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Leveraging limited clinical and nonclinical data through modeling approaches facilitates new drug development and regulatory decision making amid the coronavirus disease 2019 (COVID-19) pandemic. Model-informed drug development (MIDD) is an essential tool to integrate those data and generate evidence to (i) provide support for effectiveness in repurposed or new compounds to combat COVID-19 and dose selection when clinical data are lacking; (ii) assess efficacy under practical situations such as dose reduction to overcome supply issues or emergence of resistant variant strains; (iii) demonstrate applicability of MIDD for full extrapolation to adolescents and sometimes to young pediatric patients; and (iv) evaluate the appropriateness for prolonging a dosing interval to reduce the frequency of hospital visits during the pandemic. Ongoing research activities of MIDD reflect our continuous effort and commitment in bridging knowledge gaps that leads to the availability of effective treatments through innovation. Case examples are presented to illustrate how MIDD has been used in various stages of drug development and has the potential to inform regulatory decision making.

Regular immunoglobulin treatment maintains strength and prevents disability in chronic inflammatory demyelinating polyneuropathy (CIDP). Discrimination between active disease, with optimum symptom control on treatment, and disease in remission not requiring treatment is essential for therapeutic decision-making and clinical trial design. To compare treatment cessation versus gradual dose reduction in assessment of disease activity (immunoglobulin dependence) in a cohort of stable CIDP patients on maintenance immunoglobulin treatment. An approach to restabilization of immunoglobulin-dependent individuals is also described. Retrospective review of IVIg cessation or gradual reduction in 33 patients with stable CIDP on maintenance IVIg. Demographic, clinical and treatment data were collected; clinical monitoring data were recorded prospectively as part of routine clinical practice. A total of 21/33 patients (62.6%) were immunoglobulin dependent, (gradual dose reduction:11, cessation:10). Mean change in Inflammatory Rasch-built Overall Disability Scale (I-RODS) (-15, standard deviation [SD] 16) and Medical Research Council Sum Score (MRC-SS) (-4, SD: 4) was clinically and statistically meaningful (>75% exceeded minimum clinically important differences). Mean time to deterioration was 5.0 (SD: 4.6) months, shorter in cessation group (3.5 months) than gradual reduction group (8.8 months). All patients were restabilized to previous baseline (M: 2.3, SD: 4.3 months), half within 1 week of retreatment. A total of 12 patients (37.4%) remained stable without treatment for ≥2 years (remission). A total of 50% were identified rapidly by cessation and 50% by gradual dose reduction requiring mean 4.8 (SD: 2.8) years follow-up and costing £113 623 per person Ig spend. No predictors of disease activity were identified. A treatment cessation trial with close clinical monitoring is an efficient, cost-effective and safe approach to assessing disease activity in CIDP.

Introduction Sonidegib is a Hedgehog pathway inhibitor approved to treat locally advanced basal cell carcinoma and, depending on regulatory approval, metastatic basal cell carcinoma. Results from the BOLT study demonstrated robust efficacy and continued tolerability through 42 months. This analysis evaluated the impact of sonidegib dose reductions and interruptions in patients with advanced basal cell carcinoma through 42 months. Methods BOLT was a randomized, double-blind, multicenter, phase 2 study. Adults with no previous Hedgehog pathway inhibitor therapy were randomized 1:2 to sonidegib 200 or 800 mg once daily. Primary endpoint was objective response rate. Dose modifications were permitted in patients unable to tolerate the dosing schedule or if a treatment-related adverse event was suspected. Results The incidence of dose interruptions was similar between the 200- and 800-mg groups (68.4% vs 65.3%, respectively). Dose reductions occurred more frequently in patients receiving sonidegib 800 mg (36.7%) than 200 mg (16.5%). Overall response rate for all patients receiving sonidegib 200 mg daily was 48.1% and was similar to those of patients without dose reduction or interruption (48.5%) and patients with at least one dose reduction or interruption (46.2%). Conclusion Dose reductions and interruptions were practical and did not impact the efficacy of sonidegib. In patients with advanced basal cell carcinoma who necessitate long-term treatment, dose interruptions may be beneficial for continued treatment and disease control. Trial registration: ClinicalTrials.gov identifier, NCT01327053. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00619-4.

Toxic erythema of chemotherapy is an umbrella term for several non-allergic cutaneous reactions to chemotherapeutic agents. Given the heterogenous range of presentations, we will review the differential diagnoses and treatment approaches, particularly for hospitalized patients. Early recognition, holding chemotherapy, or dose reduction and monitoring fluid balance for severely ill patients is the mainstay of treatment. Supportive care with topical steroids, emollients, and wound care have shown benefit. Toxic erythema of chemotherapy can mimic several common eruptions seen in oncologic patients. The recognition of both clinical and pathological features by inpatient dermatologists allows for appropriate management, and dose reduction if necessary, in order for patients to continue oncologic treatment.

Background Levocarnitine deficiency has been observed in patients receiving parenteral nutrition (PN) and can cause or worsen hypertriglyceridemia. The objective was to characterize use of levocarnitine supplementation in PN and evaluate its effect on triglyceride levels in hospitalized adults. Methods This retrospective, single-center study included patients with triglyceride levels ≥175 mg/dl while receiving PN who had a subsequent reduction in lipid injectable emulsion dose. A piecewise linear regression was used to evaluate trends in triglyceride levels before and after the intervention, defined as initiation of levocarnitine in PN for the levocarnitine group, or reduction in lipid injectable emulsion alone for the control group. Results Two hundred sixty-one patients who received PN had an elevated triglyceride level and lipid injectable emulsion dose reduction, of which 97 (37.2%) received levocarnitine in PN. The median (IQR) levocarnitine dose added to PN was 8.0 (5.7-9.9) mg/kg. Triglyceride levels at 30 days post-intervention did not differ between groups (125 vs 176 mg/dl, P = .345). The addition of levocarnitine to PN was associated with a significantly greater rate of reduction in triglyceride levels pre-intervention to post-intervention compared with a reduction in lipid injectable emulsion alone (-11 vs -3 mg/dl per day; 95% CI, -15 to -2; P = .012). Conclusion In hospitalized adults with hypertriglyceridemia who had a lipid injectable emulsion dose reduction, the addition of levocarnitine in PN was not associated with a difference in triglyceride levels at 30 days; however, a greater rate of improvement in pre-intervention to post-intervention triglyceride levels was observed.

Background Antipsychotic medications are used to treat schizophrenia and may be associated with adverse effects, including tardive dyskinesia (TD), following prolonged use or upon changes in dosing regimen. Objective This retrospective analysis evaluated the burden of antipsychotic dose reduction in Medicare patients with schizophrenia. Methods This matched cohort study used Medicare claims data (2006–2017) analyzed for patients with schizophrenia and two or more claims for antipsychotics, with one or more antipsychotic monotherapy period ≥ 90 days. Cohorts were defined for patients with antipsychotic dose reductions ≥ 10% and stable doses. A separate analysis was conducted using patients with dose reductions ≥ 30%. Outcomes included all-cause emergency room (ER) visits, all-cause inpatient visits, schizophrenia relapse, other psychiatric relapse, and TD diagnosis. Covariates included age, disease duration, comorbidities, and medication use. Results The analysis included 276,030 patients with ≥ 10% dose reductions and 211,575 patients with ≥ 30% dose reductions. Patient characteristics were balanced between cohorts. Patients with ≥ 10% or ≥ 30% dose reductions had a shorter time to ER visit, inpatient visit, schizophrenia relapse, other psychiatric relapse, and TD diagnosis versus those receiving stable doses (all p

Erlotinib is used to treat advanced non-small-cell lung cancer (NSCLC), the common serious adverse events are skin disorders. The dose intensity of erlotinib should be maintained as much as possible by an appropriate control of adverse events in order to maintain its efficacy. Therefore, the management of these adverse events related to skin disorders would enable a continuous erlotinib treatment without interruption and dose reduction. This study assessed the effect of pharmaceutical consultation in outpatients who received erlotinib. Participants included patients with NSCLC who received erlotinib therapy for more than 6 months between December 2007 and March 2019. The participants were divided into two groups: the intervention group that included patients who received pharmaceutical consultation targeting outpatients by a pharmacist and the nonintervention group that included patients who did not. We retrospectively investigated patient characteristics, treatment regimens, and treatment efficacy. We included a total of 33 patients (18 and 15 patients in the nonintervention and intervention groups, respectively) in this study. The intervention group had a significantly higher median relative dose intensity (RDI) of erlotinib than the nonintervention group (P = 0.0437). In addition, the pharmaceutical consultation targeting outpatients was identified as a factor contributing to the maintenance of RDI ≥ 90% (P = 0.0269). The present study indicated that there was improvement in RDI with pharmaceutical consultation targeting outpatients with advanced NSCLC.

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.

Objectives: Toxicities of the oral soft and hard tissues due to the radiotherapy of the head and neck cancer can potentially lead to interruptions of cancer treatment and/or dose reduction, resulting in poorer outcomes. The aim of this study was to assess the knowledge of dental practitioners in Saudi Arabia about oral and dental assessment for and complications of radiotherapy of head and neck cancer. Materials and Methods: An online, already validated, self-administered questionnaire was sent via an online link through WhatsApp groups and other Social Media platforms to reach out to the majority of targeted samples (dental practitioners working in Saudi Arabia). Responses were statistically described and analyzed based on the different grouping factors: gender, specialty, working sector, region of work and experience. Results: There were 370 respondents, 257 (69.5%) of them were males. Most of the respondents were general dental practitioners [144 (38.9%)], The percentages of the correct answers range from as low as 26.2 to as high as 97%. The per cent of correct answers by the respondents in 18 out of 31 questions was above 75%. Females, dental specialists (specifically prosthodontics), working in public sectors and in the central and western regions of Saudi Arabia were associated with higher levels of knowledge. Conclusion: Our results show highly variable knowledge of dental practitioners on oral and dental assessment for, and complications and management of radiotherapy to the head and neck area; that knowledge seems to fluctuate considerably with gender, experience, work sector and specialty.

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

Oropharyngeal cancers related to the human papillomavirus are a growing segment of head and neck cancers throughout the world. These cancers are biologically and demographically unique with patients presenting at younger ages and with more curable disease. This combination of factors heightens the importance of normal tissue sparing because patients will live a long time with treatment sequelae. Proton therapy has demonstrated benefits in reducing normal tissue exposure, which may lead to less toxicity, a higher quality of life, less immunologic suppression, and lower cost. Research investigating deintensified radiation volumes and doses are also underway. These deintensification studies synergize well with the beam characteristics of proton beam therapy and can decrease that already reduced normal tissue exposure enabled by proton therapy. Future studies should refine patient selection to best allow for volume and dose reduction paired with proton therapy.

Nowadays due to modern risk-adapted treatment protocols high survival rates have been achieved in patients with aggressive B-cell lymphomas, even at stages III–IV these indicators overrun 90 %. Mainly these successes were associated with the inclusion of rituximab in the standard chemotherapy regimens. As the follow up period of the patients is lengthened, it has become clear that ongoing treatment is associated with the development of immediate and long-term adverse effects of chemoimmunotherapy. In Russia and the world, there are multicenter studies aimed at studying prognostic factors that make it possible to reduce single and/or total doses of chemotherapy drugs, and therefore, to reduce chemotherapy toxicity. The obtained data allow considering the early complete antitumor effect (after 2 courses of therapy) as an advantage factor, so it is possible to reduce program chemoimmunotherapy intensity without reducing high patients survival rates.

Introduction: Glucocorticoids represent a highly effective treatment for giant cell arteritis (GCA); however, steroid-dependency frequently hinders an adequate dose reduction. This has led to a flo...

Dosage of pharmaceuticals is determined and approved based on pivotal clinical trial results in Phase 3. However, in the post-marketing setting, it is often adjusted according to conditions of individual patients. Some pharmaceuticals are used at a lower dose than the approved dose for safety reasons or in elderly patients. In this study, we examined the relationships between dose discontinuation or dose reduction, for safety reasons as well as participation of elderly patients in clinical trials, and lower-dose prescriptions in the post-marketing setting. We collated the dataset of 113 eligible pharmaceuticals from those that were approved in Japan between 2005 and 2014. Subsequently, we calculated the proportions of patients who withdrew from the study, whose medication was discontinued, or dose reduced due to adverse events, and of elderly patients (over sixty-five years old) to those who were exposed to the approved dose range in the pivotal clinical trials. Then their relationships with lower-dose prescription in the post-marketing setting were examined using Mann-Whitney U test. The proportions of patients who withdrew from the study (p=0.0019), whose medication was discontinued owing to adverse events (p=0.0007), or whose dose was reduced owing to adverse events (p

Background and Aim Medication nonadherence is common in patients with inflammatory bowel disease (IBD) and has been associated with worse outcomes. The coronavirus disease 2019 (COVID‐19) pandemic led to significant consumer and medical concern regarding the possible risks of immunosuppressive medications during the pandemic. This study aimed to examine medication adherence and complementary and alternative medicine (CAM) usage during the COVID‐19 pandemic. Methods An online survey was sent to patients from two tertiary IBD units. The survey included medication nonadherence attributed to the COVID‐19 pandemic, complementary therapy, and IBD medication use. Validated measures of IBD disease activity, medication adherence, and beliefs about medicines were obtained. Results Of 262 respondents (median age of 46, 58% female) 14 (5%) patients reported self‐initiated missed doses or dose reduction of IBD medications directly attributed to the COVID‐19 pandemic. Positive associations with medication nonadherence included current corticosteroid requirement (P = 0.022), higher disease activity scores (P = 0.026), and higher concern about medicines score (P = 0.04). CAM usage was common, aimed at treating mental health in most cases, and infrequently attributed to the COVID‐19 pandemic. Conclusions Even in the setting of low COVID‐19 prevalence, the pandemic reduced IBD medication adherence in 1 in 20 patients. This reduced adherence was co‐associated with increased disease activity and corticosteroid use. Understanding the underlying beliefs driving suboptimal IBD medication adherence is critical to prevent avoidable adverse IBD outcomes., The coronavirus disease 2019 (COVID‐19) pandemic resulted in widespread concern that inflammatory bowel disease (IBD) medications may result in higher infection risk and poor outcomes. The rate of medication nonadherence attributed to the COVID‐19 pandemic in an Australian IBD population was low and associated with increased IBD disease activity, corticosteroid use, and patient concern over medications. Understanding the underlying beliefs driving suboptimal IBD medication adherence is critical to prevent avoidable adverse IBD outcomes.

To unveil and delineate the elements applicable to the radiation protection of a femoral entry shield, calculate its mass attenuation coefficient, and demonstrate its dose reduction efficacy for interventional radiologist performing transarterial embolization (TAE) of ruptured hepatocellular carcinoma (rHCC). The lead equivalency of the shield was firstly validated. Electron microscopy was used to confirm the femoral entry shield being lead-free and to analyze the elemental content, with which the mass attenuation coefficient of the shield was calculated. An adult phantom, irradiated at the upper abdomen to simulate the TAE of rHCC, was used together with a dosimeter attached to the palm of a hand phantom. The dose rates at the hand phantom were measured, with the rHCC clinical protocol, without and with the femoral entry shield placed over the right femoral access site of the adult phantom. Without using the shield, the average hand dose rate was measured to be 0.325 μSv/sec. While using the shield, it was determined to be 0.110 μSv/sec. There was significant 66% dose reduction to the hand dose of IRs performing angiographic intervention with the femoral entry shield.

Purpose The purpose of this study was to assess the quality of treatment planning using the PlanIQTM software and to investigate whether it is possible to improve the quality of treatment planning using the “Feasibility dose‐volume histogram (DVH)TM” implemented in the PlanIQTM software. Methods Using the PlanIQTM software, we retrospectively analyzed the learning curve regarding the quality of the treatment plans for 148 patients of prostate intensity‐modulated radiation therapy and volumetric‐modulated radiation therapy performed at our institution over the past eight years. We also sought to examine the possibility of improving treatment planning quality by re‐planning in 47 patients where the quality of the target dose and the dose limits for organs at risk (OARs) were inadequate. The re‐planning treatment plans referred to the Feasibility DVHTM implemented in the PlanIQTM software and modified the treatment planning system based on the target dose and OAR constraints. Results Analysis of the learning curve of the treatment plans quality using PlanIQTM software retrospectively showed a trend of improvement in the treatment plan quality from year to year. The improvement in the treatment plans quality was more influenced by dose reduction in the OARs than by target coverage. In all cases where re‐planning was performed, the improvement in the treatment plan's quality resulted in a better treatment plan than the one adopted for delivery to patients in the clinical plan. Conclusions The PlanIQTM provided insights into the quality of the treatment plans at our institution and identified problems and areas for improvement in the treatment plans, allowing for the development of appropriate treatment plans for specific patients.

Immunotherapy-related hepatitis accounts for 3-6% of all immune-related adverse events (irAE). Reintroduction of checkpoint inhibitors after irAE is matter of debate, weighing the risk of a relapse of adverse events against the possibility of improving disease control. Pharmacokinetic modelling has changed the paradigm of weight-based dosing to flat dose for checkpoint inhibitors, however, it is currently unknown if this poses underweight (80 kg) patients to a higher risk of toxicity. Weight-based dosing has been opted as a less dangerous and more economic option, especially for underweight patients. Is dose reduction dosing a strategy to permit checkpoint inhibitors reintroduction after immune-related adverse events?We describe a case of checkpoint inhibitor reintroduction after immunotherapy-related hepatitis, with dose reduction based on weight-based dosing (nivolumab 165 mg Q2w) in a patient with metastatic renal cell cancer.After three cycles, he had a relapse of hepatitis leading to prolonged steroid use and opportunistic infections.Dose reduction in underweight patients is not the preferred strategy to permit rechallenge after immunotherapy-related hepatitis. Exploration of other secondary prevention strategies is warranted.

The emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initially managed as a septic shock with broad-spectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever.

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.

Aim: Patient-reported symptoms, functioning and overall quality of life (QoL) were compared between dacomitinib and gefitinib in ARCHER 1050. Patients & methods: Patients (n = 448) with advanced EGFR mutation-positive non-small-cell lung cancer completed the EORTC-QLQ-C30 questionnaire and its lung-specific module, LC-13. Mean scores over time were analyzed using a mixed model for repeated measures. Results: Both treatments showed early improvement in disease-related symptoms that was maintained during treatment. Treatment-related diarrhea and sore mouth decreased following dose reduction with dacomitinib. There were no clinically meaningful changes in functioning and overall QoL in either treatment group. Conclusion: Longer treatment duration, enabled by dose reduction, allowed patients on dacomitinib to improve treatment-related symptoms and maintain functioning and overall QoL for longer than gefitinib.

The aim of this review is to provide clinicians and technicians with an overview of the development of CT protocols in lung cancer screening. CT protocols have evolved from pre-fixed settings in early lung cancer screening studies starting in 2004 towards automatic optimized settings in current international guidelines. The acquisition protocols of large lung cancer screening studies and guidelines are summarized. Radiation dose may vary considerably between CT protocols, but has reduced gradually over the years. Ultra-low dose acquisition can be achieved by applying latest dose reduction techniques. The use of low tube current or tin-filter in combination with iterative reconstruction allow to reduce the radiation dose to a submilliSievert level. However, one should be cautious in reducing the radiation dose to ultra-low dose settings since performed studies lacked generalizability. Continuous efforts are made by international radiology organizations to streamline the CT data acquisition and image quality assurance and to keep track of new developments in CT lung cancer screening. Examples like computer-aided diagnosis and radiomic feature extraction are discussed and current limitations are outlined. Deep learning-based solutions in post-processing of CT images are provided. Finally, future perspectives and recommendations are provided for lung cancer screening CT protocols.

Background Vitamin K antagonists (VKAs) are still in use for oral anticoagulation, but not all indications allow their replacement by direct oral anticoagulants. Although formal dose reduction is not required in patients with impaired kidney function, case reports indicate that acute kidney injury (AKI) might be associated with derailment of VKA therapy. Methods The study retrospectively collected patients from a tertiary nephrology care centre who experienced AKI while being treated with VKA. In these individuals, the international normalized ratio (INR) as a measure of anticoagulant effect during renal failure was compared with a reference time point with stable kidney function. Results A total of 100 patients with AKI and ongoing VKA therapy met the inclusion criteria. The majority (76%) of patients had AKI with CKD. Volume depletion (n = 43), septic renal failure (n = 22), decompensated heart failure (n = 18) and toxic renal damage (n = 11) were the most important causes of AKI. The average INR values at the time of AKI were higher than at the reference time point [median 3.17 (range 1.10–13.0) versus 2.24 (1.07–5.17); P Conclusions The effect of AKI on anticoagulation by VKA has not been systematically described. This risk should be considered in patients at high risk for AKI.

Ketoconazole (Ketoconazole HRA™), an imidazole derivative, is a useful treatment option in the management of endogenous Cushing’s syndrome in adults and adolescents > 12 years of age, based on evidence from more than three decades of use of the drug in clinical practice. Originally developed as an antifungal agent, ketoconazole is a potent steroidogenesis inhibitor. Approximately 60% (range, 45–88% across key studies) of patients with Cushing’s syndrome who are treated with ketoconazole achieve control of hypercortisolism, with efficacy demonstrated in all aetiologies of the disease. Furthermore, reductions in cortisol levels in patients treated with ketoconazole are associated with improvements in clinical and biochemical features of Cushing’s syndrome and common comorbidities. Hepatotoxicity, the main safety concern with ketoconazole, can be managed effectively with careful monitoring of hepatic enzymes, with hepatic enzyme abnormalities generally being mild to moderate, asymptomatic and reversible upon dose reduction or drug withdrawal.

The Department of Veterans Affairs and Department of Defense (VA/DoD) Clinical Practice Guideline for PTSD recommends against the use of benzodiazepines. Despite the recommendation, clinicians continue potentially inappropriate benzodiazepine prescribing practices for veterans with PTSD. We designed an educational product aimed at decreasing benzodiazepine use in PTSD care. Using VA data, the booklet was mailed to over 1300 New England veterans. Veterans were advised to discuss the booklet's information with their medical provider on their next appointment. The intervention resulted in a significant decrease in benzodiazepine use in veterans with PTSD, with 66% of the sample showing a dose reduction from pre- to post-booklet time points. Longitudinal analyses noted that rural veterans were significantly more likely to reduce benzodiazepine use than those in urban settings. Direct to consumer education appears to be an effective strategy to empower rural veterans to improve benzodiazepine prescribing safety and quality.

Background: Hemispherotomy is the treatment of choice for children with refractory epilepsy. Although hemiplegia, sensory and motor impairments result from this surgical procedure, seizure control is effective as well as anticonvulsant dose reduction. Description of functional gains after rehabilitation of these children are still incomplete. Aims: To evaluate the effects of an early intensive rehabilitation program in the gross motor function of lower limbs after 30, 90, 180 and 360 days of surgery for the treatment of epilepsy (hemispherotomy), and compare to historic controls. Materials and Methods: prospective and longitudinal case series, with historic controls. Fourteen out of sixteen children who underwent hemispherotomy from January 2012 to February 2013 received an early rehabilitation protocol (ERP). Functional assessment included the Berg Balance Scale (BBS), Fugl-Meyer Scale (FMS) lower limb subscale, and Gross Motor Function System of Classification (GMFCS), as well as the need of wheelchairs and walking aids. A historical group of 13 children who received a conventional rehabilitation protocol (CRP) was used as control. Results: FMS and BBS improved in ERP subjects until 6 months after surgery and reached a plateau. One year after hemispherotomy, all children in the ERP group could walk independently and had mild limitations to mobility whereas, among those in the CRP subjects, there was a higher prevalence of musculoskeletal deformities and severe gait restrictions. Conclusions: ERP promotes rapid functional recovery during one-year follow-up and, as compared to the CRP group, the average functional capacity of the ERP group was considerably higher. These data support the beneficial effects of a specific, individualized and early rehabilitation approach for such patients.

Background Rituximab is safe and effective for treating relapsing–remitting multiple sclerosis (RRMS) according to phase II and observational studies. There are limited data on disease activity after discontinuation and dose reduction. The objective of this study was to evaluate the effects on inflammatory disease activity after discontinuation or dose reduction of rituximab in patients with RRMS or clinically isolated syndrome (CIS). Methods In this retrospective observational study, we included all RRMS and CIS patients ever treated with rituximab at the University Hospital of Umeå who had either; (1) discontinued treatment at any time or (2) reduced the dose to a mean of Results A total of 225 patients treated with mean (SD) 6256 (2456) mg rituximab during mean (SD) 6.5 (2.0) years were included. There were no differences regarding the annualized relapse rates during full dose versus reduced dose or off treatment (0.02 versus p = 0.09), neither regarding proportion MRI scans with new or enlarged T2 lesions (0.03 versus 0.01 and 0.03, p = 0.37) or contrast-enhancing lesions (p = 0.22). Conclusions This study indicates that rituximab has long-term effects on inflammatory disease activity and that disease reactivation is rare in MS patients who discontinued treatment for any reason. It also suggests that treatment with low-dose rituximab (

Background: Lung cancer patients struggle with high toxicity rates. This study investigates if IMRT plans with individually set beam angles or uni-lateral VMAT plans results in dose reduction to OARs. We investigate if introduction of a RapidPlan model leads to reduced dose to OARs. Finally, the model is validated prospectively. Material and methods: Seventy-four consecutive lung cancer patients treated with IMRT were included. For all patients, new IMRT plans were made by an experienced dose planner re-tuning beam angles aiming for minimized dose to the lungs and heart. Additionally, VMAT plans were made. The IMRT plans were selected as input for a RapidPlan model, which was used to generate 74 new IMRT plans. The new IMRT plans were used as input for a second RapidPlan model. This model was clinically implemented and used for generation of clinical treatment plans. Dosimetric parameters were compared using a Wilcoxon signed rank test or a 1-sided student’s t-test. p

Computed tomography (CT) plays a pivotal role as a diagnostic tool in many diagnostic and diffuse pancreatic diseases. One of the major limits of CT is related to the radiation exposure of young patients undergoing repeated examinations. Besides the standard CT protocol, the most recent technological advances, such as low-voltage acquisitions with high performance X-ray tubes and iterative reconstructions, allow for significant optimization of the protocol with dose reduction. The variety of CT tools are further expanded by the introduction of dual energy: the production of energy-selective images (i.e., virtual monochromatic images) improves the image contrast and lesion detection while the material-selective images (e.g., iodine maps or virtual unenhanced images) are valuable for lesion detection and dose reduction. The perfusion techniques provide diagnostic and prognostic information lesion and parenchymal vascularization and interstitium. Both dual energy and perfusion CT have the potential for pushing the limits of conventional CT from morphological evaluation to quantitative imaging applied to inflammatory and oncological diseases. Advances in post-processing of CT images, such as pancreatic volumetry, texture analysis and radiomics provide relevant information for pancreatic function but also for the diagnosis, management and prognosis of pancreatic neoplasms. Artificial intelligence is promising for optimization of the workflow in qualitative and quantitative analyses. Finally, basic concepts on the role of imaging on screening of pancreatic diseases will be provided.

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.

Older patients tend to have multimorbidity represented by multiple chronic diseases or geriatric conditions due to aging changes of organs, which require a variety of medical management. Currently, there are no sufficient disease treatment guidelines for older people with multimorbidity, therefore physicians have difficulty managing multimorbidity, such as which diseases should be treated intensively or to what extent the conditions should be improved. Furthermore, there are other points to be considered when initiating the treatment of diseases. For example, physicians must assess physical function. Some people have no difficulty with ambulation, but some are bedridden and have difficulty getting up on their own. As there are differences in disease severity, comorbid conditions and life expectancy, there should be differences in deciding treatment and prescribing drugs. It may be necessary to change the option for treatment depending on cognitive function, the living environment and the care environment, using comprehensive geriatric assessments. In addition, when treating multimorbidity, patients tend to have polypharmacy, which is a risk for adverse drug events. Because of this, it is necessary to consider dose reduction and drug discontinuation in patients with polypharmacy. Because of the global increase in older patients with multimorbidity, developing an essential method for managing multimorbidity is an urgent issue. More research and practices are necessary to achieve high-quality care in patients with multimorbidity. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; ••: ••-••.

Edoxaban is used for venous thromboembolism (VTE) treatment. Real-life data are lacking about its use in long-term therapy. We aimed to assess the efficacy and the safety of edoxaban for long-term VTE treatment in a real-life setting. Patients with VTE included in the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry, receiving edoxaban 60 or 30 mg daily were prospectively followed up to validate the benefit of using different dosages. The main outcome was the composite of VTE recurrences or major bleeding in patients with or without criteria for dose reduction. Multivariable analysis to identify predictors for the composite outcome was performed. From October 2015 to November 2019, 562 patients received edoxaban for long-term therapy. Most (94%) of the 416 patients not meeting criteria for dose reduction received 60 mg daily, and 92 patients meeting criteria (63%) received 30 mg daily. During treatment, two patients developed recurrent VTE, six had major bleeding and nine died (2 from fatal bleeding). Among patients not meeting criteria for dose reduction, those receiving 30 mg daily had a higher rate of the composite event (hazard ratio (HR) 8.37; 95% confidence interval (CI) 1.12–42.4) and a significant higher mortality rate (HR 31.1; 95% CI 4.63–262) than those receiving 60 mg. Among patients meeting criteria for dose reduction, those receiving 60 mg daily had no events, and a nonsignificantly higher mortality rate (HR 5.04; 95% CI 0.54–133) than those receiving 30 mg daily. In conclusion, edoxaban seems to be effective and safe for long-term VTE treatment in real life. Criteria for dose reduction should be reformulated., No funding was received for this work

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.

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

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) is notable for the fusion of chromosomes 9 and 22, forming the BCR-ABL1 gene [1]. This fusion is observed in 20–40% of adult...

Despite major advances in the management and high cure rates of childhood acute lymphoblastic leukemia (ALL), patients still suffer from many drug-induced toxicities, sometimes necessitating dose reduction, or halting of cytotoxic drugs with a secondary risk of disease relapse. In addition, investigators have noted significant inter-individual variability in drug toxicities and disease outcomes, hence the role of pharmacogenetics (PGx) in elucidating genetic polymorphisms in candidate genes for the optimization of disease management. In this review, we present the PGx data in association with main toxicities seen in children treated for ALL in addition to efficacy, with a focus on the most plausible germline PGx variants. We then follow with a summary of the highest evidence drug-gene annotations with suggestions to move forward in implementing preemptive PGx for the individualization of treatment regimens for children with ALL.

Introduction Up to 20% of patients with brain metastases treated with immune checkpoint inhibitor (ICI) therapy and concomitant stereotactic radiosurgery (SRS) suffer from symptomatic radiation necrosis. The goal of this study is to evaluate Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) on six-month symptomatic radiation necrosis rates. Methods This study is a prospective single arm Phase I pilot study which will recruit patients with brain metastases receiving ICI delivered within 30 days before SRS. All patients will be treated with RADREMI dosing, which involves SRS doses of 18 Gy for 0−2 cm lesions, 14 Gy for 2.1−3 cm lesions, and 12 Gy for 3.1−4 cm lesions. All patients will be monitored for six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis) and six-month local control. We expect that RADREMI dosing will significantly reduce the symptomatic radiation necrosis rate of concomitant SRS + ICI without significantly sacrificing the local control obtained by the present RTOG 90−05 SRS dosing schema. Local control will be defined according to the Response Assessment in Neuro-Oncology (RANO) criteria. Discussion This study is the first prospective trial to investigate the safety of dose-reduced SRS in treatment of brain metastases with concomitant ICI. The findings should provide fertile soil for future multi-institutional collaborative efficacy trials of RADREMI dosing for this patient population. Trial Registration Clinicaltrials.gov identifier: NCT04047602 (registration date: July 25, 2019).

Two female patients aged 70 and 72 with video-urodynamics-confirmed detrusor overactivity and detrusor underactivity (DO-DU) were treated. Patients were refractory to medical therapies and had previously failed intravesical botulinum toxin type A (BoNT-A) at other centers secondary to urinary retention and difficulty with self-catheterization. Placement of an Interstim II device (Medtronic, Minneapolis, Minnesota) for sacral neuromodulation (SNM) as alternative third-line treatment partially improved overactive bladder (OAB) symptoms while significantly improving voiding symptoms. Postvoid residual (PVR) of patients improved from a median of 118 mL (110-125 mL) to 20 mL (18-26 mL) and 213 mL (195-230 mL) to 70 mL (60-73 mL), respectively. Addition of medical therapies post SNM failed to modify OAB symptoms further and a rechallenge with dose-reduced BoNT-A was undertaken.OAB symptoms were significantly improved by addition of BoNT-A, while urinary retention was avoided (median PVR post BoNT-A 38 mL [34-40 mL] and 185 mL [150-205 mL], respectively). Reduction in incontinence pad use as well as resolution of nighttime incontinence in both patients and daytime incontinence in one patient was achieved. DO-DU patients treated by SNM who have improved bladder emptying (PVR

To evaluate the proportion of patients underdosed (prescribed a reduced dose despite lack of indication) with a novel oral anticoagulant (NOAC) in an older and frail population with atrial fibrillation (AF). Around half (51%) of patients received a reduced dose despite lacking formal criteria for dose reduction. Adjusted combined stroke, systemic embolism and major bleeding event rate was higher in underdosed patients, but not adjusted survival. A very significant proportion of frail and older patients with AF remains under an inappropriately reduced-dosed NOAC, and these patients have a worse prognosis. An individualized approach should be taken regarding the use of novel oral anticoagulants (NOAC) in frail and older patients with atrial fibrillation (AF). We hypothesized that there would be a high proportion of underdosed patients among an older and frail population, where bleeding risk is higher. We retrospectively analyzed patients admitted to an Internal Medicine ward with a previous diagnosis of AF and discharged with a NOAC (n = 327). We compared survival and incidence of dosing-related events (stroke, systemic embolism, and major bleeding) at 1-year between inappropriately underdosed patients (dose reduction without a formal indication) and the rest of the population. A total of 167 patients (51%) received a reduced dose despite lacking formal criteria for dose reduction. Before adjustment, underdosed patients, in comparison with non-underdosed patients, had a higher mortality at 1 year (HR = 1.6, 95% CI 1.2–2.1, p = 0.003) and a higher combined stroke, systemic embolism, and major bleeding event rate at 1-year (HR = 3.2, 95% CI 1.3–8.0, p = 0.015). After adjustment, combined stroke, systemic embolism, and major bleeding event rate was higher in underdosed patients (HR 3.7, 95% CI 1.1–12.3, p = 0.030), but survival was not different in the adjusted model (HR 1.4, 95% CI 0.9–2.1, p = 0.110). Underdosed patients have a significant survival disadvantage and this may be due to clinician prescription bias, since this difference does not remain after adjusting for confounders. Combined stroke, systemic embolism, and major bleeding event rate was higher in underdosed patients.

Sorafenib is a current first-line treatment option for advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the impact of early adverse events (AEs) requiring sorafenib dose adjustment on survival outcomes of patients with advanced HCC. The study was a secondary analysis of the phase III clinical trial NCT00699374. A landmark Cox proportional hazard analysis was used to evaluate the association between early AEs requiring sorafenib dose adjustment with survival outcomes. The primary outcome was overall survival (OS) with progression-free survival (PFS) as secondary. AEs requiring sorafenib dose adjustment within the first 28 days of therapy were significantly associated with OS (HR [95% CI]; dose interruption = 0.9 [0.7–1.2]; dose reduction = 0.6 [0.5–0.9]; discontinuation = 1.7 [0.9–3.4]; P = 0.005). No statistically significant association with PFS was identified (P = 0.148). Sorafenib dose interruptions and reduction due to AEs did not compromise the survival outcomes of patient with advanced HCC. Patients who required a sorafenib dose reduction were observed to have more favourable OS compared to those who did not experience an AE which required a dose adjustment.

Over the past 2 decades, rapid advancement in systemic anticancer therapeutics has led to astounding improvement in survival rates of patients with cancer. However, this celebrated progress has brought with it an evolving spectrum of drug toxicities that limit their prodigious capabilities. Cutaneous adverse events are of the most frequent of these toxicities, with substantial impact on quality of life and commonly resulting in dose reduction or change in therapy. Thus, familiarity with the array of dermatologic manifestations caused by these drugs is prudent for patient treatment. As such, the advent of dedicated oncodermatologists, and their introduction into multidisciplinary cancer care, has been crucial in optimizing treatment through therapeutic achievement and overall well-being. This review will address the epidemiology, clinical presentations, and management strategies of the major dermatologic adverse events of systemic anticancer agents, including cytotoxic chemotherapy, targeted therapy, and immunotherapy.

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

Objectives To systematically review the impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and severe adverse events (SAEs) in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) in remission or low disease activity (LDA) state. Materials and methods A meta-analysis based on a systematic review of PubMed, Embase, Cochrane, until August 2019, as well as relevant databases of international conferences, was used to evaluate the risk difference (RD) at 95% confidence interval (95% CI) of incidence density of serious infections, SAEs, malignancies, cardiovascular adverse events (CV AEs), or deaths after tapering (dose reduction or spacing) compared to continuation of targeted therapies. Results Of the 1957 studies initially identified, 13 controlled trials (9 RA and 4 SpA trials) were included in the meta-analysis. 1174 patient-years were studied in the tapering group (TG) versus 1086 in the usual care group (UC). There were 1.7/100 patient-year (p-y) serious infections in TG versus 2.6/100 p-y in UC (RD (95% CI) 0.01 (0.00 to 0.02), p = 0.13) and 7.4/100 p-y SAEs in TG versus 6.7/100 p-y in UC (RD 0.00 (− 0.02 to 0.02), p = 0.82). The risk of malignancies, CV AEs, or deaths did not differ between the tapering and the usual care groups. Subgroup analysis (RA and SpA) detected no significant differences between the two groups. Conclusion We could not show significant impact of tapering bDMARD or JAKi over continuation concerning the risk of serious infections, SAEs, malignancies, CV AEs, or deaths in RA and SpA patients in remission or LDA state.

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.

Background Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced doses is common. Methods Data from an observational registry including patients admitted with acute cerebral ischemia while taking oral Factor Xa inhibitors for atrial fibrillation between April 2016 and December 2018 were investigated. The dose regimen of the Xa inhibitor was classified as “appropriate”, “underdosed” and “overdosed” in conformity with the European Medicines Agency labelling. The effect of underdosing on the functional factor Xa plasma level on admission, the clinical stroke severity and the functional outcome after 3 months were investigated. Results 254 patients with cerebral ischemia while on Factor Xa inhibitors were included. The dose regimen of the Factor Xa inhibitor was appropriate in 166 patients (65%), underdosed in 67 patients (26%) and overdosed in 21 patients (8%). Underdosing was associated with female sex, diabetes mellitus and higher CHA2DS2–Vasc scores. Underdosing independently predicted lower anti-Xa plasma levels on admission [median 69.4 ng/ml (IQR 0.0–121.6) vs. 129.2 ng/ml (65.5–207.2); p p = 0.041] and worse functional outcome after 3 months (favorable outcome 26.9% vs. 46.9%; p = 0.025). Conclusion One in three patients with ischemic stroke during treatment with oral Xa inhibitors used inappropriate dose regimens. Underdosing was associated with lower functional plasma levels, higher clinical stroke severity and worse functional outcome.

Introduction To reduce myasthenia gravis (MG) patient risk of immunosuppressant (IS) exposure adverse events (AEs), such as infections and malignancies, and to reduce treatment burden, international guidelines recommend decreasing IS dose in stable MG patients. Methods Online surveys were conducted of self-identified MG patients and MG physician experts about the importance of IS dose reduction for MG patients who achieve prolonged periods of disease stability. Results Eighty-four percent of MG patients (n = 283) and 100% of physicians (n = 45) were concerned about long-term IS-associated AEs. Although both groups favored attempting IS reduction, they raised concerns including MG relapse, hospitalization, and uncertainty about the future. Presented with an estimated 12% significant relapse rate with IS dose reduction, 76% of patients would be willing to enroll in a randomized IS dose reduction trial. Discussion Patients and physicians favor considering IS dose reduction but are also concerned about potential negative sequelae.

ZusammenfassungDie Myocardperfusionsszintigrafie stellt unverändert eine wichtige diagnostische Methode zur Evaluation der hämodynamischen Relevanz einer koronaren Herzkrankheit dar. Mit der Einführung der CZT-Kameras sowie anderer technischer Neuerungen auch bei konventionellen Gammakameras wie z. B. die IQ-SPECT-Technologie sowie verbesserte Auswertealgorithmen, konnte die Strahlenbelastung pro Untersuchung kontinuierlich gesenkt werden, sodass sich die moderne nuklearmedizinische Perfusionsbildgebung sowohl hinsichtlich der diagnostischen Spezifität und Sensitivität als auch der Strahlenbelastung gegenüber den konkurrierenden Methoden nicht zu verstecken braucht.

When increasing the PET acquisition time to match the longer MRI protocol in simultaneous PET/MR, the injected PET tracer dose can possibly be lowered to reduce radiation exposure. Moreover, applying new commercially available time-of-flight (TOF) block sequential regularized expectation maximization (BSREM)–based reconstruction algorithms could allow for further dose reductions. The purpose of this study was to find the minimal dose of the tracer targeting the prostate specific membrane antigen (68Ga-PSMA-11) for a dedicated 15-min pelvic PET/MR scan that still matches the image quality of a reference 3-min scan at 100% (150 MBq) dose. In this retrospective analysis, 25 patients were included. PET emission datasets were edited to simulate stepwise reductions of injected tracer dose. Reference TOF ordered subset expectation maximum (OSEM) and new TOF BSREM reconstructions were performed and differences in the resulting PET images were visually and quantitatively assessed. Visually, TOF BSREM reconstructions with relatively high regularization parameter (β) values are preferred. Quantitatively, however, high β-values result in lower lesion maximum standardized uptake values (SUVmax) compared to the reference. A β-value of 550 was considered the optimal compromise for the lowest possible 10% dose reconstructions, resulting in comparable visual assessment and lesion SUVmax. This study indicates that the injected 68Ga-PSMA-11 tracer dose for a standard 3-min PET scan can be reduced to approximately 10% (15 MBq) when the PET acquisition time is matched to the 15-min pelvic MRI protocol, and when reconstructed with TOF BSREM using β = 550. This decreases the effective dose from 3.54 to 0.35 mSv. • Low-dose dedicated pelvic 68 Ga-PSMA-11 PET/MR reduces radiation exposure for patients. • Retrospective study investigating the minimal dose needed for adequate image quality for 15-min PET frames over the pelvis showed using quantitative and qualitative analysis that a substantial dose reduction is possible without significant loss of image quality when using the TOF BSREM reconstruction algorithm. • With the introduction of low-dose pelvic 68 Ga-PSMA-11 PET/MR, new potential applications of 68 Ga-PSMA-11 PET for local staging or investigation of equivocal MRI findings could become applicable, even for patients without confirmed prostate cancer.