Introduction: The aim of the study was to investigate current practice and policies of therapeutic drug monitoring (TDM) service requesting and result reporting in Czechia and Slovakia. Materials and methods: All 149 laboratories that measure plasma drug concentrations were given an online questionnaire during a regular external quality assessment TDM cycle. The questionnaire consisted of 17 questions. The optimal TDM practice was defined as the application of all elements (age, body weight, time of sampling, date of the first administration, time of the last dose administration, the dose, the dosing interval, the route of administration, information on reason of testing, and information on other co-administered drugs) needed for reporting a recommendation for further drug dosing (positive response to question number 16). Results: The response rate was 69%, 103 out of 149 laboratories measuring drug concentrations. Only 12% (12 out of 103 laboratories) of the laboratories implemented all elements needed for optimal TDM practice and reported a recommendation. Both paper and electronic request forms were used by 77 out of 103 (75%) laboratories. A total of 69 out of 103 laboratories (67%) specified the type of sampling tube on their request form. Cystatin C was used for prediction of renal drug elimination by 24% (25 out of 103) of participants. Conclusions: Small number of laboratories implemented all elements needed for optimal TDM practice and report a recommendation on further dosing. Further efforts in education on optimal TDM practice as well as harmonization of service are desirable.
- MeSH
- Internet MeSH
- Laboratories standards statistics & numerical data MeSH
- Humans MeSH
- Drug Monitoring methods statistics & numerical data trends MeSH
- Surveys and Questionnaires MeSH
- Reproducibility of Results MeSH
- Quality Control MeSH
- Quality Assurance, Health Care MeSH
- Health Policy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
PURPOSE: The advent of tyrosine kinase inhibitor (TKI) therapies has revolutionized the treatment of chronic myeloid leukemia (CML). The European LeukemiaNet (ELN) recommends quantification of BCR-ABL1 transcripts by real-time quantitative PCR every 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR4, MR4.5, MR5) maintain remission after treatment stop, assessment of DMR is crucial. However, systematically collected molecular data, monitored with sensitive standardized assays, are not available outside clinical trials. METHODS: Data were collected on the standardized assessment of molecular response in the context of real-life practice. BCR-ABL1 transcript levels after > 2 years of TKI therapy were evaluated for DMR by local laboratories as well as standardized EUTOS laboratories. Since standardized molecular monitoring is a prerequisite for treatment discontinuation, central surveillance of the performance of the participating laboratories was carried out. RESULTS: Between 2014 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR-ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the patients, the initial transcript type had not been reported. Response levels (EUTOS laboratory) were: no MMR, n = 197 (6.51%); MMR, n = 496 (16.40%); MR4, n = 685 (22.64%); MR4.5, n = 937 (30.98%); MR5, n = 710 (23.47%). With a Cohen's kappa coefficient of 0.708, a substantial agreement between EUTOS-certified and local laboratories was shown. CONCLUSIONS: Multicenter DMR assessment is feasible in the context of real-life clinical practice in Europe. Information on the BCR-ABL1 transcript type at diagnosis is crucial to accurately monitor patients' molecular response during or after TKI therapy.
- MeSH
- Leukemia, Myeloid, Chronic-Phase blood drug therapy genetics MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive blood drug therapy genetics MeSH
- Adult MeSH
- Protein Kinase Inhibitors administration & dosage MeSH
- Cohort Studies MeSH
- Laboratories standards statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Registries MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
- MeSH
- Communicable Diseases MeSH
- Laboratories * statistics & numerical data MeSH
- Publication type
- Directory MeSH
- Geographicals
- Czech Republic MeSH
A collaborative effort was carried out by the Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) to promote knowledge exchange between associate laboratories interested in the implementation of indel-based methodologies and build allele frequency databases of 38 indels for forensic applications. These databases include populations from different countries that are relevant for identification and kinship investigations undertaken by the participating laboratories. Before compiling population data, participants were asked to type the 38 indels in blind samples from annual GHEP-ISFG proficiency tests, using an amplification protocol previously described. Only laboratories that reported correct results contributed with population data to this study. A total of 5839 samples were genotyped from 45 different populations from Africa, America, East Asia, Europe and Middle East. Population differentiation analysis showed significant differences between most populations studied from Africa and America, as well as between two Asian populations from China and East Timor. Low FST values were detected among most European populations. Overall diversities and parameters of forensic efficiency were high in populations from all continents.
- MeSH
- Databases, Nucleic Acid MeSH
- DNA Fingerprinting MeSH
- Ethnicity genetics MeSH
- Gene Frequency MeSH
- Genotype MeSH
- Polymorphism, Single Nucleotide * MeSH
- Laboratories statistics & numerical data MeSH
- Humans MeSH
- Microsatellite Repeats MeSH
- INDEL Mutation * MeSH
- Genetics, Population * MeSH
- Racial Groups genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
One of the main goals of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the field of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, six exercises have been organized. At the present edition (GHEP-MIX06), with 25 participant laboratories, the exercise main aim was to assess mixture profiles results by issuing a report, from the proposal of a complex mock case. One of the conclusions obtained from this exercise is the increasing tendency of participating laboratories to validate DNA mixture profiles analysis following international recommendations. However, the results have shown some differences among them regarding the edition and also the interpretation of mixture profiles. Besides, although the last revision of ISO/IEC 17025:2017 gives indications of how results should be reported, not all laboratories strictly follow their recommendations. Regarding the statistical aspect, all those laboratories that have performed statistical evaluation of the data have employed the likelihood ratio (LR) as a parameter to evaluate the statistical compatibility. However, LR values obtained show a wide range of variation. This fact could not be attributed to the software employed, since the vast majority of laboratories that performed LR calculation employed the same software (LRmixStudio). Thus, the final allelic composition of the edited mixture profile and the parameters employed in the software could explain this data dispersion. This highlights the need, for each laboratory, to define through internal validations its criteria for editing and interpreting mixtures, and to continuous train in software handling.
- MeSH
- DNA Fingerprinting standards MeSH
- Laboratories statistics & numerical data MeSH
- Humans MeSH
- Microsatellite Repeats * MeSH
- Likelihood Functions MeSH
- Software MeSH
- Forensic Genetics standards MeSH
- Societies, Scientific * MeSH
- Research Report standards MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Keywords
- identifikace vzorku, externí hodnocení kvality, citlivost k antibiotiku,
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Bacteriological Techniques methods utilization MeSH
- Bacteriology * standards organization & administration statistics & numerical data MeSH
- Laboratories * standards organization & administration statistics & numerical data MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Keywords
- enterococcus gallinarum,
- MeSH
- Bacteriological Techniques * statistics & numerical data MeSH
- Bordetella pertussis isolation & purification MeSH
- Enterococcus isolation & purification drug effects MeSH
- Erysipelothrix isolation & purification MeSH
- Escherichia coli isolation & purification drug effects MeSH
- Bordetella Infections diagnosis MeSH
- Laboratories statistics & numerical data MeSH
- Microbial Sensitivity Tests * statistics & numerical data MeSH
- Quality Control MeSH
- Laboratory Proficiency Testing * statistics & numerical data MeSH
- Yersinia enterocolitica isolation & purification MeSH
- Publication type
- Tables MeSH
- MeSH
- Hepatitis B e Antigens blood MeSH
- Hepatitis B Surface Antigens blood MeSH
- Hepatitis C Antigens blood MeSH
- Laboratories statistics & numerical data utilization MeSH
- Quality Control MeSH
- Serologic Tests * standards statistics & numerical data MeSH
- Laboratory Proficiency Testing * statistics & numerical data MeSH
- Publication type
- Tables MeSH
