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Background Purpose Methods Results Conclusions The field of artificial intelligence (AI)‐based patient‐specific quality assurance (PSQA) for volumetric modulated arc therapy (VMAT) faces challenges in terms of developing general models across institutions due to the prevalence of multi‐institution data collection and multivariate heterogeneity. Building a general model that is capable of handling diverse multi‐institution data is critical for enabling large‐scale integration and analysis.This study aims to develop a star generative adversarial network (StarGAN) and transformer‐based hybrid classification‐regression PSQA framework to address unification of heterogeneous data from different institutions.A StarGAN and transformer‐based hybrid classification‐regression model was developed as a general PSQA framework to predict gamma passing rates (GPRs) and classify quality assurance (QA) results as “Pass” or “Fail” at multiple institutions. A total of 1815 VMAT plans were collected from eight institutions to develop the general PSQA framework and perform clinical commissioning and implementation. Among them, 20 independent clinical plans from each of eight institutions, for a total of 160 plans, were used for the clinical commissioning, and 205 new clinical plans from eight institutions were used for clinical implementation.For the 3%/3, 3%/2, and 2%/2 mm gamma criteria, the sensitivity of the proposed PSQA framework with pretraining was 90.13%, 92.03%, and 95.84%, respectively, while the specificity was 76.01%, 76.12%, and 85.34%, respectively. The mean absolute errors (MAEs) of the proposed PSQA framework with pretraining were 1.36%, 2.37%, and 3.96%, respectively, while the root‐mean‐square errors (RMSEs) were 2.31%, 3.89%, and 5.17%, respectively. The results demonstrated visible improvement at multiple institutions. For clinical commissioning, the deviations between the predicted and measured results were all within 3% for 3%/3 and 3%/2 mm at eight institutions. For clinical implementation, all failure plans were correctly identified by the proposed PSQA framework.The general PSQA framework enables diverse clinical data sources to be handled to achieve enhanced model performance and generalizability, and provides a solution to the unification of heterogeneous data from different institutions to construct robust QA models. This approach can be clinically deployed for VMAT QA. [ABSTRACT FROM AUTHOR]

BackgroundAimMethod & ProceduresOutcomes & ResultsConclusionsAphasia therapy software: aninvestigation of the research literature and the challenges of software developmentDigital aphasia therapy has become increasingly popular over the past years. However, not all software described in the literature appears to reach clinical practice. It is currently unclear why this is the case.We had two aims. First, we aimed to create an overview of the digital aphasia therapy described and its clinical availability bysystematically searching and reviewing the research literature. Second, we aimed to investigate the experiences of researchers/developers of aphasia therapy software.We conducted a systematic search and review, screening references against our inclusion criteria. Clinical availability of the software was established through reading literature, conducting internet searches, and by contacting the researchers/developers who were associated with the software. Researchers/developers of the reported software were surveyed about their experiences with software development. Responses were the matically analysed into themes and subthemes.We identified a total of 63 unique pieces of software across 125 references. The software was mainly developed for English speakers and mainly focused on word retrieval or a combination of language skills. We established clinical availability with certainty for 35 pieces of software, with the remaining software (likely) currently clinically unavailable. From the survey data, we identified five recurring themes: 1) software development can be expensive and insufficient funding hinders their clinical availability; 2) commercialisation of software is often new and daunting to researchers but essential for making software available; 3) clinicians and people with aphasia are valuable sources of feedback; 4) working with software developers can be difficult; and 5) aphasia therapy software should combine both the evidence base and current clinical need.Aminority of aphasia therapy software described in the literature reaches clinical practice. It is clear that the development and subsequent dissemination of aphasia therapy software requires large amounts of time, energy, and funds but we conclude that this is essential for successful clinical implementation. [ABSTRACT FROM AUTHOR]

Abstract As the prevalence of Alzheimer’s disease (AD) and its impact on healthcare systems increase, developing tools for accurate diagnosis and monitoring of disease progression is a priority. Recent technological advancements have allowed for the development of blood-based biomarkers (BBMs) to aid in the diagnosis of AD, but many questions remain regarding the clinical implementation of these BBMs. This review outlines the historical timeline of AD BBM development. It highlights key breakthroughs that have transformed the perspective of AD BBMs from theoretically ideal but unattainable markers, to clinically valid and reliable BBMs with potential for implementation in healthcare settings. Technological advancements like single-molecule detection and mass spectrometry methods have significantly improved assay sensitivity and accuracy. High-throughput, fully automated platforms have potential for clinical use. Despite these advancements, however, significant work is needed before AD BBMs can be implemented in widespread clinical practice. Cutpoints must be established, the influence of chronic conditions and medications on BBM levels must be better understood, and guidelines must be created for healthcare providers related to interpreting and communicating information obtained from AD BBMs. Additionally, the development of BBMs for synaptic dysfunction, inflammation, and cerebrovascular disease may provide better precision medicine approaches to treating AD and related dementia. Future research and collaboration between scientists and physicians are essential to addressing these challenges and further advancing AD BBMs, with the goal of integration in clinical practice.

As the prevalence of Alzheimer's disease (AD) and its impact on healthcare systems increase, developing tools for accurate diagnosis and monitoring of disease progression is a priority. Recent technological advancements have allowed for the development of blood-based biomarkers (BBMs) to aid in the diagnosis of AD, but many questions remain regarding the clinical implementation of these BBMs. This review outlines the historical timeline of AD BBM development. It highlights key breakthroughs that have transformed the perspective of AD BBMs from theoretically ideal but unattainable markers, to clinically valid and reliable BBMs with potential for implementation in healthcare settings. Technological advancements like single-molecule detection and mass spectrometry methods have significantly improved assay sensitivity and accuracy. High-throughput, fully automated platforms have potential for clinical use. Despite these advancements, however, significant work is needed before AD BBMs can be implemented in widespread clinical practice. Cutpoints must be established, the influence of chronic conditions and medications on BBM levels must be better understood, and guidelines must be created for healthcare providers related to interpreting and communicating information obtained from AD BBMs. Additionally, the development of BBMs for synaptic dysfunction, inflammation, and cerebrovascular disease may provide better precision medicine approaches to treating AD and related dementia. Future research and collaboration between scientists and physicians are essential to addressing these challenges and further advancing AD BBMs, with the goal of integration in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose We describe the implementation and ongoing maintenance of CYP2C19 and CYP2D6 focused pharmacogenetic (PGx) testing to guide antidepressant and antianxiety medication prescriptions in a large rural, nonprofit health system. Summary Depression and anxiety are common psychiatric conditions. Sanford Health implemented PGx testing for metabolism of cytochrome P450 (CYP) isozymes 2C19 and 2D6 in 2014 to inform prescribing for multiple medications, including antidepressant and antianxiety therapies. As guidelines, genotype to phenotype translation, panel offerings, and other resources are updated, we adapt our approach. We make educational and informational materials available to providers and patients. Pharmacogenomic clinical pharmacists review PGx results with discrete values and provide guidance documentation in the electronic medical record. A robust clinical decision support system is in place to provide interruptive alerts, noninterruptive alerts, and genomic indicators. A referral-based interdisciplinary clinic is also available to provide in-depth education to patients regarding PGx results and implications. Additionally, partnering with our health plan has expanded access to PGx testing for patients with anxiety or depression. Conclusion The implementation and maintenance of Sanford Health's PGx program to guide antidepressant and antianxiety medication use continues to evolve and requires a multipronged approach relying on both human and informatics-based resources. [ABSTRACT FROM AUTHOR]

Purpose: Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are at high risk for severe and fatal toxicity from fluoropyrimidine (FP) chemotherapy. Pre-treatment DPYD testing is standard of care in many countries, but not the United States (US). This survey assessed pre-treatment DPYD testing approaches in the US to identify best practices for broader adoption. Methods: From August to October 2023, a 22-item QualtricsXM survey was sent to institutions and clinicians known to conduct pre-treatment DPYD testing and broadly distributed through relevant organizations and social networks. Responses were analyzed using descriptive analysis. Results: Responses from 24 unique US sites that have implemented pre-treatment DPYD testing or have a detailed implementation plan in place were analyzed. Only 33% of sites ordered DPYD testing for all FP-treated patients; at the remaining sites, patients were tested depending on disease characteristics or clinician preference. Almost 50% of sites depend on individual clinicians to remember to order testing without the assistance of electronic alerts or workflow reminders. DPYD testing was most often conducted by commercial laboratories that tested for at least the four or five DPYD variants considered clinically actionable. Approximately 90% of sites reported receiving results within 10 days of ordering. Conclusion: Implementing DPYD testing into routine clinical practice is feasible and requires a coordinated effort among the healthcare team. These results will be used to develop best practices for the clinical adoption of DPYD testing to prevent severe and fatal toxicity in cancer patients receiving FP chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: The Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q) is well validated and commonly used to assess difficulties in everyday functioning regarding dementia. To facilitate interpretation and clinical implementation across different European countries, we aim to provide normative data and a diagnostic cutoff for dementia. Methods: Cross-sectional data from Dutch Brain Research Registry (N = 1,064; mean (M) age = 62 ± 11 year; 69.5% female), European Medial Information Framework-Alzheimer's Disease 90 + (N = 63; Mage = 92 ± 2 year; 52.4% female), and European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (N = 247; Mage = 63 ± 7 year; 72.1% female) were used. The generalized additive models for location, scale, and shape framework were used to obtain normative values (Z -scores). The beta distribution was applied, and combinations of age, sex, and educational attainment were modeled. The optimal cutoff for dementia was calculated using area under receiver operating curves (AUC-ROC) and Youden Index, using data from Amsterdam Dementia Cohort (N = 2,511, Mage = 64 ± 8 year, 44.4% female). Results: The best normative model accounted for a cubic-like decrease of IADL performance with age that was more pronounced in low compared to medium/high educational attainment. The cutoff for dementia was 1.85 standard deviation below the population mean (AUC = 0.97; 95% CI [0.97–0.98]). Conclusion: We provide regression-based norms for A-IADL-Q and a diagnostic cutoff for dementia, which help improve clinical assessment of IADL performance across European countries. [ABSTRACT FROM AUTHOR]

Community agencies and practitioners around the globe seek opportunities to learn various assessment tools and interventions rooted in attachment theory. However, information regarding the feasibility of implementation and sustainability of these tools once participants have been trained to use them, is limited. This study investigated the perceived acceptability, feasibility, utility, relevance, fidelity, and sustainability of the Atypical Maternal Behavior Instrument for Assessment and Classification‐Brief (AMBIANCE‐Brief) among practitioners who had taken a training. Practitioners (N = 59) who attended a virtual AMBIANCE‐Brief training originating from Canada between June 2020 and November 2021 completed an online follow‐up survey. Practitioners reported that they primarily used the AMBIANCE‐Brief for case conceptualization (68%). Additionally, 95% agreed that the AMBIANCE‐Brief was relevant to their clinical practice, 98% agreed it was useful for their clinical work, 76% agreed that it was feasible to implement into their clinical work, and 59% found it easy to incorporate into their treatment planning with clients. Findings suggest that the AMBIANCE‐Brief may be acceptable, feasible, and useful for practitioners. Avenues for continuing to evaluate the AMBIANCE‐Brief include cross‐cultural validity, coder drift, and booster sessions. Additional work clarifying how practitioners integrate the measure into practice would be valuable. [ABSTRACT FROM AUTHOR]

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs. We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35–23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41–28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: malnutrition is a very frequent problem in oncology patients and may have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. Objective: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. Methods: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. Results: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. Conclusions: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation. [ABSTRACT FROM AUTHOR]

Background: Challenging behaviours are often a significant difficulty faced following acquired brain injury (ABI), for which PBS+PLUS (a Positive Behaviour Support framework) is an effective intervention. Clinicians report experiencing a range of barriers to supporting behaviour change for individuals with ABI and require tailored resources to support the implementation of PBS+PLUS. This study aimed to describe the process of co-designing a PBS+PLUS intervention guidebook and podcast series together with individuals with ABI, close-others, and clinicians, and qualitatively examine co-design experiences. Methods: The Knowledge-To-Action Framework was followed to support the translation of PBS+PLUS into clinical practice. Participants with ABI (n = 4), close-others (n = 7), and clinicians (n = 3) participated in focus groups contributing to the development of a PBS+PLUS intervention guidebook and podcast series. Following completion of the groups, qualitative interviews were conducted to understand participants' perspectives of the co-design experience. Transcripts were analysed using reflexive thematic analysis. Results: Co-design processes are described, and participants provided practical suggestions for co-design and the dissemination of developed resources. Two core themes encapsulating four sub-themes were identified. Firstly, ' Esteeming Experiences ' described the person-driven approach of co-design whereby participants felt supported and connected with other contributors and facilitators through sharing their perspectives. Secondly, ' Empowerment ' reflected participants' increased confidence and skills in applying PBS+PLUS. Conclusions: Overall, participants endorsed the therapeutic benefits of co-design engagement and high utility of PBS+PLUS resources. This study adds to the growing literature supporting the use of co-design methodology within clinical implementation, and is inclusive of individuals with ABI, close-others, and clinicians. Behaviour change is common and distressing after acquired brain injury (ABI); however, clinicians report a lack of training to address this. An intervention guidebook and podcast series were co-designed as training resources in PBS+PLUS, a behaviour support intervention. Participants with ABI, family members, and clinicians reported on many benefits of being involved in this co-design process and on the high utility of co-designed PBS+PLUS resources. Findings highlight the importance of involving stakeholders when implementing research into clinical settings. This article belongs to the Collection Clinical Implementation to Optimise Outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Target volume delineation is routinely performed in postoperative radiotherapy (RT) for breast cancer patients, but it is a time-consuming process. The aim of the present study was to validate the quality, clinical usability and institutional-specific implementation of different auto-segmentation tools into clinical routine. Methods: Three different commercially available, artificial intelligence-, ESTRO-guideline-based segmentation models (M1-3) were applied to fifty consecutive reference patients who received postoperative local RT including regional nodal irradiation for breast cancer for the delineation of clinical target volumes: the residual breast, implant or chestwall, axilla levels 1 and 2, the infra- and supraclavicular regions, the interpectoral and internal mammary nodes. Objective evaluation metrics of the created structures were conducted with the Dice similarity index (DICE) and the Hausdorff distance, and a manual evaluation of usability. Results: The resulting geometries of the segmentation models were compared to the reference volumes for each patient and required no or only minor corrections in 72 % (M1), 64 % (M2) and 78 % (M3) of the cases. The median DICE and Hausdorff values for the resulting planning target volumes were 0.87–0.88 and 2.96–3.55, respectively. Clinical usability was significantly correlated with the DICE index, with calculated cut-off values used to define no or minor adjustments of 0.82–0.86. Right or left sided target and breathing method (deep inspiration breath hold vs. free breathing) did not impact the quality of the resulting structures. Conclusion: Artificial intelligence-based auto-segmentation programs showed high-quality accuracy and provided standardization and efficient support for guideline-based target volume contouring as a precondition for fully automated workflows in radiotherapy treatment planning.

Background and purpose: The emergence of synthetic CT (sCT) in MR-guided radiotherapy (MRgRT) represents a significant advancement, supporting MR-only workflows and online treatment adaptation. However, the lack of consensus guidelines has led to varied practices. This study reports results from a 2023 ESTRO survey aimed at defining current practices in sCT development and use. Materials and methods: An survey was distributed to ESTRO members, including 98 questions across four sections on sCT algorithm generation and usage. By June 2023, 100 centers participated. The survey revealed diverse clinical experiences and roles, with primary sCT use in the pelvis (60%), brain (15%), abdomen (11%), thorax (8%), and head-and-neck (6%). sCT was mostly used for conventional fractionation treatments (68%), photon SBRT (40%), and palliative cases (28%), with limited use in proton therapy (4%). Results: Conditional GANs and GANs were the most used neural network architectures, operating mainly on 1.5 T and 3 T MRI images. Less than half used paired images for training, and only 20% performed image selection. Key MR image quality parameters included magnetic field homogeneity and spatial integrity. Half of the respondents lacked a dedicated sCT-QA program, and many did not apply sanitychecks before calculation. Selection strategies included age, weight, and metal artifacts. A strong consensus (95%) emerged for vendor neutral guidelines. Conclusion: The survey highlights the need for expert-based, vendor-neutral guidelines to standardize sCT tools, metrics, and clinical protocols, ensuring effective sCT use in MR-guided radiotherapy.

Abstract Background Non-invasive prenatal testing (NIPT) has been clinically available in Australia on a user-pays basis since 2012. There are numerous providers, with available tests ranging from targeted NIPT (only trisomies 21, 18, and 13 +/- sex chromosome aneuploidy) to genome-wide NIPT. While NIPT is being implemented in the public health care systems of other countries, in Australia, the implementation of NIPT has proceeded without public funding. The aim of this study was to investigate how NIPT has been integrated into antenatal care across Australia and reveal the successes and challenges in its implementation in this context. Methods An anonymous online survey was conducted from September to October 2022. Invitations to participate were sent to healthcare professionals (HCPs) involved in the provision of NIPT in Australia through professional society mailing lists and networks. Participants were asked questions on their knowledge of NIPT, delivery of NIPT, and post-test management of results. Results A total of 475 HCPs responded, comprising 232 (48.8%) obstetricians, 167 (35.2%) general practitioners, 32 (6.7%) midwives, and 44 (9.3%) genetic specialists. NIPT was most commonly offered as a first-tier test, with most HCPs (n = 279; 60.3%) offering it to patients as a choice between NIPT and combined first-trimester screening. Fifty-three percent (n = 245) of respondents always offered patients a choice between NIPT for the common autosomal trisomies and expanded (including genome-wide) NIPT. This choice was understood as supporting patient autonomy and informed consent. Cost was seen as a major barrier to access to NIPT, for both targeted and expanded tests. Equitable access, increasing time demands on HCPs, and staying up to date with advances were frequently reported as major challenges in delivering NIPT. Conclusions Our findings demonstrate substantial variation in the clinical implementation of NIPT in Australia, including in the offers of expanded screening options. After a decade of clinical use, Australian clinicians still report ongoing challenges in the clinical and equitable provision of NIPT.

Abstract Background In order to facilitate the development and implementation of innovative technology in clinical practice, it is important to understand the user experience of end-users. Virtual Reality (VR) offers the possibility to assess cognitive functioning in a dynamic environment that simulates real-world situations. The purpose of this cross-sectional study was to investigate the feasibility of a VR Serious Game for cognitive assessment in school-aged children with congenital heart disease (CHD). The sub-aims were two-fold: (1) to objectively evaluate the feasibility of the VR Serious Game in children with CHD in comparison to typically developing (TD) children and (2) to explore the user experience of both groups following their interaction with the VR Serious Game. Results A total of 101 children participated in this study; 98 children were included in the final analysis (CHD: n = 54; TD: n = 47). The VR Serious Game appeared feasible for both children with CHD and TD children, with 88% children completing the innovative VR assessment without encountering any issues. There were no discernible differences in completion rates between groups. Children with CHD reported significantly lower scores than TD children on three user experience scales: Engagement, Flow and Presence. Nonetheless, the scores for Engagement and Flow were still considered "moderate to good". Both groups reported minimal adverse physiological reactions. Conclusions The findings suggested that the VR Serious Game was feasible for children with CHD and that the user experience was positive. Future research should investigate the effectiveness of the VR Serious Game compared with a conventional or digital neuropsychological assessment, prioritising the development of novel outcome measures that can better estimate and explain the impact of cognitive impairment on daily functioning.

Background: Non-invasive prenatal testing (NIPT) has been clinically available in Australia on a user-pays basis since 2012. There are numerous providers, with available tests ranging from targeted NIPT (only trisomies 21, 18, and 13 +/- sex chromosome aneuploidy) to genome-wide NIPT. While NIPT is being implemented in the public health care systems of other countries, in Australia, the implementation of NIPT has proceeded without public funding. The aim of this study was to investigate how NIPT has been integrated into antenatal care across Australia and reveal the successes and challenges in its implementation in this context. Methods: An anonymous online survey was conducted from September to October 2022. Invitations to participate were sent to healthcare professionals (HCPs) involved in the provision of NIPT in Australia through professional society mailing lists and networks. Participants were asked questions on their knowledge of NIPT, delivery of NIPT, and post-test management of results. Results: A total of 475 HCPs responded, comprising 232 (48.8%) obstetricians, 167 (35.2%) general practitioners, 32 (6.7%) midwives, and 44 (9.3%) genetic specialists. NIPT was most commonly offered as a first-tier test, with most HCPs (n = 279; 60.3%) offering it to patients as a choice between NIPT and combined first-trimester screening. Fifty-three percent (n = 245) of respondents always offered patients a choice between NIPT for the common autosomal trisomies and expanded (including genome-wide) NIPT. This choice was understood as supporting patient autonomy and informed consent. Cost was seen as a major barrier to access to NIPT, for both targeted and expanded tests. Equitable access, increasing time demands on HCPs, and staying up to date with advances were frequently reported as major challenges in delivering NIPT. Conclusions: Our findings demonstrate substantial variation in the clinical implementation of NIPT in Australia, including in the offers of expanded screening options. After a decade of clinical use, Australian clinicians still report ongoing challenges in the clinical and equitable provision of NIPT. [ABSTRACT FROM AUTHOR]

Purpose: Experimental patient‐specific QA (PSQA) is a time and resource‐intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center. Methods: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined. Results: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg‐Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by ‐0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated. Conclusion: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year. [ABSTRACT FROM AUTHOR]

Background and purpose: Implementing any radiopharmaceutical therapy (RPT) program requires a comprehensive review of system readiness, appropriate workflows, and training to ensure safe and efficient treatment delivery. A quantitative assessment of the dose delivered to targets and organs at risk (OAR) using RPT is possible by correlating the absorbed doses with the delivered radioactivity. Integrating dosimetry into an established RPT program demands a thorough analysis of the necessary components and system finetuning. This study aims to report an optimized workflow for molecular radiation therapy using 177Lu with a primary focus on integrating patient-specific dosimetry into an established radiopharmaceutical program in a radiation oncology setting. Materials and methods: We comprehensively reviewed using the Plan-Do-Check-Act (PDCA) cycle, including efficacy and accuracy of delivery and all aspects of radiation safety of the RPT program. The GE Discovery SPECT/CT 670DR™ system was calibrated per MIM protocol for dose calculation on MIM SurePlan™ MRT software. Jaszcak Phantom with 15-20 mCi of 177Lu DOTATATE with 2.5 µM EDTA solution was used, with the main energy window defined as 208 keV ±10% (187.6 to 229.2 keV); the upper scatter energy window was set to 240 keV ±5% (228 to 252 keV), while the lower scatter energy window was 177.8 keV ±5% (168.9 to 186.7 keV). Volumetric quality control tests and adjustments were performed to ensure the correct alignment of the table, NM, and CT gantry on SPECT/CT. A comprehensive end-to-end (E2E) test was performed to ensure workflow, functionality, and quantitative dose accuracy. Results: Workflow improvements and checklists are presented after systematically analyzing over 400 administrations of 177Lu-based RPT. Injected activity to each sphere in the NEMA Phantom scan was quantified, and the MIM Sureplan MRT reconstruction images calculated activities within ±12% of the injected activity. Image alignment tests on the SPECT/CT showed a discrepancy of more than the maximum tolerance of 2.2mmon any individual axis. As a result of servicing the machine and updating the VQC and COR corrections, the hybrid imaging system was adjusted to achieve an accuracy of <1 mm in all directions. Conclusion: Workflows and checklists, after analysis of system readiness and adequate training for staff and patients, are presented. Hardware and software components for patient-specific dosimetry are presented with a focus on hybrid image registration and correcting any errors that affect dosimetric quantification calculation. Moreover, this manuscript briefly overviews the necessary quality assurance requirements for converting diagnostic images into dosimetry measurement tools and integrating dosimetry for RPT based on 177Lu. [ABSTRACT FROM AUTHOR]

Background: In order to facilitate the development and implementation of innovative technology in clinical practice, it is important to understand the user experience of end-users. Virtual Reality (VR) offers the possibility to assess cognitive functioning in a dynamic environment that simulates real-world situations. The purpose of this cross-sectional study was to investigate the feasibility of a VR Serious Game for cognitive assessment in school-aged children with congenital heart disease (CHD). The sub-aims were two-fold: (1) to objectively evaluate the feasibility of the VR Serious Game in children with CHD in comparison to typically developing (TD) children and (2) to explore the user experience of both groups following their interaction with the VR Serious Game. Results: A total of 101 children participated in this study; 98 children were included in the final analysis (CHD: n = 54; TD: n = 47). The VR Serious Game appeared feasible for both children with CHD and TD children, with 88% children completing the innovative VR assessment without encountering any issues. There were no discernible differences in completion rates between groups. Children with CHD reported significantly lower scores than TD children on three user experience scales: Engagement, Flow and Presence. Nonetheless, the scores for Engagement and Flow were still considered "moderate to good". Both groups reported minimal adverse physiological reactions. Conclusions: The findings suggested that the VR Serious Game was feasible for children with CHD and that the user experience was positive. Future research should investigate the effectiveness of the VR Serious Game compared with a conventional or digital neuropsychological assessment, prioritising the development of novel outcome measures that can better estimate and explain the impact of cognitive impairment on daily functioning. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) ultrasound can assess the margins of resected tongue carcinoma during surgery. Manual segmentation (MS) is time-consuming, labour-intensive, and subject to operator variability. This study aims to investigate use of a 3D deep learning model for fast intraoperative segmentation of tongue carcinoma in 3D ultrasound volumes. Additionally, it investigates the clinical effect of automatic segmentation. A 3D No New U-Net (nnUNet) was trained on 113 manually annotated ultrasound volumes of resected tongue carcinoma. The model was implemented on a mobile workstation and clinically validated on 16 prospectively included tongue carcinoma patients. Different prediction settings were investigated. Automatic segmentations with multiple islands were adjusted by selecting the best-representing island. The final margin status (FMS) based on automatic, semi-automatic, and manual segmentation was computed and compared with the histopathological margin. The standard 3D nnUNet resulted in the best-performing automatic segmentation with a mean (SD) Dice volumetric score of 0.65 (0.30), Dice surface score of 0.73 (0.26), average surface distance of 0.44 (0.61) mm, Hausdorff distance of 6.65 (8.84) mm, and prediction time of 8 seconds. FMS based on automatic segmentation had a low correlation with histopathology (r = 0.12, p = 0.67); MS resulted in a moderate but insignificant correlation with histopathology (r = 0.4, p = 0.12, n = 16). Implementing the 3D nnUNet yielded fast, automatic segmentation of tongue carcinoma in 3D ultrasound volumes. Correlation between FMS and histopathology obtained from these segmentations was lower than the moderate correlation between MS and histopathology. [ABSTRACT FROM AUTHOR]

Lower limb robotic exoskeletons can assist movement, however, clinical uptake in neurorehabilitation is limited. The views and experiences of clinicians are pivotal to the successful clinical implementation of emerging technologies. This study investigates therapist perspectives of the clinical use and future role of this technology in neurorehabilitation. Australian and New Zealand-based therapists with lower limb exoskeleton experience were recruited to complete an online survey and semi-structured interview. Survey data were transposed into tables and interviews transcribed verbatim. Qualitative data collection and analysis were guided by qualitative content analysis and interview data were thematically analysed. Five participants revealed that the use of exoskeletons to deliver therapy involves the interplay of human elements – experiences and perspectives of use, and mechanical elements – the device itself. Two overarching themes emerged: the "journey", with subthemes of clinical reasoning and user experience; and the "vehicle" with design features and cost as subthemes, to explore the question "Are we there yet?" Therapists expressed positive and negative perspectives from their experiences with exoskeletons, giving suggestions for design features, marketing input, and cost to enhance future use. Therapists are optimistic that this journey will see lower limb exoskeletons integral to rehabilitation service delivery. Further innovation of design features, marketing, and cost are needed to enhance ongoing development and integration. Routine clinical implementation of lower limb exoskeletons is unlikely at this time in Australia and New Zealand. Therapists do expect lower limb exoskeletons to have an ongoing role in future rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Conferences are a widespread method of research dissemination; however, their impact on practice is not well understood empirically. We aimed to investigate how conference participation influences clinical and research practice in the stroke field and to explore which presentation formats are most impactful. Methods: Clinicians, researchers and doctoral students who attended a multidisciplinary stroke conference were invited to participate. Surveys were administered at the conference and 3 months later. Both surveys contained questions about how respondents remember and apply information learnt at conferences in their clinical and/or research practice. Results: Baseline survey responses from 120 conference participants were analysed (80.8% female, 69.0% clinicians, 60.8% aged 31–50 years), and 53 participants completed the follow-up survey. Of the 87 clinician respondents, 73 (83.9%) reported that their clinical practice had changed as a result of attending conferences. Workshops incorporating skill demonstrations were rated most useful for changing clinical practice, whereas oral presentations detailing methodology were more influential on research practice. Attending conferences was rated more impactful on clinical practice than reading journal articles or textbooks. Conclusion: Conference presentations can be a useful method for disseminating research findings to influence clinical practice and should be considered by researchers to maximise the translation and impact of their work. Scientific conferences are a common way for researchers to share their findings, but the impact of conference participation on clinical and research practice is not well understood. In our survey of clinicians, researchers and students who attended a stroke conference, participants reported that conferences are more influential in changing clinical practice than journal articles. This suggests that conference presentations can be a useful method for enhancing evidence‐based practice. [ABSTRACT FROM AUTHOR]

This report covers clinical implementation of a low kV intraoperative radiation therapy (IORT) program with the INTRABEAM® System (Carl Zeiss Meditec AG, Jena, Germany). Based on collective user experience from eight institutions, we discuss best methods of INTRABEAM quality assurance (QA) tests, commissioning measurements,clinical workflow, treatment planning,and potential avenues for research.The guide provides pertinent background information and clinical justification for IORT. It describes the INTRABEAM system and commissioning measurements along with a TG100 risk management analysis to ensure safety and accuracy of the IORT program. Following safety checks, dosimetry measurements are performed for verification of field flatness and symmetry, x-ray output, and depth dose. Also discussed are dose linearity checks, beam isotropy, ion chamber measurements, calibration protocols, and in-vivo dosimetry with optically stimulated luminescence dosimeters OSLDs, and radiochromic film. Emphasis is placed on the importance of routine QA procedures (daily, monthly, and annual) performed at regular intervals for a successful IORT program. For safe and accurate dose delivery, tests of important components of IORT clinical workflow are emphasized,such as,dose prescription, pre-treatment QA, treatment setup, safety checks, radiation surveys, and independent checks of delivered dose. Challenges associated with in-vivo dose measurements are discussed, along with special treatment procedures and shielding requirements. The importance of treatment planning in IORT is reviewed with reference to a Monte Carlo-based commercial treatment planning system highlighting its main features and limitations. The report concludes with suggested topics for research including CT-based image-guided treatment planning and improved prescription dose accuracy. We hope that this multi-institutional report will serve as a guidance document on the clinical implementation and use of INTRABEAM IORT. [ABSTRACT FROM AUTHOR]

The interest in machine learning (ML) has grown tremendously in recent years, partly due to the performance leap that occurred with new techniques of deep learning, convolutional neural networks for images, increased computational power, and wider availability of large datasets. Most fields of medicine follow that popular trend and, notably, radiation oncology is one of those that are at the forefront, with already a long tradition in using digital images and fully computerized workflows. ML models are driven by data, and in contrast with many statistical or physical models, they can be very large and complex, with countless generic parameters. This inevitably raises two questions, namely, the tight dependence between the models and the datasets that feed them, and the interpretability of the models, which scales with its complexity. Any problems in the data used to train the model will be later reflected in their performance. This, together with the low interpretability of ML models, makes their implementation into the clinical workflow particularly difficult. Building tools for risk assessment and quality assurance of ML models must involve then two main points: interpretability and data-model dependency. After a joint introduction of both radiation oncology and ML, this paper reviews the main risks and current solutions when applying the latter to workflows in the former. Risks associated with data and models, as well as their interaction, are detailed. Next, the core concepts of interpretability, explainability, and data-model dependency are formally defined and illustrated with examples. Afterwards, a broad discussion goes through key applications of ML in workflows of radiation oncology as well as vendors' perspectives for the clinical implementation of ML.

BackgroundMachine learning (ML) models can improve prediction of major adverse cardiovascular events (MACE), but in clinical practice some values may be missing. We evaluated the influence of missing values in ML models for patient-specific prediction of MACE risk.MethodsWe included 20,179 patients from the multicenter REFINE SPECT registry with MACE follow-up data. We evaluated seven methods for handling missing values: 1) removal of variables with missing values (ML-Remove), 2) imputation with median and unique category for continuous and categorical variables, respectively (ML-Traditional), 3) unique category for missing variables (ML-Unique), 4) cluster-based imputation (ML-Cluster), 5) regression-based imputation (ML-Regression), 6) missRanger imputation (ML-MR), and 7) multiple imputation (ML-MICE). We trained ML models with full data and simulated missing values in testing patients. Prediction performance was evaluated using area under the receiver-operating characteristic curve (AUC) and compared with a model without missing values (ML-All), expert visual diagnosis and total perfusion deficit (TPD).ResultsDuring mean follow-up of 4.7 ± 1.5 years, 3,541 patients experienced at least one MACE (3.7% annualized risk). ML-All (reference model-no missing values) had AUC 0.799 for MACE risk prediction. All seven models with missing values had lower AUC (ML-Remove: 0.778, ML-MICE: 0.774, ML-Cluster: 0.771, ML-Traditional: 0.771, ML-Regression: 0.770, ML-MR: 0.766, and ML-Unique: 0.766; p

Introduction: The practice of informed consent (IC) for pharmacogenomic testing in clinical settings varies, and there is currently no consensus on which elements of IC to provide to patients. This study aims to assess current IC practices for pharmacogenomic testing. Methods: An online survey was developed and sent to health providers at institutions that offer clinical germline pharmacogenomic testing to assess current IC practices. Results: Forty-six completed surveys representing 43 clinical institutions offering pharmacogenomic testing were received. Thirty-two (74%) respondents obtain IC from patients with variability in elements incorporated. Results revealed that twenty-nine (67%) institutions discuss the benefits, description, and purpose of pharmacogenomic testing with patients. Less commonly discussed elements included methodology and accuracy of testing, and laboratory storage of samples. Discussion: IC practices varied widely among survey respondents. Most respondents desire the establishment of consensus IC recommendations from a trusted pharmacogenomics organization to help address these disparities. [ABSTRACT FROM AUTHOR]

BackgroundAimMain ContributionConclusionsThe Intensive Comprehensive Aphasia Program (ICAP) is a rehabilitation service delivery model initially articulated in a seminal article featured in the 2013 Special Issue of Topics in Stroke Rehabilitation. Over the past decade, the ICAP model has experienced a notable surge in prominence, leading to a burgeoning research base and worldwide implementation in clinical practice.This special issue serves as a comprehensive exploration of how the theoretical underpinnings of the ICAP components manifest in contemporary practice by presenting recent outcomes from active clinical ICAPs. The primary objective of this introduction is to establish a contextual framework for the articles comprising this special issue.The introduction delineates the fundamental components of the ICAP model, offering succinct summaries of the relevant literature that catalyzed the conceptualization of these components by Rose and colleagues.This introduction along with the collective works within this issue, positions the ICAP model within the broader aphasia rehabilitation continuum of care. Furthermore, it serves as a pivotal starting point for shaping the ICAP research agenda for the next decade. Specific expansions to the evidence are imperative, including single-site and multi-site randomized controlled trials featuring consistent outcome measures that include discourse measures and follow-up data points, investigations into cost-effectiveness and sustainability, and systematic examinations of the active ingredients of therapeutic elements within the model. [ABSTRACT FROM AUTHOR]

Decades of pharmacogenetic research have revealed genetic biomarkers of clinical response to antipsychotics. Genetic variants in antipsychotic targets, dopamine and serotonin receptors in particular, and in metabolic enzymes have been associated with the efficacy and toxicity of antipsychotic treatments. However, genetic prediction of antipsychotic response based on these biomarkers is far from accurate. Despite the clinical validity of these findings, the clinical utility remains unclear. Nevertheless, genetic information on CYP metabolic enzymes responsible for the biotransformation of most commercially available antipsychotics has proven to be effective for the personalisation of clinical dosing, resulting in a reduction of induced side effects and in an increase in efficacy. However, pharmacogenetic information is rarely used in psychiatric settings as a prescription aid. Lack of studies on cost-effectiveness, absence of clinical guidelines based on pharmacogenetic biomarkers for several commonly used antipsychotics, the cost of genetic testing and the delay in results delivery hamper the implementation of pharmacogenetic interventions in clinical settings. This narrative review will comment on the existing pharmacogenetic information, the clinical utility of pharmacogenetic findings, and their current and future implementations. [ABSTRACT FROM AUTHOR]

Clinical implementation of pharmacogenetics (PGx) into routine care will elevate the current paradigm of treatment decisions. However, while PGx tests are increasingly becoming reliable and affordable, several barriers have limited their widespread usage in Canada. Globally, over ninety successful PGx implementors can serve as models. The purpose of this paper is to outline the PGx implementation barriers documented in Quebec (Canada) to suggest efficient solutions based on existing PGx clinics and propose an adapted clinical implementation model. We conclude that the province of Quebec is ready to implement PGx. [ABSTRACT FROM AUTHOR]

Genome-wide association studies have been employed to develop numerous risk prediction models using polygenic risk scores (PRSs) for multifactorial diseases. However, healthcare providers lack confidence in their understanding of PRS risk stratification for multifactorial diseases, which underscores the need to assess the readiness of PRSs for clinical use. To address this issue, we surveyed the perceptions of healthcare providers as stakeholders in the clinical implementation of genetic-based risk prediction for multifactorial diseases. We conducted a web-based study on the need for risk prediction based on genetic information and the appropriate timing of testing for 12 multifactorial diseases. Responses were obtained from 506 stakeholders. Positive perceptions of genetic risk testing were found for adult-onset chronic diseases. As per participant opinion, testing for adult-onset diseases should be performed after the age of 20 years, whereas testing for psychiatric and allergic disorders that manifest during childhood should be performed from birth to 19 years of age. The stakeholders recognized the need for genetic risk testing for diseases that develop in adulthood, believing that the appropriate testing time is after maturity. This study contributes to the discussion on the clinical implementation of the PRS for genetic risk prediction of multifactorial diseases. [ABSTRACT FROM AUTHOR]

Purpose To develop a pharmacist-driven, exploratory pharmacogenomics implementation model with the goal of creating a process for pharmacists to interpret pharmacogenomics results from RIGHT 10K Study samples and provide electronic consults to providers. Summary A train-the-trainer model program was initiated whereby pharmacogenomics pharmacists developed a documentation template and a quick reference guide as a standard guide to train other pharmacists. Pharmacists completed electronic consults (e-consults) reviewing pharmacogenomics results, with reference to drug-gene interactions, for patients with "semi-urgent" and "clinically actionable" results, defined as those indicating a potential for gene-drug interactions to cause major harm and those indicating a potential for an adverse drug reaction or reduced efficacy, respectively. Outcomes measured included the number of consults over time, number and role of pharmacists involved, average time to complete e-consults over time, and gene-drug pairs for semi-urgent consults per month. A total of 395 pharmacists were trained. The total number of e-consults completed was 2,843: 61 semi-urgent and 2,782 clinically actionable consults. The average time spent per consult was 24 minutes, and the average number of e-consults per pharmacist was 7. CYP2C19 -clopidogrel was the most common gene-drug pair targeted in semi-urgent consults. Conclusion Pharmacy leaders planning to implement similar pharmacogenomics programs can utilize this data to estimate hiring needs for future pharmacogenomics implementation, while also considering the potential additional cost of developing resources. [ABSTRACT FROM AUTHOR]

Summary: Background: Pharmacogenomics (PGx) holds promise to revolutionize modern healthcare. Although there are several prospective clinical studies in oncology and cardiology, demonstrating a beneficial effect of PGx-guided treatment in reducing adverse drug reactions, there are very few such studies in psychiatry, none of which spans across all main psychiatric indications, namely schizophrenia, major depressive disorder and bipolar disorder. In this study we aim to investigate the clinical effectiveness of PGx-guided treatment (occurrence of adverse drug reactions, hospitalisations and re-admissions, polypharmacy) and perform a cost analysis of the intervention. Methods: We report our findings from a multicenter, large-scale, prospective study of pre-emptive genome-guided treatment named as PREemptive Pharmacogenomic testing for preventing Adverse drug REactions (PREPARE) in a large cohort of psychiatric patients (n = 1076) suffering from schizophrenia, major depressive disorder and bipolar disorder. Findings: We show that patients with an actionable phenotype belonging to the PGx-guided arm (n = 25) present with 34.1% less adverse drug reactions compared to patients belonging to the control arm (n = 36), 41.2% less hospitalisations (n = 110 in the PGx-guided arm versus n = 187 in the control arm) and 40.5% less re-admissions (n = 19 in the PGx-guided arm versus n = 32 in the control arm), less duration of initial hospitalisations (n = 3305 total days of hospitalisation in the PGx-guided arm from 110 patients, versus n = 6517 in the control arm from 187 patients) and duration of hospitalisation upon readmission (n = 579 total days of hospitalisation upon readmission in the PGx-guided arm, derived from 19 patients, versus n = 928 in the control arm, from 32 patients respectively). It was also shown that in the vast majority of the cases, there was less drug dose administrated per drug in the PGx-guided arm compared to the control arm and less polypharmacy (n = 124 patients prescribed with at least 4 psychiatric drugs in the PGx-guided arm versus n = 143 in the control arm) and smaller average number of co-administered psychiatric drugs (2.19 in the PGx-guided arm versus 2.48 in the control arm. Furthermore, less deaths were reported in the PGx-guided arm (n = 1) compared with the control arm (n = 9). Most importantly, we observed a 48.5% reduction of treatment costs in the PGx-guided arm with a reciprocal slight increase of the quality of life of patients suffering from major depressive disorder (0.935 versus 0.925 QALYs in the PGx-guided and control arm, respectively). Interpretation: While only a small proportion (∼25%) of the entire study sample had an actionable genotype, PGx-guided treatment can have a beneficial effect in psychiatric patients with a reciprocal reduction of treatment costs. Although some of these findings did not remain significant when all patients were considered, our data indicate that genome-guided psychiatric treatment may be successfully integrated in mainstream healthcare. Funding: European Union Horizon 2020.

Abstract Background Despite a growing number of publications highlighting the potential impact on the therapy outcome, rare genetic variants (minor allele frequency

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35–23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41–28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.

Background and purposeImplementing any radiopharmaceutical therapy (RPT) program requires a comprehensive review of system readiness, appropriate workflows, and training to ensure safe and efficient treatment delivery. A quantitative assessment of the dose delivered to targets and organs at risk (OAR) using RPT is possible by correlating the absorbed doses with the delivered radioactivity. Integrating dosimetry into an established RPT program demands a thorough analysis of the necessary components and system fine-tuning. This study aims to report an optimized workflow for molecular radiation therapy using 177Lu with a primary focus on integrating patient-specific dosimetry into an established radiopharmaceutical program in a radiation oncology setting.Materials and methodsWe comprehensively reviewed using the Plan–Do–Check–Act (PDCA) cycle, including efficacy and accuracy of delivery and all aspects of radiation safety of the RPT program. The GE Discovery SPECT/CT 670DR™ system was calibrated per MIM protocol for dose calculation on MIM SurePlan™ MRT software. Jaszcak Phantom with 15–20 mCi of 177Lu DOTATATE with 2.5 µM EDTA solution was used, with the main energy window defined as 208 keV ±10% (187.6 to 229.2 keV); the upper scatter energy window was set to 240 keV ±5% (228 to 252 keV), while the lower scatter energy window was 177.8 keV ±5% (168.9 to 186.7 keV). Volumetric quality control tests and adjustments were performed to ensure the correct alignment of the table, NM, and CT gantry on SPECT/CT. A comprehensive end-to-end (E2E) test was performed to ensure workflow, functionality, and quantitative dose accuracy.ResultsWorkflow improvements and checklists are presented after systematically analyzing over 400 administrations of 177Lu-based RPT. Injected activity to each sphere in the NEMA Phantom scan was quantified, and the MIM Sureplan MRT reconstruction images calculated activities within ±12% of the injected activity. Image alignment tests on the SPECT/CT showed a discrepancy of more than the maximum tolerance of 2.2 mm on any individual axis. As a result of servicing the machine and updating the VQC and COR corrections, the hybrid imaging system was adjusted to achieve an accuracy of

Introduction: The practice of informed consent (IC) for pharmacogenomic testing in clinical settings varies, and there is currently no consensus on which elements of IC to provide to patients. This study aims to assess current IC practices for pharmacogenomic testing.Methods: An online survey was developed and sent to health providers at institutions that offer clinical germline pharmacogenomic testing to assess current IC practices.Results: Forty-six completed surveys representing 43 clinical institutions offering pharmacogenomic testing were received. Thirty-two (74%) respondents obtain IC from patients with variability in elements incorporated. Results revealed that twenty-nine (67%) institutions discuss the benefits, description, and purpose of pharmacogenomic testing with patients. Less commonly discussed elements included methodology and accuracy of testing, and laboratory storage of samples.Discussion: IC practices varied widely among survey respondents. Most respondents desire the establishment of consensus IC recommendations from a trusted pharmacogenomics organization to help address these disparities.

Background: Despite a growing number of publications highlighting the potential impact on the therapy outcome, rare genetic variants (minor allele frequency < 1%) in genes associated to drug adsorption, distribution, metabolism, and elimination are poorly studied. Previously, rare germline DPYD missense variants were shown to identify a subset of fluoropyrimidine-treated patients at high risk for severe toxicity. Here, we investigate the impact of rare genetic variants in a panel of 54 other fluoropyrimidine-related genes on the risk of severe toxicity. Methods: The coding sequence and untranslated regions of 54 genes related to fluoropyrimidine pharmacokinetics/pharmacodynamics were analyzed by next-generation sequencing in 120 patients developing grade 3–5 toxicity (NCI-CTC vs3.0) and 104 matched controls. Sequence Kernel Association Test (SKAT) analysis was used to select genes with a burden of genetic variants significantly associated with risk of severe toxicity. The statistical association of common and rare genetic variants in selected genes was further investigated. The functional impact of genetic variants was assessed using two different in silico prediction tools (Predict2SNP; ADME Prediction Framework). Results: SKAT analysis highlighted DPYS and PPARD as genes with a genetic mutational burden significantly associated with risk of severe fluoropyrimidine-related toxicity (Bonferroni adjusted P = 0.024 and P = 0.039, respectively). Looking more closely at allele frequency, the burden of rare DPYS variants was significantly higher in patients with toxicity compared with controls (P = 0.047, Mann–Whitney test). Carrying at least one rare DPYS variant was associated with an approximately fourfold higher risk of severe cumulative (OR = 4.08, P = 0.030) and acute (OR = 4.21, P = 0.082) toxicity. The burden of PPARD rare genetic variants was not significantly related to toxicity. Some common variants with predictive value in DPYS and PPARD were also identified: DPYS rs143004875-T and PPARD rs2016520-T variants predicted an increased risk of severe cumulative (P = 0.002 and P = 0.001, respectively) and acute (P = 0.005 and P = 0.0001, respectively) toxicity. Conclusion: This work demonstrated that the rare mutational burden of DPYS, a gene strictly cooperating with DPYD in the catabolic pathway of fluoropyrimidines, is a promising pharmacogenetic marker for precision dosing of fluoropyrimidines. Additionally, some common genetic polymorphisms in DPYS and PPARD were identified as promising predictive markers that warrant further investigation. [ABSTRACT FROM AUTHOR]

Purpose of Review: Advances in pharmacogenomics have paved the way for personalized medicine. Cardiovascular diseases still represent the leading cause of mortality in the world. The aim of this review is to summarize the background, rationale, and evidence of pharmacogenomics in cardiovascular medicine, in particular, the use of antiplatelet drugs, anticoagulants, and drugs used for the treatment of dyslipidemia. Recent findings: Randomized clinical trials have supported the role of a genotype-guided approach for antiplatelet therapy in patients with coronary heart disease undergoing percutaneous coronary interventions. Numerous studies demonstrate how the risk of ineffectiveness of new oral anticoagulants and vitamin K anticoagulants is linked to various genetic polymorphisms. Furthermore, there is growing evidence to support the association of some genetic variants and poor adherence to statin therapy, for example, due to the appearance of muscular symptoms. There is evidence for resistance to some drugs for the treatment of dyslipidemia, such as anti-PCSK9. Summary: Pharmacogenomics has the potential to improve patient care by providing the right drug to the right patient and could guide the identification of new drug therapies for cardiovascular disease. This is very important in cardiovascular diseases, which have high morbidity and mortality. The improvement in therapy could be reflected in the reduction of healthcare costs and patient mortality. [ABSTRACT FROM AUTHOR]

Pharmacogenomics (PGx) is an integral part of precision medicine and contributes to the maximization of drug efficacy and reduction of adverse drug event risk. Accurate information on PGx allele frequencies improves the implementation of PGx. Nonetheless, curating such information from published allele data is time and resource intensive. The limited number of allelic variants in most studies leads to an underestimation of certain alleles. We applied the Pharmacogenomics Clinical Annotation Tool (PharmCAT) on an integrated 200K UK Biobank genetic dataset (N = 200,044). Based on PharmCAT results, we estimated PGx frequencies (alleles, diplotypes, phenotypes, and activity scores) for 17 pharmacogenes in five biogeographic groups: European, Central/South Asian, East Asian, Afro-Caribbean, and Sub-Saharan African. PGx frequencies were distinct for each biogeographic group. Even biogeographic groups with similar proportions of phenotypes were driven by different sets of dominant PGx alleles. PharmCAT also identified "no-function" alleles that were rare or seldom tested in certain groups by previous studies, e.g., SLCO1B1 ∗31 in the Afro-Caribbean (3.0%) and Sub-Saharan African (3.9%) groups. Estimated PGx frequencies are disseminated via the PharmGKB (The Pharmacogenomics Knowledgebase: www.pharmgkb.org). We demonstrate that genetic biobanks such as the UK Biobank are a robust resource for estimating PGx frequencies. Improving our understanding of PGx allele and phenotype frequencies provides guidance for future PGx studies and clinical genetic test panel design, and better serves individuals from wider biogeographic backgrounds. The frequencies of pharmacogenomic alleles/haplotypes, diplotypes, and phenotypes in five biogeographic groups were estimated using an integrated UK Biobank genetic data set and the Pharmacogenomics Clinical Annotation Tool (PharmCAT). Rare partial alleles and combinations of known pharmacogenomic alleles were reported. The frequencies will be disseminated via the Pharmacogenomics Knowledgebase (PharmGKB). [ABSTRACT FROM AUTHOR]

Background and Aim: Evidence-based practice improves the quality of clinical performance. Attitude affects the implementation of research findings into practice. The Evidence-Based Practice Attitude Scale (EBPAS-36) evaluates the attitude of therapists toward evidence-based practice. The present study aimed to provide a validated Persian translation of the EBPAS-36 for audiologists. Methods: The original EBPAS-36 was translated by using the international quality of life assessment protocol. The validity of translated version was surveyed by an expert panel and the Persian version with 35 questions was yielded. A demographic questionnaire and EBPAS P-35 were given to 182 audiologists to evaluate the psychometric properties. The reliability was evaluated by completing the EBPAS P-35 after 2 weeks by 30 of the participants and Cronbach's alpha and Intra-Class Correlation (ICC) were calculated. Confirmatory Factor Analyses (CFA) were also conducted. Results: The content validity ratio was above 0.33 for all except item 10 which was removed from the Persian version. The mean(SD) total score was 2.38(0.46). A significant relationship was observed between the total score and all subscales (p<0.05). The original factor structure showed an acceptable model fit (CMIN/DF=1.39, GFI=0.84, CFI=0.94, IFI=0.94, RMSEA=0.04) confirming the 12-factor structure of the EBPAS-36. The internal consistency was very good for the total score (α=0.88) and adequate to very good for the subscales (0.65--0.84), indicating high reliability. The ICC showed good agreement in the score of test-retest (total ICC=0.65). Conclusion: This study confirms good psychometric properties and validity of the EBPAS P-35 in a sample of audiologists. [ABSTRACT FROM AUTHOR]

Pharmacogenetics (PGx) can explain/predict drug therapy outcomes. There is, however, unclarity about the use and usefulness of PGx in primary care. In this study, we investigated PGx tests ordered by general practitioners (GPs) in 2021 at Dept. Clinical Chemistry, Erasmus MC, and analyzed the gene tests ordered, drugs/drug groups, reasons for testing and single-gene versus panel testing. Additionally, a survey was sent to 90 GPs asking about their experiences and barriers to implementing PGx. In total, 1206 patients and 6300 PGx tests were requested by GPs. CYP2C19 was requested most frequently (17%), and clopidogrel was the most commonly indicated drug (23%). Regarding drug groups, antidepressants (51%) were the main driver for requesting PGx, followed by antihypertensives (26%). Side effects (79%) and non-response (27%) were the main indicators. Panel testing was preferred over single-gene testing. The survey revealed knowledge on when and how to use PGx as one of the main barriers. In conclusion, PGx is currently used by GPs in clinical practice in the Netherlands. Side effects are the main reason for testing, which mostly involves antidepressants. Lack of knowledge is indicated as a major barrier, indicating the need for more education on PGx for GPs. [ABSTRACT FROM AUTHOR]

Introduction: Dihydropyrimidine dehydrogenase (DPD), encoded by DPYD gene, is the rate-limiting enzyme responsible for fluoropyrimidine (FP) catabolism. DPYD gene variants seriously affect DPD activity and are well validated predictors of FPassociated toxicity. DPYD variants rs3918290, rs55886062, rs67376798, and rs75017182 are currently included in FP genetic-based dosing guidelines and are recommended for genotyping by the European Medicines Agency (EMA) before treatment initiation. In Greece, however, no data exist on DPYD genotyping. The aim of the present study was to analyze prevalence of DPYD rs3918290, rs55886062, rs67376798, rs75017182, and, additionally, rs1801160 variants, and assess their association with FP-induced toxicity in Greek cancer patients. Methods: Study group consisted of 313 FP-treated cancer patients. DPYD genotyping was conducted on QuantStudio ™ 12K Flex Real-Time PCR System (ThermoFisher Scientific) using the TaqMan® assays C__30633851_20 (rs3918290), __11985548_10 (rs55886062), C_;_27530948_10 (rs67376798), C_104846637_10 (rs75017182) and C__11372171_10 (rs1801160). Results: Any grade toxicity (1-4) was recorded in 208 patients (66.5%). Out of them, 25 patients (12%) experienced grade 3-4 toxicity. DPYD EMA recommended variants were detected in 9 patients (2.9%), all experiencing toxicity (p = 0.031, 100% specificity). This frequency was found increased in grade 3-4 toxicity cases (12%, p = 0.004, 97.9% specificity). DPYD deficiency increased the odds of grade 3-4 toxicity (OR: 6.493, p = 0.014) and of grade 1-4 gastrointestinal (OR: 13.990, p = 0.014), neurological (OR: 4.134, p = 0.040) and nutrition/metabolism (OR: 4.821, p = 0.035) toxicities. FP dose intensity was significantly reduced in DPYD deficient patients (β = -0.060, p <0.001). DPYD rs1801160 variant was not associated with FP-induced toxicity or dose intensity. Triple interaction of DPYD*TYMS*MTHFR was associated with grade 3-4 toxicity (OR: 3.725, p = 0.007). Conclusion: Our findings confirm the clinical validity of DPYD reduced function alleles as risk factors for development of FP-associated toxicity in the Greek population. Pre-treatment DPYD genotyping should be implemented in clinical practice and guide FP dosing. DPYD*gene interactions merit further investigation as to their potential to increase the prognostic value of DPYD genotyping and improve safety of FP-based chemotherapy. [ABSTRACT FROM AUTHOR]