Selva Leticia Luna, MSc, PhD, Member of Chilean Clinical Chemistry Society, is a professor in clinical biochemistry, endocrinology and quality management for clinical laboratory at Universidad de Valparaíso (Chile).
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Abstract 1
Semiology and the value of the laboratory test
Semiology is defined as the science that studies signs and symptoms. Biochemical parameters measured in the clinical laboratory have greater semiological value than symptoms because their objectivity. The semiological value of a test, however, depends on its intended application Screening, Individual Health Status, Diagnosis or Monitoring a patient's evolution.
The clinical contribution of any test is based on comparison against a Gold Standard: The diagnostic technique that defines the presence or absence of the condition under study with the maximum certainty.The Gold Standard, while ideal, cannot always be applied to a patient because the technique may be too expensive, very invasive, or even risky. Diagnostic Accuracy is the ability of a test or diagnostic procedure to discriminate between a diseased and a healthy population. This discrimination is often based on establishing a Cut-Off Value. The primary parameters used to measure diagnostic accuracy are Sensitivity and Specificity.
Sensitivity: The probability that a sick person will yield a positive result on the test. It measures the capacity to detect the disease when it is present: Highly sensitive tests are useful for excluding a disease (low False Negatives).
Specificity: The probability that a healthy person will yield a negative result on the test: It measures the capacity to rule out the disease when it is not present. Highly specific tests are useful for confirming a disease (low False Positives).
These concepts are calculated using a Contingency Table which classifies subjects based on the Gold Standard result and the new test result (Positive/Negative). The four quadrants defined are: True Positives (VP), True Negatives (VN), False Negatives (FN), and False Positives (FP).
Receiver Operating Characteristic (ROC) Curve, is a statistical method used to determine the diagnostic accuracy of tests that use continuous scales.
ROC Curves are used to: Choose the best Cut-Off Point, Evaluate Discriminating Capacity, Compare Tests. The discriminating capacity of a test is often quantified by calculating the Area Under the Curve (AUC). Examples of ROC curves are offered about tumor markers in blood.
Abstract 2
Laboratory quality managementToday's seminar moves beyond the concepts governing quality and comparability in the clinical laboratory. Activities of a clinical laboratory constitute a circular process, often referred to as the "brain to brain loop," intricately involving the patient, physician, laboratory staff, and management.
A foundational principle is the commitment to quality. While implementation of a quality management system may involve initial costs, it demonstrably leads to long-term savings in economic resources. Furthermore, we must continually address error sources. Despite ongoing debate, the consensus suggests that the largest percentage of errors occurs during the pre-analytical phase. The laboratory's responsibility is holistic, encompassing the entire process from recognizing user needs to ensuring final satisfaction.
Achieving analytical quality hinges on rigorous qualification of equipment and methods. Equipment Qualification must cover the full lifecycle: design, installation, operation, and performance.
Method Qualification has two components:
- Validation: The primary evaluation of analytical performance, typically carried out by the manufacturer.
- Verification: The laboratory's internal process to confirm the method's performance under its specific operational conditions.
Once a method is qualified, a robust quality control to monitor the method's routine performance must be developed regularly in order to assure, precision and accuracy.
The ultimate goal in modern laboratory medicine is harmonization. This means ensuring that patient results reported across different laboratories and using multiple instruments are equivalent.
Achieving harmonization is critical for patient safety and consistent clinical decision-making.
Two advanced concepts support this goal:
- Traceability: Ensuring the result is linked to higher-order references.
- Commutability: This is an essential property of reference materials and controls. It is the degree of agreement between results from a reference material and clinical (patient) samples when measured by two or more procedures. Commutability ensures that if a patient switches from a test performed by Method A to Method B, the results are comparable. This prevents incorrect treatment decisions caused by method variability.
We can now move into a discussion on the practical challenges of demonstrating commutability for complex analytes.
Abstract 3
Plasma levels of clozapine and norclozapine in a national reference psychiatric institution
Clozapine, a first-line antipsychotic drug for the management of treatment-resistant Schizophrenia, has a metabolism influenced by age, sex, smoking habit, and drug interaction with other medications. In Chile, the information available from local patients is limited.
The aim of the present study is to evaluate, in the population treated at the Dr. José Horwitz Psychiatric Institute (IPS), the plasma levels of clozapine and norclozapine in relation to the prescribed dose and factors that influence pharmacokinetics.
This retrospective observational study was carried out with information from 333 clozapine users, over 15 years of age, who were treated at the IPS between April 2022 and April 2023. Plasma concentrations of clozapine and norclozapine were measured by HPLC with UV detection.
Daily doses of clozapine were from 75 to 800 mg/day (median 400 mg/day), plasma concentrations of clozapine varied between 20.8 and 3461.4 ng/mL and of norclozapine between 22.9 and 1287, 4 ng/mL. Women presented higher values than men, users aged 60 years or more were 26% higher than young users (< 26 years old). Smokers had concentrations 35% lower than non-smokers. Concomitant use of fluoxetine affects the level of clozapine, while valproic acid influences plasma concentrations of norclozapine.
In Chile, this analytical method for determining the drug and its metabolite is not available in most public hospitals, so the present results provide valuable information to apply in the clinical context in order to optimize treatment and improve therapeutic goals.
Autors: Herrera M. de los A.(1, 2), Díaz C.(1), Mena C.(1), Luna S.L.(2.3)
(1)Instituto Psiquiátrico Dr. José Horwitz, Santiago, Chile. (2). Magíster en Análisis Clínico, Universidad de Valparaíso. (3) Escuela de Química y Farmacia, Facultad de Farmacia, Universidad de Valparaíso, Chile