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Alzheimer's disease is a fatal illness associated with two persistent problems in treatment i. ineffective drug transportation across the bio-membranes and ii. on-site targeting. Such problems originate from the combinational factors for non-specific targets, physicochemical limitations in the delivery of the active agents and insignificant permeability across blood-brain-barrier. In this context, block copolymers such as PLGA-PEG, PEG-PLA, Poloxamers, PLGA-PEG-PLGA triblock copolymers, etc. present interesting potential in the development of nano-sized carrier systems like polymerosomes, polymeric micelles, etc. for the management and treatment of Alzheimer's disease. Modifications of block copolymers display improvement in solubility and reduction in toxicity due to the process of complexation, functionalization, dose reduction and modification of kinetics for the rate of release. This review article focuses on new insights into different copolymers and their superiority over conventional polymers in Alzheimer's disease for long-term therapy in the body. Association of block copolymers to therapy of Alzheimer's disease overcome the limitations of drug delivery by offering attributes such as smaller molecular size (less than 150 nm), higher solubility owing to hydrophilic interactions between polymeric components and systemic environment, better entrapment efficiency (above 80%) due to large effective surface area and long-term stability for sensitive actives such as peptides, monoclonal antibodies, curcumin, resveratrol, catechins, etc. With such multifunctional features, block copolymers actively permeate the bio-membrane as polymeric nanoparticles, nanomicelles and polymerosomes using different mechanisms such as transcellular- and receptor-mediated transportation to reach target neural network as well as extra-neuronal amyloid-β plaques for anti-Alzheimer's disease activity with neuroprotective action. These polymers emerge as important components for personalized therapy with potential applications in biosensing, drug delivery, theranostics, etc. for qualitative and quantitative predictions in the detection and treatment of Alzheimer's disease.

PURPOSE To assess outcomes of small and medium choroidal melanoma (less than 5.0 mm in height) following Iodine-125 episcleral brachytherapy. METHODS AND MATERIALS Patients with small and medium choroidal melanoma that underwent Iodine-125 brachytherapy with apical height of 1.0 mm to 5.0 mm and largest basal diameter of ≤16.0 mm were included. Data were extracted from the original dosimetry plans to determine doses to vision critical structures with the prescription point to the apical height (actual dose, ABS guidelines) and, after simulation, with the prescription point to the height of 5.0 mm (simulated dose, COMS protocol). Visual acuity (VA) outcomes with actual dose and that predicted with the simulated dose were estimated along with local recurrence, ocular survival, and survival at 5 years. RESULTS A total of 339 patients with a mean age of 61.5 years with a mean follow up duration of 43.4 months were included. The mean dose reduction for lens, optic disc, and fovea was 34%, 39.4%, and 41.4%, respectively with actual dose when compared with simulated dose. The Kaplan-Meier estimations for 3 year event free rate of VA of 20/50 or better were 56% and 31% for actual dose and simulated dose, respectively. Only 3 events of local recurrence were observed (enucleated) yielding 5 year local control and ocular survival rate of 98%. Overall survival (OS) and metastasis free survival (MFS) were 95% and 87.5% at 5 years, respectively. CONCLUSIONS Small and medium choroidal melanoma treated according to ABS has excellent outcomes. Brachytherapy planning using ABS guidelines as compared to COMS protocol may be associated with lower rates of radiation toxicity and vision loss.

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.

Background: Polypharmacy and inappropriate medication use are an increasing concern. Deprescribing may improve medication use through planned and supervised dose reduction or stopping of medications. As most medication management occurs in primary health care, which is generally described as the first point of access for day-to-day care, deprescribing in primary health care is the focus on this review. Objective: This scoping review aimed to identify and characterize strategies for deprescribing in primary health care and map the strategies to the Behaviour Change Wheel (BCW). Methods: A scoping review was conducted that involved searches of six databases (2002–2018) and reference lists of relevant systematic reviews and included studies. Studies that described and evaluated deprescribing strategies in primary health care were eligible. Two independent reviewers screened articles and completed data charting with charting verified by a third. Deprescribing strategies were mapped to the intervention functions of the BCW and linked to specific Behaviour Change Techniques (BCT). Results: Searches yielded 6871 citations of which 43 were included. Nineteen studies were randomized, 24 were non-randomized. Studies evaluated deprescribing in terms of medication changes, feasibility, and prescriber/patient perspectives. Deprescribing strategies involved various professionals (physicians, pharmacists, nurses), as well as patients and were generally multifaceted. A wide range of intervention functions were identified, with 41 BCTs mapped to Environmental restructuring, 38 BCTs mapped to Enablement, and 34 BCTs mapped to Persuasion. Conclusions: Deprescribing strategies in primary health care have used a variety of BCTs to address individual professionals (e.g. education) as well as strategies that addressed the practice setting, including support from additional team members (e.g. pharmacists, nurses and patients). Further research is warranted to determine comparative effectiveness of different BCTs, which can help facilitate implementation of deprescribing strategies, thereby reducing polypharmacy, in primary health care. Refereed/Peer-reviewed

There have been substantial advances in computed tomography (CT) technology since its introduction in the 1970s. More recently, these advances have focused on image reconstruction. Deep learning reconstruction (DLR) is the latest complex reconstruction algorithm to be introduced, which harnesses advances in artificial intelligence (AI) and affordable supercomputer technology to achieve the previously elusive triad of high image quality, low radiation dose, and fast reconstruction speeds. The dose reductions achieved with DLR are redefining ultra-low-dose into the realm of plain radiographs whilst maintaining image quality. This review aims to demonstrate the advantages of DLR over other reconstruction methods in terms of dose reduction and image quality in addition to being able to tailor protocols to specific clinical situations. DLR is the future of CT technology and should be considered when procuring new scanners.

International audience; Aberrant activation of RET is a critical driver of growth and proliferation in diverse solid tumours. Multikinase inhibitors (MKIs) showing anti-RET activities have been tested in RET-altered tumours with variable results. The low target specificity with consequent increase in side-effects and off-target toxicities resulting in dose reduction and drug discontinuation are some of the major issues with MKIs. To overcome these issues, new selective RET inhibitors such as pralsetinib (BLU-667) and selpercatinib (LOXO-292) have been developed in clinical trials, with selpercatinib recently approved by the Food and Drug Administration (FDA). The results of these trials showed marked and durable antitumour activity and manageable toxicity profiles in patients with RET-altered tumours. The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) launched a collaborative project to review the available methods for the detection of RET gene alterations, their potential applications and strategies for the implementation of a rational approach for the detection of RET fusion genes and mutations in human malignancies. We present here recommendations for the routine clinical detection of targetable RET rearrangements and mutations.

PURPOSE: Although 24 Gy single-dose radiation therapy (SDRT) renders >90% 5-year local relapse-free survival in human solid tumor lesions, SDRT delivery is not feasible in ~50% of oligometastatic lesions owing to interference by dose/volume constraints of a serial organ at risk (OAR). Conformal OAR avoidance is based on a hypothetical model positing that the recently described SDRT biology specifically permits volumetric subdivision of the SDRT dose, such that high-intensity vascular drivers of SDRT lethality, generated within a major tumor subvolume exposed to a high 24 Gy dose (high-dose planning target volume [PTV(HD])), would equilibrate SDRT signaling intensity throughout the tumor interstitial space, rendering bystander radiosensitization of a minor subvolume (perfusion-modulated dose sculpting PTV [PTV(PMDS)]), dose-sculpted to meet a serial OAR dose/volume constraint. An engineered PTV(PMDS) may thus yield tumor ablation despite PMDS dose reduction and conformally avoiding OAR exposure to a toxic dose. METHODS AND MATERIALS: Dose fall-off within the PTV(PMDS) penumbra of oligometastatic lesions was planned and delivered by intensity modulated inverse dose painting. SDRT- and SDRT-PMDS–treated lesions were followed with periodic positron emission tomography/computed tomography imaging to assess local tumor control. RESULTS: Cumulative baseline 5-year local relapse rates of oligometastases treated with 24 Gy SDRT alone (8% relapses, n = 292) were similar in moderate PTV(PMDS) dose-sculpted (23-18 Gy, n = 76, 11% relapses, P = .36) and extreme dose-sculpted (

Objective Endovascular aneurysm repair (EVAR) can result in high radiation dose to patients and operators. This prospective randomized study aimed to assess whether patient radiation dose sustained during EVAR could be decreased by predominantly using digital fluoroscopy (DF) vs the standard technique using digital subtraction angiography (DSA). Methods Between February 2011 and June 2017, patients with EVAR of infrarenal abdominal aortic aneurysms were prospectively enrolled and randomly assigned to a standard treatment DSA cohort or a DF cohort in which two or fewer DSA acquisitions were allowed for confirmatory imaging. Primary end points included dose-area product (DAP) and cumulative air kerma. Secondary end points included technical success and conversion to DSA standard treatment (if DF was inadequate for visualization). Results For all 43 patients enrolled (26 in the DF cohort, 17 in the DSA cohort), technical success was 100%. Of the 26 DF patients, 5 (19%) required conversion to the DSA cohort. In an intention-to-treat analysis, mean DAP was significantly lower in the DF cohort than in the DSA cohort (132 vs 174 Gy·cm2; P = .04). When patients were separated by number of DSA acquisitions (two or fewer vs three or more), mean DAP decreased 41% (109 vs 185 Gy·cm2; P = .005) and cumulative air kerma decreased 40% (578 vs 964 mGy; P = .004). Conclusions In most patients (81%), DF or limited DSA was adequate for visualization during EVAR. In both intention-to-treat DF and limited-DSA cohorts, mean DAP was significantly decreased. If image quality allows, a DF-only or limited-DSA approach to EVAR decreases radiation dose.

This review addresses the risks and benefits of long-term maintenance antipsychotic treatment for patients that extends beyond two years. It focuses on framing discussions with patients who are recovering from a first episode. For these patients the evidence strongly supports the benefits over the risk for the first two years. However, both the clinical side effects of antipsychotics and the possible long-term effects of dopamine blocking drugs on the brain require a more nuanced discussion beyond this initial period. In most cases, the decision will be to continue antipsychotics but to consider strategies for mitigating the risks of drugs. This review provides information about the relative risks of dose reduction and intermittent treatment.

Total-body PET (TB-PET) is a technical advancement providing improved signal detection (effective sensitivity). This is achieved through a novel extended detector geometry among many other fine attunements. This technical evolution will ripple through molecular imaging revolutionizing clinical practice beyond the expectations of its designers. This article explores how this leap forward in effective sensitivity through TB-PET could enable dose reduction, faster imaging, temporal resolution improvement, dynamic imaging, and the in vivo noninvasive study of clinical systems biology. TB-PET has the potential to be an enabler of disruptive innovations in molecular imaging. This will change the landscape of medical imaging.

Increasing integration of computed tomography (CT) into routine patient care has escalated concerns regarding associated radiation exposure. Specific patient cohorts, particularly those with cystic fibrosis (CF) and Crohn's disease, have repeat exposures and thus have an increased risk of high lifetime cumulative effective dose exposures. Thoracic CT is the gold standard imaging method in the diagnosis, assessment and management of pulmonary disease. In the setting of CF, CT demonstrates increased sensitivity compared with pulmonary function tests and chest radiography. Furthermore, in specific cases of Crohn's disease, CT demonstrates diagnostic superiority over magnetic resonance imaging (MRI) for radiological evaluation. Low dose CT protocols have proven beneficial in the evaluation of CF, Crohn's disease and renal calculi, and in the follow up of testicular cancer patients. For individuals with chronic conditions warranting frequent radiological follow up, the focus must continue to be the incorporation of appropriate CT use into patient care. This is of particular importance for the paediatric population who are most susceptible to potential radiation induced malignancy. CT technological developments continue to focus on radiation dose optimisation. This article aims to highlight these advancements, which prioritise the acquisition of diagnostically satisfactory images with the least amount of radiation possible.

Purpose The appropriate object thickness to start using anti-scatter grids (grids) has not sufficiently investigated in previous studies, and thus we rigorously investigated the effectiveness of two generally used grids with grid ratios of 6 and 10 (G6 and G10) for different 50–200 mm thicknesses at tube voltages of 60–100 kV. Methods Acrylic phantoms with 30 × 30 cm2 and different thicknesses were used to measure the signal-to-noise ratio improvement factors (SIFs) of grids. To evaluate the infants’ conditions, field sizes of 225, 400, and 625 cm2 were also evaluated at 60–80 kV. In addition, the signal difference-to-noise ratio (SDNR) was used to evaluate tube voltage dependencies of grids for each thickness. Results SIF values exceeded 1.0 for ≥70 mm thicknesses and mostly exceeded 1.07 for the 100 mm thickness with 400 cm2 field size corresponding to a 1-year-old infant abdomen. The estimated dose reduction capabilities for a 1-year-old infant were approximately 15% using G10 at 70 and 80 kV. The tube voltage dependencies for grid use was almost not prominent for all conditions tested, except for some conditions that are not clinically realistic. Conclusions G6 and G10 can improve SNR for ≥100 mm thickness. The results from this work demonstrate approximately 15% dose reduction or image quality improvements at the same dose level for the use of G6 and G10 grids for 100 mm thickness, traditionally excluded from the recommended grid use conditions.

Background and objectives\ud It was postulated that Aripiprazole may cause impulse-control problems. Therefore, real-world data on the effects and side effects of Aripiprazole 400 mg depot are needed to review the utility, safety and the clinical effectiveness of Aripriprazole 400 mg depot and highlight the occurrence of adverse effects including impulsivity in a naturalistic treatment settings.\ud \ud Methods\ud A non-interventional, retrospective study was conducted to examine the electronic records of all patients who were receiving or had received Aripiprazole Lauroxil in South West London before May 2017. Disorder symptoms and side effects were compared between pre- and post-Aripiprazole PO and Aripiprazole Depot treatments.\ud \ud Results\ud Data were considered for 57 patients who switched to Aripiprazole depot due to non-compliance and/or side effects. Most were suffering from chronic schizophrenia (75.4 %) and half (50.9 %) had comorbid alcohol and/or illicit drug use. Oral Aripiprazole was effective in improving hallucinations, delusions and depressive symptoms (P

Extracorporeal photopheresis (ECP) is an established treatment strategy in steroid-refractory graft-versus-host disease (GVHD). This study's main objective was to analyze the clinical response and impact of ECP therapy in steroid dose reduction. A retrospective observational series of 113 patients from 7 transplantation centers was analyzed. Sixty-five patients (58%) had acute GVHD (aGVHD), and 48 (42%) had chronic GVHD (cGVHD). All ECP procedures were performed with the off-line system. The median number of procedures until achievement of initial response was 3 for both patients with aGVHD and those with cGVHD. ECP was the second-line therapy in 48% of the aGVHD cases and in 50% of the cGVHD cases. 71% of the cases of aGVHD were grade III-IV, and 69% of the cases of cGVHD were severe. The overall response rate on day 28 was 53% (complete response [CR] rate, 45%) in the patients with aGVHD and 67% (CR, 23%) in those with cGVHD. Skin was the most frequently involved organ, with a response rate of 58% (CR, 49%) in the patients with aGVHD and 69% (CR 29%) in those with cGVHD. At the end of ECP treatment, 60% of patients treated for aGVHD who responded were able to stop steroid therapy, with a median dose reduction of 100%. Significant differences in overall survival were observed for patients responding to ECP with aGVHD (hazard ratio [HR], 4.3; P.001) and with cGVHD (HR, 4.8; P = .003). Our data indicate that ECP is a valid therapeutic alternative in patients with steroid-refractory aGVHD and cGVHD, permitting significant steroid dosage reductions.

The safety and effectiveness of reduced-dose apixaban 2.5mg twice daily (BID) have not been elucidated thoroughly in Japanese patients with nonvalvular atrial fibrillation (NVAF).A post-marketing survey study included NVAF patients who newly initiated apixaban for prevention of thromboembolism, and followed them for 104 weeks. Apixaban doses were selected at the discretion of treating physicians. Hemorrhagic and thromboembolic (ischemic stroke, systemic embolism, and transient ischemic attack) events were examined. The relationship between dose reduction criteria (DRC), selected doses, and outcome events was also examined.Of 6306 patients, 3600 (57.1%) received the standard dose (5mg BID) and 2694 (42.7%) received the reduced dose. Compared with the standard-dose group, the reduced-dose group had more female patients; the patients were older, of lower body weight, with reduced creatinine clearance, higher thromboembolic and hemorrhagic risk scores, and more frequent antiplatelet use. Incidence rates of major hemorrhage and thromboembolism were higher in the reduced-dose group compared with the standard-dose group (3.00%/year vs 1.93%/year, p=0.001 and 1.40%/year vs 0.72%/year, p=0.001, respectively). In the standard-dose group, 90.0% of patients did not meet the DRC (recommended standard-dose group). In the reduced-dose group, 62.4% of patients met the DRC (recommended reduced-dose group) and 34.9% did not (non-recommended reduced-dose group). Incidence rates of major hemorrhage and thromboembolism were numerically highest in the recommended reduced-dose group (3.30%/year, p=0.007 and 1.69%/year, p0.001, respectively), followed by the non-recommended reduced-dose group. In multivariate analysis, apixaban dose was not associated with these outcome events.The reduced-dose group showed higher incidence rates of thromboembolic and major hemorrhagic events than the standard-dose group due to baseline clinical characteristics. The safety and effectiveness of reduced-dose apixaban need to be carefully monitored in clinical practice.

Background We updated our previous systematic review regarding clinical guidelines and algorithms on antipsychotic treatment in the maintenance phase of schizophrenia (doi: 10.1016/j.schres.2011.11.021) to incorporate and synthesize more recent findings to guide clinical practice. Methods We conducted a systematic literature search to identify clinical guidelines and algorithms describing antipsychotic treatment in the maintenance phase of schizophrenia using MEDLINE and Embase. We assessed overall quality of the guidelines/algorithms according to the AGREE II instrument and extracted information on treatment recommendations. Results We identified 20 guidelines/algorithms from various regions, including 11 updated or newly launched ones after the previous systematic review in 2012. All of the guidelines/algorithms satisfied a certain level of quality. Where mentioned, endorsements were sorted into “recommended”, “partially recommended”, or “not recommended”. As for antipsychotic discontinuation strategy, a majority of guidelines/algorithms that mentioned this strategy did not recommend it for multiple-episode schizophrenia (N = 5/6). On the other hand, the guidelines/algorithms tended to shift from “not recommended” to “partially recommended” both for schizophrenia in general (N = 7/13, N = 7/8 for those published after 2013) and first-episode schizophrenia (N = 10/11, N = 7/7 for those published after 2013) regarding this strategy. All guidelines/algorithms (N = 9/9) converged to discourage antipsychotic intermittent/targeted strategy. Similar to antipsychotic discontinuation strategy, all of the updated or new guidelines/algorithms (N = 6/6) endorsed antipsychotic dose reduction/lower dose strategy. Conclusion Recent clinical guidelines and algorithms on antipsychotic maintenance treatment in schizophrenia shifted more toward a possibility of antipsychotic discontinuation and dose reduction/lower dose strategies. Nonetheless, clinicians need to contemplate on the risk-benefit balance of these strategies for individual patients.

Eosinophilic esophagitis (EoE) is an immune-mediated condition characterized by symptoms of esophageal dysfunction and an eosinophilic inflammation of the esophagus.1 Swallowed topical steroids represent one of the possible strategies for inducing and maintaining remission in EoE.2 To date, a validated maintenance strategy has yet to be defined, especially in children. The available evidence suggests decreasing the dose after a successful induction therapy.3 No study has reported the efficacy of a continuous progressive dose reduction; thus, it is unknown if all patients need to use the same dosages and for how long.4,5.

Coronary artery calcium (CAC) is a strong predictor for future cardiovascular events. Traditionally CAC has been quantified using the Agatston score, which was developed in the late 1980s for electron beam tomography (EBT). While EBT has been completely replaced by modern multiple-detector row CT technology, the traditional CAC scoring method by Agatston remains in use, although the literature indicates suboptimal reproducibility and subjects being incorrectly classified. The traditional Agatston scoring method counteracts the technical advances of CT technology, and prevents the use of thinner sections, obtained at lower tube voltage and overall decreased radiation exposure that has become available to other CT applications. Moreover, recent studies have shown that not only the total amount of CAC, but also its density and distribution in the coronary arterial tree may be of prognostic value. Acquisition and reconstruction techniques thus need to be adapted for modern CT technology and optimized for CAC quantification. In this review we describe the technical limitations of the Agatston score followed by our suggestions for developing a new and more robust CAC quantification method.

Background The effectiveness and safety of dabigatran etexilate (DE) have not been elucidated thoroughly in clinical practice for Japanese patients with non-valvular atrial fibrillation (NVAF). In particular, those of DE at a reduced dose due to dose reduction recommendations (DRR) remain unknown. Methods NVAF patients who had newly initiated DE treatment for prevention of thromboembolic events between December 2011 and November 2013 were enrolled. They were followed until August 2016. Outcome events included thromboembolism, major bleeding, and all-cause death. Results The study group consisted of 6443 patients (mean age, 70.9 years; male, 66.9%; and mean CHADS2 score, 1.8). During a follow-up period of 610 days (median), stroke, transient ischemic attack (TIA), and systemic embolism (SE) occurred at 1.4%/year for DE 110 mg twice daily (BID) (DE220, n = 4759) and 0.8% for dabigatran 150 mg BID (DE300, n = 1571, unadjusted p = 0.0317). Major bleeding occurred at 1.3 and 0.6%/year for DE220 and DE300, respectively (unadjusted p = 0.0097). All-cause death occurred at 1.5 and 0.5%/year for DE220 and DE300, respectively (unadjusted p = 0.0005). When patients were divided into four groups based on DRR and DE doses (DE300 groups meeting and not meeting DRR, and DE220 groups meeting and not meeting DRR), incidence rates of stroke/TIA/SE and major bleeding differed among the four groups (unadjusted p = 0.0026 and 0.0194 for trend, respectively); DE220 group meeting DRR had the highest rates (1.7% and 1.4%/year, respectively). However, in multivariate analysis, no differences between doses were observed regarding any outcomes. Conclusions The present results are indicative of the favorable benefit-risk profile of dabigatran in Japanese clinical practice. Dabigatran dose was not independently associated with thromboembolic and bleeding events in Japanese NVAF patients.

Objectives To compare the virtual non-contrast (VNC) images acquired through dual-energy computed tomography (DECT) with the true non-contrast (TNC) images in the detection of biliary stones and to calculate dose reduction by replacing TNC images with VNC images. Methods Between March 2017 and April 2018, we retrospectively enrolled 75 patients with suspicious biliary disease who underwent dual-source DECT and surgery and/or endoscopic intervention within 2 months from the CT. Biliary stones were present in 45 patients. The sensitivity and specificity for detecting gallstone and common bile duct (CBD) stone were compared between the VNC and TNC using McNemar test. In addition, the possible reduction in radiation dose was calculated. Results In our study, 37 patients had gallstones, 2 had CBD stones, and 6 had both gallstone and CBD stones. For detection of gallstones, the sensitivity and specificity were 90.7% (39/43) and 87.5% (28/32), respectively, for the TNC images, and 88.4% (38/43) and 90.6% (29/32), respectively, for the VNC images. With respect to CBD stones, the sensitivity and specificity were 87.5% (7/8) and 98.5% (66/67), respectively, for the TNC images, and 75.0% (6/8) and 100% (67/67), respectively, for the VNC images. There was no significant difference in the sensitivity and specificity between each image set (P > 0.05). The radiation dose reduction of 22.4 ± 1.3% is expected by omitting TNC images. Conclusions The VNC images derived from DECT were comparable to the TNC images for the detection of biliary stones and may replace the TNC images to reduce radiation dose.

Deprescribing, an integral component of a continuum of good prescribing practices, is the process of medication withdrawal or dose reduction to correct or prevent medication-related complications, improve outcomes, and reduce costs. Deprescribing is particularly applicable to the commonly encountered multimorbid older adult with cardiovascular disease and concomitant geriatric conditions such as polypharmacy, frailty, and cognitive dysfunction-a combination rarely addressed in current clinical practice guidelines. Triggers to deprescribe include present or expected adverse drug reactions, unnecessary polypharmacy, and the need to align medications with goals of care when life expectancy is reduced. Using a framework to deprescribe, this review addresses the rationale, evidence, and strategies for deprescribing cardiovascular and some noncardiovascular medications.

The use of IR in CT previously has been prohibitively complicated and time consuming, however improvements in computer processing power now make it possible on almost all CT scanners. Due to its potential to allow scanning at lower doses, IR has received a lot of attention in the medical literature and has become a successful commercial product. Its use in cardiovascular CT has been driven in part due to concerns about radiation dose and image quality. This manuscript discusses the various vendor permutations of iterative reconstruction (IR) in detail and critically appraises the current clinical research available on the various IR techniques used in cardiovascular CT.

Eye lenses lie within the radiation field during computed tomography (CT) procedures of the brain. Therefore, patients are at risk of forming eye lens opacity when exposures exceed the threshold for such onset. The purpose of this study was to estimate the eye lens equivalent and radiation effective doses during CT procedures of the brain, facial bones, and paranasal sinuses. A total of 85 patients were examined using a 16-detector CT machine. The organ and surface dose received by specific radiosensitive organs was carried out using software from the National Radiological Protection Board (NRPB). The overall mean patient doses were as follows: CTDIvol, 45.7 ± 15.6 mGy for brain; and 7.6 mSv for the eye lens. The mean eye lens equivalent dose per CT procedure was 11.5 mSv, 4.5 mSv, and 6.7 mSv for the brain, paranasal sinuses, and facial bones, respectively. The radiation risk per procedure equates to 1 cancer case per 11 × 10−3 procedures. The study shows there to be great need for improving the imaging protocol and for continuous training of staff. Dose reduction techniques in brain CT are required, eye lens irradiations potentially generating lens opacities.

The aim of this study was to investigate the extent of dose reduction and comparability of standard dose CT vs Ultra low dose CT in evaluating pulmonary emphysema.Forty-nine patients with emphysema were recruited from a tertiary referral respiratory clinic. Each patient had a non-contrast Standard Dose (SD) and Ultra Low Dose (ULD) thoracic CT. The images were reconstructed using contemporary iterative reconstruction with a standard lung kernel. Lung volumes and emphysema severity was calculated using a commercially available automated densitometry segmentation package. The effective dose was calculated for both CT protocols.Automated densitometry calculated the total lung volume and percentage lung area of emphysema. The findings were highly comparable between ULD and SD protocols. A strong correlation was seen between ULD and SD images in measurement of total lung volume (R = 0.925, p 0.001) and percentage lung involvement by densitometry (R = 0.940, p 0.001). There is a 95% dose reduction with the ULD protocol, the mean effective dose is 0.12 ± 0.09 mSv versus 2.33 ± 1.54 mSv for the SD protocol.ULD thoracic CT is a comparable protocol for the assessment of emphysema severity relative to standard dose CT. ULD CT is performed at a 95% dose reduction compared to SD CT.

A B S T R A C T Objective: The objective of this study was to establish recommendations for the reduction and discontinuation of biological disease-modifying antirheumatic drugs, with the aim of becoming a guide document for health professionals involved in the management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Materials and methods: The recommendations were established through consensus by a panel of experts in rheumatology, and based on the analysis of available scientific evidence obtained from systematic reviews and the clinical experience of the panellists. Results: A total of 33 rheumatoid arthritis related studies were included, with 6 psoriatic arthritis related, and 9 ankylosing Spondylitis related. The recommendations for the reduction of biological therapies were made by establishing a plan to determine when and how to reduce the biological disease-modifying antirheumatic drugs in patients with these 3 diseases, and in some cases lead to the discontinuation of these treatments. Conclusion: The recommendations established in this document will serve as a guide to improve the efficiency of biological therapy in these diseases, reduce the variability in clinical practice, and establish an adequate risk/benefit ratio. RESUMEN Objetivo: El objetivo de este estudio fue establecer recomendaciones para la disminución y descontinuación de la terapia biológica con el fin de que se convierta en un documento guía para los profesionales de la salud involucrados en el manejo de pacientes con artritis reumatoide, espondilitis anquilosante y artritis psoriásica. Materiales y métodos: Las recomendaciones fueron establecidas mediante consenso desarrollado a través de un panel de expertos en reumatología, basado en el análisis de la evidencia científica disponible obtenida de revisiones sistemáticas y sobre la experiencia clínica de los panelistas. Resultados: Se incluyeron 33 estudios relacionados con artritis reumatoide, 6 de artritis psoriásica y 9 de espondilitis anquilosante. Las recomendaciones para la disminución de las terapias biológicas se realizaron estableciendo un plan para determinar cuándo y cómo reducir los fármacos biológicos modificadores de enfermedades reumáticas en pacientes con estas 3 enfermedades y en algunos casos conducir a la descontinuación de estos tratamientos. Conclusión: Las recomendaciones establecidas en este documento servirán de guía para mejorar la eficiencia de la terapia biológica en estas enfermedades, reducir la variabilidad en la práctica clínica y establecer de manera adecuada una relación riesgo/beneficio.

Once remission or low disease activity (LDA) is attained in established rheumatoid arthritis (RA) patients, attempting disease-modifying anti-rheumatic drug (DMARD) tapering appears to be a viable option to avoid patient overtreatment. Potential benefits include reduction in the treatment burden and the risk of adverse events, although the latter has not been demonstrated convincingly. The feasibility of DMARD discontinuation has been tested in numerous studies or trials. All have revealed a high risk of relapse, ranging from 56%-87% at one year. Although remission/LDA can usually be re-established by re-initiation of the previous treatment, the associated risk appears to be more harmful than beneficial. DMARD tapering, either by dose reduction or by injection spacing, is conceptually more acceptable and two superiority randomized controlled trials (RCTs) comparing half-dose etanercept to full-dose continuation demonstrated no significant difference at one year. By contrast, two equivalence RCTs that tested disease activity-guided dose optimization by progressive etanercept and adalimumab injection spacing versus continuation revealed an increased risk of acute flare. Interestingly, one of these also demonstrated the equivalence of increasing injection spacing and standard of care in terms of recurrent flare and overall disease activity over the 18-month follow-up period. The risk of structural damage progression was minimal or null. Reintroduction of DMARD at the previous dose was associated with remission being achieved in the majority of patients who flared. Tapering strategies that adhere to the Tight Control and Treat-to-Target principles appear to be suitable options for RA patients who have achieved sustained remission or low disease activity.

Background: In MONALEESA-2, -3, and -7, ribociclib plus endocrine therapy (ET) prolonged progression-free survival (PFS) versus placebo plus ET in women with hormone receptor-positive, HER2– advanced breast cancer (ABC). This pooled analysis of the MONALEESA studies further evaluated the safety of ribociclib plus ET and provides insight into the efficacy of ribociclib based on dose intensity (DI). Methods: Data were pooled from MONALEESA-2 (all patients), MONALEESA-3 (patients receiving treatment as first-line ET), and MONALEESA-7 (patients receiving combination therapy with an NSAI as initial ET). Efficacy (PFS, overall response rate [ORR], and clinical benefit rate [CBR]) was analyzed according to ribociclib relative dose intensity. Safety was analyzed in all patients and those with and without ≥1 ribociclib dose reduction. Findings: The adverse event (AE) profile in the 1066 and 823 women in this analysis who received ribociclib plus ET and placebo plus ET, respectively, was consistent with previous reports. All-grade neutropenia (74% vs 5%) and nausea (45% vs 27%) were the most common AEs with ribociclib vs placebo, and neutropenia was the most frequent grade 3/4 AE (60% vs 2%). Across MONALEESA-2, -3 and -7, 41.8% of patients (range, 32.8% to 54.5%) required ≥1 dose reduction due to AEs (most commonly, neutropenia). Median ribociclib relative DI in patients without and with dose reductions was 99.3% and 65.6% in MONALEESA-2, 98.4% and 67.8% in MONALEESA-3, and 98.0% and 66.3% in MONALEESA-7. Median PFS was 24.8, 24.9, and 29.6 months for patients who received 30th, 60th, and 90th percentile ribociclib relative DI, respectively, with a numerically higher ORR observed in the lowest relative DI group. Interpretation: This analysis confirms the safety profile of ribociclib plus ET in women with HR+/HER2– advanced breast cancer and demonstrates that the clinical benefit of ribociclib is preserved when dose modifications are undertaken to manage AEs. Trial Registration: MONALEESA-2 (NCT01958021), MONALEESA-3 (NCT02422615), MONALEESA-7 (NCT02278120) Funding Statement: MONALEESA-2, -3, and -7 were supported by Novartis Pharmaceuticals Corporation. Declaration of Interests: Dr. Burris reports consulting or advisory for AstraZeneca, Bristol-Myers Squibb, FORMA Therapeutics, Janssen, MedImmune, Mersana, Novartis, Roche/Genentech, TG Therapeutics; grants from AbbVie, Agios, AstraZeneva, Bayer, BioMed Valley Discoveries, Boehringer Ingleheim, Bristol-Myers Squibb, Celgene, Celdex, CytomX Therapeutics, eFFECTOR Therapeutics, Gilead Sciences, GlaxoSmithKline, Immunocore, Incyte, Janssen, Jounce Therapeutics, Lilly, Loxo, Macrogenics, MedImmune, Merck, Mersana, Milennium, Moderna Therapeutics, Novartis, Pfizer, PTC Therapeutics, Roche/Genentech, Seattle Genetics, Takeda, Tarveda Therapeutics, Tesaro, TG Therapeutics, Valent Technologies, Vasastern, Vertex; Dr. Chan has nothing to disclose; Dr. Bardia reports consulting or advisory for Immunomedics, Pfizer, Novartis, Genentech/Roche, Merck, Radius Health, Spectrum Pharma, Taiho Pharma, Biothernostics Inc., Sanofi, Daichi Pharma, Puma; personal fees from Biothernostics Inc., Pfizer, Novartis, Genentech/Roche, Merck, Radius Health, Immunomedics, Spectrum Pharma, Taiho Pharma, Sanofi, Daiichi Pharma, Puma; grants from Genentech/Roche, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Mersana, Innocrin, Biothernostics Inc.; Dr. Beck has nothing to disclose; Dr. Sohn has nothing to disclose; Dr. Neven has nothing to disclose; Dr. Tripathy reports consulting or advisory for Novartis, Pfizer, Genomic Health, GlaxoSmithKline; personal fees from Novartis, Pfizer, Genomic Health, GlaxoSmithKline; research grant from Novartis; Dr. Im reports consulting or advisory for AstraZeneca, Novartis, Hanmi, Pfizer, Eisai, Amgen, MediPacto, Genentech/Roche, Lilly; personal fees from AstraZeneca, Novartis, Hanmi, Pfizer, Eisai, Amgen; MediPacto, Genentech/Roche, Lilly; grants from AstraZeneca, Pfizer, Genentech/Roche; Dr. Chia reports consulting or advisory for Novartis, Pfizer, Hoffman LaRoche, Eli Lilly; personal fees from Novartis, Pfizer, Hoffman LaRoche, Eli Lilly; Dr. Esteva reports consulting or advisory for Novartis, Pfizer, Genentech/Roche, Celltrion Healthcare, Seattle Genetics; personal fees from Novartis, Pfizer, Genentech/Roche, Celltrion Healthcare, Seattle Genetics; grants from Novartis, Pfizer, GlaxoSmithKline, Genentech/Roche; Dr. Hart reports consulting or advisory for Novartis; personal fees from Novartis; grants from Novartis; Dr. Zarate reports employment and stock ownership from Novartis; Dr. Antonia Ridolfi reports employment and stock ownership from Novartis; Dr. Rodriguez-Lorenc reports employment and stock ownership from Novartis; Dr. Yardley reports consulting or advisory for Biothernostics Inc., Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Eisai, Genentech/Roche, NanoString Technologies, Novartis; personal fees from Biothernostics Inc., Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Lilly, Eisai, Genentech/Roche, NanoString Technologies, Novartis; grants from Daiichi Sankyo, Lilly, Eisai, Novartis, Abbvie, AstraZeneca, Clovis Oncology, Immunomedics, InventisBio, Lilly, MedImmune, Medivation, Merck, Oncothyreon, Pfizer, Syndax, Tesaro. Ethics Approval Statement: All studies were conducted in accordance with Good Clinical Practice guidelines and the provisions of the Declaration of Helsinki. The institutional review board at each participating center reviewed the protocol and any amendments, and all patients provided written informed consent.

Oropharyngeal carcinomas related to the human papilloma virus (HPV; usually HPV16) exhibit biological differences in terms of carcinogenesis and are of relatively better prognosis (in the absence of tobacco consumption) compared to tobacco-related cancers. The therapeutic strategies between these two forms of cancers of the upper aerodigestive tract related to different risk factors are however identical, except therapeutic trial. In the absence of a sufficient level of evidence to define a specific strategy for induced HPV carcinomas, the analysis of the recent literature nonetheless allows us to suggest ways to guide the clinician in his therapeutic choice. Given the relative good prognosis HPV+ oropharyngeal cancers, an important goal is to avoid if possible a multimodal treatment that increases the sequelae and could degrade the quality of life. For the early stages I/II, it may be desirable to propose minimally invasive surgery if radiotherapy is avoidable or an exclusive conformal radiation therapy by intensity modulation in the opposite case. For the advanced stages III/IV, the recommendations are similar to those of cancers not related to HPV. Current trials should provide answers on the relevance of therapeutic deflation (absence of chemotherapy in the event of capsular rupture, dose reduction or irradiation volumes, etc.).

Purpose: Chronic relapsing inflammatory optic neuropathy (CRION) is a type of idiopathic recurrent optic neuritis that responds to systemic corticosteroids and relapses on steroid withdrawal or dose reduction. Central serous chorioretinopathy (CSCR) is often associated with glucocorticoid therapy. This paper aims to highlight CSCR as a cause of visual loss in patients being treated with corticosteroids for optic neuritis. Observations: We describe the case of a 42-year-old woman with a history of CRION in her left eye who presented with painful vision loss in the right eye and diffuse right optic disc edema. Steroid therapy was initiated, leading to visual and perimetric improvement. Two months later however, the patient returned with painless visual loss, now related to CSCR. Despite oral steroids being continued, there was spontaneous tomographic and visual recovery after four months. Conclusions and importance: We believe this is the first report of CSCR causing vision loss in a patient with CRION treated with oral corticosteroids. CSCR should be suspected in patients with optic neuritis of any cause who develop vision loss while on treatment with steroids. Keywords: Chronic relapsing inflammatory optic neuropathy, Optic neuritis, Central serous chorioretinopathy, Steroids

Lack of coordination between the beginning of the inhalation and device triggering is one of the most frequent errors reported in connection with the use of pMDI devices. Earlier results suggested a significant loss in lung deposition as a consequence of late actuation. However, most of our knowledge on the effect of poor synchronization is based on earlier works on CFC devices emitting large particles with high initial velocities. The aim of this study was to apply numerical techniques to analyse the effect of late device actuation on the lung dose of a HFA pMDI drug emitting high fraction of extrafine particles used in current asthma and COPD therapy. A computational fluid and particle dynamics model was combined with stochastic whole lung model to quantify the amount of drug depositing in the extrathoracic airways and in the lungs. High speed camera measurements were also performed to characterize the emitted spray plume. Our results have shown that for the studied pMDI drug late actuation leads to reasonable loss in terms of lung dose, unless it happens in the second half of the inhalation period. Device actuation at the middle of the inhalation caused less than 25% lung dose reduction relative to the value characterizing perfect coordination, if the inhalation time was between 2 and 5 s and inhalation flow rate between 30 and 150 L/min. This dose loss is lower than the previously known values of CFC devices and further support the practice of triggering the device shortly after the beginning of the inhalation instead of forcing a perfect synchronization and risking mishandling and poor drug deposition.

Rationale and Objectives Implementation of low dose computed tomography (LDCT) lung cancer screening programs has followed the demonstration of reduced lung cancer mortality in the National Lung Screening Trial and subsequent consensus screening recommendations. Here we aim to assess the initial results of a screening program at an academic medical center, to discuss the challenges of implementing such a program, and suggest strategies for reducing patient dose. Materials and Methods Retrospective review of all patients who underwent LDCT lung cancer screening at our institution between March 2015 and July 2016 was performed to assess the lung cancer detection rate, the spectrum of imaging findings (nodule or mass characteristics, degree of emphysema, etc.), and patient radiation dose indices. Results A total of 272 patients were screened during the study period. Approximately 50% (n = 135) were women. The lung cancer detection rate was 2.2% (n = 6). One patient underwent chemoradiation therapy, whereas the remainder underwent uneventful thoracoscopic resection. Approximately, 80% of screened patients met United States Preventative Services Task Force criteria for LDCT screening. The median pack-years of smoking was 42 pack-years. The mean volume CT dose index for the screening CTs was 3.12 mGy. Utilizing tube current modulation and iterative reconstruction, where available, resulted in lower patient doses. Conclusion Initial LDCT lung cancer screening at our institution yielded results similar to those of the National Lung Screening Trial. Thorough prescreening evaluation, joint decision-making, centralized coordination of screening-related care, and patient size conscious scanning protocols are critical elements of a safe and successful lung cancer screening program.

Purpose Stereotactic ablative radiation therapy (SABR) to lung tumors close to the chest wall can cause rib fractures or chest wall pain. We evaluated and propose a clinically practical solution of using noncoplanar volumetric modulated arc radiation therapy (VMAT) to reduce chest wall dose from lung SABR. Methods and materials Twenty lung SABR VMAT plans in which the chest wall volume receiving 30 Gy or higher (V30) exceeded 30 mL were replanned by noncoplanar VMAT with opposite 15° couch kicks. Dosimetric parameters including chest wall V30 and V40; lung V5, V10, V20, and mean dose; Paddick high-dose conformity index; intermediate-dose conformity index; and monitor units (MU) for each plan were used to evaluate the plan quality. The treatment time was also estimated by delivering the entire treatment. Two-sided paired t test was used to evaluate the difference of the dosimetric parameters between coplanar 1 arc (cVMAT1), coplanar 2 arcs (cVMAT2), and noncoplanar two arcs (nVMAT2) plans; differences with P Results V30 and V40 for chest wall were reduced on average by 20% ± 9% and 15% ± 11% (mean ± standard deviation) from cVMAT2 plans to nVMAT2 plans (P Conclusions We found that noncoplanar VMAT plans are feasible, clinically practical to deliver, and significantly reduce V30 and V40 of chest wall without increasing lung dose.

In order to estimate residents’ external dose due to radionuclide exposure resulting from fallout deposit on the ground, the shielding and dose reduction effects provided by structures such as houses and workplaces are taken into account as most individuals spend a large portion of their time indoors. Many works on both calculation and measurement for European and American settlements have been reported and factors such as, shielding factors, protection factors, reduction factors, and location factors have been determined. However, measurement data for Japanese settlements are lacking. Thus, the Japanese government used reduction factors given in the International Atomic Energy Agency documents from American and European settlements when Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident occurred. The United Nations Scientific Committee on the Effects of Atomic Radiation used location factors from European settlements for the same reason. Soon after the FDNPP accident, several measurements and calculations were performed to obtain specific reduction factors for Japanese settlements due to this lack of data. This research reviews previous studies that determined factors such as, shielding factors, protection factors, reduction factors, and location factors and summarizes specific results for Japan. We discuss the issues in determining these factors and in applying them to estimate indoor dose. The contribution of surface contamination to the indoor ambient dose equivalent rate is also discussed.

Introduction The primary aim of this study was to examine the impact of deep inspiration breath-hold (DIBH) amplitude on subsequent mean heart dose and V30 during radiotherapy. The secondary aim was to investigate if patient age influenced DIBH amplitude. Method A retrospective study of 30 patients with left-sided breast cancer was completed. Patients were randomly selected from the total number of patients dual scanned in free breathing (FB) and DIBH over a 2-year period. Plans were retrospectively virtually simulated and statistical analysis performed. Results All patients achieved decreased V30 and mean cardiac dose using DIBH. A positive correlation was found between DIBH amplitude and cardiac V30 dose reduction (p = 0.007, R = 0.48). Ratio of amplitude increase from FB to DIBH and cardiac V30 reduction was positively correlated and statistically significant (p = 0.04, R = 0.38); Ratio of amplitude increase of at least 15 times FB achieved 100% V30 dose reduction, however this was also achieved with ratio increase as low as 6.25 times FB. A statistically significant positive correlation was identified between DIBH amplitude and mean cardiac dose reduction (p = 0.003, R = 0.523). No correlation was found between patient age and amplitude ratio increase (p = 0.602, R = −0.099). Conclusion A 100% reduction in cardiac V30 can be achieved with a DIBH amplitude increase of 15 times FB. A full reduction can also be achieved at much lower levels (6.25 times FB in current study); however there appears to be no pre-determining patient factors to identify this. DIBH amplitudes of 1 cm–4 cm reduce cardiac mean dose by at least 50%.

Introduction Aim of the present study is to evaluate homolateral and contralateral hippocampus (H-H, C-H, respectively) dose during Fractionated Stereotactic Radiotherapy (FSRT) or Radiosurgery (SRS) for brain metastases (BM). Materials & methods Patients with BM 3 months, were considered for SRS/FSRT (total dose 15–30 Gy, 1–5 fractions). For each BM, a Flattening Filter Free (FFF) Volumetric Modulated Arc Therapy (VMAT) plan was generated with one or two arcs. Hippocampi were not considered during optimizations phase and were contoured and evaluated retrospectively in terms of dose: the Dmedian, Dmean, D0.1cc and the V1Gy, V2Gy, V5Gy and V10Gy were analyzed. Results From April 2014 to December 2015, 81 BM were treated with FFF-FSRT/SRS. For the H-H, the average values of Dmedian, Dmean and D0.1cc were 1.5Gy, 1.54Gy and 2.2Gy, respectively, while the V1Gy, V2Gy, V5Gy and V10Gy values were 25%, 8.9%, 8.9% and 2.1%, respectively. For the C–H, the average Dmedian, Dmean and D0.1 cc were 0.7Gy, 0.7Gy, 0.9Gy, respectively, while the average values of V1Gy, V2Gy, V5Gy and V10Gy were 18%, 10.2%, 2.8% and 1.4%, respectively. Tumor dimension, tumor cranial-caudal length and the distance between BM and H-H were correlated to Dmedian, Dmean and D0.1cc. For C-H, only the distance from PTV was correlated with a dose reduction. Conclusion During FFF-FSRT/SRS, hippocampus received a negligible dose. Despite its clinical significance is still under evaluation, in patients with a long life expectancy, H-H should be considered during Linac-based FSRT/SRS.

Background The cumulative exposure and risk of anesthesia, vascular access, contrast agents and radiation is emerging as a significant lifelong burden in patients with congenital heart disease (CHD). Latest generation computerized tomographic (CT) scanners are increasingly used for high resolution cardiovascular imaging and have both hardware and post processing radiation dose reduction strategies that can be implemented. Currently, these dose reduction strategies are not uniformly applied and there is a large variability in radiation dose used for the performance of CT in CHD. Methods We propose the development and implementation of a prospective, multi-center and multi-specialty consortium to measure the variability of use, risk and image quality of CT scans in patients of all ages with CHD. The primary goals of this collaboration are 1) define variability of use, diagnostic quality, and risk of cardiac CT 2) establish best practice guidelines designed to optimize diagnostic image quality with appropriate use of radiation and anesthesia exposure 3) provide institution specific feedback compared with the group norm across participating centers 4) improve the level of evidence for the use of CT in CHD through the collection of prospective and multi-institutional data. Conclusions Prospective multi-institutional data is needed to inform risk estimates of CT in CHD using current generation scanners and aggressive dose optimization techniques. This registry will provide a platform for future collaboration establishing a multi-modality risk assessment tool specific to patients with CHD.

Purpose To investigate lens dose reduction with organ based tube current modulation (TCM) using the Monte Carlo method. Methods To calculate lens dose with organ based TCM, 36 pairs of X-ray sources with bowtie filters were placed around the patient head using a projection angle interval of 10° for one rotation of Computed Tomography (CT). Each projection was simulated respectively. Both voxelized and stylized eye models and Chinese reference male phantoms were used in the simulation, and tube voltages 80, 100, 120 and 140 kVp were used. Results Dose differences between two eye models were less than 20%, but large variations were observed among dose results from different projections of all tube voltages investigated. Dose results from 0° (AP) directions were 60 times greater than those from 180° (PA) directions, which enables organ based TCM reduce lens doses by more than 47%. Conclusions Organ based TCM may be used to reduce lens doses. Stylized eye models are more anatomically realistic compared with voxelized eye models and are more reliable for dose evaluation.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 10 janvier 2018

To reduce the radiation dose to patients by optimizing oncological FDG PET/CT protocols.The baseline PET/CT protocol in our institution for oncological PET/CT examinations consisted of the administration of 5.18 MBq/kg of FDG and a CT acquisition with a reference current-time product of 120 mAs. In 2016, FDG activity was reduced to 4.44 and 3.70 MBq/kg and reference CT current-time-product was reduced to 100 and 80 mAs. 322 patients scanned with different protocols were retrospectively evaluated. For each patient, effective dose was calculated. The overall image quality was subjectively rated by the referring physician on a 4-point scale (IQ score: 1 excellent, 2 good, 3 poor but interpretable, 4 poor not interpretable). Image quality was quantitatively evaluated measuring noise in the liver.CT Results: Effective dose was progressively reduced from 9.5 ± 2.8 to 8.0 ± 2.3 and 6.2 ± 1.5 mSv (p 0.001). A mean dose reduction of 34.9% was achieved. There was a significant degradation of IQ score (p 0.05) and noise (p 0.001). Nevertheless, the number of poor quality studies (IQ score2) did not increase. PET Results: Effective dose was gradually reduced from 6.5 ± 1.4 to 5.7 ± 1.3 and 5.0 ± 1.0 mSv (p 0.001). Average dose reduction was 23.4%. IQ score (p 0.05) and noise (p 0.001) significantly degraded for lower activity protocols. However, all images with reduced activity were scored as interpretable (IQ score ≤ 3).A significant radiation dose reduction of 28.7% was reached. Despite a slight reduction in image quality, the new regime was successfully implemented with readers reporting unchanged clinical confidence.

Rationale and Objectives This study aimed to determine the optimal tube potential for unenhanced chest computed tomographies (CTs) with age-related phantoms. Materials and Methods Three physical anthropomorphic phantoms (newborn, 5-year-old child, and adult) were scanned on a third-generation dual-source CT using CAREkV in semi-mode and CAREDose4D (ref. KV: 120; ref. mAs 50). Scans were performed with all available tube potentials (70–150 kV and Sn150 kV). The lowest volume computed tomography dose index (CTDIvol) was selected to perform additional Sn100-kV scans with matched and half (Sn100-half) CTDIvol value. Image quality was evaluated on the basis of contrast-to-noise ratio (CNR). Results For the newborn phantom, 70–110 kV was selected as the optimal range (0.36–0.37 mGy). Using Sn150 kV led to an increase in radiation dose (0.75 mGy) without improving CNR (96.9 vs 101.5). Sn100-half showed a decrease in CNR (73.1 vs 101.5). The lowest CTDIvol for the child phantom was achieved between 100 and 120 kV (0.78–0.80 mGy). Using Sn150 kV increased radiation dose (1.02 mGy) without improvement of CNR (92.4 vs 95.8). At Sn100-half CNR was decreased (61.4 vs 95.8). For adults, 140 and 150 kV revealed the lowest CTDIvol (2.68 and 2.67 mGy). The Sn150 kV scan delivered comparable CNR (54.4 vs 56.6), but a lower CTDIvol (2.08 mGy). At Sn100-half CNR was comparable to the 150 kV scan (58.1 vs 56.6). Conclusion Unenhanced chest CT performed at 100 kV or 150 kV with tin filtration enables radiation dose reduction for the adult phantom, but not for the pediatric phantoms.

Pediatric barium meal procedures result in a higher patient dose than conventional X-ray imaging. Due to the fact that pediatric patients are more radiosensitive and more likely to develop mutations because of the radiation exposure during their lifetime a high patient dose is a concerning issue. The aim of this work was to test the applied earlier dose-area evaluation method comparing with direct DAP measurements and to see the changes in patient dose with the acquisition of a new, more modern, equipment. The direct measurements with a DAP meter confirmed the dose evaluation method used in our earlier works and the possibility of dose reduction shown there. Implementation of a modern equipment with new features enabling dose reduction does not guarantee a positive result without staff training and even standardization of the technical parameters with subsequent demand to follow them.

The positron emitters (18F-Sodium Fluoride (NaF)) and X-rays used in Positron emission tomography (PET) combined with computed tomography (PET/CT) imaging have a high radiation dose, which results in a high patient dose. The present research intends to determine the radiation dose and risks associated with PET/CT- 18F-Sodium fluoride examinations in patients. The 18F–NaF PET/CT was used to investigate the doses of 86 patients. Patient exposure parameters and ImPACT software were used to calculate mean effective doses. The administered activity of 185 MBq (5.0 mCi) per procedure has a mean and range based on the patient's BMI (BMI). The range of patient effective doses per procedure was found to be 4–10 mSv, with a radiation risk of 1 × 10−5 per procedure. Patient doses are determined by the patient's size, scanner type, imaging protocol, and reconstruction method. For further dose reduction, proper justification and radiation dose optimization is required.

The recommended starting dose of bosutinib is 500 mg/day for chronic-phase (CP) or accelerated-/blast-phase Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy. However, some patients may require dose reductions to manage the occurrences of adverse events (AEs). Bosutinib efficacy and safety were evaluated following dose reductions in a phase I/II study of Ph+ patients with CP CML resistant/intolerant to imatinib or imatinib plus dasatinib and/or nilotinib, and those with accelerated-/blast-phase CML or acute lymphoblastic leukemia after at least imatinib treatment. In all, 570 patients with ≥4 years’ follow-up were included in this analysis. Among 144 patients who dose-reduced to bosutinib 400 mg/day (without reduction to 300 mg/day), 22 (15 %) had complete cytogenetic response (CCyR) before and after reduction, 40 (28 %) initially achieved CCyR after reduction, and 4 (3 %) only had CCyR before reduction. Among 95 patients who dose-reduced to bosutinib 300 mg/day, 23 (24 %) had CCyR before and after reduction, 13 (14 %) initially achieved CCyR after reduction, and 3 (3 %) only had CCyR before reduction. Results were similar to matched controls who remained on 500 mg/day, indicating dose reductions had not substantially affected efficacy. The incidence of treatment-emergent AEs was lower after dose reductions, particularly for gastrointestinal events. The incidence of hematologic toxicities generally was similar before and after dose reduction. The management of AEs with bosutinib through dose reduction can lead to improved/maintained efficacy and better tolerability; still, approximately half of patients on treatment at year 4 maintained a dose of ≥500 mg/day. ClinicalTrials.gov: NCT00261846.

Interferon-free regimens achieve sustained virologic response (SVR) rates of over 90%, have generally well-tolerated adverse effects and involve 12-week treatment durations for most patients with chronic hepatitis C, including naive or previously treated patients and patients with or without cirrhosis. However, some of the treatment options recommended by the guidelines require the addition of ribavirin (RBV) or extend the duration of treatment to increase efficacy. The use of RBV is a useful tool in those difficult-to-cure patients such as patients with decompensated or genotype-3-infected cirrhosis and those who have not achieved SVR after treatment with direct-acting antivirals (DAA). Overall, adding RBV to the different combinations causes adverse effects related to a decrease in haemoglobin and involves inconveniences such as its dosage, which requires patients to take several tablets twice daily. However, severe anaemia is rare and easily manageable with a dose reduction. In addition, RBV is teratogenic. In practice, because RBV is inexpensive and well tolerated when combined with an interferon-free regimen, it continues to be a useful tool to optimise the results of some HCV treatment regimens. RBV-free regimens eliminate RBV-related adverse effects related, resulting in better tolerability, improving patient adherence and quality of life and reducing the cost of treatment.

Computed tomography (CT) frequency is approximately 11% of medical radiological procedures. Nevertheless, CT examinations contribute up to 70% collective doses. CT procedures carried out in pediatric patients represent 33% of CT procedures. This study aimed to assess pediatric doses during chest and abdomen procedures and estimated the projected radiogenic risk. In total, 83 pediatric were divided into four groups, according to their age (years). The patients were ≤six months, six months - ≤3 years, 4 - ≤ 6 years and, 7 - ≤ 15 years. The mean and range of DLP (mGy.cm) and CTDIvol (mGy) for pediatric CT chest were 42 (33–52) and 2 (1.9–2.2), respectively. The mean and range of DLP (mGy.cm) and CTDIvol (mGy) for pediatric CT abdomen pelvic region were 116 (105–129) and 3.8 (3.7–3.9), in that order. Even though pediatric' radiation doses are below the published diagnostic reference levels (DRL), additional dose reduction is required and achievable if the imaging protocol is adjusted according to the child size.