Dose Monitoring Research Articles

Assessment of background radiation level in different tourism beach of Bengkayang, West Borneo

Environmental radiation and radioactivity monitoring has become important to investigate to generate a baseline database in Bengkayang Sea-Beach area, West Borneo. There is a need to conduct an environmental monitoring program to determine any change due to radioactivity radiation released from the nuclear installation in case of normal operation or emergency conditions, where Bengkayang is a candidate site of Indonesia’s Nuclear Power Plant. In this study, the background radiation levels have been measured at 9 different tourism beach areas of Bengkayang. Natural background radiation is the main source of radiation for the public of tourism. Calibrated gamma dose monitor were used for the measurement of dose level where reading was taken by placing the survey meter at ground level and at a height of 1 m from the ground (gonad level). The observed background radiation dose rate of 9 beach areas is below the world average. The mean Annual Effective Dose Equivalent (AED) is found comparable to other studies. The radiation the population receives due to beach sands mainly results from the time spent on the beach during recreation. The results show that 9 tourism beaches of Bengkayang are considered as safe areas with natural background radiation.

A selective dual quenching sensor (EY/BG@CDs) for simultaneous monitoring of gentamicin and ketorolac levels in plasma: a highly efficient platform that caters to the needs of therapeutic drug monitoring.

This research work introduces a novel sensor that utilizes two fluorophores to enable simultaneous monitoring of gentamicin sulphate (GNT) and ketorolac tromethamine (KET). The innovative sensor is composed of carbon dots (CDs) derived from black grapes (BG) and eosin Y (EY) dye. The interaction between the studied drugs and EY/BG@CDs sensor components allows for their simultaneous detection where GNT quenches the fluorescence of EY at 535 nm without affecting the fluorescence of CDs, while KET quenches the fluorescence of BG@CDs at 385 nm without impacting EY fluorescence. The BG@CDs probe was successfully characterized using various techniques such as absorption spectrophotometry, spectrofluorimetry, TEM imaging, infrared spectroscopic analysis, and XRD analysis. The suggested methodology was observed to be highly sensitive for the simultaneous determination of GNT and KET in their spiked rabbit plasma samples, with wide linear ranges and low limit of detection (LOD) values. The studied drugs were extracted using a highly selective extraction method involving protein precipitation followed by mixed mode solid phase extraction using an Oasis WCX cartridge. The simultaneous determination of GNT and KET is essential due to the potential interactions between the studied drugs. Therefore, this analysis can be used to evaluate the necessity of dose monitoring and the potential adverse effects of co-administration of these drugs.

Comparison of Hematological Parameters between Diagnostic Radiation Workers and Non-Radiation Workers

Purpose: Radiation workers are exposed to chronic effects due to long-term exposure to low levels of ionizing radiation. One of the biological indicators to evaluate these chronic radiation effects is the study of the hematopoietic system. The purpose of this study is to compare the changes in blood parameters of radiology staff and staff of other wards of the hospital.
 Materials and Methods: In this study, 47 radiology staff working in the radiology department of the hospital as the study group and 94 personnel in other departments as the control group were included. Demographic data including age, gender, and work experience were obtained. Hematological parameters were extracted from the complete blood count tests of participants.
 Results: The results of this study showed that the Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC) parameters significantly decreased in the male study group, whereas no significant differences were observed in the blood parameters of the female study group in comparison to those of the control group. There was a significant positive correlation between the parameters of Hemoglobin and age. There was a significant negative correlation between work experience and white blood cells, while there was a significant positive correlation between work experience and Hemoglobin.
 Conclusion: Correlation between collective absorbed dose and changes in blood parameters is suggested for future studies. Based on the results of this study and other studies, it can be concluded that long-term exposure to low levels of radiation may change blood parameters. Therefore, regular and periodic complete blood count tests along with absorbed dose monitoring of radiation workers are recommended.

Identification and characterization of patients being exposed to computed-tomography associated radiation-doses above 100 mSv in a real-life setting.

Rationale and objectivesPatients receiving high cumulative effective doses (CED) from recurrent computed tomography (CT) in a real-life setting are not well identified. Evaluation of causes and patient characteristics may help to define individuals potentially at risk of radiation-induced secondary malignancies. Materials and methodsPatients who received a CED > 100 mSv from CT scans during October 2012 and April 2020 at a tertiary university center were identified with the help of a radiological radiation dose monitoring system. The primary disease and referral diagnosis, number of CT exams, time period, age, BMI and gender distribution of the 1000 patients with the highest CED were analysed. Results3431 patients had a CED of more than 100 mSv, which corresponded to 2.75% of all patients who received a CT exam. From the 1000 patients with the highest CED, mean number of CT exams per patient was 14.6, mean CED was 257 mSv (SD 98, range 177–1339). Mean age of patients was 63.9 years (SD 10.6), male to female ratio 3:2, and mean BMI 28.7 kg/m2 (SD 5.5). 728 (72.9%) patients had cancer. The leading primary diagnosis was liver cirrhosis in 197 patients and 103 patients had a liver transplantation. In patients with liver cirrhosis, 750 exams were indicated for the follow-up of the disease, 662 for the clarification of an acute clinical condition, and 202 for CT-guided stereotactic radiofrequency ablation. ConclusionRecurrent CT scans of patients with cancer, liver cirrhosis and liver transplantation may lead to critically high CED.

Management of doses from medical exposures in interventional radiology: an integrative review

Interventional radiology (IR) uses minimally invasive image-guided procedures that may require a long duration and deliver high radiation doses to the patient. The most current studies on management and dose reduction in IR have shown to be of fundamental importance in radiation protection practices. The objective of this study was to survey what has been published in the national and international literature on the doses received by patients undergoing IR procedures. It consisted of an integrative review study carried out in Scielo, Pubmed, and INIS databases in the time frame of 2016-2021, using as descriptors: interventional radiology, radiation injuries, radiological protection, dosimetry; and their equivalents in English: interventional radiology, radiation injuries, radiological protection, and dosimetry. The initial sample consisted of 68 full articles related to the theme, published during the study period. Of these, 11 articles were selected and made up the final sample. The results indicate that the use of software in dose management and monitoring has proven to be an important tool in radiological protection. The implementation of dose reduction strategies and increased awareness about the use and effects of radiation result in significantly lower doses to both professionals and patients. No national study on dose management has been identified, highlighting the need to promote the subject in the country. The main recommendations identified were the introduction of technologies and the training of the workers involved.

Absolute dose measurement and energy dependence of LiF dosimeters in proton therapy beam dosimetry

Background: For the purpose of patient dose monitoring, thermoluminescent dosimeters (TLDs) can report any dose point of interest as in vivo dosimetry. However, energy dependence of TLDs may perturb proton beam dosimetry, particularly for low-energy proton beams. The purpose of this study was to evaluate the energy dependence of TLDs for proton beams and influence on dosimetry.

Cangrelor Dosing and Monitoring for Prevention of Acute Systemic-to-Pulmonary Artery Shunt Thrombosis in Neonates.

Systemic-to-pulmonary artery shunts are amongst the most common palliative procedures performed in neonates with congenital heart defects. These procedures require immediate postoperative thromboprophylaxis to prevent life-threatening shunt thrombosis. The novel use of intravenous P2Y12 platelet receptor antagonists has led to a need for dosing recommendations and monitoring. This study aims to determine cangrelor dosing in neonates through laboratory assessment of P2Y12 receptor reactivity and adverse events. Observational retrospective cohort study on the use of cangrelor for thromboprophylaxis in the immediate postoperative period of neonates undergoing placement of systemic-to-pulmonary artery shunts in a tertiary children's hospital from March 2020 to March 2021. Ten neonates receiving cangrelor post systemic-to-pulmonary artery shunt placement were included in the study. Median age and weight were 4 days (IQR, 2.75-5.25) and 3.49 kg (IQR, 3.1-3.75), respectively. Five (50%) patients received a 3.5-mm shunt, while the remaining patients received a 4-mm shunt. For thrombin inhibition, 5 (50%) patients received heparin and 5 (50%) received bivalirudin. Median cangrelor dose was 0.1 mcg/kg/min (IQR, 0.1-0.1). Median achieved P2Y12 reaction units (PRU) at this cangrelor dose was 127.5 (IQR, 72.5-173.75). No shunt thrombosis occurred in these patients; however, there was 1 minor hemorrhagic event. Our study suggests that a cangrelor dose of 0.1 mcg/kg/min is associated with therapeutic PRU and prevents shunt thrombosis in neonates post systemic-to-pulmonary artery shunt, with minimal hemorrhagic complications.

Surgeon eye lens dose monitoring in interventional neuroradiology, cardiovascular and radiology procedures

PurposeThis study investigated the radiation dose to surgeon eye lens for single procedure and normalised to exposure parameters for eight selected neuroradiology, cardiovascular and radiology interventional procedures. MethodsThe procedures investigated were diagnostic study, Arteriovenous Malformations treatment (AVM) and aneurysm embolization for neuroradiology procedures, Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty (CA-PTCA), Pacemaker and Implantable Cardioverter-Defibrillator implantation (PM-ICD), Endovascular Aortic Repair (EVAR) and Fenestrated Endovascular Aortic Repair (FEVAR) for cardiovascular and electrophysiology procedures. CT-guided lung biopsy was also monitored.All procedures were performed with table-mounted and ceiling-suspended shields (0.5 mm lead equivalent thickness), except for FEVAR and PM-ICD where only a table mounted shield was present, and CT-guided lung biopsy where no shield was used. Dose assessment was performed using a dosemeter positioned close to the most exposed eye of the surgeon, outside the protective eyewear. ResultsThe surgeon most exposed eye lens median Hp(3) equivalent dose for a single procedure, without protective eyewear contribution, was 18 μSv for neuroradiology diagnostic study, 62 μSv for AVM, 38 μSv for aneurysm embolization, 33 μSv for CA-PTCA, 39 μSv for PM-ICD, 49 μSv for EVAR, 2500 μSv for FEVAR, 153 μSv for CT-guided lung biopsy. ConclusionsIn interventional procedures, the 20 mSv/year dose limit for surgeon eye lens exposure might be exceeded if shields or protective eyewear are not used.Surgeon eye lens doses, normalised to single procedures and to exposure parameters, are a valuable tool for determining appropriate radiation protection measures and dedicated eye lens dosemeter assignment.

Dosage, Safety and Efficacy of Posaconazole As Primary Antifungal Prophylaxis in High-Risk Recipients of Allogeneic Stem Cell Transplantation

Introduction: The use of anti-mold prophylaxis with anti-aspergillus activity is recommended for patients (pts) undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with high risk of fungal infection (Maertens, J Antimicrob Chemother 2018). Yet, few data are available regarding the use of posaconazole. Methods: This retrospective study included all Allo-HSCT adult recipients having benefited from posaconazole therapy in our center as a primary anti-fungal prophylaxis for high-risk of fungal infection. The latter was defined as use of i)an alternative donor, ii)sequential conditioning regimen, iii)a regimen associated with severe mucositis, iv) post-transplant cyclophosphamide (PT-Cy) or v) previous allo-HSCT. Posaconazole was programmed to be initiated at day (D) 0 or D5/6 (in case of PT-Cy) and administered up to day 100. We report here on the residual concentration of posaconazole during the neutropenic phase then on the tolerance and efficacy of such prophylaxis in this cohort. Results: Seventy high-risk pts (males 63.3%, median age 54 years old, range 20-73) received Allo-HSCT between April 2020 and December 2021 for a myeloid (n=51), lymphoid (n=17) or non-malignant hematological (n=2) disease and received posaconazole as a primary prophylaxis. The Sorror score at transplant time was ≥ 3 for 24 pts (33.8%). Twenty-two patients had already received posaconazole as a primary prophylaxis before Allo-SCT including 26 during the neutropenic phase of their induction for AML or MDS, 3 for prolonged neutropenia, 2 during treatment with alemtuzumab for T-cell leukemia/lymphoma, and 1 during a previous AlloHCST. Four patients had also received other antifungal agentsbefore Allo-SCT (caspofongine (n=1), voriconazole (n=1) or liposomal amphotericin B (n=2)) because of a suspected mold infection which has been finally excluded. All pts had at least one high-risk criterion of fungal infection. These included the use of an alternative donor in 42 pts (haplo-identical donor n= 41, umbilical cord blood n=1), sequential conditioning regimen in 9, with PT-Cy in 57, second or third allo-HSCT in 8 and conditioning regimen associated with severe mucositis in 11 (TBI 8-12gy n=3, thiotepa-based n=8). All but one pts received posaconazole using the gastroresistant tablet form at a dose of 300mg/day. One patient received the drinkable suspension form at a dose of 200mg 3 times a day. Following prophylaxis initiation, serum posaconazole concentrations were available in 51 and 16 patients at medians of 9 and 39 days, respectively. A protective residual level of posaconazole (> 0.5mg/L) was achieved in 57% of the patients (n=29) at first assessment and 87.5% (n=12) at second evaluation. Posaconazole was stopped early due to related-toxicity in 9 cases (12.6%), including liver toxicity in 7 pts, QT prolongation in 1 and skin hyperesthesia in 1. Treatment was restarted without recurrence of toxicity in 2 cases. Posaconazole was stopped early in 2 patients due to non-related toxicity, including one veno-occlusive disease and one hepatic acute GVHD. Posaconazole was temporary discontinued in 4 patients due to a suspected fungal infection before being restarted. Most patients (n=59/70, 84.2%) did not present fungal infections while being under posaconazole therapy. Only 11 cases were documented with this complication (Table 1), including 8 invasive pulmonary aspergillosis (IPA; possible n=3; probable n=5), one possible invasive fungal infection and 2 mucormycoses (1 with possible IPA). Fungal infections occurred despite documentation of a protective residual level of posaconazole (> 0.5mg/L) in 5 of 6 evaluable patients. Of note, 9/11 patients had received PTCY as GVHD prophylaxis. Posaconazole was stopped (before D7 in 3) and other antifungal drugs started (voriconazole or liposomal amphotericin B) allowing to fungal infection cure in 5 pts. However, 7 pts died including 2 of an uncontrolled fungal infection. Conclusion: Posaconazole is a well-tolerated and efficient primary prophylaxis in recipients of Allo-HSCT at high-risk of fungal infection. As some fungal infections occured very early after D0 while prophylaxis started only a D5/6 after PTCY, our results suggests to propose posaconazole as early as the beginning of the conditionning together with dose monitoring. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long Term Results of Phase 2 Study of Pegylated Interferon in Patients with Essential Thrombocythemia and Polycythemia Vera: Median Follow-up of 15 Years

Introduction: Pegylated interferon alfa-2a [PEG-IFN] have been used for almost 3 decades in patients with polycythemia vera [PV] and essential thrombocythemia [ET], but long-term data from prospective studies are limited. Objective: We present results of our single center, prospective, phase II study of PEG-IFN in patients with ET and PV with a median follow up of 183 months (range, 6-198, at data lock June 2022; previous data lock was May 2015). Methods: The study enrolled patients with ET (n=40) or PV (n=43) over the age of 18, irrespectively of previous therapy (37% untreated). PEG-IFN dose modifications, monitoring, and response assessment were as published (Masarova et al, Lancet Haematology, 2017). Testing sensitivity for JAK2V167F mutation allele burden was 1% till 2018, and 0.1% since then. Molecular response [MR; assessed in patients with baseline JAK2 ≥20%] was defined as complete (CMR; undetectable), partial (PMR; decrease by ≥50% but detectable) and minor (mMR; decrease by 20-49%). Results: Among 83 enrolled patients (median age 53 years, 29 males), after median follow up of 183 months (range, 6-198), 11 patients (13%) continue on active therapy on study. Current doses range from 45 mcg every 9 weeks to 180 mcg weekly. Forty-six (55%), 18 (22%) and 6 (7%) patients were treated for ≥5, ≥10 and ≥15 years, respectively. The overall median exposure to PEG-IFN (n = 83) was 95 months (range, 3-191). Twenty-seven patients (41%) from the initial 66 hematologic responders [HR; 80%] were in HR at the time of their last follow-up, including 5 patients who lost but regained HR with longer therapy. Table 1 shows responses in patients who remained on study for 4+ years. Median duration of HR was 137 months (range, 2.2-189). Thirty-five (63%) of 55 JAK2 mutated patients with molecular sequencing achieved molecular response: 10 CMR (18%), 20 PMR (36%) and 5 mMR (9%). At the time of last follow-up on study, 24 patients remained in MR (67%). Only 17 treated patients underwent repeated molecular sequencing since the last study update; 3 of them experienced change: 1 lost PMR (JAK2: 38%->61%), 1 lost CMR (JAK2: 0%-6%) and 1 regained PMR (JAK2: 13%->7%). Median duration on study in months [range] was 127 [25-189], 91 [11-192], 15 [2-183] and 81.5 [6-187] for JAK2(+) patients who achieved CMR (n = 10), PMR & mMR (n = 25), without MR (n = 25) and in JAK2(-) (n = 23), respectively. Five patients with previous CMR had subsequent testing, 4 of them had detectable JAK2 allele in the range of 0.1%-0.5% using more sensitive assay. Median duration of MR was unreached in patients who achieved < 1% JAK2 and it was 96 months (range, 6-155) in patients with 20-99% JAK2 allele decrease. Reasons for therapy discontinuation included treatment-related toxicities in 20 patients (24%; 11/13 for grade ≥3), patient's decision in 19 (23%), ET/PV progression or lack of response in 12 (14%), other reasons in 10 (12%, e.g., motor vehicle accident), transformation to myelofibrosis or acute leukemia [MF/AML] in 7 (8%) and death in 4 patients (5%, all unrelated). Medical reasons for discontinuation after 10 years on study included 3 carcinomas: 1 head squamous cell, 1 pancreatic and 1 ovarian; and 2 adverse events: grade 3 Sjogren syndrome and grade 2 recurrent transaminitis. Annual discontinuation rates are shown in graph. There were no transformations to MF/AML on therapy since the last study update for a total number of cases of 7. No additional vascular thrombotic events occurred with overall incidence of 0.9 / 100 person-years. Five patients experienced new adverse events after 10 years on therapy: mild flu-like symptoms, fatigue or diarrhea (3); grade 2 transaminitis (1) and Sjogren syndrome (1). Twenty-five patients continued on active follow-up after PEG-IFN discontinuation until the current data lock with a median follow-up off therapy of 92 months (range, 8-132). Twenty patients are alive (on cytoreductive therapy in 11), 5 died (acute leukemia in 2, other medical condition, bleeding, stroke for 1 each). As of last follow-up, 25% (n = 21) of originally enrolled patients died. Median overall survival (n = 83) since enrollment was unreached. Conclusions: Our 15 years of follow-up of pegylated interferon in patients with ET and PV confirms durability of responses and disease control in patients who are able to tolerate long therapy and an acceptable safety profile. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Optimizing Dose and Limiting Laboratory Monitoring of Hydroxyurea in Africa: Design of the Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa (PUSH-UP) Trial

Background: More than 90% of the global burden of sickle cell anemia (SCA) occurs in sub-Saharan Africa (SSA) where efforts to expand newborn screening are likely to reduce early mortality. With an increasing number of infants diagnosed and surviving, it is critical to expand access to disease modifying therapy with hydroxyurea (HU) to reduce the risk of SCA complications. Despite increasing evidence demonstrating safety and effectiveness of HU in SSA, access to and use of HU remains limited. In high-resource settings, HU monitoring is performed through routine complete blood counts (CBCs) to monitor for hematologic toxicity and guide dose escalation. Unfortunately, in most SSA settings, access to CBCs is limited due to combination of lack of laboratory equipment, insufficient supply of reagents, or excess cost to the patient or healthcare system. The lack of capacity to perform a CBC is an insurmountable barrier in many SSA settings resulting in lack of access to this highly effective and lifesaving medication. There are some who argue that lower doses (10-15 mg/kg/day) in places where laboratory monitoring may not be readily available may reduce the theoretical risk of "toxicity." While this low dose strategy is likely to have some clinical benefit compared to no treatment at all, there is now sufficient evidence to demonstrate that higher doses of HU result in more significant clinical benefits without evidence that lower dosing prevents toxicity. In the US, we have recently developed and validated an individualized, pharmacokinetics (PK)-guided dosing strategy that optimizes the starting dose immediately without the need for dose escalation. The Prioritizing Utilization and Safety of Hydroxyurea Using Precision (PUSH-UP, ClinicalTrials.gov NCT05285917) trial is an NHLBI-funded clinical trial that will evaluate the utility and effectiveness of this individualized dosing strategy in addition to a limited laboratory monitoring strategy for children with SCA in Luanda, Angola. Study Design and Methods:The PUSH-UP trial is a randomized clinical trial of HU for 450 children aged 6 months through 12 years of age with SCA that will be performed at Hospital Geral dos Cajueiros, a national health reference center in Luanda, Angola. The primary aim of the study will determine the optimal dosing strategy, including a direct comparison of using an individualized, PK-guided starting dose to the more traditional, weight-based starting dose strategies. A second but equally important aim of the study will be to evaluate the safety of HU therapy with limited laboratory monitoring. The study will evaluate the feasibility and utility of measuring HU concentrations using a battery-powered HPLC machine (SmartLife LC™) and an automated individualized dose selection tool based on PK results. An important novel and real-world aspect of the trial is the use of only 500 mg capsules, the generic form of HU that is becoming increasingly available across many African countries. The study will utilize innovative dosing strategies, including every other day or 3-4 times per week dosing, with 500 mg capsules to achieve a safe daily dose in these young children. Following informed consent, prior to HU initiation, there will be a 3-month run-in period, followed by a 24-month treatment period. After initial dose selection and study arm assignment, there will be no dose escalations, to evaluate the most likely real-world scenarios where dose escalation is not feasible. Doses will be adjusted to account for weight-gain to maintain the same mg/kg dose throughout the study. CBCs will be performed monthly for 3 months before and 3 months after HU initiation of treatment to compare the incidence of hematologic "toxicities" and to test the hypothesis that there will be no increase in toxicity with HU treatment. After this, laboratory monitoring will be sparse, relying on clinical examination and point-of-care hemoglobin only without routine CBCs. The primary study endpoint will be SCA-related adverse events and secondary endpoints will include hematologic toxicities, infections and other non-SCA-related events to assess the safety of HU therapy with limited laboratory monitoring, and quality of life measures. Conclusions: The PUSH-UP trial will address important knowledge gaps related to hydroxyurea dosing and laboratory monitoring in low-resource settings that can be used to inform clinical guidelines in sub-Saharan Africa.

Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Persons Aged ≥12 Years - United States, August 31-October 23, 2022.

On August 31, 2022, the Food and Drug Administration (FDA) authorized bivalent formulations of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines; these vaccines include mRNA encoding the spike protein from the original (ancestral) strain of SARS-CoV-2 (the virus that causes COVID-19) and from the B.1.1.529 (Omicron) variants BA.4 and BA.5 (BA.4/BA.5). These bivalent mRNA vaccines were authorized for use as a single booster dose ≥2 months after completion of primary series or monovalent booster vaccination; Pfizer-BioNTech bivalent booster was authorized for persons aged ≥12 years and Moderna for adults aged ≥18 years.*,† On September 1, 2022, the Advisory Committee on Immunization Practices (ACIP) recommended that all persons aged ≥12 years receive an age-appropriate bivalent mRNA booster dose.§ To characterize the safety of bivalent mRNA booster doses, CDC reviewed adverse events and health impacts reported after receipt of bivalent Pfizer-BioNTech and Moderna booster doses during August 31-October 23, 2022, to v-safe,¶ a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor adverse events after COVID-19 vaccination, and the Vaccine Adverse Event Reporting System (VAERS),** a U.S. passive vaccine safety surveillance system managed by CDC and FDA (1). During August 31-October 23, 2022, approximately 14.4 million persons aged ≥12 years received a bivalent Pfizer-BioNTech booster dose, and 8.2 million adults aged ≥18 years received a bivalent Moderna booster dose.†† Among the 211,959 registrants aged ≥12 years who reported receiving a bivalent booster dose to v-safe, injection site and systemic reactions were frequently reported in the week after vaccination (60.8% and 54.8%, respectively); fewer than 1% of v-safe registrants reported receiving medical care. VAERS received 5,542 reports of adverse events after bivalent booster vaccination among persons aged ≥12 years; 95.5% of reports were nonserious and 4.5% were serious events. Health care providers and patients can be reassured that adverse events reported after a bivalent booster dose are consistent with those reported after monovalent doses. Health impacts after COVID-19 vaccination are less frequent and less severe than those associated with COVID-19 illness (2).

Edoxaban for Thromboembolism Prevention in Pediatric Patients With Cardiac Disease

BackgroundStandard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants in children. ObjectivesThe investigators aimed to obtain safety and efficacy data for edoxaban in children. MethodsWe performed a phase 3, multinational, prospective, randomized, open-label, blinded-endpoint trial in patients <18 years of age with cardiac disease (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots (Thrombotic Events) in Children at Risk Because of Cardiac Disease] trial). Patients were randomized 2:1 to age- and weight-based oral edoxaban once daily vs SOC for 3 months (main study period), stratified by cardiac diagnosis. Both groups could continue in an open-label edoxaban extension arm through 1 year. The primary endpoint was adjudicated clinically relevant bleeding (CRB). The main secondary endpoint was symptomatic TE or asymptomatic intracardiac thrombosis. ResultsThe modified intention-to-treat cohort included 167 children. One patient per group experienced a nonmajor CRB in the main period. Treatment-emergent adverse events occurred in 46.8% (51 of 109) with edoxaban and 41.4% (24 of 58) with SOC. One SOC patient experienced 2 TE events (DVT with PE). Among 147 children in the extension, 1 CRB event (0.7%) and 4 TEs occurred (2.8%; 2 strokes and 2 of 33 Kawasaki disease patients with coronary artery thromboses and/or myocardial infarctions). ConclusionsEdoxaban is a potential alternative mode of thromboprophylaxis in children with cardiac disease showing low rates of CRB and TEs with advantages of once daily dosing and infrequent monitoring requirement. (ENNOBLE-ATE [Edoxaban for Prevention of Blood Vessels Being Blocked by Clots] (Thrombotic Events) in Children at Risk Because of Cardiac Disease trial; NCT03395639).

Tomographic detection of photon pairs produced from high-energy X-rays for the monitoring of radiotherapy dosing

Measuring the radiation dose reaching a patient’s body is difficult. Here we report a technique for the tomographic reconstruction of the location of photon pairs originating from the annihilation of positron–electron pairs produced by high-energy X-rays travelling through tissue. We used Monte Carlo simulations on pre-recorded data from tissue-mimicking phantoms and from a patient with a brain tumour to show the feasibility of this imaging modality, which we named ‘pair-production tomography’, for the monitoring of radiotherapy dosing. We simulated three image-reconstruction methods, one applicable to a pencil X-ray beam scanning through a region of interest, and two applicable to the excitation of tissue volumes via broad beams (with temporal resolution sufficient to identify coincident photon pairs via filtered back projection, or with higher temporal resolution sufficient for the estimation of a photon’s time-of-flight). In addition to the monitoring of radiotherapy dosing, we show that image contrast resulting from pair-production tomography is highly proportional to the material’s atomic number. The technique may thus also allow for element mapping and for soft-tissue differentiation.

Single Institute Experience – Linear Accelerator Based Total Body Irradiation Using Volumetric Modulated Arc Therapy Planning in Standard Size Linear Accelerator Room

<h3>Purpose/Objective(s)</h3> To share experience of linear accelerator based total body irradiation (TBI) with volumetric modulated arc therapy (VMAT) in a standard size linear accelerator room <h3>Materials/Methods</h3> 30 patients aged 2-18 years (between 2018-2021) were treated with TBI as conditioning for bone marrow transplant (BMT)using VMAT based plan on our linear accelerator in a standard sized linear accelerator room. Indication of BMT was – acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myeloid leukemia, myelodysplasia, aplastic anemia etc. Patient selection involved assessment regarding need of anesthesia, details of previous radiation, details of conditioning regimen for scheduling, organs dysfunction, adequate counselling and written consent from parents. With or without anesthesia, patients were immobilized using full body vacloc, head rest, brain orfit cast and knee rest. Position was supine, hands by side. Both head first (HF) and feet first (FF) scans were acquired if body length was more than 120 cm (for 120 cm, HF scan alone was acquired). A wire was placed on thigh to aid fusion of HF and FF scans for plan evaluation. Fiducials at three levels and optically stimulated luminescent dosimeter for dose monitoring were placed. Dose was 2-4 Gy single fraction and 12-13.2Gy/6 fractions (twice daily over 3 days, with 6 hours gap) based on chemotherapy conditioning regimen- delivered to 14 and 16 patients respectively. The planning objective was 90-100% coverage and dose max less than 120%. For multifraction plans, target was mean dose to lungs and kidney less than 10 Gy and 8Gy respectively. VMAT plans were generated with 3-5 iso-centers with fixed couch vertical and lateral values and changing longitudinal value, ensuring only longitudinal couch movement. Plan was made using 6MV energy and 5-9 arcs and 3 cm overlap between fields (avoid over joints to prevent effusion and over lungs to reduce lung dose) <h3>Results</h3> Mean PTV V95 – 93% (92-96%), Dmax – 115% mean (109%-120%). Mean lung dose (for 12-13.2Gy plans) was 9.4Gy/ (9-10 Gy), kidney mean dose was 7.8Gy (7.5-8 Gy). Mean monitor units in the plans were 1120 for complete arc and 690 for partial arcs. Treatment was delivered in strict aseptic precautions, under cover of steroids and antiemetics - in presence of radiation oncologist and physicist. Cone beam CT scan was used for position verification before and after treatment. The mean duration of treatment was 75 mins (range 60-90 minutes). 18 patients had grade 2 nausea and vomiting, one had knee joint effusion. No other side effects were reported. All transplants were successful except one reported graft versus host disease. <h3>Conclusion</h3> The procedure needs careful planning and delivery. It is feasible and possible to deliver TBI using VMAT in a standard sized linear accelerator room and should be offered to patients requiring the same.

Comparative Evaluation of Brachial Plexus Sparing for Comprehensive Reirradiation of High Risk Recurrent or New Primary Breast Cancer

<h3>Purpose/Objective(s)</h3> Recurrent or new primary breast cancer with an indication for comprehensive regional nodal irradiation (RNI) in the setting of prior radiotherapy (RT) to the supraclavicular area (SCV) and upper axilla presents a unique treatment challenge due to cumulative brachial plexus (BP) dose tolerance. Brachial plexopathy is a debilitating potential consequence of RT, and BP dose monitoring is needed for comprehensive reirradiation (reRT). We hypothesize that pencil beam scanning proton therapy (PBS-PT) and photon volumetric-modulated arc therapy (VMAT) are conformal techniques that allow BP relative dose-sparing, while maintaining target volume (TV) dose. A comparative evaluation was performed to assess each approach. <h3>Materials/Methods</h3> In this IRB-approved retrospective study, all patients with ipsilateral recurrent or new primary breast cancer previously treated with photon RT, then receiving PBS-PT reRT to TV with at least partial BP overlap, were identified. VMAT plans were developed by photon breast dosimetrists using matched individualized BP dose constraints (BP maximum 17.1-53.9 Gy) used in the PBS-PT course. BP and TV DVH parameters were assessed. Patient and tumor characteristics, treatment parameters, clinical outcomes, and toxicities were collected. The median follow-up from the start of reRT was 10.5 months. <h3>Results</h3> Ten consecutive patients were identified. Median patient age was 58 years (41-82), with median time between RT courses of 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (42.6-60.0), 50.4 Gy(RBE) (45.0-64.4), and 102.4 Gy(RBE) (95.0-120.0), respectively. PBS-PT and VMAT plans matched BP doses, with the median maximum and mean BP cumulative doses 86.6 Gy (RBE) and 60.7 Gy (RBE) for PBS-PT and 87.5 Gy and 60.2 Gy for VMAT, respectively. TV coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were generally lower for VMAT vs. IMPT plans: axilla level II were 84.8%, 91.8%, and 75.7% vs. 90.9% (p=0.17), 88.3% (p=0.04), and 84.5% (p<0.01); axilla level III were 89.8%, 75.1%, and 64.0% vs. 95.4% (p=0.39), 91.8% (p=0.12), and 86.5% (p=0.32); and SCV were 83.0%, 74.3%, and 67.2% vs. 90.9% (p=0.41), 82.1% (p=0.13), and 68.2% (p=0.76), respectively. One patient developed symptoms of brachial plexopathy with neuropathy in the ulnar nerve distribution without pain or weakness. This patient had the highest maximum cumulative BP dose of the entire cohort (106.1 Gy(RBE)). <h3>Conclusion</h3> VMAT and PBS-PT provide conformal RT plans that can provide BP dose sparing but some surrounding compromise of the adjacent TV at risk. In this cohort, PBS-PT improved BP sparing and TV coverage versus VMAT. Further study with uniform TV and prescription parameters will be useful for direct comparison of the two modalities as the approach to this clinical situation continues to be refined. Longer follow-up will be needed to characterize the implication of cumulative BP dose on risk of developing clinically-significant brachial plexopathy.

Patient dose monitoring software in radiology

An increase in the number of diagnostic procedures using ionizing radiation (computed tomography, interventional procedures, and the use of nuclear medicine) results in an increase in radiation exposure and, consequently, an increase in collective and individual doses of radiation to patients.&#x0D; Diagnostic studies from the international professional community are extensively focusing on issues such as management and dose optimization. Worldwide practice can resolve these issues using software for monitoring patient doses to automatically collect, analyze, and account for patient doses in various types of diagnostic studies. The software allows to obtain data on the doses of patients from X-ray procedures and detailed information about studies, track the total accumulated dose of the patient, and maintain statistics on the device, X-ray laboratory, and the medical organization. It also helps analyze the collected dosimetric data, deduce the causal relationship between dose indications and diagnostic procedure conditions, and monitor the effectiveness of the equipment.&#x0D; The basic capabilities of patient dose monitoring software (DMS) available on the global market were investigated. The major technical requirements for the software functional needed in practical work were defined.&#x0D; Modern DMS have a wide range of possibilities for automated collection, storage, and management of patient radiation exposure data in radiology departments. DMS increase the quality of healthcare services, provide patient safety, and optimize the workflow of medical organizations.

Emerging therapies for the treatment of rare pediatric bone disorders.

In recent years, new therapies for the treatment of rare pediatric bone disorders have emerged, guided by an increasing understanding of the genetic and molecular etiology of these diseases. Herein, we review three such disorders, impacted by debilitating deficits in bone mineralization or cartilage ossification, as well as the novel disease-modifying drugs that are now available to treat these conditions. Specifically, we discuss asfotase alfa, burosumab-twza, and vosoritide, for the treatment of hypophosphatasia, X-linked hypophosphatemia and achondroplasia, respectively. For each skeletal disorder, an overview of the clinical phenotype and natural history of disease is provided, along with a discussion of the clinical pharmacology, mechanism of action and FDA indication for the relevant medication. In each case, a brief review of clinical trial data supporting drug development for each medication is provided. Additionally, guidance as to drug dosing and long-term monitoring of adverse events and pediatric efficacy is presented, to aid the clinician seeking to utilize these novel therapies in their practice, or to become familiar with the healthcare expectations for children receiving these medications through specialized multidisciplinary clinics. The availability of these targeted therapies now significantly augments treatment options for conditions in which past therapy has relied upon less specific, symptomatic medical and orthopedic care.

Cardioprotection against cardiac dysfunction from breast cancer chemotherapy: a bayesian and frequentist network meta-analysis of randomised controlled trials

Abstract Background Anthracyclines (ANT) are the cornerstone of multiple chemotherapy regimens but at the risk of potential cardiotoxicity. Previous RCTs have tested the prophylactic effects of multiple cardioprotective agents to prevent ANT-related cardiotoxicity. Unfortunately, attempts to combine RCT findings in previous meta-analyses have been heterogeneous, creating further uncertainty. There remains an unmet need to determine the role of cardio-protective agents in breast cancer. Purpose To assess the comparative efficacy of cardioprotective drugs in patients with breast cancer using both Bayesian and frequentist analyses of randomised controlled trials Methods We performed a systematic review using four databases (CENTRAL, Cochrane Reviews, MEDLINE, SCOPUS), to find RCTs evaluating cardio protective drugs in breast cancer patients without prior ANT exposure. The population included was anthracycline naïve, and trials were excluded if cardio-protective agents were commenced post anthracycline treatment. The primary outcome was a mean change in LVEF pre and post ANT dosing. Results were pooled with both Bayesian and frequentist approaches using random effects models in R statistical software. Results We identified 12 RCTs from 2807 search results (n=1126, Age 51 years, ANT dose 412m/m2, baseline LVEF 62.6%) with comparisons including beta-blockers (BB) (n=9), Angiotensin Converting Enzyme inhibitors (ACEi)/Angiotensin Receptor Blockers (ARB) (n=3), combination BB + AA (n=2), spironolactone (n=1) and statins (n=1). All included trials had either intermediate or high risk of bias, with marked heterogeneity in ANT dosing and LVEF monitoring. Overall, our Bayesian network meta-analysis showed no statistically significant difference in mean LVEF preservation between AA (1.3%, 95% credible interval [−0.20, 2.9]), BB (0.77, [−0.21, 1.8]), AABB (0.84 [−1.1, 2.8]), SPR (0.72, [−2.3, 3.7]) or statin (0.60, [−2.4, 3.6]) when compared against placebo. After ranking for efficacy, ACEi/ARBs achieved the most protection against LVEF decline of 1.3% [95% CI: −0.2, 2.9] although still not significant. Conversely, frequentist analysis showed benefit in using AA (Standardised Mean Difference (SMD) 1.32% [0.32, 2.33]) and BB (SMD 0.76% [0.12, 1.4]). Conclusion Bayesian analysis demonstrated no difference in LVEF with cardio-protective agents. In contrast, frequentist analysis showed that AA and BB may provide significant cardio-protection. The quality of RCT data to date is limited by a high risk of bias and significant heterogeneity between RCA reporting. Larger trials with clear population definition are required to determine whether any drug class provides benefit in this setting. Funding Acknowledgement Type of funding sources: None.

250 Dosing and therapeutic drug monitoring of intravenous vancomycin in cystic fibrosis: A practice survey

250 Dosing and therapeutic drug monitoring of intravenous vancomycin in cystic fibrosis: A practice survey