Audit of sweat chloride testing reveals analytical errors

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Freerk Prenzel ◽  
Uta Ceglarek ◽  
Ines Adams ◽  
Jutta Hammermann ◽  
Ulrike Issa ◽  
...  
Keyword(s):  
Proficiency Testing ◽  
Sample Volume ◽  
Pass Rate ◽  
Counseling Session ◽  
Sweat Chloride ◽  
Technical Errors ◽  
Coefficients Of Variation ◽  
Before And After ◽  
Rater Variability ◽  
Quality Assessments

Abstract Objectives Sweat chloride testing (SCT) is the mainstay for the diagnosis of cystic fibrosis (CF) and biomarker in the evaluation of CFTR-modifying drugs. To be a reliable and valid tool, analytical variance (CVA) must be minimized. However, external quality assessments have revealed significant deviations in routine clinical practice. Our goal was to identify and quantify technical errors through proficiency testing and simulations. Methods Chloride concentrations of three blinded samples (each as triplicates) were measured in 9 CF centers using a chloridometer in a routine setting. Technical errors were simulated and quantified in a series of measurements. We compared imprecision and bias before and after a counseling session by evaluating coefficients of variation (CV), adherence to tolerance limits, and inter-rater variability coefficients. Results Pipetting errors resulting in changes in sample volume were identified as the main source of error with deviations up to 41%. After the counseling session, the overall CVA decreased from 7.6 to 5.2%, the pass rate increased from 67 to 92%, and the inter-rater variability diminished. Significant deviations continued to be observed in individual centers. Conclusions Prevention of technical errors in SCT decreases imprecision and bias. Quality assurance programs must be established in all CF centers, including staff training, standard operating procedures, and proficiency testing.

Percentile transformation and recalibration functions allow harmonization of thyroid-stimulating hormone (TSH) immunoassay results

2020 ◽  
Vol 58 (10) ◽  
pp. 1663-1672 ◽  
Author(s):  
Andrea Padoan ◽  
Aldo Clerico ◽  
Martina Zaninotto ◽  
Tommaso Trenti ◽  
Renato Tozzoli ◽  
...  
Keyword(s):  
Robust Regression ◽  
Reference Intervals ◽  
Thyroid Stimulating Hormone ◽  
Validation Dataset ◽  
New Approach ◽  
Coefficients Of Variation ◽  
Significant Difference ◽  
Before And After ◽  
Roche Diagnostics ◽  
Stimulating Hormone

AbstractBackgroundThe comparability of thyroid-stimulating hormone (TSH) results cannot be easily obtained using SI-traceable reference measurement procedures (RPMs) or reference materials, whilst harmonization is more feasible. The aim of this study was to identify and validate a new approach for the harmonization of TSH results.MethodsPercentile normalization was applied to 125,419 TSH results, obtained from seven laboratories using three immunoassays (Access 3rd IS Thyrotropin, Beckman Coulter Diagnostics; Architect System, Abbott Diagnostics and Elecsys, Roche Diagnostics). Recalibration equations (RCAL) were derived by robust regressions using bootstrapped distribution. Two datasets, the first of 119 EQAs, the second of 610, 638 and 639 results from Access, Architect and Elecsys TSH results, respectively, were used to validate RCAL. A dataset of 142,821 TSH values was used to derive reference intervals (RIs) after applying RCAL.ResultsAccess, Abbott and Elecsys TSH distributions were significantly different (p < 0.001). RCAL intercepts and slopes were −0.003 and 0.984 for Access, 0.032 and 1.041 for Architect, −0.031 and 1.003 for Elecsys, respectively. Validation using EQAs showed that before and after RCAL, the coefficients of variation (CVs) or among-assay results decreased from 10.72% to 8.16%. The second validation dataset was used to test RCALs. The median of between-assay differences ranged from −0.0053 to 0.1955 mIU/L of TSH. Elecsys recalibrated to Access (and vice-versa) showed non-significant difference. TSH RI after RCAL resulted in 0.37–5.11 mIU/L overall, 0.49–4.96 mIU/L for females and 0.40–4.92 mIU/L for males. A significant difference across age classes was identified.ConclusionsPercentile normalization and robust regression are valuable tools for deriving RCALs and harmonizing TSH values.

Single-site sampling versus multi-site sampling for blood cultures; A retrospective clinical study

2021 ◽  
Author(s):  
Anna Larsson ◽  
David Yu ◽  
Patrik Dinnétz ◽  
Hampus Nordqvist ◽  
Volkan Özenci
Keyword(s):  
Clinical Study ◽  
Diagnostic Performance ◽  
Sample Volume ◽  
Blood Cultures ◽  
Single Site ◽  
Optimal Sampling ◽  
Sampling Protocol ◽  
Anaerobic Bottle ◽  
Retrospective Clinical Study ◽  
Before And After

Objectives The performance of blood cultures (BC) relies on optimal sampling. Sepsis guidelines do not specify which sampling protocol to use, but recommend two sets of BC bottles, each set containing one aerobic and one anaerobic bottle. For the single-site sampling (SSS) protocol, only one venipuncture is performed for all four bottles. The predominating multi-site sampling (MSS) protocol implies that BC bottles are collected from two separate venipuncture sites. The aim of this study was to compare SSS and MSS. Primary outcomes were number of BC sets collected, sample volume and diagnostic performance. Methods This was a retrospective clinical study comparing BC results in an emergency department before and after changing the sampling protocol to SSS from MSS. All BC samples were incubated in the BacT/ALERT BC system. Results The analysis included 5,248 patients before and 5,364 patients after the implementation of SSS. There was a significantly higher proportion of positive BCs sampled with SSS compared to MSS, 1,049/5,364 (19.56%) and 932/5,248 (17.76%) respectively ( P =0.018). This difference was due to a higher proportion of solitary BC sets (two BC bottles) in MSS. Analyzing only patients with the recommended four BC bottles, there was no difference in positivity. SSS had a higher proportion of BC bottles with the recommended sample volumes of 8-12 ml than MSS ( P <0.001). Conclusions Changing the sampling protocol to SSS from MSS resulted in higher positivity rates, higher sample volume and fewer solitary BC sets. These advantages of SSS should be considered in future sepsis guidelines.

Heat acclimation in cystic fibrosis

1984 ◽  
Vol 57 (2) ◽  
pp. 408-412 ◽  
Author(s):  
D. M. Orenstein ◽  
K. G. Henke ◽  
C. G. Green
Keyword(s):  
Cystic Fibrosis ◽  
Rectal Temperature ◽  
Heat Acclimation ◽  
Heat Illness ◽  
Cycle Exercise ◽  
Control Temperature ◽  
Control Subjects ◽  
Sweat Chloride ◽  
Before And After ◽  
Normal Controls

Cystic fibrosis (CF) patients may be at risk for heat illness because of their high sweat chloride and sodium concentrations ([Cl-], [Na+]), but it is not known if they can heat acclimate. We studied 10 CF patients and 10 normal controls on 8 consecutive days of cycle exercise in the heat (37 degrees C dry bulb, 24–29 degrees C wet bulb). Both groups acclimated. CF peak rectal temperature (Tre) was 38.2 +/- 0.3 degrees C on day 1 and 37.8 +/- 0.4 degrees C on day 8 (P less than .005), and peak heart rates (HR) were 151 +/- 24 beats/min on day 1 and 136 +/- 22 beats/min on day 8 (P less than 0.025). Control temperature (T) and HR were similar. Controls decreased sweat [Cl-] from 37.2 +/- 14.6 meq/l on day 1 and to 24.9 +/- 10.6 meq/l on day 8 (P less than 0.005). CF sweat [Cl-] was significantly higher and did not change with acclimation (day 1, 71.1 +/- 20.9 meq/l; day 8, 72.6 +/- 21.6 meq/l, NS). Before and after acclimation, exercise-heat sessions resulted in significant decreases in serum [Cl-] in CF patients (104.5 +/- 4.6 to 101.3 +/- 4.4 meq/l on day 1, P less than 0.05; 103.5 +/- 5.1 to 99.7 +/- 4.2 meq/l on day 8, P less than 0.025) but not in controls. Serum [Cl-] was significantly lower in CF than control subjects at every measurement. Both groups had significant renal Na+ conservation after exercise on both days.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals DEVELOPMENT AND VALIDATION OF LC-MS/MS METHOD FOR ESTIMATION OF UROCARB IN HUMAN PLASMA

2019 ◽  
pp. 125-130
Author(s):  
IRYNA DRAPAK ◽  
BORYS ZIMENKOVSKY ◽  
LINA PEREKHODA ◽  
SERGIY KOVALENKO ◽  
LILIYA LOGOYDA
Keyword(s):  
Formic Acid ◽  
Human Plasma ◽  
Internal Standard ◽  
Sample Volume ◽  
Pharmacokinetic Studies ◽  
Coefficients Of Variation ◽  
Highly Sensitive ◽  
Regulatory Guidelines ◽  
Initial Content ◽  
Development And Validation

Objective: The present study was aimed to develop a rapid, specific and sensitive method based on LC-MS/MS method was developed for the determination of urocarb using etomidate as an internal standard. Methods: Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B of 8%, which increases linearly to 1.0 min to 100%, is maintained up to 1.5 min and returned to the original 8% to 1.51 min. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 4 μl. Results: The total chromatographic run time was 2.0 min and the elution of urocarb and IS (etomidate) occurred at ~1.53 and 1.67 min, respectively. A linear response function was established at 1-100 ng/ml for urocarb and etomidate in human plasma. The % mean recovery for urocarb in LQC, MQC and HQC was 104.1 %, 100.0 % and 97.4 %. The lowest concentration with the RSD<20% was taken as LLOQ and was found to be 1.03 ng/ml for urocarb. The within-run coefficients of variation ranged between 0.271 % and 0.478 % for urocarb. The within-run percentages of nominal concentrations ranged between 99.12 % and 100.21 % for urocarb. The between-run coefficients of variation ranged between 0.388 % and 0.601 % for urocarb. The between-run percentages of nominal concentrations ranged between 98.78 % and 101.11 % for urocarb. Conclusion: A highly sensitive, specific, reproducible, rapid and high-throughput LC-MS/MS assay was developed and validated to quantify urocarb in human plasma as per the regulatory guidelines. Due to the sensitivity of the developed method, it can be applied to the monitoring of plasma levels in the analysis of drug in preclinical and clinical pharmacokinetic studies. All the parameters and results were found within the acceptance limit as given in the validation protocol.

scholarly journals LC-MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF CARDIAZOL IN HUMAN PLASMA

2019 ◽  
pp. 380-385
Author(s):  
IRYNA DRAPAK ◽  
BORYS ZIMENKOVSKY ◽  
LINA PEREKHODA ◽  
SERGIY KOVALENKO ◽  
Liliya Logoyda
Keyword(s):  
Formic Acid ◽  
Human Plasma ◽  
Method Development ◽  
Accurate Method ◽  
Sample Volume ◽  
Ich Guidelines ◽  
Coefficients Of Variation ◽  
Method Development And Validation ◽  
Development And Validation

Objective: The main purpose of this study was to develop a simple, precise, rapid and accurate method for the quantification of cardiazol in human plasma. Methods: Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B of 8%, which increases linearly to 1.0 min to 100%, is maintained up to 1.5 min and returned to the original 8% to 1.51 min. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 300 μl. Results: The total chromatographic run time was 2.5 min and the elution of cardiazol and IS (difenoconazole) occurred at ~2.15 and 1.98 min, respectively. A linear response function was established at 1-100 ng/ml for cardiazol and difenoconazole in human plasma. The % mean recovery for cardiazol in LQC, MQC and HQC was 102.8 %, 100.3 % and 95.9 %. The lowest concentration with the RSD<20% was taken as LLOQ and was found to be 1.10 ng/ml for cardiazol. The % accuracy of LLOQ samples prepared with the different biological matrix lots was found 109.7 %, which were found within the range of 80.00-120.00 % for the seven different plasma lots. % CV for LLOQ samples was observed as 11.9 %, which are within 20.00% of the acceptance criteria. The within-run coefficients of variation ranged between 0.311 % and 0.601 % for cardiazol. The within-run percentages of nominal concentrations ranged between 99.80 % and 100.41 % for cardiazol. The between-run coefficients of variation ranged between 0.332 % and 0.615 % for cardiazol. The between-run percentages of nominal concentrations ranged between 98.18 % and 101.21 % for cardiazol. Conclusion: A rapid method was developed for simultaneous determination of cardiazol in human plasma. The method was strictly validated according to the ICH guidelines. Acquired results demonstrate that the proposed strategy can be effortlessly and advantageously applied for routine examination of cardiazol in human plasma.

The Application of In Situ 3D X-Ray Diffraction in Annealing Experiments: First Interpretation of Substructure Development in Deformed NaCl

2012 ◽  
Vol 715-716 ◽  
pp. 461-466 ◽  
Author(s):  
Verity Borthwick ◽  
Søren Schmidt ◽  
Sandra Piazolo ◽  
Carsten Gundlach ◽  
Albert Griera ◽  
...  
Keyword(s):  
Subgrain Boundary ◽  
Surface Effects ◽  
Sample Volume ◽  
European Synchrotron Radiation Facility ◽  
X Ray Diffraction ◽  
Boundary Misorientation ◽  
X Ray ◽  
Before And After ◽  
Annealing Experiments

n-situ 3D X-ray diffraction (3DXRD) annealing experiments were conducted at the ID-11 beamline at the European Synchrotron Radiation Facility in Grenoble. This allowed us to non-destructively document and subsequently analyse the development of substructures during heating, without the influence of surface effects. A sample of deformed single crystal halite was heated to between 260-400 °C. Before and after heating a volume of 500 by 500 by 300 μm was mapped using a planar beam, which was translated over the sample volume at intervals of 5-10 µm in the vertical dimension. In the following we present partially reconstructed orientation maps over one layer before and after heating for 240min at 260 °C. Additional small syn-heating maps over a constrained sample rotation of 12-30º. The purpose of this was to illuminate a few reflections from 1 or 2 subgrains and follow their evolution during heating. Preliminary results show that significant changes occurred within the sample volume, for which, surface effects can be excluded. Results show a number of processes, including: i) change in subgrain boundary misorientation angle and ii) subgrain subdivision into areas of similar lattice orientation with new subgrain boundary formation. These results demonstrate that 3DXRD coupled with in-situ heating is a successful non-destructive technique for examining real-time post-deformational annealing in strongly deformed crystalline materials with complicated microstructures.

scholarly journals Efektivitas Konseling Realita Terhadap Rasa Rendah Diri Pada Siswa Kelas X Sekolah Menengah Atas Negeri 1 Surabaya

2020 ◽  
Vol 6 (1) ◽  
pp. 12-18
Author(s):  
Aniek Wirastania
Keyword(s):  
System Development ◽  
Self Esteem ◽  
Negative Influence ◽  
Counseling Session ◽  
Self Evaluation ◽  
Before And After ◽  
Quasi Experimental ◽  
Inferiority Complex ◽  
The Individual ◽  
High Level

Low self-esteem is a form of attitude that arises from the feeling of someone who feels himself feeling inadequate when compared with the condition of others and this condition continues with feelings that result in negative attitudes of the individual can even make self-judgment. The high level of low self-esteem owned by a student will be able to have a negative influence, especially in learning activities at school. A service that is considered to be able to overcome the problem of high self-esteem is to use reality counseling techniques. This study aims to look at the effectiveness of reality counseling techniques in reducing students' inferiority complex. This research is a quasi-experimental study with the research design used is non-equivalent pretest-posttest one group design. Reality counseling technique is carried out in this counseling is to use the WDEP system development. The WDEP system that is carried out at each reality counseling session is done through a strategy that consists of wants and needs, namely wants and needs, direction and doing, namely direction and action, self evaluation, which is evaluation carried out on oneself, and the last is planning, which is plan continue on what action will be taken. The treatment that was done by using reality group technical counseling was considered effective in reducing the sense of inferiority and developing the successful identity of each student. This study shows the results that there are differences in the level of low self-esteem of students before and after following the reality engineering counseling session. Reality counseling techniques are effective in reducing the level of low self-esteem of students.Keywords: Low self-esteem, Counseling, Reality Techniques, Quasi Experiment

Differential assay of zidovudine and its glucuronide metabolite in serum and urine with a radioimmunoassay kit

1990 ◽  
Vol 36 (6) ◽  
pp. 897-900 ◽  
Author(s):  
S M Tadepalli ◽  
L Puckett ◽  
S Jeal ◽  
L Kanics ◽  
R P Quinn
Keyword(s):  
Inhibitory Concentration ◽  
Serum Samples ◽  
Lower Detection Limit ◽  
Coefficients Of Variation ◽  
Lower Detection ◽  
Before And After ◽  
The Difference ◽  
Glucuronide Metabolite ◽  
Serum And Urine

Abstract We developed an ancillary procedure for the ZDV-Trac RIA (Incstar) to allow simultaneous determination of both zidovudine (3'-azido-3'-deoxythymidine, ZDV, AZT, Retrovir) and its metabolite, the glucuronide of ZDV (3'-azido-3'-deoxy-5'-O-beta-D-glucopyranuronosylthymidine, ZDVG, GAZT), in human serum and urine. Using the ZDV-Trac RIA, we measured ZDV concentrations before and after ZDVG in samples was hydrolyzed to ZDV by beta-glucuronidase (EC 3.2.1.31); ZDVG concentration was calculated as the difference between the two results. This method enables rapid evaluation of a large number of samples with a total turn-around time of 6 h. The lower detection limit of the RIA was 0.27 micrograms/L; the measurements varied linearly with ZDV concentrations from 0.27 to 217 micrograms/L, with the 50% inhibitory concentration being approximately 10 micrograms/L. Analytical recoveries of inhouse serum and urine controls for both ZDV and ZDVG exceeded 90%. Coefficients of variation (CVs) of serum controls were less than 6% for ZDV and less than 11% for ZDVG; for urine controls, CVs for both ZDV and ZDVG were less than 6%. Results for ZDVG concentrations obtained by HPLC and by the ZDV-Trac RIA system compared well: r = 0.978, slope 1.0, for serum samples, and r = 0.993, slope 1.09, for urine samples.

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