How to optimize the prescription of laboratory tests? Success and failures in an academic hospital.

In the context of the flat-rate reimbursements in healthcare, we reviewed physicians' behavior towards laboratory test ordering. We demonstrated how it could be improved when a specific stage of the patient management is considered. We took a multi-step approach to analyze the laboratory test orders in the context of planned laparoscopic cholecystectomy in a general teaching hospital. A reference order set was defined through a collaborative analysis between clinicians and laboratory physicians. The clinical and financial impacts were then evaluated over a period of 24 months. After the introduction of the reference order set, the number of laboratory tests per order decreased significantly for patients with cholecystitis of low severity. Above the monitoring of repeated orderings during a single stay, the major impacts were achieved by a drastic reduction of inappropriate orders, particularly in the field of bacteriology. The main effects of the order set were maintained throughout a follow-up period of 24 months. Our study demonstrated that, when considering laboratory test ordering optimization, reference order sets could achieve high levels of efficiency. To ensure high compliance to reference order sets, extensive collaboration between clinicians and laboratory physician is mandatory even if very sophisticated information systems are available.

Acute-phase response in pigs undergoing laparoscopic, transgastric or transcolonic notes peritoneoscopy with us or eus exploration.

BACKGROUND: Laparoscopic surgery is associated with reduced surgical trauma, therefore with acute-phase response of lower magnitude as compared with open surgery. We hypothesized that NOTES might induce reduced immune response as compared with laparoscopy. OBJECTIVE: To compare acute-phase reactants in a controlled trial of laparoscopic peritoneoscopy and ultrasonography versus transgastric or transcolonic NOTES peritoneoscopy and intraperitoneal endoscopic US. METHODS: Eighteen pigs were divided in 3 groups: laparoscopy, transgastric and transcolonic NOTES. Serum levels of IL-6 and TNF-α were determined preoperatively and at day 2. Serum levels of haptoglobin and IL-6 mRNA levels from isolated white blood cells were measured by RT-PCR at days 0, 1, 2 and 7. Necropsy was performed at sacrifice, with peritoneal fluid microbiological analysis, macroscopic and microscopic examinations on gastrotomy/colotomy or abdominal wall closure sites, liver and parietal peritoneum biopsy sites and any area suggestive of infection. RESULTS: The groups were similar with regards to peritoneoscopy completeness, ultrasonographic examination and biopsies. The duration of NOTES procedures was significantly longer than laparoscopic procedures. Minor complications were observed in most animals by macroscopic and microscopic examination, but NOTES procedures were associated with severe complications in 3 pigs (fistula, abscess, mortality). No significant differences in acute-phase reactants levels were found between groups. CONCLUSIONS: No significant difference in the acute-phase reactants could be demonstrated between surgical and NOTES procedures. NOTES was however associated with more severe septic complications. Optimal closure remains a challenge and better devices are needed to avoid them.

Results of the recalibration of creatinine measurement with the modular Beckman Coulter Jaffe creatinine method.

BACKGROUND: Serum creatinine is important for detecting the beginning of a decline in kidney function. The Beckman Coulter Jaffe reagents for measuring creatinine have been standardized to the internationally accepted reference method: isotope dilution mass spectrometry (IDMS). The impact of this recalibration on the Beckman Coulter modular or cup (stat) Jaffe method is studied. METHODS: Recalibrated Jaffe (calibrator set points IDMS traceable) and classic National Institute of Standards and Technology (NIST) creatinine methods (traceable to NIST 914a) were compared with an enzymatic method (Sentinel, traceable to NIST SRM 967). All measurements were performed on Synchron DxC 800 systems. Imprecision of the routine methods was studied using the Clinical and Laboratory Standards Institute (CLSI) protocols and laboratory quality survey. Thirteen plasma pools, with concentrations < 354 mmol/L, were analyzed with a gas chromatography isotope dilution mass spectrometry (GC-IDMS) method and routine methods. Total error of 8.2% based on biological variability, set on the GC-IDMS values and acceptance criteria (bias < 5%, imprecision < 8% at concentrations ≥ 88.4 mmol/L and a maximum 10% increase in the relative error of estimated glomerular filtration rate (eGFR) of the National Kidney Disease Educational Program (NKDEP) were used for evaluating analytical performance of the routine methods studied. RESULTS: After recalibration of the Jaffe method, median bias (mmol/L) decreased from 12.4 (95% CI: 9.1-21.2) to 7.3 (95% CI: 1.5-10.5). Imprecision of the Jaffe method is in agreement with the claim of the manufacturer, namely < 9 mmol/L or < 3% below or above 292 mmol/L. Below creatinine of 88.4 mmol/L, imprecision of the recalibrated Jaffe and enzymatic methods is between 4.1% and 6.9%, and 5.0% and 7.1%, respectively, and significantly different (p = 0.02 for both the Jaffe and enzymatic methods) from the goal, based on biological variability, of 2.7%. For the adult pools, all recalibrated Jaffe and enzymatic results fall within the total error of 8.2%. In the pediatric samples, one-third of the recalibrated Jaffe and three of the six enzymatic results fall within this total error goal. CONCLUSIONS: Recalibration significantly reduced bias of the Jaffe method. For pediatric samples, recalibrated Jaffe results do not comply with either the imprecision goal or the total error based on biological variability. Adult recalibrated Jaffe results are in compliance with the goals based on biological variability and with the acceptance criteria from the NKDEP.

Prostate cancer screening: clinical impact of WHO calibration of Beckman Coulter Access prostate-specific antigen assays.

BACKGROUND: The goal of this study was to evaluate the clinical impact of using the same total prostate-specific antigen (tPSA) and free PSA (fPSA) assays calibrated with World Health Organization (WHO) materials or with Hybritech Tandem-R calibrator. METHODS: From the initial correlation study that included 150 patients, the clinical impact of the WHO calibration was simulated using a large cohort (n=4548) of referred patients. Interim reports of the European Study of Screening for Prostate Cancer (ERSPC) were used to evaluate the clinical outcomes of patients and the risk of prostate cancer (PCa). RESULTS: WHO calibration of tPSA assays leads to a reduction of about 20% in measured results (tPSA WHO=0.81 tPSA Hybritech+0.04; fPSA WHO=0.78 fPSA Hybritech+0.00; %fPSA WHO=0.92 %fPSA Hybritech+0.00). The simulation showed that the WHO calibration is associated with a risk of missing 15% of PCa. CONCLUSIONS: The discrepancies between the two calibrations lead to significant clinical misinterpretation with decreased detection of PCa if tPSA cut-off thresholds are not adjusted.

20-25% lower concentrations of total and free prostate-specific antigen (PSA) after calibration of PSA assays to the WHO reference materials--analysis of 1098 patients in four centers.

AIM: To examine the potential clinical implications of the recalibration of total prostate-specific antigen (PSA) and free PSA (fPSA) assays to the World Health Organization (WHO) standard materials. MATERIAL AND METHODS: Data from 1098 patients with or without clinically detected prostate cancer (PCa) from four independent cohort studies were compared using commercial assays calibrated to the traditional Hybritech PSA (PSA-Hyb) and fPSA (fPSA-Hyb) standards and to the WHO 96/670 (PSA-WHO) and 96/668 (fPSA-WHO) standards. The Access Immunoassay System (Beckman Coulter, Inc.) was used in all studies. RESULTS: All studies showed 20% to 25% lower PSA and fPSA test results with the WHO-standardized assays. No significant change in %fPSA (fPSA/PSA x 100) was observed. Continuing to use the traditional clinical PSA cutoffs obtained with the Hybritech standard after changing to the PSA-WHO standard could result in up to one-third of prostate cancer cases being missed. CONCLUSIONS: Manufacturers should fully inform laboratories about a calibration change and its clinical impact. Laboratory reports for PSA measurements should indicate the assay's manufacturer and which calibration standard was used to avoid misleading information concerning PCa risk.

Application of the Six Sigma concept in clinical laboratories: a review.

Six Sigma is a global management strategy introduced to the industrial world in the 1980s. This methodology has been widely implemented in companies such as Motorola, General Electric, Allied Signal and many others, with tremendous success in terms of customer satisfaction and global profitability. To achieve similar benefits in the healthcare field, Six Sigma is currently being deployed in several laboratories around the world. Despite this situation, few articles have been published in the peer-reviewed literature on this subject. The aim of this article is to clarify the different aspects of Six Sigma and their potential applications in clinical laboratories, as well as to systematically review articles and books discussing Six Sigma strategy implementation in the laboratory field.

Release of cardiac bio-markers during high mechanical index contrast-enhanced echocardiography in humans.

BACKGROUND: Recent experimental data have shown that the combined exposure of rodent hearts to high acoustic pressure and ultrasound contrast agents can induce vascular injury and cell damage. The aim of the present work was to test whether similar effects can be observed in humans. METHODS AND RESULTS: Twenty patients underwent simultaneous arterial and coronary sinus blood sampling during contrast-enhanced echocardiography using Perfluorocarbon-enhanced Sonicated Dextrose Albumin. Control subjects were compared to groups of patients exposed to either high mechanical index (MI = 1.5) triggered second harmonic (1.3-2.6 MHz) imaging or low mechanical index (MI = 0.2) real-time power modulation imaging for 15 min. No significant changes arterio-venous differences in lactate, total creatine kinase (CK) and myoglobin occurred over time in the three groups. Similarly, the arterio-venous difference in CK-MB and troponin I remained stable over time in control and low-MI patients. By contrast, these two parameters progressively increased over time in the high-MI group (P < 0.05 vs. baseline and vs. controls). CONCLUSION: Our data suggest that high-MI contrast-enhanced echocardiography can cause subclinical release of cardiac bio-markers in humans, while low-MI real-time imaging appears to be safer.

Evaluation of a new Sebia kit for analysis of hemoglobin fractions and variants on the Capillarys system.

We evaluated the analytical performances of the new Sebia kit for quantification of hemoglobin fractions (HbA, HbF and HbA2) and structural hemoglobin variants on the Capillarys system. This automated capillary zone electrophoresis method uses an alkaline buffer with silica capillaries and spectrophotometric detection. Specimen stability was evaluated during 1 month. The reproducibility of migration and the imprecision of quantification were also investigated. Comparison with the Beckman P/ACE system was performed on 202 samples. A total of 131 subjects without any hematological abnormality were analyzed to establish the HbA2 reference ranges based on our local population. Quantification of the Hb fractions and variants exhibited excellent stability for 4 weeks of storage at 4 degrees C, with CVs < 0.3%. The imprecision of the migration normalized to that of HbA2 for all hemoglobins tested (fractions and variants) was low, with a CV of < 2.5%. At physiological and pathological levels, total imprecision ranged from 1.9% to 4.6% for HbA2, from 0.6% to 9.7% for HbF, and from 0.6% to 1% for HbS. Statistical analysis revealed a small proportional negative bias for HbA2 (-8.6%). Small systematic bias (-0.2%) and proportional bias (-28%) were observed for HbF. No statistically significant difference was found for HbS. The reference range for HbA2 was 2.1-3.2%. The Capillarys system is a fully automated and accurate system that gives high-resolution performance and displays appropriate characteristics for use as a routine method for the diagnosis of thalassemias and hemoglobinopathies.

Polyclonal versus monoclonal ELISA for the determination of fecal elastase 1: diagnostic value in cystic fibrosis and chronic pancreatic insufficiency.

BACKGROUND: Several clinical studies have evaluated the diagnostic efficiency of fecal elastase 1 (FE1) determination using monoclonal antibodies (ScheBo-Tech, Wettenberg, Germany). We report the results of the comparison of this method with a polyclonal based assay (BioServ AG, Rostock, Germany). METHODS: We collected single spot samples from two groups of patients. The group of adults included 13 healthy subjects (HS), 12 patients with non-pancreatic gastrointestinal disease (NPGD), 26 with chronic pancreatitis with presence of calcification (CCP) and 14 without calcification (NCP). The group of children included 17 cases of cystic fibrosis (CF) and 21 controls (CO). After a common extraction, both assays were performed as recommended by the manufacturers. RESULTS: Both tests showed a statistically significant difference between patients with normal pancreatic function and patients with pancreatic disorders. Neither showed a significant difference between HS and NPGD. CONCLUSIONS: Although a statistical difference was found between the two methods for the normal groups (HS and CO), both kits are suitable for the detection of severe pancreatic insufficiency either in adult patients or in children. However, caution should be taken in case of patients with liquid stool specimens.

Performance evaluation of the Precision PCx point-of-care blood glucose analyzer using discriminant ratio methodology.

Point-of-care glucose testing needs to be integrated into a laboratory information system to provide continuous care. Selecting a particular glucose monitoring system is based on both analytical performance and on user's preference. We evaluated accuracy, performance and regulatory compliance of the Precision PCx glucose analyzer (Abbott), with automatic download into a central station, for remote quality control (QC) management and automatic upgrading. We used the discriminant ratio (DR) methodology, which determines the DR of a test (e.g. the ratio between the underlying SD and the within-subject SD), and compares it to that of another test allegedly measuring the same parameter. Accuracy was evaluated by Clarke's error grid method. Seven hundred and ninety four blood samples were taken from 22 diabetic patients, combined with two capillary blood samples: one for analysis by reference method and the second for PCx analysis. Linear regression analysis revealed, over a 2.1 to 26.9 mmol/l glucose concentration range, a correlation coefficient of 0.963, an intercept of 0.7 mmol/l and a slope of 0.851. Mean difference between meter-generated results and the reference method was -7.1+/-10.8%. Between-run imprecision for PCx using Abbott's controls at low and mid-low concentrations was 5.4 and 3.8%, respectively. Clarke's error grid did not show any clinical impact related to difference between methods. DRs were of similar magnitude using both methods. Nursing staff found PCx easy for everyday use. Our data show that PCx results agree with those obtained with the reference method, as shown by lack of significant difference in DRs, and by excellent correlation.