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Introduction: The significant increases in the use of imaging and interventional procedures in recent times have brought along the issue of safety and protection of patients and users of diagnostic and interventional radiology equipment for complex procedures. Additionally, due to potential risk associated with these procedures, patients' radiation protection issues have become the focus of most fluoroscopy guided interventional procedures globally. The objective of this study is to evaluate optimized angiographic exposure parameters, radiation dose, estimated risk levels and develop a radiation dose reference chart for the most commonly routine protocol in interventional procedures in Ghana. Methodology: Patients dose parameters were obtained from the structured dose reports of the PAC system of five diagnostic interventional equipment facilities, together with number of images per procedure and image quality assessment for dose optimisation protocols. The data retrieved from the PAC System include patients' biodata, input and output indices including Kerma-Area Product (KAP) Fluoro and total Kerma-Area Product values. Additionally, fluoroscopy time and the number of radiographic images of at least 50 patients for each FGI procedure based on ICRP Publication 135 recommendations were also collected. The PC based Monte Carlo simulation software (PCXMC) was used to estimate ED from the total KAP and the KAP Fluoro values. Image quality (IQ) was assessed using human observer assessment and evaluation based on the assessment of the radiologists, who ranked the images from most acceptable images to least acceptable images and whether accepted on not accepted for clinical use. Patient radiation exposure was evaluated using estimated KAP Fluoro and Total KAP to estimate ED from each of the measured parameters. That is radiation risk levels were estimated based on Biological Effects of Ionising radiation (BEIR) report VII predictive models. These were done by assessing the dose and risk to patients and practioners during fluoroscopy guided interventional procedures for each of the nine most common routine procedure and the possible corrective measures needed for effective management of these procedure. Results: The study shows that the total KAP median dose value was 109 with a minimum and maximum values in the range of 2 to 835 Gy.cm2 were recorded during Abdominal Aorta Endoprosthesis procedure. While KAP Fluoro minimum and maximum dose value were ranged from 1.59 to 734 Gy.cm2 with a median value of 86 Gy.cm2. The trend of the study shows significant comparative estimated dose values in terms of effective dose from the KAP median values with other studies. Additionally, abdominal aorta endoprosthesis procedures took much longer time to perform relative to the other studies with resultant high ED values. It was observed that, time taken, and images acquired for abdominal aorta endoprosthesis procedure could be as much as three-fold with significant dose value compared to other procedures. Furthermore, higher radiation dose quantity, in terms of KAP Fluoro and total KAP, in the case of Abdominal Aorta Endoprosthesis had a direct correlation to the number of images and the time taken to complete the procedure. Comparative analysis between these procedures shows significant variation among them. For instance Percutaneous Liver Drainage had the least effective dose and risk factors of 0.94 mSv and 0.34 LAR respectively. Whilst Abdominal Aorta Endoprosthesis had the highest effective dose and risk factor of 32 mSv and 29 LAR respectively. Finally, the number of images and the corresponding image quality assessment shows significant variation from a minimum of 2.7 to a maximum of 167 Gy.cm2. This resulted in highest ED of 59.4 mSv with significant risk levels to both patients and practitioners (1 in 1000 to 1 in 500). Most of the procedures had low radiation risk levels (1 in 10,000 to 1 in 1000). Additionally, all the images were good enough for clinical use and ranged from 3 to 5 with less than 2% of the procedure having relative poor image quality with significant positive correlation to the dose and risk factor metrics. Conclusion: In conclusion it was observed that, the study results were comparable to other regional and international studies. In addition, it was also observed that, the time taken for each procedure to be completed had direct positive correlation with estimated patient dose metrics. That is, the higher the time taken for a procedure to be completed, the higher the dose values in terms of KAP Fluoro (Gy·cm2) and Total KAP (Gy·cm2) with significant correlation with the quality of images used during the procedure. Finally, the study found that the angiographic exposure input parameters were optimized and within accepted and recommened dose estimates (effective dose, estimated risk levels) and radiation dose reference chart has been developed for the most commonly routine protocol in interventional procedures in Ghana. [ABSTRACT FROM AUTHOR]

To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose. Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula. In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was −8.73%, 1.37%, and −0.48%, respectively. The corresponding value was −11.15%, 1.99%, and −0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was −12.63%, −6.47%, and −0.54% when the sampling time shifted. The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic. [ABSTRACT FROM AUTHOR]

Abstract In the face of increasing antimicrobial tolerance and resistance there is a global obligation to optimise oral antimicrobial dosing strategies including narrow spectrum penicillins, such as penicillin-V. We conducted a randomised, crossover study in healthy volunteers to characterise the influence of probenecid on penicillin-V pharmacokinetics and estimate the pharmacodynamics against Streptococcus pneumoniae. Twenty participants took six doses of penicillin-V (250 mg, 500 mg or 750 mg four times daily) with and without probenecid. Total and free concentrations of penicillin-V and probenecid were measured at two timepoints. A pharmacokinetic model was developed, and the probability of target attainment (PTA) calculated. The mean difference (95% CI) between penicillin-V alone and in combination with probenecid for serum total and free penicillin-V concentrations was significantly different at both timepoints (total: 45 min 4.32 (3.20–5.32) mg/L p

AbstractTo assess the efficacy and safety of capecitabine in treating advanced colon cancer. Patients with advanced colon cancer were randomized into three groups: control group (n = 50, daily dose 2,500 mg/m2), the medium-dose group (n = 50, daily dose 2,000 mg/m2), and the low-dose group (n = 50, daily dose 1,500 mg/m2) capecitabine for 4 cycles(12 weeks). Afterwards, the response rate, quality of life, and adverse reactions of the three groups were collected for comparison. Efficacy rates were 50%, 70%, and 72%, respectively, with the low-dose group showing the highest efficacy (χ2 = 6.424, p = 0.040); Quality of life comparison results indicated significant differences in physical function (F = 98.528, p < 0.001), role function (F = 123.418, p < 0.001), social function(F = 89.539, p < 0.001), emotional function (6 F = 77.295, p < 0.001), cognitive function (F = 83.529, p < 0.001), and overall quality of life (F = 99.528, p < 0.001) among the three groups, and the three groups returned consistent scores, with the low-dose group scoring highest. Incidence rates were 86.00%, 46.00%, 34.00%, with the control group having the highest rate (χ2 = 16.505, p < 0.001). Capecitabine at a dosage of 1,500 mg/m2 demonstrated a good therapeutic effect and improved the quality of life in patients with advanced colon cancer, with a lower incidence of adverse reactions. A prolonged treatment cycle with reduced dosage is suggested to further improve treatment outcomes and patient prognosis. Trial registration The study was registered on clicaltrials.gov ‘NCT06246461’ on 30/01/2024. [ABSTRACT FROM AUTHOR]

In the face of increasing antimicrobial tolerance and resistance there is a global obligation to optimise oral antimicrobial dosing strategies including narrow spectrum penicillins, such as penicillin-V. We conducted a randomised, crossover study in healthy volunteers to characterise the influence of probenecid on penicillin-V pharmacokinetics and estimate the pharmacodynamics against Streptococcus pneumoniae. Twenty participants took six doses of penicillin-V (250 mg, 500 mg or 750 mg four times daily) with and without probenecid. Total and free concentrations of penicillin-V and probenecid were measured at two timepoints. A pharmacokinetic model was developed, and the probability of target attainment (PTA) calculated. The mean difference (95% CI) between penicillin-V alone and in combination with probenecid for serum total and free penicillin-V concentrations was significantly different at both timepoints (total: 45 min 4.32 (3.20–5.32) mg/L p < 0.001, 180 min 2.2 (1.58–3.25) mg/L p < 0.001; free: 45 min 1.15 (0.88–1.42) mg/L p < 0.001, 180 min 0.5 (0.35–0.76) mg/L p < 0.001). There was no difference between the timepoints in probenecid concentrations. PTA analysis shows probenecid allows a fourfold increase in MIC cover. Addition of probenecid was safe and well tolerated. The data support further research into improved dosing structures for complex outpatient therapy and might also be used to address penicillin supply shortages. [ABSTRACT FROM AUTHOR]

Diagnostic reference levels (DRLs) and achievable doses (ADs) provide guidance to optimise radiation doses for patients undergoing medical imaging procedures. This multi-centre study aimed to compare institutional DRLs (IDRLs) across hospitals, propose ADs and multi-centric DRLs (MCDRLs) for four common x-ray examinations in Sri Lanka, and assess the potential for dose reduction. A prospective cross-sectional study of 894 adult patients referred for abdomen anteroposterior (AP), kidney-ureter-bladder (KUB) AP, lumbar spine AP, and lumbar spine lateral (LAT) x-ray examinations was conducted. Patient demographic information (age, sex, weight, BMI) and exposure parameters (tube voltage, tube current-exposure time product) were collected. Patient dose indicators were measured in terms of kerma-area product (PKA) using a PKA meter. IDRLs, ADs, and MCDRLs were calculated following the International Commission on Radiological Protection guidelines, with ADs and MCDRLs defined as the 50th and 75th percentiles of the median PKA distributions, respectively. IDRL ranges varied considerably across hospitals: 1.42–2.42 Gy cm2 for abdomen AP, 1.51–2.86 Gy cm2 for KUB AP, 0.83–1.65 Gy cm2 for lumbar spine AP, and 1.76–4.10 Gy cm2 for lumbar spine LAT. The proposed ADs were 1.82 Gy cm2 (abdomen AP), 2.03 Gy cm2 (KUB AP), 1.27 Gy cm2 (lumbar spine AP), and 2.21 Gy cm2 (lumbar spine LAT). MCDRLs were 2.24 Gy cm2 (abdomen AP), 2.40 Gy cm2 (KUB AP), 1.43 Gy cm2 (lumbar spine AP), and 2.38 Gy cm2 (lumbar spine LAT). Substantial intra- and inter-hospital variations in PKA were observed for all four examinations. Although ADs and MCDRLs in Sri Lanka were comparable to those in the existing literature, the identified intra- and inter-hospital variations underscore the need for dose reduction without compromising diagnostic information. Hospitals with high IDRLs are recommended to review and optimise their practices. These MCDRLs serve as preliminary national DRLs, guiding dose optimisation efforts by medical professionals and policymakers. [ABSTRACT FROM AUTHOR]

The adoption of size-specific dose estimate (SSDE) in clinical practice is still limited owing to the tedious and complex manual measurement of individual patient size for the clinical calculation of SSDE. Thus, the automation of SSDE is imperative. This study aims to evaluate a predictive equation for the automated calculation of SSDE. A user-friendly software was developed to accurately predict the individual size-specific dose estimation of paediatric patients undergoing computed tomography (CT) scans of the head, thorax, and abdomen. The software includes a calculation equation developed based on a novel SSDE prediction equation that used a population's pre-determined percentage difference between volume-weighted computed tomography dose index (CTDI vol) and SSDE with age. American Association of Physicists in Medicine (AAPM RPT 204) method (manual) and segmentation-based SSDE calculators (indoseCT and XXautocalc) were used to assess the proposed software predictions comparatively. The results of this study show that the automated equation-based calculation of SSDE and the manual and segmentation-based calculation of SSDE are in good agreement for patients. The differences between the automated equation-based calculation of SSDE and the manual and segmentation-based calculation are less than 3%. This study validated an accurate SSDE calculator that allows users to enter key input values and calculate SSDE. The automated equation-based SSDE software (PESSD) seems a promising tool for estimating individualised CT doses during CT scans. [ABSTRACT FROM AUTHOR]

Background: Diagnostic reference levels (DRLs) are an important metric in identifying abnormally high radiation doses in diagnostic examinations. National DRLs for CT colonography do not currently exist in South Africa, but there are efforts to collect data for a national DRL project. Objectives: This study investigated radiation doses for CT colonography in adult patients at a large tertiary hospital in South Africa with the aim of setting local DRLs. Method: Patient data from two CT scanners (Philips Ingenuity and Siemens Somatom go.Top) in the period March 2020 -- March 2023 were obtained from the hospital's picture archiving and communication system (PACS) (n = 115). Analysis involved determining the median computed tomography dose index-volume (CTDIvol) and dose-length product (DLP) values. The findings were compared with DRLs established internationally. Results: Ingenuity median CTDIvol was 20 mGy and DLP was 2169 mGy*cm; Somatom median CTDIvol was 6 mGy and DLP was 557 mGy*cm. Ingenuity exceeded the United Kingdom's (UK) recommended DRLs by 82% and 214%, respectively. Somatom median CTDIvol and DLP were 45% and 19% lower than UK NDRLs. Conclusion: Somatom's tin filter and other dose reduction features provided significant dose reduction. These data were used to set DRLs for CT colonography at the hospital; CTDIvol: 6 mGy and DLP: 557 mGy*cm. Contribution: In addition to informing radiation protection practices at the level of the institution, the established local DRLs contribute towards implementing regional and national DRLs. [ABSTRACT FROM AUTHOR]

The establishment of diagnostic reference levels (DRLs) is an effective tool for optimising radiation doses delivered to patients during medical imaging procedures. This study aimed to compare the institutional DRLs (IDRLs) and propose a multi-centric diagnostic reference level (MCDRL) for chest x-ray examinations in adult patients in Sri Lanka. A prospective cross-sectional study was conducted with 1091 adult patients across six major tertiary care hospitals. Data on patient characteristics, such as age, sex, weight, and body mass index, and exposure parameters, such as tube voltage (kVp) and the product of tube current and exposure time (mAs), were collected. Patient doses were measured in terms of kerma-area product (PKA) using a PKA meter mounted on the collimator of the x-ray tube. IDRLs were computed for each hospital according to the International Commission on Radiological Protection guidelines, and the 75th percentile PKA was used to propose the MCDRL. The relationship between patient weight and exposure parameters was examined using Spearman's rank correlation to investigate the radiographic practice among hospitals. Results showed that IDRLs varied from 0.10 to 0.26 Gy cm2. The proposed MCDRL was 0.23 Gy cm2, substantially higher than the recently published DRLs from other countries. The median kVp ranged from 95 to 104, while mAs ranged from 2.5 to 5.6. Large variations in the PKA and exposure parameters were observed within and among hospitals. The elevated PKA values observed in this study were mostly due to the use of high mAs in clinical practice. The weak correlation observed between patient weight and exposure parameters suggests the need to standardise examination protocols concerning patient size. The observed dose variations demonstrate the need for the establishment of national DRLs. Until then, the proposed MCDRL can be considered as the benchmark dose level for chest x-ray examinations in Sri Lanka. [ABSTRACT FROM AUTHOR]

Background: Diagnostic reference levels (DRLs) are an important metric in identifying abnormally high radiation doses in diagnostic examinations. National DRLs for CT colonography do not currently exist in South Africa, but there are efforts to collect data for a national DRL project. Objectives: This study investigated radiation doses for CT colonography in adult patients at a large tertiary hospital in South Africa with the aim of setting local DRLs. Method: Patient data from two CT scanners (Philips Ingenuity and Siemens Somatom go.Top) in the period March 2020 – March 2023 were obtained from the hospital’s picture archiving and communication system (PACS) (n = 115). Analysis involved determining the median computed tomography dose index-volume (CTDIvol) and dose-length product (DLP) values. The findings were compared with DRLs established internationally. Results: Ingenuity median CTDIvol was 20 mGy and DLP was 2169 mGy*cm; Somatom median CTDIvol was 6 mGy and DLP was 557 mGy*cm. Ingenuity exceeded the United Kingdom’s (UK) recommended DRLs by 82% and 214%, respectively. Somatom median CTDIvol and DLP were 45% and 19% lower than UK NDRLs. Conclusion: Somatom’s tin filter and other dose reduction features provided significant dose reduction. These data were used to set DRLs for CT colonography at the hospital; CTDIvol: 6 mGy and DLP: 557 mGy*cm. Contribution: In addition to informing radiation protection practices at the level of the institution, the established local DRLs contribute towards implementing regional and national DRLs.

1. This study aimed to establish a population pharmacokinetic (PPK) model of mycophenolic acid (MPA), quantify the effect of clinical factors and pharmacogenomics of MPA, and optimise the dosage for adult kidney transplant recipients. 2. One-hundred and four adult renal transplant patients were enrolled. The PPK model was established using the Phoenix® NMLE software and the stepwise methods were filtered for significant covariates. Monte Carlo simulations were performed to optimise the dosage regimen. 3. A two-compartment model with first-order absorption and elimination (including lag time) provided a more accurate description of MPA pharmacokinetics. Serum albumin (ALB) significantly affected the central apparent clearance (CL/F), whereas post-transplant time and creatinine clearance were associated with a central apparent volume of distribution (V/F). The estimated population values obtained by the final model were 17.5 L/h and 93.97 L for CL/F and V/F, respectively. Simulation results revealed that larger mycophenolate mofetil doses are required as the ALB concentration decreases. This study established a PPK model of MPA and validated it using various methods. ALB significantly affected CL/F and recommended optimal dose strategies were given based on the final model. These results provide a reference for the personalised therapy of MPA for kidney transplant patients. [ABSTRACT FROM AUTHOR]

The UNITI trial reports efficacy of ustekinumab (UST) dose intensification in Crohn's disease (CD) from 12- to 8-weekly, but not 4-weekly. We aimed 1) to assess the cumulative incidence of UST dose intensification to 4- or 6-weekly, 2) to identify factors associated with dose intensification, and 3) to assess the effectiveness of this strategy. We performed a retrospective, observational cohort study in NHS Lothian including all UST treated CD patients (2015–2020). 163 CD patients were treated with UST (median follow-up: 20.3 months [13.4–38.4]), of whom 55 (33.7%) underwent dose intensification to 4-weekly (n = 50, 30.7%) or 6-weekly (n = 5, 3.1%). After 1 year 29.9% were dose intensified. Prior exposure to both anti-TNF and vedolizumab (HR 9.5; 1.3–70.9), and concomitant steroid use at UST start (HR 1.8; 1.0–3.1) were associated with dose intensification. Following dose intensification, 62.6% patients (29/55) remained on UST beyond 1 year. Corticosteroid-free clinical remission was achieved in 27% at week 16 and 29.6% at last follow-up. One third of CD patients treated with UST underwent dose intensification to a 4- or 6-weekly interval within the first year. Patients who failed both anti-TNF and vedolizumab, or required steroids at initiation were more likely to dose intensify. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring and Model-informed precision dosing allow dose individualization to increase drug effectivity and reduce toxicity. To evaluate the available evidence on the clinical efficacy of individualized antimicrobial dosing optimization. Data sources : PubMed, Embase, Web of Science, and Cochrane Library databases from database inception to 11 November 2022. Published peer-reviewed randomized controlled trials. Human subjects aged ≥18 years receiving an antibiotic or antifungal drug. Patients receiving individualized antimicrobial dose adjustment. Cochrane risk-of-bias tool for randomized trials. The primary outcome was the risk of mortality. Secondary outcomes included target attainment, treatment failure, clinical and microbiological cure, length of stay, treatment duration, and adverse events. Effect sizes were pooled using a random-effects model. Statistical heterogeneity was assessed by inconsistency testing (I2). Ten randomized controlled trials were included in the meta-analysis (1241 participants; n = 624 in the individualized antimicrobial dosing group and n = 617 in the control group). Individualized antimicrobial dose optimization was associated with a numerical decrease in mortality (risk ratio [RR] = 0.86; 95% CI, 0.71–1.05), without reaching statistical significance. Moreover, it was associated with significantly higher target attainment rates (RR = 1.41; 95% CI, 1.13–1.76) and a significant decrease in treatment failure (RR = 0.70; 95% CI, 0.54–0.92). Individualized antimicrobial dose optimization was associated with improvement, but not significant in clinical cure (RR = 1.33; 95% CI, 0.94–1.33) and microbiological outcome (RR = 1.25; CI, 1.00–1.57), as well as with a significant decrease in the risk of nephrotoxicity (RR = 0.55; 95% CI, 0.31–0.97). This meta-analysis demonstrated that target attainment, treatment failure, and nephrotoxicity were significantly improved in patients who underwent individualized antimicrobial dose optimization. It showed an improvement in mortality, clinical cure or microbiological outcome, although not significant. [Display omitted] [ABSTRACT FROM AUTHOR]

Cross-sectional study to assess the body composition of patients with Crohn's disease (CD) on standard (SDCT) and low dose CT (LDCT) protocols for the abdomen and pelvis (CTAP). We aimed to assess if a low dose CT protocol reconstructed with model-based iterative reconstruction (IR) could evaluate body morphometric data comparable to standard dose examination. The CTAP images of 49 patients who underwent a low dose CT scan (20% of standard dose) and a second at standard dose minus 20% were assessed retrospectively. Images were collected from the PACS system, deidentified and analysed using a web-based semi-automated threshold-based segmentation tool (CoreSlicer), capable of identifying tissue type based on differences in attenuation co-efficient. The cross-sectional area (CSA) and Hounsfield units (HU) of each tissue was recorded. Muscle and fat CSA is well preserved on comparing these derived metrics from low dose and standard dose CT scans of abdomen and pelvic in CD ((LDCT:SDCT mean CSA (cm2); Psoas muscle - 29.00:28.67, total lumbar muscle - 127.45:125.55, visceral fat- 110.44:114.16, subcutaneous fat - 250.88:255.05)). A fixed difference exists when assessing the attenuation of muscle, with higher attenuation on the low dose protocol (LDCT:SDCT mean attenuation (HU); Psoas muscle - 61.67:52.25, total lumbar muscle - 49.29:41.20). We found comparable CSA across all tissues (muscle and fat) on both protocols with a strong positive correlation. A marginally lower muscle attenuation suggestive of less dense muscle was highlighted on SDCT. This study augments previous studies suggesting that comparable and reliable morphomic data may be generated from low dose and standard dose CT images. Threshold-based segmental tools can be used to quantify body morphomics on standard and low dose computed tomogram protocols. [ABSTRACT FROM AUTHOR]

The FDA recommended dose of rasburicase 0.2 mg/kg/day till the resolution of TLS or up to 5 days, might be in excess and is prohibitively expensive. The quality of evidence supporting low dose rasburicase is limited. The objective is to study the plasma uric acid response rate. This is a single center, non-randomised phase II study. Duration is 10 June 2017 till 30 July 2019. Study setting is at Adult Hematolymphoid Unit, Tata Memorial Center. Participants are patients with acute leukemia and high-grade lymphomas aged >/=18 years, with ECOG PS of 0–3, with either laboratory or clinical TLS. Rasburicase was administered at fixed-dose of 1.5 mg. The subsequent doses (1.5 mg each dose) were administered only if plasma UA levels did not decline by >50% on day 2, at the physician's discretion. We demonstrate that a low-dose rasburicase strategy leads to rapid and sustained reductions of uric acid in about 52% patients. [ABSTRACT FROM AUTHOR]

The use of computed tomography (CT) in healthcare institutions has increased rapidly in recent years. The Singapore Health Services (SingHealth) cluster of healthcare institutions has taken the first step in establishing a local cluster-wide CT Diagnostic Reference Levels (DRL) in Singapore. CT dose data from each institution were collected through two primary dosimetry metrics: volume CT dose index (CTDI vol measured in mGy) and dose-length product (DLP measured in mGy.cm). Data from 19 CT scanners in seven institutions under one of Singapore healthcare cluster were retrospectively collected and analysed. The five common adult CT examinations analysed were CT Brain (non-contrast enhanced), CT Chest (IV contrast enhanced), CT Kidney-Ureter-Bladder (CT KUB, non-contrast enhanced), CT Pulmonary Angiogram (CT PA, IV contrast enhanced) and CT Abdomen-Pelvis (CT AP, IV contrast enhanced, single phase). Median CTDI vol and DLP values for the five CT examinations from each institution were derived, with the cluster DRLs determined as the 75th percentile of the distribution of the institution median dose values. A total of 2413 dose data points were collected over a six-month period from June to November 2020. The cluster CT DRLs for the five CT examinations were determined to be 47 mGy and 820 mGy.cm for CT Brain, 5.4 mGy and 225 mGy.cm for CT Chest, 6.7 mGy and 248 mGy.cm for CT PA, 4.6 mGy and 190 mGy.cm for CT KUB and 6.9 mGy and 349 mGy.cm for CT AP. The establishment of the cluster CT DRLs provided individual institutions with a better understanding if their CT doses are unusually high or low, while emphasising that these DRLs are not meant as hard dose limits or constraints to follow strictly. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the disease characteristics of familial Mediterranean fever (FMF) patients undergoing dose optimisation and discontinuation of canakinumab therapy. A total of 61 patients diagnosed with FMF and using canakinumab for the resistant disease were enrolled on this retrospective study. Patients' characteristics, disease activity, treatment response, dose optimisation, dose intervals, attack-free periods, drug-free periods and side effects were noted. Dose intervals were extended in patients who achieved remission without being bound by any protocol at the discretion of the rheumatology physician who followed up with the patients in the outpatient clinic. The drug was discontinued in some patients whose dose intervals were 2 months or longer and remained in remission for 6 months or longer. A total of 57 patients (56% female, median age 32.4 years) were included. The mean attack frequency before canakinumab was 3.4/6 months, while it was 1.2 at the last post-treatment visit (p < 0.001). The median duration of canakinumab use was 46 months. After the first 6 months, the dosing interval was extended in 22 patients, and then treatment was discontinued in 12 of them who did not have an attack in the last 6 months. Three of the 12 patients whose treatment was discontinued started monthly treatment again after their attacks recurred. In the remaining ten patients, dose intervals were extended to 8–12 weeks after 6 months of monthly treatment. Nine patients are still being followed up without attacks and receive only colchicine therapy. Canakinumab is a safe and effective treatment, dose intervals may be extended, and follow-up without medication may be possible for eligible patients. However, there is a need for a consensus on dose optimisation or tapering. [ABSTRACT FROM AUTHOR]

ABSTRACT: Tigecycline, a new first-in-class glycylcycline antibiotic, has shown promising efficacy against a broad range of micro-organisms. It is widely prescribed for various infections, with most prescriptions being considered for off-label use. However, only a few years after its approval by the US Food and Drug Administration (FDA), tigecycline is suspected of increasing all-cause mortality. Some clinicians have suggested such unfavourable outcomes correlate with inadequate drug exposure at the infection site. The pharmacokinetic/pharmacodynamic (PK/PD) profile of a drug plays an important role in predicting its antibiotic effect, which for tigecycline is determined as the ratio of area under the concentration–time curve (AUC) to minimum inhibitory concentration (MIC). In this study, PK/PD targets based on infection sites, bacterial isolates and patient populations are discussed. Generally, a higher dosage of tigecycline for the treatment of serious infections has been recommended in previous reports. However, the latest finding of tigecycline's atypical protein binding property requires consideration when recommending further use. In addition, combination therapy with other antibiotics provides another option by potentially lowering the MICs of multidrug-resistant bacteria.

Abstract Introduction Uterine artery embolisation (UAE) is regarded as a safe and effective treatment for symptomatic uterine fibroids and/or adenomyosis. Dose reduction during UAE is critical for this reproductive‐age patient population to minimise the risks of radiation‐induced effects. The aim of this study was to identify the predictors of radiation dose which can be controlled and optimised for patients during UAE. Methods A total of 150 patients between June 2018 and August 2019 were included in this study. Demographic and clinical information such as age, body mass index (BMI), total number of fibroids, total fibroid volume, total uterus volume and dosimetric measurements on Dose Area Product (DAP), Air Kerma (AK) and fluoroscopy time were recorded. Total digital subtraction angiography (DSA), total conventional roadmap (CRM), total last‐image hold (LIH) and total fluoroscopy were calculated from the dose report. Multiple linear regression analysis was used to identify the independent predictor variables of total dose (DAP) using a regression model. Results Total DSA, total CRM and total LIH were identified as the determinants of dose for UAE (P

To investigate the dose-area product (DAP) of cone-beam computed tomography (CBCT) examinations for different scan settings and imaging indications, and to establish institutional diagnostic reference levels (DRLs) for dose optimisation. A retrospective analysis of the DAP values of 3568 CBCT examinations taken from two different devices at the Prince Philip Dental Hospital, Hong Kong between 2016 and 2021 was performed. Patient- (age, gender, and imaging indication) and imaging-related (CBCT device, field-of-view (FOV), and voxel size) were correlated with the DAPs. The indication-oriented third-quartile DAP values were compared with DRLs from the UK, Finland, and Switzerland. The obtained third-quartile DAPs lower than the national DRLs and those for which no national DRLs have been proposed were used to establish institutional DRLs. In the investigated CBCTs, the DAP value for large FOV scans was significantly lower than medium/small FOVs. CBCTs with a small voxel size exhibited a significantly higher DAP than those with a medium/large voxel size. CBCTs for endodontic, periodontal, orthodontic, or orthognathic evaluation exhibited a significantly higher DAP than other indications. Twelve indication-oriented institutional DRLs were established and five of them were lower than the national DRLs: third molars (229 mGy×cm2), jaw cysts/tumours (410 mGy×cm2), maxillary sinus pathology (520 mGy×cm2), developing dentition (164 mGy×cm2), and periapical lesions (564 mGy×cm2). CBCT examinations for endodontic, periodontal, orthodontic, or orthognathic evaluation may deliver a higher radiation dose to the patient than other imaging tasks. A periodic review of the patient dose from CBCT imaging and establishment of institutional DRLs for specific clinical settings are needed for monitoring patient dose and to optimise indication-oriented scanning protocols. [ABSTRACT FROM AUTHOR]

Abstract Background Reports indicated that numerous factors, including inadequate personnel knowledge, contributes to insufficient patient data for setting up diagnostic reference levels (DRLs) in developing countries. This study aims to evaluate the knowledge of DRLs as an optimisation tool amongst computed tomography (CT) radiographers in northern Nigeria. This is a quantitative cross-sectional study. A structured questionnaire was devised and distributed on site to sixty-two CT radiographers in northern Nigeria. A total of fifteen questions were included in the questionnaire focusing on DRLs, dose optimisation and dose descriptors generating quantitative data concerning overall CT radiographers’ perceived knowledge and awareness about DRLs. Results A response rate of 77.4% (48/62) was achieved. About 83.3% of the participants declare DRLs awareness, and 37.5% carried out a local dose survey. The percentage correctly perceived knowledge of concepts; DRLs was 45.8%, dose optimisation (42%) and CT dose descriptor (39%). Radiographers with work experience ranging from 4-10 years had the highest score. Conclusion In this survey, deficiencies were noted in radiographers’ knowledge about DRLs with precise knowledge gap in the implementation of local dose survey for DRLs and optimisation. There is a need for continuous radiographers’ training with greater emphasis on dose optimisation and institutional based dose evaluation.

Aim: This study investigates the pharmacokinetic/pharmacodynamic (PK/PD) target attainment of linezolid in patients infected with multidrug‐resistant (MDR) tuberculosis (TB). Methods: A pharmacometric model was developed including 244 timed linezolid concentration samples from 39 patients employing NONMEM 7.4. The probability of target attainment (PTA, PK/PD target: unbound (f) area‐under‐the‐concentration‐time‐curve (AUC)/minimal inhibitory concentration (MIC) of 119) as well as a region‐specific cumulative fraction of response (CFR) were estimated for different dosing regimens. Results: A one‐compartment model with linear elimination with a clearance (CL) of 7.69 L/h (interindividual variability 34.1%), a volume of distribution (Vd) of 45.2 L and an absorption constant (KA) of 0.679 h−1 (interoccasion variability 143.7%) allometric scaled by weight best described the PK of linezolid. The PTA at an MIC of 0.5 mg/L was 55% or 97% if patients receiving 300 or 600 mg twice daily, respectively. CFRs varied greatly among populations and geographic regions. A desirable global CFR of ≥90% was achieved if linezolid was administered at a dose of 600 mg twice daily but not at a dose of 300 mg twice daily. Conclusion: This study showed that a dose of 300 mg twice daily of linezolid might not be sufficient to treat MDR‐TB patients from a PK/PD perspective. Thus, it might be recommendable to start with a higher dose of 600 mg twice daily to ensure PK/PD target attainment. Hereby, therapeutic drug monitoring and MIC determination should be performed to control PK/PD target attainment as linezolid shows high variability in its PK in the TB population. [ABSTRACT FROM AUTHOR]

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Abstract Introduction 3D‐printed imaging phantoms are now increasingly available and used for computed tomography (CT) dose optimisation study and image quality analysis. The aim of this study was to evaluate the integrated 3D‐printed cardiac insert phantom when evaluating iterative reconstruction (IR) algorithm in coronary CT angiography (CCTA) protocols. Methods The 3D‐printed cardiac insert phantom was positioned into a chest phantom and scanned with a 16‐slice CT scanner. Acquisitions were performed with CCTA protocols using 120 kVp at four different tube currents, 300, 200, 100 and 50 mA (protocols A, B, C and D, respectively). The image data sets were reconstructed with a filtered back projection (FBP) and three different IR algorithm strengths. The image quality metrics of image noise, signal–noise ratio (SNR) and contrast–noise ratio (CNR) were calculated for each protocol. Results Decrease in dose levels has significantly increased the image noise, compared to FBP of protocol A (P

Objective. The introduction of automatic tube current modulation (ATCM) has resulted in complex relationships between scanner parameters, patient body habitus, radiation dose, and image quality. ATCM adjusts tube current based on x-ray attenuation variations in the scan region, and overall patient dose depends on a combination of factors. This work aims to develop mathematical models that predict CT radiation dose and image noise in terms of attenuating diameter and all relevant scanner parameters. Approach. A homogenous phantom, equipped with the features to conduct discrete and continuous adaption tests, was developed to model ATCM in a Philips CT scanner. Scanner parameters were varied based on theoretical dose relationships, and a MATLAB script was developed to extract data from DICOM images. R statistical software was employed for data analysis, plotting, and regression modelling. Main Results. Phantom data provided the following insights: Median tube current decreased by 81% as tube potential varied from 80 kVp to 140 kVp. Doubling the DoseRight Index (DRI) from 12 to 24, at 24 cm diameter, produced a 294% increase in mA and a 46% decrease in noise. Mean mA increased by 53% whilst mean noise increased by 5.7% as helical pitch increased from 0.6 to 0.925. Changing rotation time from 0.33s to 0.75s gave a 56% reduction in mean mA and no change in image noise. Increasing detector collimation ( n × T ) resulted in higher tube currents and lower output image noise values, as n and T were varied independently. Interpreting these results to apply transformations relevant to each independent variable produced models for tube current and noise with adjusted R-squared values of 0.965 and 0.912, respectively. Significance. The models developed more accurately predict radiation dose and image quality for specific patients and scanner settings. They provide imaging professionals with a practical tool to optimize scan protocols according to patient diameters and clinical objectives., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective of study was to optimise the dose of EC37, EC39 and EC40 against Colletotrichum coccodes in tomato fruit by response surface methodology. In the in-vitro assay, three products were tested against C. coccodes by minimum inhibition concentration, then by using model to test the effects of three levels of two factors (concentration and treatment time) for post-harvest treatment of tomato fruits. The results indicated that 0.55% product concentration with 15 min exposure time was the effective optimised dose treatment with least fruit rot spoilage with retention of fruit texture and colour during storage, on par with the positive control (0.1% Difenoconazole). Storage studies (28 ± 2 °C, 70 ± 5% RH) with above optimised dosage of these product treatments showed less anthracnose incidence, better retention of fruit quality of treated tomato fruits as compared with the positive control and the control fruits after 12 days of storage. Supplemental data for this article is available online at https://doi.org/10.1080/03235408.2022.2033566. [ABSTRACT FROM AUTHOR]

Low-dose computed tomography tends to produce lower image quality than normal dose computed tomography (CT) although it can help to reduce radiation hazards of CT scanning. Research has shown that Artificial Intelligence (AI) technologies, especially deep learning can help enhance the image quality of low-dose CT by denoising images. This scoping review aims to create an overview on how AI technologies, especially deep learning, can be used in dose optimisation for low-dose CT. Literature searches of ProQuest, PubMed, Cinahl, ScienceDirect, EbscoHost Ebook Collection and Ovid were carried out to find research articles published between the years 2015 and 2020. In addition, manual search was conducted in SweMed+, SwePub, NORA, Taylor & Francis Online and Medic. Following a systematic search process, the review comprised of 16 articles. Articles were organised according to the effects of the deep learning networks, e.g. image noise reduction, image restoration. Deep learning can be used in multiple ways to facilitate dose optimisation in low-dose CT. Most articles discuss image noise reduction in low-dose CT. Deep learning can be used in the optimisation of patients' radiation dose. Nevertheless, the image quality is normally lower in low-dose CT (LDCT) than in regular-dose CT scans because of smaller radiation doses. With the help of deep learning, the image quality can be improved to equate the regular-dose computed tomography image quality. Lower dose may decrease patients' radiation risk but may affect the image quality of CT scans. Artificial intelligence technologies can be used to improve image quality in low-dose CT scans. Radiologists and radiographers should have proper education and knowledge about the techniques used. • Less dose may lower patient radiation risk but may impact image quality of CT scans. • Artificial intelligence technologies can improve image quality in low-dose CT scans. • Different deep learning models have been developed to facilitate dose optimisation in low-dose CT. • Radiologists and radiographers should have proper education and knowledge about the techniques used. [ABSTRACT FROM AUTHOR]

Maize is sown in Iran from mid‐April to early September. Weather, weed flora and crop growth stage all vary over this time span, which changes herbicide efficacy. To avoid any excessive or inadequate usage of herbicide, we propose an empirical model that predicts the optimum dose based on the thermal time accumulated by maize after sowing. We planted maize in May and August in 2016 and 2017, arranged in a split‐plot design with four replications. Main plots were herbicide timing ranging from 2 to 8 leaves of maize, and sub‐plots were herbicide dose. Weed response to herbicide dose was parameterised using the standard dose–response model against thermal time (TT) of application. The parameter W0 weed fresh weight (WFW) in plots not treated with herbicide increased linearly, ED50 (the dose to decrease W0 by 50%) increased exponentially, and b (the slope of the curve at linear decrease) decreased exponentially with TT. We replaced the parameters by their specified function of change over TT resulting in a combined model, which predicts WFW from herbicide dose and application time. A hyperbolic model described the yield loss as a function of WFW. We included this relationship in a more developed model, which predicts per cent yield loss based on herbicide dose and application TT. The model performed well over validation tests with R2 ≥ 0.90. We recommend an early herbicide application not later than 600 TT after maize sowing that allows reduced dose, as we found a steady decrease in herbicide efficiency with delaying application time. [ABSTRACT FROM AUTHOR]

• Quality of Life (QOL)-optimised radiotherapy for head and neck cancer. • Efficient and consistent QOL-weighted NTCP-guided optimisation. • Prioritised sparing of OARs related to high impact toxicities. • QOL-based treatment plan evaluation and selection. • Systematic improvement of QOL compared to conventional VMAT. To evaluate the feasibility of semi-automatic Quality of Life (QOL)-weighted normal tissue complication probability (NTCP)-guided VMAT treatment plan optimisation in head and neck cancer (HNC) and compare predicted QOL to that obtained with conventional treatment. This study included 30 HNC patients who were treated with definitive radiotherapy. QOL-weighted NTCP-guided VMAT plans were optimised directly on 80 multivariable NTCP models of 20 common toxicities and symptoms on 4 different time points (6, 12, 18 and 24 months after radiotherapy) and each NTCP model was weighted relative to its impact on QOL. Planning results, NTCP and predicted QOL were compared with the clinical conventional VMAT plans. QOL-weighted NTCP-guided VMAT plans were clinically acceptable, had target coverage equally adequate as the clinical plans, but prioritised sparing of organs at risk (OAR) related to toxicities and symptoms that had the highest impact on QOL. NTCP was reduced for, e.g., dysphagia (−6.1% for ≥grade 2/−7.6% for ≥grade 3) and moderate-to-severe fatigue/speech problems/hoarseness (−0.7%/−1.5%/−2.5%) at 6 months, respectively. Concurrently, the average NTCP of toxicities related to salivary function increased with +0.4% to +5.7%. QOL-weighted NTCP-guided plans were produced in less time, were less dependent on the treatment planner experience and yielded more consistent results. The average predicted QOL improved by 0.7, 0.9, 1.0, and 1.1 points on a 0–100 scale (p < 0.001) at 6, 12, 18, and 24 months, respectively, compared to the clinical plans. Semi-automatic QOL-weighted NTCP-guided VMAT treatment plan optimisation is feasible. It prioritised sparing of OARs related to high-impact toxicities and symptoms and resulted in a systematic improvement of predicted QOL compared to conventional VMAT. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to optimise patient dose and image quality of Varian TrueBeam cone beam computed tomography (CBCT) pelvis, thorax and head and neck (H&N) images based on patient size. Methods: An elliptical phantom of small, medium and large size was designed representative of a local population of pelvis, thorax and H&N patients. The phantom was used to establish the relationship between image noise, CT and CBCT exposure settings. Using this insight, clinical images were optimised in phases and the image quality graded qualitatively by radiographers. At each phase, the time required to match the images was recorded from the record and verify system. Results: Average patient diameter was a suitable metric to categorise patient size. Phantom measurements showed the power relationship between noise and CBCT exposure settings of value −0·15, −0·35 and −0·43 for thorax, pelvis and H&N, respectively. These quantitative phantom measurements provided confidence that phased variation of ~±20% in mAs should result in clinically usable images. Qualitative assessment of almost 2000 images reduced the exposure settings in H&N images by −50%, thorax images by up to −66% and pelvis images by up to −80%. These optimised CBCT settings did not affect the time required to match images. Findings: Varian TrueBeam CBCT mAs settings have been optimised for dose and image quality based on patient size for three treatment sites: pelvis, thorax and H&N. Quantitative phantom measurements provided insight into the magnitude of change to implement clinically. The final optimised exposure settings were determined from radiographer qualitative image assessment. [ABSTRACT FROM AUTHOR]

• External validated Quality of Life (QOL) model for head and neck cancer patients. • Model provides relative impact on QOL of 20 common late toxicities and symptoms. • It allows for prioritised organs at risk sparing during radiotherapy. • QOL model allows for dose plan comparison based on differences in predicted QOL. The aim of this study is to establish the relative impact of physician-rated toxicities and patient-rated symptoms in head and neck cancer (HNC) on quality of life (QOL) and to weigh the various toxicities and symptoms during treatment plan optimization and selection. This prospective cohort study comprised 1083 HNC patients (development: 750, validation: 333) treated with definitive radiotherapy with or without chemotherapy. Clinical factors were scored at baseline. Physician-rated and patient-rated outcome measures and QOL (EORTC QLQ-HN35 and QLQ-C30) were prospectively scored at baseline and 6, 12, 18 and 24 months after radiotherapy. The impact of 20 common toxicities and symptoms (related to swallowing, salivary function, speech, pain and general complaints) on QOL (0–100 scale) was established for each time point by combining principal component analysis and multivariable linear regression. Radiation-induced toxicities and symptoms resulted in a significant decline in QOL of patients with 12.4 ± 12.8 points at 6 months to 16.6 ± 17.1 points at 24 months. The multivariable linear models described the QOL points subtracted for each toxicity and symptom after radiotherapy. For example, xerostomia and weight loss had a significant but minor effect (on average –0.5 and –0.6 points) while speech problems and fatigue had a much greater impact (on average –11.9 and –17.4 points) on QOL. R 2 goodness-of-fit values for the QOL models ranged from 0.64 (6 months) to 0.72 (24 months). The relative impact of physician-rated toxicities and patient-rated symptoms on QOL was quantified and can be used to optimize, compare and select HNC radiotherapy treatment plans, to balance the relevance of toxicities and to achieve the best QOL for individual patients. [ABSTRACT FROM AUTHOR]

Introduction: Uterine artery embolisation (UAE) is regarded as a safe and effective treatment for symptomatic uterine fibroids and/or adenomyosis. Dose reduction during UAE is critical for this reproductive‐age patient population to minimise the risks of radiation‐induced effects. The aim of this study was to identify the predictors of radiation dose which can be controlled and optimised for patients during UAE. Methods: A total of 150 patients between June 2018 and August 2019 were included in this study. Demographic and clinical information such as age, body mass index (BMI), total number of fibroids, total fibroid volume, total uterus volume and dosimetric measurements on Dose Area Product (DAP), Air Kerma (AK) and fluoroscopy time were recorded. Total digital subtraction angiography (DSA), total conventional roadmap (CRM), total last‐image hold (LIH) and total fluoroscopy were calculated from the dose report. Multiple linear regression analysis was used to identify the independent predictor variables of total dose (DAP) using a regression model. Results: Total DSA, total CRM and total LIH were identified as the determinants of dose for UAE (P < 0.05) and together accounted for 95.2% of the variance. Conclusions: This study identified the key imaging predictors of dose for UAE. Total DSA, total CRM and total LIH were shown to have a greater impact on the outcome DAP compared to other demographic or dosimetric measurements. Optimisation of these predictors during future UAE procedures can facilitate radiation dose reduction to the pelvis and reproductive organs. [ABSTRACT FROM AUTHOR]

Background: Reports indicated that numerous factors, including inadequate personnel knowledge, contributes to insufficient patient data for setting up diagnostic reference levels (DRLs) in developing countries. This study aims to evaluate the knowledge of DRLs as an optimisation tool amongst computed tomography (CT) radiographers in northern Nigeria. This is a quantitative cross-sectional study. A structured questionnaire was devised and distributed on site to sixty-two CT radiographers in northern Nigeria. A total of fifteen questions were included in the questionnaire focusing on DRLs, dose optimisation and dose descriptors generating quantitative data concerning overall CT radiographers' perceived knowledge and awareness about DRLs. Results: A response rate of 77.4% (48/62) was achieved. About 83.3% of the participants declare DRLs awareness, and 37.5% carried out a local dose survey. The percentage correctly perceived knowledge of concepts; DRLs was 45.8%, dose optimisation (42%) and CT dose descriptor (39%). Radiographers with work experience ranging from 4-10 years had the highest score. Conclusion: In this survey, deficiencies were noted in radiographers' knowledge about DRLs with precise knowledge gap in the implementation of local dose survey for DRLs and optimisation. There is a need for continuous radiographers' training with greater emphasis on dose optimisation and institutional based dose evaluation. [ABSTRACT FROM AUTHOR]

The field of artificial intelligence (AI) is transforming almost every aspect of modern society, including medical imaging. In computed tomography (CT), AI holds the promise of enabling further reductions in patient radiation dose through automation and optimisation of data acquisition processes, including patient positioning and acquisition parameter settings. Subsequent to data collection, optimisation of image reconstruction parameters, advanced reconstruction algorithms, and image denoising methods improve several aspects of image quality, especially in reducing image noise and enabling the use of lower radiation doses for data acquisition. Finally, AI-based methods to automatically segment organs or detect and characterise pathology have been translated out of the research environment and into clinical practice to bring automation, increased sensitivity, and new clinical applications to patient care, ultimately increasing the benefit to the patient from medically justified CT examinations. In summary, since the introduction of CT, a large number of technical advances have enabled increased clinical benefit and decreased patient risk, not only by reducing radiation dose, but also by reducing the likelihood of errors in the performance and interpretation of medically justified CT examinations. [ABSTRACT FROM AUTHOR]

Little is known about the variations in pathology visibility (PV) and their corresponding radiation dose values for neonatal chest radiography, between and within hospitals. Large variations in PV could influence the diagnostic outcome and the variations in radiation dose could affect the risk to patients. The aim of this study is to compare the PV and radiation dose for standard neonatal chest radiography protocols among a series of public hospitals. A Gammex 610 neonatal chest phantom was used to simulate the chest region of neonates. Radiographic acquisitions were conducted on 17 X-ray machines located in eight hospitals, utilising their current neonatal chest radiography protocols. Six qualified radiographers assessed PV visually using a relative visual grading analysis (VGA). Signal to noise ratios (SNR) and contrast to noise ratios (CNR) were measured as a measure of image quality (IQ). Incident air kerma (IAK) was measured using a solid-state dosimeter. PV and radiation dose varied substantially between and within hospitals. For PV, the mean (range) VGA scores, between and within the hospitals, were 2.69 (2.00–3.50) and 2.73 (2.33–3.33), respectively. For IAK, the mean (range), between and within the hospitals, were 24.45 (8.11–49.94) μGy and 34.86 (22.26–49.94) μGy, respectively. Between and within participating hospitals there was wide variation in the visibility of simulated pathology and radiation dose (IAK). X-ray units with lower PV and higher doses require optimisation of their standard clinical protocols. Institutions which can offer acceptable levels of PV but with lower radiation doses should help facilitate national optimisation processes. [ABSTRACT FROM AUTHOR]

Introduction: 3D‐printed imaging phantoms are now increasingly available and used for computed tomography (CT) dose optimisation study and image quality analysis. The aim of this study was to evaluate the integrated 3D‐printed cardiac insert phantom when evaluating iterative reconstruction (IR) algorithm in coronary CT angiography (CCTA) protocols. Methods: The 3D‐printed cardiac insert phantom was positioned into a chest phantom and scanned with a 16‐slice CT scanner. Acquisitions were performed with CCTA protocols using 120 kVp at four different tube currents, 300, 200, 100 and 50 mA (protocols A, B, C and D, respectively). The image data sets were reconstructed with a filtered back projection (FBP) and three different IR algorithm strengths. The image quality metrics of image noise, signal–noise ratio (SNR) and contrast–noise ratio (CNR) were calculated for each protocol. Results: Decrease in dose levels has significantly increased the image noise, compared to FBP of protocol A (P < 0.001). As a result, the SNR and CNR were significantly decreased (P < 0.001). For FBP, the highest noise with poor SNR and CNR was protocol D with 19.0 ± 1.6 HU, 18.9 ± 2.5 and 25.1 ± 3.6, respectively. For IR algorithm, the highest strength (AIDR3Dstrong) yielded the lowest noise with excellent SNR and CNR. Conclusions: The use of IR algorithm and increasing its strengths have reduced noise significantly and thus increased the SNR and CNR when compared to FBP. Therefore, this integrated 3D‐printed phantom approach could be used for dose optimisation study and image quality analysis in CCTA protocols. [ABSTRACT FROM AUTHOR]

The present study aimed to optimize the injected dose of 18F-FDG in whole-body PET/CT scans and assess its effect on noise-equivalent count rate (NECR) and visual image quality (IQ). Methods: Patients scheduled to undergo 18F-FDG PET/CT were prospectively recruited in the study from January to December 2019, regardless of the indication or underlying disease. Patients were divided into 4 groups and injected with different amounts of 18F-FDG radioactivity per kilogram of body weight (1.85, 3.7, 5.5, and 7.4 MBq/kg). All patients underwent 18F-FDG PET/CT studies, and NECRlocal was calculated by noting the trues rate, total prompts, and randoms rate for each bed position. Whole-body NECRglobal was calculated as the average NECR for all bed positions. IQ was qualitatively assessed for each bed position (IQlocal) and for whole-body PET (IQglobal) by 2 readers using 5-point scores based on prevalence of noise, contrast, and lesion detectability. NECR and IQ were compared among all 4 activity groups. Patients were also subdivided into 4 body-mass-index groups (group I, 15-20 kg/m2; group II, 20.1-25 kg/m2; group III, 25.1-30 kg/m2; and group IV, 30.1-35 kg/m2) for comparison. A P value of less than 0.05 was considered significant. Results: In total, 109 patients underwent 18F-FDG PET/CT studies after injection of different amounts of 18F-FDG radioactivity and a mean uptake time of 62.32 min. The mean NECRglobal and IQglobal for each group were significantly different from other groups (P < 0.05), with NECR and IQ being higher in high-activity groups than in low-activity groups. The overall IQ was acceptable in all patients, even in the lowest-activity group (1.84 MBq/kg). The mean NECRglobal and IQglobal were significantly different in all 4 body-mass-index groups (P < 0.05), except between groups II and III (P > 0.05). NECRlocal and IQlocal correlated moderately (r = 0.64). Conclusion: Optimization of injected 18F-FDG radioactivity from 7.4 MBq/kg (200 μCi/kg) to 1.85 MBq/kg (50 μCi/kg) resulted in acceptable IQ, despite a reduction in NECR. [ABSTRACT FROM AUTHOR]

Positioning relative to the lateral automatic exposure control (AEC) chambers (cranial/caudal orientation) optimises dose and image quality in pelvic radiography. In the cranial orientation introducing gonad shielding (GS) in females may increase radiation dose. The aim of this study was to fully optimise the combination of pelvis orientation and use of GS in both male and females. An anthropomorphic pelvis phantom was exposed, with dose area product (DAP) recorded, in both orientations without GS and four conditions with GS: cranial orientation (female/male), caudal orientation (female/male). A 4 cm × 4 cm grid incorporating thirteen positions for the GS resulted in 52 experimental settings. Blind image quality assessment, utilising a modified scale, was undertaken by two experienced observers. Comparing no GS (caudal orientation) to female GS, no significant change in DAP was seen (3.97 v 4.03 dGy*cm2; Mann–Whitney p = 0.060). Comparing no GS (cranial orientation) to male GS no significant change in DAP was seen (8.66 v 8.77 dGy*cm2; Mann–Whitney; p = 0.210). DAP increased significantly with introduction of female GS in the cranial orientation (23%: 8.66 v 10.65 dGy*cm2, Mann–Whitney; p < 0.001) and male GS in the caudal orientation (22.8%: 3.97 v 4.87 dGy*cm2, Mann–Whitney; p < 0.001). Significantly higher repeat rates (Chi-squared test; p < 0.001) were seen for GS in female (85–100%) compared to male (30.8%). The use of gonad shielding can increase DAP and lead to repeats being required, with more required for female GS usage, suggesting the utility of GS for pelvis examinations is questionable. Optimisation of radiation dose in pelvic radiographic examinations utilising AEC terminated exposures requires consideration of AEC chamber position and GS usage. [ABSTRACT FROM AUTHOR]

Objectives: The second‐generation antipsychotic quetiapine has been demonstrated to undergo gestation‐related changes in pharmacokinetics. This study applied pharmacokinetic modelling principles to investigate the mechanism of these changes and to propose new dosing strategies to counteract these changes. Methods: A pharmacokinetic modelling approach was implemented using virtual population groups. Changes in quetiapine trough plasma concentration during gestation were quantified across all trimesters, and dose adjustment strategies were applied to counteract these changes by targeting a therapeutic range of 50–500 ng/ml throughout gestation. Key findings: The application of the model during gestation predicted a decrease in trough concentration. A maximum decrease of 58% was predicted during trimester 2, and being associated with a statistically significant decrease in oral clearance at gestation week 25, 204 l/h ± 100.8 l/h compared with non‐pregnant subjects, 121.9 l/h ± 51.8 l/h. A dosing optimisation strategy identified that dose increases to 500–700 mg twice daily would result in 32–55% of subjects possessing trough concentration in excess of 50 ng/ml. Conclusions: Quetiapine doses in pregnancy should be increased to 500–700 mg twice daily to counteract a concomitant increase in metabolic clearance, increase in volume of distribution and decrease in plasma protein binding. [ABSTRACT FROM AUTHOR]

Adolescent idiopathic scoliosis (AIS) is a spinal deformity that causes the spine to bend laterally. Patients with AIS undergo frequent X-ray examinations to monitor the progression of the disorder by through the measurement of the Cobb angle. Frequent exposure of adolescents poses the risk of radiation-induced cancer. The aim of this research was to design and build a bespoke phantom representing a 10-year-old child with AIS to allow optimisation of imaging protocols for AIS assessment through the accuracy of Cobb angle measurements. Poly-methyl methacrylate (PMMA) and plaster of Paris (PoP) were used to represent human soft tissue and bone tissue, respectively, to construct a phantom exhibiting a 15° lateral curve of the spine. The phantom was validated by comparing the Hounsfield unit (HU) of its vertebrae with that of human and sheep. Additionally, comparisons of signal-to-noise ratio (SNR) to those from a commercially available phantom. An assessment of the accuracy of the radiographic assessment of the Cobb angle measurement was performed. The HU of the PoP vertebrae was 628 (SD = 56), human vertebrae was 598 (SD = 79) and sheep vertebra was 605 (SD = 83). The SNR values of the two phantoms correlated strongly (r = 0.93 (p = 0.00)). The measured scoliosis angle was 14°. The phantom has physical characteristics (in terms of spinal deformity) and radiological characteristics (in terms of HU and SNR values) of the spine of a 10-year-old child with AIS. This phantom has utility for the optimisation of x-ray imaging techniques in 10 year old children. A phantom to investigate new x-ray imaging techniques and technology in the assessment of scoliosis and to optimise currently used protocols. [ABSTRACT FROM AUTHOR]

Background: Clozapine is a key antipsychotic drug for treatment-resistant schizophrenia but exhibits highly variable pharmacokinetics and a propensity for serious adverse effects. Currently, these challenges are addressed using therapeutic drug monitoring (TDM). This study primarily sought to (i) verify the importance of covariates identified in a prior clozapine population pharmacokinetic (popPK) model in the absence of environmental covariates using physiologically based pharmacokinetic (PBPK) modelling, and then to (ii) evaluate the performance of the popPK model as an adjunct or alternative to TDM-guided dosing in an active TDM population. Methods: A popPK model incorporating age, metabolic activity, sex, smoking status and weight was applied to predict clozapine trough concentrations (Cmin) in a PBPK-simulated population and an active TDM population comprising 142 patients dosed to steady state at Flinders Medical Centre in Adelaide, South Australia. Post hoc analyses were performed to deconvolute the impact of physiological and environmental covariates in the TDM population. Results: Analysis of PBPK simulations confirmed age, cytochrome P450 1A2 activity, sex and weight as physiological covariates associated with variability in clozapine Cmin (R2 = 0.7698; p = 0.0002). Prediction of clozapine Cmin using a popPK model based on these covariates accounted for min in the TDM population. Conclusions: Variability in clozapine exposure was primarily driven by environmental covariates in an active TDM population. Pharmacokinetic modelling can be used as an adjunct to TDM to deconvolute sources of variability in clozapine exposure.

Introduction With regards to the use of ionisation radiation in the computed tomography (CT), optimal parameters should be used to reduce the risk of incidence of secondary cancers in patients who are constantly exposed to X-rays. The aim of this study was to optimise the parameters used in CT scan of cervical vertebrae and neck soft tissue with minimal loss of image quality in emergency patients. Materials and methods In this study, the patients were divided into two groups. The first group consisted of patients scanned with default parameters and the second group scanned with optimised parameters. All the study has been implemented in emergency settings. The cases included cervical vertebrae and soft tissue protocols. Common CT dose descriptors including weighted computed tomography dose index (CTDIw), volumetric CTDI (CTDIvol), dose length product (DLP), effective dose (ED) and image noise were measured for each group. The ImpactDose program was used to estimate the organs doses. Statistical analysis was performed using Kruskal-Wallis test using SPSS software. Results There was no significant quality reduction in the optimised images. Decreasing in radiation dose parameters for the soft tissue was: kVp=16.7%, mAs=64.3% and pitch=24.1%, and for the cervical vertebrae was: kVp=16.7%, mAs=54.2% and pitch=48.3%. Consequently, decreasing these parameters reduced CTDIw=81.0%, CTDIvol=90.0% and DLP = 90.2% in the cervical vertebral protocol, as well as CTDIw=75.5%, CTDIvol=81.3% and DLP = 81.4% in the soft tissue protocol. Conclusion Regarding the results, the optimised parameters in the mentioned organ scan reduce the radiation dose in the target area and the organs surrounding. Therefore, these protocols can be used for reducing the risk of cancer. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that reducing radiotherapy dose delivered to specific anatomical swallowing structures [Swallowing Organs at Risk (SWOARs)] may improve swallowing outcomes post-treatment for patients with head and neck cancer. However, for those patients with tumours of the oropharynx, which typically directly overlap the SWOARs, reducing dose to these structures may be unachievable without compromising on the treatment of the disease. To assess the feasibility of dose reduction in this cohort, standard IMRT plans (ST-IMRT) and plans with reduced dose to the SWOARs (SW-IMRT) were generated for 25 oropharyngeal cancer patients (Brouwer et al. in Radiother Oncol 117(1):83-90, https://doi.org/10.1016/j.radonc.2015.07.041 , 2015; Christianen et al. in Radiother Oncol 101(3):394-402, https://doi.org/10.1016/j.radonc.2011.05.015 , 2011). ST-IMRT and SW-IMRT plans were compared for: mean dose to the SWOARs, volume of pharynx and larynx receiving 50 Gy and 60 Gy (V50 and V60 respectively) and overlap between the tumour volume and the SWOARs. Additionally, two different SWOARs delineation guidelines (Brouwer et al. in Radiother Oncol 117(1):83-90, https://doi.org/10.1016/j.radonc.2015.07.041 , 2015; Christianen et al. in Radiother Oncol 101(3):394-402, https://doi.org/10.1016/j.radonc.2011.05.015 , 2011) were used to highlight differences in calculated volumes between existing contouring guidelines. Agreement in SWOARs volumes between the two guidelines was calculated using a concordance index (CI). Despite a large overlap between the tumour and SWOARs, significant (p < 0.05) reductions in mean dose to 4 of the 5 SWOARs, and V50/V60 for the pharynx and larynx were achieved with SW-IMRT plans. Low CIs per structure (0.15-0.45) were found between the two guidelines highlighting issues comparing data between studies when different guidelines have been used (Hawkins et al. in Semin Radiat Oncol 28(1):46-52, https://doi.org/10.1016/j.semradonc.2017.08.002 , 2018; Brodin et al. in Int J Radiat Oncol Biol Phys 100(2):391-407, https://doi.org/10.1016/j.ijrobp.2017.09.041 , 2018). This study found reducing dose to the SWOARs is a feasible practice for patients with oropharyngeal cancer. However, future prospective research is needed to determine if the extent of dose reduction achieved equates to clinical benefits. [ABSTRACT FROM AUTHOR]

• Scattering system designed via genetic algorithm efficiently shapes laser-driven proton beam. • Scattering system placed along a quadrupole system improves beam shaping by mixing trajectories. • Genetic approach efficiently flattens the dose distribution in 2D sample. Laser-accelerated protons have a great potential for innovative experiments in radiation biology due to the sub-picosecond pulse duration and high dose rate achievable. However, the broad angular divergence makes them not optimal for applications with stringent requirements on dose homogeneity and total flux at the irradiated target. The strategy otherwise adopted to increase the homogeneity is to increase the distance between the source and the irradiation plane or to spread the beam with flat scattering systems or through the transport system itself. Such methods considerably reduce the proton flux and are not optimal for laser-accelerated protons. In this paper we demonstrate the use of a Genetic Algorithm (GA) to design an optimal non-flat scattering system to shape the beam and efficiently flatten the transversal dose distribution at the irradiated target. The system is placed in the magnetic transport system to take advantage of the presence of chromatic focusing elements to further mix the proton trajectories. The effect of a flat scattering system placed after the transport system is also presented for comparison. The general structure of the GA and its application to the shaping of a laser-accelerated proton beam are presented, as well as its application to the optimisation of dose distribution in a water target in air. [ABSTRACT FROM AUTHOR]

Background and Aims In nonresponders to golimumab induction for ulcerative colitis, we assessed clinical response rates and golimumab serum concentrations when the 100-mg dose was used early in the course of maintenance. Methods This post-hoc analysis of golimumab maintenance dosing [in the PURSUIT-M study] examined clinical outcomes and golimumab concentrations in early [Week 6] responders and nonresponders to induction, including subgroups based on body weight. Results In nonresponders to golimumab induction [assessed at Week 6], the 100-mg maintenance dose [starting at Week 6] resulted in a meaningful proportion [28.1%] of patients achieving a partial Mayo response at Week 14. After 1 year of maintenance, clinical outcome [response, remission, mucosal healing, corticosteroid-free state] rates in these "late" [Week 14] responders were similar to those in early [Week 6] responders. Golimumab concentrations in early nonresponders were approximately half those of early responders, suggesting that early nonresponders had more rapid golimumab clearance. Examined by body weight, the early nonresponders weighing <80 kg and receiving 100 mg had golimumab concentrations similar to the early responders [weighing <80 kg or ≥80 kg and receiving 50 mg or 100 mg, respectively]. Conclusions Early use of the 100-mg maintenance dose leads to positive clinical outcomes in a meaningful proportion of patients who did not respond to golimumab at Week 6. Early nonresponders <80 kg who received the 100-mg maintenance dose achieved adequate golimumab concentrations and a clinically meaningful proportion of these patients had a late clinical response. PURSUIT-M protocol number C0524T18; ClinicalTrials.gov, NCT00488631; EudraCT, 2006-003399-37. [ABSTRACT FROM AUTHOR]