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Table of Contents
Front Cover
Contemporary Practice in Clinical Chemistry
Copyright Page
Contents
List of contributors
Preface
1 Preanalytical variation
Order entry
Patient preparation
Specimen collection
Tube type and order of draw
Needle size, tourniquet use, and line collection
Processing and transportation
Detecting preanalytical errors
Summary
References
Self-assessment questions
Answers
2 Statistical methods in laboratory medicine
Introduction
Basic descriptive statistical analysis
Central tendency and dispersion
Mean
Median
Standard deviation, interquartile range, and quantiles
Quantiles and the interquartile range
Is my data normally distributed?
Make a histogram
Prepare a normal QQ plot
Calculate the skewness and kurtosis
Statistical tests for normality
The Shapiro-Wilk test
The Shapiro-Francia test
The Lilliefors test
The Anderson-Darling test
Detecting outliers
The Grubbs test
Dixon test
Tukey's fences
Chauvenet's criterion
Common inferential statistics
The two-sample t-test
Examples
The paired t-test
Wilcoxon rank-sum test (Mann-Whitney U-test)
Wilcoxon signed-rank test
The chi-square test
Application to proportions
General application to contingency tables
Methods of regression
Ordinary least squares
Weighted ordinary least squares
Deming regression
Passing-Bablok regression
Evaluation of diagnostic test performance
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Likelihood ratios
Example calculation
Receiver operating characteristic curves
Interpreting a receiver operating characteristic curve
Preparing a receiver operating characteristic curve
Suggested additional topics for study
References
Self-assessment questions
Answers.
3 Reference intervals: theory and practice
Introduction
Concept of reference intervals and importance to laboratory medicine
Reference intervals versus clinical decision limits
Current gaps and recent initiatives in reference interval establishment
Methodological approaches to establishment of reference intervals
Population-based reference intervals
Selection of reference individuals
Direct versus indirect sampling
A priori versus a posteriori sampling
Preanalytical and analytical variables
Outlier exclusion
Partitioning and minimum sample size
Statistical determination of reference intervals
Nonparametric analysis
Robust analysis
Parametric analysis
Covariates that affect reference interval determination
Age-dependent reference curves
Pediatric and geriatric reference intervals: challenges and recent advances
Pediatric reference intervals
Geriatric reference intervals
Reference interval transference and verification
Methodological approach to transference
Limitations of the transference method
Transference initiatives
Verification of transferred reference intervals
Toward reference interval harmonization
Limitations of population-based reference intervals
Concluding remarks
References
Self-assessment questions
Answers
4 Method validation
Introduction
Regulations
Analytical goals and method selection
Helpful tips and tools prior to performing validation
Method validation basics
Precision and accuracy
Reportable range
Method comparison
Validation of laboratory developed tests
Carryover validation
Stability validation
Selectivity/specificity and interference validation
Matrix effects validation
Recovery validation
Sensitivity validation
Dilution validation
Reference standards.
The role of the medical laboratory director
References
Self-assessment questions
Answers
5 Quality control
Introduction
Implementing statistical process control
Selection of quality control materials
Limitations of quality control materials
Frequency to assay quality control samples
Establishing quality control target values and acceptance ranges that represent a stable measurement operating condition
Establishing acceptance criteria to evaluate quality control results
Corrective action when a quality control result indicates a measurement problem
Verifying quality control evaluation parameters following a reagent lot change
Verifying method performance following use of a new lot of calibrator
Calibration issues in quality control
Development of a quality control plan based on risk management
Reviewing the quality control plan
Using patient data in quality control procedures
Delta check with a previous result for a patient
Verify consistency between more than one instrument or method
Using patient data for statistical process control
Proficiency testing
Noncommutability of proficiency testing/external quality assessment materials and peer group grading
Reporting proficiency testing/external quality assessment results when one method is adjusted to agree with another method
Interpretation of proficiency testing/external quality assessment results
Accuracy-based proficiency testing/external quality assessment programs
References
Further reading
Self-assessment questions
Answers
6 Laboratory calculations
Analytical calculations
Dimensional analysis
Centrifugation
Concentration
Dilutions
Equilibrium calculations and pH
Buffer calculations
Ionic strength
Photometry calculations
Electrophoresis
Electrochemistry
Enzyme kinetics.
Chromatography
Clinical calculations
Electrolytes
Osmolality and osmolal gap
Renal function calculations
Iron calculations
Lipid calculations
Statistics
Mean
Median
Standard deviation
Coefficient of variation
Variance
Standard error of the mean
Method evaluation
Accuracy: regression analysis of method comparison data
Accuracy: recovery studies
Precision: repeatability and within-lab precision studies
Total error
Detection limits
Clinical performance of laboratory tests: predictive value theory
Laboratory management
Budget justification
Full-time equivalent
Cost per reportable result
Capital equipment justification
References
7 Spectrophotometry
Principles of light absorption and emission
Principles of spectrophotometric measurement
Configuration of spectrophotometers
Critical operating parameters: accuracy
Bandpass
Stray light
Wavelength accuracy
Absorbance accuracy
Chromogen limitations
Calibration of spectrophotometric measurements
Molar absorptivity
Calibration relationship
Critical operating parameters: precision
Interferences
Bichromatic and polychromatic measurements
Other applications of spectrophotometric or light emission measurements
Cooximetry
Reflectance spectrophotometry
Densitometry
Turbidimetry and nephelometry
Atomic absorption
Atomic emission
Fluorescence
Fluorescence lifetime
Fluorescence polarization (depolarization)
Chemiluminescence
References
Suggested reading
Self-assessment questions
Answers
8 Chromatography and electrophoresis
Introduction to chromatography
General terms and concepts
Theory of chromatography
Evaluating and optimizing chromatographic separations
Gas chromatography
General terms and concepts.
Gas chromatography mobile phases and elution methods
Gas chromatography supports and stationary phases
Gas chromatography detectors
Methods for sample injection and pretreatment in gas chromatography
Liquid chromatography
General terms and concepts
Liquid chromatography mobile phases and elution methods
Types of liquid chromatography
Adsorption chromatography
Partition chromatography
Ion-exchange chromatography
Size-exclusion chromatography
Affinity chromatography
Liquid chromatography detectors
Introduction to electrophoresis
General terms and concepts
Theory of electrophoresis
Gel electrophoresis
General terms and concepts
Supports and sample application in gel electrophoresis
Detection in gel electrophoresis
Special types of gel electrophoresis
Capillary electrophoresis
General terms and concepts
Supports and sample application in capillary electrophoresis
Detection in capillary electrophoresis
Special types of capillary electrophoresis
References
Self-assessment questions
Answers
9 Electrochemistry
Introduction
Potentiometric methods in clinical chemistry
Redox electrodes
Ion-selective electrodes
Glass membrane electrodes
Polymer membrane electrodes
Gas-sensing electrodes
Ion-selective electrodes-units of measure and reporting for clinical application
Amperometric methods in clinical chemistry
Conductometric methods in clinical chemistry
Coulometric methods in clinical chemistry
Interferences for potentiometric and amperometric sensors
Biosensors based on electrochemical methods
Enzyme-based biosensors with amperometric and potentiometric detection
Affinity biosensors with electrochemical detection
References
Self-assessment questions
Answers
10 Mass spectrometry
Basic mass spectrometry concepts.
Sample introduction.
Contemporary Practice in Clinical Chemistry
Copyright Page
Contents
List of contributors
Preface
1 Preanalytical variation
Order entry
Patient preparation
Specimen collection
Tube type and order of draw
Needle size, tourniquet use, and line collection
Processing and transportation
Detecting preanalytical errors
Summary
References
Self-assessment questions
Answers
2 Statistical methods in laboratory medicine
Introduction
Basic descriptive statistical analysis
Central tendency and dispersion
Mean
Median
Standard deviation, interquartile range, and quantiles
Quantiles and the interquartile range
Is my data normally distributed?
Make a histogram
Prepare a normal QQ plot
Calculate the skewness and kurtosis
Statistical tests for normality
The Shapiro-Wilk test
The Shapiro-Francia test
The Lilliefors test
The Anderson-Darling test
Detecting outliers
The Grubbs test
Dixon test
Tukey's fences
Chauvenet's criterion
Common inferential statistics
The two-sample t-test
Examples
The paired t-test
Wilcoxon rank-sum test (Mann-Whitney U-test)
Wilcoxon signed-rank test
The chi-square test
Application to proportions
General application to contingency tables
Methods of regression
Ordinary least squares
Weighted ordinary least squares
Deming regression
Passing-Bablok regression
Evaluation of diagnostic test performance
Sensitivity
Specificity
Positive predictive value
Negative predictive value
Likelihood ratios
Example calculation
Receiver operating characteristic curves
Interpreting a receiver operating characteristic curve
Preparing a receiver operating characteristic curve
Suggested additional topics for study
References
Self-assessment questions
Answers.
3 Reference intervals: theory and practice
Introduction
Concept of reference intervals and importance to laboratory medicine
Reference intervals versus clinical decision limits
Current gaps and recent initiatives in reference interval establishment
Methodological approaches to establishment of reference intervals
Population-based reference intervals
Selection of reference individuals
Direct versus indirect sampling
A priori versus a posteriori sampling
Preanalytical and analytical variables
Outlier exclusion
Partitioning and minimum sample size
Statistical determination of reference intervals
Nonparametric analysis
Robust analysis
Parametric analysis
Covariates that affect reference interval determination
Age-dependent reference curves
Pediatric and geriatric reference intervals: challenges and recent advances
Pediatric reference intervals
Geriatric reference intervals
Reference interval transference and verification
Methodological approach to transference
Limitations of the transference method
Transference initiatives
Verification of transferred reference intervals
Toward reference interval harmonization
Limitations of population-based reference intervals
Concluding remarks
References
Self-assessment questions
Answers
4 Method validation
Introduction
Regulations
Analytical goals and method selection
Helpful tips and tools prior to performing validation
Method validation basics
Precision and accuracy
Reportable range
Method comparison
Validation of laboratory developed tests
Carryover validation
Stability validation
Selectivity/specificity and interference validation
Matrix effects validation
Recovery validation
Sensitivity validation
Dilution validation
Reference standards.
The role of the medical laboratory director
References
Self-assessment questions
Answers
5 Quality control
Introduction
Implementing statistical process control
Selection of quality control materials
Limitations of quality control materials
Frequency to assay quality control samples
Establishing quality control target values and acceptance ranges that represent a stable measurement operating condition
Establishing acceptance criteria to evaluate quality control results
Corrective action when a quality control result indicates a measurement problem
Verifying quality control evaluation parameters following a reagent lot change
Verifying method performance following use of a new lot of calibrator
Calibration issues in quality control
Development of a quality control plan based on risk management
Reviewing the quality control plan
Using patient data in quality control procedures
Delta check with a previous result for a patient
Verify consistency between more than one instrument or method
Using patient data for statistical process control
Proficiency testing
Noncommutability of proficiency testing/external quality assessment materials and peer group grading
Reporting proficiency testing/external quality assessment results when one method is adjusted to agree with another method
Interpretation of proficiency testing/external quality assessment results
Accuracy-based proficiency testing/external quality assessment programs
References
Further reading
Self-assessment questions
Answers
6 Laboratory calculations
Analytical calculations
Dimensional analysis
Centrifugation
Concentration
Dilutions
Equilibrium calculations and pH
Buffer calculations
Ionic strength
Photometry calculations
Electrophoresis
Electrochemistry
Enzyme kinetics.
Chromatography
Clinical calculations
Electrolytes
Osmolality and osmolal gap
Renal function calculations
Iron calculations
Lipid calculations
Statistics
Mean
Median
Standard deviation
Coefficient of variation
Variance
Standard error of the mean
Method evaluation
Accuracy: regression analysis of method comparison data
Accuracy: recovery studies
Precision: repeatability and within-lab precision studies
Total error
Detection limits
Clinical performance of laboratory tests: predictive value theory
Laboratory management
Budget justification
Full-time equivalent
Cost per reportable result
Capital equipment justification
References
7 Spectrophotometry
Principles of light absorption and emission
Principles of spectrophotometric measurement
Configuration of spectrophotometers
Critical operating parameters: accuracy
Bandpass
Stray light
Wavelength accuracy
Absorbance accuracy
Chromogen limitations
Calibration of spectrophotometric measurements
Molar absorptivity
Calibration relationship
Critical operating parameters: precision
Interferences
Bichromatic and polychromatic measurements
Other applications of spectrophotometric or light emission measurements
Cooximetry
Reflectance spectrophotometry
Densitometry
Turbidimetry and nephelometry
Atomic absorption
Atomic emission
Fluorescence
Fluorescence lifetime
Fluorescence polarization (depolarization)
Chemiluminescence
References
Suggested reading
Self-assessment questions
Answers
8 Chromatography and electrophoresis
Introduction to chromatography
General terms and concepts
Theory of chromatography
Evaluating and optimizing chromatographic separations
Gas chromatography
General terms and concepts.
Gas chromatography mobile phases and elution methods
Gas chromatography supports and stationary phases
Gas chromatography detectors
Methods for sample injection and pretreatment in gas chromatography
Liquid chromatography
General terms and concepts
Liquid chromatography mobile phases and elution methods
Types of liquid chromatography
Adsorption chromatography
Partition chromatography
Ion-exchange chromatography
Size-exclusion chromatography
Affinity chromatography
Liquid chromatography detectors
Introduction to electrophoresis
General terms and concepts
Theory of electrophoresis
Gel electrophoresis
General terms and concepts
Supports and sample application in gel electrophoresis
Detection in gel electrophoresis
Special types of gel electrophoresis
Capillary electrophoresis
General terms and concepts
Supports and sample application in capillary electrophoresis
Detection in capillary electrophoresis
Special types of capillary electrophoresis
References
Self-assessment questions
Answers
9 Electrochemistry
Introduction
Potentiometric methods in clinical chemistry
Redox electrodes
Ion-selective electrodes
Glass membrane electrodes
Polymer membrane electrodes
Gas-sensing electrodes
Ion-selective electrodes-units of measure and reporting for clinical application
Amperometric methods in clinical chemistry
Conductometric methods in clinical chemistry
Coulometric methods in clinical chemistry
Interferences for potentiometric and amperometric sensors
Biosensors based on electrochemical methods
Enzyme-based biosensors with amperometric and potentiometric detection
Affinity biosensors with electrochemical detection
References
Self-assessment questions
Answers
10 Mass spectrometry
Basic mass spectrometry concepts.
Sample introduction.