Verification of successful maintenance by serum drug level during a guided antipsychotic reduction to reach minimum effective dose (GARMED) trial.

BACKGROUND: Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages. METHODS: A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups. RESULTS: A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL. CONCLUSIONS: The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Biological effective dose as a predictor of local tumor control in stereotactic radiosurgery treated parasellar meningioma patients.

INTRODUCTION: The radio-surgical literature increasingly uses biological effective dose (BED) as a replacement for absorbed dose to analyze outcome of stereotactic radiosurgery (SRS). There are as yet no studies which specifically investigate the association of BED to local tumor control in para-sellar meningioma. METHODS: we did a retrospective analysis of patients underwent stereotactic radiosurgery (SRS) for para-sellar meningioma during the period of 1995-2022. Demographic, clinical, SRS parameters, and outcome data were collected. The target margin BED with and without a model for sub-lethal repair was calculated, as well as a ratio of BED at the target margin to the absorbed dose at the target margin. Factors related to local control were further analyzed. RESULTS: The study was comprised of 91 patients, 20 (22.0%) and 71 (78.0%) of whom were male and female, respectively. The median age was 55.0 (interquartile range Q1, Q3:47.5,65.5years). 34 (37%) patients had a resection of their meningioma prior to SRS. The median interval from SRS to last clinical follow up or progression was 89 months. 13 (14.3%) patients were found to have progression. 3-, 5- and 10-years local tumor control were 98%, 92% and 77%, respectively. In cox univariate analysis, the following factors were significant: Number of prior surgical resections (Hazard Ratio [HR] = 1.82, 95% CI = 1.08-3.05, p = 0.024), BED (HR = 0.96, 95% CI = 0.92-1.00, p = 0.03), and BED/margin (HR = 0.44, 95% CI = 0.21-0.92, p = 0.028). A BED threshold above 68 Gy was associated significantly with tumor control (P = 0.04). CONCLUSION: BED and BED /margin absorbed dose ratio can be predictors of local control after SRS in parasellar meningioma. Optimizing the BED above 68Gy2.47 may afford better long-term tumor control.

Dose length product to effective dose coefficients in adults.

OBJECTIVES: The most accurate method for estimating patient effective dose (a principal metric for tracking patient radiation exposure) from computed tomography (CT) requires time-intensive Monte Carlo simulation. A simpler method multiplies a scalar coefficient by the widely available scanner-reported dose length product (DLP) to estimate effective dose. We developed new adult effective dose coefficients using actual patient scans and assessed their agreement with Monte Carlo simulation. METHODS: A multicenter sample of 216,906 adult CT scans was prospectively assembled in 2015-2020 from the University of California San Francisco International CT Dose Registry and the University of Florida library of computational phantoms. We generated effective dose coefficients for eight body regions, stratified by patient sex, diameter, and scanner manufacturer. We applied the new coefficients to DLPs to calculate effective doses and assess their correlations with Monte Carlo radiation transport-generated effective dose. RESULTS: Effective dose coefficients varied by body region and decreased in magnitude with increasing patient diameter. Coefficients were approximately twofold higher for torso scans in smallest compared with largest diameter categories. For example, abdomen and pelvis coefficients decreased from 0.027 to 0.013 mSv/mGy-cm between the 16-20 cm and 41+ cm categories. There were modest but consistent differences by sex and manufacturer. Diameter-based coefficients used to estimate effective dose produced strong correlations with the reference standard (Pearson correlations 0.77-0.86). The reported conversion coefficients differ from previous studies, particularly in neck CT. CONCLUSIONS: New effective dose coefficients derived from empirical clinical scans can be used to easily estimate effective dose using scanner-reported DLP. CLINICAL RELEVANCE STATEMENT: Scalar coefficients multiplied by DLP offer a simple approximation to effective dose, a key radiation dose metric. New effective dose coefficients from this study strongly correlate with gold standard, Monte Carlo-generated effective dose, and differ somewhat from previous studies. KEY POINTS: • Previous effective dose coefficients were derived from theoretical models rather than real patient data. • The new coefficients (from a large registry/phantom library) differ from previous studies. • The new coefficients offer reasonably reliable values for estimating effective dose.

Fosfatriclaben: Effective dose determination and comparative efficacy assessment with closantel, triclabendazole+ivermectin, triclabendazole+albendazole in artificially infected cattle.

Two controlled efficacy studies were conducted to determine the effective dose of fosfatriclaben (FTCB) and compare its fasciolicidal efficacy with that of three commercial products against eggs and adult stages of Fasciola hepatica in artificially infected cattle. In study 1, 20 trematode-free Holstein Friesian steers were infected on day 0 with 500 F. hepatica metacercariae. Ten weeks after infection and the steers were confirmed to be positive for trematode eggs through a modified sedimentation method. On day 75, they were divided into five groups of four animals each for treatment. Group 1 (G1) served as the untreated control; G2, G3, and G4 received FTCB at 4, 6, and 8 mg/kg/intramuscularly (IM), respectively. G5 received a combined treatment of triclabendazole (TCBZ) (12 mg/kg IM + ivermectin (0.2 mg/kg IM). Individual faecal analyses were performed on days -8, 0, 70, 75, and 105 to evaluate the reduction in trematode eggs. Four weeks after treatment, the steers were humanely slaughtered to harvest the livers and remove the parasites present in the bile ducts. Efficacy was evaluated by the reduction in fecal egg counts or in number of adult parasites, compared to the untreated control. The effective FTCB dose was 6 mg/kg. Once the effective dose was determined, study 2 was conducted on another 20 steers infected with 500 F. hepatica metacercariae, to compare the effectiveness of FTCB with three commercials fasciolicides. All procedures were performed as described in study 1, and treatments were as follows: Group 1 (G1), closantel (5 mg/kg subcutaneously (SC)); G2, TCBZ (12 mg/kg IM) + ivermectin (0.2 mg/kg IM); G3, FTCB (6 mg/kg IM); G4, triclabendazole (12 mg/kg) + albendazole (5 mg/kg/PO (orally); and G5 served as an untreated control. The results indicated that all tested compounds were highly effective in the reduction of faecal egg excretion (99.7-100%) and adult parasites (98.9-100%), except closantel, which exhibited low efficacy (74.4%) when tested against adult trematodes. We concluded that the effective dose of FTCB for cattle was 6 mg/kg IM, which is half the recommended clinical dose of the commercial combination of TCBZ and ivermectin. The fasciolicidal efficacy of FTCB was like the other three flukicides in reducing adult F. hepatica and Fasciola eggs; however, closantel was not sufficiently efficient against adult flukes.

Effective dose of propofol combined with intravenous esketamine for smooth flexible laryngeal mask airway insertion in two distinct age groups of preschool children.

BACKGROUND: There is limited research on the combined use of propofol and esketamine for anesthesia induction during flexible laryngeal mask airway (FLMA) in pediatric patients, and the effective dosage of propofol for FLMA smooth insertion remains unclear. We explored the effective dose of propofol combined with intravenous esketamine for the smooth insertion of FLMA in two distinct age groups of preschool children. METHODS: This is a prospective, observer-blind, interventional clinical study. Based on age, preschool children scheduled for elective surgery were divided into group A (aged 1-3 years) and group B (aged 3-6 years). Anesthesia induction was started with intravenous administration of esketamine (1.0 mg.kg- 1) followed by propofol administration. The FLMA was inserted 2 min after propofol administration at the target dose. The initial dose of propofol in group A and group B was 3.0 mg.kg- 1 and 2.5 mg.kg- 1, respectively. The target dose of propofol was determined with Dixon's up-and-down method, and the dosing interval of propofol was 0.5 mg.kg- 1. If there was smooth insertion of FLMA in the previous patient, the target dose of propofol for the next patient was reduced by 0.5 mg.kg- 1; otherwise, it was increased by 0.5 mg.kg- 1. The median 50% effective dose (ED50) for propofol was estimated using Dixon's up-and-down method and Probit analysis, while the 95% effective dose (ED95) was estimated through Probit analysis. Vital signs and adverse events during induction were recorded. RESULTS: Each group included 24 pediatric patients. Using Dixon's up-and-down method, the ED50 of propofol combined with esketamine for smooth insertion of FLMA in group A was 2.67 mg.kg- 1 (95%CI: 1.63-3.72), which was higher than that in group B (2.10 mg. kg- 1, 95%CI: 1.36-2.84) (p = 0.04). Using Probit analysis, the ED50 of propofol was calculated as 2.44 (95% CI: 1.02-3.15) mg.kg- 1 in group A and 1.93 (95% CI: 1.39-2.32) mg.kg- 1 in group B. The ED95 of propofol was 3.72 (95%CI: 3.07-15.18) mg.kg- 1 in group A and 2.74 (95%CI: 2.34-5.54) mg.kg- 1 in group B. In Group B, one pediatric patient experienced laryngospasm. CONCLUSION: The effective dose of propofol when combined with intravenous esketamine for smooth insertion of FLMA in children aged 1-3 years is 2.67 mg.kg- 1, which is higher than that in children aged 3-6 years (2.10 mg. kg- 1). TRIAL REGISTRATION: Chinese Clinical Trial Registry Center (Registration Number: ChiCTR2100044317; Registration Date: 2021/03/16).

The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP.

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

Combined sedation in pediatric magnetic resonance imaging: determination of median effective dose of intranasal dexmedetomidine combined with oral midazolam.

BACKGROUND: The exact median effective dose (ED50) of intranasal dexmedetomidine combined with oral midazolam sedation for magnetic resonance imaging (MRI) examination in children remains unknow and the aim of this study was to determine the ED50 of their combination. METHODS: This is a prospective dose-finding study. A total of 53 children aged from 2 months to 6 years scheduled for MRI examination from February 2023 to April 2023 were randomly divided into group D (to determine the ED50 of intranasal dexmedetomidine) and group M (to determine the ED50 of oral midazolam). The dosage of dexmedetomidine and midazolam was adjusted according to the modified Dixon's up-and-down method, and the ED50 was calculated with a probit regression approach. RESULTS: The ED50 of intranasal dexmedetomidine when combined with 0.5 mg∙kg- 1 oral midazolam was 0.39 µg∙kg- 1 [95% confidence interval (CI) 0.30 to 0.46 µg∙kg- 1] while the ED50 of oral midazolam was 0.17 mg∙kg- 1 (95% CI 0.01 to 0.29 mg∙kg- 1) when combined with 1 µg∙kg- 1 intranasal dexmedetomidine. The sedation onset time of children with successful sedation in group D was longer than in group M (30.0[25.0, 38.0]vs 19.5[15.0, 35.0] min, P < 0.05). No other adverse effects were observed in the day and 24 h after medication except one dysphoria. CONCLUSION: This drug combination sedation regimen appears suitable for children scheduled for MRI examinations, offering a more precise approach to guide the clinical use of sedative drugs in children. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2300068611(24/02/2023).

Effective doses of ciprofol combined with alfentanil in inhibiting responses to gastroscope insertion, a prospective, single-arm, single-center study.

BACKGROUND: Ciprofol is a novel intravenous sedative and anesthetic. Studies have shown that it features a rapid onset of action, a fast recovery time, slight inhibition of respiratory and cardiovascular functions, and a low incidence of adverse reactions. This study aims to explore the median effective dose (ED50) and the 95% effective dose (ED95) of ciprofol in inhibiting responses to gastroscope insertion when combined with a low dose of alfentanil, and to evaluate its safety, to provide a reference for the rational use of ciprofol in clinical practices. METHODS: We included 25 patients aged 18-64 years of either sex who underwent gastroscopy under intravenous general anesthesia, with a Body Mass Index (BMI) 18-28 kg/m2, and an American Society of Anesthesiologists (ASA) grade I or II. In this study, the dose-finding strategy of ciprofol followed a modified Dixon's up-and-down method with an initial dose of 0.30 mg/kg and an increment of 0.02 mg/kg. Ciprofol was administered after intravenous injection of 7 µg/kg of alfentanil, and 2 min later a gastroscope was inserted. When the insertion response of one participant was positive (including body movement, coughing, and eye opening), an escalation of 0.02 mg/kg would be given to the next participant; otherwise, a de-escalation of 0.02 mg/kg would be administered. The study was terminated when negative response and positive response alternated 8 times. A Probit model was used to calculate the ED50 and ED95 of ciprofol in inhibiting responses to gastroscope insertion when combined with alfentanil. Patients' recovery time, discharge time, vital signs and occurrence of adverse reactions were recorded. RESULTS: The ED50 of single-dose intravenous ciprofol injection with 7 µg/kg of alfentanil in inhibiting gastroscope insertion responses was 0.217 mg/kg, and the ED95 was 0.247 mg/kg. Patients' recovery time and discharge time were 11.04 ± 1.49 min and 9.64 ± 2.38 min, respectively. The overall incidence of adverse reactions was 12%. CONCLUSION: The ED50 of ciprofol combined with 7 µg/kg of alfentanil in inhibiting gastroscope insertion responses was 0.217 mg/kg, and the ED95 was 0.247 mg/kg. Ciprofol showed a low incidence of anesthesia-related adverse events. TRIAL REGISTRATION: http://www.chictr.org.cn (ChiCTR2200061727).

Impact of biologically effective dose on tremor decrease after stereotactic radiosurgical thalamotomy for essential tremor: a retrospective longitudinal analysis.

Stereotactic radiosurgery (SRS) is one of the surgical alternatives for drug-resistant essential tremor (ET). Here, we aimed at evaluating whether biologically effective dose (BEDGy2.47) is relevant for tremor improvement after stereotactic radiosurgical thalamotomy in a population of patients treated with one (unplugged) isocenter and a uniform dose of 130 Gy. This is a retrospective longitudinal single center study. Seventy-eight consecutive patients were clinically analyzed. Mean age was 69.1 years (median 71, range 36-88). Mean follow-up period was 14 months (median 12, 3-36). Tremor improvement was assessed at 12 months after SRS using the ET rating assessment scale (TETRAS, continuous outcome) and binary (binary outcome). BED was defined for an alpha/beta of 2.47, based upon previous studies considering such a value for the normal brain. Mean BED was 4573.1 Gy2.47 (median 4612, 4022.1-4944.7). Mean beam-on time was 64.7 min (median 61.4; 46.8-98.5). There was a statically significant correlation between delta (follow-up minus baseline) in TETRAS (total) with BED (p = 0.04; beta coefficient - 0.029) and beam-on time (p = 0.03; beta coefficient 0.57) but also between TETRAS (ADL) with BED (p = 0.02; beta coefficient 0.038) and beam-on time (p = 0.01; beta coefficient 0.71). Fractional polynomial multivariate regression suggested that a BED > 4600 Gy2.47 and a beam-on time > 70 min did not further increase clinical efficacy (binary outcome). Adverse radiation events (ARE) were defined as larger MR signature on 1-year follow-up MRI and were present in 7 out of 78 (8.9%) cases, receiving a mean BED of 4650 Gy2.47 (median 4650, range 4466-4894). They were clinically relevant with transient hemiparesis in 5 (6.4%) patients, all with BED values higher than 4500 Gy2.47. Tremor improvement was correlated with BED Gy2.47 after SRS for drug-resistant ET. An optimal BED value for tremor improvement was 4300-4500 Gy2.47. ARE appeared for a BED of more than 4500 Gy2.47. Such finding should be validated in larger cohorts.

Note on dose conversion for radon exposure.

The epidemiological approach to converting radon exposure to effective dose is examined. Based on the definition of the effective dose, the dose conversion is obtained from the equivalence of lung-specific detriment associated with low-LET radiation and with radon exposure. This approach most reliably estimates effective dose per radon exposure on the basis of epidemiological data and implicitly includes the radiation weighting factor required to calculate the effective dose from radon exposure using the dosimetric approach, applying biokinetic and dosimetric models. Consistency between the results of the epidemiological and dosimetric approaches is achieved by using a radiation weighting factor of about 10 for alpha particles instead of the current ICRP value of 20. In contrast, the epidemiological approach implemented in ICRP 65, and referred to as dose conversion convention, was based on direct comparison of total radiation detriment with lung detriment from radon exposure. With the revision of radiation detriments in ICRP 103, this approach can be judged to overestimate the effective dose per radon exposure by about a factor of two because the tissue weighting factor for lung differs from the value of relative detriment to which it relates.

The activity of 210Pb in cigarette smoked in Kazakhstan.

The radon decay product 210Pb is a known component of tobacco. In this study, the activity concentration of 210Pb in the most popular cigarette brands (six samples) for Kazakhstan consumers was determined by beta spectrometry. The activity levels of 210Pb ranged between 2.69 ± 0.27 and 27.42 ± 2.74 mBq per cigarette. Higher activity concentrations for 210Pb were found in Sample No.4 and showed an excess of the world average by 1.8 times. The average activity concentrations of 210Pb in cigarette tobacco were 10.42 ± 1.04 mBq cig-1. The daily activities inhaled in the lungs of a smoker, and the resulting effective doses due to cigarette smoking were calculated. Effective doses per year due to cigarette smoking were calculated assuming that 42.13% of the 210Pb in tobacco were retained in the lungs of the smokers. It is concluded that for a smoker in Kazakhstan, the average effective dose ranges from 9.1 ± 0.9 µSv/year to 92.8 ± 9.3 µSv/year for a cigarette consumption of one pack of cigarettes per day. The results indicate that the annual effective doses from inhalation of 210Pb due to smoking one pack of cigarettes per day are from 7 to 58 times (for different types of cigarettes) greater than the annual effective doses from ingestion of radionuclides via the diet.

Radiation doses and diagnostic reference levels for common CT scans in adults in Northwest region of Iran.

This study aims to estimate organ dose and cancer risks, establish region-specific diagnostic reference levels (DRLs), and determine achievable doses (ADs) for common CT procedures in adults in the northwest of Iran. Effective and organ doses were estimated using VirtualDoseCT software in a sample of 480 adult patients who underwent head, sinus, chest, and abdomen-pelvis (AP) CT scans. The guidelines provided by the BEIR VII report were utilized to estimate cancer risks. Effective and organ doses for specific procedures were determined, with the highest mean organ dose being observed in the brain during head CT examinations, with a value of 54.02 mGy. It was observed that the lungs in chest examinations and the colon in AP examinations had the highest risk of cancer, with rates of 30.72 and 21.37 per 100,000 persons, respectively. Higher cancer risk values were generally exhibited by females compared to males. The DRLs for common CT examinations were established as follows: Head CT (CTDIvol 41 mGy, DLP 760 mGy cm), Sinus CT (CTDIvol 16 mGy, DLP 261 mGy cm), Chest CT (CTDIvol 8 mGy, DLP 287 mGy cm), and AP CT (CTDIvol 9 mGy, DLP 508 mGy cm). Significant variations in dose distribution among facilities were identified, indicating the need for optimization. The study highlights the importance of minimizing radiation exposure to critical organs and promoting patient safety in CT examinations. The establishment of region-specific DRLs and ADs can help optimize radiation doses and reduce cancer risks for patients.

Comparison of CBCT radiation doses with conventional radiographs in TMJ imaging using Monte Carlo simulations.

Three-dimensional imaging methods are widely used for evaluation of bony changes of temporomandibular joint (TMJ). Besides, lateral and posterio-anterior TMJ projections in both closed- and open-jaw positions for each temporomandibular joint are used as two-dimensional diagnostic tools. The purpose of the present study was to compare effective and mean organ absorbed doses of plain radiography techniques with those of different modalities of cone beam computed tomography (CBCT) scanning of an adult's temporomandibular joint. PCXMC 2.0 software was used to calculate mean organ and effective doses. A NewTom CBCT device (Newtom 5G XL; QR systems; Verona, Italy) was simulated at 360° rotation using a 6 × 6 cm2 FOV in standard and high-resolution modes. Lateral and posterio-anterior TMJ plain projections were simulated according to recommendations of the manufacturer of the Planmeca ProMax® 2D S3 device. Doses for both projections were simulated with Monte Carlo methods and the International Commission on radiological protection adult reference computational phantoms. The highest mean organ absorbed doses occurred in bone surfaces, salivary glands, and skull for posterio-anterior TMJ and lateral TMJ, and for CBCT scanning in all examinations. The effective doses of posterio-anterior and lateral TMJ plain radiographs were found to be higher than those of the Standard Mode-Eco Scan CBCT. Therefore, the lowest effective dose was calculated in Standard Mode-Eco Scan CBCT. It is concluded that NewTom 5G XL Standard Mode-Eco Scan CBCT can be used instead of plain radiographs (lateral and posterio-anterior TMJ) in temporomandibular joint imaging as it allows visualizing the three-dimensional structure of the temporomandibular joint as an advantage.

Evaluation of organ dose using size-specific dose estimation (SSDE) and related cancer risk due to chest CT scan during the COVID-19 pandemic.

This study aimed to estimate lung and breast doses for individual patients using the size-specific dose estimate (SSDE) method, as well as calculating effective doses, in patients who underwent chest CT scans during the COVID-19 pandemic. Cancer risk incidence was estimated using excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) models from the Biological Effects of Ionizing Radiation Report VII (BEIR-VII). Data from about 570 patients who underwent CT scans for COVID-19 screening were utilized for this study. Using the header of the CT images in a Python script, SSDE and effective dose were calculated for each patient. The SSDE obtained by water equivalent effective diameter (wSSDE) was considered as lung and breast dose, and applied in organ-specific cancer risk estimation. The mean wSSDE value for females (13.3 mGy) was slightly higher than that for males (13.1 mGy), but the difference was not statistically significant (P value = 0.41). No significant differences were observed between males and females in terms of calculated EAR and ERR for lung cancer at 5 and 30 years after exposure (P value = 0.47, 0.46, respectively). Similarly, there was no significant difference in lung cancer LAR values between females and males (P value = 0.48). The results also indicated a decrease in LAR values for both lung and breast cancers with increasing exposure age. In accordance with the ALARA (as low as reasonably achievable) principle, it is important for medical staff and the general public to consider the benefits of CT imaging in detecting such infections. Additionally, imaging medical physicists and CT scan experts should optimize imaging protocols and strike a balance between image quality for detecting abnormalities and radiation dose, all while adhering to the ALARA principle.

Reparametrized Firth's Logistic Regressions for Dose-Finding Study With the Biased-Coin Design.

Finding an adequate dose of the drug by revealing the dose-response relationship is very crucial and a challenging problem in the clinical development. The main concerns in dose-finding study are to identify a minimum effective dose (MED) in anesthesia studies and maximum tolerated dose (MTD) in oncology clinical trials. For the estimation of MED and MTD, we propose two modifications of Firth's logistic regression using reparametrization, called reparametrized Firth's logistic regression (rFLR) and ridge-penalized reparametrized Firth's logistic regression (RrFLR). The proposed methods are designed by directly reducing the small-sample bias of the maximum likelihood estimate for the parameter of interest. In addition, we develop a method on how to construct confidence intervals for rFLR and RrFLR using profile penalized likelihood. In the up-and-down biased-coin design, numerical studies confirm the superior performance of the proposed methods in terms of the mean squared error, bias, and coverage accuracy of confidence intervals.

Efficient Study Design and Analysis of Longitudinal Dose-Response Data Using Fractional Polynomials.

Correctly characterising the dose-response relationship and taking the correct dose forward for further study is a critical part of the drug development process. We use optimal design theory to compare different designs and show that using longitudinal data from all available timepoints in a continuous-time dose-response model can substantially increase the efficiency of estimation of the dose-response compared to a single timepoint model. We give theoretical results to calculate the efficiency gains for a large class of these models. For example, a linearly growing Emax dose-response in a population with a between/within-patient variance ratio ranging from 0.1 to 1 measured at six visits can be estimated with between 1.43 and 2.22 times relative efficiency gain, or equivalently, with 30% to a 55% reduced sample size, compared to a single model of the final timepoint. Fractional polynomials are a flexible way to incorporate data from repeated measurements, increasing precision without imposing strong constraints. Longitudinal dose-response models using two fractional polynomial terms are robust to mis-specification of the true longitudinal process while maintaining, often large, efficiency gains. These models have applications for characterising the dose-response at interim or final analyses.

Overview of radon gas in groundwater around the world: Health effects and treatment technologies.

The natural radioactive decay of uranium in rocks and soils gives rise to the presence of radon in groundwater. The existence of radon in groundwater at activity levels way higher than the reference limits set by US-EPA and WHO was widely covered in literature. The exposure to elevated levels of radon in ground and drinking water have been reported in literature to cause adverse health impacts. The aim of the present paper is to give an overview of radon gas in groundwater followed by the safe limits suggested by international organizations and agencies such as US-EPA and WHO. The paper also discusses the health effects associated with the exposure to radon levels and the estimation of the annual effective dose through ingestion and inhalation. This is followed by the radon levels around the world as well as the corresponding annual effective doses reported in literature. The determination techniques of radon levels in water covered in literature such as liquid scintillation counting, gamma-ray spectrometry and emanometry were also discussed and reviewed in the present work. Next, the paper sheds light on the most frequently used treatment techniques such as aeration, adsorption, filtration as well as biological techniques and evaluates their efficiency in mitigating radon levels in water. The paper also highlights the main precautions and future mitigation plans for radon in groundwater as well as delved onto future research perspectives of radon. It was found out that the type of rock played a key role in determining the radon levels. For instance, granitic rock types were reported to contribute to the elevation in the groundwater radon levels due to their characteristic permeability as a result of the formed fractures as well as their natural incorporation of high levels of uranium. Some of the reported radon levels in groundwater in literature were way higher than the guidelines set by the World Health Organization (WHO) for drinking water and US-EPA alternative higher maximum contaminant level. This review paper could be of importance to researchers working on the evaluation as well as the treatment of radon gas in water as it will provide a critical and state of the art review on radon gas in groundwater.

Volatile Compound Markers in Beef Irradiated with Accelerated Electrons.

This study focuses on the behavior of volatile organic compounds in beef after irradiation with 1 MeV accelerated electrons with doses ranging from 0.25 kGy to 5 kGy to find reliable dose-dependent markers that could be used for establishing an effective dose range for beef irradiation. GC/MS analysis revealed that immediately after irradiation, the chemical yield and accumulation rate of lipid oxidation-derived aldehydes was higher than that of protein oxidation-derived aldehydes. The nonlinear dose-dependent relationship of the concentration of volatile organic compounds was explained using a mathematical model based on the simultaneous occurrence of two competing processes: decomposition of volatile compounds due to direct and indirect action of accelerated electrons, and accumulation of volatile compounds due to decomposition of other compounds and biomacromolecules. A four-day monitoring of the beef samples stored at 4 °C showed that lipid oxidation-derived aldehydes, protein oxidation-derived aldehydes and alkanes as well as alcohol ethanol as an indicator of bacterial activity were dose-dependent markers of biochemical processes occurring in the irradiated beef samples during storage: oxidative processes during direct and indirect action of irradiation, oxidation due to the action of reactive oxygen species, which are always present in the product during storage, and microbial-enzymatic processes. According to the mathematical model of the change in the concentrations of lipid oxidation-derived aldehydes over time in the beef samples irradiated with different doses, it was found that doses ranging from 0.25 kGy to 1 kGy proved to be most effective for beef irradiation with accelerated electrons, since this dose range decreases the bacterial content without considerable irreversible changes in chemical composition of chilled beef during storage.

Dose assessment from exposure to uranium and radon in groundwater in Safi province, Morocco.

In this study we evaluate the uranium and radon concentrations in groundwater from the Province of Safi. The samples were collected from 58 wells across five communes and analyzed using the LR-115 type II detector. Results indicate that uranium concentrations ranged from the Limit of Detection (LLD) to 3.73 µg/l, with a mean of 0.72 µg/l, well below the World Health Organization's safe limit of 30 µg/l. Radon levels varied from LLD to 2.39 Bq/l, with an average of 0.60 Bq/l, also below the United States Environmental Protection Agency's limit of 11 Bq/l. The estimated total annual effective dose due to uranium and radon ranged from 3.47 to 18.84 µSv/y, with an average of 7.54 µSv/y, which is significantly lower than the European Commission's recommended limit of 100 µSv/y. This investigation represents the first study of uranium and radon levels in groundwater in the Province of Safi, providing valuable data for future research and public health.

Assessment of internal radiation exposure caused by radon in commercially bottled spring waters consumed in Turkey.

The variation of dissolved radon levels in water supplies remains of interest since radon ingested through drinking water can give considerable radiation to the lining of the stomach. This study aims to determine the radon concentration levels in bottled spring drinking water (BSW) brands commercially sold in Turkey using a radon gas monitor and to assess the internal radiation exposure caused by the ingestion and inhalation of radon. The activity concentrations of radon analyzed in 77 BSW brands varied from 7.1±0.8 to 28.7±2.7 mBq/L with an average of 15.7±5.1 mBq/L. The total annual effective dose was estimated to assess the radiological risk for three age groups in four different scenarios based on annual drinking water intake. All estimated dose values are well below the recommended reference dose of 100 µSv for drinking water. Therefore, radon gas in the investigated BSW samples poses no significant radiological risk to the public.