Average Dose Research Articles

Implementation and Evaluation of APOTECAchemo in a Community Cancer Center: A Comparative Study of Robotic Versus Manual Antineoplastic Preparation.

Background: The ever-increasing complexity and demand for antineoplastic therapy necessitates innovative solutions to improve the accuracy and safety of drug preparation. Objective: To evaluate the utilization of an advanced robotic chemotherapy drug compounding system (APOTECAchemo) at a Community Cancer Center (CCC), examining accuracy, efficiency, and staff perceptions. Methods: This single-center, retrospective study evaluated the preparation of 7 intravenous (IV) antineoplastics at a CCC over a 1-year period. We compared manual methods with the APOTECAchemo system. The primary measure of accuracy was the absolute drug error percentage, with a comparison of pass and fail rates. Secondary endpoints included the overall use of APOTECAchemo for all IV antineoplastic preparations and average preparation times. An end-user satisfaction survey gathered feedback from pharmacists and pharmacy technicians. Results: A total of 8210 doses were prepared at the CCC, with 52.1% compounded by APOTECAchemo and 47.9% manually. Of these, the CCC prepared 5526 doses of the 7 routinely compounded antineoplastics. APOTECAchemo prepared 3851 (69.7%) doses, while manual compounding accounted for 1675 (30.3%) doses. The average absolute drug error was 1.44% (95% CI, 1.35-1.53) with robot compounding versus 1.17% (95% CI, 1.03-1.32) with manual (P < 0.001). The overall failure rate was 0.72%. There were 25 failed doses (0.45%), with 8 (0.2%) failures attributed to APOTECAchemo and 17 (1%) to manual compounding (P < 0.001). The average dose preparation time was longer with APOTECAchemo compared with manual methods. The end-user satisfaction survey indicated a positive reception toward APOTECAchemo. Conclusions: Our study demonstrates the successful implementation, extensive utilization, and high accuracy of both APOTECAchemo and manual compounding methods in the preparation of routinely administered antineoplastics at a CCC.

Radiation protection in dental imaging: Evaluating the impact of the SABA thyroid shield during panoramic and cone beam computed tomography

BackgroundDental panoramic radiography (DPR) and cone beam computed tomography (CBCT) are an imaging modalities in dentistry. However, these procedures involve exposure to ionising radiation, raising concerns about radiation-induced thyroid damage. To mitigate these risks, thyroid shields have been introduced. This study aimed to evaluate the effectiveness of the SABA thyroid shield in reducing thyroid radiation exposure during DPR and CBCT scans. MethodAn experimental study to measure surface dose in the thyroid region during (DPR) and (CBCT) scans using an Anthropomorphic Phantom and a Solid-State Detector. The attenuation percentage was calculated between radiation surface doses with and without shielding. The significance of the Saba thyroid shield was calculated using a t-test. ResultsFor DPR scans, the average surface doses in the thyroid reduced significantly from 301.1 μGy (at 85 kVp) and 170.3 μGy (at 60 kVp) to 64.43 μGy and 12.94 μGy, respectively, when the Saba thyroid shield was used. For CBCT scans, the average surface doses in the thyroid decreased significantly from 814.43 μGy (for 11 × 13 cm2 field size) and 32.40 μGy (for 5 × 5 cm2 field size) to 62.91 μGy and 12.07 μGy, respectively, with the application of the Saba thyroid shield. The maximum attenuation percentages in the thyroid for the DPR and CBCT scans were 92.40% and 92.27%, respectively. Statistically significant differences between the surface dose reduction with the Saba shield and without it was observed in both DPR scans (p < 0.0000) and CBCT scans (p < 0.0003). ConclusionThe study demonstrates that Saba thyroid shields effectively reduce doses in the thyroid region during dental DPR and CBCT scans. The dose reduction depends on tube voltage for DPR scans, field size, and its position for CBCT scans. Findings highlight the importance of using Saba thyroid shields to minimise radiation exposure and protect the thyroid gland during dental scans.

Differences in opioid prescriptions by race among U.S. older adults with a hip fracture transitioning to community care.

Appropriate pain management can facilitate rehabilitation after a hip fracture as patients transition back to the community setting. Differences in opioid prescribing by race may exist during this critical transition period. We conducted a retrospective cohort study of older adult U.S. Medicare beneficiaries with a hip fracture to examine whether the receipt and dose of opioids differs between Black and White patients as they transitioned back to the community setting. We stratified beneficiaries by whether they received institutional post-acute care (PAC). Outcomes were (1) receipt of an opioid and (2) opioid doses in the first 90 days in the community in milligram morphine equivalents (MMEs; also presented in mg oxycodone). We estimated relative rates and risk differences of opioid receipt and dose differences using Poisson and linear regression models, respectively, using the parametric g-formula to standardize for age and sex. We identified 164,170 older adults with hip fracture (mean age = 82.7 years; 75% female; 72% with PAC; 46% with opioid use after fracture). Overall use of opioids in the community was similar between Black and white beneficiaries. Black beneficiaries had lower average doses in their first 90 days in both total cumulative doses (PAC group: 165 [95% CI -264 to -69] fewer MMEs [-248 mg oxycodone]; no PAC: 167 [95% CI -274 to -62] fewer MMEs [-251 mg oxycodone]) and average MME per days' supply of medication (PAC: -3.0 [-4.6 to -1.4] fewer MMEs per day [-4.5 mg oxycodone]; no PAC: -4.7 [-4.6 to -1.4] fewer MMEs per day [-7.1 mg oxycodone]). In secondary analyses, Asian beneficiaries experienced the greatest differences (e.g., 617-653 fewer cumulative mg oxycodone). Racial differences exist in pain management for Medicare beneficiaries after a hip fracture. Future work should examine whether these differences result in disparities in short- and long-term health outcomes.

Characterization of a new low-dose and low-energy Gafchromic film LD-V1.

To characterize the dose-response, energy dependence, postexposure changes, orientation dependence, and spatial capabilities of LD-V1, a new low-dose Gafchromic film for low-energy x-ray dosimetry. A single sheet of LD-V1 Gafchromic film was cut into 15 × 20mm2 rectangles with a notch to track orientation. Eight different doses between 5 and 320mGy were delivered by an MXR-160/22 x-ray tube using x-ray beams of 90, 100, and 120kVp filtered with 3mm of Al and 2mm of Ti. The 120kVp films were scanned at 1, 1.5, 2, 3, 12, 24, 48, 72, and 168h postexposure in portrait orientation and additionally scanned in landscape orientation at 24h. The 90 and 100kVp films were scanned at 24h postexposure in portrait orientation. Lastly, a 20 × 200mm2 strip of film was irradiated using a thin-slit imaging collimator and scanned 24h postexposure to test the film performance in an x-ray imaging application. Of the three color channels, the red channel was found to produce a dose-response curve with a large range of net optical density (netOD) values across the considered dose range. A prominent energy dependence was discovered, resulting in dose discrepancies on the scale of 17mGy between 90 and 120kVp for a dose of 80mGy. The measured postexposure changes suggest that the calibration irradiation-to-scan time should be longer than 12h with a±4h scanning time window for dose errors of<0.5%. An average dose difference of 3.4% was found between the two scanning orientations. Lastly, noise of 4% was measured in the thin slit collimator film for a dose of 30mGy. We have characterized the LD-V1 film for low-energy, low-dose x-ray dosimetry. Energy, scan-time, and orientation dependencies should be considered when using this film.

Assuring reclaimed water quality using a multi-barrier treatment train according to the new EU non-potable water reuse regulation

In this study, we evaluated the ability of various pilot-scale treatment train combinations to meet the microbial requirements of the new European non-potable water reuse regulation 2020/741. The study utilized non-disinfected secondary effluent from the wastewater treatment plant in Schweinfurt, Germany, as feedwater for two pilot-scale treatment trains. The first, a reference treatment train (Train A), consisted of filtration and UV disinfection as specified for reclaimed water class A in the EU regulation. The second, an advanced treatment train (Train B), included ceramic ultrafiltration (UF), ozonation, biological activated carbon filtration (BAC), and final UV disinfection. Based on a Monte Carlo simulation for Train A, the EU requirements for pathogen removal were not met when an average UV dose of 400-600 J m−2 was applied. This shortcoming was likely due to a moderate transmittance range (50–65 %), resulting in decreased UV fluence. These findings suggest that operational conditions for disinfection should be more clearly specified to ensure consistent pathogen inactivation both during validation and regular operation. In contrast, treatment train B successfully met the requirements of the EU regulations by reducing pathogens to below the detection limit. The UF membrane demonstrated a positive effect on the overall log reduction values (LRVs) throughout the water reclamation system. It also enhanced the efficiency of downstream processes, such as ozonation and UV disinfection, by lowering total suspended solids and turbidity. However, even without the UF membrane, treatment train B was still able to meet the pathogenic EU requirements for non-potable reuse applications. Furthermore, the study observed that the inclusion of biologically activated carbon (BAC) filtration requires a final disinfection step (e.g., UV disinfection) to prevent the potential occurrence of heterotrophic bacteria that proliferate in the BAC filter. For process validation it is recommended to use at least two different virus surrogates (MS2 and PhiX174), rather than just one or total coliphage as required in the EU regulation.

Concurrent Opioid and Psychotropic Drug Use During Pregnancy: Descriptive Study from Two Canadian Provinces

ObjectivesThis study aims to describe the patterns of concurrent opioid and psychotropic drug use (CU) during pregnancy and the characteristics of the mothers dispensed these drugs. MethodsPregnancies between 2000-2020 were identified using administrative data from Manitoba and British Columbia, Canada. Prenatal opioid and psychotropic drug dispensations were assessed, and exposure groups created based on the number of dispensations within each drug category. Descriptive statistics are reported. ResultsApproximately 1.4% of 1,040,021 pregnancies involved CU. Odds of CU were greater for 2+ opioid pregnancies compared to pregnancies with only 1 opioid (OR=4.05). Among CU pregnancies, it was more likely for 2+ types of psychotropics to be dispensed for those involving 2+ opioids compared to 1 (OR=2.23). Percent of CU pregnancies did not change over time, while opioid pregnancies decreased, and psychotropic pregnancies increased. Average morphine equivalent dose of opioids/pregnancy was higher in CU than opioid only pregnancies. Compared to mothers without exposure, CU exposed mothers were of similar age, more likely to live rurally, in lower income areas, and have lower care continuity. ConclusionCU pregnancies remained stable over time. It was more likely for mothers dispensed 2+ opioids to be CU than mothers dispensed only 1 opioid, and more likely for CU mothers dispensed 2+ opioids to be dispensed 2+ psychotropic types. Overall strength of opioids was higher for CU mothers compared to opioid only exposed mothers. ImplicationsStudies measuring the impact of CU on maternal and child outcomes should be conducted to inform safe prescribing practices.

Temporal variations in airborne PCDD/F and dl-PCB concentrations surrounding the dioxin-remediated areas in Da Nang, Vietnam, and health risk assessments.

The air pollution levels from polychlorodibenzo-p-dioxins/polychlorodibenzofurans (PCDD/Fs) and dioxin-like polychlorobiphenyls (dl-PCBs) in three residential areas located north, west, and south of the Da Nang airport were determined by using passive air samplers containing polyurethane foam (PUF) discs with 3-month sampling intervals from 2017 to 2020. The total toxic equivalents (∑TEQs) of the PCDD/Fs and dl-PCBs, using WHO2005-TEFs, were highest north of the airport (134 to 10610fg WHO-TEQ/PUF day, with an average of 1108fg WHO-TEQ/PUF day). The ∑TEQs were lower west of the airport, between 159 and 381fg WHO-TEQ/PUF day and averaged 230fg WHO-TEQ/PUF day. The lowest ∑TEQs occurred south of the airport, with ranges of 76 and 331fg WHO-TEQ/PUF day and an average of 152fg WHO-TEQ/PUF day. Construction activities, including excavation and transportation of dioxin-contaminated soil north of the airport, have increased airborne PCDD/F and dl-PCB contamination and health risks. The average daily doses of PCDD/Fs and dl-PCBs through inhalation (ADDA) for residents located north of the airport were the highest (10.9 to 3434fg WHO-TEQ/kg BW/day and average: 597fg WHO-TEQ/kg BW/day). Residents located west of the airport faced lower health risks (13-123fg WHO-TEQ/kg BW/day and average: 39fg WHO-TEQ/kg BW/day). Residents south of the airport were exposed to a minimum of 6.2-107fg WHO-TEQ/kg BW/day, with an average of 28fg WHO-TEQ/kg BW/day. The maximum and average ADDA values for residents north of the airport exceeded 10% of the tolerable daily intake (TDI) recommended by the WHO (100-400fg WHO-TEQ/kg BW/day). In comparison, all the ADDA values for residents located west and south of the airport were less than and within 10% of the TDI.

Analysis of Wedge Angle Variations in the Treatment Planning System Based on Dose Volume Histogram on Ca Mammae Sinistra

Breast cancer ranks first in terms of the highest number of cancers in Indonesia and is one of the first contributors to cancer deaths. According to IARC, radiotherapy is one of the most important modalities in the treatment of breast cancer. Radiotherapy is a type of treatment that uses ionizing radiation to kill cancer cells without damaging surrounding healthy tissue. To obtain an even or homogeneous dose distribution on an uneven skin surface, a wedge is used so that the radiation given to the tumor area is truly optimal and the surrounding healthy tissue receives a minimum dose. This research was carried out by evaluating the Planning Target Volume (PTV) value based on ICRU-83 and dose distribution in Organs at Risk (OAR) based on QUANTEC standards at four different wedge angles, namely 15°, 30°, 45°, and 60°, used the 3D-CRT technique of tangential radiation with a dose of 50 Gy in 25 fractions on 5 left-sided breast cancer patients. The research results showed that the average Homogeneity Index (HI) values for the 15°, 30°, 45° and 60° wedges were 0.286, 0.346, 0.436 and 0.578, respectively. In the left and right lung dose distribution, the results obtained for the 15°, 30°, 45°, and 60° wedge were respectively 2231.4 and 116.2 cGy, 2257.8 and 114.6 cGy, 2141 and 100 cGy, and 2059.4 and 88.8 cGy. For the average dose distribution to the heart, the values obtained at the 15°, 30°, 45°, and 60° wedges were 2005.6 cGy, 2040.4 cGy, 1930.6 cGy, and 1844.4 cGy, respectively. where the average dose received by OAR is still below the limit allowed by QUANTEC. Using a wedge angle of 15° provides a homogeneous dose distribution for the PTV and a wedge angle of 60° provides the lowest dose distribution for the OAR.

Vaginal Progesterone Gel versus Intramuscular Progesterone for Luteal Phase Support in Suboptimal Responders Undergoing Assisted Reproductive Cycles

Background: The purpose of this research is to compare the efficacy of 8% micronized vaginal progesterone gel (VAG) at 180 mg daily versus intramuscular progesterone (IMP) in oil at 100 mg daily for luteal phase support (LPS) after fresh single embryo transfer (SET) in Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 1b patients, and to ascertain whether the type of LPS predicts live birth in these patients. Methods: A total of 2420 assisted reproductive technology (ART) cycles performed in Ondokuz Mayıs University IVF Unit were analysed retrospectively. The data of POSEIDON Group 1b (unexpected suboptimal responders) who underwent antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were included. All patients were categorized into groups according to the form of LPS, specifically VAG and IMP. Pregnancy, clinical pregnancy rate (CPR), live birth rate (LBR), spontaneous abortion rate and predictors of live birth (age, infertility duration, body mass index (BMI), type of progesterone used for luteal support, serum day 3 estradiol, serum progesterone on the day of human coryonic gonadotrophin (HCG), total duration of induction, serum estradiol on the day of HCG, the total number of oocytes retrieved, number of mature oocytes obtained, average gonadotropin dose per day, total gonadotropin dose administered and total number of embryos retrieved) were analyzed. Results: There was no statistically significant difference between the micronized VAG and IMP groups in terms of age (31 (23–35) vs. 27 (23–35), p = 0.319). There were no statistically significant differences in pregnancy outcomes between the two groups concerning CPR per transfer (70.6% vs. 75.6%; p = 0.364), ongoing pregnancy per cycle (36.2% vs. 39.5%; p = 0.577), and LBR per cycle (34.4% vs. 36.1%; p = 0.785). The spontaneous abortion rates (36.2% vs. 36.8%; p = 0.921) were similar between VAG and IMP groups. The type of LPS did not emerge as a parameter predicting pregnancy (odds ratio (OR): 0.718, 95% confidence interval (95% CI): 0.652–1.313, p = 0.451), clinical pregnancy (OR: 0.598, 95% CI: 0.592–1.289, p = 0.562) and live birth (OR: 0.802, 95% CI: 0.661–1.202, p = 0.580). The logistic regression analysis aimed at assessing the influence of confounding factors, namely age, BMI, and duration of infertility on pregnancy rate, CPR and LBR, did not reveal statistically significant results (p &gt; 0.05). Conclusions: VAG 180 mg daily provide similar pregnancy outcomes compared to 100 mg daily IMP in POSEIDON Group 1b patients undergoing antagonist fresh IVF/ICSI cycles.

Chemometric evaluation, source apportionment, and health risk analysis of natural spring water in Murree, outer Himalayas

IntroductionContamination of water is a critical threat to human health at a global level. Water pollutants, such as heavy metals, can have adverse effects on the well-being of humans, animals, and the natural ecosystem of a region. Study AreaMurree is the most visited tourist destination in Pakistan. The rural population of Murree uses natural spring water for drinking, household use, and irrigation. MethodsThis study assessed the elemental concentration of water from 20 natural springs in Murree using Inductively Coupled Plasma Optical Emission Spectroscopy. Source apportionment and spatial distribution of heavy metals were assessed using statistical approaches such as Pearson's correlation coefficient, principal component analysis, and interpolation. The study assessed the quality of water for drinking and irrigation in Murree's natural spring water using the metal index, sodium absorption ratio, magnesium absorption ratio, percentage sodium, Kelly's ratio, and salinity hazard. The health risks associated with heavy metals were assessed by computing Average daily dose, Hazard quotient, Hazard Index, and Cancer Risk. ResultsThe mean concentration of metals in mgL-1 varied in the following order: Ca (51.23) > Na (22.3) > Mg (16.26) > Si (6.51) > K (1.59) > Se (1.17) > Sr (0.48) > Ba (0.209) > Al (0.060) > Li (0.015) > Zn (0.005) > Fe (0.0033) > Ni (0.0032) > Cr (0.001). Metal index was calculated for Al (0.3), Ba (0.29), Cr (0.024), Ni (0.14), Fe (0.004), Zn (0.002), Sr (0.07), Mg (0.32), and Ca (0.25), revealing low levels of metal pollution. The geology of the study area was identified as the primary source of heavy metals in the water. The estimated values of health hazards showed that ingestion is the primary exposure pathway, with children having a higher risk. The health hazards posed by the heavy metal contact from the waters of Murree are not alarming. Quality indices show that the irrigation water sourced from the natural springs is of satisfactory quality. ConclusionThe study concluded that the spring water of Murree has low concentrations of heavy metals; their concentration is dependent upon the geology of the study area and is good for drinking and irrigation.

Ibrutinib plus rituximab and mini-CHOP in older patients with newly diagnosed DLBCL: a phase 2 ALLG study

AbstractThe multicenter, prospective phase 2 Australasian Leukaemia & Lymphoma Group NHL29 trial was conducted to assess the addition of ibrutinib to R-mini-CHOP (dose attenuated R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients aged ≥75 years with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Treatment consisted of six 21-day cycles of ibrutinib–R-mini-CHOP followed by two 21-day cycles of R-ibrutinib. Coprimary end points were deliverability and 2-year overall survival (OS). The median average relative total dose and average relative dose intensity for the entire regimen were both 97% (interquartile range, 82-100 and 88-100, respectively). With a median follow-up of 35.5 months, the 2-year OS was 68% (95% confidence interval [CI], 55.6-77.4) with a 2-year progression-free survival (PFS) of 60.0% (95% CI, 47.7-70.3). Median OS and PFS were 72 months (95% CI, 35 to not reached) and 40 months (95% CI, 20.4 to not reached), respectively. The overall response rate was 76% (61/79) of patients, with a complete response rate of 71% (56/79). Deaths occurred in 34 of 79 patients (43%), including 17 from progressive disease and 5 treatment related. Overall, 67% patients experienced at least 1 serious adverse event. Most common adverse events were infections and diarrhea (the majority grade 1-2). In both health-related quality of life measures, there was an improvement in functional and symptom scales, median health state classification score, and median visual analogue scale in responders over time. In conclusion, this study showed that the addition of ibrutinib to R-mini-CHOP was both deliverable and efficacious in elderly DLBCL patients.

Effects of nano-Rhodiola rosea combined with treadmill exercise on anti-exercise fatigue in rats.

To explore the potential strategies and mechanisms for enhancing the bioavailability of Rhodiola rosea. 36 Sprague-Dawley rats (8-weeks-old) were randomly assigned to six groups (n = 6 per group). Groups I and II received nano-dose forms of R. rosea, groups III and IV received normal dose form of R. rosea, and groups V and VI served as distilled water control groups. Groups II, IV, and VI were combined with moderate -intensity treadmill exercise. Each group received a daily gavage with 0.5 mL of nano -R. rosea solution (0.01 mg/mL), normal R. rosea solution, and distilled water. All rats were subjected to exhaustive swimming after 4 weeks. Outcome measures include GSH-px activity, T-AOC activity, MDA content, hepatic glycogen content, and T-SOD activity. For plasma MDA content, group I was lower than group III (p < 0.01) and group V (p < 0.01), group II was lower than group III (p < 0.01), group VI was higher than group II (p < 0.05) and group IV (p < 0.05). For plasma T-AOC activity, group II was higher than group VI (p < 0.01). For plasma GSH-px activity, group I was lower than group IV (p < 0.05), groups II, III, and IV were higher than group V (p < 0.05), and group V was lower than that of group VI (p < 0.05). For T-SOD activity of quadriceps muscle, groups I and III were higher than that in group V (p < 0.05). R. rosea has a positive effect on anti-exercise fatigue in rats, with the nano-dosage form of R. rosea showing more significant efficacy than the normal form especially combined with aerobic exercise.

EVALUATION OF THE GLYCOREGULATION EFFICACY BEFORE AND AFTER TREATMENT WITH INSULIN DEGLUDEC IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN THE REPUBLIC OF NORTH MACEDONIA

Patients with type 2 diabetes mellitus (T2DM) who have unsatisfactory glycoregulation with concurrent use of basal insulin and oral hypoglycemics, should be switched to a more intensive therapy regime. To evaluate the efficacy of newly available insulin degludec 70/insulin aspart 30 (IDegAsp), we retrospectively analyzed glycoregulation in 131 patients with T2DM treated with this insulin. All 131 patients were with unsatisfactory glycoregulations, and were switched to IDegAsp from other insulins (except basal-bolus insulin regimen). After a mean period of 11.75±5 months of the treatment with IDegAsp, we found statistically significant improvement in fasting and postprandial glucose levels, and HbA1c (12.5±4.4 vs. 8.8±3.9mmol/l, 13.2±4.6 vs. 9.6±4.1mmol/l, 9.7±1.8 vs. 8.1±1.6%, p&lt;0.01, respectively). The total average daily dose of insulin units (IU) was the same, and there weren’t statistically significant differences in the frequency of hypoglycaemia (p&lt;0.05). From the results, we can conclude that patients with T2DM, who switched to IDegAsp from previous antidiabetic insulin treatment (except basal-bolus insulin regimen) had improved glycaemic control without increased insulin units, and without higher risk for hypoglycemia.

Доклиническая оценка безопасности нового лекарственного препарата для собак и кошек Supramil® эмульсия

This article presents the results of a toxicological evaluation of a new drug for veterinary use, Supramil® emulsion based on R-praziquantel and milbemycin oxime. The drug is intended for the treatment of intestinal nematodes and cestodes, mixed infestations in cats and dogs, as well as for the prevention of dirofilariasis. A single intragastric administration of the drug in doses of a toxic level for rats and mice did not cause toxicosis or death in laboratory animals, on the basis of which the average lethal dose (LD50) for the drug Supramil® emulsion could not be determined. As a result of the assessment of subchronic oral toxicity, it was established that the tested doses of the drug when administered daily to white outbred rats for 14 days are ineffective. An assessment of the ability of the drug, when introduced into the body, to cause a state of hypersensitivity did not reveal an allergenic effect. Thus, the results of this study allow us to conclude that the Supramil® emulsion does not have toxic or allergenic properties and is well tolerated by laboratory animals.

Moving beyond mean heart dose: The importance of cardiac substructures in radiation therapy toxicity.

Normal tissue tolerance dose limits to the heart have been established to reduce the risk of radiation-induced cardiac disease (RICD). Dose constraints have been developed based on either the mean dose delivered to the whole heart (MHD) or the dose delivered to a specific volume, for example, volume of heart receiving equal to or greater than 30 Gy (V30). There is increasing evidence that the impact of thoracic radiation on cardiac morbidity and mortality has been underestimated. Consequently, there is a need to reduce the dose delivered to the heart in radical radiotherapy treatment planning. The pathophysiology of RICD may relate to dose to specific cardiac substructures (CS) rather than the traditionally observed MHD for common toxicities. The MHD or V30 Gy threshold dose rarely represents the true dose delivered to individual CS. Studies have shown the dose to specific areas may be more strongly correlated with overall survival (OS). With advances in modern radiotherapy techniques, it is vital that we develop robust, evidence-based dose limits for CS, to fully understand and reduce the risk of RICD, particularly in high-risk populations with cardiac risk factors. The following review will summarise the existing evidence of dose limits to CS, explain how dose limits may vary according to different disease sites or radiation techniques and propose how radiotherapy plans can be optimised to reduce the dose to these CS in clinical practice.

Evaluation of levetiracetam loading dose in adult patients with benzodiazepine-refractory status epilepticus

BackgroundStatus epilepticus (SE) is a neurologic emergency defined as continued seizure activity greater than five minutes or recurrent seizure activity without return to baseline. Benzodiazepine-refractory SE is continuous seizure activity despite treatment with a benzodiazepine. Treatment of benzodiazepine-refractory SE includes levetiracetam with loading doses ranging from 20 mg/kg to 60 mg/kg up to a maximum dose of 4500 mg. While levetiracetam has minimal adverse effects, there is currently a lack of studies directly comparing the safety and efficacy of various loading doses of levetiracetam. ObjectiveThe objective of this study was to evaluate the safety and efficacy of three loading doses of levetiracetam in the setting of benzodiazepine-refractory SE. MethodsThis was a single center, retrospective cohort study of adult patients with benzodiazepine-refractory SE who were treated with levetiracetam from April 1, 2016, to August 31, 2023. Patients with documented hypersensitivity to levetiracetam, those who were pregnant or incarcerated and patients who received an alternative antiepileptic drug (AED) prior to levetiracetam were excluded. Patients with other identifiable causes of SE including hyperglycemia, hypoglycemia, hyponatremia or who were post cardiac arrest were also excluded. Patients were divided into three arms based on loading dose of levetiracetam administered (≤20 mg/kg [LEVlow], 21‐–39 mg/kg [LEVmed] or ≥40 mg/kg [LEVhigh]). The primary endpoint was the rate of seizure termination, defined as the lack of need for an additional AED within 60 min following levetiracetam administration. Secondary outcomes included the rate of intubation, and recurrent seizure activity 60 min to 24 h post seizure termination as defined by positive EEG results or need for an additional AED. Subgroup analyses were performed to assess the influence of adequate loading doses of benzodiazepines, and outpatient levetiracetam use. ResultsOverall, 740 patients were screened for inclusion, with 218 patients being included in the primary analysis. Patients were divided into three groups with an average levetiracetam loading dose of 14.5 mg/kg in the LEVlow group, 28.8 mg/kg in the LEVmed group, and 48.8 mg/kg in the LEVhigh group. There was no difference in rates of seizure termination at 60 min (92.9% LEVlow vs 89.3% LEVmed vs 84.7% LEVhigh; p = 0.377). Additionally, no difference was found in rates of recurrent seizure activity between 60 min and 24 h post levetiracetam loading dose (32.1% LEVlow vs 32.0% LEVmed vs 28.8% LEVhigh; p = 0.899). However, the LEVhigh group did have a higher rate of intubation (45.8%) compared to the LEVmed (28.2%) and LEVlow (26.8%) group (p = 0.040). ConclusionThe loading of levetiracetam did not result in a statistically significant difference in rate of seizure termination at 60 min nor did it appear to impact the rate of recurrent seizures at 24 h. However, we did find higher rates of intubation in patients who received levetiracetam >40 mg/kg. Further research is warranted to determine the optimal loading dose of levetiracetam in benzodiazepine-refractory SE.

Estimate of the Deterministic Neutron RBE for Radiation-induced Pseudo-Pelger Huët Cell Formation.

Using archival peripheral blood slides from radiation accident patients, we have recently described the pseudo-Pelger Huët anomaly (PPHA) in neutrophils as a new radiation-induced biomarker, useful for dosimetry not only immediately after a radiation incident but also potentially helpful as a tool in retrospective dosimetry. In conjunction with the Radiation Accident Registry at the Radiation Emergency Assistance Center/Training Site (REAC/TS), the frequency of PPHA cells has been compared from selected patients in the Y-12 criticality accident in Oak Ridge, TN, in 1958 and from the patient in the 1971 60Co accident at the USAEC Comparative Animal Research Laboratory (CARL), also in Oak Ridge. Patients A, C, and D in the Y-12 accident are described as having an average dose of 2.53 ± 0.14 Gy gamma + 0.90 ± 0.05 Gy neutron, while the patient in the CARL event had 2.6 Gy gamma dose from event reconstruction. Since the average gamma energies are almost identical in these two cohorts, it is possible to estimate the deterministic neutron relative biological effectiveness (RBEd) for PPHA formation in a criticality event. The neutron RBEd calculated in this way is an average value over the neutron fission energy spectrum and is found to be 3.4 ± 0.6, in good agreement with the currently recommended value of 3 for acute neutron dose to red marrow.

Data analysis of average glandular dose in mammography toward revision of the diagnostic reference level of Japan.

Diagnostic reference level (DRL) for mammography for 2015 and 2020 has been published by J-RIME. More new dose studies are needed to revise the next DRL. In preparation for the next revision of the DRL for mammography, this study investigated data from the Japan Central Organization on Quality Assurance of Breast Cancer Screening on the mean average glandular dose (AGD) for institutional image accreditation in 2019-2023 and the relationship between the average at eligible institutions to date and the type of breast X-ray system. The 95th percentile values of the AGD distributions for the Computed Radiography (CR) and Flat Panel Detector (FPD) systems were 2.5mGy and 2.0mGy, respectively. Moreover, it is assumed that AGD is decreasing due to the spread of FPD systems, and it is expected that the further spread of FPD systems and systems with W/Rh target/filter will reduce AGD in future.

Nutritional habits of professional team sport athletes: An insight into the carbohydrate, fluid, and caffeine habits of English Premier League football players during match play

ABSTRACT To better understand the in-match fuelling practices of elite football players and compare against current guidelines, we quantified the carbohydrate, fluid, and caffeine intake of players from an English Premier League club (n = 22) during 90 min of competitive match-play. Mean carbohydrate intake across match-play was 17 ± 11 g.h−1 with players demonstrating a preference towards CHO-containing fluids (58%) when compared with semi-solids (38%) and solids (14%), respectively. CHO intake was significantly lower than reported by players (17 ± 11 vs 24.8 ± 11 g.h−1, p < 0.001) during initial consultation. Fluid was ingested at a rate of 0.45 ± 0.14 L.h−1, with 54, 40 and 6% of ingested fluid coming from water, carbohydrate, and electrolyte-only solutions, respectively. The majority of players (91%) met the UEFA guidelines for fluid consumption. Of the players who consumed caffeine across match-play (55%) the average dose was 233 ± 148 mg (2.8 ± 1.1 mg.kg−1 body mass [BM]), which meets the UEFA consensus guidelines for caffeine intake. Caffeine capsules (42%) and caffeine containing fluids (30%) were the preferred format prior to the warm-up whilst caffeine gum was exclusively used prior to kick-off and during the half-time period (100%). We conclude that 81% of the total playing squad failed to meet the current UEFA CHO intake recommendations of 30–60 g.h−1, which may be attributed to the preference towards fluid-based CHOs as the chosen format of delivery.

Evaluation of radiation dose to the lens in interventional cardiology physicians before and after dose limit regulation changes.

In response to the International Commission on Radiological Protection, which lowered the lens equivalent dose limit, Japan lowered the lens dose limit from 150 mSv y-1to 100 mSv/5 years and 50 mSv y-1, with this new rule taking effect on 1 April 2021. DOSIRIS®is a dosimeter that can accurately measure lens dose. Herein, we investigated lens dose in interventional cardiology physicians 1 year before and after the reduction of the lens dose limit using a neck dosimeter and lens dosimeter measurements. With an increase in the number of cases, both personal dose equivalent at 0.07 mm depth [Hp(0.07), neck dosimeter] and personal dose equivalent at 3 mm depth [Hp(3), lens dosimeter] increased for most of the physicians. The Hp(3) of the lens considering the shielding effect of the Pb glasses using lens dosimeter exceeded 20 mSv y-1for two of the 14 physicians. Protection from radiation dose will become even more important in the future, as these two physicians may experience radiation dose exceeding 100 mSv/5 years. The average dose per procedure increased, but not significantly. There was a strong correlation between the neck dosimeter and lens dosimeter scores, although there was no significant change before and after the lens dose limit was lowered. This correlation was particularly strong for physicians who primarily treated patients. As such, it is possible to infer accurate lens doses from neck doses in physicians who primarily perform diagnostics. However, it is desirable to use a dosimeter that can directly measure Hp(3) because of the high lens dose.