Miniaturized sample preparation needle: a versatile design for the rapid analysis of smoking-related compounds in hair and air samples

Miniaturized needle extraction device has been developed as a versatile sample preparation device designed for the rapid and simple analysis of smoking-related compounds in smokers' hair samples and environmental tobacco smoke. Packed with polymeric particle, the resulting particle-packed needle was employed as a miniaturized sample preparation device for the analysis of typical volatile organic compounds in tobacco smoke. Introducing a bundle of polymer-coated filaments as the extraction medium, the needle was further applied as a novel sample preparation device containing simultaneous derivatization/extraction process of volatile aldehydes. Formaldehyde (FA) and acetaldehyde (AA) in smoker's breath during the smoking were successfully derivatized with two derivatization reagents in the polymer-coated fiber-packed needle device followed by the separation and determination in gas chromatography (GC). Smokers' hair samples were also packed into the needle, allowing the direct extraction of nicotine from the hair sample in a conventional GC injector. Optimizing the main experimental parameters for each technique, successful determination of several smoking-related compounds with these needle extraction methods has been demonstrated.     

Comparison of extraction techniques for spray dried dispersion tablet formulations

Non-traditional sample preparation/extraction techniques that utilized the Caliper Life Sciences Tablet Processing Workstation II (TPW II), Microwave Assisted Extraction (MAE), and Accelerated Solvent Extraction (ASE) were evaluated for the extraction of Compound A from a 50 mgA, 15% Spray Dried Dispersion (SDD) immediate released (IR) tablet formulation. The TPW II consistently provided complete recoveries with very short preparation/extraction times (approximately 30 min). MAE also provided complete recovery of the API from the tablet formulation, but required approximately twice the extraction time, while ASE provided the lowest recovery of the three non-traditional techniques. The sample preparation/extraction efficiencies of the three non-traditional techniques were compared to that of the 5.5 h long manual method.     

Rapid on-line extraction and quantification of escitalopram from urine using sol-gel columns and mass spectrometric detection

A fast and easy way to quantify escitalopram in urine has been developed. A capillary with a silica based monolithic bed inside is used to extract escitalopram from urine and the for mass spectrometry detrimental matrix is washed away by applied pressure. The analyte is eluted by a solution containing organic modifier and directly electrosprayed into a time-of-flight mass spectrometer, ESI-TOF-MS. This method makes it possible to load large volumes of sample onto the column and preconcentrate escitalopram on-line before detection. Standard addition of escitalopram to the urine sample gave a linear calibration curve (R(2)=0.988). The analyzed sample was found to contain an escitalopram concentration of 0.62 ng/ml, well in line with earlier publications. The calculated LOD was 10 pg/ml and LOQ was 34 pg/ml as compared to earlier reports with a LLOQ of 1 ng/ml. The intra day variation of the escitalopram peak area is less than 6.3%.     

National hospital volume in acute pancreatitis: analysis of the Nationwide Inpatient Sample 1998–2006

Background:

The optimal management of acute pancreatitis remains controversial and current treatment protocols vary in degrees of medical and surgical management. Our group has previously shown in population-based studies that high-volume (HV) hospitals have lower rates of in-hospital mortality after pancreatectomy. We sought to examine if a similar mortality benefit exists for patients admitted with acute pancreatitis.

Methods:

Using the Nationwide Inpatient Sample (NIS), we examined discharge records for all adult admissions during 1998–2006 with a primary diagnosis of acute pancreatitis of any aetiology. Unique hospital identifiers were used to divide hospital volumes into equal thirds based on the number of admissions for acute pancreatitis per year (lowest tertile [low volume, LV]≤64 admissions/year; medium tertile [medium volume, MV] 65–117 admissions/year; highest tertile [high volume, HV]≥118 admissions/year). Covariates included patient demographics, hospital characteristics and patient co-morbidities using the Elixhauser index. Adjusted mortality represented the primary outcome measure and adjusted length of stay (LOS) and total charges were considered secondary measures.

Results:

There were 416 489 primary admissions for acute pancreatitis during the study period. In-hospital mortality for the cohort amounted to 1.6% (n= 6446). Hospital admissions for acute pancreatitis increased over the study period (P < 0.0001). High-volume hospitals tended to be large (82%), urban (99%) teaching (59%) centres (P < 0.0001), which cared for patients with more co-morbidities (35.9% of patients at HV hospitals vs. 29.1% at LV hospitals had at least three co-morbidities; P < 0.0001). Low-volume centres appeared more likely to perform pancreatic procedures than HV hospitals (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.32–1.70). Patients at HV hospitals had a lower likelihood of a prolonged adjusted LOS compared with those at LV (OR 0.75, 95% CI 0.71–0.79) or MV (OR 0.82, 95% CI 0.79–0.85) hospitals. After adjusting for patient and hospital factors, there was an in-hospital mortality benefit associated with being treated at an HV centre (OR 0.70, 95% CI 0.63–0.77). The decision to operate on a given patient did not alter the mortality benefit of the HV hospital.

Conclusions:

Rates of admissions for acute pancreatitis in the USA are increasing. High annual hospital volume of acute pancreatitis cases confers a shorter LOS, lower adjusted mortality and a lower likelihood of pancreatic procedure for patients admitted with acute pancreatitis. Although HV hospitals were less likely than MV or LV centres to perform pancreatic procedures, the role of surgery remains unclear. Further studies should examine other possible reasons for this mortality benefit, such as the availability of specialists, the quality of critical care facilities and the timing of operative intervention.     

Capillary electrophoresis–mass spectrometry: Recent trends in clinical proteomics

The increasing attention now paid to the elucidation of human proteome strengthened the development of analytical instruments able to provide reliable proteins and peptides quantitation and characterization in biological fluids and tissues. Emerging from proteomics, clinical proteomics exclusively considers its biomedical applications. It evaluates, often by high-throughput comparative platforms, the protein and peptide variations in body fluids, cells and tissues under different physiological and pathological conditions with the aim of discovering disease biomarkers. Among the available analytical methodologies, mass spectrometry in coupling with liquid chromatography or capillary electrophoresis demonstrated to be the eligible technique for protein detection and identification. This review summarizes the most recent applications of capillary electrophoresis–mass spectrometry to clinical proteomics, focusing on capillary zone electrophoresis separation mode and ESI and MALDI ionizations, which are the most frequently applied capillary electrophoresis–mass spectrometry hyphenated techniques.     

Determination of fluorides in pharmaceutical products for oral hygiene

Fluorides are common ingredients in pharmaceutical products for oral hygiene due to their recognized effect in the prevention of tooth decay. In dental products, fluorides can be added in several different forms, such as sodium fluoride, sodium monofluorophosphate, tin fluoride, or in the form of different amines. This work describes potentiometric determination of fluorides in the samples of toothpastes and mouthwash. The method was optimized for the particular analytical purpose; namely, for the analysis of toothpastes and mouthwash by applying different sample preparation protocols depending on the fluoride source. Good recovery (93–103%) confirmed the correctness of the sample preparation procedures. Calculated limit of detection and limit of quantification for the optimized method were 1 × 10^?3 mg/L and 2.8 × 10^?3 mg/L fluoride, respectively. In the minority of the analyzed samples, calculated contents agreed well with the certified values, whereas the samples of mouthwash demonstrated better agreement.     

ESTIMATION FOLLOWING EXTENSION OF A STUDY ON THE BASIS OF CONDITIONAL POWER

Proschan and Hunsberger [1] Proschan, M A and Hunsberger, S A. 1995. Designed Extension of Studies Based on Conditional Power. Biometrics, 51: 1315–1324. [Crossref], [PubMed], [Web of Science ®] , [Google Scholar] propose a method based on conditional power for designed extension of a study beyond its originally intended sample size. Their data-dependent sampling method can be viewed as a two-stage procedure in which the target total sample size is dependent upon the data observed at the first stage. We demonstrate that the maximum likelihood estimate of the parameter of interest upon completion may be biased, and that this bias is similar in direction and magnitude to that commonly associated with estimation following a group sequential test with predetermined target total sample size. Furthermore, we show how a bias adjusted estimate may be formed.     

Tests for Equivalence Based on Odds Ratio for Matched-Pair Design

Currently, methods for evaluation of equivalence under a matched-pair design use either difference in proportions or relative risk as measures of risk association. However, these measures of association are only for cross-sectional studies or prospective investigations, such as clinical trials and they cannot be applied to retrospective research such as case-control studies. As a result, under a matched-pair design, we propose the use of the conditional odds ratio for assessment of equivalence in both prospective and retrospective research. We suggest the use of the asymptotic confidence interval of the conditional odds ratio for evaluation of equivalence. In addition, a score test based on the restricted maximum likelihood estimator (RMLE) is derived to test the hypothesis of equivalence under a matched-pair design. On the other hand, a sample size formula is also provided. A simulation study was conducted to empirically investigate the size and power of the proposed procedures. Simulation results show that the score test not only adequately controls the Type I error but it can also provide sufficient power. A numerical example illustrates the proposed methods.     

A Note on Ethnic Sensitivity Studies

In this article, we propose a similarity criterion for ethnic sensitivity studies in pharmacokinetic variables. We present how this criterion can be used in the context of different dose-exposure models and how sample size and power calculations can be done. Examples for the planning and analysis of ethnic sensitivity studies are provided.     

Group Sequential Design for Randomized Phase III Trials under the Weibull Model

In this article, a parametric sequential test is proposed under the Weibull model. The proposed test is asymptotically normal with an independent increment structure. The sample size for a fixed sample test is derived for the purpose of group sequential trial design. In addition, a multi-stage group sequential procedure is given under the Weibull model by applying the Brownian motion property of the test statistic and sequential conditional probability ratio test methodology.