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.     

Pulsed Doppler Ultrasonography Guidance for Catheterization of the Subclavian Vein: A Randomized Study

Background: Catheterization of the subclavian vein may lead to severe complications. The current randomized study compared a technique of pulsed Doppler ultrasonography guidance and the standard method for subclavian vein catheterization.

Methods: Standard and Doppler ultrasonography guidance methods were performed by the same physician in 286 patients, 143 in each group. Primary end points were immediate complications (arterial puncture, pneumothorax, wrong position of catheter tip), failures, the number of subclavian vein catheterizations with immediate complication or failure, the number of skin punctures per catheterization, and the time to placement of the guide wire. The secondary end points were the determination of predicting factors of successful cannulation in each group.

Results: Both groups were similar according to morphologic parameters of the patients. A greater number of subclavian vein catheterizations were performed on the right side using Doppler guidance (105 vs. 73, P < 0.01). Doppler guidance decreased complications (5.6% vs. 16.8%, P < 0.01), largely because of a smaller number of catheters for which the tip was defined to be in incorrect position (0.7% vs. 7.7%, P < 0.01). The time to catheterization was longer with Doppler guidance (300 vs. 27 s, P < 0.001). Failures, catheterizations of the subclavian vein with immediate complications or failure, and the total number of skin punctures per catheterization were similar in both groups. Using Doppler guidance, the presence of a good Doppler signal (124 of 143) was predictive of successful catheterization (123 successful cannulations, P < 0.001).     

Food-cobalamin malabsorption in elderly patients: clinical manifestations and treatment

PURPOSE: Approximately 15% of people aged more than 60 years old have a cobalamin (vitamin B12) deficiency, mainly in relation with food-cobalamin malabsorption (FCM). To date, no study has documented this disorder in the elderly. There is also little information on clinical consequences. SUBJECTS AND METHODS: We studied 92 elderly patients with well-established FCM who were extracted from an observational cohort study (1995-2004) of 172 consecutive elderly patients with documented cobalamin deficiency. RESULTS: The median patient age was 76 +/- 8 years; 60 patients were women. The most common clinical manifestations were neurologic or psychologic: mild sensory polyneuropathy (44.6%), confusion or impaired mental functioning (22.8%), and physical asthenia (20.7%). Hematologic abnormalities were reported in at least one third of the patients: anemia (21%), leukopenia (10.9%), thrombopenia (8.7%), and pancytopenia (6.5%). All patients had low serum vitamin B12 levels (<200 pg/mL), with a mean value (+/- standard deviation) of 131 +/- 38 pg/mL and total serum homocysteine level of 22.1 +/- 9.3 micromol/L. The mean hemoglobin level was 10.9 +/- 2.5 g/dL and the mean erythrocyte cell volume 95.7 +/- 12.7 fL. Correction of the serum vitamin B12 levels and hematologic abnormalities was achieved equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. CONCLUSIONS: This study suggests that in elderly patients, FCM may be associated with significant neurologic, psychologic, and hematologic abnormalities, which seem to respond equally well to either oral or parenteral vitamin B12 therapy.     

Mutation Landscape of Acquired Cross-Resistance to Glycopeptide and β-Lactam Antibiotics in Enterococcus faecium

Bypass of the d,d-transpeptidase activity of penicillin-binding proteins by an l,d-transpeptidase (Ldt_fm) results in resistance to ampicillin and glycopeptides in Enterococcus faecium M9, a mutant obtained by nine consecutive selection steps. Resistance requires activation of a cryptic locus for production of the essential tetrapeptide-containing substrate of Ldt_fm and impaired activity of protein phosphatase StpA. Here, whole-genome sequencing revealed a high mutation rate for the entire selection procedure (79 mutations in 900 generations). Acquisition of a mutation in the mismatch repair gene mutL had little impact on the frequency of rifampin-resistant mutants although the mutation spectrum of M9 was typical of impaired MutL with high transversion to transition (40/11) and substitution to deletion (51/28) ratios. M9 did not mainly accumulate neutral mutations since base substitutions occurred more frequently in coding sequences than expected (χ² = 5.0; P < 0.05) and silent mutations were underrepresented (χ² = 5.72; P < 0.02). None of the mutations directly affected recognition of the tetrapeptide substrate of Ldt_fm by peptidoglycan synthesis enzymes. Instead, mutations appear to remodel regulatory circuits involving two-component regulatory systems and sugar metabolism. The high number of mutations required for activation of the l,d-transpeptidase pathway may strongly limit emergence of cross-resistance to ampicillin and glycopeptides by this mechanism.     

Rapid Cytolysis of Mycobacterium tuberculosis by Faropenem,an Orally Bioavailable β-Lactam Antibiotic

Recent clinical studies indicate that meropenem, a β-lactam antibiotic, is a promising candidate for therapy of drug-resistant tuberculosis. However, meropenem is chemically unstable, requires frequent intravenous injection, and must be combined with a β-lactamase inhibitor (clavulanate) for optimal activity. Here, we report that faropenem, a stable and orally bioavailable β-lactam, efficiently kills Mycobacterium tuberculosis even in the absence of clavulanate. The target enzymes, l,d-transpeptidases, were inactivated 6- to 22-fold more efficiently by faropenem than by meropenem. Using a real-time assay based on quantitative time-lapse microscopy and microfluidics, we demonstrate the superiority of faropenem to the frontline antituberculosis drug isoniazid in its ability to induce the rapid cytolysis of single cells. Faropenem also showed superior activity against a cryptic subpopulation of nongrowing but metabolically active cells, which may correspond to the viable but nonculturable forms believed to be responsible for relapses following prolonged chemotherapy. These results identify faropenem to be a potential candidate for alternative therapy of drug-resistant tuberculosis.     

Critères des réponses thérapeutiques TEP dans les hémopathies lymphoïdes

Metabolic imaging, primarily positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG), is an investigation modality that provides additional information on the tumour viability and progression, complementary to that obtained by conventional anatomic imaging. As such, FDG-PET has become an essential modality in the clinical management of patients with lymphoma for staging, detecting recurrence, and assessing the therapeutic response, both during the chemotherapy and at the end of treatment, which is conditional upon the availability of objective, reliable and reproducible PET criteria. This assessment relies usually on a simple and basic visual analysis of images, most often in a comparative manner. In some cases, using semi-quantitative analysis as Standardized Uptake Value (SUV) can be useful, keeping in mind the limitations of this method. This article reviews the recent literature on this topic to define, site by site, pathological uptake values in lymphoma, during and after treatment.     

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/m²), 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.     

In Vitro Cross-Linking of Mycobacterium tuberculosis Peptidoglycan by l,d-Transpeptidases and Inactivation of These Enzymes by Carbapenems

The Mycobacterium tuberculosis peptidoglycan is cross-linked mainly by l,d-transpeptidases (LDTs), which are efficiently inactivated by a single β-lactam class, the carbapenems. Development of carbapenems for tuberculosis treatment has recently raised considerable interest since these drugs, in association with the β-lactamase inhibitor clavulanic acid, are uniformly active against extensively drug-resistant M. tuberculosis and kill both exponentially growing and dormant forms of the bacilli. We have purified the five l,d-transpeptidase paralogues of M. tuberculosis (Mt1 to -5) and compared their activities with those of peptidoglycan fragments and carbapenems. The five LDTs were functional in vitro since they were active in assays of peptidoglycan cross-linking (Mt5), β-lactam acylation (Mt3), or both (Mt1, Mt2, and Mt4). Mt3 was the only LDT that was inactive in the cross-linking assay, suggesting that this enzyme might be involved in other cellular functions such as the anchoring of proteins to peptidoglycan, as shown in Escherichia coli. Inactivation of LDTs by carbapenems is a two-step reaction comprising reversible formation of a tetrahedral intermediate, the oxyanion, followed by irreversible rupture of the β-lactam ring that leads to formation of a stable acyl enzyme. Determination of the rate constants for these two steps revealed important differences (up to 460-fold) between carbapenems, which affected the velocity of oxyanion and acyl enzyme formation. Imipenem inactivated LDTs more rapidly than ertapenem, and both drugs were more efficient than meropenem and doripenem, indicating that modification of the carbapenem side chain could be used to optimize their antimycobacterial activity.