Consideration of the contribution of the natural background component during individual control of radiation doses to personnel

When ensuring radiation safety in the Russian Federation, there is a principle of separate independent assessment of doses from natural, medical, emergency and technogenic exposure. In practice, it is not always possible to comply with this principled approach. The established dose limits are related only to man-made radiation during normal operation of sources of ionizing radiation. However, during the formation of regional and federal databases on individual doses of personnel exposure, information is entered not on technogenic exposure, but on industrial exposure, that is, without subtracting the natural radiation background. The natural component of the individual dose at low radiation doses is quite significant. Failure to its subtraction leads to an overestimation of the individual dose of external exposure of personnel. Difficulties arise in the implementation of the subtraction of the natural radiation background: 1) in what cases it is necessary to subtract the background, 2) what value to choose for the subtracted background, 3) what method to measure the background, 4) at what stage of processing the measurement information to subtract the background. This article proposes a method for solving the problem of subtracting the natural background radiation from the values of individual doses of external exposure to personnel based on results of individual dosimetric control. Using the example of the city of St. Petersburg, the natural background radiation was measured by the thermoluminescent method of individual dosimetry at 50 control points for three consecutive years (2018-2020). To measure the natural background, we used individual thermoluminescent dosimeters of the same type as those used to measure individual equivalents of external radiation doses to personnel. The choice of using the thermoluminescent method as a predominant one for adjusting the average doses of external radiation from technogenic sources of ionizing radiation when subtracting the natural component of the dose has been substantiated. Comparison of official data on personnel exposure doses with the data obtained as a result of our own measurements is made. Recommendations are given on the use of the obtained values of the average natural radiation background in the formation of regional and federal databases on individual doses of personnel exposure.

PRELIMINARY DEVELOPMENT OF RADIONUCLIDES RELEASE OF INDIVIDUAL DOSE CODE PROGRAM FOR RADIATION MONITORING PURPOSES

Environmental radiation monitoring is one of the important efforts in protecting society and the environment from radiation hazards, both natural and artificial. The presence of three nuclear research reactors and plans to build a nuclear power plant reactor prompted Indonesia to prepare a radiation monitoring system for safety and security (SPRKK). The goal of the study is to provide an appropriate method for developing radiation monitoring system to support the development of nuclear power plant in the near future. For this preliminary study, the author developed a code program using Gaussian distribution model approach for predicting radionuclide release and individual dose acceptancy by human being within 16 wind directions sectors and up to 50 km distance. The model includes estimation of source term from the nuclear installation, release of radionuclides source into air following Gaussian diffusion model, some of the release deposit to the land and entering human being through inhalation, direct external exposure, and resuspension, and predicted its accepted individual dose. This model has been widely used in various code program such as SimPact and PC-Cosyma. For this study, the model will be validated using SimPact code program. The model has been successfully developed with less than 5% deviation. Further study will be done by evaluating the model with real measuring data from research reactor installation and prepare for interfacing with real time radiation data acquisition and monitoring as part of radiation monitoring system during normal and accident condition.

Neutron dosimetry at workplaces of JC “Institute of Nuclear Materials”

If the neutron fields at personnel workplaces differ from the neutron fields in which individual dosimeters are verified, there is a possibility of additional errors in the assessment of such dosimetric quantities as ambient dose equivalent, individual dose equivalent or effective dose. To take into account the energy distribution of the neutron radiation flux density and the geometry of the irradiation of workers, it is necessary to study the characteristics of the fields of neutron radiation at the workplaces of the personnel. In order to obtain conditionally true levels of personnel exposure to neutron radiation at nuclear facilities, studies of the energy and angular distribution of the neutron radiation flux density were carried out at the workplaces of the Institute of Reactor Materials JSC, Zarechny. The energy distribution of the neutron radiation flux density was obtained using an MKS-AT1117M multi-sphere dosimeter-radiometer with a BDKN-06 detection unit and a set of polyethylene spheres-moderators. The angular distribution of the neutron radiation flux density was estimated from the results of measurements of the accumulated dose of neutron radiation by individual thermoluminescent dosimeters placed on four vertical planes of a heterogeneous human phantom. The results of measurements of the energy and angular distribution of the neutron radiation flux density made it possible to estimate the conditionally true values of the ambient and individual dose equivalents. The calculated conventionally true values differ from the measured values from 0.7 to 8.9 times for the ambient dose equivalent and from 6 to 50 times for the individual dose equivalent. In order to reduce the error in assessing the effective dose of personnel using personal dosimeters, correction factors were determined. For different workplaces and types of personal dosimeters, correction factors are in the range of values from 0.02 to 0.16.

Personalized Dosing of Intravenous Vancomycin Among Critically Ill Neonates in Hong Kong: Harnessing Electronic Health Records to Develop a Web-Based Dosing Interface (Preprint)

BACKGROUND Intravenous (IV) vancomycin is used in the treatment of severe infection in neonates. It is efficacious but also associated with elevated risks of developing acute kidney injury. The risk is even higher in neonates admitted to the neonatal intensive care unit (NICU) because the pharmacokinetics of vancomycin in neonates vary widely. Therapeutic drug monitoring has been an integral part of the management to guide individual dose adjustments based on observed serum vancomycin concentrations (Cs) to balance efficacy against toxicity. However, the existing trough-based approach shows poor evidence for improved clinical outcomes. The updated clinical practice guideline recommends population pharmacokinetic (popPK) model-based approaches, targeting area under curve preferably through the Bayesian approach. Since Bayesian methods cannot be performed manually and require specialized computer programs, there is an urgent need to provide the clinicians with a user-friendly interface to facilitate accurate, personalized dosing recommendations for vancomycin in critically ill neonates. OBJECTIVE To utilize medical data from electronic health records (EHRs) to develop a popPK model and subsequently a web-based interface to perform model-based approaches to individual dose optimization of IV vancomycin for NICU patients in local medical institutions. METHODS Data were collected from EHR sources, namely Clinical Information System, In-Patient Medication Order Entry, and electronic Patient Record for subjects prescribed IV vancomycin in the NICU of Prince of Wales Hospital and Queen Elizabeth Hospital in Hong Kong. Patient demographics, serum creatinine (SCr), vancomycin administration records and Cs were collected. The popPK model used comprises a two-compartment infusion model, and various covariate models were tested against body weight, postmenstrual age (PMA), and SCr for the best goodness-of-fit. A previously published web-based dosing interface was replicated and adapted to the needs in this study. RESULTS The final dataset consisted of EHR data extracted from 207 subjects, obtaining a total of 689 Cs measurements. The final model chosen explains 82% of the variability in vancomycin clearance. All parameter estimates are within the bootstrapping confidence intervals. Predictive plots, residual plots, and visual predictive checks demonstrate good model predictability. Model approximations show that the model-based Bayesian approach consistently promotes the probability of target attainment (PTA) above 75%, while only half of the subjects can achieve PTA over 50% with the trough-based approach. The dosing interface was developed with the capability to optimize individual doses with the model-based empirical or Bayesian approach. CONCLUSIONS Utilizing EHRs, a satisfactory popPK model has been verified and used to develop the web-based individual dose optimization interface. The interface is expected to improve treatment outcomes of IV vancomycin in the treatment of severe infections among neonates in local NICUs. This study provides the foundation upon which to conduct a cohort study to demonstrate the utility of the new approach compared with previous dosing methods.

CYP2D6 Reduced Function Variants and Genotype/Phenotype Translations of CYP2D6 Intermediate Metabolizers: Implications for Personalized Drug Dosing in Psychiatry

Genetic differences in cytochrome P450 (CYP)-mediated metabolism have been known for several decades. The clinically most important polymorphic CYP enzyme is CYP2D6, which plays a key role in the metabolism of many antidepressants and antipsychotics, along with a range of non-psychiatric medications. Dose individualization based on CYP2D6 genotype to improve the effect and safety of drug treatment has been an ambition for a long time. Clinical use of CYP2D6 genotyping is steadily increasing; however, for pre-emptive genotyping to be successful in predicting individual dose requirements, high precision of genotype-to-phenotype translations are required. Recently, guidelines for assigning CYP2D6 enzyme activity scores of CYP2D6 variant alleles, and subsequent diplotype-to-phenotype translations, were published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group. Consensus on assigning activity scores of CYP2D6 variant alleles and translating diplotype scores into CYP2D6 poor, intermediate, normal, or ultrarapid metabolizer groups were obtained by consulting 37 international experts. While assigning enzyme activities of non-functional (score 0) and fully functional (score 1) alleles are straightforward, reduced function variant alleles are more complex. In this article, we present data showing that the assigned activity scores of reduced function variant alleles in current guidelines are not of sufficient precision; especially not for CYP2D6*41, where the guideline activity score is 0.5 compared to 0.05–0.15 in pharmacogenetic studies. Due to these discrepancies, CYP2D6 genotypes with similar guidelinediplotype scores exhibit substantial differences in CYP2D6 metabolizer phenotypes. Thus, it is important that the guidelines are updated to be valid in predicting individual dose requirements of psychiatric drugs and others metabolized by CYP2D6.

Тhe effect of cancer patients’ positioning accuracy during radiation therapy sessions using medical linear electron accelerators on the parameters of their individual 3D dose distribution

Due to the rapid development and further improvement of radiation treatment technologies oncologists have an opportunity to precisely deliver individual dose distributions to the tumor, minimizing the doses obtained by critical organs and healthy structures. For the correct and successful application of these complex methods of radiation therapy, it was necessary to enforce the requirements for the technical and dosimetric parameters of the radiotherapy equipment. The purpose of the research is to determine the magnitude of the possible error for patients’ positioning during their radiotherapy treatments using medical linear accelerators by modeling the impact of the patient’s body on the treatment couch. To determine the values of a possible error, the authors have considered the design and characteristics of a typical treatment couch, developed a model of the “average” patient’s body (phantom), which allowed changing the load to the treatment couch with a step of 1 kg. The position parameters of treatment couches were determined for the main types of localization of radiation therapy for malignant tumors: head and neck tumors, breast tumors and pelvic tumors. Numerical values of the treatment coach deviations from prescribed horizontal position were experimentally established for a load from 40 to 180 kg for a treatment couch used at the N.N. Alexandrov National Cancer Centre of Belarus. Based on the obtained experimental data, the necessity to correct the patient's treatment conditions at the stage of treatment planning were confirmed in order to ensure the delivery accuracy of individual dose distributions as required by the radiation therapy protocols. Authors stated that an analysis of the dependence of the deviations in the dose delivered to the patients on the deviation of the radiotherapy table from its horizontal position should be carried out for each radiotherapy table used in clinical practice. The development and implementation of a mechanism that will allow considering this information when choosing the parameters of the patient’s treatment session and prescribing the dose for any localization of malignant neoplasms is needed.