Early Physician Gestalt Versus Usual Screening Tools for the Prediction of Sepsis in Critically Ill Emergency Patients.

STUDY OBJECTIVE: Compare physician gestalt to existing screening tools for identifying sepsis in the initial minutes of presentation when time-sensitive treatments must be initiated. METHODS: This prospective observational study conducted with consecutive encounter sampling took place in the emergency department (ED) of an academic, urban, safety net hospital between September 2020 and May 2022. The study population included ED patients who were critically ill, excluding traumas, transfers, and self-evident diagnoses. Emergency physician gestalt was measured using a visual analog scale (VAS) from 0 to 100 at 15 and 60 minutes after patient arrival. The primary outcome was an explicit sepsis hospital discharge diagnosis. Clinical data were recorded for up to 3 hours to compare Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), quick SOFA (qSOFA), Modified Early Warning Score (MEWS), and a logistic regression machine learning model using Least Absolute Shrinkage and Selection Operator (LASSO) for variable selection. The screening tools were compared using receiver operating characteristic analysis and area under the curve calculation (AUC). RESULTS: A total of 2,484 patient-physician encounters involving 59 attending physicians were analyzed. Two hundred seventy-five patients (11%) received an explicit sepsis discharge diagnosis. When limited to available data at 15 minutes, initial VAS (AUC 0.90; 95% confidence interval [CI] 0.88, 0.92) outperformed all tools including LASSO (0.84; 95% CI 0.82 to 0.87), qSOFA (0.67; 95% CI 0.64 to 0.71), SIRS (0.67; 95% 0.64 to 0.70), SOFA (0.67; 95% CI 0.63 to 0.70), and MEWS (0.66; 95% CI 0.64 to 0.69). Expanding to data available at 60 minutes did not meaningfully change results. CONCLUSION: Among adults presenting to an ED with an undifferentiated critical illness, physician gestalt in the first 15 minutes of the encounter outperformed other screening methods in identifying sepsis.

Multi-institutional intervention to improve patient perception of physician empathy in emergency care.

BACKGROUND: Physician empathy has been linked to increased patient satisfaction, improved patient outcomes and reduced provider burnout. Our objective was to test the effectiveness of an educational intervention to improve physician empathy and trust in the ED setting. METHODS: Physician participants from six emergency medicine residencies in the US were studied from 2018 to 2019 using a pre-post, quasi-experimental non-equivalent control group design with randomisation at the site level. Intervention participants at three hospitals received an educational intervention, guided by acognitivemap (the 'empathy circle'). This intervention was further emphasised by the use of motivational texts delivered to participants throughout the course of the study. The primary outcome was change in E patient perception of resident empathy (Jefferson scale of patient perception of physician empathy (JSPPPE) and Trust in Physicians Scale (Tips)) before (T1) and 3-6 months later (T2). RESULTS: Data were collected for 221 residents (postgraduate year 1-4.) In controls, the mean (SD) JSPPPE scores at T1 and T2 were 29 (3.8) and 29 (4.0), respectively (mean difference 0.8, 95% CI: -0.7 to 2.4, p=0.20, paired t-test). In the intervention group, the JSPPPE scores at T1 and T2 were 28 (4.4) and 30 (4.0), respectively (mean difference 1.4, 95% CI: 0.0 to 2.8, p=0.08). In controls, the TIPS at T1 was 65 (6.3) and T2 was 66 (5.8) (mean difference -0.1, 95% CI: -3.8 to 3.6, p=0.35). In the intervention group, the TIPS at T1 was 63 (6.9) and T2 was 66 (6.3) (mean difference 2.4, 95% CI: 0.2 to 4.5, p=0.007). Hierarchical regression revealed no effect of time×group interaction for JSPPPE (p=0.71) nor TIPS (p=0.16). CONCLUSION: An educational intervention with the addition of text reminders designed to increase empathic behaviour was not associated with a change in patient-perceived empathy, but was associated with a modest improvement in trust in physicians.

Hypoglycemia as a complication of intravenous insulin to treat hyperkalemia in the emergency department.

INTRODUCTION: Complications associated with the emergency department (ED) management of hyperkalemia are not well characterized. The goals of this study were to describe the frequency of hypoglycemia following the use of insulin to shift potassium intracellularly and to examine the association of key variables with this complication. METHODS: Adult ED patients (≥18 years old) with hyperkalemia (>5.3 mmol/L) were identified in the electronic medical record over a 5-year period at the study site. Patient characteristics, laboratory results, and treatments in the ED were captured. A generalized estimating equation (GEE) model was utilized to determine independent associations with the development of hypoglycemia. RESULTS: 1307 encounters were identified where hyperkalemia was present. Hypoglycemia (defined as a glucose <70 mg/dL) occurred in 68/409 (17%) of patients given insulin, compared to 4% of patients who did not receive insulin. Lower glucose prior to insulin (adjusted odds ratio [aOR] 0.90; 95% confidence interval [95% CI] 0.85 to 0.96), higher doses of insulin (aOR 1.07; 95% CI 1.01 to 1.15) and lower doses of D50 (aOR 0.98; 95% CI 0.97 to 0.99) were independently associated with hypoglycemia in the multivariate analysis. Age, history of diabetes, and history renal failure were not independently associated. CONCLUSION: Hypoglycemia is a frequent complication of treatment with IV insulin in the ED. Interventions such as standardized protocols to assist with the ED management of hyperkalemia should be developed; their efficacy and safety should be compared.

Validation of a 5-item tool to measure patient assessment of clinician compassion in the emergency department.

BACKGROUND: To test if the 5-item compassion measure (a tool previously validated in the outpatient setting to measure patient assessment of clinician compassion) is a valid and reliable tool to quantify a distinct construct (i.e. clinical compassion) among patients evaluated in the emergency department (ED). METHODS: Cross-sectional study conducted in three academic emergency departments in the U.S. between November 2018 and April 2019. We enrolled adult patients who were evaluated in the EDs of the participating institutions and administered the 5-item compassion measure after completion of care in the ED. Validity testing was performed using confirmatory factor analysis. Cronbach's alpha was used to test reliability. Convergent validity with patient assessment of overall satisfaction questions was tested using Spearman correlation coefficients and we tested if the 5-item compassion measure assessed a construct distinct from overall patient satisfaction using confirmatory factor analysis. RESULTS: We analyzed 866 patient responses. Confirmatory factor analysis found all five items loaded well on a single construct and our model was found to have good fit. Reliability was excellent (Cronbach's alpha = 0.93) among the entire cohort. These results remained consistent on sub-analyses stratified by individual institutions. The 5-item compassion measure had moderate correlation with overall patient satisfaction (r = 0.66) and patient recommendation of the ED to friends and family (r = 0.57), but reflected a patient experience domain (i.e. compassionate care) distinctly different from patient satisfaction. CONCLUSIONS: The 5-item compassion measure is a valid and reliable tool to measure patient assessment of clinical compassion in the ED.

Is Transcellular Potassium Shifting With Insulin, Albuterol, or Sodium Bicarbonate in Emergency Department Patients With Hyperkalemia Associated With Recurrent Hyperkalemia After Dialysis?

BACKGROUND: Emergency department (ED) treatment of hyperkalemia often involves shifting potassium into the intracellular space. There is uncertainty whether transcellular shifting causes insufficient potassium removal during hemodialysis, resulting in a subsequent need for further medical therapy or multiple sessions of hemodialysis. OBJECTIVE: We sought to determine whether transcellular potassium shifting in ED patients with hyperkalemia who undergo hemodialysis is associated with recurrent hyperkalemia with or without repeat hemodialysis within 24 h. METHODS: This was a retrospective observational study of ED patients with a potassium value > 5.3 mmol/L and ≥1 hemodialysis run. Transcellular shifting medications were defined as albuterol, insulin, and sodium bicarbonate. Primary outcomes were recurrent hyperkalemia with and without repeat hemodialysis within 24 h of the initial dialysis run. Generalized estimating equation models were created for the outcomes using administration of a shifting medication as the primary predictor. RESULTS: Four hundred seventy-nine encounters were identified. In 238 (50%) encounters, a shifting medication was administered. There were 85 outcomes of recurrent hyperkalemia and 36 outcomes of recurrent hyperkalemia with repeat hemodialysis. After adjustment, administration of shifting medications was not associated with recurrent hyperkalemia (adjusted odds ratio 1.26, 95% confidence interval 0.71-2.23) or recurrent hyperkalemia with repeat dialysis (adjusted odds ratio 1.90, 95% confidence interval 0.80-4.48). CONCLUSIONS: Administration of transcellular shifting medications for hyperkalemia in the ED was not associated with either recurrent hyperkalemia after hemodialysis or the need for a second dialysis session within 24 h. Our findings address the uncertainty regarding transcellular potassium shifting before emergent dialysis and support safe ED administration of medications that shift potassium to the intracellular space.

Diagnostic Performance of High Sensitivity Compared with Contemporary Cardiac Troponin I for the Diagnosis of Acute Myocardial Infarction.

BACKGROUND: We examined the diagnostic performance of high-sensitivity cardiac troponin I (hs-cTnI) vs contemporary cTnI with use of the 99th percentile alone and with a normal electrocardiogram (ECG) to rule out acute myocardial infarction (MI) and serial changes (deltas) to rule in MI. METHODS: We included consecutive patients presenting to a US emergency department with serial cTnI onclinical indication. Diagnostic performance for acute MI, including MI subtypes, and 30-day outcomes were examined. RESULTS: Among 1631 patients, MI was diagnosed in 12.9% using the contemporary cTnI assay and in 10.4% using the hs-cTnI assay. For ruling out MI, contemporary cTnI ≤99th percentile at 0, 3, and 6 h and a normal ECG had a negative predictive value (NPV) of 99.5% (95% CI, 98.6-100) and a sensitivity of 99.1% (95% CI, 97.4-100) for diagnostic and safety outcomes. Serial hs-cTnI measurements ≤99th percentile at 0 and 3 h and a normal ECG had an NPV and sensitivity of 100% (95% CI, 100-100) for diagnostic and safety outcomes. For ruling in MI, contemporary cTnI measurements had specificities of 84.4% (95% CI, 82.5-86.3) at presentation and 78.7% (95% CI, 75.4-82.0) with serial testing at 0, 3, and 6 h, improving to 89.2% (95% CI, 87.1-91.3) by using serial cTnI changes (delta, 0 and 6 h) >150%. hs-cTnI had specificities of 86.9% (95% CI, 85.1-88.6) at presentation and 85.7% (95% CI, 83.5-87.9) with serial testing at 0 and 3 h, improving to 89.3% (95% CI, 87.3-91.2) using a delta hs-cTnI (0 and 3 h) >5 ng/L. CONCLUSIONS: hs-cTnI and contemporary cTnI assays are excellent in ruling out MI following recommendations predicated on serial testing and the 99th percentile with a normal ECG. For ruling in MI, deltas improve the specificity. ClinicalTrials.gov Identifier: NCT02060760.

Discordance between ICD-Coded Myocardial Infarction and Diagnosis according to the Universal Definition of Myocardial Infarction.

BACKGROUND: International Classification of Diseases (ICD) coding is the standard diagnostic tool for healthcare management. At present, type 2 myocardial infarction (T2MI) classification by the Universal Definition of Myocardial Infarction (MI) remains ignored in the ICD system. We determined the concordance for the diagnosis of MI using ICD-9 coding vs the Universal Definition. METHODS: Cardiac troponin I (cTnI) was measured by both contemporary (cTnI) and high-sensitivity (hs-cTnI) assays in 1927 consecutive emergency department (ED) patients [Use of TROPonin In Acute coronary syndromes (UTROPIA) cohort] who had cTnI ordered on clinical indication. All patients were adjudicated using both contemporary and hs-cTnI assays. The Kappa index and McNemar test were used to assess concordance between ICD-9 code 410 and type 1 MI (T1MI) and type 2 MI (T2MI). RESULTS: Among the 249 adjudicated MIs using the contemporary cTnI, only 69 (28%) were ICD-coded MIs. Of 180 patients not ICD coded as MI, 34 (19%) were T1MI and 146 (81%) were T2MI. For the ICD-coded MIs, 79% were T1MI and 21% were T2MI. A fair Kappa index, 0.386, and a McNemar difference of 0.0892 (P < 0.001) were found. Among the 207 adjudicated MIs using the hs-cTnI assay, 67 (32%) were ICD coded as MI. Of the 140 patients not ICD coded as MI, 27 (19%) were T1MI and 113 (81%) were T2MI. For the ICD-coded MIs, 85% were T1MI and 15% T2MI. A moderate Kappa index, 0.439, and a McNemar difference of 0.0674 (P < 0.001) were found. CONCLUSIONS: ICD-9-coded MIs captured only a small proportion of adjudicated MIs, primarily from not coding T2MI. Our findings emphasize the need for an ICD code for T2MI.

Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors treated with therapeutic hypothermia*.

OBJECTIVES: To characterize the prevalence of withdrawal of life-sustaining treatment, as well as the time to awakening, short-term neurologic outcomes, and cause of death in comatose survivors of out-of-hospital resuscitated cardiopulmonary arrests treated with therapeutic hypothermia. DESIGN: Single center, prospective observational cohort study of consecutive patients with out-of-hospital cardiopulmonary arrests. SETTING: Academic tertiary care hospital and level one trauma center in Minneapolis, MN. PATIENTS: Adults with witnessed, nontraumatic, out-of-hospital cardiopulmonary arrests regardless of initial electrocardiographic rhythm with return of spontaneous circulation who were admitted to an ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study cohort included 154 comatose survivors of witnessed out-of-hospital cardiopulmonary arrests who were admitted to an ICU during the 54-month study period. One hundred eighteen patients (77%) were treated with therapeutic hypothermia. The mean age was 59 years, 104 (68%) were men, and 83 (54%) had an initial rhythm of ventricular tachycardia or fibrillation. Only eight of all 78 patients (10%) who died qualified as brain dead; and 81% of all patients (63 of 78) who died did so after withdrawal of life-sustaining treatment. Twenty of 56 comatose survivors (32%) treated with hypothermia who awoke (as defined by Glasgow Motor Score of 6) and had good neurologic outcomes (defined as Cerebral Performance Category 1-2) did so after 72 hours. CONCLUSIONS: Our study supports delaying prognostication and withdrawal of life-sustaining treatment to beyond 72 hours in cases treated with therapeutic hypothermia. Larger multicenter prospective studies are needed to better define the most appropriate time frame for prognostication in comatose cardiac arrest survivors treated with therapeutic hypothermia. These data are also consistent with the notion that a majority of out-of-hospital cardiopulmonary arrest survivors die after a decision to withdrawal of life-sustaining treatment and that very few of these survivors progress to brain death.

Interunit handoffs of patients and transfers of information: a survey of current practices.

STUDY OBJECTIVE: We describe the current state of emergency department to inpatient handoffs and assess handoff best practices between emergency physicians and hospitalist medicine physicians. METHODS: A survey was distributed electronically to emergency medicine and internal medicine physicians at 10 hospitals across the United States. Descriptive and quantitative analysis was performed on survey results. Additionally, qualitative data were obtained from an expert focus group of both emergency medicine and hospital medicine clinicians. RESULTS: Seven hundred fifty of 1,799 physicians (42.2%) responded to our Web-based survey. Attending physicians (45%) described themselves as practicing emergency medicine (51%) or internal medicine (56%). Responding residents were 55% internal medicine, 43% emergency medicine, and 13% dual emergency medicine/internal medicine. Of the responding departments, use of standardized tools was reported by less than 20% and only one third of residents reported formal handoff training. Handoff factors identified as important include identifying "high-risk" patients, designating uninterrupted time to perform the handoff, and standardizing information provided during the handoff. Qualitative results mirrored these themes and acknowledged the importance of bedside handoffs. CONCLUSION: To our knowledge, this is the largest multispecialty survey to date, including both resident and attending physicians in emergency medicine and hospital medicine. Standardized tools are rarely used and training of residents in this critical task is uncommon. Physicians in both specialties agree on the important content and structure of handoff, including the ideal situation of face-to-face bedside discussion. A curriculum and assessment tool for this practice should be developed.

Point-of-care ultrasound to estimate central venous pressure: a comparison of three techniques.

OBJECTIVE: To determine the most accurate predictor of central venous pressure among three point-of-care venous ultrasound techniques. DESIGN: Cross-sectional study. SETTING: Medical ICU in an academic medical center. PATIENTS: Convenience sample of 67 spontaneously breathing patients who had an intrathoracic central venous catheter to allow measurement of central venous pressure. INTERVENTION: Measurement of the internal jugular vein height to width ratio (aspect ratio), the inferior vena cava diameter, and the percent collapse of the inferior vena cava with inspiration (collapsibility index) by ultrasound. MEASUREMENTS AND MAIN RESULTS: Complete data for analysis were available in 65 patients, as the inferior vena cava could not be visualized in two patients. A central venous pressure of 10 mm Hg was chosen a priori as a clinically significant cutoff. The range of central venous pressure values was 1-23 mm Hg with a median value of 7 mm Hg. The maximal inferior vena cava diameter correlated moderately with central venous pressure (R = 0.58), whereas the inferior vena cava collapsibility index and the internal jugular vein aspect ratio showed poor correlation (R = 0.16 and 0.21, respectively). The area under the receiver operating characteristics curve (area under the curve) to discriminate a low central venous pressure (< 10 mm Hg) was 0.91 for inferior vena cava diameter (95% confidence interval 0.84-0.98), which was significantly higher than the internal jugular vein aspect ratio (area under the curve 0.76; 95% confidence interval 0.65-0.89) or the inferior vena cava collapsibility index (area under the curve 0.66; 95% confidence interval 0.51-0.80) (p = 0.0001). An inferior vena cava diameter < 2 cm predicted a central venous pressure < 10 mm Hg with a sensitivity of 85% (95% confidence interval 69% to 94%), specificity of 81% (95% confidence interval 60% to 93%), and positive predictive value of 87% (95% confidence interval 71% to 95%). Inferior vena cava collapsibility index was not an independent predictor of central venous pressure after adjusting for inferior vena cava diameter in a multiple linear regression model. CONCLUSION: Among spontaneously breathing patients largely without vasopressor support, the maximal inferior vena cava diameter is a more robust estimate of central venous pressure than the inferior vena cava collapsibility index or the internal jugular vein aspect ratio.

Emergency Medicine/Internal Medicine Combined Residency Graduates Have High Career Satisfaction and Commonly Practice in Both Specialties.

OBJECTIVES: The first combined emergency medicine/internal medicine (EM/IM) residency was established in 1991. As the 30th anniversary of this unique dual-training opportunity approaches, multiple changes to the practice and educational landscape have occurred. Previous surveys examining this topic are now more than 10 years old and occurred prior to the establishment of the EM/IM/critical care medicine (EM/IM/CCM) pathway. We conducted a survey to investigate career trajectories, satisfaction, and opportunities available to EM/IM graduates. METHODS: Survey questions were developed to both allow for comparison with previously published data and examine new topics not previously investigated. A group of EM/IM and EM/IM/CCM program directors validated the survey questions. Eligible respondents were identified and contacted through their previous residency program leadership. RESULTS: Fifty-two percent (152/290) of graduates completed the survey. Thirty-seven percent of respondents practice both EM and IM, 51% practice EM only, and the remainder practice IM only. Thirty-one percent of total respondents completed a fellowship, with critical care being the most popular choice. Seventy-one percent of graduates practice in an academic center, and many hold leadership positions within education, research, and hospital administration. Eighty-seven percent of graduates were "extremely satisfied" with their choice to pursue EM/IM or EM/IM/CCM and 95% reported that they would choose this path again. CONCLUSIONS: Most respondents are satisfied with their residency choice and would choose to pursue this training again, despite the additional years of training. The proportion of graduates pursuing fellowship is higher than previously published data. Most continue to work in academics, and many are leaders within their institutions. The changing health care landscape offers multiple opportunities to dually trained graduates.

A multicentre and multi-national evaluation of the accuracy of quantitative Lu-177 SPECT/CT imaging performed within the MRTDosimetry project.

PURPOSE: Patient-specific dosimetry is required to ensure the safety of molecular radiotherapy and to predict response. Dosimetry involves several steps, the first of which is the determination of the activity of the radiopharmaceutical taken up by an organ/lesion over time. As uncertainties propagate along each of the subsequent steps (integration of the time-activity curve, absorbed dose calculation), establishing a reliable activity quantification is essential. The MRTDosimetry project was a European initiative to bring together expertise in metrology and nuclear medicine research, with one main goal of standardizing quantitative 177Lu SPECT/CT imaging based on a calibration protocol developed and tested in a multicentre inter-comparison. This study presents the setup and results of this comparison exercise. METHODS: The inter-comparison included nine SPECT/CT systems. Each site performed a set of three measurements with the same setup (system, acquisition and reconstruction): (1) Determination of an image calibration for conversion from counts to activity concentration (large cylinder phantom), (2) determination of recovery coefficients for partial volume correction (IEC NEMA PET body phantom with sphere inserts), (3) validation of the established quantitative imaging setup using a 3D printed two-organ phantom (ICRP110-based kidney and spleen). In contrast to previous efforts, traceability of the activity measurement was required for each participant, and all participants were asked to calculate uncertainties for their SPECT-based activities. RESULTS: Similar combinations of imaging system and reconstruction lead to similar image calibration factors. The activity ratio results of the anthropomorphic phantom validation demonstrate significant harmonization of quantitative imaging performance between the sites with all sites falling within one standard deviation of the mean values for all inserts. Activity recovery was underestimated for total kidney, spleen, and kidney cortex, while it was overestimated for the medulla. CONCLUSION: This international comparison exercise demonstrates that harmonization of quantitative SPECT/CT is feasible when following very specific instructions of a dedicated calibration protocol, as developed within the MRTDosimetry project. While quantitative imaging performance demonstrates significant harmonization, an over- and underestimation of the activity recovery highlights the limitations of any partial volume correction in the presence of spill-in and spill-out between two adjacent volumes of interests.

Optimising quantitative 90Y PET imaging: an investigation into the effects of scan length and Bayesian penalised likelihood reconstruction.

BACKGROUND: Positron emission tomography (PET) imaging of 90Y following selective internal radiation therapy (SIRT) is possible, but image quality is poor, and therefore, accurate quantification and dosimetry are challenging. This study aimed to quantitatively optimise 90Y PET imaging using a new Bayesian penalised likelihood (BPL) reconstruction algorithm (Q.Clear, GE Healthcare). The length of time per bed was also investigated to study its impact on quantification accuracy. METHODS: A NEMA IQ phantom with an 8:1 sphere-to-background ratio was scanned overnight on a GE Discovery 710 PET/CT scanner. Datasets were rebinned into varying lengths of time (5-60 min); the 15-min rebins were reconstructed using BPL reconstruction with a range of noise penalisation weighting factors (beta values). The metrics of contrast recovery (CR), background variability (BV), and recovered activity percentage (RAP) were calculated in order to identify the optimum beta value. Reconstructions were then carried out on the rest of the timing datasets using the optimised beta value; the same metrics were used to assess the quantification accuracy of the reconstructed images. RESULTS: A beta value of 1000 produced the highest CR and RAP (76% and 73%, 37 mm sphere) without overly accentuating the noise (BV) in the image. There was no statistically significant increase (p < 0.05) in either the CR or RAP for scan times of > 15 min. For the 5-min acquisitions, there was a statistically significant decrease in RAP (28 mm sphere, p < 0.01) when compared to the 15-min acquisition. CONCLUSION: Our results indicate that an acquisition length of 15 min and beta value of 1000 (when using Q.Clear reconstruction) are optimum for quantitative 90Y PET imaging. Increasing the acquisition time to more than 15 min reduces the image noise but has no significant impact on image quantification.

Appropriateness of Cardiac Troponin Testing: Insights from the Use of TROPonin In Acute coronary syndromes (UTROPIA) Study.

OBJECTIVE: Our objective was to examine the appropriateness of cardiac troponin (cTn) testing among patients with cTn increases. METHODS: This is a planned secondary analysis of the Use of TROPonin In Acute coronary syndromes (UTROPIA, NCT02060760) observational cohort study. Appropriateness of cTn testing was adjudicated for emergency department patients with cTn increases >99th percentile and analyzed using both contemporary and high-sensitivity (hs) cTnI assays according to sub-specialty, diagnoses, and symptoms. RESULTS: Appropriateness was determined from 1272 and 1078 adjudication forms completed for 497 and 422 patients with contemporary and hs-cTnI increases, respectively. Appropriateness of cTnI testing across adjudication forms was 71.5% and 72.0% for cTnI and hs-cTnI, respectively. Compared with emergency physicians, cardiologists were less likely to classify cTnI orders as appropriate (cTnI: 79% vs 56%, P < .0001; hs-cTnI: 82% vs 51%, P < .0001). For contemporary cTnI, appropriateness of 95%, 70%, and 39% was observed among adjudication forms completed by cardiologists for type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively; compared with 90%, 86%, and 71%, respectively, among emergency physicians. Similar findings were observed using hs-cTnI. Discordance in appropriateness adjudication forms occurred most frequently in cases of myocardial injury (62% both assays) or type 2 myocardial infarction (cTnI 31%; hs-cTnI 23%). CONCLUSIONS: Marked differences exist in the perception of what constitutes appropriate clinical use of cTn testing between cardiologists and emergency physicians, with emergency physicians more likely to see testing as appropriate across a range of clinical scenarios. Discordance derives most often from cases classified as myocardial injury or type 2 myocardial infarction.

Type 1 and 2 Myocardial Infarction and Myocardial Injury: Clinical Transition to High-Sensitivity Cardiac Troponin I.

BACKGROUND: Studies addressing patients with type 2 myocardial infarction and myocardial injury, including the impact of using high-sensitivity (hs) cardiac troponin (cTn) assays on their incidence are needed. METHODS: Ours is a prospective, observational US cohort study. Consecutive emergency department patients with serial cTnI measurements were studied. Outcomes included 180-day mortality and major adverse cardiac events, including 2-year follow-up for those with myonecrosis. RESULTS: Among 1640 patients, using a contemporary cTnI assay, 30% (n = 497) had ≥1 cTnI >99th percentile, with 4.7% (n = 77), 8.5% (n = 140), and 17% (n = 280) classified as type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively. Compared with patients without myonecrosis, 180-day mortality was higher for type 2 myocardial infarction (4% vs 13%, P < .0001) (adjusted hazard ratio 2.7; 95% confidence interval, 1.6-4.8; P = .0005) and myocardial injury (4% vs 11%, P < .0001) (adjusted hazard ratio 1.8; 95% confidence interval, 1.1-3.0; P = .02), both with mortality >20% at 2 years. Predictors of 2-year mortality for type 2 myocardial infarction included age, congestive heart failure, and beta-blockers. Relative to the contemporary cTnI assay, hs-cTnI had less myonecrosis (30% vs 26%, P = .003) and acute myocardial infarction (13.2% vs 10.8%, P = .032), including fewer type 2 myocardial infarctions (8.5% vs 6.3, P = .01), with no difference in myocardial injury (17% vs 15%, P = .1). CONCLUSIONS: cTnI increases are encountered in approximately a third of patients, the majority due to nonatherothrombotic conditions. Compared with patients without myonecrosis, type 2 myocardial infarction and myocardial injury have worse short-term outcomes, with mortality rates >20% at 2 years. hs-cTnI assay does not lead to more myocardial injury or infarction.

Detection of influenza antigen with rapid antibody-based tests after intranasal influenza vaccination (FluMist).

Rapid tests for influenza antigen detection are frequently used, but it is not known how receipt of intranasal influenza vaccine affects results of these tests. We tested healthy adults who received either intranasal or intramuscular influenza vaccine. Of the 14 intranasal vaccine recipients, 7 (50%) had a direct fluorescent antibody test (DFA) result and 2 (14%) had an enzyme immunoassay (EIA) result that was positive for influenza antigen within 7 days after vaccination. No subjects had positive EIA results on day 12 or 13 after vaccination. For some intranasal vaccine recipients, rapid influenza-antigen detection tests yield positive results within 1 week after vaccination.

Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system.

BACKGROUND: CKS257 (Salmonella typhimurium SL1344 DeltaphoP/phoQDelta aroA Deltaasd DeltastrA/strB pSB2131) is a live oral vaccine vector expressing HIV Gag. METHODS: HIV Gag was expressed as a fusion protein of a Salmonella Type III secretion system protein SopE, from a balanced lethal asd-based plasmid. Eighteen healthy adults were given single escalating oral doses of 5 x 10(6) to 1 x 10(10)CFU of CKS257 and were monitored for clinical events, shedding and immune responses. RESULTS: Adverse events were mild except at the highest dose. Volunteers shed the organism an average of 5.1 days (range 0-13 days). Eighty-three percent (15/18) of subjects had a mucosal immune response to Salmonella LPS and flagella by IgA ELISPOT assay. Seventy-two percent (13/18) of subjects seroconverted to Salmonella antigens. No volunteer had a response to recombinant Gag as measured by serology, IgA ELISPOT, or immediate ex vivo gamma-interferon ELISPOT response to Gag peptide pools. Two volunteers responded to Gag peptides by IL-2 ELISPOT, and 4 of 10 volunteers receiving >or=5 x 10(8)CFU had a response to HIV peptides in a cultured gamma-interferon ELISPOT assay. CONCLUSIONS: Although immunogenicity of the HIV antigen needs augmentation, the attenuated Salmonella strain proved to be an excellent platform for vaccine development.