Point-of-care high-sensitivity cardiac troponin in suspected acute myocardial infarction assessed at baseline and 2†h.

BACKGROUND AND AIMS: Strategies to assess patients with suspected acute myocardial infarction (AMI) using a point-of-care (POC) high-sensitivity cardiac troponin I (hs-cTnI) assay may expedite emergency care. A 2-h POC hs-cTnI strategy for emergency patients with suspected AMI was derived and validated. METHODS: In two international, multi-centre, prospective, observational studies of adult emergency patients (1486 derivation cohort and 1796 validation cohort) with suspected AMI, hs-cTnI (Siemens Atellica® VTLi) was measured at admission and 2 h later. Adjudicated final diagnoses utilized the hs-cTn assay in clinical use. A risk stratification algorithm was derived and validated. The primary diagnostic outcome was index AMI (Types 1 and 2). The primary safety outcome was 30-day major adverse cardiac events incorporating AMI and cardiac death. RESULTS: Overall, 81 (5.5%) and 88 (4.9%) patients in the derivation and validation cohorts, respectively, had AMI. The 2-h algorithm defined 66.1% as low risk with a sensitivity of 98.8% [95% confidence interval (CI) 89.3%-99.9%] and a negative predictive value of 99.9 (95% CI 99.2%-100%) for index AMI in the derivation cohort. In the validation cohort, 53.3% were low risk with a sensitivity of 98.9% (95% CI 92.4%-99.8%) and a negative predictive value of 99.9% (95% CI 99.3%-100%) for index AMI. The high-risk metrics identified 5.4% of patients with a specificity of 98.5% (95% CI 96.6%-99.4%) and a positive predictive value of 74.5% (95% CI 62.7%-83.6%) for index AMI. CONCLUSIONS: A 2-h algorithm using a POC hs-cTnI concentration enables safe and efficient risk assessment of patients with suspected AMI. The short turnaround time of POC testing may support significant efficiencies in the management of the large proportion of emergency patients with suspected AMI.

Analytical validation of the Mindray CL1200i analyzer high sensitivity cardiac troponin I assay: MERITnI study.

OBJECTIVES: This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. METHODS: LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. RESULTS: The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. CONCLUSIONS: Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.

Large-Scale Scientific Study Led by a Professional Organization during the COVID-19 Pandemic: Operations, Best Practices, and Lessons Learned.

In 2021, the Association for Diagnostics & Laboratory Medicine (ADLM) (formerly the American Association for Clinical Chemistry [AACC]) developed a scientific study that aimed to contribute to the understanding of SARS-CoV-2 immunity during the evolving course of the pandemic. This study was led by a group of expert member volunteers and resulted in survey data from 975 individuals and blood collection from 698 of those participants. This paper describes the formulation and execution of this large-scale scientific study, encompassing best practices and insights gained throughout the endeavor.

Machine learning for diagnosis of myocardial infarction using cardiac troponin concentrations.

Although guidelines recommend fixed cardiac troponin thresholds for the diagnosis of myocardial infarction, troponin concentrations are influenced by age, sex, comorbidities and time from symptom onset. To improve diagnosis, we developed machine learning models that integrate cardiac troponin concentrations at presentation or on serial testing with clinical features and compute the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) score (0-100) that corresponds to an individual's probability of myocardial infarction. The models were trained on data from 10,038 patients (48% women), and their performance was externally validated using data from 10,286 patients (35% women) from seven cohorts. CoDE-ACS had excellent discrimination for myocardial infarction (area under curve, 0.953; 95% confidence interval, 0.947-0.958), performed well across subgroups and identified more patients at presentation as low probability of having myocardial infarction than fixed cardiac troponin thresholds (61 versus 27%) with a similar negative predictive value and fewer as high probability of having myocardial infarction (10 versus 16%) with a greater positive predictive value. Patients identified as having a low probability of myocardial infarction had a lower rate of cardiac death than those with intermediate or high probability 30 days (0.1 versus 0.5 and 1.8%) and 1 year (0.3 versus 2.8 and 4.2%; P < 0.001 for both) from patient presentation. CoDE-ACS used as a clinical decision support system has the potential to reduce hospital admissions and have major benefits for patients and health care providers.

Rapid Rule-Out of Myocardial Infarction Using a Single High-Sensitivity Cardiac Troponin I Measurement Strategy at Presentation to the Emergency Department: The SAFETY Study.

BACKGROUND: Our study addressed the diagnostic performance of the Atellica® IM High-Sensitivity Troponin I (hs-cTnI) assay for the rapid rule-out of myocardial infarction (MI) using a single hs-cTnI measurement at presentation in patients presenting to a US emergency department (ED). METHODS: This was a prospective, observational, cohort study of consecutive ED patients with suspected acute coronary syndrome, using 12-lead electrocardiogram and serial hs-cTnI measurements ordered on clinical indication (SAFETY, NCT04280926). ST-segment elevation MI patients were excluded. The optimal threshold required a sensitivity ≥99% and a negative predictive value (NPV) ≥99.5% for MI during index hospitalization as primary outcome. Type 1 MI (T1MI), myocardial injury, and 30-day adverse events were considered secondary outcomes. Event adjudications were established using the hs-cTnI assay used in clinical care. RESULTS: In 1171 patients, MI occurred in 97 patients (8.3%), 78.3% of which were type 2 MI. The optimal rule out hs-cTnI threshold was <10 ng/L, which identified 519 (44.3%) patients as low risk at presentation, with sensitivity of 99.0% (95% CI, 94.4-100) and NPV of 99.8% (95% CI, 98.9-100). For T1MI, sensitivity was 100% (95% CI, 83.9-100) and NPV 100% (95% CI, 99.3-100). Regarding myocardial injury, the sensitivity and NPV were 99.5% (95% CI, 97.9-100) and 99.8% (95% CI, 98.9-100), respectively. For 30-day adverse events, sensitivity was 96.8% (95% CI, 94.3-98.4) and NPV 97.9% (95% CI, 96.2-98.9). CONCLUSIONS: A single hs-cTnI measurement strategy enabled the rapid identification of patients at low risk of MI and 30-day adverse events, allowing potential discharge early after ED presentation. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT04280926.

Analytical performance comparing siemens whole blood point of care Atellica VTLi to the central laboratory plasma Atellica IM high-sensitivity cardiac troponin I assays.

INTRODUCTION: This study examined the analytical performance of a whole blood (WB) point of care (POC) hs-cTnI assay compared to a plasma central laboratory hs-cTnI assay in patients presenting with ischemic symptoms to a US emergency department. METHODS: Fresh WB specimens collected at 0 and 2 h from 1089 consecutive patients (2152 total from 1076 matched specimens) were analyzed for hs-cTnI using WB on POC Siemens Atellica VTLi assay and plasma on central laboratory Siemens Atellica IM assay. Concordances were determined based on concentrations ranging from < limit of detection (LoD), LoD to overall and sex specific 99th percentiles from both the IFCC manufacturer package inserts and Universal Sample Bank (USB) data, and > 99th percentiles. Method comparisons were calculated using Passing Bablok regression and Bland Altmann plots, and linear regression determined by Pearson correlation coefficient. RESULTS: Baseline concentration comparisons showed: POC VTLi < LoD 4-5 %, ≥ LoD 95 %; Atellica IM < LoD 5-7 %, and ≥ LoD 94-95 %. From the 2152 paired 0 and 2-hour samples, based on 99th percentiles, overall concordance was 91-92 % (kappa 0.72-0.77) and discordance 8 %. Passing Bablok regression analysis using 1924 specimens between LoD to 500 ng/L showed: slopes 0.469-0.490; y-intercepts 1.753-2.028; r values 0.631-0.817. Pearson correlation coefficient showed moderate to strong correlation strength, even with up to 53 % cTnI concentrations variance (Passing Bablok slopes) vs 27.0-40.1 % (Bland-Altmann plots). CONCLUSIONS: Up to 95 % of measured samples were > LoD for both the POC (Atellica VTLi) and central laboratory (Atellica IM) hs-cTnI assays. Moderate to strong concordance and correlation were observed between assays, despite up to 53 % variances in cTnI concentration.

Tolerance for three commonly administered COVID-19 vaccines by healthcare professionals.

Importance: Most healthcare institutions require employees to be vaccinated against SARS-CoV-2 and many also require at least one booster. Objective: We determine the impact of vaccine type, demographics, and health conditions on COVID-19 vaccine side effects in healthcare professionals. Design: A COVID-19 immunity study was performed at the 2021 American Association for Clinical Chemistry Annual Scientific meeting. As part of this study, a REDCap survey with cascading questions was administered from September 9, 2021 to October 20, 2021. General questions included participant demographics, past and present health conditions, smoking, exercise, and medications. COVID-19 specific questions asked about SARS-CoV-2 vaccine status and type, vaccine-associated side effects after each dose including any boosters, previous infection with COVID-19, diagnostic testing performed, and type and severity symptoms of COVID-19. Results: There were 975 participants (47.1% male, median age of 50 years) who completed the survey. Pfizer was the most commonly administered vaccine (56.4%) followed by Moderna (32.0%) and Johnson & Johnson (7.1%). There were no significant differences in vaccine type received by age, health conditions, smoking, exercise, or type or number of prescription medications. Side effects were reported more frequently after second dose (e.g., Moderna or Pfizer) (54.1%) or single/only dose of Johnson & Johnson (47.8%). Males were significantly more likely to report no side effects (p < 0.001), while females were significantly more likely to report injection site reactions (p < 0.001), fatigue (p < 0.001), headache (p < 0.001), muscle pain (p < 0.001), chills (p = 0.001), fever (p = 0.007), and nausea (p < 0.001). There was a significant upward trend in participants reporting no side effects with increasing age (p < 0.001). There were no significant trends in side effects among different races, ethnicities, health conditions, medications, smoking status or exercise. In multivariate logistic regressions analyses, the second dose of Moderna was associated with a significantly higher risk of side effects than both the second dose of Pfizer and the single dose of Johnson & Johnson. Conclusions and relevance: Younger people, females, and those receiving the second dose of Moderna had more COVID-19 vaccine side effects that per self-report led to moderate to severe limitations. As reported in other studies, the increase in side effects from Moderna may be explained by higher viral mRNA concentrations but be associated with additional protective immunity.

Single High-Sensitivity Point-of-Care Whole-Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) laboratory assays are used to rule out myocardial infarction (MI) on presentation, but prolonged result turnaround times can delay patient management. Our primary aim was to identify patients at low risk of index MI using a rapid point-of-care (POC) whole-blood hs-cTnI assay at presentation with potential early patient discharge. METHODS: Consecutive patients presenting to the emergency department from 2 prospective observational studies with suspected acute coronary syndrome were enrolled. A POC hs-cTnI assay (Atellica VTLi) threshold using whole blood at presentation, which resulted in a negative predictive value of ≥99.5% and sensitivity of >99% for index MI, was derived (SEIGE [Safe Emergency Department Discharge Rate]) and validated with plasma (SAMIE [Suspected Acute Myocardial Infarction in Emergency]). Event adjudications were established with hs-cTnI assay results from routine clinical care. The primary outcome was MI at 30 days. RESULTS: A total of 1086 patients (8.1% with MI) were enrolled in a US derivation cohort (SEIGE) and 1486 (5.5% MI) in an Australian validation cohort (SAMIE). A derivation whole-blood POC hs-cTnI concentration of <4 ng/L provided a sensitivity of 98.9% (95% CI, 93.8%-100%) and negative predictive value of 99.5% (95% CI, 97.2%-100%) for ruling out MI. In the validation cohort, the sensitivity was 98.8% (95% CI, 93.3%-100%), and negative predictive value was 99.8% (95% CI, 99.1%-100%); 17.8% and 41.8%, respectively, were defined as low risk for discharge. The 30-day adverse cardiac events were 0.1% (n=1) for SEIGE and 0.8% (n=5) for SAMIE. CONCLUSIONS: A POC whole-blood hs-cTnI assay permits accessible, rapid, and safe exclusion of MI and may expedite discharge from the emergency department. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04772157. URL: https://www.australianclinicaltrials.gov.au/anzctr_feed/form; Unique identifier: 12621000053820.

Observational Study of Receptor Binding Domain Spike Antibody Responses to 3 SARS-CoV-2 Vaccinations in Noninfected Subjects: Parallel Neutralizing Antibody and Cardiac Troponin I and T Observations.

BACKGROUND: Our goals were to demonstrate receptor binding domain spike 1 (RBD S1) protein antibody (Ab) kinetic responses to multiple vaccines over approximately 180 days, neutralizing Ab effectiveness, and high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) responses in postvaccinated, non-SARS-CoV-2-infected subjects. METHODS: Blood specimens were collected pre- and postvaccinations from seronegative subjects. RDB S1 Abs were measured by the novel Qorvo Biotechnologies Omnia platform. Neutralizing Abs and hs-cTnI and hs-cTnT were measured on the ET Healthcare Pylon 3D. RESULTS: Two-dose vaccines (Pfizer, Moderna) had peak RBD S1 Ab concentrations about 45 to 55 days after both doses and showed declines over the next 50 to 70 days. The Janssen vaccine showed lower RBD S1 Ab peak concentrations, continued to increase over time, and plateaued after 60 days. There was strong neutralizing Ab response post vaccinations, with only 3 specimens, shortly before and shortly after vaccination, not showing a response. Specimens showed no hs-cTnI (all < 3 ng/L) and hs-cTnT (all < 6 ng/L) increases or changes over time. CONCLUSIONS: We demonstrate in seronegative SARS-CoV-2 subjects that Pfizer and Moderna vaccinations provide strong, neutralizing RBD S1 Ab effectiveness, based on 2 different assays after 2 doses, with the Janssen single-dose vaccine showing a lower RBD S1 Ab response over 4 to 6 months. No myocardial injury was associated with the Pfizer postvaccination. The Qorvo Biotechnologies RBD S1 Ab assay measured on the Omnia platform has potential as a point-of-care platform.

Diagnostic performance of a rapid, novel, whole blood, point of care high-sensitivity cardiac troponin I assay for myocardial infarction.

BACKGROUND: We evaluated the diagnostic performance of a whole blood, point of care (POC) high-sensitivity cardiac troponin I (hs-cTnI) assay for myocardial infarction (MI) compared to central laboratory assays. METHODS: Consecutive patients presenting to the emergency department with symptoms of ischemia were studied. Serial hs-cTnI testing was based on clinical indication at presentation. Parallel measurements were made using fresh whole blood on Siemens Atellica VTLi POC assay, EDTA plasma on Abbott ARCHITECT i2000 used in practice, and heparin plasma on Siemens Atellica. MI was determined according to the Fourth Universal Definition of MI using 99th percentiles. Sensitivities and negative predictive values (NPV) were calculated using 99th percentile URLs. RESULTS: 1089 Patients, 418 females and 671 males, were enrolled. There were 91 (8.4%) MIs. At baseline (0 h), POC hs-cTnI assay had a sensitivity of 65.7% (95% CI 47.8-80.9) for females and 67.9% (54.0-79.7) for males and NPV of 96.4% (93.9-98.1) for females and 96.7% (94.9-98.0) for males. At 2 h, sensitivity improved to 82.9% (66.4-93.4) for females and 80.4% (67.6-89.8) for males, while NPV improved to 98.2% (96.1-99.3) and 97.9% (96.3-99.0), respectively. For central laboratory assays, comparable diagnostics were observed at 2 h: females - sensitivity 94.3% (80.8-99.3) for ARCHITECT and 79.4% (62.1-91.3) for Atellica, and NPV 99.3% (97.6-99.9) and 98.0% (95.8-99.2), respectively; males - sensitivity 87.5% (75.9-94.8) for ARCHITECT and 80.4% (67.6-89.8) for Atellica, NPVs of 98.7% (97.3-99.5) and 97.9% (96.3-99.0), respectively. CONCLUSIONS: The POC, whole blood Atellica VTLi hs-cTnI assay demonstrated comparable diagnostic accuracy for MI to central laboratory assays using 99th percentiles.

Determination of sex-specific 99th percentile upper reference limits for a point of care high sensitivity cardiac troponin I assay.

OBJECTIVES: High sensitivity (hs) cardiac troponin (cTn) assays are defined per the IFCC Committee on Clinical Application of Cardiac Biomarker (C-CB) by the ability to measure ≥ 50% of concentrations greater than the limit of detection (LoD) with an impression of ≤10% at sex-specific 99th percentiles. Our study determined the sex-specific 99th percentile upper reference limits for males and females utilizing heparinized plasma from AACC universal sample bank for the Siemens point of care (POC) Atellica® VTLi hs-cTnI immunoassay. METHODS: Apparently healthy subjects, included overall 693, males 363, and females 330, following exclusionary surrogate biomarker use of hemoglobin A1c, NT-proBNP, and eGFR, along with statin medication. hs-cTnI was measured in a central laboratory, on multiple POC Atellica® VTLi immunoassay analyzers. The LoD was 1.24 ng/L and the 10%CV concentration was 6.7 ng/L. 99th percentile URLs were determined by the nonparametric (NP) method. RESULTS: Histograms of the hs-cTnI concentrations (ng/L) for males and females were used to visualize the distributions and concentrations in men and women and differed significantly (pre- and post-exclusion, both p <0.001). 99th percentile URLs were: overall 23 ng/L (90% CI 20-32 ng/L); male 27 ng/L (CI 21-37 ng/L); female 18 ng/L (CI 9-78 ng/L). The percentages of subjects having a measurable concentration ≥ the LoD were: overall 83.7%, male 87.3%, female 79.7%. CONCLUSIONS: Our findings show the novel POC Atellica® VTLi hs-cTnI assay meets the designation of a 'high-sensitivity' assay using heparinized plasma.

Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays.

OBJECTIVES: This study compared the independent and combined effects of hemolysis and biotin on cardiac troponin measurements across nine high-sensitivity cardiac troponin (hs-cTn) assays. METHODS: Parallel cTn measurements were made in pooled lithium heparin plasma spiked with hemolysate and/or biotin using nine hs-cTn assays: Abbott Alinity, Abbott ARCHITECT i2000, Beckman Access 2, Ortho VITROS XT 7600, Siemens Atellica, Siemens Centaur, Siemens Dimension EXL cTnI, and two Roche Cobas e 411 Elecsys Troponin T-hs cTnT assays (outside US versions, with and without increased biotin tolerance). Absolute and percent cTn recovery relative to two baseline concentrations were determined in spiked samples and compared to manufacturer's claims. RESULTS: All assays except the Ortho VITROS XT 7600 showed hemolysis and biotin interference thresholds equivalent to or greater than manufacturer's claims. While imprecision confounded analysis of Ortho VITROS XT 7600 data, evidence of biotin interference was lacking. Increasing biotin concentration led to decreasing cTn recovery in three assays, specifically both Roche Cobas e 411 Elecsys Troponin T-hs assays and the Siemens Dimension EXL. While one of the Roche assays was the most susceptible to biotin among the nine studied, a new version showed reduced biotin interference by approximately 100-fold compared to its predecessor. Increasing hemolysis also generally led to decreasing cTn recovery for susceptible assays, specifically the Beckman Access 2, Ortho VITROS XT 7600, and both Roche Cobas e 411 Elecsys assays. Equivalent biotin and hemolysis interference thresholds were observed at the two cTn concentrations considered for all but two assays (Beckman Access 2 and Ortho VITROS XT 7600). When biotin and hemolysis were present in combination, biotin interference thresholds decreased with increasing hemolysis for two susceptible assays (Roche Cobas e 411 Elecsys and Siemens Dimension EXL). CONCLUSIONS: Both Roche Cobas e 411 Elecsys as well as Ortho VITROS XT assays were susceptible to interference from in vitro hemolysis at levels routinely encountered in clinical laboratory samples (0-3 g/L free hemoglobin), leading to falsely low cTn recovery up to 3 ng/L or 13%. While most assays are not susceptible to biotin at levels expected with over-the-counter supplementation, severely reduced cTn recovery is possible at biotin levels of 10-2000 ng/mL (41-8,180 nmol/L) for some assays. Due to potential additive effects, analytical interferences should not be considered in isolation.

A Structured Approach for Safely Reintroducing Bariatric Surgery in a COVID-19 Environment.

Due to the profound effect of novel coronavirus disease 2019 (COVID-19) on healthcare systems, surgical programs across the country have paused surgical operations and have been utilizing virtual visits to help maintain public safety. For those who treat obesity, the importance of bariatric surgery has never been more clear. Emerging studies continue to identify obesity and several other obesity-related comorbid conditions as major risk factors for a more severe COVID-19 disease course. However, this also suggests that patients seeking bariatric surgery are inherently at risk of suffering severe complications if they were to contract COVID-19 in the perioperative period. The aim of this protocol is to utilize careful analysis of existing risk stratification for bariatric patients, novel COVID-19-related data, and consensus opinion from multiple academic bariatric centers within our organization to help guide the reanimation of our programs when appropriate and to use this template to prospectively study this risk-stratified population in real time. The core principles of this protocol can be applied to any surgical specialty.

Sex-Specific 99th Percentile Upper Reference Limits for High Sensitivity Cardiac Troponin Assays Derived Using a Universal Sample Bank.

BACKGROUND: How to select healthy reference subjects in deriving 99th percentiles for cardiac troponin assays still needs to be clarified. To assist with global implementation of high sensitivity (hs)-cardiac troponin (cTn) I and hs-cTnT assays in clinical practice, we determined overall and sex-specific 99th percentiles in 9 hs-cTnI and 3 hs-cTnT assays using a universal sample bank (USB). METHODS: The Universal Sample Bank (USB) comprised healthy subjects, 426 men and 417 women, screened using a health questionnaire. Hemoglobin A1c (>URL 6.5%), NT-proBNP (>URL 125 ng/L) and eGFR (<60 mL/min), were used as surrogate biomarker exclusion criteria along with statin use. 99th percentiles were determined by nonparametric, Harrell--Davis bootstrap, and robust methods. RESULTS: Subjects were ages 19 to 91 years, Caucasian 58%, African American 27%, Pacific Islander/Asian 11%, other 4%, Hispanic 8%, and non-Hispanic 92%. The overall and sex-specific 99th percentiles for all assays, before and after exclusions (n = 694), were influenced by the statistical method used, with substantial differences noted between and within both hs-cTnI and hs-cTnT assays. Men had higher 99th percentiles (ng/L) than women. The Roche cTnT and Beckman and Abbott cTnI assays (after exclusions) did not measure cTn values at ≥ the limit of detection in ≥50% women. CONCLUSIONS: Our findings have important clinical implications in that sex-specific 99th percentiles varied according to the statistical method and hs-cTn assay used, not all assays provided a high enough percentage of measurable concentrations in women to qualify as a hs-assay, and the surrogate exclusion criteria used to define normality tended to lower the 99th percentiles.

Use of objective evidence of myocardial ischemia to facilitate the diagnostic and prognostic distinction between type 2 myocardial infarction and myocardial injury.

AIMS: First, describe how acute myocardial infarction criteria are used to diagnose type 1 (T1MI) and 2 (T2MI) myocardial infarction. Second, determine whether subjective or objective criteria are used for T2MI. Third, examine outcomes for T2MI based on the presence or absence of objective evidence of myocardial ischemia compared with myocardial injury. METHODS AND RESULTS: Post-hoc analysis of UTROPIA (NCT02060760), a prospective, observational, cohort study involving 1640 consecutive emergency department patients with serial high-sensitivity cardiac troponin I among whom 74 (4.5%) had T1MI, 103 (6.3%) T2MI, and 245 (15%) myocardial injury. Compared with T1MI, patients with T2MI were less likely to have ischemic symptoms (97% vs. 83%), Q waves (24% vs. 1%), new ST-T wave changes (74% vs. 51%), new regional wall motion abnormality (64% vs. 11%), and a culprit lesion on coronary angiography (59% vs. 0%) (all p <0.05). T2MIs were more likely to be diagnosed using subjective criteria (symptoms alone) than T1MI (42% vs. 12%, p <0.0001). Patients with objective T2MI, but not subjective T2MI, had a two-fold increase in early mortality compared with myocardial injury, with 30- and 60-day hazard ratios (95% confidence interval) of 2.3 (0.9, 6.2) and 2.0 (0.9, 4.7) respectively. CONCLUSIONS: Among patients with T2MI, many cases are diagnosed using subjective criteria. The presence of objective evidence of myocardial ischemia may identify a higher-risk group of T2MI patients in whom early outcomes are worse than myocardial injury. Emphasis on using objective evidence of myocardial ischemia to diagnose T2MI may result in a more precise and specific disease definition.

Clinical Evaluation of a New Point-of-Care System for Chemistry Panel Testing.

BACKGROUND: GEM Premier ChemSTAT™ is a point-of-care (POC) system that measures Na+, K+, Ca++, Cl-, glucose, hematocrit, creatinine, blood urea nitrogen (BUN), tCO2, pH, pCO2, and lactate from a single whole blood specimen, providing rapid results in POC settings such as the emergency department (ED). Accurate measurements of creatinine in whole blood and reporting of estimated glomerular filtration rate (eGFR) can minimize adverse effects of contrast-induced nephropathy. METHODS: Heparinized whole blood specimens from the ED were analyzed on the ChemSTAT by POC staff. Method comparison was performed against the cobas Integra c501 for creatinine, BUN, and tCO2, and against the GEM Premier 4000 for all other analytes. Precision was conducted with whole blood specimens assayed in triplicate over 6 days. Creatinine results from whole blood and plasma were used for eGFR, by isotope dilution mass spectrometry-traceable Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, and eGFR concordance was assessed. RESULTS: Creatinine, BUN, and tCO2 correlated well with plasma samples on the cobas, and all other analytes correlated well with whole blood specimens on the GEM Premier 4000 across the tested sample ranges. The regression slope was 0.951 to 1.047, along with a correlation coefficient (r) of ≥0.982 for all analytes. The pooled within-sample precision was 0% to 2.5% for all analytes. CONCLUSIONS: ChemSTAT demonstrated a strong correlation with the comparative methods and excellent precision. The system's analytical performance and continuous quality management make it suitable for use in the ED to provide rapid reliable test results, which could minimize the time to treatment and improve ED efficiency.

Spinal manipulative therapy and exercise for older adults with chronic low back pain: a randomized clinical trial.

Background: Low back pain (LBP) is a common disabling condition in older adults which often limits physical function and diminishes quality of life. Two clinical trials in older adults have shown spinal manipulative therapy (SMT) results in similar or small improvements relative to medical care; however, the effectiveness of adding SMT or rehabilitative exercise to home exercise is unclear. Methods: We conducted a randomized clinical trial assessing the comparative effectiveness of adding SMT or supervised rehabilitative exercise to home exercise in adults 65 or older with sub-acute or chronic LBP. Treatments were provided over 12-weeks and self-report outcomes were collected at 4, 12, 26, and 52 weeks. The primary outcome was pain severity. Secondary outcomes included back disability, health status, medication use, satisfaction with care, and global improvement. Linear mixed models were used to analyze outcomes. The primary analysis included longitudinal outcomes in the short (week 4-12) and long-term (week 4-52). An omnibus test assessing differences across all groups over the year was used to control for multiplicity. Secondary analyses included outcomes at each time point and responder analyses. This study was funded by the US Department of Health and Human Services, Health Resources and Services Administration. Results: 241 participants were randomized and 230 (95%) provided complete primary outcome data. The primary analysis showed group differences in pain over the one-year were small and not statistically significant. Pain severity was reduced by 30 to 40% after treatment in all 3 groups with the largest difference (eight percentage points) favoring SMT and home exercise over home exercise alone. Group differences at other time points ranged from 0 to 6 percentage points with no consistent pattern favoring one treatment. One-year post-treatment pain reductions diminished in all three groups. Secondary self-report outcomes followed a similar pattern with no important group differences, except satisfaction with care, where the two combination groups were consistently superior to home exercise alone. Conclusions: Adding spinal manipulation or supervised rehabilitative exercise to home exercise alone does not appear to improve pain or disability in the short- or long-term for older adults with chronic low back pain, but did enhance satisfaction with care. Trial registration: NCT00269321.