Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection.

BACKGROUND: The effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear. METHODS: In 14 U.S. hospitals with high adherence to quality measures for the treatment of pneumonia, we provided guidance for clinicians about national clinical practice recommendations for the treatment of lower respiratory tract infections and the interpretation of procalcitonin assays. We then randomly assigned patients who presented to the emergency department with a suspected lower respiratory tract infection and for whom the treating physician was uncertain whether antibiotic therapy was indicated to one of two groups: the procalcitonin group, in which the treating clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels, or the usual-care group. We hypothesized that within 30 days after enrollment the total antibiotic-days would be lower - and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher - in the procalcitonin group than in the usual-care group. RESULTS: A total of 1656 patients were included in the final analysis cohort (826 randomly assigned to the procalcitonin group and 830 to the usual-care group), of whom 782 (47.2%) were hospitalized and 984 (59.4%) received antibiotics within 30 days. The treating clinician received procalcitonin assay results for 792 of 826 patients (95.9%) in the procalcitonin group (median time from sample collection to assay result, 77 minutes) and for 18 of 830 patients (2.2%) in the usual-care group. In both groups, the procalcitonin-level tier was associated with the decision to prescribe antibiotics in the emergency department. There was no significant difference between the procalcitonin group and the usual-care group in antibiotic-days (mean, 4.2 and 4.3 days, respectively; difference, -0.05 day; 95% confidence interval [CI], -0.6 to 0.5; P=0.87) or the proportion of patients with adverse outcomes (11.7% [96 patients] and 13.1% [109 patients]; difference, -1.5 percentage points; 95% CI, -4.6 to 1.7; P<0.001 for noninferiority) within 30 days. CONCLUSIONS: The provision of procalcitonin assay results, along with instructions on their interpretation, to emergency department and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infection. (Funded by the National Institute of General Medical Sciences; ProACT ClinicalTrials.gov number, NCT02130986 .).

Elucidating the mechanism of the halide-induced ligand rearrangement reaction.

The formation of heteroligated Rh(I) complexes containing two different hemilabile phosphinoalkyl ligands, (κ(2)-Ph(2)PCH(2)CH(2)S-Aryl)(κ(1)-Ph(2)PCH(2)CH(2)O-C(6)H(5))RhCl, through a halide-induced ligand rearrangement (HILR) reaction has been studied mechanistically. The half-life of this rearrangement reaction depends heavily on the Rh(I) precursor used and the chelating ability of the phosphinoalkyl thioether (PS) ligand, while the chelating ability of the phosphinoalkyl ether (PO) ligand has less of an effect. An intermediate complex which contains two PO ligands, (nbd)(κ(1)-Ph(2)PCH(2)CH(2)O-C(6)H(5))(2)RhCl (nbd = norbornadiene), converts to (nbd)(κ(1)-Ph(2)PCH(2)CH(2)O-C(6)H(5))RhCl resulting in a free PO ligand. The free PO ligand can then react with a homoligated PS complex [(κ(2)-Ph(2)PCH(2)CH(2)S-Aryl)(2)Rh](+)Cl(-) producing the heteroligated product. The PS ligand generated during the reaction pathway can be trapped by the monoligated PO complex (nbd)(κ(1)-Ph(2)PCH(2)CH(2)O-C(6)H(5))RhCl, leading to the formation of the same heteroligated product. In this study, some of the key intermediates and reaction steps underlying the HILR reaction have been identified by variable temperature (31)P{(1)H} NMR spectroscopy and in two cases by single-crystal X-ray diffraction studies. Significantly, this work provides mechanistic insight into the HILR process, which is a key reaction used to prepare a large class of highly sophisticated three-dimensional metallosupramolecular architectures and allosteric catalysts.

Journal club: outcome measures, interim analyses, and bayesian approaches to randomized trials.

Editor's Capsule Summary for Ferre et al(1) WHAT IS ALREADY KNOWN ON THIS TOPIC: Patients with ureteral calculi are often prescribed adjunctive treatment with an alpha-blocking agent to enhance spontaneous stone passage. This practice has not been validated in emergency department (ED) patients. WHAT QUESTION THIS STUDY ADDRESSED: Does the addition of a 10-day course of tamsulosin to standard therapy after discharge from the ED increase the rate of passage of distal ureteral stones? WHAT THIS STUDY ADDS TO OUR KNOWLEDGE: In this randomized trial of 80 patients, most of whom had stones of 4 mm or less, time to stone passage was similar in tamsulosin and control patients. HOW THIS MIGHT CHANGE CLINICAL PRACTICE: This study does not support the routine use of tamsulosin in ED patients, though it is possible that it would be beneficial in patients with larger stones.

ST2 in emergency department chest pain patients with potential acute coronary syndromes.

STUDY OBJECTIVE: The emergency department (ED) evaluation of potential acute coronary syndrome patients is limited by the initial sensitivity of cell injury biochemical markers. Increased ST2, a protein thought to participate in the response to cardiovascular injury, has been noted to be prognostic in patients with acute myocardial infarction. We hypothesize that ST2 would be increased at presentation in ED chest pain patients with myocardial ischemia, thus allowing for the early identification of acute myocardial infarction, acute coronary syndrome, and 30-day adverse cardiovascular events, with an area under the receiver operator characteristic curve (AUC) for each outcome of greater than 0.7. METHODS: Patients aged 25 years or older and presenting to the ED with chest pain prompting an ECG were prospectively enrolled. ST2 was measured at presentation. Main outcomes were acute myocardial infarction, acute coronary syndrome, and 30-day events (death, acute myocardial infarction, or revascularization). Median ST2 values were calculated for patients with and without each outcome. The AUCs were calculated for each outcome. In a post hoc analysis, patients with outlying increased ST2 values were examined to determine possible alternative causes for ST2 expression. RESULTS: There were 348 patients enrolled. The outcomes were acute myocardial infarction 17 patients (4.9%), acute coronary syndrome 39 (11.2%), and 30-day events 23 (6.6%). The AUCs for acute myocardial infarction, acute coronary syndrome, and 30-day events were 0.636, 0.630, and 0.579, respectively. ST2 did not predict acute myocardial infarction, acute coronary syndrome, or 30-day events. It was increased in a small number of patients with pulmonary disease, notably, pulmonary emboli, systemic infection or inflammation, and alcohol abuse. CONCLUSION: ST2 was not of value in the evaluation of ED patients with potential acute coronary syndrome.

The impact of B-type natriuretic peptide in addition to troponin I, creatine kinase-MB, and myoglobin on the risk stratification of emergency department chest pain patients with potential acute coronary syndrome.

STUDY OBJECTIVE: The emergency department (ED) evaluation of chest pain patients with potential acute coronary syndrome is limited by the initial sensitivity of cell injury markers. BNP is increased during myocardial ischemia and is associated with adverse outcomes. We determine whether the addition of B-type natriuretic peptide (BNP) to troponin I, creatine kinase-MB (CK-MB), and myoglobin increases the sensitivity and negative predictive value (NPV) for acute myocardial infarction, acute coronary syndrome, and 30-day adverse events among chest pain patients with potential acute coronary syndrome. METHODS: A convenience sample of patients aged 30 years or older and presenting to an urban academic ED with nontraumatic chest pain, thus prompting an ECG, was enrolled, and consent was obtained. Blood samples were drawn at 0 and 90 minutes. Thirty-day follow-up was performed for all enrolled patients. Main outcomes were acute myocardial infarction, acute coronary syndrome, and 30-day events (death, acute myocardial infarction, or revascularization). BNP cutoffs were derived from receiver operator characteristics curves. The sensitivity, specificity, positive predictive value (PPV), and NPV with 95% confidence intervals (CIs) were calculated with and without BNP. Differences in sensitivity and specificity with the addition of BNP were calculated with 95% CIs, and McNemar's test was performed to compare sensitivities and specificities. RESULTS: Four hundred twenty-six patients were enrolled and analyzed. The cohort was 54.7+/-13.9 years old, 47.7% men, and 63.5% black. The outcomes were acute myocardial infarction, 39 (9.2%), acute coronary syndrome, 101 (23.7%), and 30-day adverse cardiovascular events 52 (12.2%). BNP cutoffs derived were 51, 31, and 31 pg/mL for acute myocardial infarction, acute coronary syndrome, and 30-day events, respectively. The addition of BNP showed increased sensitivity at the cost of decreased specificity for all 3 outcomes, as follows: (1) acute myocardial infarction: sensitivity: 87.2% (95% CI 72.6% to 95.7%) to 97.4% (95% CI 86.5% to 100%), difference 10.3% (95% CI-0.2% to 24.6%), P=.125; specificity: 62.3% (95% CI 57.2% to 67.1%) to 47.8% (95% CI 42.7% to 52.9%), difference 14.5% (95% CI 11.1% to %18.4), P<.0001; (2) acute coronary syndrome: sensitivity: 75.2% (95% CI 65.7% to 83.3%) to 88.1% (95% CI 80.2% to 93.7%), difference 12.9% (95% CI 7.0% to 21.0%), P=.0002; specificity: 68.0% (95% CI 62.6% to 73.0%) to 48.6% (95% CI 43.1% to 54.2%), difference 19.4% (95% CI 15.2% to 24.1%), P<.0001; (3) 30-day events: sensitivity: 71.2% (95% CI 56.9% to 82.9%) to 88.5% (95% CI 76.6% to 95.7%), difference 17.3% (95% CI 7.7% to 30.3%), P=.004; specificity: 61.8% (95% CI 56.6% to 66.7%) to 43.9% (95% CI 38.8% to 49.0%), difference 17.9% (95% CI 14.2% to 22.2%), P<.0001. There were trends toward increased NPV and decreased PPV for all outcomes, and the addition of BNP achieved a NPV of 99.5% (95% CI 97.0% to 100%) compared with 98.0% (95% CI 95.3% to 99.3%) for acute myocardial infarction. CONCLUSION: The addition of BNP as a dichotomous test to troponin I, CK-MB, and myoglobin produces increased sensitivity at a cost of decreased specificity for acute myocardial infarction, acute coronary syndrome, and 30-day adverse events. Because of this tradeoff, BNP cannot be recommended for use among all ED chest pain patients. However, the improved sensitivity may make this test useful in selected cohorts when the decreased specificity is less important.

The risk for acute coronary syndrome associated with atrial fibrillation among ED patients with chest pain syndromes.

OBJECTIVE: We sought to determine if atrial fibrillation is associated with an increased risk for an acute coronary syndrome (ACS) among emergency department (ED) patients with chest pain syndromes. METHODS: We performed a retrospective analysis of a prospectively collected database on ED patients with chest pain by selecting patients with atrial fibrillation and frequency-matched control subjects without atrial fibrillation. Measured outcomes were acute myocardial infarction (AMI), ACS, and unstable angina (UA). The relative risks of AMI, ACS, and UA associated with atrial fibrillation were calculated. RESULTS: One hundred forty patients with atrial fibrillation and 683 matched control subjects were identified. The rates of AMI for the atrial fibrillation and control groups were 11.4% and 10.8%, respectively; those of ACS were 27.9% and 26.7%, respectively; and those of UA were 16.4% and 15.8%, respectively. The relative risks of AMI and ACS did not increase in patients with atrial fibrillation: AMI, 1.05 (95% confidence interval [CI] = 0.63-1.75); ACS, 1.05 (95% CI = 0.78-1.40); and UA, 1.05 (95% CI = 0.6-1.7). CONCLUSION: Among patients presenting to the ED with chest pain syndromes, atrial fibrillation is not associated with an increased risk for AMI, ACS, and UA.

Application of the TIMI risk score in ED patients with cocaine-associated chest pain.

OBJECTIVE: The TIMI risk score has been validated as a risk stratification tool in emergency department (ED) patients with potential acute coronary syndrome. The goal of this study was to assess its ability to predict adverse cardiovascular outcomes in cocaine-associated chest pain. METHODS: This was a prospective cohort study of ED patients with chest pain with cocaine use. Data included demographics, medical history, and TIMI risk score. The main outcomes were acute myocardial infarction, revascularization, or death within 30 days of ED presentation. RESULTS: There were 261 patient visits. Patients were 43.2+8 years old, 73% male, 92% black, and 75% smokers. There were 33 patients with the composite outcome. The incidence of 30-day outcomes according to TIMI score is as follows: TIMI 0, 3.7% (95% CI, 0.1-8.3); TIMI 1, 13.2% (5.7-20.7); TIMI 2, 17.1% (4.3-29.8); TIMI 3, 21.4% (4.4-38.4); TIMI 4, 20.0% (0.1-43.6); TIMI 5/6, 50.0% (0.1-100). CONCLUSIONS: The TIMI risk score has no clinically useful predictive value in patients with cocaine-associated chest pain.

Tetrametallic rectangular box complexes assembled from heteroligated macrocycles.

The reaction of a heteroligated Rh(I) bimetallic macrocycle with rigid ditopic ligands (1,4-dicyanobenzene, 4-4'-dicyanobiphenyl, or dipyridyl terminated salen ligand 5) results in the formation of tetrametallic rectangular box complexes.

Impact of a negative prior stress test on emergency physician disposition decision in ED patients with chest pain syndromes.

OBJECTIVE: Many emergency department (ED) patients with potential acute coronary syndromes (ACS) have prior visits and prior cardiac testing; however, the effect of knowledge of prior testing on the emergency physician disposition decision making is not known. We studied the impact of prior noninvasive testing (ie, stress testing) for myocardial ischemia on disposition decision making in ED patients with potential ACS. METHODS: We performed a prospective cohort study of ED patients with chest pain who received an electrocardiogram for potential ACS. Data included demographics, medical history, stress test history, and TIMI risk score. Patients were followed in-house; 30-day telephone interviews were performed for follow-up. Main outcomes were ED disposition (admit/discharge) and a composite of 30-day death, acute myocardial infarction, and revascularization stratified on the basis of prior stress testing known at the time of presentation. Standard statistical techniques were used with 95% confidence intervals (CI). RESULTS: There were 1853 patients enrolled and 97% had follow-up. Patients had a mean age of 53 +/- 14 years; 60% were women, 67% were black. There were 1491 (79%) patients without a prior stress test, 291 (16%) had a normal prior stress test result, and 89 (5%) had an abnormal prior stress test result. Admission rates were 92% (95% CI, 87%-98%) for patients with a prior abnormal stress test, 73% (95% CI, 67%-78%) for patients with a normal prior stress test, and 70% (95% CI, 67%-72%) for patients without a prior stress test. Adverse outcomes were the highest among patients with prior abnormal stress test but did not differ significantly between patients with no prior stress test and patients with prior normal stress test (10.1% [95% CI, 3.6-16.7%] vs 5.2% [95% CI, 4.1-6.4%] vs 4.8% [95% CI, 2.4-7.3%]). CONCLUSION: Patients without prior stress tests and patients with prior normal stress tests were admitted for potential ACS at the same rate and had the same 30-day cardiovascular event rates. This suggests that prior stress testing does not affect subsequent disposition decisions. Perhaps cardiac catheterization or computed tomography coronary angiograms would have more of an impact on subsequent visits, making them potentially more cost-effective in the low-risk patient.

Computed tomography coronary angiography for rapid disposition of low-risk emergency department patients with chest pain syndromes.

BACKGROUND: Patients with recent normal cardiac catheterization are at low risk for complications of ischemic chest pain. Computed tomography (CT) coronary angiography has high correlation with cardiac catheterization for detection of coronary stenosis. Therefore, the investigators' emergency department (ED) incorporated CT coronary angiography into the evaluation of low-risk patients with chest pain. OBJECTIVES: To report on the 30-day cardiovascular event rates of the first 54 patients evaluated by this strategy. METHODS: Low-risk chest pain patients (Thrombolysis In Myocardial Infarction [TIMI] score of 2 or less) without acute ischemia on an electrocardiogram had CT coronary angiography performed in the ED. If the CT coronary angiography was negative, the patient was discharged home. The main outcomes were death and myocardial infarction within 30 days of ED discharge, as determined by telephone follow up and record review. Data are presented as percentage frequency of occurrence with 95% confidence intervals (CIs). RESULTS: Of the 54 patients evaluated, after CT coronary angiography, 46 patients (85%) were immediately released from the ED, and none had cardiovascular complications within 30 days. Eight patients were admitted after CT coronary angiography: one had >70% stenosis, five patients had 50%-69% stenosis, and two had 0-49% stenosis. Three patients had further noninvasive testing; one had reversible ischemia, and catheterization confirmed the results of CT coronary angiography. All patients were followed for 30 days, and none (0; 95% CI = 0 to 6.6%) had an adverse event during index hospitalization or at 30-day follow up. CONCLUSIONS: When used in the clinical setting for the evaluation of ED patients with low-risk chest pain, CT coronary angiography may safely allow rapid discharge of patients with negative studies. Further study to conclusively determine the safety and cost effectiveness of this approach is warranted.

Spontaneous formation of heteroligated PtII complexes with chelating hemilabile ligands.

The spontaneous formation of the heteroligated complex [PtCl(kappa(2)-Ph(2)PCH(2)CH(2)SMe)(Ph(2)PCH(2)CH(2)SPh)]Cl (8 a) by a novel ligand rearrangement process has been observed. By using the weak-link approach, the relative arrangement of the alkyl and aryl groups can be controlled by abstraction of chloride from 8 a to form the closed complex [Pt(kappa(2)-Ph(2)PCH(2)CH(2)SMe)(kappa(2)-Ph(2)PCH(2)CH(2)SPh)][BF(4)](2) (5) and reopening using halide ions to form semi-open complexes [PtX(kappa(2)-Ph(2)PCH(2)CH(2)SMe)(Ph(2)PCH(2)CH(2)SPh)]BF(4) (8 b; X=Cl(-)) and (8 c; X=I(-)). Analogous procedures using Ph(2)PCH(2)CH(2)SMe and 1,4-(Ph(2)PCH(2)CH(2)S)(2)C(6)H(4) lead to heteroligated bimetallic complexes 7 and 9, illustrating that this ligand rearrangement process can be used as a tool for the assembly of complementary metallosupramolecular structures.

Relationship between a clear-cut alternative noncardiac diagnosis and 30-day outcome in emergency department patients with chest pain.

BACKGROUND: Accurate identification of patients with acute coronary syndromes (ACSs) in the emergency department (ED) remains problematic. Studies have not been able to identify a cohort of patients that are safe for immediate ED discharge; however, prior studies have not examined the utility of a clear-cut alternative noncardiac diagnosis. OBJECTIVES: To compare the 30-day event rate in ED chest pain patients who were diagnosed with a clear-cut alternative noncardiac diagnosis with the 30-day event rate in the cohort of patients in whom a definitive diagnosis could not be made in the ED. METHODS: This was a prospective cohort study of consecutive ED patients with potential ACS. Data included demographics, medical and cardiac history, laboratory and electrocardiogram results, and whether or not the treating physician ascribed the condition to a clear-cut alternative noncardiac diagnosis. The main outcome was death, acute myocardial infarction (AMI), or revascularization within 30 days, as determined by phone follow-up or medical record review. RESULTS: The investigators enrolled 1,995 patients in the ED who had potential ACSs. Overall, 77 had a final hospital diagnosis of AMI (4%). Within 30 days, 73 patients received revascularization (4%), and 26 died (1%). There were 599 (30%) patients given a clear-cut alternative noncardiac diagnosis. Comparing the patients with a clear-cut alternative noncardiac diagnosis with those without an obvious noncardiac diagnosis, the presence of a clear-cut alternative noncardiac diagnosis was associated with a reduced risk of an in-hospital triple-composite endpoint (death, MI, and revascularization), with a risk ratio of 0.32 (95% confidence interval [CI] = 0.19 to 0.55) and 30-day triple-composite endpoint with a risk ratio of 0.45 (95% CI = 0.29 to 0.69); however, patients with a clear-cut alternative noncardiac diagnosis still had a 4% event rate at 30 days (95% CI = 2.4% to 5.6%). CONCLUSIONS: In the ED chest pain patient, the presence of a clear-cut alternative noncardiac diagnosis reduces the likelihood of a composite outcome of death and cardiovascular events within 30 days. However, it does not reduce the event rate to an acceptable level to allow ED discharge of these patients.

Triple-Decker Complexes Formed via the Weak Link Approach.

Through the weak link approach and a halide-induced ligand rearrangement process, semi-open and condensed triple-decker complexes (TDCs) were prepared and fully characterized. These triple-decker structures with tailorable layers through choice of hemilabile ligand starting materials can be chemically opened and closed to expose the interior layer in a reversible fashion using small-molecule and elemental anion ligand substitution reactions.

Prognostic value of symptoms during a normal or nonspecific electrocardiogram in emergency department patients with potential acute coronary syndrome.

OBJECTIVES: Emergency department (ED) patients with symptoms concerning for acute coronary syndrome (ACS) and a normal electrocardiogram (ECG) are at risk for adverse cardiovascular events. The authors hypothesized that patients with a normal or nonspecific ECG during symptoms have a lower risk for ACS than do those who are asymptomatic. METHODS: This was a prospective cohort study of ED patients with potential ACS. Outcomes were acute myocardial infarction (AMI), ACS, and 30-day cardiovascular events (death, AMI, revascularization). Fisher's exact test, t-tests, and logistic regression were used for data analysis. RESULTS: Of 2,593 patient visits, 2,007 patients had normal or nonspecific ECG findings. There were 1,196 who had symptoms during ECG, whereas 811 did not. Patients with symptoms at ECG acquisition were younger (49.9 vs. 55.2 years; p < 0.001) and were more likely to be black (70% vs. 64%; p = 0.002), female (63% vs. 58%; p = 0.03), and to have used cocaine (5% vs. 2%; p = 0.004). They were less likely to have hypertension (49% vs. 58%; p < 0.001), and diabetes (22% vs. 17%; p = 0.002). Patients with and without symptoms were equally likely to have AMI (both 2.8%; p > 0.99), ACS (10.1% vs. 11.5%; p = 0.34), and 30-day adverse outcomes (both 5.3%; p > 0.99). After adjustment for baseline cardiovascular-risk factors, odds ratios for patients with symptoms at the time of ECG acquisition were not significantly different for any of the outcomes: AMI (1.1; 95% confidence interval [CI] = 0.6 to 1.9); ACS (1.1; 95% CI = 0.8 to 1.4); or 30-day events (1.2; 95% CI = 0.8 to 1.9). CONCLUSIONS: Patients who are symptomatic during acquisition of a normal or nonspecific ECG have rates of adverse cardiovascular events similar to those of patients without symptoms. Clinicians should not rely on the absence of ECG abnormalities during symptoms to help exclude ACS.

Halide-induced supramolecular ligand rearrangement.

A novel reaction involving the halide-induced rearrangement of ligands within supramolecular Rh(I) complexes containing hemilabile ligands is presented. Three analogous bis- and trishemilabile ligands have been synthesized to construct bi- and trimetallic Rh(I) macrocyclic complexes. An intentionally added halide source results in the formal rotation of only one hemilabile ligand along the axis that is perpendicular to the plane defined by the aryl backbone of the hemilabile ligands. X-ray structures, as determined by X-ray crystallography, of key intermediates and products are presented.

Heteroligated metallomacrocycles generated via the weak-link approach.

Sequential reaction of two different hemilabile ligands (Ph(2)PCH(2)CH(2)X)(2)Ar (X = S, Ar = C(6)H(4) or C(6)(CH(3))(4); X = NCH(3), Ar = C(6)H(4); X = O, Ar = 9,10-C(14)H(8)) with a Rh(I) metal center resulted in the formation of heteroligated metallomacrocycles in high yield. The specific reaction conditions for each pair of hemilabile ligands are discussed. The solid-state structure of [[1,4-(Ph(2)PCH(2)CH(2)S)(2)C(6)H(4)]-[1,4-(Ph(2)PCH(2)CH(2)S)(2)C(6)(CH(3))(4)]Rh(2)](BF(4))(2), as determined by X-ray crystallography, is presented.