[How to value the work of geriatric caregivers]. / De l'importance de valoriser le travail des soignants en gériatrie.

Geriatric caregivers are subjected to physically and psychologically demanding situations. A geriatric short-stay service has implemented measures with a unique, creative and dynamic approach. These include participatory management, benevolence and the enhancement of the quality of work.

High-Flow Nasal Cannula in Early Emergency Department Management of Acute Hypercapnic Respiratory Failure Due to Cardiogenic Pulmonary Edema.

BACKGROUND: Noninvasive ventilation (NIV) is the recommended ventilatory support for acute cardiogenic pulmonary edema (CPE) associated with acute respiratory failure or hypercapnia. High-flow nasal cannula (HFNC) has emerged as an alternative to NIV in acute hypoxemic respiratory failure. We aimed to assess the efficacy of HFNC on early changes in [Formula: see text] and respiratory parameters in patients in the emergency department with acute hypercapnic CPE and to compare it to NIV. METHODS: We conducted a prospective observational study in consecutive emergency department patients with acute hypercapnic CPE. Subjects received either HFNC or NIV, according to the attending emergency physician's expertise in HFNC. The primary outcome was change in [Formula: see text] after treatment for 1 h. Secondary outcomes were change in pH, breathing frequency, signs of work of breathing, and comparisons to NIV. RESULTS: Twenty-seven subjects with a discharge diagnosis of hypercapnic CPE were analyzed. Subjects had a median age of 87 y (interquartile range [IQR] 78-93); 37% were male. Twelve (44%) received HFNC, and 15 (56%) received NIV. Median of changes in [Formula: see text] from baseline to after 1 h of treatment were 7 mm Hg (IQR 4-11, P = .002) for HFNC and 3 mm Hg (IQR 1-8, P = .02) for NIV, with no between-group difference. pH, breathing frequency and signs of work of breathing also improved after both HFNC and NIV. CONCLUSIONS: This preliminary study suggests that HFNC treatment for 1 h improves [Formula: see text] and respiratory parameters in subjects with hypercapnic acute CPE in a manner that is comparable to NIV. Further studies are needed to assess HFNC as a possible alternative to NIV in early management of acute hypercapnic respiratory failure of cardiogenic origin. (ClinicalTrials.gov registration NCT03883555.).

Is high-sensitivity troponin, alone or in combination with copeptin, sensitive enough for ruling out NSTEMI in very early presenters at admission? A post hoc analysis performed in emergency departments.

OBJECTIVES: Copeptin and high-sensitivity cardiac troponin (HS-cTn) assays improve the early detection of non-ST-segment elevation myocardial infarction (NSTEMI). Their sensitivities may, however, be reduced in very early presenters. SETTING: We performed a post hoc analysis of three prospective studies that included patients who presented to the emergency department for chest pain onset (CPO) of less than 6 hours. PARTICIPANTS: 449 patients were included, in whom 12% had NSTEMI. CPO occurred <2 hours from ED presentation in 160, between 2 and 4 hours in 143 and >4 hours in 146 patients. The prevalence of NSTEMI was similar in all groups (9%, 13% and 12%, respectively, p=0.281). MEASURES: Diagnostic performances of HS-cTn and copeptin at presentation were examined according to CPO. The discharge diagnosis was adjudicated by two experts, including cardiac troponin I (cTnI). HS-cTn and copeptin were blindly measured. RESULTS: Diagnostic accuracies of cTnI, cTnI +copeptin and HS-cardiac troponin T (HS-cTnT) (but not HS-cTnT +copeptin) lower through CPO categories. For patients with CPO <2 hours, the choice of a threshold value of 14 ng/L for HS-cTnT resulted in three false negative (Sensitivity 80%(95% CI 51% to 95%); specificity 85% (95% CI 78% to 90%); 79% of correctly ruled out patients) and that of 5 ng/L in two false negative (sensitivity 87% (95% CI 59% to 98%); specificity 58% (95% CI 50% to 66%); 52% of correctly ruled out patients). The addition of copeptin to HS-cTnT induced a decrease of misclassified patients to 1 in patients with CPO <2 hours (sensitivity 93% (95% CI 66% to 100%); specificity 41% (95% CI 33% to 50%)). CONCLUSION: A single measurement of HS-cTn, alone or in combination with copeptin at admission, seems not safe enough for ruling out NSTEMI in very early presenters (with CPO <2 hours). TRIAL REGISTRATION NUMBER: DC-2009-1052.

Arterial pH selectively predicts critical care needs in emergency department obese patients with acute dyspnea: A prospective comparative study.

INTRODUCTION: Obese patients with acute dyspnea may be prone to misorientation from the emergency department (ED), due to impaired gas exchange evaluation and altered basal respiratory profiles. This study aims to evaluate the prognostic value of arterial blood pH in obese ED patients with acute dyspnea in comparison to non-obese counterparts. METHODS: Single-center observational study of a cohort of 400 consecutive ED patients with acute dyspnea. The primary endpoint was a composite of Intensive Care Unit admission (with critical care needs) or in ED mortality. Predictors of the primary endpoint were assessed using multivariable logistic regression and ROC curve analysis, in obese (BMI ≥ 30 kg·m-2) and non-obese patients. RESULTS: 252 patients who had arterial blood gas testing were analyzed including 76 (30%) obese comparable to non-obese in terms of clinical history. 51 patients were admitted to ICU and 2 deceased before admission (20 obese (26%) vs 33 non-obese (19%); p = 0.17). Factors associated with ICU admission were arterial blood pH (pH < 7.36 vs pH ≥ 7.36) and gender. In multivariate models adjusted for risk factors, pH remained the sole independent predictor in obese patients, with no predictive value in non-obese patients (ROC AUC: 0.74, 95% CI [0.60; 0.87], optimal threshold for pH: 7.36, odds ratio: 10.5 [95% CI 3.18; 34.68]). CONCLUSION: Arterial blood pH may selectively predict critical care needs in ED obese patients with acute dyspnea, in comparison to non-obese. A falsely reassuring pH < 7.36 should be regarded as a marker of severity when assessing acute dyspnea in obese ED patients.

Dysregulated TRAF3 and BCL2 Expression Promotes Multiple Classes of Mature Non-hodgkin B Cell Lymphoma in Mice.

TNF-Receptor Associated Factor (TRAF)-3 is a master regulator of B cell homeostasis and function. TRAF3 has been shown to bind and regulate various proteins involved in the control of innate and adaptive immune responses. Previous studies showed that TRAF3 overexpression renders B cells hyper-reactive to antigens and Toll-like receptor (TLR) agonists, while TRAF3 deficiency has been implicated in the development of a variety of B cell neoplasms. In this report, we show that transgenic mice overexpressing TRAF3 and BCL2 in B cells develop with high incidence severe lymphadenopathy, splenomegaly and lymphoid infiltrations into tissues and organs, which is the result of the growth of monoclonal and oligoclonal B cell neoplasms, as demonstrated by analysis of VHDJH gene rearrangement. FACS and immunohistochemical analyses show that different types of mature B cell neoplasms arise in TRAF3/BCL2 double-transgenic (tg) mice, all of which are characterized by the loss of surface IgM and IgD expression. However, two types of lymphomas are predominant: (1) mature B cell neoplasms consistent with diffuse large B cell lymphoma and (2) plasma cell neoplasms. The Ig isotypes expressed by the expanded B-cell clones included IgA, IgG, and IgM, with most having undergone somatic hypermutation. In contrast, mouse littermates representing all the other genotypes (TRAF3-/BCL2-; TRAF3+/BCL2-, and TRAF3-/BCL2+) did not develop significant lymphadenopathy or clonal B cell expansions within the observation period of 20 months. Interestingly, a large representation of the HCDR3 sequences expressed in the TRAF3-tg and TRAF3/BCL2-double-tg B cells are highly similar to those recognizing pathogen-associated molecular patterns and damage-associated molecular patterns, strongly suggesting a role for TRAF3 in promoting B cell differentiation in response to these antigens. Finally, allotransplantation of either splenocytes or cell-containing ascites from lymphoma-bearing TRAF3/BCL2 mice into SCID/NOD immunodeficient mice showed efficient transfer of the parental expanded B-cell clones. Altogether, these results indicate that TRAF3, perhaps by promoting exacerbated B cell responses to certain antigens, and BCL2, presumably by supporting survival of these clones, cooperate to induce mature B cell neoplasms in transgenic mice.

Effect of Weight Loss on Postural Changes in Pulmonary Function in Obese Subjects: A Longitudinal Study.

BACKGROUND: Postural changes are known to affect normal lung volumes. A reduction in sitting to supine functional residual capacity (FRC) is well-described in non-obese subjects adopting a supine position. However, postural changes in lung volumes in the obese require further exploration. We aimed to longitudinally address the effects of weight loss on postural changes in lung volumes and pulmonary function in obese subjects. We tested the hypothesis that supine reduction in FRC would be absent in morbid obesity and recovered upon weight loss. METHODS: This was a prospective, observational, longitudinal study. Consecutive morbidly obese adults (N = 12, age: 44 ± 14 y, body mass index: 45 ± 5 kg/m(2)) enrolled in a bariatric surgery program were included. Standard pulmonary function tests and blood gas analysis were performed both before and 1 y after surgery. Pulmonary function was assessed in both the sitting and supine position using spirometry and multi-breath helium dilution. Parameters recorded before and after weight loss were compared. The main outcome measure was FRC. RESULTS: Ten subjects were retested 1 y after surgery (body mass index: 31 ± 5 kg/m(2)). FRC was not affected by change in posture before surgery. Supine reduction in FRC was observed after weight loss (ΔFRC: -0.6 ± 0.4 L, sitting vs supine, P = .002). Pulmonary gas exchange improved (alveolar-to-arterial oxygen partial pressure difference: -8 ± 11 mm Hg, P = .035). CONCLUSIONS: Although postural change in FRC is absent when the morbidly obese adopt a supine position, supine reduction in FRC can be recovered following gastroplasty-induced weight loss, despite residual mild to moderate obesity. This also shows that mild to moderate obesity may affect supine FRC more than morbid obesity. (ClinicalTrials.gov registration NCT02207192.).

Performances of the heart fatty acid protein assay for the rapid diagnosis of acute myocardial infarction in ED patients.

OBJECTIVE: We sought to evaluate the added value of heart fatty acid protein assay (HFABP) for rapid diagnosis of acute myocardial infarction in a prospective cohort of emergency department (ED) patients with acute chest pain. METHODS: High-sensitivity cardiac troponin T (hs-cTnT; Roche Diagnostics, Meylan, France) and HFABP (Randox, Mauguio, France) were blindly assayed from venous blood samples obtained at admission. Diagnosis was made by 2 ED physicians using all available data and serial cardiac troponin I as the biochemical standard. Diagnostic performances of HFABP combined with hs-cTnT were assessed using logistic regression. Analysis was conducted in all patients and in patients without ST-elevation myocardial infarction. RESULTS: A total of 181 patients were included (age, 61 ±17 years; male sex, 66%). Acute myocardial infarction occurred in 47 (25.9%) patients, including non-ST-elevation myocardial infarction in 31 (17.1%). The receiver operating characteristic area under the curve was 0.893 for hs-cTnT levels at presentation (95% confidence interval, 0.812-0.974) and 0.908 (95% confidence interval, 0.839-0.977) for the combination of hs-cTnT and HFABP, with no significant (P=.07). Adding HFABP to hs-cTnT increased both sensitivity and negative predictive value (NPV) for non-ST-elevation myocardial infarction diagnosis, with about 13% and 3% increase, respectively, leading to a sensitivity of 97% and an NPV of 99%. CONCLUSION: The assessment of HFABP at ED admission adds incremental value to initial hs-cTnT. The increase of sensitivity and NPV without sacrificing the specificity and positive predictive value in patients with chest pain with noncontributive electrocardiogram could potentially allow safe and early rule out of acute myocardial infarction without the need for further serial troponin testing.

A systematic review and collaborative meta-analysis to determine the incremental value of copeptin for rapid rule-out of acute myocardial infarction.

Multiple studies have evaluated copeptin, a surrogate for arginine vasopressin, in the diagnosis of acute myocardial infarction (AMI) with mixed results. A systematic review and collaborative meta-analysis were performed for diagnosis of AMI and assessment of prognosis in patients presenting to the emergency department with chest pain. MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing copeptin in such patients. Study investigators were contacted, and many provided previously unpublished data. Random-effects methods were used to compare the data for copeptin, troponin, and their combination. There were a total of 9,244 patients from the 14 included studies. Mean age was 62 years; 64% were men; and 18.4% were ultimately diagnosed with AMI. Patients with AMI had a higher presentation copeptin level than those without AMI (22.8 vs 8.3 pmol/L, respectively, p <0.001). Although troponin had better diagnostic accuracy than copeptin for AMI, the combination of copeptin and troponin significantly improved the sensitivity (0.905 [0.888 to 0.921] vs 0.686 [0.661 to 0.710], respectively, p <0.001) and negative predictive value (0.97 [0.964 to 0.975] vs 0.93 [0.924 to 0.936], respectively, p <0.001) compared with troponin alone. Elevation in copeptin carried a similar risk of all-cause mortality to an elevation in troponin (odds ratio 5.84 vs 6.74, respectively, p = 0.67). In conclusion, copeptin not only identifies patients at risk of all-cause mortality, but its addition to troponin improved the sensitivity and negative likelihood ratio for diagnosis of AMI compared with troponin alone. Thus, copeptin may help identify patients who may be safely discharged early from the emergency department.

Early rule out of acute myocardial infarction in ED patients: value of combined high-sensitivity cardiac troponin T and ultrasensitive copeptin assays at admission.

OBJECTIVE: We sought to evaluate the added value of ultrasensitive copeptin (us-copeptin) for early rule out of acute myocardial infarction in a prospective cohort of emergency department (ED) patients with acute chest pain. METHODS: This was a prospective study including consecutive patients with acute chest pain presenting to the ED within 12 hours of symptom onset. High-sensitivity cardiac troponin T (hs-cTnT, Roche Diagnostics, Meylan, France) and us-copeptin (ThermoFisher Scientific, Clichy, France) were blindly assayed from venous blood samples obtained at admission. Diagnosis was made by 2 ED physicians using all available data and serial cardiac troponin I as the biochemical standard. Diagnostic performances of us-copeptin combined with hs-cTnT were assessed using logistic regression. Analysis was conducted in all patients and in patients without ST-elevation myocardial infarction. RESULTS: A total of 194 patients were included (age, 61 [48-75] years; male sex, 63%). Acute myocardial infarction occurred in 52 (27%) patients, including non-ST-elevation myocardial infarction (NSTEMI) in 25 (13%). Patients with acute myocardial infarction had higher levels of hs-cTnT (50 [95% confidence interval, 19-173] ng/L) and us-copeptin (30 [13-113] pmol/L) at admission compared with those without (P < .05). Combination of markers significantly improved receiver operating characteristic area under the curve (from 0.89 [0.85-0.92] for hs-cTnT alone to 0.93 [0.89-0.97], P = .018). Sensitivity and negative predictive value were increased, particularly for NSTEMI diagnosis (sensitivity, 76% [54.9-90.6] to 96% [79.6-99.9]; negative predictive value, 95% [90.4-98.3] to 98.9% [94.2 to 100]). CONCLUSION: Assessment of us-copeptin combined with hs-cTnT on ED admission could allow safe and early rule out of NSTEMI for patients with negative results on both markers and help identify patients who may be suitable for discharge.

In vitro activity of daptomycin against Enterococcus faecalis under various conditions of growth-phases, inoculum and pH.

Enterococcus faecalis (E. faecalis) has become a major leading cause of nosocomial endocarditis. Treatment of such infections remains problematic and new therapeutic options are needed. Nine E. faecalis strains were tested: six obtained from patients presenting endocarditis, one with isolated bacteremia, and two reference strains. Antibiotics included daptomycin, alone or in combination, linezolid, tigecycline, rifampicin, gentamicin, teicoplanin, ceftriaxone and amoxicillin. Time-kill studies included colony counts at 1, 4 and 24 h of incubation. Significant bactericidal activity was defined as a decrease of ≥3log10CFU/ml after 24 h of incubation. Antibiotics were tested at a low (10(6) CFU/ml) and high (10(9) CFU/ml) inoculum, against exponential- and stationary-phase bacteria. We also performed time kill studies of chemically growth arrested E. faecalis. Various pH conditions were used during the tests. In exponential growth phase and with a low inoculum, daptomycin alone at 60 µg/ml and the combination amoxicillin-gentamicin both achieved a 4-log10 reduction in one hour on all strains. In exponential growth phase with a high inoculum, daptomycin alone was bactericidal at a concentration of 120 µg/ml. All the combinations tested with this drug were indifferent. In stationary phase with a high inoculum daptomycin remained bactericidal but exhibited a pH dependent activity and slower kill rates. All combinations that did not include daptomycin were not bactericidal in conditions of high inoculum, whatever the growth phase. The results indicate that daptomycin is the only antibiotic that may be able of overcoming the effects of growth phase and high inoculum.

Emergency department management of suspected carbon monoxide poisoning: role of pulse CO-oximetry.

BACKGROUND: The RAD-57 pulse CO-oximeter is a lightweight device allowing noninvasive measurement of blood carboxyhemoglobin (S(pCO)). We assessed the diagnostic value of pulse CO-oximetry, comparing S(pCO) values from the RAD-57 to standard laboratory blood carboxyhemoglobin (COHb) measurement in emergency department patients with suspected carbon monoxide (CO) poisoning. METHODS: This was a prospective, diagnostic accuracy study according to the Standards for the Reporting of Diagnostic Accuracy Studies criteria in consecutive adult emergency department patients with suspected CO poisoning. S(pCO) was measured with the RAD-57 simultaneously with blood sampling for laboratory blood gas analysis. We made no changes to our standard management of CO poisoning. Blood COHb > 5% for non-smokers, and > 10% for smokers were applied as the reference standard. RESULTS: We included 93 subjects: 37 smokers and 56 non-smokers. CO poisoning was diagnosed in 26 subjects (28%). The S(pCO) values ranged from 1% to 30%, with a median of 4% (IQR 2.7-7.3%). The COHb values ranged from 0% to 34%, with a median of 5% (IQR 2-9%). The mean differences between the COHb and S(pCO) values were -0.2% ± 3.3% (95% limits of agreement of -6.7% and 6.3%) for the whole cohort, -0.7% (limits of agreement -7.7% and 6.2%) for the non-smokers, and 0.6% (limits of agreement -5.0% and 6.2%) for the smokers. The optimal thresholds for detecting CO poisoning were S(pCO) of 9% and 6% for smokers and non-smokers, respectively. CONCLUSIONS: S(pCO) measured with the RAD-57 was not a substitute for standard blood COHb measurement. However, noninvasive pulse CO-oximetry could be useful as a first-line screening test, enabling rapid detection and management of CO-poisoned patients in the emergency department.

Predicting peripheral venous access difficulty in the emergency department using body mass index and a clinical evaluation of venous accessibility.

BACKGROUND: Peripheral venous (PV) cannulation, one of the most common technical procedures in Emergency Medicine, may prove challenging, even to experienced Emergency Department (ED) staff. Morbid obesity (body mass index [BMI] ≥ 40) has been reported as a risk factor for PV access failure in the operating room. OBJECTIVES: We investigated PV access difficulty in the ED, across BMI categories, focusing on patient-related predicting factors. METHODS: Prospective, observational study including adult patients requiring PV lines. Operators were skilled nurses and physicians. PV accessibility was clinically evaluated before all cannulation attempts, using vein visibility and palpability. Patient and PV placement characteristics were recorded. Primary outcome was failure at first attempt. Outcome frequency and comparisons between groups were examined. Predictors of difficult cannulation were explored using logistic regression. A p-value <0.05 was considered significant. RESULTS: PV lines were placed in 563 consecutive patients (53 ± 23 years, BMI: 26 ± 7 kg/m(2)), with a success rate of 98.6%, and a mean attempt of 1.3 ± 0.7 (range 1-7). Failure at the first attempt was recorded in 21% of patients (95% confidence interval [CI] 17.6-24.4). Independent risk factors were: a BMI ≥ 30 (odds ratio [OR] 1.98, 95% CI 1.09-3.60), a BMI < 18.5 (OR 2.24; 95% CI 1.07-4.66), an unfavorable (OR 1.66, 95% CI 1.02-2.69), and very unfavorable clinical assessment of PV accessibility (OR 2.38, 95% CI 1.15-4.93). CONCLUSION: Obesity, underweight, an unfavorable, and a very unfavorable clinical evaluation of PV accessibility are independent risk factors for difficult PV access. Early recognition of patients at risk could help in planning alternative approaches for achieving rapid PV access.

Proadrenomedullin, a useful tool for risk stratification in high Pneumonia Severity Index score community acquired pneumonia.

The aim of the present study was, first, to evaluate the prognostic value of mid-regional proadrenomedullin (proADM) in emergency department (ED) patients with a diagnosis of community acquired pneumonia (CAP) and, second, to analyze the added value of proADM as a risk stratification tool in comparison with other biomarkers and clinical severity scores. We evaluated proADM, C-reactive protein and procalcitonin, along with the Pneumonia Severity Index (PSI) score in consecutive CAP patients. Ability to predict 30-day mortality was assessed using receiver operating characteristic curve analysis, logistic regression, and reclassification metrics for all patients and for patients with high PSI scores. Primary outcome was death within 30 days after ED admission. One hundred nine patients were included (median age [interquartile range] 71 [27] years). Nine patients died within 30 days. A significant correlation between proADM and PSI was found (ρ = 0.584, P < .001). PSI and proADM levels were significantly predictive of risk of death. In patients with PSI class IV and V (score >90), proADM levels significantly predicted risk of death (OR [95% CI], 4.681 (1.661-20.221), P = .012) whereas PSI score did not (P = .122). ROC(AUC) (area under the receiver operating characteristic curve) was higher for proADM than for PSI score (ROC(AUC) [95% CI], 0.810 [0.654-0.965] and 0.669 [0.445-0.893] respectively). Reclassification analysis revealed that combination of PSI and proADM allows a better risk assessment than PSI alone (P = .001). MR-proADM may be helpful in individual risk stratification of CAP patients with a high PSI score in the ED, allowing to a better identification of patients at risk of death.

Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.

A novel series of alkoxyimino derivatives as S1P1 agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure-activity relationship studies led to the discovery of (E)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)benzyl)oxy)imino)ethyl)-2-ethylbenzyl)azetidine-3-carboxylic acid (32, BAF312, Siponimod), which has recently completed phase 2 clinical trials in patients with relapsing-remitting multiple sclerosis.

Analytical performances of the newly developed, fully automated Kryptor Copeptin assay: which impact factor for myocardial infarction rules out in the emergency department?

BACKGROUND: We evaluated the essential assay characteristics of the newly developed, fully automated Kryptor Copeptin assay including the assay performances and the clinical implications in parallel with the dosage of the cardiac Troponin I (cTnI) in patients presenting to the Emergency Department with chest pain with or without ECG abnormalities. METHODS: Analytical performance of the B-R-A-H-M-S Copeptin Kryptor was carried out according to the CLSI protocol EP17-A, volume 24, number 34 [3] including linearity imprecision, determination of quantification, and detection limits. An evaluation of the clinical concordance between cTnI and copeptin results was performed on consecutive patients, with chest pain suggestive of acute coronary syndromes (ACS), admitted to the Emergency Department of our hospital. RESULTS: At a total imprecision of 20% (which corresponds to the limit of the quantification) and the level giving a CV of 10%, the functional sensitivity was approximately 10.4 and 23 pmol/L, respectively. The mean detection limit for the B-R-A-H-M-S Copeptin Kryptor assay was 8 pmol/L (range 5.57-10.37 pmol/L) in our study. Clearly, the combination of the cTnI and copeptin markers at the decision limit of 0.04 microg/L and 10.4 pmol/L, respectively, improves the diagnosis of exclusion of ACS. CONCLUSIONS: The combination of negative troponin and negative copeptin (< quantification limit) could improve rapid sorting of ACS patients in an emergency. The Copeptin Kryptor assay is a useful diagnosis tool to rule out ACS and might be further enhanced by the recent development of sensitive troponins.

Chest compressions performed by ED staff: a randomized cross-over simulation study on the floor and on a stretcher.

BACKGROUND: Multiple factors may contribute to the observed survival variability following in-hospital cardiopulmonary resuscitation (CPR). While in-hospital CPR is most often performed on patients lying on a bed or stretcher, CPR training uses primarily manikins placed on the floor. We analyzed the quality of external chest compressions (ECC) in simulated cardiac arrest scenarios occurring both on a stretcher and on the floor. METHODS: Prospective cross-over simulation study enrolling ED nurses and nurse's aides as part of an annual evaluation. Simulated CPR was performed in the 2 rescuer-mode for 2 min, both kneeling on the floor, and standing beside a knee high stretcher. The order of position was randomized. ECC parameters were compared. RESULTS: ED nurses (n=48) and nurse's aides (n=26) performed 128 scenarios. Mean ECC depth was 32 ± 13 mm on the floor and 27 ± 11 mm on a stretcher (∆: 5 mm, 95%CI [3-7], P<.001). Participants last trained within a year (n=17) developed deeper ECCs than their colleagues (n=47) in both positions (floor: 39 ± 12 mm vs stretcher: 34 ± 11 mm (p=0.016) for those trained within the year, and floor: 29 ± 12 mm vs stretcher: 24 ± 10 mm (P<.001) for those trained over a year ago). CONCLUSIONS: The quality of chest compressions performed by ED staff was below 2005 guideline standards, with decreased ECC depth during CPR on a stretcher. Annual refresher courses should be implemented in the ED, with a focus on obtaining required ECC depth while standing next to a stretcher.

Breath analyzer screening of emergency department patients suspected of alcohol intoxication.

BACKGROUND: Acute alcohol intoxication is a frequent cause of emergency department (ED) visits. Evaluating a patient's alcohol intoxication is commonly based on both a physical examination and determination of blood alcohol concentration (BAC). OBJECTIVE: To demonstrate the feasibility and usefulness of using a last-generation infrared breath analyzer as a non-invasive and rapid screening tool for alcohol intoxication in the ED. METHODS: Adult patients suspected of acute alcohol intoxication were prospectively enrolled over 10 days. Breath alcohol concentrations (BrAC) were measured using a handheld infrared breath analyzer. BAC was determined simultaneously by automated enzymatic analysis of a venous blood sample. The relationship between BAC and BrAC values was examined by both linear regression and Bland-Altman analysis. RESULTS: The study included 54 patients (mean age 40±14 years, sex ratio M/F of 3/1). Breath and blood alcohol concentrations ranged from 0 to 1.44 mg/L and from 0 to 4.40 g/L (0-440 mg/dL), respectively. The mean individual BAC/BrAC ratio was 2615±387, 95% confidence interval 2509-2714, which is 30% higher than the legal ratio in France (2000). The correlation between both measurements was excellent: r=0.95 (0.92-0.97). Linear regression revealed BAC=0.026+1.29 (BrAC×2000) and BAC=0.026+0.99 (BrAC×2615). Mean BAC-BrAC differences and limits of agreement were 0.49 g/L [-0.35, 1.34] (or 49 mg/dL [-35, 134] and 0.01 g/L [-0.68, 0.71] (or 1 mg/dL [-68, 71]), for the 2000 and 2615 ratios, respectively. CONCLUSION: The calculated conversion coefficient provided a satisfactory determination of blood alcohol concentration. Breath alcohol testing, using appropriate BAC/BrAC conversion, different from the legal BAC/BrAC, could be a reliable alternative for routine screening and management of alcohol intoxication in the ED.

Potent activity against K562 cells by polyamide-seco-CBI conjugates targeting histone H4 genes.

We designed and synthesized conjugates between pyrrole-imidazole polyamides and seco-CBI that alkylate within the coding regions of the histone H4 genes. DNA alkylating activity on the histone H4 fragment and cellular effects against K562 chronic myelogenous leukemia cells were investigated. One of the conjugates, 5-CBI, showed strong DNA alkylation activity and good sequence specificity on a histone H4 gene fragment. K562 cells treated with 5-CBI down-regulated the histone H4 gene and induced apoptosis efficiently. Global gene expression data revealed that a number of histone H4 genes were down-regulated by 5-CBI treatment. These results suggest that sequence-specific DNA alkylating agents may have the potential of targeting specific genes for cancer chemotherapy.

Lymphocyte-specific TRAF3 transgenic mice have enhanced humoral responses and develop plasmacytosis, autoimmunity, inflammation, and cancer.

Tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) regulates both innate and adaptive immunity by modulating signaling by Toll-like receptors (TLR) and TNF receptors. TRAF3 was recently identified as a tumor suppressor in human multiple myeloma, suggesting a prominent role in plasma cell homeostasis. We have generated transgenic mice expressing human TRAF3 in lymphocytes. These mice are normal at birth, but they develop over time plasmacytosis and hypergammaglobulinemia, as well as systemic inflammation and tertiary lymphoid organ formation. The analysis of the humoral responses of the TRAF3 mice demonstrated increased responses to T-dependent and T-independent antigens with increased production of antigen-specific immunoglobulin Gs (IgGs) compared with wild-type mice. Furthermore, TLR-mediated IgG production is also increased in TRAF3 B cells. In addition, TRAF3 mice develop autoimmunity and are predisposed to cancer, particularly squamous cell carcinomas of the tongue ( approximately 50% incidence) and salivary gland tumors. In summary, TRAF3 renders B cells hyperreactive to antigens and TLR agonists, promoting autoimmunity, inflammation, and cancer, hereby providing a new model for studying de novo carcinogenesis promoted by B cell-initiated chronic inflammation.

Growth arrest of BCR-ABL positive cells with a sequence-specific polyamide-chlorambucil conjugate.

Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model.