Patrick Ray

Statistical evaluation of a biomarker.

A biomarker may provide a diagnosis, assess disease severity or risk, or guide other clinical interventions such as the use of drugs. Although considerable progress has been made in standardizing the methodology and reporting of randomized trials, less has been accomplished concerning the assessment of biomarkers. Biomarker studies are often presented with poor biostatistics and methodologic flaws that precludes them from providing a reliable and reproducible scientific message. A host of issues are discussed that can improve the statistical evaluation and reporting of biomarker studies. Investigators should be aware of these issues when designing their studies, editors and reviewers when analyzing a manuscript, and readers when interpreting results.

Cerebral cortex activation during experimentally induced ventilator fighting in normal humans receiving noninvasive mechanical ventilation.

Background:Mechanical ventilation is delivered to sedated patients during anesthesia, but also to nonsedated patients (ventilator weaning, noninvasive ventilation). In these circumstances, patient–ventilator asynchrony may occur, provoking discomfort and unduly increasing work of breathing. In certain cases, it is associated with an increased inspiratory load. Inspiratory loading in awake humans activates the premotor cortical regions, as illustrated by the occurrence of electroencephalographic premotor potentials. In normal humans during noninvasive ventilation, the authors used an experimental model of patient–ventilator asynchrony to determine whether premotor cortical activation occurs in this setting. Methods:Noninvasive pressure support ventilation was administered to seven healthy volunteers aged 22–27 yr with continuous electroencephalographic recordings in Cz. The ventilator settings were first adjusted to make the subjects feel comfortable (“comfort”), and then modified to induce respiratory “discomfort” (evaluated on a 10-cm visual analog scale). This was achieved by setting the ventilator to a higher trigger level, reducing the slope of the pressure support rise, and reducing the level of pressure support. The settings were finally brought back to their initial values. To identify a respiratory-related premotor activity, a minimum of 80 preinspiratory electroencephalographic epochs were averaged. Results:Altering ventilator settings induced respiratory discomfort (average visual scale 4 [1.5–6.0] vs. 0 [0–1.0] cm during “comfort”; P < 0.0001). This was associated with premotor potentials in all cases, which disappeared upon return to “comfort.” Conclusions:This study indicates that “ventilator fighting” in healthy humans is associated with an activation of higher cerebral areas. Premotor potentials could thus be markers of patient–ventilator asynchrony at the brain level. Both corroboration in patients and the elucidation of the causative or reactive nature of the association are needed before determining clinical implications.

Cardiac asthma in elderly patients: incidence, clinical presentation and outcome

BackgroundCardiac asthma is common, but has been poorly investigated. The objective was to compare the characteristics and outcome of cardiac asthma with that of classical congestive heart failure (CHF) in elderly patients.MethodsProspective study in an 1,800-bed teaching hospital.ResultsTwo hundred and twelve consecutive patients aged ≥ 65 years presenting with dyspnea due to CHF (mean age of 82 ± 8 years) were included. Findings of cardiac echocardiography and natriuretic peptides levels were used to confirm CHF. Cardiac asthma patients were defined as a patient with CHF and wheezing reported by attending physician upon admission to the emergency department. The CHF group (n = 137) and the cardiac asthma group (n = 75), differed for tobacco use (34% vs. 59%, p < 0.05), history of chronic obstructive pulmonary disease (16% vs. 47%, p < 0.05), peripheral arterial disease (10% vs. 24%, p < 0.05). Patients with cardiac asthma had a significantly lower pH (7.38 ± 0.08 vs. 7.43 ± 0.06, p < 0.05), and a higher PaCO2 (47 ± 15 vs. 41 ± 11 mmHg, p < 0.05) at admission. In the cardiac asthma group, patients had greater distal airway obstruction: forced expiratory volume in 1 second of 1.09 vs. 1.33 Liter (p < 0.05), and a forced expiratory flow at 25% to 75% of vital capacity of 0.76 vs. 0.99 Liter (p < 0.05). The in-hospital (23% vs. 19%) and one year mortality (48% vs. 43%) rates were similar.ConclusionPatients with cardiac asthma represented one third of CHF in elderly patients. They were more hypercapnic and experienced more distal airway obstruction. However, outcomes were similar.

Comparison of troponin I and N-terminal-pro B-type natriuretic peptide for risk stratification in patients with pulmonary embolism.

Objective We compared the usefulness of plasma N-terminal-pro B-type natriuretic peptide and troponin I levels for risk stratification of patients with pulmonary embolism. Methods This was a prospective study performed in an emergency department. N-terminal-B-type natriuretic peptide assay and troponin I were performed blindly at admission in patients with pulmonary embolism confirmed by imaging tests. A complicated pulmonary embolism was defined as any of the following: death, cardiopulmonary resuscitation, requirement for mechanical ventilation, use of pressors, thrombolysis, surgical embolectomy or admission in an intensive care unit. Results Sixty patients (mean age±standard deviation of 72±15 years) were included. Seventeen (28%) patients had adverse events: all were admitted in intensive care unit, one was treated with surgical embolectomy and one with thrombolysis, and three died. The median N-terminal-pro B-type natriuretic peptide level (95% confidence interval) was higher in the group of patients with complicated pulmonary embolism, 4086u2009pg/ml (505–8998) versus 352u2009pg/ml (179–662), respectively (P<0.05). The mean value of troponin I was similar in the complicated pulmonary embolism group, 0.09±0.17u2009μg/l versus 0.08±0.41u2009μg/l, respectively (P=0.93). The best threshold value of N-terminal-pro B-type natriuretic peptide was 1000u2009pg/ml, and the receiver operating characteristic curve demonstrated that N-terminal-pro B-type natriuretic peptide significantly predicted the complicated pulmonary embolism with an area under the receiver operative curve of 0.72 (0.58–0.83) (P<0.05), whereas troponin I did not [area under the receiver operative curve of 0.58 (0.42–0.71)]. Conclusion Unlike troponin I, N-terminal-pro B-type natriuretic peptide may be an accurate marker of in-hospital complication after pulmonary embolism.

Natriuretic peptide testing in EDs for managing acute dyspnea: a meta-analysis ☆

PURPOSESnThe aim of the study was to assess the usefulness of systematic natriuretic peptide testing in the management of patients presenting with acute dyspnea to emergency departments (EDs).nnnMETHODSnWe performed a systematic review and meta-analysis of randomized controlled trials assessing the usefulness of B-type natriuretic peptide (BNP) or its N-terminal fragment (NT-proBNP) in the management of patients presenting with dyspnea into ED. We searched Medline, Embase, and conference proceedings without restriction on neither language nor publication year. Selection of studies, data collection, and assessment of risk of bias were performed by 2 reviewers independently and in duplicate. Outcomes included hospital admission rate, time to discharge, and length of hospital stay, mortality and rehospitalization rates, and total direct medical costs. Combined risk ratios were estimated using fixed or random effects model. Duration and cost data were not combined.nnnFINDINGSnFour randomized controlled trials, representing 2041 patients, were selected. In 4 trials, there was a tendency for hospital admission to be reduced in the intervention group (combined risk ratio, 0.95; 95% confidence interval, 0.89-1.01). Time to discharge was significantly reduced in 2 trials, whereas there was no significant reduction in hospital length of stay in 3 trials. There was no significant effect on in-hospital and 30-day mortality rates or rehospitalization rates (3 trials reporting each outcome). Two trials found significant reduction in direct costs.nnnCONCLUSIONSnThe current evidence remains inconclusive on whether systematic natriuretic peptide testing is useful for the management of patients presenting to ED with acute dyspnea.

Concordance between capnography and capnia in adults admitted for acute dyspnea in an ED

BACKGROUNDnEnd-tidal carbon dioxide pressure (etCO(2)) is widely used in anaesthesia and critical care in intubated patients. The aim of our preliminary study was to evaluate the feasibility of a simple device to predict capnia in spontaneously breathing patients in an emergency department (ED).nnnPATIENTS AND METHODSnThis study was a prospective, nonblind study performed in our teaching hospital ED. We included nonintubated patients with dyspnea (> or =18 years) requiring measurement of arterial blood gases, as ordered by the emergency physician in charge. There were no exclusion criteria. End-tidal CO(2) was measured by an easy-to-use device connected to a microstream capnometer, which gave a continuous measurement and graphical display of the etCO(2) level of a patients exhaled breath.nnnRESULTSnA total of 43 patients (48 measurements) were included, and the majority had pneumonia (n = 12), acute cardiac failure (n = 8), asthma (n = 7), or chronic obstructive pulmonary disease exacerbation (n = 6). Using simple linear regression, the correlation between etCO(2) and Paco(2) was good (R = 0.82). However, 18 measurements (38%) had a difference between etCO(2) and Paco(2) of 10 mm Hg or more. The mean difference between the Paco(2) and etCO(2) levels was 8 mm Hg. Using the Bland and Altman matrix, the limits of agreement were -10 to +26 mm Hg.nnnCONCLUSIONnIn our preliminary study, etCO(2) using a microstream method does not seem to accurately predict Paco(2) in patients presenting to an ED for acute dyspnea.

Meningitis in elderly patients.

Meningitis is uncommon in elderly patients in emergency department (ED). The characteristics of bacterial meningitis (BM) and nonbacterial meningitis (NBM) occurring in older patients are compared. A prospective multicenter study was conducted in the EDs of three teaching hospitals. Consecutive adult patients (n=159) with a confirmed meningitis [cerebrospinal fluid (CSF) leukocyte count greater than 5u2009mm3] were included in this study. Eighteen consecutive patients (11%) aged more than or equal to 60 years (median age of 67 years) presenting with confirmed meningitis were included. In the older group, the prevalence of BM was higher than in the younger group (50% vs. 11%, P<0.05). At admission in the ED, older patients experienced less typical symptoms of meningitis than the younger. Conversely, elderly patients presented more frequent signs of encephalitis. In older adults, CSF white blood cells count, CSF protein, and CSF/blood glucose ratio were different between NBM and BM. The causative species of BM were Streptococcus species other than pneumoniae in two episodes, and Streptococcus pneumoniae in two patients; the causative species of NBM were enterovirus in one episode, herpes simplex virus 1 in four (compared with the younger group, P<0.05), and varicella zoster virus in one. The prevalence of BM was higher in the older group than in the younger. Older patients experienced less typical symptoms of meningitis and more frequently signs of encephalitis, with a high prevalence of herpes simplex virus 1 meningitis.

Isosorbide dinitrate bolus for heart failure in elderly emergency patients: a retrospective study.

In this study we aimed to determine whether isosorbide dinitrate (ISDN) bolus is associated with hypotension in patients aged at least 75 years presenting to an emergency department (ED) with acute heart failure (AHF) syndrome. This is a retrospective study, and all patients with AHF presenting in our ED during 2007 were included. We included 136 patients: 25 (18%) of them received ISDN in bolus (group B) among other treatments, and 111 (82%) did not (group O). Baseline characteristics of the two groups were not similar, with a higher rate of hypertension in group B. The mean lower systolic blood pressure after treatment was similar: 116±18 mmHg in group O compared with 116±19 mmHg in group B+, and was less than 90 mmHg in 0% cases in group B+ versus 3% in group O (P=0.5). Secondary endpoints were not significant, with mortality in group B of 4% versus 10% in group O (P=0.32). ISDN is not associated with more hypotension when used in bolus for elderly patients treated in the ED for AHF.

Reliability of electronic recording of waiting times in the emergency department: a prospective multicenter study.

We aimed to evaluate the reliability of waiting times (WT) measures electronically retrieved. We prospectively collected true WT in four emergency departments during 20 predefined 2-h inclusion periods, and compared them with the electronically retrieved waiting time (ERWT). We assessed agreement with calculation of rate of outliers (difference exceeding 20u2009min), bias, and its 95% limits of agreements, and associated Bland and Altman plot. We analyzed 274 patients. The mean difference was −2u2009min (SD 13) between ERWT and true WT, with a 95% limits of agreements (−28 to 24u2009min). Bland and Altman plot showed a good agreement, and we report 7% of outliers. Using ERWT, 14 patients (5%) were misclassified as having their target WT exceeded or not. ERWT agree well with the true WT, although the significant rate of outlier and misclassification calls for caution in their interpretation.

Accuracy of oxygen tissue saturation values in assessing severity in patients with sepsis admitted to emergency departments.

Introduction Near-infrared spectrometry assesses hemoglobin saturation of oxygen in tissues (StO2). Although it may provide additional information on local microcirculation function, the usefulness of near-infrared spectrometry in septic patients is debated. This study evaluated whether baseline StO2 value is useful in septic patients admitted to the emergency department with a diagnosis of severe sepsis. Materials and methods We carried out a prospective multicenter study in three emergency departments in Paris, France. Triage nurses were to record StO2, the results were blinding to the emergency physicians. Patients were eligible when presenting with at least two of the following parameters: temperature higher than 38°C or less than 36°C, respiratory rate greater than 30/min, heart rate greater than 120/min, and systolic arterial blood pressure less than 110 mmHg. Patients with a final diagnosis of sepsis and severe sepsis were analyzed. Results We analyzed 98 patients (70 with sepsis and 28 with severe sepsis). Thirty-day mortality was 2.9 versus 14.3% (P=0.048) in the sepsis and the severe sepsis group, respectively. No significant difference in the median StO2 was observed in patients with sepsis and severe sepsis [79% (74–85%) vs. 77% (72–83%), respectively; P=0.66]. The area under the curve of the receiver operating characteristic curve for StO2 to predict severe sepsis was 0.53 (0.39–0.66; P=0.5) and the cutoff value was 77%. Median StO2 did not differ in patients admitted to the ICU [80% (60–88%) vs. 79% (74–84%); P=0.78] and in nonsurvivors compared with that of survivors [79% (74–85%) vs. 76% (73–83%); P=0.64]. Conclusion This study fails to show any value of StO2 baseline at triage for early detection of severe sepsis in emergency patients.