Performance of the European Society of Cardiology 0/1-hour algorithm with high-sensitivity cardiac troponin T at 90 days among patients with known coronary artery disease.

BACKGROUND: The European Society of Cardiology (ESC) 0/1-h high sensitivity troponin T (hs-cTnT) algorithm does not differentiate risk based on known coronary artery disease (CAD: prior myocardial infarction [MI], coronary revascularization, or ≥ 70% coronary stenosis). We recently evaluated its performance among patients with known CAD at 30-days, but little is known about its longer-term risk prediction. The objective of this study is to determine and compare the performance of the algorithm at 90-days among patients with and without known CAD. METHODS: We performed a pre-planned subgroup analysis of the STOP-CP cohort, which prospectively enrolled ED patients ≥21 years old with symptoms suggestive of ACS without ST-elevation on initial ECG across 8 US sites (1/25/2017-9/6/2018). Participants with 0- and 1-h hs-cTnT measures (Roche, Basel, Switzerland) were stratified into rule-out, observe, and rule-in groups using the ESC 0/1-h algorithm. Algorithm performance was tested among patients with or without known CAD, as determined by the treating provider. The primary outcome was cardiac death or MI at 90-days. Fisher's exact tests were used to compare 90-day event and rule-out rates between patients with and without known CAD. Negative predictive values (NPVs) for 90-day cardiac death or MI with exact 95% confidence intervals were calculated and compared using Fisher's exact test. RESULTS: The STOP-CP study accrued 1430 patients, of which 31.4% (449/1430) had known CAD. Cardiac death or MI at 90 days was more common in patients with known CAD than in those without [21.2% (95/449) vs. 10.0% (98/981); p < 0.001]. Using the ESC 0/1-h algorithm, 39.6% (178/449) of patients with known CAD and 66.1% (648/981) of patients without known CAD were ruled-out (p < 0.001). Among rule-out patients, 90-day cardiac death or MI occurred in 3.4% (6/178) of patients with known CAD and 1.2% (8/648) without known CAD (p = 0.09). NPV for 90-day cardiac death or MI was 96.6% (95%CI 92.8-98.8) among patients with known CAD and 98.8% (95%CI 97.6-99.5) in patients without known CAD (p = 0.09). CONCLUSION: Patients with known CAD who were ruled-out using the ESC 0/1-h hs-cTnT algorithm had a high rate of missed 90-day cardiac events, suggesting that the ESC 0/1-h hs-cTnT algorithm may not be safe for use among patients with known CAD. TRIAL REGISTRATION: High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP; ClinicalTrials.gov: NCT02984436; https://clinicaltrials.gov/ct2/show/NCT02984436).

Derivation and validation of a high sensitivity troponin-T HEART pathway.

BACKGROUND: The HEART Pathway is widely used for chest pain risk stratification but has yet to be optimized for high sensitivity troponin T (hs-cTnT) assays. METHODS: We conducted a secondary analysis of STOP-CP, a prospective cohort study enrolling adult ED patients with symptoms suggestive of acute coronary syndrome at 8 sites in the United States (US). Patients had a 0- and 1-hour hs-cTnT measured and a HEAR score completed. A derivation set consisting of 729 randomly selected participants was used to derive a hs-cTnT HEART Pathway with rule-out, observation, and rule-in groups for 30-day cardiac death or myocardial infarction (MI). Optimal baseline and 1-hour troponin cutoffs were selected using generalized cross validation to achieve a negative predictive value (NPV) >99% for rule out and positive predictive value (PPV) >60% or maximum Youden index for rule-in. Optimal 0-1-hour delta values were derived using generalized cross validation to maximize the NPV for the rule-out group and PPV for the rule-in group. The hs-cTnT HEART Pathway performance was validated in the remaining cohort (n = 723). RESULTS: Among the 1452 patients, 30-day cardiac death or MI occurred in 12.7% (184/1452). Within the derivation cohort the optimal hs-cTnT HEART Pathway classified 36.5% (266/729) into the rule-out group, yielding a NPV of 99.2% (95% CI: 98.2-100) for 30-day cardiac death or MI. The rule-in group included 15.4% (112/729) with a PPV of 55.4% (95% CI: 46.2-64.6). In the validation cohort, the hs-cTnT HEART Pathway ruled-out 37.6% (272/723), of which 2 had 30-day cardiac death or MI, yielding a NPV of 99.3% (95% CI: 98.3-100). The rule-in group included 14.5% (105/723), yielding a PPV of 57.1% (95% CI: 47.7-66.6). CONCLUSIONS: A novel hs-cTnT HEART Pathway with serial 0- and 1-hour hs-cTnT measures has high NPV and moderate PPV for 30-day cardiac death or MI.

Diagnostic Performance of High-Sensitivity Cardiac Troponin T Strategies and Clinical Variables in a Multisite US Cohort.

BACKGROUND: European data support the use of low high-sensitivity troponin (hs-cTn) measurements or a 0/1-hour (0/1-h) algorithm for myocardial infarction to exclude major adverse cardiac events (MACEs) among patients in the emergency department with possible acute coronary syndrome. However, modest US data exist to validate these strategies. This study evaluated the diagnostic performance of an initial hs-cTnT measure below the limit of quantification (LOQ: 6 ng/L), a 0/1-h algorithm, and their combination with history, ECG, age, risk factors, and initial troponin (HEART) scores for excluding MACE in a multisite US cohort. METHODS: A prospective cohort study was conducted at 8 US sites, enrolling adult patients in the emergency department with symptoms suggestive of acute coronary syndrome and without ST-elevation on ECG. Baseline and 1-hour blood samples were collected, and hs-cTnT (Roche; Basel, Switzerland) was measured. Treating providers blinded to hs-cTnT results prospectively calculated HEART scores. MACE (cardiac death, myocardial infarction, and coronary revascularization) at 30 days was adjudicated. The proportion of patients with initial hs-cTnT measures below the LOQ and risk according to a 0/1-h algorithm was determined. The negative predictive value (NPV) was calculated for both strategies when used alone or with a HEART score. RESULTS: Among 1462 participants with initial hs-cTnT measures, 46.4% (678 of 1462) were women and 37.1% (542 of 1462) were Black with an age of 57.6±12.9 (mean±SD) years. MACEs at 30 days occurred in 14.4% (210 of 1462) of participants. Initial hs-cTnT measures below the LOQ occurred in 32.8% (479 of 1462), yielding an NPV of 98.3% (95% CI, 96.7-99.3) for 30-day MACEs. A low-risk HEART score with an initial hs-cTnT below the LOQ occurred in 20.1% (294 of 1462), yielding an NPV of 99.0% (95% CI, 97.0-99.8) for 30-day MACEs. A 0/1-h algorithm was complete in 1430 patients, ruling out 57.8% (826 of 1430) with an NPV of 97.2% (95% CI, 95.9-98.2) for 30-day MACEs. Adding a low HEART score to the 0/1-h algorithm ruled out 30.8% (441 of 1430) with an NPV of 98.4% (95% CI, 96.8-99.4) for 30-day MACEs. CONCLUSIONS: In a prospective multisite US cohort, an initial hs-cTnT below the LOQ combined with a low-risk HEART score has a 99% NPV for 30-day MACEs. The 0/1-h hs-cTnT algorithm did not achieve an NPV >99% for 30-day MACEs when used alone or with a HEART score. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02984436.

Length of Stay and Hospital Cost Reductions After Implementing Bedside Percutaneous Ultrasound Gastrostomy (PUG) in a Critical Care Unit.

Background: Critical care patients receive 50% of gastrostomy tubes placed in the United States. Several gastrostomy placement methods exist, however care processes remain variable and often lack health system cost effectiveness. No data exists on efficiency or cost impact of performing bedside percutaneous ultrasound gastrostomy (PUG) on patients with ventilator-dependent respiratory failure. This study's objective was to determine if implementing bedside PUG would positively impact efficiency and cost outcomes in intensive care unit (ICU) patients compared to usual care gastrostomy. Design and Methods: This is a retrospective cohort study of patients with ventilator-dependent respiratory failure who received a gastrostomy consult or procedure in the ICU. Patients received PUG or usual care gastrostomy, determined by the presiding attending's skillset, and both groups were compared across patients' demographics, clinical characteristics and outcomes. Primary outcomes were length of stay (LOS) and total hospital costs. Results: A total of 88 patients were included in the analysis, 45 patients in the PUG group and 43 in the usual care gastrostomy group. No differences were observed in demographic and clinical characteristics. Patients who received PUG had a significantly shorter mean ICULOS and hospital LOS, with reductions of 5.0 and 8.7 days, respectively. Total hospital costs were significantly reduced in the PUG group, with a cost savings of US $26,621 per patient. No differences in mortality or discharge disposition were observed. PUG patients received concomitant percutaneous dilatation tracheostomy (PDT) and PUG ("TPUG") 70% of the time, whereas no usual care patients received concomitant procedures. Off-hour procedures occurred in 53.3% of PUG and 4.6% of usual care gastrostomy. Conclusions: This study demonstrates bedside PUG leads to decreased LOS and total hospital costs in patients with ventilator-dependent respiratory failure. Hospital costs were significantly reduced with a per patient savings of $26,621 compared to usual care gastrostomy.

Patterns of opioid prescribing in emergency departments during the early phase of the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic was superimposed upon an ongoing epidemic of opioid use disorder and overdose deaths. Although the trend of opioid prescription patterns (OPP) had decreased in response to public health efforts before the pandemic, little is known about the OPP from emergency department (ED) clinicians during the COVID-19 pandemic. METHODS: We conducted a pre-post study of adult patients who were discharged from 13 EDs and one urgent care within our academic medical system between 01/01/2019 and 09/30/2020 using an interrupted time series (ITS) approach. Patient characteristics and prescription data were extracted from the single unified electronic medical record across all study sites. Prescriptions of opioids were converted into morphine equivalent dose (MED). We compared the "Covid-19 Pandemic" period (C19, 03/29/2020-9/30/2020) and the "Pre-Pandemic" period (PP, 1/19/2020-03/28/2020). We used a multivariate logistic regression to assess clinical factors associated with opioid prescriptions. RESULTS: We analyzed 361,794 ED visits by adult patients, including 259,242 (72%) PP and 102,552 (28%) C19 visits. Demographic information and percentages of patients receiving opioid prescriptions were similar in both groups. The median [IQR] MED per prescription was higher for C19 patients (70 [56-90]) than for PP patients (60 [60-90], P < 0.001). ITS demonstrated a significant trend toward higher MED prescription per ED visit during the pandemic (coefficient 0.11, 95% CI 0.05-0.16, P = 0.002). A few factors, that were associated with lower likelihood of opioid prescriptions before the pandemic, became non-significant during the pandemic. CONCLUSION: Our study demonstrated that emergency clinicians increased the prescribed amount of opioids per prescription during the COVID-19 pandemic compared to the pre-pandemic period. Etiologies for this finding could include lack of access to primary care and other specialties during the pandemic, or lower volumes allowing for emergency clinicians to identify who is safe to be prescribed opioids.

Bilateral Hyphema - An Unexpected Complication of Exercise Resistance Band Use: A Case Report.

BACKGROUND: Resistance bands commonly used for strength training exercise come with an unexpected risk for ocular trauma. CASE REPORT: In this report, we describe an unintended consequence of a 28-year-old man sustaining an unusual injury-bilateral hyphema-as a result of the use of elastic resistance bands. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Resistance bands are commonly used for strength training exercise and, in this case, a potentially severe, vision-threatening injury-traumatic hyphema-occurred. Traumatic hyphema occurs when blood pools in the anterior chamber of the eye, usually as the result of blunt force trauma or penetrating injury. Early recognition of this condition is imperative, as complications of traumatic hyphema, such as intraocular hypertension or rebleeding, can lead to permanent vision loss.

Not Feeling Swell: Superior Vena Cava (SVC) Syndrome Falsely Attributed to COVID-19 Vaccine Reaction.

BACKGROUND: The mass immunization campaign against Coronavirus disease 2019 (COVID-19) has resulted in more patients presenting to the emergency department (ED) with concern for a vaccine reaction. CASE REPORT: A 68-year-old man presented to the ED reporting an allergic reaction to the COVID-19 vaccine. He initially noted swelling of his face, neck, and right arm after receiving the first dose of the vaccine. After his second dose of the vaccine, the swelling became more pronounced and prompted him to seek care. On examination, he had fullness of the neck and engorgement of the left external jugular vein, which were exacerbated when the patient raised his arms above his head, consistent with Pemberton's sign. Apart from the swelling of the head and neck, there were no other findings consistent with an allergic reaction. The presence of Pemberton's sign prompted a computed tomography scan of the chest with contrast, which revealed a paratracheal mass measuring 4.5 × 2.0 cm with marked narrowing of the superior vena cava (SVC). The patient was admitted to the hospital for SVC syndrome, and further workup revealed a non-small cell lung cancer. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients may misattribute their symptoms to a COVID vaccine reaction when they are, in fact, experiencing a more serious underlying disease. This case highlights the importance of a thorough physical examination and maintaining a broad differential diagnosis. In this case, the presence of Pemberton's sign raised suspicion for SVC syndrome, and prompted further workup.

The Rapid Evaluation of COVID-19 Vaccination in Emergency Departments for Underserved Patients Study.

STUDY OBJECTIVE: Emergency departments (EDs) often serve vulnerable populations who may lack primary care and have suffered disproportionate COVID-19 pandemic effects. Comparing patients having and lacking a regular source of medical care and other ED patient characteristics, we assessed COVID-19 vaccine hesitancy, reasons for not wanting the vaccine, perceived access to vaccine sites, and willingness to get the vaccine as part of ED care. METHODS: This was a cross-sectional survey conducted from December 10, 2020, to March 7, 2021, at 15 safety net US EDs. Primary outcomes were COVID-19 vaccine hesitancy, reasons for vaccine hesitancy, and sites (including EDs) for potential COVID-19 vaccine receipt. RESULTS: Of 2,575 patients approached, 2,301 (89.4%) participated. Of the 18.4% of respondents who lacked a regular source of medical care, 65% used the ED as their usual source of health care. The overall rate of vaccine hesitancy was 39%; the range among the 15 sites was 28% to 58%. Respondents who lacked a regular source of medical care were more commonly vaccine hesitant than those who had a regular source of medical care (47% versus 38%, 9% difference, 95% confidence interval 4% to 14%). Other characteristics associated with greater vaccine hesitancy were younger age, female sex, Black race, Latinx ethnicity, and not having received an influenza vaccine in the past 5 years. Of the 61% who would accept a COVID-19 vaccine, 21% stated that they lacked a primary physician or clinic at which to receive it; the vast majority (95%) of these respondents would accept the COVID-19 vaccine as part of their care in the ED. CONCLUSION: ED patients who lack a regular source of medical care are particularly hesitant regarding COVID-19 vaccination. Most COVID-19 vaccine acceptors would accept it as part of their care in the ED. EDs may play pivotal roles in COVID-19 vaccine messaging and delivery to highly vulnerable populations.

Association of Resident Shift Length with Procedural Complications.

BACKGROUND: Training programs for resident physicians struggle to balance the need for clinical experience with the impact of fatigue on patient safety. The length of shifts worked by emergency medicine (EM) residents is likely an important determinant of resident fatigue. OBJECTIVE: Assess the impact of a longer clinical shift on procedural competency. METHODS: We conducted a retrospective chart review of arterial line placements, central venous catheterizations, tube thoracostomies, endotracheal intubations, and lumbar punctures performed by EM residents working 12-h shifts in the emergency department of an academic medical center over an academic year. We compared complication rates between procedures performed in the first 8 vs. the last 4 h of a 12-h shift. Procedures without complication were defined as successful on first-pass attempt and without a downstream mechanical or medical complication. Multivariable modified Poisson regression was used to simultaneously control for possible confounders affecting procedure success. RESULTS: We identified 548 eligible procedures: 307 performed in the first 8 h of a 12-h shift and 241 in the last 4 h. The complication rate across all procedures was higher in the last 4 h of the shift (pooled risk ratio 1.41, 95% confidence interval 1.18-1.67). This effect persisted when adjusting for potential confounders (adjusted risk ratio 1.42, 95% confidence interval 1.19-1.69). CONCLUSION: Overall, complication rates of included procedures performed by EM residents were higher during the last 4 vs. first 8 h of a 12-h shift. Training programs should consider the impact of resident fatigue on patient safety when making work schedules.

Clinical Practice Statement: What is the Emergency Department Management of Patients with Angioedema Secondary to an ACE-Inhibitor?

BACKGROUND: Angioedema is a complication that has been reported in up to 1.0% of individuals taking angiotensin-converting enzyme inhibitors (ACE-Is). Importantly, the onset of angioedema can occur anywhere from hours to several years after initiation of therapy with ACE-Is. Although most cases of ACE-I-induced angioedema (ACE-I-AE) are self-limiting, a major clinical concern is development of airway compromise, which can potentially require emergent airway management. The underlying pathophysiology of ACE-I-AE is incompletely understood, but is considered to be due in large part to excess bradykinin. Numerous medications have been proposed for the treatment of ACE-I-AE. This article is an update to the 2011 Clinical Practice Committee (CPC) statement from the American Academy of Emergency Medicine. METHODS: A literature search in PubMed was performed with search terms angioedema and ACE inhibitors from August 1, 2012 to May 13, 2019. Following CPC guidelines, articles written in English were identified and then underwent a structured review for evaluation. RESULTS: The search parameters resulted in 323 articles. The abstracts of these articles were assessed independently by the reviewers, who determined there were 63 articles that were specific to ACE-I-AE, of which 46 were deemed appropriate for grading in the final focused review. CONCLUSIONS: The primary focus for the treatment of ACE-I-AE is airway management. In the absence of high-quality evidence, no specific medication therapy is recommended for its treatment. If, however, the treating physician feels the patient's presentation is more typical of an acute allergic reaction or anaphylaxis, it may be appropriate to treat for those conditions. Any patient with suspected ACE-I-AE should immediately discontinue that medication.

Silent hypoxia: A harbinger of clinical deterioration in patients with COVID-19.

Patients infected with the SARS-CoV-2 virus can present with a wide variety of symptoms including being entirely asymptomatic. Despite having no or minimal symptoms, some patients may have markedly reduced pulse oximetry readings. This has been referred to as "silent" or "apathetic" hypoxia (Ottestad et al., 2020 [1]). We present a case of a 72-year-old male with COVID-19 syndrome who presented to the emergency department with minimal symptoms but low peripheral oxygen saturation readings. The patient deteriorated over the following days and eventually died as a result of overwhelming multi-organ system failure. This case highlights the utility of peripheral oxygen measurements in the evaluation of patients with SARS-CoV-2 infection. Self-monitoring of pulse oximetry by patients discharged from the emergency department is a potential way to identify patients needing to return for further evaluation.

Evaluation of Ketamine for Excited Delirium Syndrome in the Adult Emergency Department.

BACKGROUND: Excited delirium syndrome (ExDS) is characterized by delirium, agitation, and hyperadrenergic autonomic dysfunction. A guideline for ExDS management, which recommends the use of ketamine as a second-line agent, was implemented in our hospital's adult emergency department (ED). OBJECTIVE: The primary objective was to determine whether ketamine, 1 mg/kg intravenous (i.v.) or 2 mg/kg intramuscular (i.m.), is being used according to the ExDS guideline. Secondary objectives included evaluating the specific agents, routes, and dosages used to manage ExDS and the safety and efficacy of ketamine. METHODS: Single-center, retrospective chart review of patients who received ketamine for the management of ExDS in the ED. Efficacy was measured by documented Richmond Agitation Sedation Scale (RASS) scores. Safety was assessed through evaluation of vital signs and adverse effects. RESULTS: Thirty-one patients met inclusion criteria. Eight (25.8%) of them received ketamine for ExDS in adherence with all aspects of the guideline. Administration of ketamine led to a statistically significant decrease in median RASS score of 4 (interquartile range [IQR] 3 to 4) vs. 0 (IQR 2 to -1) (p = 0.001). There were no statistically significant differences in vital signs or RASS scores in our subgroup analyses of patients treated according to protocol and of those treated with ketamine, 2 mg/kg i.m. CONCLUSIONS: We found discordance between current practice and our department's ExDS guideline for patients managed with ketamine. Despite the lack of adherence to departmental guidelines and allowing for limitations of this analysis due to small sample size, the use of low-dose, 1 mg/kg i.v. or 2 mg/kg i.m., ketamine was effective and appears to be a reasonable option as second-line therapy for ExDS.

Emergency department management of patients with sickle cell disease.

Sickle cell disease is a chronic hematologic disease that affects over 100,000 people in the United States. Many of these patients will present to the emergency department seeking treatment for an acute complication. Vaso-occlusive crisis, the most common recurring complication, can be difficult to manage because of the stigma patients face surrounding management of their pain. Patients with sickle cell disease presenting with conditions such as pain, infection, respiratory distress, stroke, or priapism must be given special consideration, as management can differ from that of the general population. This review evaluates the current guidelines and literature on acute complications related to sickle cell disease to dispel misconceptions about seemingly harmless interventions and provide clarification on those that are more controversial. Novel treatments that may have future impact on the management of patients with sickle cell disease are also reviewed.

Sex and race differences in the performance of the European Society of Cardiology 0/1-h algorithm with high-sensitivity troponin T.

The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) European Society of Cardiology (ESC) 0/1-h algorithm in sex and race subgroups of US Emergency Department (ED) patients is unclear. A pre-planned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 1-h hs-cTnT measures from eight US EDs (1/2017 to 9/2018) were stratified into rule-out, observation, and rule-in zones using the hs-cTnT ESC 0/1 algorithm. The primary outcome was adjudicated 30-day cardiac death or MI. The proportion with the primary outcome in each zone was compared between subgroups with Fisher's exact tests. The negative predictive value (NPV) of the ESC 0/1 rule-out zone for 30-day CDMI was calculated and compared between subgroups using Fisher's exact tests. Of the 1422 patients enrolled, 54.2% (770/1422) were male and 58.1% (826/1422) white with a mean age of 57.6 ± 12.8 years. At 30 days, cardiac death or myocardial infarction (MI) occurred in 12.9% (183/1422) of participants. Among patients stratified to the rule-out zone, 30-day cardiac death or MI occurred in 1.1% (5/436) of women versus 2.1% (8/436) of men (p = .40) and 1.2% (4/331) of non-white patients versus 1.8% (9/490) of white patients (p = .58). The NPV for 30-day cardiac death or MI was similar among women versus men (98.9% [95% confidence interval, CI: 97.3-99.6] vs. 97.9% [95% CI: 95.9-99.1]; p = .40) and among white versus non-white patients (98.8% [95% CI: 96.9-99.7] vs. 98.2% [95% CI: 96.5-99.2]; p = .39). NPVs <99% in each subgroup suggest the hs-cTnT ESC 0/1-h algorithm may not be safe for use in US EDs. Trial Registration: High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP; ClinicalTrials.gov: NCT02984436; https://clinicaltrials.gov/ct2/show/NCT02984436).

Performance of the 0/2-hour high-sensitivity cardiac troponin T diagnostic protocol in a multisite United States cohort.

BACKGROUND: The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) 0/2-h algorithm is unclear among U.S. emergency department (ED) patients with acute chest pain. METHODS: A preplanned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 2-h hs-cTnT measures prospectively enrolled at eight U.S. EDs from January 2017 to September 2018 were stratified into rule-out, observation, and rule-in zones using the hs-cTnT 0/2-h algorithm alone and combined with the history, electrocardiogram, age, and risk factor (HEAR) score. The primary outcome was adjudicated 30-day cardiac death or myocardial infarction (CDMI). The sensitivity and negative predictive value (NPV) of the 0/2-h rule-out zone and specificity and positive predictive value (PPV) of the rule-in zone for 30-day CDMI were calculated. RESULTS: Of the 1307 patients accrued, 53.6% (700/1307) were male and 58.6% (762/1307) were White, with a mean ± SD age of 57.5 ± 12.7 years. At 30 days, CDMI occurred in 12.9% (168/1307) of participants. The 0/2-h algorithm ruled out 61.4% (802/1307) of patients. Among rule-out patients, 1.9% (15/802) experienced 30-day CDMI, resulting in a sensitivity of 91.1% (95% confidence interval [CI] 85.7%-94.9%) and NPV of 98.1% (95% CI 96.9%-98.9%). The 0/2-h algorithm ruled in 12.4% (162/1307) patients of whom 61.7% (100/162) experienced 30-day CDMI. The rule-in zone specificity was 94.6% (95% CI 93.1%-95.8%) and PPV was 61.7% (95% CI 53.8%-69.2%) for 30-day CDMI. The 0/2-h algorithm combined with HEAR score ruled out 30.7% (401/1307) of patients with a sensitivity and NPV for 30-day CDMI of 98.2% (95% CI 94.9%-99.6%) and 99.3% (95% CI 97.8%-99.8%), respectively. CONCLUSIONS: The hs-cTnT 0/2-h algorithm ruled out most patients. With NPV of <99% for 30-day CDMI, the hs-cTnT 0/2-h algorithm, many emergency physicians may not consider it safe to use for U.S. ED patients. When combined with a low-risk HEAR score, NPV was >99% for 30-day CDMI at the cost of reduced efficacy.

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.

Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides immunologic DHRs into 4 major pathophysiologic categories based on immunologic mechanism. Anaphylaxis is a Type I hypersensitivity reaction that requires immediate recognition and treatment. Severe cutaneous adverse reactions (SCARs) are a group of dermatologic diseases that result from a Type IV hypersensitivity process and include drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). Other types of reactions are slow to develop and do not always require rapid treatment. Emergency physicians should have a good understanding of these various types of drug hypersensitivity reactions and how to approach the patient regarding evaluation and treatment.

Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema.

Angioedema is a well-recognized and potentially lethal complication of angiotensin-converting enzyme inhibitor (ACEi) therapy. In ACEi-induced angioedema, bradykinin accumulates due to a decrease in its metabolism by ACE, the enzyme that is primarily responsible for this function. The action of bradykinin at bradykinin type 2 receptors leads to increased vascular permeability and the accumulation of fluid in the subcutaneous and submucosal space. Patients with ACEi-induced angioedema are at risk for airway compromise because of the tendency for the face, lips, tongue, and airway structures to be affected. The emergency physician should focus on airway evaluation and management when treating patients with ACEi-induced angioedema.