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PURPOSE: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben. METHODS: Cognitively impaired and unimpaired individuals (N = 250, 36% Aβ-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90-110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aβ-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aβ- and Aβ + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated. RESULTS: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were  80% for both tracers. CONCLUSION: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.

Background Purpose Methods Results Conclusion Breathing signal‐guided 4D CT sequence scanning such as the intelligent 4D CT (i4DCT) approach reduces imaging artifacts compared to conventional 4D CT. By design, i4DCT captures entire breathing cycles during beam‐on periods, leading to redundant projection data and increased radiation exposure to patients exhibiting prolonged exhalation phases. A recently proposed breathing‐guided dose modulation (DM) algorithm promises to lower the imaging dose by temporarily reducing the CT tube current, but the impact on image reconstruction and the resulting images have not been investigated.We evaluate the impact of breathing signal‐guided DM on 4D CT image reconstruction and corresponding images.This study is designed as a comparative and retrospective analysis based on 104 4D CT datasets. Each dataset underwent retrospective reconstruction twice: (a) utilizing the acquired clinical projection data for reconstruction, which yields reference image data, and (b) excluding projections acquired during potential DM phases from image reconstruction, resulting in DM‐affected image data. Resulting images underwent automatic organ segmentation (lung/liver). (Dis)Similarity of reference and DM‐affected images were quantified by the Dice coefficient of the entire organ masks and the organ overlaps within the DM‐affected slices. Further, for lung cases, (a) and (b) were deformably registered and median magnitudes of the obtained displacement field were computed. Eventually, for 17 lung cases, gross tumor volumes (GTV) were recontoured on both (a) and (b). Target volume similarity was quantified by the Hausdorff distance.DM resulted in a median imaging dose reduction of 15.4% (interquartile range [IQR]: 11.3%–19.9%) for the present patient cohort. Dice coefficients for lung (n=73$n=73$) and liver (n=31$n=31$) patients were consistently high for both the entire organs and the DM‐affected slices (IQR lung: 0.985/0.982$0.985/0.982$ [entire lung/DM‐affected slices only] to 0.992/0.989$0.992/0.989$; IQR liver: 0.977/0.972$0.977/0.972$ to 0.986/0.986$0.986/0.986$), demonstrating that DM did not cause organ distortions or alterations. Median displacements for DM‐affected to reference image registration varied; however, only two out of 73 cases exhibited a median displacement larger than one isotropic 1 mm3${\rm mm}^3$ voxel size. The impact on GTV definition for the end‐exhalation phase was also minor (median Hausdorff distance: 0.38 mm, IQR: 0.15–0.46 mm).This study demonstrates that breathing signal‐guided DM has a minimal impact on image reconstruction and image appearance while improving patient safety by reducing dose exposure. [ABSTRACT FROM AUTHOR]

ABSTRACT Neutropenia is a common chemotherapy‐associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 109/L or pretreatment ANC <1.5 × 109/L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%–69%) evaluable NEs, a nadir ANC of ≥0.75 × 109/L and pretreatment ANC of ≥1.5 × 109/L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%–48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%–70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%–69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%–27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%–25.8%) vincristine DRs. Seventy‐three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11). [ABSTRACT FROM AUTHOR]

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 (p0.001), fatigue (NRS) from 6.7±2.3 to 5.2±2.1 (p0.001), and functional impairment (NRS) from 5.4±2.1 to 3.9±2.0 (p0.001). 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. Deep learning reconstruction (DLR) algorithms exhibit object-dependent resolution and noise performance. Thus, traditional geometric CT phantoms cannot fully capture the clinical imaging performance of DLR. This study uses a patient-derived 3D-printed PixelPrint lung phantom to evaluate a commercial DLR algorithm across a wide range of radiation dose levels. Method. The lung phantom used in this study is based on a patient chest CT scan containing ground glass opacities and was fabricated using PixelPrint 3D-printing technology. The phantom was placed inside two different size extension rings to mimic a small- and medium-sized patient and was scanned on a conventional CT scanner at exposures between 0.5 and 20 mGy. Each scan was reconstructed using filtered back projection (FBP), iterative reconstruction, and DLR at five levels of denoising. Image noise, contrast to noise ratio (CNR), root mean squared error, structural similarity index (SSIM), and multi-scale SSIM (MS SSIM) were calculated for each image. Results. DLR demonstrated superior performance compared to FBP and iterative reconstruction for all measured metrics in both phantom sizes, with better performance for more aggressive denoising levels. DLR was estimated to reduce dose by 25%–83% in the small phantom and by 50%–83% in the medium phantom without decreasing image quality for any of the metrics measured in this study. These dose reduction estimates are more conservative compared to the estimates obtained when only considering noise and CNR. Conclusion. DLR has the capability of producing diagnostic image quality at up to 83% lower radiation dose, which can improve the clinical utility and viability of lower dose CT scans. Furthermore, the PixelPrint phantom used in this study offers an improved testing environment with more realistic tissue structures compared to traditional CT phantoms, allowing for structure-based image quality evaluation beyond noise and contrast-based assessments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin's lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions—Crohn's disease, vitiligo, type I diabetes, and minimal change disease—undergoing BV therapy for Hodgkin's lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Aim: Real-world treatment patterns in tenosynovial giant cell tumor (TGCT) patients remain unknown. Pexidartinib is the only US FDA-approved treatment for TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Objective: To characterize drug utilization and treatment patterns in TGCT patients. Methods: In a retrospective observational study using IQVIA's linked prescription and medical claims databases (2018–2021), TGCT patients were stratified by their earliest systemic therapy claim (pexidartinib [N = 82] or non-FDA-approved systemic therapy [N = 263]). Results: TGCT patients treated with pexidartinib versus non-FDA-approved systemic therapies were predominantly female (61 vs 50.6%) and their median age was 47 and 54 years, respectively. Pexidartinib-treated patients had the highest 12-month probability of remaining on treatment (54%); 34.1% of pexidartinib users had dose reduction after their first claim. Conclusion: This study provides new insights into the unmet need, utilization and treatment patterns of systemic therapies for the treatment of TGCT patients. Plain language summary Treatment patterns in patients with tenosynovial giant cell tumors in the USA This database study is the first investigation of how drugs are used to treat patients with tenosynovial giant cell tumor (TGCT) in the real world. We researched adult TGCT patients from IQVIA's prescription and medical claims databases who started treatment with pexidartinib (N = 82) or other non-US FDA-approved systemic therapies (N = 263). The patients included in this analysis were mostly women (61.0 and 50.6%) and their median age was 47 and 54 years for pexidartinib and other non-FDA-approved systemic therapies, respectively. The patients treated with pexidartinib were most likely to remain on treatment (54.0%) at the end of the first year. Most patients (79.3%) started pexidartinib treatment at a total daily dose of 800 mg/day, as per the product label. Only 34.1% of patients had reduced medication dose during follow-up. Of note, this study found that TGCT patients were treated with other systemic therapies which remain unproven to be safe and effective in medical studies of TGCT. Given the unmet need, and with pexidartinib being the only approved systemic treatment in USA, there is an opportunity for the larger population of adult TGCT patients to benefit from its use. Further research is needed to identify barriers for access to pexidartinib and treatment of TGCT patients. Summary points Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm affecting the synovial membrane lining joints, bursae and tendon sheaths. Pexidartinib is currently the only systemic treatment approved by the US FDA for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Other systemic therapies have been investigated in clinical studies of TGCT patients, none of them have been approved by the FDA for the treatment of TGCT specifically. Using a real-world claims database, this study characterized TGCT patients newly treated with pexidartinib or other unapproved systemic treatments and described their treatment patterns, including treatment duration and dosing. In this study, we found that although the median duration of pexidartinib treatment was not reached, patients on pexidartinib had the highest 12-month probability of remaining on treatment. Dose reductions after the first medication claim were commonly observed in the pexidartinib cohort (34.1%) and some patients (9.8%) had evidence of dose increase. Dose levels of the non-FDA-approved systemic therapies were consistent with the recommended dosages for other indications, as per their label, none of which were TGCT. As expected, 63.6–82.9% of TGCT patients treated with non-FDA-approved systemic therapies discontinued treatment at 12 months. This study provided novel insights into how systemic therapies for TGCT are used in real-world clinical practice, where surgery has been the standard of care. Given the large unmet need for the treatment of TGCT patients, and as pexidartinib is the only regulatory-approved systemic treatment, there is opportunity for its wider use in this patient population. [ABSTRACT FROM AUTHOR]

Background/Aim: Colorectal cancer (CRC) is the third-leading cause of death in the world. Although the prognosis has improved due to improvement of chemotherapy, metastatic CRC is still a recalcitrant disease, with a 5-year survival of only 13%. Irinotecan (IRN) is used as first-line chemotherapy for patients with unresectable CRC. However, there are severe side effects, such as neutropenia and diarrhea, which are dose-limiting. We have previously shown that methionine restriction (MR), effected by recombinant methioninase (rMETase), lowered the effective dose of IRN of colon-cancer cells in vitro. The aim of the present study was to evaluate the efficacy of the combination of low-dose IRN and MR on colon-cancer in nude mice. Materials and Methods: HCT-116 colon-cancer cells were cultured and subcutaneously injected into the flank of nude mice. After the tumor size reached approximately 100 mm³, 18 mice were randomized into three groups; Group 1: untreated control on a normal diet; Group 2: high-dose IRN on a normal diet (2 mg/kg, i.p.); Group 3: low-dose IRN (1 mg/kg i.p.) on MR effected by a methionine-depleted diet. Results: There was no significant difference between the control mice and the mice treated with high-dose IRN, without MR. However, low-dose IRN combined with MR was significantly more effective than the control and arrested colon-cancer growth (p=0.03). Body weight loss was reversible in the mice treated by low-dose IRN combined with MR. Conclusion: The combination of lowdose IRN and MR acted synergistically in arresting HCT-116 colon-cancer grown in nude mice. The present study indicates the MR has the potential to reduce the effective dose of IRN in the clinic. [ABSTRACT FROM AUTHOR]

Abstract Background 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient’s feeling of autonomy and psychiatric rehabilitation. Case presentation We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down. Conclusions Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse. Impact and implications Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery.

Abstract Shading, the predominant condition in most of the eucalyptus cultivation cycle, causes changes in the morphological and physiological weed's characteristics, which can alter their responses to glyphosate and carfentrazone-ethyl, important herbicides for the crop. The objective was to evaluate the influence of light on the efficiency of glyphosate and carfentrazone-ethyl used alone and in a mixture in Digitaria insularis control, a priority pest in the crop. The experiment was carried out in a 3 × 6 factorial scheme. The first factor corresponded to 3 cultivation environments (full sunlight, 45 and 63% shading) and the second factor to doses of glyphosate and carfentrazone-ethyl applied isolated (1920 and 40 g ai ha−1) and mixed (1536 + 8; 1152 + 16; 768 + 24 and 384 + 32 g ai ha−1), respectively. Shading increased D. insularis sensitivity to glyphosate alone and in a mixture with carfentrazone-ethyl. In shading, the glyphosate application alone at a dose of 1920 g ha−1 and in a mixture with carfentrazone-ethyl at doses of 1536 + 8 and 1152 + 16 g ha−1 were efficient in D. insularis control. In the environment of 63% shading, the dose of 768 + 24 g ha−1 was also efficient in this species control. None of the doses were effective in controlling D. insularis in full sunlight. Isolated carfentrazone-ethyl was inefficient in controlling D. insularis, regardless of the growth environment. Shading increases the quantum yield of photosystem II and reduces the electron transport rate, photosynthetic rate, stomatal conductance, and transpiration rate of D. insularis. In shady environments, it is possible to control D. insularis with lower glyphosate doses, used alone and mixed with carfentrazone-ethyl.

Abstract Purpose Unenhanced abdominal CT constitutes the diagnostic standard of care in suspected urolithiasis. Aiming to identify potential for radiation dose reduction in this frequent imaging task, this experimental study compares the effect of spectral shaping and tube voltage modulation on image quality. Methods Using a third-generation dual-source CT, eight cadaveric specimens were scanned with varying tube voltage settings with and without tin filter application (Sn 150, Sn 100, 120, 100, and 80 kVp) at three dose levels (3 mGy: standard; 1 mGy: low; 0.5 mGy: ultralow). Image quality was assessed quantitatively by calculation of signal-to-noise ratios (SNR) for various tissues (spleen, kidney, trabecular bone, fat) and subjectively by three independent radiologists based on a seven-point rating scale (7 = excellent; 1 = very poor). Results Irrespective of dose level, Sn 100 kVp resulted in the highest SNR of all tube voltage settings. In direct comparison to Sn 150 kVp, superior SNR was ascertained for spleen (p ≤ 0.004) and kidney tissue (p ≤ 0.009). In ultralow-dose scans, subjective image quality of Sn 100 kVp (median score 3; interquartile range 3–3) was higher compared with conventional imaging at 120 kVp (2; 2–2), 100 kVp (1; 1–2), and 80 kVp (1; 1–1) (all p

IntroductionOur objective was to provide expert consensus recommendations to improve treatment tolerability through dose adjustments of concomitant antiseizure medications (ASMs) during addition of cenobamate to existing ASM therapy in adult patients with uncontrolled focal seizures.MethodsA panel of seven epileptologists experienced in the use of ASMs, including cenobamate, used a modified Delphi process to reach consensus. The panelists discussed tolerability issues with concomitant ASMs during cenobamate titration and practical strategies for dose adjustments that may prevent or mitigate adverse effects. The resulting recommendations consider concomitant ASM dose level and specify proactive (prior to report of an adverse effect) and reactive (in response to report of an adverse effect) dose adjustment suggestions based on concomitant ASM pharmacokinetic and pharmacodynamic interactions with cenobamate. Specific dose adjustment recommendations are provided.ResultsWe recommend proactively lowering the dose of clobazam, phenytoin, and phenobarbital due to their known drug-drug interactions with cenobamate, and lacosamide due to a pharmacodynamic interaction with cenobamate, to prevent adverse effects during cenobamate titration. Reactive lowering of a concomitant ASM dose is sufficient for other ASMs at standard dosing owing to quick resolution of adverse effects. For carbamazepine and lamotrigine doses exceeding the upper end of standard dosing (e.g., carbamazepine, greater than 1200 mg/day; lamotrigine, greater than 500 mg/day), we encourage consideration of proactive dose reduction at cenobamate 200 mg/day to prevent potential adverse effects. All dose reductions for adverse effects can be repeated every 2 weeks as dictated by the adverse effects. At cenobamate 200 mg/day, we recommend that patients be evaluated for marked improvement of seizures and further dose reductions be considered to reduce potentially unnecessary polypharmacy.ConclusionThe primary goal of the recommended dose reductions of concomitant ASMs is to prevent or resolve adverse effects, thereby allowing cenobamate to reach the optimal dose to achieve the maximal potential of improving seizure control.

Dose reduction (DR) of first-generation biologics for plaque psoriasis (TNF-alpha inhibitors (i) and interleukin (IL)-12/23i) has been described in a previous scoping review. The literature on the DR of the newest generation of biologics (IL-17/23i) was scarce. The current review provides a literature update on the previous scoping review on the DR of all biologics, including the newest generation, with a focus on the uptake and implementation of DR in practice. The current literature search on DR revealed 14 new articles in addition to those in the previous review. Four of the newly found articles tested DR strategies, mostly focusing on firstgeneration biologics; only guselkumab (IL-23i) was included in one study. The other 10 studies showed data on regaining response after failure of DR, safety, cost-effectiveness, and uptake and implementation, as well as information about IL-17/23i. The eligibility criteria to start DR included both absolute and relative Psoriasis Area and Severity Index (PASI) scores (PASI ≤3/≤5/PASI 75-100) and/or Dermatology Life Quality Index (DLQI) ≤3/≤5, or BSA ≤1/≤2, or Physician Global Assessment (PGA) ≤1/0-2 during a period ranging from 12 weeks to ≥1 year. Most studies used PASI ≤5 and/or DLQI ≤5 or PGA ≤1 for ≥6 months. DR strategies were mostly performed by stepwise interval prolongation in two steps (to 67% of the standard dose, followed by 50%). Some studies of IL-17/23i reduced the dose to ±25%. The tested DR strategies on stepwise or fixed DR on TNF-αi and IL-12/ 23i (three studies), as well as one "on-demand" dosing study on IL-23i guselkumab, were successful. In the case of relapse of DR on TNF-αi and IL-12/23i, clinical effectiveness was regained by retreatment with the standard dose. All studies showed substantial cost savings with the biologic DR of TNF-αi and IL-12/23i. The identified barriers against the implementation of DR were mainly a lack of guidelines and scientific evidence on effectiveness and safety, and a lack of time and (technical) support. The identified facilitators were mainly clear guidelines, feasible protocols, adequate education of patients and physicians, and cost reduction. In conclusion, DR seems promising, but a research gap still exists in randomized, prospective studies testing DR strategies, especially of IL-17/23i, hampering the completion of guidelines on DR. Taking into account the identified barriers and facilitators most likely results in a more successful implementation of biologic DR in practice. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone. Reducing the dose of first-generation antipsychotics (FGA) might also improve cognitive function. This study compared the cognitive effects in long-stay patients who were randomized to groups who underwent FGA dose reduction or switched to ziprasidone. Methods: High-dose FGA was reduced to an equivalent of 5 mg of haloperidol in 10 patients (FGA-DR-condition), and 13 patients switched to ziprasidone 80 mg b.i.d. (ZIPRA condition). Five domains of cognitive function were assessed before dose reduction or switching (T0) and after 1 year (T1). This study was approved by the ethics committee of the Open Ankh (CCMO number 338) and registered at the Netherlands Trial Register (code 5864). Results: Non-significant deterioration was seen in all cognitive domains studied in the FGA-DR condition, whereas there was a non-significant improvement in all cognitive domains in the ZIPRA condition. The most robust difference between conditions, in favor of ziprasidone, was in executive function. Conclusions: In patients with severe chronic schizophrenia, ziprasidone had a non-significant and very modest beneficial effect on cognitive function compared with FGA dose reduction. Larger trials are needed to further investigate this effect. [ABSTRACT FROM AUTHOR]

Introduction Biologic therapy is an effective treatment for inflammatory bowel disease [IBD]. However due to cost and safety concerns, dose de-escalation strategies after achieving remission have been suggested. Aim To critically review available data on dose de-escalation of biologics [or other advanced therapies] in IBD. We will focus on studies evaluating de-escalation to standard dosing in patients initially optimised, and also on studies assessing de-escalation from standard dosing. Methods A systematic bibliographic search was performed. Results The mean frequency of de-escalation after previous dose intensification [12 studies, 1,474 patients] was 34%. The corresponding frequency of de-escalation from standard dosing [five studies, 3,842 patients] was 4.2%. The relapse rate of IBD following anti-tumour necrosis factor [TNF] de-escalation to standard dosing in patients initially dose-escalated [10 studies, 301 patients] was 30%. The corresponding relapse rate following anti-TNF de-escalation from standard dosing [nine studies, 494 patients] was 38%. The risk of relapse was lower for patients in clinical, biologic, and endoscopic/radiological remission at the time of de-escalation. A role of anti-TNF therapeutic drug monitoring in the decision to dose de-escalate has been demonstrated. In patients relapsing after de-escalation, re-escalation is generally effective. De-escalation is not consistently associated with a better safety profile. The cost-effectiveness of the de-escalation strategy remains uncertain. Finally, there is not enough evidence to recommend dose de-escalation of biologics different from anti-TNFs or small molecules. Conclusions Any consideration for de-escalation of biologic therapy in IBD must be tailored, taking into account the risks and consequences of a flare and patients' preferences. [ABSTRACT FROM AUTHOR]

Background: 80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient's feeling of autonomy and psychiatric rehabilitation. Case presentation: We present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down. Conclusions: Reducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse. Impact and implications: Some patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery. [ABSTRACT FROM AUTHOR]

Objectives: To introduce an automated computational algorithm that estimates the global noise level across the whole imaging volume of PET datasets. Methods: [18F]FDG PET images of 38 patients were reconstructed with simulated decreasing acquisition times (15–120 s) resulting in increasing noise levels, and with block sequential regularized expectation maximization with beta values of 450 and 600 (Q.Clear 450 and 600). One reader performed manual volume-of-interest (VOI) based noise measurements in liver and lung parenchyma and two readers graded subjective image quality as sufficient or insufficient. An automated computational noise measurement algorithm was developed and deployed on the whole imaging volume of each reconstruction, delivering a single value representing the global image noise (Global Noise Index, GNI). Manual noise measurement values and subjective image quality gradings were compared with the GNI. Results: Irrespective of the absolute noise values, there was no significant difference between the GNI and manual liver measurements in terms of the distribution of noise values (p = 0.84 for Q.Clear 450, and p = 0.51 for Q.Clear 600). The GNI showed a fair to moderately strong correlation with manual noise measurements in liver parenchyma (r = 0.6 in Q.Clear 450, r = 0.54 in Q.Clear 600, all p < 0.001), and a fair correlation with manual noise measurements in lung parenchyma (r = 0.52 in Q.Clear 450, r = 0.33 in Q.Clear 600, all p < 0.001). Classification performance of the GNI for subjective image quality was AUC 0.898 for Q.Clear 450 and 0.919 for Q.Clear 600. Conclusion: An algorithm provides an accurate and meaningful estimation of the global noise level encountered in clinical PET imaging datasets. Clinical relevance statement: An automated computational approach that measures the global noise level of PET imaging datasets may facilitate quality standardization and benchmarking of clinical PET imaging within and across institutions. Key Points: • Noise is an important quantitative marker that strongly impacts image quality of PET images. • An automated computational noise measurement algorithm provides an accurate and meaningful estimation of the global noise level encountered in clinical PET imaging datasets. • An automated computational approach that measures the global noise level of PET imaging datasets may facilitate quality standardization and benchmarking as well as protocol harmonization. [ABSTRACT FROM AUTHOR]

Purpose: Unenhanced abdominal CT constitutes the diagnostic standard of care in suspected urolithiasis. Aiming to identify potential for radiation dose reduction in this frequent imaging task, this experimental study compares the effect of spectral shaping and tube voltage modulation on image quality. Methods: Using a third-generation dual-source CT, eight cadaveric specimens were scanned with varying tube voltage settings with and without tin filter application (Sn 150, Sn 100, 120, 100, and 80 kVp) at three dose levels (3 mGy: standard; 1 mGy: low; 0.5 mGy: ultralow). Image quality was assessed quantitatively by calculation of signal-to-noise ratios (SNR) for various tissues (spleen, kidney, trabecular bone, fat) and subjectively by three independent radiologists based on a seven-point rating scale (7 = excellent; 1 = very poor). Results: Irrespective of dose level, Sn 100 kVp resulted in the highest SNR of all tube voltage settings. In direct comparison to Sn 150 kVp, superior SNR was ascertained for spleen (p ≤ 0.004) and kidney tissue (p ≤ 0.009). In ultralow-dose scans, subjective image quality of Sn 100 kVp (median score 3; interquartile range 3–3) was higher compared with conventional imaging at 120 kVp (2; 2–2), 100 kVp (1; 1–2), and 80 kVp (1; 1–1) (all p < 0.001). Indicated by an intraclass correlation coefficient of 0.945 (95% confidence interval: 0.927–0.960), interrater reliability was excellent. Conclusions: In abdominal CT with maximised dose reduction, tin prefiltration at 100 kVp allows for superior image quality over Sn 150 kVp and conventional imaging without spectral shaping. [ABSTRACT FROM AUTHOR]

Shading, the predominant condition in most of the eucalyptus cultivation cycle, causes changes in the morphological and physiological weed's characteristics, which can alter their responses to glyphosate and carfentrazone-ethyl, important herbicides for the crop. The objective was to evaluate the influence of light on the efficiency of glyphosate and carfentrazone-ethyl used alone and in a mixture in Digitaria insularis control, a priority pest in the crop. The experiment was carried out in a 3 × 6 factorial scheme. The first factor corresponded to 3 cultivation environments (full sunlight, 45 and 63% shading) and the second factor to doses of glyphosate and carfentrazone-ethyl applied isolated (1920 and 40 g ai ha−1) and mixed (1536 + 8; 1152 + 16; 768 + 24 and 384 + 32 g ai ha−1), respectively. Shading increased D. insularis sensitivity to glyphosate alone and in a mixture with carfentrazone-ethyl. In shading, the glyphosate application alone at a dose of 1920 g ha−1 and in a mixture with carfentrazone-ethyl at doses of 1536 + 8 and 1152 + 16 g ha−1 were efficient in D. insularis control. In the environment of 63% shading, the dose of 768 + 24 g ha−1 was also efficient in this species control. None of the doses were effective in controlling D. insularis in full sunlight. Isolated carfentrazone-ethyl was inefficient in controlling D. insularis, regardless of the growth environment. Shading increases the quantum yield of photosystem II and reduces the electron transport rate, photosynthetic rate, stomatal conductance, and transpiration rate of D. insularis. In shady environments, it is possible to control D. insularis with lower glyphosate doses, used alone and mixed with carfentrazone-ethyl. [ABSTRACT FROM AUTHOR]

Background: Many healthcare institutions have guidelines concerning the usage of protective procedures, and various x‐ray shields have been used to reduce unwanted radiation exposure to medical staff and patients when using x‐rays. Most x‐ray shields are in the form of sheets and lack elasticity, which limits their effectiveness in shielding areas with movement, such as the thyroid. To overcome this limitation, we have developed an innovative elastic x‐ray shield. Purpose: The purpose of this study is to explain the methodology for developing and evaluating a novel elastic x‐ray shield with sufficient x‐ray shielding ability. Furthermore, valuable knowledge and evaluation indices are derived to assess our shield's performance. Methods: Our x‐ray shield was developed through a process of embedding Bi2O3 particles into porous polyurethane. Porous polyurethane with a thickness of 10 mm was dipped into a solution of water, metal particles, and chemical agents. Then, it was air‐dried to fix the metal particles in the porous polyurethane. Thirteen investigational x‐ray shields were fabricated, in which Bi2O3 particles at various mass thicknesses (ranging from 585 to 2493 g/m2) were embedded. To determine the performance of the shielding material, three criteria were evaluated: (1) Dose Reduction Factor (DRF$DRF$), measured using inverse broad beam geometry; (2) uniformity, evaluated from the standard deviation (SD$SD$) of the x‐ray image obtained using a clinical x‐ray imaging detector; and (3) elasticity, evaluated by a compression test. Results: The elastic shield with small pores, containing 1200 g/m2 of the metal element (Bi), exhibited a well‐balanced performance. The DRF$DRF$ was approximately 80% for 70 kV diagnostic x‐rays. This shield's elasticity was −0.62 N/mm, a loss of only 30% when compared to porous polyurethane without metal. Although the non‐uniformity of the x‐ray shield leads to poor shielding ability, it was found that the decrease in the shielding ability can be limited to a maximum of 6% when the shield is manufactured so that the SD$SD$ of the x‐ray image of the shield is less than 10%. Conclusions: It was verified that an elastic x‐ray shield that offers an appropriate reduction in radiation exposure can be produced by embedding Bi2O3 particles into porous polyurethane. Our findings can lead to the development of novel x‐ray shielding products that can reduce the physical and mental stress on users. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effect of CAREdose4D on the dose and image quality in Brain Computed Tomography (CT). Materials and Methods: Noise, Signal-to-Noise Ratio (SNR), and Contrast-to-Noise Ratio (CNR) for Gray Matter (GM), White Matter (WM), Cerebrospinal Fluid (CSF), and skull bones were investigated in brain CT scans of 60 patients. In addition, a phantom study was conducted to examine the effect of CAREdose 4D on the same subject in the brain, chest, abdomen, and pelvic CT protocols. Volume CT dose index (CTDIvol) and Dose Length Product (DLP) were recorded for each scan. Data were analyzed by T-test and Mann-Whitney statistical test with a significance level of less than 0.05. Results: The following results were obtained in active and passive modes of CAREdose 4D in brain CT of patients, respectively: CTDIvol, 15.76±3.94 and 16.96±2.14 mGy (p0.05). There was no significant difference between SNRs and noise of various tissues of the brain (p>0.05) but CNR difference for gray matter, white matter, and cerebrospinal fluid (CSF) was significant (p

Background: Abdominal radiographs remain useful in newborns. Given the high radiation sensitivity of this population, it is necessary to optimize acquisition techniques to minimize radiation exposure. Objective: Evaluate the effects of three additional filtrations on radiation dose and image quality in abdominal X-rays of newborns using an anthropomorphic phantom. Material and method: Abdominal radiographs of an anthropomorphic newborn phantom were performed using acquisition parameters ranging from 55 to 70 kV and from 0.4 to 2.5 mAs, without and with three different additional filtrations: 0.1 mm copper (Cu) + 1 mm aluminum (Al), 0.2 mm copper + 1 mm aluminum, and 2 mm aluminum. For each X-ray the dose area product (DAP) was measured, the signal-to-noise ratio (SNR) was calculated, and image quality (IQ) was evaluated by two blinded radiologists using the absolute visual grading analysis (VGA) method. Results: Adding an additional filtration resulted in a significant reduction in DAP, with a decrease of 42% using 2 mm Al filtration, 65% with 0.1 mm Cu + 1 mm Al filtration, and 78% with 0.2 mm Cu + 1 mm Al filtration (p < 0.01). The addition of 2 mm aluminum filtration does not significantly decrease the SNR (p = 0.31), CNR (p = 0.52) or the IQ (p = 0.12 and 0.401 for reader 1 and 2, respectively). However, adding copper-containing filtration leads to a significant decrease in, SNR, CNR and IQ. Conclusion: Adding a 2 mm Al additional filtration for abdominal radiographs in newborns can significantly reduce the radiation dose without causing a significant decrease in image quality.

Introduction: The KRAS G12C inhibitor sotorasib was approved for treating advanced NSCLC in the second line or later on the basis of the CodeBreaK100 trial. Nevertheless, data on the real-world efficacy and safety of sotorasib, and to its optimal dose, remain limited. Methods: Patients treated with sotorasib for NSCLC through the Veterans Health Administration were retrospectively identified from the Corporate Data Warehouse. Survival, response, and toxicity data were obtained from chart review. Results: Among the 128 patients treated with sotorasib through the Veterans Health Administration, objective response rate was 34%, progression-free survival (PFS) six months, and overall survival 12 months. Similar PFS was observed among the 16 patients who received frontline sotorasib without any prior systemic therapy for NSCLC. Toxicity leading to sotorasib interruption or dose reduction occurred in 37% of patients, whereas sotorasib discontinuation for toxicity occurred in 25%. Notably, sotorasib dose reduction was associated with substantially improved PFS and OS. Conclusions: In this real-world study, the observed efficacy of sotorasib was similar to the results of CodeBreaK100. Patients who received frontline sotorasib had similar PFS to our overall cohort, suggesting that first-line sotorasib monotherapy may benefit patients who are not eligible for chemotherapy. Toxicities leading to sotorasib interruption, dose reduction, or discontinuation were common. Sotorasib dose reduction was associated with improved survival, suggesting that sotorasib dose reduction may not compromise efficacy.

Background: Measuring left ventricular ejection fraction (LVEF) is important for detecting heart failure, e.g., in treatment with potentially cardiotoxic chemotherapy. MRI is considered the reference standard for LVEF, but availability may be limited and claustrophobia or metal implants still present challenges. CT has been shown to be accurate and would be advantageous, as LVEF could be measured in conjunction with routine chest–abdomen–pelvis oncology CT. However, the use of CT is not recommended due to the excessive radiation dose. This study aimed to explore the potential for dose reduction using simulation. Using an anthropomorphic heart phantom scanned at 13 dose levels, a noise simulation algorithm was developed to introduce controlled Poisson noise. Filtered backprojection parameters were iteratively tested to minimise differences in myocardium-to-ventricle contrast/noise ratio, as well as structural similarity index (SSIM) differences between real and simulated images at all dose levels. Fifty-one clinical CT coronary angiographies, scanned with full dose through end-systolic and -diastolic phases, were located retrospectively. Using the developed algorithm, noise was introduced corresponding to 25, 10, 5 and 2% of the original dose level. LVEF was measured using clinical software (Syngo.via VB50) with papillary muscles in and excluded from the LV volume. At each dose level, LVEF was compared to the 100% dose level, using Bland–Altman analysis. The effective dose was calculated from DLP using a conversion factor of 0.026 mSv/mGycm. Results: In the clinical images, mean CTDIvol and DLP were 47.1 mGy and 771.9 mGycm, respectively (effective dose 20.0 mSv). Measurements with papillary muscles excluded did not exhibit statistically significant LVEF bias to full-dose images at 25, 10 and 5% simulated dose. At 2% dose, a significant bias of 4.4% was found. With papillary muscles included, small but significant biases were found at all simulated dose levels. Conclusion: Provided that measurements are performed with papillary muscles excluded from the LV volume, the dose can be reduced by a factor of 20 without significantly affecting LVEF measurements. This corresponds to an effective dose of 1 mSv. CT can potentially be used for LVEF measurement with minimal excessive radiation.

Anna Clennon,1 Megan Hinkley,1 Kristen Nymberg,1 Lauren Ledbetter,1 Demond Handley,2 Eric McLaughlin,2 Amir Mortazavi,3 Katharine A Collier3 1Department of Pharmacy, the James Cancer Hospital at the Ohio State University, Columbus, OH, USA; 2Department of Statistics, the Ohio State University, Columbus, OH, USA; 3Division of Medical Oncology, Department of Internal Medicine, College of Medicine, OH, USA State University, and the Comprehensive Cancer Center, Columbus, OH, USACorrespondence: Katharine A Collier, Division of Medical Oncology, Department of Internal Medicine, College of Medicine, OH, USA State University, and the Comprehensive Cancer Center, 400 W. 12th Ave, Wiseman Hall Rm 310, Columbus, OH, 43210, USA, Tel +1 614-293-2886, Fax +1 614-293-7525, Email katharine.collier@osumc.edu

Background: The use of computed tomography (CT) for attenuation correction (AC) in whole‐body PET/CT can result in a significant contribution to radiation exposure. This can become a limiting factor for reducing considerably the overall radiation exposure of the patient when using the new long axial field of view (LAFOV) PET scanners. However, recent CT technology have introduced features such as the tin (Sn) filter, which can substantially reduce the CT radiation dose. Purpose: The purpose of this study was to investigate the ultra‐low dose CT for attenuation correction using the Sn filter together with other dose reduction options such as tube current (mAs) reduction. We explore the impact of dose reduction in the context of AC‐CT and how it affects PET image quality. Methods: The study evaluated a range of ultra‐low dose CT protocols using five physical phantoms that represented a broad collection of tissue electron densities. A long axial field of view (LAFOV) PET/CT scanner was used to scan all phantoms, applying various CT dose reduction parameters such as reducing tube current (mAs), increasing the pitch value, and applying the Sn filter. The effective dose resulting from the CT scans was determined using the CTDIVol reported by the scanner. Several voxel‐based and volumes of interest (VOI)‐based comparisons were performed to compare the ultra‐low dose CT images, the generated attenuation maps, and corresponding PET images against those images acquired with the standard low dose CT protocol. Finally, two patient datasets were acquired using one of the suggested ultra‐low dose CT settings. Results: By incorporating the Sn filter and adjusting mAs to the lowest available value, the radiation dose in CT images of PBU‐60 phantom was significantly reduced; resulting in an effective dose of nearly 2% compared to the routine low dose CT protocols currently in clinical use. The assessment of PET images using VOI and voxel‐based comparisons indicated relative differences (RD%) of under 6% for mean activity concentration (AC) in the torso phantom and patient dataset and under 8% for a source point in the CIRS phantom. The maximum RD% value of AC was 14% for the point source in the CIRS phantom. Increasing the tube current from 6 mAs to 30 mAs in patients with high BMI, or with arms down, can suppress the photon starvation artifact, whilst still preserving a dose reduction of 90%. Conclusions: Introducing a Sn filter in CT imaging lowers radiation dose by more than 90%. This reduction has minimal effect on PET image quantification at least for patients without Body Mass Index (BMI) higher than 30. Notably, this study results need validation using a larger clinical PET/CT dataset in the future, including patients with higher BMI. [ABSTRACT FROM AUTHOR]

Background: Radiation dose reduction has been the focus of many research activities in x‐ray CT. Various approaches were taken to minimize the dose to patients, ranging from the optimization of clinical protocols, refinement of the scanner hardware design, and development of advanced reconstruction algorithms. Although significant progress has been made, more advancements in this area are needed to minimize the radiation risks to patients. Purpose: Reconstruction algorithm‐based dose reduction approaches focus mainly on the suppression of noise in the reconstructed images while preserving detailed anatomical structures. Such an approach effectively produces synthesized high‐dose images (SHD) from the data acquired with low‐dose scans. A representative example is the model‐based iterative reconstruction (MBIR). Despite its widespread deployment, its full adoption in a clinical environment is often limited by an undesirable image texture. Recent studies have shown that deep learning image reconstruction (DLIR) can overcome this shortcoming. However, the limited availability of high‐quality clinical images for training and validation is often the bottleneck for its development. In this paper, we propose a novel approach to generate SHD with existing low‐dose clinical datasets that overcomes both the noise texture issue and the data availability issue. Methods: Our approach is based on the observation that noise in the image can be effectively reduced by performing image processing orthogonal to the imaging plane. This process essentially creates an equivalent thick‐slice image (TSI), and the characteristics of TSI depend on the nature of the image processing. An advantage of this approach is its potential to reduce impact on the noise texture. The resulting image, however, is likely corrupted by the anatomical structural degradation due to partial volume effects. Careful examination has shown that the differential signal between the original and the processed image contains sufficient information to identify regions where anatomical structures are modified. The differential signal, unfortunately, contains significant noise and has to be removed. The noise removal can be accomplished by performing iterative noise reduction to preserve structural information. The processed differential signal is subsequently subtracted from TSI to arrive at SHD. Results: The algorithm was evaluated extensively with phantom and clinical datasets. For better visual inspection, difference images between the original and SHD were generated and carefully examined. Negligible residual structure could be observed. In addition to the qualitative inspection, quantitative analyses were performed on clinical images in terms of the CT number consistency and the noise reduction characteristics. Results indicate that no CT number bias is introduced by the proposed algorithm. In addition, noise reduction capability is consistent across different patient anatomical regions. Further, simulated water phantom scans were utilized in the generation of the noise power spectrum (NPS) to demonstrate the preservation of the noise‐texture. Conclusions: We present a method to generate SHD datasets from regularly acquired low‐dose CT scans. Images produced with the proposed approach exhibit excellent noise‐reduction with the desired noise‐texture. Extensive clinical and phantom studies have demonstrated the efficacy and robustness of our approach. Potential limitations of the current implementation are discussed and further research topics are outlined. [ABSTRACT FROM AUTHOR]

Background: Follow-up scoliosis radiographs are performed to assess the degree of spinal curvature and skeletal maturity, which can be done at lower radiation exposures than those in standard-dose radiography. Objective: Describe and evaluate a protocol that reduced the radiation in follow-up frontal-view scoliosis radiographs. Materials and methods: We implemented a postero-anterior lower dose modified-technique for scoliosis radiography with task-based definition of adequate image quality and use of technique charts based on target exposure index and patient's height and weight. We subsequently retrospectively evaluated 40 consecutive patients who underwent a follow-up radiograph using the modified-technique after an initial standard-technique radiograph. We evaluated comparisons of proportions for subjective assessment with chi-squared tests, and agreements of reader's scores with intraclass correlation coefficients and Bland–Altman plots. We determined incident air kerma, exposure index, deviation index/standard deviation, dose-area product (DAP), and effective dose for each radiograph. We set statistical significance at P<0.05. Results: Forty patients (65% female), aged 4–17 years. Median effective dose was reduced from 39 to 10 µSv (P<0.001), incident air kerma from 139 to 29 µSv (P<0.001), and DAP from 266 to 55 mGy*cm2 (P<0.001). All modified-technique parameters were rated with a mean score of acceptable or above. All modified-technique measurements obtained inter- and intra-observer correlation coefficient agreements of 0.86 ("Good") or greater. Conclusion: Substantial dose reduction on follow-up scoliosis imaging with existing radiography units is achievable through task-based definition of adequate image quality and tailoring of radiation to each patient's height and weight, while still allowing for reliable assessment and reproducible measurements. [ABSTRACT FROM AUTHOR]

The direct anticoagulants (DOACs), apixaban and rivaroxaban, are used for extended-phase treatment of venous thromboembolism (VTE) and have labeling for dose reduction for this indication. The objective of this study was to better understand primary care clinician prescribing patterns of apixaban and rivaroxaban for extended-phase anticoagulation. We conducted a 21-question survey targeting members of the American College of Physicians and United States Veterans Administration anticoagulation management services. Survey questions covered prescribing behaviors for dose reduction of apixaban and rivaroxaban for extended VTE treatment, as well as questions related to the respondent's practice setting. We used logistic regression to assess associations between demographics and prescribing behaviors. We used k-means clustering to identify distinct groups of prescribing patterns. Among 227 respondents, most were attending physicians (60%) and one-third (34%) practiced in internal medicine or primary care. Most (59%) indicated they dose-reduced DOACs. Hospitalists (no outpatient care) were least likely to dose-reduce (OR 0.09 [95% CI 0.03–0.22]), as well as early-career clinicians (0.53 [0.30–0.91]). Pharmacists and clinicians who treat over 500 VTE patients annually were most likely to dose reduce (6.4 [2.9–16.3]), (2.9 [1.5–6.0]), respectively. We identified five clusters of dosing behaviors and characterized clinician makeup. Clusters were primarily differentiated by frequency of dose reduction, DOAC preference, and temporary re-escalation of doses. We identified clinician characteristics that are associated with dose-reduction prescribing behaviors; these analyses provide insight into where targeted interventions, such as protocolization and education, would be most beneficial. [ABSTRACT FROM AUTHOR]

Imaging of the cervical spine in general radiography is most frequently performed using an anti-scatter grid. The purpose of this study was to investigate the effects of a gridless setting on image quality and radiation dose during digital radiography of the anteroposterior (AP) and lateral (LAT) cervical spine. A phantom study was performed with a variety of tube voltages (63–75 kV) with and without an anti-scatter grid. The tube current time product (mAs) and dose area product (DAP) were recorded and used to calculate effective dose (ED) and individual organ dose using PCXMC 2.0 software, as well as entrance surface dose (ESD) and objective image quality: signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective visual image quality grading characteristics (VGC) was performed by five qualified radiographers. In a gridless setting, the AP and LAT positions showed significantly lower DAP (1.6 μGym2; 61.3 % and 1.6 μGym2; 51.2%), ESD (27.6 μGy; 57.3% and 77.2 μGy; 47.2%) and ED (4.2 μSv; 61.3% and 2.3 μSv; 48.9%). In a gridless setting in the AP position, there is a slight significant deterioration in image quality. In the lateral projection, on the other hand, the image quality without the use of grid was only significantly reduced in three of six criteria and there was no difference in the objective image quality between the two settings examined. The results of this study show that gridless setting significantly decreases radiation dose and image quality, but the quality in the lateral projection is still acceptable for diagnostic purpose. The protocol without the use of the anti-scatter grid in cervical spine radiography leads to a reduction in the radiation dose in both projections, but the image quality in the AP is significantly reduced for all criteria examined, with a slight deterioration in image quality in the lateral projection. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to use electronic opioid dispensing data to develop an individual segmented trajectory approach for identifying opioid use patterns. The resulting opioid use patterns can be used for examining the association between opioid use and drug overdose. Methods: We retrospectively assembled a cohort of members on long‐term opioid therapy (LTOT) between January 1, 2006 and June 30, 2019 who were 18 years and older and enrolled in one of three health care systems in the US. We have developed an individual segmented trajectory analysis for identifying various opioid use patterns by scanning over the follow‐up and finding distinct opioid use patterns based on variability measured with coefficient of variation and trends of milligram morphine equivalents levels. Results: Among 31, 865 members who were on LTOT between January 1, 2006 and June 30, 2019, 58.3% were female, and the average age was 55.4 years (STD = 15.4). The study population had 152 557 person‐years of follow‐up, with an average follow‐up of 4.4 years per enrollment per person (STD = 3.4). This novel approach identified up to 13 distinct patterns including 88 756 episodes of "stable" pattern (42.1%) with an average follow‐up of 11.2 months, 29 140 episodes of "increasing" pattern (13.8%) with an average follow‐up of 6.0 months, 13 201 episodes of ≤10% dose reduction (6.3%) with an average follow‐up of 10.4 months, 7286 episodes of 11%–20% dose reduction (3.5%) with an average follow‐up of 5.3 months, 4457 episodes of 21%–30% dose reduction (2.1%) with an average follow‐up of 4.0 months, and 9903 episodes of >30% dose reduction (4.7%) with an average follow‐up of 2.6 months. Conclusions: A novel approach was developed to identify 13 distinct opioid use patterns using each individual's longitudinal dispensing data and these patterns can be used in examining overdose risk during the time that these patterns are ongoing. [ABSTRACT FROM AUTHOR]

Objective: To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis. Design: A retrospective cohort study. Setting: Tertiary-care academic medical center. Population: A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020. Methods: A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed. Main outcome measures: The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate. Results: We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16mmon trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups. Conclusion: The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the experience with imaging children using photon-counting CT and to point out the basic procedures how to use the method in diagnosing diseases in childhood. Method: Over a period of 22 months, we performed a total of 209 examinations of children using a CT system with a photon-counting detector (Naeotom Alpha, Siemens Healthineers, Forchheim, Germany). Results: The most frequent indication in imaging was examination of the skeleton of the limbs in 64 cases, chest with a focus on pulmonary parenchyma in 56 cases, examination of the abdomen in 32 cases. Examinations of children over 6 years of age (144 times) were indicated more often than in younger children (65 times). Up to six years of age, children's protocols adjusted to the given age and weight category were also used almost exclusively, while in children over 6 years of age, imaging by modified protocols began to predominate. In addition to skeletal imaging, children are dominated by the use of 70 kV protocols, which allowed for effective dose reduction and also have the highest effect of iodine attenuation when contrast medium was administered. The spectral method of imaging was used mainly in skeletal imaging. Conclusion: Photon-counting CT is an imaging method that can take advantage of the advantages of high resolution and increased detection capabilities to increase image quality while reducing the dose. [ABSTRACT FROM AUTHOR]

Background: Respiratory signal‐guided 4D CT sequence scanning such as the recently introduced Intelligent 4D CT (i4DCT) approach reduces image artifacts compared to conventional 4D CT, especially for irregular breathing. i4DCT selects beam‐on periods during scanning such that data sufficiency conditions are fulfilled for each couch position. However, covering entire breathing cycles during beam‐on periods leads to redundant projection data and unnecessary dose to the patient during long exhalation phases. Purpose: We propose and evaluate the feasibility of respiratory signal‐guided dose modulation (i.e., temporary reduction of the CT tube current) to reduce the i4DCT imaging dose while maintaining high projection data coverage for image reconstruction. Methods: The study is designed as an in‐silico feasibility study. Dose down‐ and up‐regulation criteria were defined based on the patients' breathing signals and their representative breathing cycle learned before and during scanning. The evaluation (including an analysis of the impact of the dose modulation criteria parameters) was based on 510 clinical 4D CT breathing curves. Dose reduction was determined as the fraction of the downregulated dose delivery time to the overall beam‐on time. Furthermore, under the assumption of a 10‐phase 4D CT and amplitude‐based reconstruction, beam‐on periods were considered negatively affected by dose modulation if the downregulation period covered an entire phase‐specific amplitude range for a specific breathing phase (i.e., no appropriate reconstruction of the phase image possible for this specific beam‐on period). Corresponding phase‐specific amplitude bins are subsequently denoted as compromised bins. Results: Dose modulation resulted in a median dose reduction of 10.4% (lower quartile: 7.4%, upper quartile: 13.8%, maximum: 28.6%; all values corresponding to a default parameterization of the dose modulation criteria). Compromised bins were observed in 1.0% of the beam‐on periods (72 / 7370 periods) and affected 10.6% of the curves (54/510 curves). The extent of possible dose modulation depends strongly on the individual breathing patterns and is weakly correlated with the median breathing cycle length (Spearman correlation coefficient 0.22, p < 0.001). Moreover, the fraction of beam‐on periods with compromised bins is weakly anti‐correlated with the patient's median breathing cycle length (Spearman correlation coefficient ‐0.24; p < 0.001). Among the curves with the 17% longest average breathing cycles, no negatively affected beam‐on periods were observed. Conclusion: Respiratory signal‐guided dose modulation for i4DCT imaging is feasible and promises to significantly reduce the imaging dose with little impact on projection data coverage. However, the impact on image quality remains to be investigated in a follow‐up study. [ABSTRACT FROM AUTHOR]

Background: Measuring left ventricular ejection fraction (LVEF) is important for detecting heart failure, e.g., in treatment with potentially cardiotoxic chemotherapy. MRI is considered the reference standard for LVEF, but availability may be limited and claustrophobia or metal implants still present challenges. CT has been shown to be accurate and would be advantageous, as LVEF could be measured in conjunction with routine chest–abdomen–pelvis oncology CT. However, the use of CT is not recommended due to the excessive radiation dose. This study aimed to explore the potential for dose reduction using simulation. Using an anthropomorphic heart phantom scanned at 13 dose levels, a noise simulation algorithm was developed to introduce controlled Poisson noise. Filtered backprojection parameters were iteratively tested to minimise differences in myocardium-to-ventricle contrast/noise ratio, as well as structural similarity index (SSIM) differences between real and simulated images at all dose levels. Fifty-one clinical CT coronary angiographies, scanned with full dose through end-systolic and -diastolic phases, were located retrospectively. Using the developed algorithm, noise was introduced corresponding to 25, 10, 5 and 2% of the original dose level. LVEF was measured using clinical software (Syngo.via VB50) with papillary muscles in and excluded from the LV volume. At each dose level, LVEF was compared to the 100% dose level, using Bland–Altman analysis. The effective dose was calculated from DLP using a conversion factor of 0.026 mSv/mGycm. Results: In the clinical images, mean CTDIvol and DLP were 47.1 mGy and 771.9 mGycm, respectively (effective dose 20.0 mSv). Measurements with papillary muscles excluded did not exhibit statistically significant LVEF bias to full-dose images at 25, 10 and 5% simulated dose. At 2% dose, a significant bias of 4.4% was found. With papillary muscles included, small but significant biases were found at all simulated dose levels. Conclusion: Provided that measurements are performed with papillary muscles excluded from the LV volume, the dose can be reduced by a factor of 20 without significantly affecting LVEF measurements. This corresponds to an effective dose of 1 mSv. CT can potentially be used for LVEF measurement with minimal excessive radiation. [ABSTRACT FROM AUTHOR]

The aim of this phantom study was to assess the detectability and volumetric accuracy of pulmonary nodules on photon-counting detector CT (PCD-CT) at different low-dose levels compared to conventional energy-integrating detector CT (EID-CT). In-house fabricated artificial nodules of different shapes (spherical, lobulated, spiculated), sizes (2.5–10 mm and 5–1222 mm3), and densities (−330 HU and 100 HU) were randomly inserted into an anthropomorphic thorax phantom. The phantom was scanned with a low-dose chest protocol with PCD-CT and EID-CT, in which the dose with PCD-CT was lowered from 100% to 10% with respect to the EID-CT reference dose. Two blinded observers independently assessed the CT examinations of the nodules. A third observer measured the nodule volumes using commercial software. The influence of the scanner type, dose, observer, physical nodule volume, shape, and density on the detectability and volumetric accuracy was assessed by a multivariable regression analysis. In 120 CT examinations, 642 nodules were present. Observer 1 and 2 detected 367 (57%) and 289 nodules (45%), respectively. With PCD-CT and EID-CT, the nodule detectability was similar. The physical nodule volumes were underestimated by 20% (range 8–52%) with PCD-CT and 24% (range 9–52%) with EID-CT. With PCD-CT, no significant decrease in the detectability and volumetric accuracy was found at dose reductions down to 10% of the reference dose (p > 0.05). The detectability and volumetric accuracy were significantly influenced by the observer, nodule volume, and a spiculated nodule shape (p < 0.05), but not by dose, CT scanner type, and nodule density (p > 0.05). Low-dose PCD-CT demonstrates potential to detect and assess the volumes of pulmonary nodules, even with a radiation dose reduction of up to 90%. [ABSTRACT FROM AUTHOR]

Purpose: Anti-Xa peak level monitoring is recommended during LMWH treatment in renal impairment or obesity. The trough level has been proposed as marker for bleeding. We studied the influence of renal impairment and obesity on anti-Xa levels. Methods: Peak and trough levels were collected during therapeutic nadroparin treatment in patients with renal impairment, obese patients, and controls. 27 patients (n = 68 samples) were evaluated and combined with published data (n = 319 samples from 35 patients) using population pharmacokinetic (popPK) modelling. Results: Median peak level was 0.44 and 0.95 IU/mL in renal impairment with and without dose reduction and 0.60 and 0.43 IU/mL in obesity and controls, respectively. Trough levels were < 0.5 IU/mL in all patients with renal impairment with dose reduction and in 5/6 control patients. In the popPK model, total body weight and eGFR were covariates for clearance and lean body weight for distribution volume. Model-based evaluations demonstrated peak levels below the therapeutic window in controls and increased levels in renal impairment. Dose reductions resulted in a different effect on peak and trough levels. Obese patients (BMI up to 32 kg/m2) had similar levels upon weight-based dosing. Conclusion: In renal impairment, anti-Xa peak levels after dose reduction are comparable to those in controls. Weight-based dosing is suitable for obese patients. Aiming for peak levels between 0.6 and 1.0 IU/mL in these patients would result in overexposure compared to controls. Considering the association of trough levels and bleeding risk and our findings, trough monitoring seems to be a suitable parameter to identify nadroparin accumulation. [ABSTRACT FROM AUTHOR]

Purpose To explore the data and supporting evidence for the 2019 statement by the American Association of Physicists in Medicine (AAPM) that recommends limits to the routine use of fetal and gonadal shielding in medical imaging. Methods Three researchers searched 5 online databases, selecting articles from scholarly journals and radiology trade publications. Search results were filtered to include literature published from January 1, 2016, to August 9, 2022, to ensure relevance and provide historical background for the 2019 AAPM statement. Results The use of patient shielding during medical imaging did not reduce dose, and in certain instances, increased dose received by patients during computed tomography, fluoroscopy, or dental imaging. The use of shielding interfered with technology designed to reduce patient dose, including automatic exposure control and dose modulation. Research showed that errors in shield placement were common and that shields can act as sources of infection or carriers of harmful lead dust. Discussion In each article reviewed, a compelling case was made for discontinuing routine patient shielding during radiographic procedures. Serious opposition to the discontinuation of the shielding practice was not found. Opportunities exist for further study into technologists' and the public's understanding of the effects of radiation and technologists' compliance with new shielding policies. Conclusion The challenges with properly using shielding, paired with recent technological advancements and a new understanding of radiation protection, have negated the need for contact shielding. This legacy practice can be discontinued in clinical settings, and educational materials for technologists and students should be updated to reflect these changes. [ABSTRACT FROM AUTHOR]

Dose reduction (DR) of first-generation biologics for plaque psoriasis (TNF-alpha inhibitors (i) and interleukin (IL)-12/23i) has been described in a previous scoping review. The literature on the DR of the newest generation of biologics (IL-17/23i) was scarce. The current review provides a literature update on the previous scoping review on the DR of all biologics, including the newest generation, with a focus on the uptake and implementation of DR in practice. The current literature search on DR revealed 14 new articles in addition to those in the previous review. Four of the newly found articles tested DR strategies, mostly focusing on first-generation biologics; only guselkumab (IL-23i) was included in one study. The other 10 studies showed data on regaining response after failure of DR, safety, cost-effectiveness, and uptake and implementation, as well as information about IL-17/23i. The eligibility criteria to start DR included both absolute and relative Psoriasis Area and Severity Index (PASI) scores (PASI ≤3/≤5/PASI 75–100) and/or Dermatology Life Quality Index (DLQI) ≤3/≤5, or BSA ≤1/≤2, or Physician Global Assessment (PGA) ≤1/0–2 during a period ranging from 12 weeks to ≥1 year. Most studies used PASI ≤5 and/or DLQI ≤5 or PGA ≤1 for ≥6 months. DR strategies were mostly performed by stepwise interval prolongation in two steps (to 67% of the standard dose, followed by 50%). Some studies of IL-17/23i reduced the dose to ±25%. The tested DR strategies on stepwise or fixed DR on TNF-αi and IL-12/23i (three studies), as well as one “on-demand” dosing study on IL-23i guselkumab, were successful. In the case of relapse of DR on TNF-αi and IL-12/23i, clinical effectiveness was regained by retreatment with the standard dose. All studies showed substantial cost savings with the biologic DR of TNF-αi and IL-12/23i. The identified barriers against the implementation of DR were mainly a lack of guidelines and scientific evidence on effectiveness and safety, and a lack of time and (technical) support. The identified facilitators were mainly clear guidelines, feasible protocols, adequate education of patients and physicians, and cost reduction. In conclusion, DR seems promising, but a research gap still exists in randomized, prospective studies testing DR strategies, especially of IL-17/23i, hampering the completion of guidelines on DR. Taking into account the identified barriers and facilitators most likely results in a more successful implementation of biologic DR in practice.

Rationale and objectives: Aim of this study was to assess the impact of contrast media dose (CMD) reduction on diagnostic quality of photon-counting detector CT (PCD-CT) and energy-integrating detector CT (EID-CT). Methods: CT scans of the abdominal region with differing CMD acquired in portal venous phase on a PCD-CT were included and compared to EID-CT scans. Diagnostic quality and contrast intensity were rated. Additionally, readers had to assign the scans to reduced or regular CMD. Regions-of-interest (ROIs) were placed in defined segments of portal vein, inferior vena cava, liver, spleen, kidneys, abdominal aorta and muscular tissue. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Results: Overall 158 CT scans performed on a PCD-CT and 68 examinations on an EID-CT were analyzed. Overall diagnostic quality showed no significant differences for PCD-CT with standard CMD which scored a median 5 (IQR:5-5) and PCD-CT with 70% CMD scoring 5 (4–5). (For PCD-CT, 71.69% of the examinations with reduced CMD were assigned to regular CMD by the readers, for EID-CT 9.09%. Averaged for all measurements SNR for 50% CMD was reduced by 19% in PCD-CT (EID-CT 34%) and CNR by 48% (EID-CT 56%). Virtual monoenergetic images (VMI)50keV for PCD-CT images acquired with 50% CMD showed an increase in SNR by 72% and CNR by 153%. Conclusions: Diagnostic interpretability of PCD-CT examinations with reduction of up to 50% CMD is maintained. PCD-CT deducted scans especially with 70% CMD were often not recognized as CMD reduced scans. Compared to EID-CT less decline in SNR and CNR is observed for CMD reduced PCD-CT images. Employing VMI50keV for CMD-reduced PCD-CT images compensated for the effects.

Background: Histogram indices (HIs) and texture features (TFs) are considered to play an important role in future oncologic PET-imaging and it is unknown how these indices are affected by changes of tracer doses. A randomized undersampling of PET list mode data enables a simulation of tracer dose reduction. We performed a phantom study to compare HIs/TFs of simulated and measured tracer dose reductions and evaluated changes of HIs/TFs in the liver of patients with PETs from simulated reduced tracer doses. Overall, 42 HIs/TFs were evaluated in a NEMA phantom at measured and simulated doses (stepwise reduction of [18 F] from 100% to 25% of the measured dose). [18 F]-FDG-PET datasets of 15 patients were simulated from 3.0 down to 0.5 MBq/kgBW in intervals of 0.25 MBq/kgBW. HIs/TFs were calculated from two VOIs placed in physiological tissue of the right and left liver lobe and linear correlations and coefficients of variation analysis were performed. Results: All 42 TFs did not differ significantly in measured and simulated doses (p > 0.05). Also, 40 TFs showed the same behaviour over dose reduction regarding differences in the same group (measured or simulated), and for 26 TFs a linear behaviour over dose reduction for measured and simulated doses could be validated. Out of these, 13 TFs could be identified, which showed a linear change in TF value in both the NEMA phantom and patient data and therefore should maintain the same informative value when transferred in a dose reduction setting. Out of this Homogeneity 2, Entropy and Zone size non-uniformity are of special interest because they have been described as preferentially considerable for tumour heterogeneity characterization. Conclusions: We could show that there was no significant difference of measured and simulated HIs/TFs in the phantom study and most TFs reveal a linear behaviour over dose reduction, when tested in homogeneous tissue. This indicates that texture analysis in PET might be robust to dose modulations.

Abstract Background The epidermal growth factor receptor (EGFR) mutation is a risk factor associated with brain metastases (BMs) in patients with non‐small cell lung cancer (NSCLC). This study aimed to evaluate the impact of osimertinib early dose reduction on BM worsening. Methods We retrospectively analyzed EGFR‐mutant NSCLC patients treated with osimertinib as first‐line treatment between August 2018 and October 2021. To evaluate the impact of osimertinib early dose reduction, we performed a landmark analysis of patients who achieved disease control at 4 months. Patients were divided into two groups according to whether the osimertinib dose was reduced or not, within 4 months after the start of treatment. We evaluated the time to BMs onset or progression, progression‐free survival, and overall survival. Results In total, 62 NSCLC patients with EGFR mutations were analyzed. Thirteen patients experienced early dose reduction of osimertinib treatment. Seven patients received osimertinib 40 mg daily, and six received 80 mg every other day. The most common reason for dose reduction was gastrointestinal toxicity (n = 4), followed by skin rashes (n = 3). The time to BMs onset or progression was significantly shorter in patients who experienced early dose reduction than in those who continued regular treatment (Hazard ratio 4.47, 95% confidence interval, 1.52–13.11). The 1‐year cumulative incidence of BM onset or progression was 23.1% in the reduced‐dose group and 5.0% in the standard dose group. The risk of worsening BMs with early dose reduction of osimertinib treatment was higher in patients who had BMs before treatment and in younger patients. Conclusion Early dose reduction of osimertinib was a risk factor for the worsening of BMs. A higher risk was associated with younger patients and those presenting BMs before treatment.

Pasireotide long-acting release is effective in achieving bioche mical control and reducing tumour volume in patients with acromegaly inadequately controll ed by first-line therapy. As part of a long-term, real-world study at our centre, 20 of 50 patients receiving pasireotide benefited from a reduction in pasireotide dose. Pasi reotide reduced insulin-like growth factor 1 (IGF1) levels to below the upper limit of the normal range, with some patients responding within 1−3 months of treatment (n = 11) and others after ≥4 months (n = 9). Following pasireotide dose reduction, IGF1 levels showed a mild increase but remained within the normal range after a median of 39 months in the early responders and 17 months in the late responders. Glucose and gl ycated haemoglobin levels decreased following dose reduction. Identifying patients who may benefit from a reduction in pasireotide dose warrants further research as it may improve the management of pasireotide-associated hyperglycaemia in susceptible patients. Significance statement: Patients with acromegaly often need medical therapy for extended periods of time, and pasireotide is an effective, long-term trea tment option. However, pasireotide may increase blood glucose levels in some patients, such as those with pre-existing diabetes. In this single-centre study, we show that fo llowing dose reduction of pasireotide over time, patients with acromegaly maintained thei r biochemical response (IGF1 < ULN) and had improved glycaemic control. As such, dose reductions may be an effective, personalised treatment approach for managing some patients receiving long-term pasireotide therapy and could allow patients to achieve early and long-term biochemical control while minimising adverse drug effects.

The monitored tomographic reconstruction (MTR) with optimized photon flux technique is a pioneering method for X-ray computed tomography (XCT) that reduces the time for data acquisition and the radiation dose. The capturing of the projections in the MTR technique is guided by a scanning protocol built on similar experiments to reach the predetermined quality of the reconstruction. This method allows achieving a similar average reconstruction quality as in ordinary tomography while using lower mean numbers of projections. In this paper, we, for the first time, systematically study the MTR technique under several conditions: reconstruction algorithm (FBP, SIRT, SIRT-TV, and others), type of tomography setup (micro-XCT and nano-XCT), and objects with different morphology. It was shown that a mean dose reduction for reconstruction with a given quality only slightlyvaries with choice of reconstruction algorithm, and reach up to 12.5 % in case of micro-XCT and 8.5 % for nano-XCT. The obtained results allow to conclude that the monitored tomographic reconstruction approach can be universally combined with an algorithm of choice to perform a controlled trade-off between radiation dose and image quality. Validation of the protocol on independent common ground truth demonstrated a good convergence of all reconstruction algorithms within the MTR protocol.