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.     

Simultaneous estimation of cyclosporin and mycophenolic acid areas under the curve in stable renal transplant patients using a limited sampling strategy

OBJECTIVES: Area under the curve (AUC)-based monitoring of cyclosporin (CsA) could help to optimise therapeutic drug monitoring in certain transplant patients in addition to trough concentration monitoring. It is the method of choice for mycophenolic acid (MPA). The objective of this study was to develop a limited sampling strategy for simultaneous estimation of CsA and MPA AUCs in long-term renal transplant patients. METHODS: Twenty kidney transplant patients treated with CsA and mycophenolate mofetil were included in a pharmacokinetic study more than 6 months after transplantation. Multilinear regression analyses were performed to develop a model enabling the estimation of both drugs' AUCs using a limited number of samples. Dose-normalised data were used throughout the analysis. RESULTS: Trough concentrations of MPA were poorly correlated with AUC, either used alone (r2 = 0.232) or together with other concentrations. Several models for CsA AUC estimation met the predefined criteria (r2>0.9, P<0.05). The AUC of MPA was best estimated by a three-concentration model (AUC=0.58 C20 min+ 0.97 C1 h + 6.64 C3 h + 3.48; r2 = 0.946). These sampling times also applied to CsA AUC (AUC = 1.17 C20 min + 0.68 C1 h + 5.36 C3 h + 4.24; r = 0.985). AUCs estimated using these models in our patients using the jack-knife procedure were found to be precise and unbiased as compared with reference trapezoidal AUCs. CONCLUSION: We were able to develop a multilinear regression model for simultaneous estimation of both CsA and MPA AUCs using only three blood samples taken up to 3 h post-dosing.     

Cardiac output measurement in critically ill patients: comparison of continuous and conventional thermodilution techniques

The purpose of the study was to compare cardiac output (CO) measurement by continuous (CTD) with that by conventional thermodilution (TD) in critically ill patients. In 19 of 20 critically ill patients requiring a pulmonary artery catheterism, 105 paired CO measurements were performed by both CTD and TD. Regression analysis showed that: CTD CO = 1.18 TD CO ? 0.47. Correlation coefficient was 0.96. Bias and limit of agreement were — 0.8 and 2.4 L · min^?1, respectively. When a Bland and Altman diagram was constructed according to cardiac index ranges, biases were ?0.2 and ?0.3 and ?0.8 L · min^?1 · m^?2 and limits of agreement were 0.3, 0.7 and 1.6 L · min^?1 · m^?2 for low (<2.5 L · min^?1 · m^?2), normal (between 2.5 and 4.5 L · min^?1 · m^?2) and high (> 4.5 L · min^?1 · m^?2) cardiac indexes, respectively. It is concluded that CTD, compared with TD, is a reliable method of measuring CO, especially when cardiac index is ≤4.5 L · min^?1 · m^?2.     

Strategies for improving quality of life in older patients with metastatic breast cancer

Given both the increase in the mean age of the population of Western countries and the high incidence of breast cancer beyond the age of 65 years, it is evident that breast cancer in older women will be a very common problem for the medical oncologist. Metastatic breast cancer is still not amenable to a cure; therefore quality of life during therapy is an important issue, which until recently has been poorly investigated. Similarly, despite recent advances in breast cancer therapy, physicians have been reluctant to enrol older patients in clinical trials, and there is a lack of data regarding this population. This review focuses on quality-of-life issues during metastatic breast cancer treatment in geriatric patients, comparing the standard therapeutic options and newer approaches. Although first-line endocrine therapy with tamoxifen remains a standard treatment, the newer third-generation aromatase inhibitors provide similar or better efficacy with fewer adverse effects and a better quality of life. It has been a common belief that chemotherapy impairs quality of life, but recent studies in advanced breast cancer have shown that this therapy has a positive effect on quality of life, at least in responders. Consequently, chemotherapy should not be denied to elderly patients with metastatic breast cancer, provided a prior geriatric assessment is performed to evaluate the risk-benefit ratio. New chemotherapy strategies, such as the taxanes and orally administered chemotherapy, represent a very attractive alternative for a better quality of life in elderly patients with metastatic breast cancer.     

Next-generation sequencing of FLT3 internal tandem duplications for minimal residual disease monitoring in acute myeloid leukemia

Minimal Residual Disease (MRD) detection can be used for early intervention in relapse, risk stratification, and treatment guidance. FLT3 ITD is the most common mutation found in AML patients with normal karyotype. We evaluated the feasibility of NGS with high coverage (up to 2.4.10⁶ PE fragments) for MRD monitoring on FLT3 ITD. We sequenced 37 adult patients at diagnosis and various times of their disease (64 samples) and compared the results with FLT3 ITD ratios measured by fragment analysis. We found that NGS could detect variable insertion sites and lengths in a single test for several patients. We also showed mutational shifts between diagnosis and relapse, with the outgrowth of a clone at relapse different from that dominant at diagnosis. Since NGS is scalable, we were able to adapt sensitivity by increasing the number of reads obtained for follow-up samples, compared to diagnosis samples. This technique could be applied to detect biological relapse before its clinical consequences and to better tailor treatments through the use of FLT3 inhibitors. Larger cohorts should be assessed in order to validate this approach.     

CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.