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Abstract The objective of this study was to evaluate the influence of light and glyphosate doses in the Euphorbia heterophylla control. The experiment was conducted in a factorial scheme. The first factor consisted of plants under full sunlight and two shadings of 40% and 65%, and the second factor represented by doses 0 (control), 370, 740, 1110, 1480 and 1850 g a.e. ha−1 of glyphosate. Shading increased E. heterophylla sensitivity to glyphosate compared to full sunlight. Under shading, the dose of 1110 g ha−1 of glyphosate was efficient in the management of this species, with control higher than 90%. However, under full sunlight, the highest doses achieved control levels around 75%, considered unsatisfactory. The variables fresh weight, quantum yield of photosystem II and electron transport rate of E. heterophylla showed a strong negative correlation with the species control by glyphosate. The glyphosate recommendations for controlling E. heterophylla needs to consider the light conditions in the plant growth environment, as an economically and sustainable practice in the integrated management of the specie. [ABSTRACT FROM AUTHOR]

Ramucirumab (RAM) plus Docetaxel (DOC) is one of the standard treatments after first-line treatment failure in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the efficacy and safety of RAM plus DOC in older patients. We aimed to clarify these and elucidate the prognostic factors. In this multicenter retrospective study, conducted at four medical facilities in Japan, we evaluated the efficacy and safety data for two groups (<65 and ≥ 65 years). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed to reveal the prognostic factors for better PFS and OS. Patient characteristics and adverse events (AEs) in both groups were compared using the Mann-Whitney's U and Fisher's exact tests for categorical variables. A total of 237 patients were included, of whom 43% (n = 103), and 57% (n = 134) were aged <65, and ≥ 65 years. Median OS was 12.2 (95% CI: 9.4–15.0), and 14.8 months (95% CI: 10.8–18.8), respectively, and there were no significant differences between the groups (p = 0.534). Multivariate analysis identified DOC dose reduction (none vs performed, HR: 2.66, 95% CI: 1.62–4.35, p < 0.001) as an independent prognostic factor for OS in older patients, and a similar result was shown for the PFS. Grade ≥ 3 all AEs were identified in 42.7% and 56.7% of younger and older patients, respectively, and there was a significant difference between the groups (p = 0.033); however, the difference between the groups disappeared with primary DOC dose reduction (p = 0.526). The efficacy of RAM plus DOC administration in older, pretreated patients with advanced NSCLC was comparable to those of younger patients, whereas RAM plus DOC should be cautiously administered to older patients because of severe toxicity. Moreover, appropriate DOC dose reduction may be recommended for increased survival benefit and safety in such patients. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the history of biologics usage in patients with ankylosing spondylitis (AS) in China and to evaluate the impact of drug reduction and withdrawal on disease activity.Methods: Drug administration intervals and disease activity indexes in patients with AS who regularly used etanercept (ETN) biosimilars for more than 1 year and those who withdrew the drugs during the same period in a single center were analyzed retrospectively.Results: A total of 108 patients with AS who used ETN biosimilars for more than a year were recruited in this study for analysis. (1) Overall, 98.1% patients with AS increased the intervals between drug administrations, averaging from 4.57 ± 0.15 days during 0-3 months to 8.53 ± 0.43 days during 3-6 months, and to 10.49 ± 0.39 days during 6-12 months. Compared with the baseline parameters, after 3-month and 12-month treatments disease activities were improved significantly, including Patient Global Assessment (PTGA), overall back pain, nocturnal pain, fatigue, Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). (2) Only 59.3% used ETN biosimilars with full dose (3.5 days' interval) in the first 3 months. At baseline, disease activities of these patients were higher than those with reduced dose (5.9 days' interval). However, at 12 months of drug administration there was no significant difference in the overall length of drug administration intervals and disease activities between the two groups. (3) Twenty patients with low disease activity (LDA) discontinued therapy spontaneously; after 3 months, 55% of them experienced disease recurrence (∆ASDAS ≥ 0.9).Conclusion: Spontaneous dose reduction was a common phenomenon among patients with AS in China, which becomes more notable with increasing relief of symptoms. Most patients could maintain an LDA state after dose reduction. Compared with dose reduction, ETN biosimilar withdrawal was more likely to induce disease recurrence. Therefore, disease activity-guided individualized stepwise tapering may become one of the feasible therapeutic strategies for AS in the future. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of this study was to assess scan parameters and to propose strategies to optimize the examinations of children (from 0 to 15 years old) on adult scanners in developing countries. Methods A study was done in 2015 and 2018 on 312 pediatric patients to verify improved practices. The study of 2015 ended with proposed strategies. Dose and scan parameters were available for prospective dose analysis. These strategies were implemented in a study of 2018. Results Amount the CT examinations study in this paper, the common was head trauma (90 %). For every pediatric CT scan in 2015, a kV of 120 was used in the various hospitals. The mAs ranged from 57.75 to 283.33, slice thicknesses from 1.25 to 2.5 mm and pitch from 0.525 to 1.375 mm. In the study of 2018, implementing the strategy defined in the methodology and proposed in 2015: CTDIVol decreased by 21.27 % for children

A body of studies has proposed to obtain high-quality images from low-dose and noisy Computed Tomography (CT) scans for radiation reduction. However, these studies are designed for population-level data without considering the variation in CT devices and individuals, limiting the current approaches' performance, especially for ultra-low-dose CT imaging. Here, we proposed PIMA-CT, a physical anthropomorphic phantom model integrating an unsupervised learning framework, using a novel deep learning technique called Cyclic Simulation and Denoising (CSD), to address these limitations. We first acquired paired low-dose and standard-dose CT scans of the phantom and then developed two generative neural networks: noise simulator and denoiser. The simulator extracts real low-dose noise and tissue features from two separate image spaces (e.g., low-dose phantom model scans and standard-dose patient scans) into a unified feature space. Meanwhile, the denoiser provides feedback to the simulator on the quality of the generated noise. In this way, the simulator and denoiser cyclically interact to optimize network learning and ease the denoiser to simultaneously remove noise and restore tissue features. We thoroughly evaluate our method for removing both real low-dose noise and Gaussian simulated low-dose noise. The results show that CSD outperforms one of the state-of-the-art denoising algorithms without using any labeled data (actual patients' low-dose CT scans) nor simulated low-dose CT scans. This study may shed light on incorporating physical models in medical imaging, especially for ultra-low level dose CT scans restoration.

The purpose of this report is to describe our experience with the implementation of a practice quality improvement (PQI) project in thoracic imaging as part of the American Board of Radiology Maintenance of Certification process. The goal of this PQI project was to reduce the effective radiation dose of routine chest CT imaging in a busy clinical practice by employing the iDose(4) (Philips Healthcare) iterative reconstruction technique. The dose reduction strategy was implemented in a stepwise process on a single 64-slice CT scanner with a volume of 1141 chest CT scans during the year. In the first annual quarter, a baseline effective dose was established using the standard filtered back projection (FBP) algorithm protocol and standard parameters such as kVp and mAs. The iDose(4) technique was then applied in the second and third annual quarters while keeping all other parameters unchanged. In the fourth quarter, a reduction in kVp was also implemented. Throughout the process, the images were continually evaluated to assure that the image quality was comparable to the standard protocol from multiple other scanners. Utilizing a stepwise approach, the effective radiation dose was reduced by 23.62 and 43.63 % in quarters two and four, respectively, compared to our initial standard protocol with no perceived difference in diagnostic quality. This practice quality improvement project demonstrated a significant reduction in the effective radiation dose of thoracic CT scans in a busy clinical practice.

Study designThe aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats.ObjectiveTo determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP.Summary of background dataBMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications.MethodsPosterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10 μg) was tested with or without "low-dose" rhBMP-2 (2 μg), and the results were compared with the "low-dose" (2 μg rhBMP-2) and "high-dose" (10 μg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro.ResultsFusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold.ConclusionCOMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose-related adverse effects, surgical costs, and improve clinical outcomes.Level of evidenceN/A.

Introduction: Several studies have reported the relation between the imaging dose and secondary cancer risk and have emphasized the need to minimize the additional imaging dose as low as reasonably achievable. The iterative cone-beam computed tomography (iCBCT) algorithm can improve the image quality by utilizing scatter correction and statistical reconstruction. We investigate the use of a novel iCBCT reconstruction algorithm to reduce the patient dose while maintaining low-contrast detectability and registration accuracy. Methods: Catphan and anthropomorphic phantoms were analyzed. All CBCT images were acquired with varying dose levels and reconstructed with a Feldkamp–Davis–Kress algorithm-based CBCT (FDK-CBCT) and iCBCT. The low-contrast detectability was subjectively assessed using a 9-point scale by 4 reviewers and objectively assessed using structure similarity index (SSIM). The soft tissue-based registration error was analyzed for each dose level and reconstruction technique. Results: The results of subjective low-contrast detectability found that the iCBCT acquired at two-thirds of a dose was superior to the FDK-CBCT acquired at a full dose (6.4 vs 5.4). Relative to FDK-CBCT acquired at full dose, SSIM was higher for iCBCT acquired at one-sixth dose in head and head and neck region while equivalent with iCBCT acquired at two-thirds dose in pelvis region. The soft tissue-based registration was 2.2 and 0.6 mm for FDK-CBCT and iCBCT, respectively. Conclusion: Use of iCBCT reconstruction algorithm can generally reduce the patient dose by approximately two-thirds compared to conventional reconstruction methods while maintaining low-contrast detectability and accuracy of registration. [ABSTRACT FROM AUTHOR]

Introduction: Reducing tube voltage is an effective dose saving method in computed tomography (CT) assuming tube current is not concurrently increased. Recent innovations in scanner technology now enable CT tube voltage reduction to 70 kV thereby increasing opportunities for dose reduction in paediatric patients, but it is unclear if the increased image noise associated with 70 kV impacts on ability to visualise renal stones accurately. The purpose was to assess detectability of nephrolithiasis using a bespoke paediatric phantom and low kV, non‐contrast CT and to assess inter‐observer agreement. Methods: Forty‐two renal stones of different size and chemical composition were inserted into porcine kidneys and positioned in a bespoke, water‐filled phantom mimicking a 9‐year‐old child weighing approximately 33kg. The phantom was scanned using 120 and 70 kV CT protocols, and the detectability of the stones was assessed by three radiologists. Absolute agreement and Fleiss' kappa regarding detectability were assessed. Results: The mean diameter of renal stones as measured physically was 4.24 mm ranging from 1 to 11 mm. Four stones were missed by at least one observer. One observer had a sensitivity of 93 and 95% at 70 and 120 kV, respectively, while the sensitivity for observers 2 and 3 was 98% at both kV levels. Specificity was 100% across readers and kV levels. Absolute agreement between the readers at 70 kV was 92% (kappa = 0.86) and 98% (kappa = 0.96) at 120 kV indicating a strong agreement at both kV levels. Conclusions: The results suggest that lowering the kV does not affect the detection rate of renal stones and may be a useful dose reduction strategy for assessment of nephrolithiasis in children. [ABSTRACT FROM AUTHOR]

Introduction: Sonidegib is a Hedgehog pathway inhibitor approved to treat locally advanced basal cell carcinoma and, depending on regulatory approval, metastatic basal cell carcinoma. Results from the BOLT study demonstrated robust efficacy and continued tolerability through 42 months. This analysis evaluated the impact of sonidegib dose reductions and interruptions in patients with advanced basal cell carcinoma through 42 months. Methods: BOLT was a randomized, double-blind, multicenter, phase 2 study. Adults with no previous Hedgehog pathway inhibitor therapy were randomized 1:2 to sonidegib 200 or 800 mg once daily. Primary endpoint was objective response rate. Dose modifications were permitted in patients unable to tolerate the dosing schedule or if a treatment-related adverse event was suspected. Results: The incidence of dose interruptions was similar between the 200- and 800-mg groups (68.4% vs 65.3%, respectively). Dose reductions occurred more frequently in patients receiving sonidegib 800 mg (36.7%) than 200 mg (16.5%). Overall response rate for all patients receiving sonidegib 200 mg daily was 48.1% and was similar to those of patients without dose reduction or interruption (48.5%) and patients with at least one dose reduction or interruption (46.2%). Conclusion: Dose reductions and interruptions were practical and did not impact the efficacy of sonidegib. In patients with advanced basal cell carcinoma who necessitate long-term treatment, dose interruptions may be beneficial for continued treatment and disease control. Trial registration: ClinicalTrials.gov identifier, NCT01327053. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether the advanced spatial noise reduction (ASNR) algorithm installed in a digital radiography system generates acceptable images at a lower dose than a conventional denoising algorithm in pediatric patients. Methods: Nine sets of 30 images of pediatric patients, classified under three protocols and three age groups, were retrospectively selected. Different levels of low-dose image sets of these 270 images were generated by a noise simulation tool after validation testing using phantoms. Each image set was obtained with both the ASNR and conventional algorithm, and grouped randomly and blinded. Three experienced pediatric radiologists were asked to pick the "image with optimum dose" among images of different dose levels with an ALARA (as low as reasonably achievable) perspective. Dose reduction rates for each protocol and age group were calculated, and entrance skin exposure (ESE) was calculated using the values of kVp and mAs, assuming a standard body depth for each age group. Results: With the ASNR algorithm, estimated dose reduction rates were highest for abdominal radiographs (45.0%, 27.3%, and 24.3% in infants, children, and adolescents, respectively, p < 0.001). The mean dose reductions for all age groups in the abdominal, chest, and skull radiographs were 32.8%, 12.9%, and 23.2%, respectively (p < 0.001). Average of the calculated ESE was lower with the ASNR algorithm than with the conventional algorithm group (p < 0.001). Conclusions: The ASNR algorithm facilitated optimization of image quality with a higher reduction in radiation dose than the conventional algorithm, making it more acceptable for use in pediatric patients. Key Points: •ASNR algorithm in DR system improves image quality via enhanced contrast and noise removal by estimating actual noise distribution based on a multi-scale noise covariance and frequency processing. •Noise simulation tool (NST) generating images of different dose levels can be used for evaluation of the optimum dose without unnecessary additional radiation exposure to pediatric patients. •Retrospective clinical study using NST showed that the ASNR algorithm enabled a higher reduction in radiation dose than the conventional algorithm in pediatric patients. [ABSTRACT FROM AUTHOR]

Female breasts are exposed to scattered radiation regardless of not being included in the primary field during head CT. This study aimed to investigate whether the use of lead shielding is beneficial in dose reduction to the breasts during head CT.

Abstract Background We assessed and compared image quality obtained with clinical 18F-FDG whole-body oncologic PET protocols used in three different, state-of-the-art digital PET/CT and two conventional PMT-based PET/CT devices. Our goal was to evaluate an improved trade-off between administered activity (patient dose exposure/signal-to-noise ratio) and acquisition time (patient comfort) while preserving diagnostic information achievable with the recently introduced digital detector technology compared to previous analogue PET technology. Methods We performed list-mode (LM) PET acquisitions using a NEMA/IEC NU2 phantom, with activity concentrations of 5 kBq/mL and 25 kBq/mL for the background (9.5 L) and sphere inserts, respectively. For each device, reconstructions were obtained varying the image statistics (10, 30, 60, 90, 120, 180, and 300 s from LM data) and the number of iterations (range 1 to 10) in addition to the employed local clinical protocol setup. We measured for each reconstructed dataset: the quantitative cross-calibration, the image noise on the uniform background assessed by the coefficient of variation (COV), and the recovery coefficients (RCs) evaluated in the hot spheres. Additionally, we compared the characteristic time-activity-product (TAP) that is the product of scan time per bed position × mass-activity administered (in min·MBq/kg) across datasets. Results Good system cross-calibration was obtained for all tested datasets with

Abstract Background Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. Methods We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. Discussion More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences. Trial registration Dutch Trial Register, NL6771. Registered on 27 November 2018 (CMO NL66181.091.18, 23 October 2018).

The purpose of this research was to determine the impact of collimation in thoracic spine radiography on patient exposure and image quality. The study was performed on 84 patients referred to thoracic spine radiography. Patients were randomly divided into two equal groups of 42. The first group was imaged according to the standard collimation protocol used in one of the hospitals in Croatia while the second group was imaged by applying “optimal” collimation, image field size was individually collimated for each patient or according to the greatest image field collimation depicted in professional literature. For each patient body mass index, image field size, exposure conditions and dose area product were noted and absorbed doses by organs were calculated, image quality was assessed. There were no statistically significant differences in BMI between the two groups of patients. With the optimal collimation the size of the imaging field in the anteroposterior projection was reduced by 45 % ( p < 0.001) and in the lateral projection by 41 % (p < 0.001). The study also showed reduced values of DAP for anteroposterior projection by 34 % ( p = 0.007) and for lateral projection by 23 % ( p = 0.040). The mean absorbed dose to the selected organs decreased by 26 % in the anteroposterior projection and by 28 % in the lateral projection. In addition, the optimal collimation protocol improved image quality by 13 % in anteroposterior projection. No differences in image quality were found in lateral projection. By carrying out this research we have demonstrated that optimal collimation in thoracic spine imaging has a strong influence on patient exposure to radiation and has a positive impact on image quality.

Computed tomography is an important technique for non-destructive analysis of an object's internal structure, relevant for scientific studies, medical applications, and industry. Pressing challenges emerging in the field of tomographic imaging include speeding up reconstruction, reducing the time required to obtain the X-ray projections, and reducing the radiation dose imparted to the object. In this paper, we introduce a model of a monitored reconstruction process, in which the acquiring of projections is interspersed with image reconstruction. This model allows to examine the tomographic reconstruction process as an anytime algorithm and consider a problem of finding the optimal stopping point, corresponding to the required number of X-ray projections for the currently scanned object. We outline the theoretical framework for the monitored reconstruction, propose ways of constructing stopping rules for various reconstruction quality metrics and provide their experimental evaluation. Due to stopping at different times for different objects, the proposed approach allows to achieve a higher mean reconstruction quality for a given mean number of X-ray projections. Conversely, fewer projections on average are used to achieve the same mean reconstruction quality.

Background and purpose: Based on artificial intelligence (AI), 3D angiography (3DA) is a novel postprocessing algorithm for “DSA-like” 3D imaging of cerebral vasculature. Because 3DA requires neither mask runs nor digital subtraction as the current standard 3D-DSA does, it has the potential to cut the patient dose by 50%. The object was to evaluate 3DA’s diagnostic value for visualization of intracranial artery stenoses (IAS) compared to 3D-DSA. Materials and methods: 3D-DSA datasets of IAS (nIAS = 10) were postprocessed using conventional and prototype software (Siemens Healthineers AG, Erlangen, Germany). Matching reconstructions were assessed by two experienced neuroradiologists in consensus reading, considering image quality (IQ), vessel diameters (VD1/2), vessel-geometry index (VGI = VD1/VD2), and specific qualitative/quantitative parameters of IAS (e.g., location, visual IAS grading [low-/medium-/high-grade] and intra-/poststenotic diameters [dintra-/poststenotic in mm]). Using the NASCET criteria, the percentual degree of luminal restriction was calculated. Results: In total, 20 angiographic 3D volumes (n3DA = 10; n3D-DSA = 10) were successfully reconstructed with equivalent IQ. Assessment of the vessel geometry in 3DA datasets did not differ significantly from 3D-DSA (VD1: r = 0.994, p = 0.0001; VD2:r = 0.994, p = 0.0001; VGI: r = 0.899, p = 0.0001). Qualitative analysis of IAS location (3DA/3D-DSA:nICA/C4 = 1, nICA/C7 = 1, nMCA/M1 = 4, nVA/V4 = 2, nBA = 2) and the visual IAS grading (3DA/3D-DSA:nlow-grade = 3, nmedium-grade = 5, nhigh-grade = 2) revealed identical results for 3DA and 3D-DSA, respectively. Quantitative IAS assessment showed a strong correlation regarding intra-/poststenotic diameters (rdintrastenotic = 0.995, pdintrastenotic = 0.0001; rdpoststenotic = 0.995, pdpoststenotic = 0.0001) and the percentual degree of luminal restriction (rNASCET 3DA = 0.981; pNASCET 3DA = 0.0001). Conclusions: The AI-based 3DA is a resilient algorithm for the visualization of IAS and shows comparable results to 3D-DSA. Hence, 3DA is a promising new method that allows a considerable patient-dose reduction, and its clinical implementation would be highly desirable.

ABSTRACT (198): Background: The multi-dose regimen is a known barrier to successful human papillomavirus (HPV) vaccination. Emerging evidence suggests that one vaccine dose could protect against HPV. While there are clear advantages to a single dose schedule, beliefs about vaccine dosage in low and middle income countries (LMICs) are poorly understood. We investigated acceptability of dose-reduction among girls, and parents/guardians of girls, randomised to receive one, two or three doses in an HPV vaccine dose-reduction and immunobridging study (DoRIS trial) in Tanzania. Methods: Semi-structured interviews with girls (n = 19), and parents/guardians of girls (n = 18), enrolled in the study and completing their vaccine course. Results: Most participants said they entrusted decisions about the number of HPV vaccine doses to experts. Random allocation to the different dose groups did not feature highly in the decision to participate in the trial. Given a hypothetical choice, girls generally said they would prefer fewer doses in order to avoid the pain of injections. Parental views were mixed, with most wanting whichever dose was most efficacious. Nonetheless, a few parents equated a higher number of doses with greater protection. Conclusion: Vaccine trials and programmes will need to employ careful messaging to explain that one dose offers sufficient protection against HPV should emerging evidence from ongoing dose-reduction clinical trials support this.

Our aim was to define a lower limit of reduced injected activity in delayed [ 18 F]FDG total-body (TB) PET/CT in pediatric oncology patients. Methods: In this single-center prospective study, children were scanned for 20 min with TB PET/CT, 120 min after intravenous administration of a 4.07 ± 0.49 MBq/kg dose of [ 18 F]FDG. Five randomly subsampled low-count reconstructions were generated using ¼, ⅛, [Formula: see text], and [Formula: see text] of the counts in the full-dose list-mode reference standard acquisition (20 min), to simulate dose reduction. For the 2 lowest-count reconstructions, smoothing was applied. Background uptake was measured with volumes of interest placed on the ascending aorta, right liver lobe, and third lumbar vertebra body (L3). Tumor lesions were segmented using a 40% isocontour volume-of-interest approach. Signal-to-noise ratio, tumor-to-background ratio, and contrast-to-noise ratio were calculated. Three physicians identified malignant lesions independently and assessed the image quality using a 5-point Likert scale. Results: In total, 113 malignant lesions were identified in 18 patients, who met the inclusion criteria. Of these lesions, 87.6% were quantifiable. Liver SUV mean did not change significantly, whereas a lower signal-to-noise ratio was observed in all low-count reconstructions compared with the reference standard ( P < 0.0001) because of higher noise rates. Tumor uptake (SUV max ), tumor-to-background ratio, and total lesion count were significantly lower in the reconstructions with [Formula: see text] and [Formula: see text] of the counts of the reference standard ( P < 0.001). Contrast-to-noise ratio and clinical image quality were significantly lower in all low-count reconstructions than with the reference standard. Conclusion: Dose reduction for delayed [ 18 F]FDG TB PET/CT imaging in children is possible without loss of image quality or lesion conspicuity. However, our results indicate that to maintain comparable tumor uptake and lesion conspicuity, PET centers should not reduce the injected [ 18 F]FDG activity below 0.5 MBq/kg when using TB PET/CT in pediatric imaging at 120 min after injection., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Clinical guidelines for the treatment of rheumatoid arthritis (RA) recommend reducing the use of glucocorticoids (GCs) due to the high risk of associated complications., Aim: To determine the frequency of GC cancellations and dose reductions in real clinical practice, while taking into account active RA therapy., Materials and Methods: The study group consisted of 303 patients with RA reliable according to ACR/EULAR criteria (women 79.9%, age 52.8±13.3, disease duration 9 [4; 16] years, DAS-28-CRP 4.9±1.0, RF seropositivity 77.4%, ACPA seropositivity 70.3%), who were prescribed or changed therapy with disease-modifying antirheumatic drugs (DMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (iJAK) due to disease exacerbation and ineffectiveness of previous treatment. All patients initially received GC (7.7±3.8 mg/day equivalent of prednisolone). After adjustment of therapy, 42.9% of patients received methotrexate, 27.6% leflunomide, 2.5% sulfasalazine, hydroxychloroquine, or a combination with an Non-steroidal anti-inflammatory drugs, 63.7% bDMARDs, and 7.2% iJAK. The need for GC intake was assessed by a telephone survey conducted 6 months after the start of follow-up., Results: Telephone survey was possible in 274 (90.4%) persons. There was a significant decrease in pain intensity (numerical rating scale, NRS 0-10) from 6.3±1.4 to 4.3±2.4 ( p <0.001), fatigue (NRS) from 6.7±2.3 to 5.2±2.1 ( p <0.001), and functional impairment (NRS) from 5.4±2.1 to 3.9±2.0 ( p <0.001). A positive PASS index (symptom status acceptable to patients) was noted in 139 (50.7%) patients. GC cancellation was noted in 19.7%, dose reduction in 25.9%, maintaining the same dose in 42.7%, and dose increase in 11.7%., Conclusion: Against the background of intensive RA therapy, including combination of DMARDs with bDMARDs or iJAK, complete withdrawal or reduction of GC dose was achieved in less than half (45.6%) of patients after 6 months.

Objective: The recommended dose of a rituximab course for the treatment of Rheumatoid Arthritis (RA) consists of two infusions of 1000 mg with a 2-week interval. Evidence is growing that a lower dose could be as effective. We aimed to investigate patients' and rheumatologists' perceptions on dose reduction of rituximab., Methods: Patients with RA treated with rituximab, and rheumatologists were invited for a qualitative study via individual semi-structured interviews. Participants were recruited based on purposive sampling to ensure diversity. Interviews were analysed according to the principles of grounded theory and the constant comparative method., Results: Sixteen patients and 13 rheumatologists were interviewed. Patients and rheumatologists perceived the benefits of rituximab dose reduction for reasons of safety and societal costs. Furthermore, available evidence for the effectiveness of lower doses was mentioned as an argument in favour, in addition to the possibility to tailor the dose based on the patients' clinical manifestations. However, patients and rheumatologists had concerns about the potential loss of effectiveness and quality of life. Moreover, some rheumatologists felt uncomfortable with dose reduction due to insufficient experience with rituximab in general. Patients and rheumatologists emphasised the importance of shared decision-making, underscoring the pivotal role of physicians in this process by explaining the reasoning behind dose reduction., Conclusion: Although some concerns on effectiveness were perceived, both patients and rheumatologists saw potential benefits of dose reduction in terms of safety, societal costs, and application of a personalised approach. As a result, most rheumatologists and patients showed a willingness to consider dose reduction strategies., (© 2024 John Wiley & Sons Ltd.)

We propose a sitting position that achieves both high image quality and a reduced radiation dose in elbow joint imaging by area detector computed tomography (ADCT), and we compared it with the 'superman' and supine positions. The volumetric CT dose index (CTDIvol) for the sitting, superman, and supine positions were 2.7, 8.0, and 20.0 mGy and the dose length products (DLPs) were 43.4, 204.7, and 584.8 mGy • cm, respectively. In the task-based transfer function (TTF), the highest value was obtained for the sitting position in both bone and soft tissue images. The noise power spectrum (NPS) of bone images showed that the superman position had the lowest value up to approx. 1.1 cycles/mm or lower, whereas the sitting position had the lowest value when the NPS was greater than approx. 1.1 cycles/mm. The overall image quality in an observer study resulted in the following median Likert scores for Readers 1 and 2: 5.0 and 5.0 for the sitting position, 4.0 and 3.5 for the superman position, and 4.0 and 2.0 for the supine position. These results indicate that our proposed sitting position with ADCT of the elbow joint can provide superior image quality and allow lower radiation doses compared to the superman and supine positions., Competing Interests: No potential conflict of interest relevant to this article was reported.

Osimertinib is used as the first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, early dose reduction is often required due to adverse events (AEs). This study aimed to evaluate the effect of early dose reduction of osimertinib on efficacy and safety. This was a retrospective study including patients with EGFR-mutated NSCLC who were started on osimertinib as the first-line therapy between August 2018 and December 2021. Patients whose doses were reduced to less than 80 mg/day within 6 months of osimertinib initiation or started at 40 mg/day were defined as the dose reduction group. The primary endpoint was progression-free survival (PFS). Factors affecting PFS were explored using the Cox proportional hazards model. A total of 85 patients were included in this study. No significant differences in patient characteristics were observed between the dose reduction (n = 25) and standard dose groups (n = 60). The median PFS in the dose reduction group was significantly prolonged compared with that in the standard dose group (26.0 months vs. 12.0 months, p = 0.03). Multivariable analysis of 84 patients, excluding a patient with unknown brain metastasis, revealed that EGFR exon 21 L858R mutation, malignant pleural effusion or pleural metastasis, liver metastasis, and dose reduction within 6 months were independent factors affecting PFS. Early dose reduction of osimertinib is an effective therapeutic strategy for prolonging PFS in patients with EGFR-mutated NSCLC., (© 2024. The Author(s).)

Background and Aim: As one of the second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors, afatinib brings survival benefits to patients with common and rare EGFR mutations. This study aimed to compare the effectiveness and safety of 30 and 40 mg of afatinib in patients with non–small cell lung cancer (NSCLC) using qualitative and quantitative analysis methods so as to provide reference for clinical medication. Methods: The PubMed, Embase, ClinicalTrials.gov, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were thoroughly searched from inception to February 26, 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality. RevMan and Stata 15.0 were used for meta-analysis. Results: Twelve cohort studies including 1290 patients for final analysis were selected; of which, 1129 patients were analyzed to measure the effectiveness outcomes and 470 patients were analyzed for safety outcomes. In patients with non-brain metastasis, the progression-free survival of the first- or second-line treatment with reduced-dose afatinib was equivalent to the conventional dose. In terms of safety, the reduced dose could significantly lower the incidence of severe diarrhea and severe rash, but not the total incidence of diarrhea, rash, and all levels of paronychia. Conclusions: The incidence of common serious adverse reactions was significantly lower with 30 mg of afatinib than with 40 mg of afatinib in patients with NSCLC. The effectiveness appeared to be similar to that in patients with non-brain metastasis. This study provides a reference for clinical dose reduction of afatinib. Systematic Review Registration: [PROSPERO], identifier [CRD42021238043] [ABSTRACT FROM AUTHOR]

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is currently the standard second-line treatment for patients with pancreatic ductal adenocarcinoma (PDAC) after previous failed gemcitabine-based therapy. This population-based study aimed to evaluate the efficacy and safety of nal-IRI + 5-FU/LV and the association of pre-emptive nal-IRI dosing with treatment outcomes in patients with PDAC. Methods: We retrospectively enrolled a total of 667 consecutive patients with PDAC who received nal-IRI plus 5-FU/LV treatment between August 2018 and November 2020 at 9 medical centers in Taiwan. Patients were allocated into groups according to pre-emptive nal-IRI dosing (⩾75%, 50–74%, <50%) for comparison of treatment efficacy and safety. Results: The median overall survival (OS) and time to treatment failure (TTF) were 5.9 months [95% confidence interval (CI), 5.3–6.5] and 2.8 months (95% CI, 2.6–3.0), respectively. The median OS was 6.5 months (95% CI, 5.7–6.7), 5.0 months (95% CI, 3.4–6.5), and 4.1 months (95% CI, 2.7–5.6), respectively, among the ⩾75%, 50–74%, and <50% pre-emptive nal-IRI dosing groups, whereas the median TTF of the three groups was 3.0 months (95% CI, 2.6–3.4), 2.6 months (95% CI, 2.3–2.9), and 1.9 months (95% CI, 1.6–2.2), respectively. Pre-emptive nal-IRI dosing <50% was an independent negative prognostic factor for OS and TTF in multivariate analyses. The most common severe adverse events were neutropenia (22.9%), anemia (21.1%), and hypokalemia (15.4%). Patients in the <50% pre-emptive nal-IRI dosing group had a significantly lower incidence of neutropenia and non-neutropenic infection than those in the other groups. Conclusion: Our results support the use of nal-IRI + 5-FU/LV as standard clinical practice for treating patients with PDAC based on this large population-based study. Our findings encourage physicians to provide adequate doses of nal-IRI in order to achieve better outcomes without compromising safety profiles. [ABSTRACT FROM AUTHOR]

Background: The whole-body low-dose CT (WBLDCT) is the first-choice imaging technique in patients with suspected plasma cell disorder to assess the presence of osteolytic lesions. We investigated the performances of an optimized protocol, evaluating diagnostic accuracy and effective patient dose reduction using a latest generation scanner. Methods and Materials: Retrospective study on 212 patients with plasma cell disorders performed on a 256-row CT scanner. First, WBLDCT examinations were performed using a reference protocol with acquisition parameters obtained from literature. A phantom study was performed for protocol optimization for subsequent exams to minimize dose while maintaining optimal diagnostic accuracy. Images were analyzed by three readers to evaluate image quality and to detect lesions. Effective doses (E) were evaluated for each patient considering the patient dimensions and the tube current modulation. Results: A similar, very good image quality was observed for both protocols by all readers with a good agreement at repeated measures ANOVA test (p>0.05). An excellent inter-rater agreement for lesion detection was achieved obtaining high values of Fleiss' kappa for all the districts considered (p<0.001). The optimized protocol resulted in a 56% reduction of median DLP (151) mGycm, interquartile range (IQR) 128–188 mGycm vs. 345 mGycm, IQR 302–408 mGycm), of 60% of CTDIvol (2.2 mGy, IQR 1.9–2.7 mGy vs. 0.9 mGy, IQR 0.8–1.2 mGy). The median E value was about 2.6 mSv (IQR 1.7–3.5 mSv) for standard protocol and about 1.5 mSv (IQR 1.4–1.7 mSv) for the optimized one. Dose reduction was statistically significant with p<0.001. Conclusions: Protocol optimization makes ultra-low-dose WBLDCT feasible on latest generation CT scanners for patients with plasma cell disorders with effective doses inferior to conventional skeletal survey while maintaining excellent image quality and diagnostic accuracy. Dose reduction is crucial in such patients, as they are likely to undergo multiple whole-body CT scans during follow-up. [ABSTRACT FROM AUTHOR]

Objective: Ultra-low radiation dose computed tomography (CT) abdominal tomography was introduced in our institution in 2016 to replace standard abdominal radiography in the investigation of emergency department patients. This project aims to ascertain whether investigation of emergency department patients using ultra-low radiation dose CT abdominal tomography complies with original indication guidelines and/or if there has been any "indication creep" 3 years after inception. Methods: Retrospective, quality assurance project with research ethics waiver. A review of 200 consecutive patients investigated with CT abdominal tomography between February and May 2017 was performed. This was compared with 200 consecutive patients investigated between February and May 2019. Data analyzed included patient demographics, indication for scan, as well as scan and patient outcomes. Results: In the 2017 group, 29/200 scans were noncompliant with approved indication guidelines. In the 2019 group, 30/200 scans were also noncompliant. There was no statistically significant difference between groups (P <.05) regarding the use of approved indications. Forty of 200 scans performed in 2017 revealed additional findings which are not specifically addressed on the reporting template. Forty-one of 200 scans in 2019 revealed these findings. Conclusions: There has been no "indication creep" for CT abdominal tomography over time. [ABSTRACT FROM AUTHOR]

Purpose To determine whether radiologic technologists are manipulating projections to lower patient dose in routine pediatric radiography examinations. Methods Using a descriptive survey approach, members from the American Society of Radiologic Technologists with a primary registration in radiography were randomly selected and invited to share their experiences using alternative projections during routine pediatric radiography examinations. Results For this study, 404 completed responses were analyzed. More than half of the participants (67.6%) strongly agreed or somewhat agreed that the use of alternative projections can reduce pediatric dose during routine radiography examinations, and more than half (61.3%) strongly agreed, agreed, or somewhat agreed that the use of alternative projections is beneficial for dose reduction. Incidentally, the most common response from participants regarding their use of alternative projections during routine pediatric radiography examinations was occasionally or sometimes. Nearly three-fourths of the participants strongly agreed that radiation protection guidelines are important to follow during routine pediatric radiography examinations. Although many radiologic technologists in this sample felt proficient using alternative projections during pediatric procedures, they also believed additional training in such methods would be beneficial. Discussion Most institutions have imaging protocols in place; however, the use of alternative methods of projection during routine pediatric radiography examinations might heighten current radiation protection guidelines, leading to protocol changes to reduce dose and improve the overall wellbeing of pediatric patients. Furthermore, recent recommendations in the field of medical imaging regarding patient shielding practices might deem positioning to be a more important method for dose reduction. Consultations from radiologists might be necessary to ensure that image quality is sufficient and diagnostic detail is not compromised. Additional training specific to using alternative projections during routine pediatric radiography examinations also might be warranted. Conclusion Current practices do not suggest alternative methods of projection are applied regularly during routine pediatric radiography examinations. Considerations should be made to allow technologists to manipulate projections when permitted. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease for which biologics are effective treatments. Dose reduction (DR) of the first generation biologics seems a promising way for more efficient use of expensive biologics. A substantial part of patients on tumor necrosis factor (TNF)-alfa inhibitors and ustekinumab could successfully lower their dose, after following a tightly controlled DR strategy. The objective of this study is to assess whether controlled DR of interleukin (IL)-17 and IL-23 inhibitors in psoriasis patients with low disease activity is non-inferior (NI) to usual care (UC).Methods: This is an international, prospective, multicenter, pragmatic, randomized, non-inferiority trial. A total of 244 patients with stable low disease activity (Psoriasis Area and Severity Index (PASI) ≤ 5) for at least 6 months and using secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, or tildrakizumab in the standard dose, together with stable low disease activity, defined as a PASI ≤ 5 and Dermatology Life Quality Index (DLQI) ≤ 5 at the moment of inclusion, will be randomized 2:1 to DR or UC. In the DR group, dosing intervals will be prolonged stepwise to achieve 66% and 50% of the original dose. Disease activity is monitored every 3 months by PASI and DLQI. In case of disease flare (i.e., PASI and/or DLQI increase), treatment is adjusted to the previous effective dose. The primary outcome is the incidence proportion of persistent flares (PASI > 5 for ≥ 3 months), which will be compared between arms. Secondary outcomes include proportion of patients with successful DR, (course of) PASI and DLQI, serious adverse events (SAEs), health-related quality of life, costs, and pharmacokinetic profile. Outcomes of DR will be compared to UC.Discussion: With this study, we aim to assess whether DR of IL-17 and IL-23 inhibiting biologics can be achieved for psoriasis patients with low disease activity, without losing disease control. Reducing the dose may lead to more efficient use of biologics.Trial Registration: ClinicalTrials.gov NCT04340076 . Registered on April 9 2020. [ABSTRACT FROM AUTHOR]

BackgroundThe whole-body low-dose CT (WBLDCT) is the first-choice imaging technique in patients with suspected plasma cell disorder to assess the presence of osteolytic lesions. We investigated the performances of an optimized protocol, evaluating diagnostic accuracy and effective patient dose reduction using a latest generation scanner.Methods and MaterialsRetrospective study on 212 patients with plasma cell disorders performed on a 256-row CT scanner. First, WBLDCT examinations were performed using a reference protocol with acquisition parameters obtained from literature. A phantom study was performed for protocol optimization for subsequent exams to minimize dose while maintaining optimal diagnostic accuracy. Images were analyzed by three readers to evaluate image quality and to detect lesions. Effective doses (E) were evaluated for each patient considering the patient dimensions and the tube current modulation.ResultsA similar, very good image quality was observed for both protocols by all readers with a good agreement at repeated measures ANOVA test (p>0.05). An excellent inter-rater agreement for lesion detection was achieved obtaining high values of Fleiss’ kappa for all the districts considered (p

Background and Aim: As one of the second-generation epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors, afatinib brings survival benefits to patients with common and rare EGFR mutations. This study aimed to compare the effectiveness and safety of 30 and 40 mg of afatinib in patients with non–small cell lung cancer (NSCLC) using qualitative and quantitative analysis methods so as to provide reference for clinical medication.Methods: The PubMed, Embase, ClinicalTrials.gov, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were thoroughly searched from inception to February 26, 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality. RevMan and Stata 15.0 were used for meta-analysis.Results: Twelve cohort studies including 1290 patients for final analysis were selected; of which, 1129 patients were analyzed to measure the effectiveness outcomes and 470 patients were analyzed for safety outcomes. In patients with non-brain metastasis, the progression-free survival of the first- or second-line treatment with reduced-dose afatinib was equivalent to the conventional dose. In terms of safety, the reduced dose could significantly lower the incidence of severe diarrhea and severe rash, but not the total incidence of diarrhea, rash, and all levels of paronychia.Conclusions: The incidence of common serious adverse reactions was significantly lower with 30 mg of afatinib than with 40 mg of afatinib in patients with NSCLC. The effectiveness appeared to be similar to that in patients with non-brain metastasis. This study provides a reference for clinical dose reduction of afatinib.Systematic Review Registration: [PROSPERO], identifier [CRD42021238043]

Purpose: The study aimed to design and validate computational phantoms (MIRD) using the MCNPX code to assess the impact of shielding on organ doses.Method: To validate the optimized phantom, the obtained results were compared with experimental results. The validation of the optimized MIRD phantom was provided by using the results of a previous anthropomorphic phantom study. MIRD phantom was designed by considering the parameters used in the anthropomorphic phantom study. A test simulation was performed to compare the dose reduction percentages (%) between the experimental anthropomorphic phantom study and the MCNPX-MIRD phantom. The simulation was performed twice, with and without shielding materials, using the same number and locations of the detector.Results: The absorbed dose amounts were directly extracted from the required organ and tissue cell parts of output files. Dose reduction percentages between the simulation with shielding and simulation without shielding were compared. The highest dose reduction was noted in the thymus (95%) and breasts (88%). The obtained dose reduction percentages between the anthropomorphic phantom study and the MCNPX-MIRD phantom were highly consistent and correlated values with experimental anthropomorphic data. Both methods showed Relative Difference (%) ranges between 0.88 and 2.22. Moreover, the MCNPX-MIRD optimized phantom provides detailed dose analysis for target and non-target organs and can be used to assess the efficiency of shielding in radiological examination.Conclusion: Shielding breasts and eyes during cervical radiography reduced the radiation dose to many organs. The decision to not shield patients should be based on research evidence as this approach does not apply to all cases.

(1) Background: CT perfusion (CTP) is a fast, robust and widely available but dose-exposing imaging technique for infarct core and penumbra detection. Carotid CT angiography (CTA) can precede CTP in the stroke protocol. Temporal information of the bolus tracking series of CTA could allow for better timing and a decreased number of scans in CTP, resulting in less radiation exposure, if the shortening of CTP does not alter the calculated infarct core and penumbra or the resulting perfusion maps, which are essential for further treatment decisions. (2) Methods: 66 consecutive patients with ischemic stroke proven by follow-up imaging or endovascular intervention were included in this retrospective study approved by the local ethics committee. In each case, six simulated, stepwise shortened CTP examinations were compared with the original data regarding the perfusion maps, infarct core, penumbra and endovascular treatment decision. (3) Results: In simulated CTPs with 26, 28 and 30 scans, the infarct core, penumbra and PRR values were equivalent, and the resulting clinical decision was identical to the original CTP. (4) Conclusions: The temporal information of the bolus tracking series of the carotid CTA can allow for better timing and a lower radiation exposure by eliminating unnecessary scans in CTP.

The use of diagnostic radiology in pediatric patients has increased, and various positive effects have been reported, including methods to reduce radiation doses in children. Research has been conducted to preserve image quality while reducing exposure and doses in pediatric patients. This study aimed to measure four different filters to identify an optimized filter for pediatric patients. The experiment was conducted using four types of filters, including aluminum, copper, molybdenum, and tungsten. The optimal filter thickness was verified using a histogram to visually evaluate the spectrum by filter thickness, effective dose on a pediatric phantom, entrance skin dose, organ absorbed dose using the PC-based Monte Carlo (PCXMC) program version 2.0 simulation, figure of merit (FOM), and image quality. As a result of measuring the spectrum according to the tube voltage and the four types of filters, dose reduction and contrast improvement effects were obtained with a 0.05 mm tungsten filter. Additionally, effective entrance skin and organ absorbed dose decreased with the said filter. The aluminum, copper, and molybdenum filters demonstrated that the effective dose scarcely decreased even when the thickness was increased; meanwhile, the effective dose decreased when the tungsten filter was 0.05 mm. The FOM with a 0.05 mm tungsten increased by 91% in the lung field and 39% in the mediastinal field. The entrance skin and organ absorbed dose in pediatric patients can be reduced by removing low-energy photons that fail in image formation using a tungsten filter.

Background and AimsWeight gain is a major adverse effect of antipsychotic medication, negatively affecting physical and mental well-being. The objective of this study was to explore if dose reduction, discontinuation, switch to a partial agonist, or switch from polypharmacy to monotherapy will lead to weight loss.MethodsControlled and uncontrolled studies reporting the effects of discontinuation, dose reduction, switch to a partial agonist, or switch from polypharmacy to monotherapy on weight were included. Primary outcome was difference in weight compared to maintenance groups based on controlled studies. Secondary outcome was change in weight from initiation of one of the included interventions until follow-up in a pre-post analysis.ResultsWe identified 40 randomized controlled trials and 15 uncontrolled studies including 12,279 individuals. The effect of the interventions, i.e. dose reduction, drug discontinuation, or switch to a partial agonis, reduced the weight with 1.5 kg (95% CI −2.03 to −0.98; P < 0.001) compared to maintenance treatment. The weight change from pre to post was a reduction of 1.13 kg (95% CI −1.36 to −0.90; P < 0.001).ConclusionWe found a significant but small reduction in weight, suggesting that antipsychotic-induced weight gain can be reversed to some degree. Only a few studies were designed to address the question as primary outcome, which limits the generalizability of our findings.

Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements. [ABSTRACT FROM AUTHOR]

Purpose: Treatment for estrogen receptor positive (ER+), human epidermal receptor 2 negative (HER2−) metastatic breast cancer (MBC) has improved with the approval of CDK 4/6 inhibitors. Clinical trials with the CDK4/6 inhibitor ribociclib, suggest that 35% to 57.5% of the patients require a dose reduction during ribociclib treatment. Data on the possible consequences of dose reduction concerning efficacy is needed. Methods: A retrospective cohort study on patients with ER+ HER2− MBC from three Danish oncology departments. Data on tolerability and progression-free survival were collected from electronic health records. Results: One hundred and twenty-eight patients with ER+ HER2− MBC who initiated ribociclib treatment between 1st of January 2018 to 31st of March 2020 were included in our analysis. Of these patients, 48.4% required one or more dose reductions. Overall median PFS was 19.2 months (CI-95% 14.3-NR). Patients with one or more dose reductions did not have decreased median PFS (19.2 months, CI-95% 14.3-NR compared to 12.2 months, CI-95% 7.3-NR, p = 0.078). Frequency of adverse events were as previously reported, with grade III and IV neutropenia occurring in 45.3% and 7% of patients, respectively. Patients treated with fulvestrant versus an aromatase inhibitor and patients with lymph node involvement at baseline had lower odds of requiring a dose reduction (ORa = 0.30, CI-95% 0.12–0.73 & ORa = 0.41, CI-95% 0.18–0.89, respectively). Conclusion: Our results indicate that dose reduction of ribociclib is safe and do not compromise the efficacy of the treatment. Furthermore, the study supports translation of results from the MONALEESA trials to patients treated in real-world clinical settings. [ABSTRACT FROM AUTHOR]

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Thoracic endovascular aortic repair (TEVAR) is a life-saving therapy for type B aortic dissection (TBAD). However, surveillance computed tomography (CT) scans in post-TEVAR patients are associated with high radiation dose, thus resulting in potential risk of radiation-induced malignancy. In this study, we developed a patient-specific three-dimensional (3D) printed phantom with stent grafts in situ, then scanned the phantom with different CT protocols to determine the optimal scanning parameters for post-treatment patients. The CT scans were conducted with different kVp and pitch values (80, 100, 120 kVp and pitch of 1.2, 1.5, 2.0, 2.5), resulting in a total of 12 datasets. Signal-to-noise ratio (SNR) was measured to determine and compare the image quality between different datasets. Results showed no significant differences in SNR between different kVp when the pitch value was 1.2. At low pitch values, a decrease in kVp from 120 to 80 led to a significant effective dose reduction by more than 20%. SNR decreased by 30% when pitch was increased from 1.2 to 2.5 at 80 kVp, and 20% at 120 kVp. In contrast, there was only a 3.9% decrease in SNR when kVp was reduced from 120 to 80 at pitch 1.2, and 15.9% at pitch 2.5. High pitch with 100 kVp can effectively reduce the dose while maintaining image quality. [ABSTRACT FROM AUTHOR]

Background and Aims: Weight gain is a major adverse effect of antipsychotic medication, negatively affecting physical and mental well-being. The objective of this study was to explore if dose reduction, discontinuation, switch to a partial agonist, or switch from polypharmacy to monotherapy will lead to weight loss. Methods: Controlled and uncontrolled studies reporting the effects of discontinuation, dose reduction, switch to a partial agonist, or switch from polypharmacy to monotherapy on weight were included. Primary outcome was difference in weight compared to maintenance groups based on controlled studies. Secondary outcome was change in weight from initiation of one of the included interventions until follow-up in a pre-post analysis. Results: We identified 40 randomized controlled trials and 15 uncontrolled studies including 12,279 individuals. The effect of the interventions, i.e. dose reduction, drug discontinuation, or switch to a partial agonis, reduced the weight with 1.5 kg (95% CI −2.03 to −0.98; P < 0.001) compared to maintenance treatment. The weight change from pre to post was a reduction of 1.13 kg (95% CI −1.36 to −0.90; P < 0.001). Conclusion: We found a significant but small reduction in weight, suggesting that antipsychotic-induced weight gain can be reversed to some degree. Only a few studies were designed to address the question as primary outcome, which limits the generalizability of our findings. [ABSTRACT FROM AUTHOR]

Purpose: Peptide-based prostate-specific membrane antigen (PSMA) targeted radionuclide therapy (TRT) agent [177Lu]-PSMA-617 has emerged as leading TRT candidate for treatment of castration-resistant prostate cancer (mCRPC). [177Lu]-PSMA-617 and other small molecule–based PSMA ligands have shown efficacy in reducing the tumor burden in mCRPC patients but irradiation to the salivary gland and kidneys is a concern and dose-limiting factor. Therefore, methods to reduce non-target organ toxicity are needed to safely treat patients and preserve their quality of life. Herein, we report that addition of cold PSMA ligand PSMA-11 can aid in reducing the uptake of [177Lu]-PSMA-617 in the salivary glands and kidneys. Methods: Groups of athymic nude mice (n = 4) bearing PC3-PIP (PSMA+) tumor xenografts were administered with [177Lu]-PSMA-617 along with 0, 5, 100, 500, 1000, and 2000 pmoles of PSMA-11 and biodistribution studies were performed at 1 h. Results: Biodistribution studies at 1 h post-administration revealed that [177Lu]-PSMA-617 uptake in PC3-PIP tumors was 21.71 ± 6.13, 18.7 ± 2.03, 26.44 ± 2.94, 16.21 ± 3.5, 13.52 ± 3.68, and 12.03 ± 1.96 %ID/g when 0, 5, 100, 500, 1000, and 2000 pmoles of PSMA-11 were added, respectively. Corresponding uptake values in kidney were 123.14 ± 52.52, 132.31 ± 47.4, 84.29 ± 78.25, 2.12 ± 1.88, 1.16 ± 0.36, and 0.64 ± 0.23 %ID/g, respectively. Corresponding salivary gland uptake values were 0.48 ± 0.11, 0.45 ± 0.15, 0.38 ± 0.3, 0.08 ± 0.03, 0.09 ± 0.07, and 0.05 ± 0.02 % ID/g, respectively. Conclusion: The uptake of [177Lu]-PSMA-617 in the salivary gland and kidney can be substantially reduced without significantly impacting tumor uptake by adding cold PSMA-11. [ABSTRACT FROM AUTHOR]

Dose reduction of apixaban is applied in atrial fibrillation (AF) patients fulfilling ≥ 2 of the following criteria: (1) age ≥ 80 years, (2) body weight ≤ 60 kg and (3) serum creatinine ≥ 1.5 mg/dL. However, the clinical significance of each criterion remains unclear. The J-ELD AF Registry is a prospective observational study of elderly (≥ 75 years) Japanese AF patients receiving on-label dose of apixaban. In patients receiving the standard dose (5 mg bid, n = 1243), the incidence rates (% per patient-year) of stroke or systemic embolism in those fulfilling none [n = 516] or one of the above criteria (1) [n = 328], (2) [n = 378] and (3) [n = 21] were 1.24, 2.32, 1.41 and 4.93 (log-rank P = 0.422), respectively, and those of bleeding requiring hospitalization were 1.03, 0.99, 1.98 and 4.93 (P = 0.318), respectively. In patients receiving a reduced dose (2.5 mg bid, n = 1,515), the incidences of stroke or systemic embolism in those fulfilling (1)/(2) [n = 1,331], (1)/(3) [n = 65], (2)/(3) [n = 23] and all three criteria [n = 96] were 1.38, 1.64, 4.67 and 3.51 (P = 0.295), respectively, and those of bleeding requiring hospitalization were 2.04, 1.64, 0.00 and 4.71 (P = 0.318), respectively. Univariate analysis demonstrated that the types or combinations of each criterion was not significantly associated with the incidence of thromboembolic or bleeding events. The types or combinations of the three apixaban dose reduction criteria did not have significant impact on effectiveness and safety in Japanese elderly AF patients receiving on-label dose of apixaban, although the impact of the creatinine criterion remains uncertain due to the few number of the patients. [ABSTRACT FROM AUTHOR]

Purpose: In this work, we explore the potential of region‐of‐interest (ROI) imaging in x‐ray computed tomography (CT). Using two dynamic beam attenuator (DBA) concepts for fluence field modulation (FFM) previously developed, we investigate and evaluate the potential dose savings in comparison with current FFM technology. Methods: ROI imaging is a special application of FFM where the bulk of x‐ray radiation is propagated toward a certain anatomical target (ROI), specified by the imaging task, while the surrounding tissue is spared from radiation. We introduce a criterion suitable to quantitatively describe the balance between image quality inside an ROI and total radiation dose with respect to a given ROI imaging task. It accounts for the mean image variance at the ROI and the effective patient dose calculated from Monte Carlo simulations. The criterion is further used to compile task‐specific DBA trajectories determining the primary x‐ray fluence, and eventually used for comparing different FFM techniques, namely the sheet‐based dynamic beam attenuator (sbDBA), the z‐aligned sbDBA (z‐sbDBA), and an adjustable static operation mode of the z‐sbDBA. Furthermore, two static bowtie filters and the influence of tube current modulation (TCM) are included in the comparison. Results: Our findings demonstrate by simulations that the presented trajectory optimization method determines reasonable DBA trajectories. The influence of TCM is strongly depending on the imaging task. The narrow bowtie filter allows for dose reductions of about 10% compared to the regular bowtie filter in the considered ROI imaging tasks. The DBAs are shown to realize substantially larger dose reductions. In our cardiac imaging scenario, the DBAs can reduce the effective dose by about 30% (z‐sbDBA) or 60% (sbDBA). We can further verify that the noise characteristics are not adversely affected by the DBAs. Conclusion: Our research demonstrates that ROI imaging using the presented DBA concepts is a promising technique toward a more patient‐ and task‐specific CT imaging requiring lower radiation dose. Both the sbDBA and the z‐sbDBA are potential technical solutions for realizing ROI imaging in x‐ray CT. [ABSTRACT FROM AUTHOR]

The US veteran population has a high proportion of chronic lymphocytic leukemia (CLL) risk factors. Using the Veterans Health Administration (VHA) population, we conducted a retrospective chart review of 1205 CLL patients who initiated treatment with a novel oral agent. For 1L ibrutinib, 33% (n = 107) discontinued therapy during the study, of which 64% discontinued due to adverse events (AEs). For relapsed/refractory (R/R) ibrutinib, 35% (n = 262) discontinued therapy, of which 63% discontinued due to AEs. For R/R venetoclax, 31% (n = 27) discontinued therapy, of which 41% were due to AEs. For idelalisib, 84% (n = 41) discontinued therapy, of which 54% were due to AEs. This real-world study suggests that AEs play an important role in dose reductions and discontinuations; however, physician inexperience in using these drugs when they were first introduced could be part of what is leading to these negative outcomes. [ABSTRACT FROM AUTHOR]