and Critical Care. NHLBI Working Group Report.

Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the NHLBI. Decades of clinical research in acute respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have yielded improvements in supportive care, which have translated into improved patient outcomes. Novel therapeutics have largely failed to translate from promising preclinical findings into improved patient outcomes in late-phase clinical trials. Recent advances in personalized medicine, "big data," causal inference using observational data, novel clinical trial designs, preclinical disease modeling, and understanding of recovery from acute illness promise to transform the methods of pulmonary and critical care clinical research. To assess the current state of, research priorities for, and future directions in adult pulmonary and critical care research, the NHLBI assembled a multidisciplinary working group of investigators. This working group identified recommendations for future research, including 1) focusing on understanding the clinical, physiological, and biological underpinnings of heterogeneity in syndromes, diseases, and treatment response with the goal of developing targeted, personalized interventions; 2) optimizing preclinical models by incorporating comorbidities, cointerventions, and organ support; 3) developing and applying novel clinical trial designs; and 4) advancing mechanistic understanding of injury and recovery to develop and test interventions targeted at achieving long-term improvements in the lives of patients and families. Specific areas of research are highlighted as especially promising for making advances in pneumonia, acute hypoxemic respiratory failure, and acute respiratory distress syndrome.

Disability After Minor Stroke and Transient Ischemic Attack in the POINT Trial.

Background and Purpose- While combination aspirin and clopidogrel reduces recurrent stroke compared with aspirin alone in patients with transient ischemic attack (TIA) or minor stroke, the effect on disability is uncertain. Methods- The POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) randomized patients with TIA or minor stroke (National Institutes of Health Stroke Scale score ≤3) within 12 hours of onset to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel versus aspirin alone. The primary outcome measure was a composite of stroke, myocardial infarction, or vascular death. We performed a post hoc exploratory analysis to examine the effect of treatment on overall disability (defined as modified Rankin Scale score >1) at 90 days, as well as disability ascribed by the local investigator to index or recurrent stroke. We also evaluated predictors of disability. Results- At 90 days, 188 of 1964 (9.6%) of patients enrolled with TIA and 471 of 2586 (18.2%) of those enrolled with stroke were disabled. Overall disability was similar between patients assigned DAPT versus aspirin alone (14.7% versus 14.3%; odds ratio, 0.97 [95% CI, 0.82-1.14]; P=0.69). However, there were numerically fewer patients with disability in conjunction with a primary outcome event in the DAPT arm (3.0% versus 4.0%; odds ratio, 0.73 [95% CI, 0.53-1.01]; P=0.06) and significantly fewer patients in the DAPT arm with disability attributed by the investigators to either the index event or recurrent stroke (5.9% versus 7.4%; odds ratio, 0.78 [95% CI, 0.62-0.99]; P=0.04). Notably, disability attributed to the index event accounted for the majority of this difference (4.5% versus 6.0%; odds ratio, 0.74 [95% CI, 0.57-0.96]; P=0.02). In multivariate analysis, age, subsequent ischemic stroke, serious adverse events, and major bleeding were significantly associated with disability in TIA; for those with stroke, female sex, hypertension, or diabetes mellitus, National Institutes of Health Stroke Scale score, recurrent ischemic stroke, subsequent myocardial infarction, and serious adverse events were associated with disability. Conclusions- In addition to reducing recurrent stroke in patients with acute minor stroke and TIA, DAPT might reduce stroke-related disability. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00991029.

A brief assessment of capacity to consent instrument in acutely intoxicated emergency department patients.

OBJECTIVE: The aim of this study was to determine to what extent acute alcohol intoxication effects capacity to assent, consent, or refuse research participation. METHODS: This was a prospective, observation study performed at our inner city, county hospital with >100,000 annual emergency department visits. Non-pregnant, English speaking patients older than 18 with evidence of acute alcohol intoxication were considered eligible. After medical screening, a trained research associate presented the study version of the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) tool. The primary outcome was the number of patients able to correctly respond to all 10 questions. RESULTS: Of 642 screened patients, 415 patients were enrolled and completed the tool. The mean alcohol concentration was 227mg/dL (range 25-500mg/dL). Sixteen patients (3.9%) answered all 10 questions correctly; by definition of the UBACC, these patients were deemed to possess capacity to consent. Mean alcohol concentrations in the capacity group were lower than in those lacking capacity; 182mg/dL (SD 6.7) versus 229mg/dL, (SD 7.9). Of the 287 patients who were interviewed upon sobriety at discharge, 182 patients (63.4%) did not recall completing the questionnaire. CONCLUSIONS: While intoxicated emergency department patients are able to complete the questionnaire, the majority do not possess capacity to provide informed consent to research. A minority of participants remember involvement once they have achieved sobriety, exception from informed consent protocols are needed to perform emergency research in this population.

Impact of individual clinical outcomes on trial participants' perspectives on enrollment in emergency research without consent.

BACKGROUND: Evidence suggests that patients are generally accepting of their enrollment in trials for emergency care conducted under exception from informed consent. It is unknown whether individuals with more severe initial injuries or worse clinical outcomes have different perspectives. Determining whether these differences exist may help to structure post-enrollment interactions. METHODS: Primary clinical data from the Progesterone for the Treatment of Traumatic Brain Injury trial were matched to interview data from the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study. Answers to three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study were analyzed in the context of enrolled patients' initial injury severity (initial Glasgow Coma Scale and Injury Severity Score) and principal clinical outcomes (Extended Glasgow Outcome Scale and Extended Glasgow Outcome Scale relative to initial injury severity). The three key questions from Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study addressed participants' general attitude toward inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial (general trial inclusion), their specific attitude toward being included in Progesterone for the Treatment of Traumatic Brain Injury trial under the exception from informed consent (personal exception from informed consent enrollment), and their attitude toward the use of exception from informed consent in the Progesterone for the Treatment of Traumatic Brain Injury trial in general (general exception from informed consent enrollment). Qualitative analysis of interview transcripts was performed to provide contextualization and to determine the extent to which respondents framed their attitudes in terms of clinical experience. RESULTS: Clinical data from Progesterone for the Treatment of Traumatic Brain Injury trial were available for all 74 patients represented in the Patients' Experiences in Emergency Research-Progesterone for the Treatment of Traumatic Brain Injury study (including 46 patients for whom the surrogate was interviewed due to the patient's cognitive status or death). No significant difference was observed regarding acceptance of general trial inclusion or acceptance of general exception from informed consent enrollment between participants with favorable neurological outcomes and those with unfavorable outcomes relative to initial injury. Agreement with personal enrollment in Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent, however, was significantly higher among participants with favorable outcomes compared to those with unfavorable outcomes (89% vs 59%, p = 0.003). There was also a statistically significant relationship between more severe initial injury and increased acceptance of personal exception from informed consent enrollment ( p = 0.040) or general exception from informed consent use ( p = 0.034) in Progesterone for the Treatment of Traumatic Brain Injury trial. Many individuals referenced personal experience as a basis for their attitudes, but these references were not used to support negative views. CONCLUSION: Patients and surrogates of patients with unfavorable clinical outcomes were somewhat less accepting of their own inclusion in the Progesterone for the Treatment of Traumatic Brain Injury trial under exception from informed consent than were patients or surrogates of patients with favorable clinical outcomes. These findings suggest a need to identify optimal strategies for communicating with patients and their surrogates regarding exception from informed consent enrollment when clinical outcomes are poor.

Patients' perspectives of enrollment in research without consent: the patients' experiences in emergency research-progesterone for the treatment of traumatic brain injury study.

OBJECTIVE: Research in acute illness often requires an exception from informed consent. Few studies have assessed the views of patients enrolled in exception from informed consent trials. This study was designed to assess the views of patients and their surrogates of exception from informed consent enrollment within the context of a randomized, placebo-controlled trial of an investigational agent for traumatic brain injury. DESIGN: Interactive interview study. SETTING: Nested within the Progesterone for the Treatment of Traumatic Brain Injury trial, a Phase III randomized controlled trial in acute traumatic brain injury. SUBJECTS: Patients and surrogates (for patients incapable of being interviewed) enrolled in Progesterone for the Treatment of Traumatic Brain Injury under exception from informed consent at 12 sites. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Interviews focused on respondents' acceptance of exception from informed consent enrollment in Progesterone for the Treatment of Traumatic Brain Injury, use of placebo and randomization, understanding of major study elements, and views regarding regulatory protections. Descriptive statistical analysis was performed; textual data were analyzed thematically. Eighty-five individuals were interviewed. Eighty-four percent had positive attitudes toward Progesterone for the Treatment of Traumatic Brain Injury inclusion. Seventy-eight percent found their inclusion under exception from informed consent acceptable, and 72% found use of exception from informed consent in Progesterone for the Treatment of Traumatic Brain Injury acceptable in general. Only two respondents clearly disagreed with both personal and general exception from informed consent enrollment. The most common concerns (26%) related to absence of consent. Eighty percent and 92% were accepting of placebo use and randomization, respectively. Although there were few black respondents (n = 11), they were less accepting of personal exception from informed consent enrollment than white respondents (55% vs 83%; p = 0.0494). CONCLUSIONS: Acceptance of exception from informed consent in this placebo-controlled trial of an investigational agent was high and exceeded acceptance among community consultation participants. Exception from informed consent enrollment appears generally consistent with patients' preferences.

Consulting communities when patients cannot consent: a multicenter study of community consultation for research in emergency settings.

OBJECTIVES: To assess the range of responses to community consultation efforts conducted within a large network and the impact of different consultation methods on acceptance of exception from informed consent research and understanding of the proposed study. DESIGN: A cognitively pretested survey instrument was administered to 2,612 community consultation participants at 12 U.S. centers participating in a multicenter trial of treatment for acute traumatic brain injury. SETTING: Survey nested within community consultation for a phase III randomized controlled trial of treatment for acute traumatic brain injury conducted within a multicenter trial network and using exception from informed consent. SUBJECTS: Adult participants in community consultation events. INTERVENTIONS: Community consultation efforts at participating sites. MEASUREMENTS AND MAIN RESULTS: Acceptance of exception from informed consent in general, attitude toward personal exception from informed consent enrollment, and understanding of the study content were assessed. Fifty-four percent of participants agreed exception from informed consent enrollment was acceptable in general in the proposed study; 71% were accepting of personal exception from informed consent enrollment. Participants in interactive versus noninteractive community consultation events were more accepting of exception from informed consent in general (63% vs 49%) and personal exception from informed consent inclusion (77% vs 67%). Interactive community consultation participants had high-level recall of study content significantly more often than noninteractive consultation participants (77% vs 67%). Participants of interactive consultation were more likely to recall possible study benefits (61% vs 45%) but less likely to recall potential risks (56% vs 69%). CONCLUSIONS: Interactive community consultation methods were associated with increased acceptance of exception from informed consent and greater overall recall of study information but lower recall of risks. There was also significant variability in exception from informed consent acceptance among different interactive consultation events. These findings have important implications for institutional review board and investigators conducting exception from informed consent research and for community engagement efforts in research more generally.

Feasibility of bedside thoracic ultrasound in the helicopter emergency medical services setting.

INTRODUCTION: Bedside thoracic ultrasound has been shown to be a valuable diagnostic tool in the emergency department. The purpose of this study was to evaluate the feasibility of bedside thoracic ultrasound in the prehospital HEMS setting. SETTING: Air ambulance helicopters during patient transportation. METHODS: This was a prospective pilot study. 71 consecutive, nonpregnant patients over 18 years old were enrolled. While in flight, providers completed limited bedside thoracic ultrasounds with the patient supine and recorded their interpretation of the presence or absence of the ultrasonographic sliding lung sign on a closed data-set instrument. RESULTS: 41 (58%) of the eligible patients had a recorded thoracic ultrasound acquired in flight. The level of agreement in image interpretation between the flight crew and expert reviewer was substantial (Kappa 0.67, CI 0.44-0.90). The reviewer rated 54% of all images as "good" in quality. The most common reason cited for not completing the ultrasound was lack of enough provider time or space limitations within the aircraft cabin. CONCLUSION: The results of this study suggest that, with limited training, bedside thoracic ultrasound image acquisition and interpretation for the sliding lung sign in the HEMS setting is feasible.

Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial.

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04312009.

Emergency medicine in Japan: past, present, and future.

Quite a few changes and challenges have arisen in society in general as technology has advanced and the aging population has increased. These can lead to the recognition of the shortcomings of a society's traditional systems and the various changes that are needed, especially in providing emergency medical care. A super-aged society has been developing in Japan, and the emergency care system needs to change according to these new demographics and society's needs. The focus has been shifting from critical care and trauma to medical and surgical conditions involving the elderly. Challenges in triage, ambulance diversion, and staffing are discussed in this review. Possible solutions currently underway, such as a public helpline, smartphone app system, coordination by designated hospitals, and universal coverage/government support, are discussed as future directions. Emergency medicine in Japan needs to develop in a more flexible way to meet the upcoming robust challenges of the changing demographics.

Randomized Double-blind Trial of Intramuscular Droperidol, Ziprasidone, and Lorazepam for Acute Undifferentiated Agitation in the Emergency Department.

BACKGROUND: The optimal agent to treat acute agitation in the emergency department (ED) has not been determined. The objective of this study was to compare the effectiveness and safety of intramuscular droperidol, ziprasidone, and lorazepam for acute agitation in the ED. METHODS: This was a randomized, double-blind trial of ED patients with acute agitation requiring parenteral sedation. The study was conducted under exception from informed consent (21 CFR 50.24) from July 2004 to March 2005. Patients were randomized to receive 5 mg of droperidol, 10 mg of ziprasidone, 20 mg of ziprasidone, or 2 mg of lorazepam intramuscularly. We recorded Altered Mental Status Scale (AMSS) scores, nasal end-tidal carbon dioxide (ETCO2 ), and pulse oximetry (SpO2 ) at 0, 15, 30, 45, 60, 90, and 120 minutes as well as QTc durations and dysrhythmias. Respiratory depression was defined as a change in ETCO2 consistent with respiratory depression or SpO2  < 90%. The primary outcome was the proportion of patients adequately sedated (AMSS ≤ 0) at 15 minutes. RESULTS: We enrolled 115 patients. Baseline AMSS scores were similar between groups. For the primary outcome, adequate sedation at 15 minutes, droperidol administration was effective in 16 of 25 (64%) patients, compared to seven of 28 (25%) for 10 mg of ziprasidone, 11 of 31 (35%) for 20 mg of ziprasidone, and nine of 31 (29%) for lorazepam. Pairwise comparisons revealed that droperidol was more effective that the other medications, with 39% (95% confidence interval [CI] = 3% to 54%) more compared to 20 mg of ziprasidone and 33% (95% CI = 8% to 58%) more compared to lorazepam. There was no significant difference between groups in need of additional rescue sedation. Numerically, respiratory depression was lower with droperidol (3/25 [12%]) compared to 10 mg of ziprasidone (10/28 [36%]), 20 mg of ziprasidone (12/31 [39%]), or lorazepam (15/31 [48%]). One patient receiving 20 mg of ziprasidone required intubation to manage an acute subdural hematoma. No patients had ventricular dysrhythmias. QTc durations were similar in all groups. CONCLUSIONS: Droperidol was more effective than lorazepam or either dose of ziprasidone for the treatment of acute agitation in the ED and caused fewer episodes of respiratory depression.

A multi-center phase II randomized clinical trial of losartan on symptomatic outpatients with COVID-19.

BACKGROUND: The SARS-CoV-2 virus enters cells via Angiotensin-converting enzyme 2 (ACE2), disrupting the renin-angiotensin-aldosterone axis, potentially contributing to lung injury. Treatment with angiotensin receptor blockers (ARBs), such as losartan, may mitigate these effects, though induction of ACE2 could increase viral entry, replication, and worsen disease. METHODS: This study represents a placebo-controlled blinded randomized clinical trial (RCT) to test the efficacy of losartan on outpatients with COVID-19 across three hospital systems with numerous community sites in Minnesota, U.S. Participants included symptomatic outpatients with COVID-19 not already taking ACE-inhibitors or ARBs, enrolled within 7 days of symptom onset. Patients were randomized to 1:1 losartan (25 mg orally twice daily unless estimated glomerular filtration rate, eGFR, was reduced, when dosing was reduced to once daily) versus placebo for 10 days, and all patients and outcome assesors were blinded. The primary outcome was all-cause hospitalization within 15 days. Secondary outcomes included functional status, dyspnea, temperature, and viral load. (clinicatrials.gov, NCT04311177, closed to new participants). FINDINGS: From April to November 2020, 117 participants were randomized 58 to losartan and 59 to placebo, and all were analyzed under intent to treat principles. The primary outcome did not differ significantly between the two arms based on Barnard's test [losartan arm: 3 events (5.2% 95% CI 1.1, 14.4%) versus placebo arm: 1 event (1.7%; 95% CI 0.0, 9.1%)]; proportion difference -3.5% (95% CI -13.2, 4.8%); p = 0.32]. Viral loads were not statistically different between treatment groups at any time point. Adverse events per 10 patient days did not differ signifcantly [0.33 (95% CI 0.22-0.49) for losartan vs. 0.37 (95% CI 0.25-0.55) for placebo]. Due to a lower than expected hospitalization rate and low likelihood of a clinically important treatment effect, the trial was terminated early. INTERPRETATION: In this multicenter blinded RCT for outpatients with mild symptomatic COVID-19 disease, losartan did not reduce hospitalizations, though assessment was limited by low event rate. Importantly, viral load was not statistically affected by treatment. This study does not support initiation of losartan for low-risk outpatients.

Nucleic-acid amplification testing of urine vs. patient complaint-driven evaluation.

The present pilot study compared the ability of a conventional patient complaint-driven approach to that of nucleic-acid amplification testing (NAAT) of urine to identify those individuals among an adult, urban, Emergency Department (ED) population infected with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Urine for NAAT was collected for testing after individuals had completed a questionnaire and before being seen by a physician. A total of 614 subjects were enrolled, and complete physical examinations were performed on 348 (56.6%) individuals, with women being significantly more likely to receive such an evaluation (odds ratio [OR] 3.09; 95% confidence interval [CI] 1.96-4.86); p < 0.001). A total of 153 (24.9%) of the study cohort tested positive for a least one sexually transmitted disease (STD), and only a reported history of STD (OR 1.74; 95% CI (1.18-2.57); p = 0.005) and a history of a new sexual partner in the last 3 months (OR 1.79; 95% CI 1.13-2.82); p = 0.012) were predictive of a positive STD test. NAAT of urine samples on patients who did not receive a complete physical examination resulted in a 33% (51/153) increase in diagnostic yield in this cohort of ED attendees.

The Incidence of QT Prolongation and Torsades des Pointes in Patients Receiving Droperidol in an Urban Emergency Department.

INTRODUCTION: Droperidol carries a boxed warning from the United States Food and Drug Administration for QT prolongation and torsades des pointes (TdP). After a six-year hiatus, droperidol again became widely available in the US in early 2019. With its return, clinicians must again make decisions regarding the boxed warning. Thus, the objective of this study was to report the incidence of QT prolongation or TdP in patients receiving droperidol in the ED. METHODS: Patients receiving droperidol at an urban Level I trauma center from 1997-2001 were identified via electronic health record query. All patients were reviewed for cardiac arrest. We reviewed electrocardiogram (ECG) data for both critically-ill and noncritical patients and recorded Bazett's corrected QT intervals (QTc). ECGs from critically-ill patients undergoing resuscitation were further risk-stratified using the QT nomogram. RESULTS: Of noncritical patients, 15,374 received 18,020 doses of droperidol; 2,431 had an ECG. In patients with ECGs before and after droperidol, the mean QTc was 424.3 milliseconds (ms) (95% confidence interval [CI], 419.7-428.9) before and 427.6 ms (95% CI, 424.3-430.9), after droperidol (n = 170). Regarding critically-ill patients, 1,172 received droperidol and 396 had an ECG. In the critically-ill group with ECGs before and after droperidol mean QTc was 435.7 ms (95% CI, 426.7-444.7) before and 435.8 ms (95% CI, 427.5-444.1) after droperidol (n = 114). Of 337 ECGs suitable for plotting on the QT nomogram, 13 (3.8%) were above the "at-risk" line; 3/136 (2.2%; 95% CI, 0.05-6.3%) in the before group, and 10/202 (4.9%; 95% CI, 2.4%-8.9%) in the after group. A single case of TdP occurred in a patient with multiple risk factors that did not reoccur after a droperidol rechallenge. Thus, the incidence of TdP was 1/16,546 (0.006%; 95% CI, 0.00015 - 0.03367%). CONCLUSION: We found the incidence of QTc prolongation and TdP in ED patients receiving droperidol to be extremely rare. Our data suggest the FDA "black box warning" is overstated, and that close ECG monitoring is useful only in high-risk patients.

The prevalence of injury of any type in an urban emergency department population.

BACKGROUND: National estimates of injury prevalence in the Emergency Department (ED) are based on medical record review and vary considerably. By using a more robust approach to surveillance, we (1) determine the prevalence of injury of any type in an urban ED population and (2) explore the association between violence-related injury and personal characteristics of injury victims. METHODS: This cross-sectional study was performed at an urban level I trauma center from June to August, 2005. We prospectively screened 4,246 consecutive ED patients for injury during a randomized schedule of shifts totaling 336 hours. The ED record of each injured patient was reviewed to catalogue injury type and intent (International Classification of External Causes of Injury, Short Form) as well as to estimate injury severity (New Injury Severity Score). We interviewed noncritically injured, adult patients who provided consent to collect demographic (race, income, and education) and personal information (substance abuse, domestic violence, handgun ownership, and homelessness). We sought independent associations between these variables and violence-related injury in an exploratory analysis using multivariate logistic regression. RESULTS: Injury contributed to 1,036 of 4,246 ED visits (24.4%, 95% confidence interval [CI], 23.1-25.7%). Eleven percent of injured patients were admitted to the hospital and two patients died in the ED. The majority of patients (75%) suffered minor injury. Among the 434 injured patients consenting to interview, the prevalence of established injury risk factors, such as substance use or handgun ownership, varied by gender. The adjusted odds of violence-related injury among this subset of patients were increased for males (odds ratio [OR], 2.22; 95% CI, 1.17-4.23), patients with an annual income less than $5,000 (OR, 2.85; 95% CI, 1.64-4.97), those reporting a history of domestic violence (OR, 2.69; 95% CI, 1.43-5.07), and heavy alcohol users (OR, 1.79; 95% CI, 1.01-3.19). CONCLUSION: One in four ED visits to this urban, county hospital is due, at least in part, to injury. Patient characteristics associated with violence-related injury may generate hypotheses for further study.

The association of a decreased level of awareness and blood alcohol concentration with both agitation and sedation in intoxicated patients in the ED.

OBJECTIVE: This study was conducted to compare the level of awareness as determined by serial bispectral index (BIS) electroencephalogram scores to a standardized Altered Mental Status (AMS) scale used to define a patient's clinical level of agitation or sedation, and the patient's concurrent breath/blood alcohol concentration (BAC). METHODS: This was an institutional review board-approved, prospective observational study of a convenience sample of patients who presented to the emergency department (ED) with the chief complaint of ethanol (ETOH) intoxication between July 19, 2003, and March 27, 2004. The AMS scale is a 9-point scale: -4 is unresponsive, 0 is normal examination, and +4 is extremely agitated. After ETOH was detected by breath analyzer, enrolled patients had a BIS monitor probe applied to their forehead. Baseline BAC, BIS, and AMS scores were recorded independently of the patients' caregivers. Bispectral index and AMS scores were repeated every 20 minutes for 1 hour. The patient's diagnosis, disposition, (any) complications, and total time in department were recorded. RESULTS: Ninety-eight patients were enrolled in the study. The median presenting AMS score was -1. The mean total time in department was 402.6 minutes (SD, 196.4; range, 246-906 minutes). The mean presenting BIS score was 77.6 (SD, 17.9; range, 26-98). The mean presenting BAC was 0.229 (SD, 0.07; range, 0.049-0.43). The mean BIS index varied from 59.6 +/- 16.9 for AMS scores of -4, to 96.3 +/- 2.7 for AMS scores of 0, to 90.5 +/- 4.9 for AMS scores of 4. The AMS scale correlated with the BIS scale (Spearman's rho = 0.67, P < or = .001), but did not correlate with BAC (Spearman's rho = -0.14, P = 0.15). CONCLUSIONS: Changes in the AMS scale corresponded to changes in the BIS index score. A decreased level of awareness, as determined on the BIS index, was observed in patients who were either agitated or sedated by the AMS. We conclude that both agitated and sedated patients with ETOH intoxication show decreases in their level of awareness. Therefore, the AMS scale, which includes both agitation and sedation, is a valid measure of a patient's decreased level of awareness.

Randomizing Patients without Consent: Waiver vs Exception from Informed Consent.

Cole JB , Ho JD , Biros MH . Randomizing patients without consent: waiver vs exception from informed consent. Prehosp Disaster Med. 2016;31(4):457-458.

Balancing ethical goals in challenging individual participant scenarios occurring in a trial conducted with exception from informed consent.

In 1996, federal regulations were put into effect that allowed enrollment of critically ill or injured patients into Food and Drug Administration (FDA)-regulated clinical trials using an exception from informed consent (EFIC) under narrowly prescribed research circumstances. Despite the low likelihood that a legally authorized representative (LAR) would be present within the interventional time frame, the EFIC regulations require the availability of an informed consent process, to be applied if an LAR is present and able to provide prospective consent for patient enrollment into the trial. The purpose of this article is to describe a series of unanticipated consent-related questions arising when a potential surrogate decision-maker appeared to be available at the time of patient enrollment into a trial proceeding under EFIC.