Dose In Situations Research Articles

Treatment and Prevention of Adrenal Crisis and Family Education

Adrenal crisis is a life threatening complication of adrenal insufficiency (AI). Its treatment is urgent and parenteral hydrocortisone (HC) should be given at 10-15 times physiological doses in this situation. If HC is not available, alternatively prednisolone or methyl prednisolone may be used. In cases where peripheral venous access cannot be achieved quickly, intramuscular (IM) administration should be performed without delay. Fluid deficit, hypoglycemia, hyponatremia and hyperkalemia should be evaluated and corrected. Stressful conditions, such as physical stress, accidents, injuries, surgical interventions and anesthesia increase the need for cortisol and may lead the development of adrenal crisis. In order to prevent adrenal crisis, glucocorticoid dose should be increased according to the magnitude and severity of the stress situation as described in this review. Patients’ and/or their families’ education may improve the management of AI and reduce the frequency of adrenal crisis and/or mortality. They should be trained about conditions leading to adrenal crisis, how to increase the glucocorticoid dose in stress situations, recognizing signs of adrenal crisis and using IM HC if it is needed. All patients should be encouraged to carry a card/information sheet/medical alert bracelet or necklace indicating the diagnosis of AI and need for HC administration. It is useful for patients and parents to have an emergency glucocorticoid injection kit and to receive self-injection training.

Benchmark Dose for Dioxin Based on Gestational Diabetes Mellitus Using Coexposure Statistical Methods and an Optimized Physiologically Based Toxicokinetic Model.

Dioxins are ubiquitous endocrine-disrupting substances, but determining the effects and benchmark doses in situations of coexposure is highly challenging. The objective of this study was to assess the relationship between dioxin andgestational diabetes mellitus (GDM), calculate the benchmark dose (BMD) of dioxin in coexposure scenarios, and derive a daily exposure threshold using an optimized physiologically based toxicokinetic (PBTK) model. Based on a nested case-control study including 77 cases with GDM and 154 controls, serum levels of 29 dioxin-like compounds (DLCs) along with 10 perfluoroalkyl acids (PFAAs), seven polybrominated diphenyl ethers (PBDEs), and five non-dioxin-like polychlorinated biphenyls (ndl-PCBs) were measured at 9-16 weeks of gestation. Bayesian machine kernel regression (BKMR) was employed to identify significant chemicals, and probit and logistic models were used to calculate BMD adjusted for significant chemicals. A physiologically based toxicokinetic (PBTK) model was optimized using polyfluorinated dibenzo-p-dioxins and dibenzofurans (PFDD/Fs) data by the Bayesian-Monte Carlo Markov chain method and was used to determine the daily dietary exposure threshold. The median serum level of total dioxin toxic equivalent (TEQ) was 7.72 pg TEQ/g fat. Logistic regression analysis revealed that individuals in the fifth quantile of total TEQ level had significantly higher odds of developing GDM compared to those in the first quantile (OR, 8.87; 95% CI 3.19, 27.58). The BKMR analysis identified dioxin TEQ and BDE-153 as the compounds with the greatest influence. The binary logistic and probit models showed that the BMD10 (benchmark dose corresponding to a 10% extra risk) and BMDL10 (lower bound on the BMD10) were 3.71 and 3.46 pg TEQ/g fat, respectively, when accounting for coexposure to BDE-153 up to the 80% level. Using the optimized PBTK model and modifying factor, it was estimated that daily exposure should be below 4.34 pg TEQ kg-1 bw week-1 in order to not reach a harmful serum concentration for GDM. Further studies should utilize coexposure statistical methods and physiologically based pharmacokinetic (PBTK) models in reference dose calculation.

The accuracy of Eclipse AXB and AAA dose algorithms with dental amalgam.

High-density materials used for dental restorations are poorly defined in CT imaging due to scanner limitations. Studies have established that Eclipse offers poor agreement with delivered dose in situations involving high-density material. Defining the accuracy of dose algorithms in situations involving high-density overrides would improve clinical outcomes both for target coverage and OAR sparing. Dental amalgam was placed within a solid water phantom and measurements were taken at 1cm increments beneath the amalgam down to a depth of 6cm. Exposed film was compared with Eclipse Treatment Planning system (TPS) calculations on a CT of the experimental setup. The amalgam was overridden with a range of HU values and material selections for dose calculation. AXB performs poorly at describing depth dose downstream of Amalgam, regardless of the override material selected. Query ID="Q2" Text="Please confirm the section headings are correctly identified." Applying the known mass density with the Anisotropic Analytical Algorithm (AAA) predicts an average of 1.8% and 2.8% for 6 MV and 10 MV beams. The closest agreement achieved using the Acuros XB (AXB) was overriding with stainless steel, which predicted approximately 1.1% and 1.8% above measured dose for 6 MV and 10 MV respectively. Without overriding the density of amalgam, AAA and AXB return depth dose predictions of 7.3% and 5.8% above film measurement for a 6 MV and 7.6% and 6.5% for 10 MV static beams. Applying override options to a clinical case using an anthropomorphic phantom showed using AXB with Stainless Steel as amalgam override returns the same results as AAA with mass density applied for amalgam. Both of these were in close agreement to the TPS.

Evaluation of pre-exposure vaccine effectiveness against mpox during the 2022–2023 mpox outbreak in the Madrid region (Spain): a test-negative design

IntroductionAn appropriate vaccination approach is critical to control the current outbreak of mpox but there is little research providing information on its effectiveness, particularly under circumstances of limited vaccine availability.MethodsPre-exposure...

Profile of Brazilian inpatients with COVID-19 vaccine breakthrough infection and risk factors for unfavorable outcome.

ABSTRACTObjective.To characterize the epidemiological and clinical profile of individuals more likely to become infected with SARS-CoV-2 after the fully vaccination schedule in order to profile priority groups to receive a booster dose in situations of vaccine doses shortage as well as for maintenance of personal protective care.Methods.This cross-sectional study used data from hospitalized COVID-19 patients aged ≥18 years, who had been fully vaccinated and had a SARS-CoV-2 infection positive diagnosis collected from the SIVEP-Gripe database (Influenza Epidemiological Surveillance Information System) from January 18, 2021 to September 15, 2021. Demographic data, clinical symptoms and preexisting medical conditions (comorbidities) were analyzed. The primary outcome was in-hospital death.Results.The majority of hospitalized patients with vaccine breakthrough infection were ≥60 years old, male, with critical or severe COVID-19. The fatality rate was extremely high (50.27%) and more pronounced in elderly groups. The most prevalent symptoms were cough, dyspnea, respiratory distress, and low blood oxygen saturation. The most frequent comorbidities were heart disease and diabetes. High fatality rates were observed among patients admitted to the intensive care units (72.88%) and those who required invasive mechanical ventilation (87.82%). The main risk factors for an unfavorable outcome were older age, respiratory compromise, inactivated virus vaccine immunization, and preexisting medical conditions.Conclusions.We characterized the profile of hospitalized Brazilian patients with COVID-19 vaccine breakthrough infection and the risk factors for an unfavorable outcome. These data allow to identify priority groups to receive a booster dose and to continue using personal protection.

New aspects of glucocorticoid substitution in adrenal insufficiency

HintergrundEine adäquate Anpassung der Glukokortikoidsubstitution an unterschiedliche Situationen ist essenziell für Leistungsfähigkeit und Lebensqualität von Patienten mit Nebennierenrindeninsuffizienz (NNRI). Sie dient darüber hinaus der Vermeidung lebensbedrohlicher adrenaler Krisen.Ziel der ArbeitVerbesserung der Versorgung von Patienten mit Nebennierenrindeninsuffizienz.Material und MethodenSelektive Literaturrecherche unter besonderer Berücksichtigung neuerer Studien.ErgebnisseEine optimale Glukokortikoidsubstitution hat das Ziel, die physiologischen Kortisolschwankungen möglichst genau nachzuahmen. Hier haben in den letzten Jahren Präparate mit veränderter Pharmakokinetik das Therapiespektrum erweitert. Im Vordergrund stehen eine adäquate Anpassung der Substitution in Stresssituationen sowie die Vermeidung und adäquate Behandlung adrenaler Krisen, die mit einer Inzidenz von 4,8 bis 8,3 Krisen pro 100 Patientenjahre auftreten und mit einer Mortalität von etwa 0,5 pro 100 Patientenjahre weiterhin eine tödliche Bedrohung darstellen.SchlussfolgerungZur Verhinderung lebensbedrohlicher Nebennierenkrisen ist eine Schulung von Patienten, Angehörigen und insbesondere auch medizinischem Personal notwendig.Zusatzmaterial onlineDie Online-Version dieses Beitrags (10.1007/s00108-021-01209-4) enthält den vollständigen Notfallausweis für Patienten mit Nebennierenrindeninsuffizienz.

RaDoM2: an improved radon dosimeter

A new dosimeter for radon progeny called RaDoM (Radon Dose Monitor) was recently developed at CERN . RaDoM is an active detector able to directly estimate the effective dose due to the radon progeny. The first version, which used the Timepix hybrid pixel detector, a system of filters and a pump, correctly assessed the effective dose in situations where the environmental conditions are characterized by a standard equilibrium factor, but showed low efficiency for low radon concentrations and in clean air environments. In this improved version, RaDoM2, the Timepix has been replaced by a silicon pin diode. This solution has allowed the optimization of the geometry, the pump flow rate and the associated electronics, improving the performance of RaDoM and substantially reducing its manufacturing costs. This paper describes the RaDoM2, its improved performance compared to RaDoM, the cloud and user interface, tests in a radon chamber and on-the-field measurements.

Failed Nerve Blocks: Prevention and Management

Failed Nerve Blocks: Prevention and Management

Dose Finding in Late-Phase Drug Development.

A drug may fail or raise concerns that must be addressed in later-phase trials because of an unacceptable toxicity profile, even if the drug meets expectations for efficacy. The problem could be due to the late onset of unacceptable toxicities that were not observed in early-phase trials. We explore methodologies to find appropriate doses in situations where a drug meets the primary efficacy objective but concerns about toxicity remain. In this manuscript, we propose a general framework to design a good phase IV trial that is designed to optimize the treatment regimen. In the first step, we learn from the existing data about the dose-response and dose-toxicity relationships and further to explore and establish the relationship using a statistical model. Noting the limitations of the exploratory analyses, these analyses are not sufficient to allow us to make definitive conclusions. However, the prediction obtained from the model, either estimated efficacy metrics or safety parameters for some doses, can be incorporated in the design of the phase IV trial. In the second step, we further propose and compare design options, including options that could effectively incorporate information from these exploratory analyses, for clinical trials to find optimal doses, including trials to fulfill postmarketing commitments or requirements.

Sci—Thur AM: YIS ‐ 11: Estimation of Bladder‐Wall Cumulative Dose in Multi‐Fraction Image‐Based Gynaecological Brachytherapy Using Deformable Point Set Registration

Dosimetric parameters based on dose‐volume histograms (DVH) of contoured structures are routinely used to evaluate dose delivered to target structures and organs at risk. However, the DVH provides no information on the spatial distribution of the dose in situations of repeated fractions with changes in organ shape or size. The aim of this research was to develop methods to more accurately determine geometrically localized, cumulative dose to the bladder wall in intracavitary brachytherapy for cervical cancer. The CT scans and treatment plans of 20 cervical cancer patients were used. Each patient was treated with five high‐dose‐rate (HDR) brachytherapy fractions of 600cGy prescribed dose. The bladder inner and outer surfaces were delineated using MIM Maestro software (MIM Software Inc.) and were imported into MATLAB (MathWorks) as 3‐dimensional point clouds constituting the “bladder wall”. A point‐set registration toolbox for MATLAB, Coherent Point Drift (CPD), was used to non‐rigidly transform the bladder‐wall points from four of the fractions to the coordinate system of the remaining (reference) fraction, which was chosen to be the emptiest bladder for each patient. The doses were accumulated on the reference fraction and new cumulative dosimetric parameters were calculated. The LENT‐SOMA toxicity scores of these patients were studied against the cumulative dose parameters. Based on this study, there was no significant correlation between the toxicity scores and the determined cumulative dose parameters.

Evaluation of a lithium formate EPR dosimetry system for dose measurements around brachytherapy sources

A dosimetry system using lithium formate monohydrate (HCO2Li x H2O) as detector material and electron paramagnetic resonance (EPR) spectroscopy for readout has been used to measure absorbed dose distributions around clinical 192Ir sources. Cylindrical tablets with diameter of 4.5 mm, height of 4.8 mm, and density of 1.26 g/cm3 were manufactured. Homogeneity test and calibration of the dosimeters were performed in a 6 MV photon beam. 192Ir irradiations were performed in a PMMA phantom using two different source models, the GammaMed Plus HDR and the microSelectron PDR-v1 model. Measured absorbed doses to water in the PMMA phantom were converted to the corresponding absorbed doses to water in water phantoms of dimensions used by the treatment planning systems (TPSs) using correction factors explicitly derived for this experiment. Experimentally determined absorbed doses agreed with the absorbed doses to water calculated by the TPS to within +/-2.9%. Relative standard uncertainties in the experimentally determined absorbed doses were estimated to be within the range of 1.7%-1.3% depending on the radial distance from the source, the type of source (HDR or PDR), and the particular absorbed doses used. This work shows that a lithium formate dosimetry system is well suited for measurements of absorbed dose to water around clinical HDR and PDR 192Ir sources. Being less energy dependent than the commonly used thermoluminescent lithium fluoride (LiF) dosimeters, lithium formate monohydrate dosimeters are well suited to measure absorbed doses in situations where the energy dependence cannot easily be accounted for such as in multiple-source irradiations to verify treatment plans. Their wide dynamic range and linear dose response over the dose interval of 0.2-1000 Gy make them suitable for measurements on sources of the strengths used in clinical applications. The dosimeter size needs, however, to be reduced for application to single-source dosimetry.

Modelling radionuclide distribution and transport in the environment

Mathematical models of radionuclide distribution and transport in the environment have been developed to assess the impact on people of routine and accidental releases of radioactivity from a variety of nuclear activities, including: weapons development, production, and testing; power production; and waste disposal. The models are used to estimate human exposures and doses in situations where measurements have not been made or would be impossible or impractical to make. Model results are used to assess whether nuclear facilities are operated in compliance with regulatory requirements, to determine the need for remediation of contaminated sites, to estimate the effects on human health of past releases, and to predict the potential effects of accidental releases or new facilities. This paper describes the various applications and types of models currently used to represent the distribution and transport of radionuclides in the terrestrial and aquatic environments, as well as integrated global models for selected radionuclides and special issues in the fields of solid radioactive waste disposal and dose reconstruction. Particular emphasis is placed on the issue of improving confidence in the model results, including the importance of uncertainty analysis and of model verification and validation.

In Vitro Exposure of Mammalian Cells to Radon: Dosimetric Considerations

We have developed a model to calculate the dose to the cell nucleus in cells exposed in suspension to radon and/or radon progeny. The model addresses the influence of (1) different radiation qualities and energies in the irradiation milieu; (2) the contribution to dose from radioactivity in the medium surrounding the cell after exposure to the radon gas as well as that from excess radon progeny associated with the cell; (3) the geometry of the cell and of the radiosensitive target, the cell nucleus; (4) the intracellular localization of the radionuclides; (5) attenuation of the alpha particles by the cytoplasm; (6) the radionuclide concentrations in the medium; and (7) the length of exposure. Investigation of the influence of these various parameters was made using an irradiation system in which cells were exposed to 212Bi, which decays to stability with the emission of an alpha particle (either 6.05 or 8.78 MeV). The information from these studies was then used to develop the system further for more complex systems in which 222Rn and its progeny are present. The model takes into account the contribution of dose from different radiation sources using scintillation counts of the medium and the cells, and it is useful for calculations of dose in situations where cells are exposed in suspension culture.

A unified approach to dose-effect relationships in radiotherapy. II: Inhomogeneous dose distributions

Conventional dose-effect relationships, such as those based upon the NSD or linear-quadratic concepts, do not account for dose inhomogeneities. Only a single “dose” value can be used in these equations and this can give rise to significant errors in the estimation of the “tolerance” dose in situations where dose distributions are inhomogeneous. This paper presents a method of “integrating” the biologically effective dose over the entire volume of each organ or tissue irradiated. Integral forms of the variable-exponent TDF and linear quadratic factor (LQF) models (ITDF and ILQF, respectively) can be used to determine whether or not any organ or tissue in an irradiated volume has exceeded tolerance, regardless of dose distribution non-uniformity. Several examples are given with comparisons to solutions obtained by conventional dose-effect models.

Radiation doses due to long-range transport of airborne radionuclides released by a reactor accident--effects of changing dispersion conditions during transport.

This paper presents a model for the estimation of radiation doses due to long-range transport of airborne radioactive material released into the atmosphere by a reactor accident. The paper includes examples of calculated doses in situations where the weather changes during the transport path. These examples show that changing dispersion conditions, such as rain, may bring about considerable changes in the individual doses. Short-term changes in turbulence, mixing depth and wind speed during the transport path also have a strong influence on doses.

Definition of Energy Imparted: A New Formulation Adapted to Exact Solutions of the Absorbed Dose Equation under Nonequilibrium Conditions

The volume- and time-dependent stochastic quantity the energy imparted, epsilon, defined by the International Commission on Radiation Units and Measurements, can be represented alternatively as the sum of volume- and time-independent contributions ..delta..epsilon from individual basic processes. In an interaction by an ionizing particle, ..delta..epsilon equals that part of the radiation energy which is converted into energy forms other than the kinetic energy of ionizing particles and rest-mass energy of nuclei and elementary particles. In a spontaneous process such as a nuclear decay, ..delta..epsilon is equal to that part of the released rest-mass energy which is not converted into the kinetic energy of ionizing particles. The nonstochastic quantity the absorbed dose, D, is the mean energy imparted per unit mass of a medium. It is a volume-independent quantity and the values of ..delta..epsilon for individual processes are the quantities of real significance in calculations of the absorbed dose in situations where radiaion equilibrium has not been established, e.g., in small Bragg--Gray cavities. More information about the values of ..delta..epsilon for individual processes and the spectral distributions of ionizing particles is needed for the accurate treatment of cavity and interface dosimetry theories.