Co-Operative Design of a Coach Dashboard for Training Monitoring and Feedback.

Athlete development depends on many factors that need to be balanced by the coach. The amount of data collected grows with the development of sensor technology. To make data-informed decisions for training prescription of their athletes, coaches could be supported by feedback through a coach dashboard. The aim of this paper is to describe the design of a coach dashboard based on scientific knowledge, user requirements, and (sensor) data to support decision making of coaches for athlete development in cyclic sports. The design process involved collaboration with coaches, embedded scientists, researchers, and IT professionals. A classic design thinking process was used to structure the research activities in five phases: empathise, define, ideate, prototype, and test phases. To understand the user requirements of coaches, a survey (n = 38), interviews (n = 8) and focus-group sessions (n = 4) were held. Design principles were adopted into mock-ups, prototypes, and the final coach dashboard. Designing a coach dashboard using the co-operative research design helped to gain deep insights into the specific user requirements of coaches in their daily training practice. Integrating these requirements, scientific knowledge, and functionalities in the final coach dashboard allows the coach to make data-informed decisions on training prescription and optimise athlete development.

Behaviour change techniques used in lifestyle support of adults with mild intellectual disabilities.

BACKGROUND: Professional caregivers are important in the daily support of lifestyle change for adults with mild intellectual disabilities; however, little is known about which behaviour change techniques (BCTs) are actually used. This study aims to gain insight in their use for lifestyle behaviour change using video observations. METHODS: Professional caregivers (N = 14) were observed in daily work supporting adults with mild intellectual disabilities. Videos were analysed using the Coventry Aberdeen London Refined (CALO-RE-NL) taxonomy and BCTs utilised were coded. RESULTS: Twenty one out of 40 BCTs were used by professional caregivers. The BCTs 'Information about others' approval', 'Identification as role model', 'Rewards on successful behaviour', 'Review behavioural goals' and 'Instructions on how to perform the behaviour' were most employed. CONCLUSION: Professional caregivers used BCTs to support healthier lifestyle behaviour of adults with mild intellectual disabilities. However, most promising of them as defined previous by professionals were rarely used by professional caregivers.

Equity-specific effects of interventions to promote physical activity among middle-aged and older adults: results from applying a novel equity-specific re-analysis strategy.

BACKGROUND: Reducing inequalities in physical activity (PA) and PA-associated health outcomes is a priority for public health. Interventions to promote PA may reduce inequalities, but may also unintentionally increase them. Thus, there is a need to analyze equity-specific intervention effects. However, the potential for analyzing equity-specific effects of PA interventions has not yet been sufficiently exploited. The aim of this study was to set out a novel equity-specific re-analysis strategy tried out in an international interdisciplinary collaboration. METHODS: The re-analysis strategy comprised harmonizing choice and definition of outcomes, exposures, socio-demographic indicators, and statistical analysis strategies across studies, as well as synthesizing results. It was applied in a collaboration of a convenience sample of eight European PA intervention studies in adults aged ≥45 years. Weekly minutes of moderate-to-vigorous PA was harmonized as outcome. Any versus no intervention was harmonized as exposure. Gender, education, income, area deprivation, and marital status were harmonized as socio-demographic indicators. Interactions between the intervention and socio-demographic indicators on moderate-to-vigorous PA were analyzed using multivariable linear regression and random-effects meta-analysis. RESULTS: The collaborative experience shows that the novel re-analysis strategy can be applied to investigate equity-specific effects of existing PA interventions. Across our convenience sample of studies, no consistent pattern of equity-specific intervention effects was found. Pooled estimates suggested that intervention effects did not differ by gender, education, income, area deprivation, and marital status. CONCLUSIONS: To exploit the potential for equity-specific effect analysis, we encourage future studies to apply the strategy to representative samples of existing study data. Ensuring sufficient representation of 'hard to reach' groups such as the most disadvantaged in study samples is of particular importance. This will help to extend the limited evidence required for the design and prioritization of future interventions that are most likely to reduce health inequalities.

Exploration of suitable behaviour change techniques for lifestyle change in individuals with mild intellectual disabilities: A Delphi study.

BACKGROUND: Promotion of a healthy lifestyle for individuals with mild intellectual disabilities is important. However, the suitability of behaviour change techniques (BCTs) for these individuals is still unclear. METHODS: A Delphi study was performed using the Coventry, Aberdeen & LOndon - REfined (CALO-RE) taxonomy of BCTs (n = 40). Health professionals (professional caregivers, behavioural scientists, health professionals, intellectual disability physicians) participated in an online survey to determine whether BCTs were suitable or unsuitable. Comments from participants were analysed qualitatively. RESULTS: Consensus was reached for 25 BCTs out of 40.The most suitable BCTs were barrier identification (97%), set graded tasks (97%) and reward effort towards behaviour (95%). No significant differences were found for intergroup effects. CONCLUSION: Regardless of their position and education level, health professionals reached consensus about the suitability of BCTs for individuals with mild intellectual disabilities. Increased use of these BCTs could result in more effective promotion of a healthy lifestyle.

Influence of respiratory gating, image filtering, and animal positioning on high-resolution electrocardiography-gated murine cardiac single-photon emission computed tomography.

Cardiac parameters obtained from single-photon emission computed tomographic (SPECT) images can be affected by respiratory motion, image filtering, and animal positioning. We investigated the influence of these factors on ultra-high-resolution murine myocardial perfusion SPECT. Five mice were injected with 99m technetium (99mTc)-tetrofosmin, and each was scanned in supine and prone positions in a U-SPECT-II scanner with respiratory and electrocardiographic (ECG) gating. ECG-gated SPECT images were created without applying respiratory motion correction or with two different respiratory motion correction strategies. The images were filtered with a range of three-dimensional gaussian kernels, after which end-diastolic volumes (EDVs), end-systolic volumes (ESVs), and left ventricular ejection fractions were calculated. No significant differences in the measured cardiac parameters were detected when any strategy to reduce or correct for respiratory motion was applied, whereas big differences (> 5%) in EDV and ESV were found with regard to different positioning of animals. A linear relationship (p < .001) was found between the EDV or ESV and the kernel size of the gaussian filter. In short, respiratory gating did not significantly affect the cardiac parameters of mice obtained with ultra-high-resolution SPECT, whereas the position of the animals and the image filters should be the same in a comparative study with multiple scans to avoid systematic differences in measured cardiac parameters.

(111)In-trastuzumab scintigraphy in HER2-positive metastatic breast cancer patients remains feasible during trastuzumab treatment.

Human epidermal growth factor receptor (HER)2 imaging with radiolabeled trastuzumab might support HER2-targeted therapy. It is, however, frequently questioned whether HER2 imaging is also possible during trastuzumab treatment as the receptor might be saturated. We studied the effect of trastuzumab treatment on 111In-trastuzumab uptake. Patients received trastuzumab weekly and paclitaxel once every 3 weeks. 111In-trastuzumab was injected on day 1 of cycle 1 and day 15 of cycle 4. Whole-body planar scintigraphy was acquired at different time points postinjection. Tumor uptake and organ distribution between the first and repeated scan series were calculated via residence times. Twenty-five tumor lesions in 12 patients were visualized on both scintigraphy series. Tumor uptake decreased (19.6%; p  =  .03). The residence times of normal organs remained similar except for the cardiac blood pool (+ 16.3%; p  =  .014). Trastuzumab treatment decreases tumor 111In-trastuzumab uptake around 20%. HER2 imaging is feasible during trastuzumab treatment.

Physical Activity Levels, Correlates, and All-Cause Mortality Risk in People Living With Different Health Conditions.

BACKGROUND: To better understand physical activity behavior and its health benefits in people living with health conditions, we studied people with and without 20 different self-reported health conditions with regard to (1) their physical activity levels, (2) factors correlated with these physical activity levels, and (3) the association between physical activity and all-cause mortality. METHODS: We used a subsample (n = 88,659) of the Lifelines cohort study from the Netherlands. For people living with and without 20 different self-reported health conditions, we studied the aforementioned factors in relation to physical activity. Physical activity was assessed with the Short Questionnaire to Assess Health-Enhancing Physical Activity Questionnaire, and mortality data were obtained from the Dutch death register. RESULTS: People with a reported health condition were less likely to meet physical activity guidelines than people without a reported health condition (odds ratios ranging from 0.55 to 0.89). Higher body mass index and sitting time, and lower self-rated health, physical functioning, and education levels were associated with lower odds of meeting physical activity guidelines across most health conditions. Finally, we found a protective association between physical activity and all-cause mortality in both people living with and without different health conditions. CONCLUSION: People living with different health conditions are generally less physically active compared with people living without a health condition. Both people living with and without self-reported health conditions share a number of key factors associated with physical activity levels. We also observed the expected protective association between physical activity and all-cause mortality.

LOFIT (Lifestyle front Office For Integrating lifestyle medicine in the Treatment of patients): a novel care model towards community-based options for lifestyle change-study protocol.

BACKGROUND: A healthy lifestyle is indispensable for the prevention of noncommunicable diseases. However, lifestyle medicine is hampered by time constraints and competing priorities of treating physicians. A dedicated lifestyle front office (LFO) in secondary/tertiary care may provide an important contribution to optimize patient-centred lifestyle care and connect to lifestyle initiatives from the community. The LOFIT study aims to gain insight into the (cost-)effectiveness of the LFO. METHODS: Two parallel pragmatic randomized controlled trials will be conducted for (cardio)vascular disorders (i.e. (at risk of) (cardio)vascular disease, diabetes) and musculoskeletal disorders (i.e. osteoarthritis, hip or knee prosthesis). Patients from three outpatient clinics in the Netherlands will be invited to participate in the study. Inclusion criteria are body mass index (BMI) ≥25 (kg/m2) and/or smoking. Participants will be randomly allocated to either the intervention group or a usual care control group. In total, we aim to include 552 patients, 276 in each trial divided over both treatment arms. Patients allocated to the intervention group will participate in a face-to-face motivational interviewing (MI) coaching session with a so-called lifestyle broker. The patient will be supported and guided towards suitable community-based lifestyle initiatives. A network communication platform will be used to communicate between the lifestyle broker, patient, referred community-based lifestyle initiative and/or other relevant stakeholders (e.g. general practitioner). The primary outcome measure is the adapted Fuster-BEWAT, a composite health risk and lifestyle score consisting of resting systolic and diastolic blood pressure, objectively measured physical activity and sitting time, BMI, fruit and vegetable consumption and smoking behaviour. Secondary outcomes include cardiometabolic markers, anthropometrics, health behaviours, psychological factors, patient-reported outcome measures (PROMs), cost-effectiveness measures and a mixed-method process evaluation. Data collection will be conducted at baseline, 3, 6, 9 and 12 months follow-up. DISCUSSION: This study will gain insight into the (cost-)effectiveness of a novel care model in which patients under treatment in secondary or tertiary care are referred to community-based lifestyle initiatives to change their lifestyle. TRIAL REGISTRATION: ISRCTN ISRCTN13046877 . Registered 21 April 2022.

Coping strategies, anxiety and depressive symptoms in family members of patients treated with extracorporeal membrane oxygenation: A prospective cohort study.

BACKGROUND: Family members of patients treated with Extracorporeal Membrane Oxygenation (ECMO) during an Intensive Care Unit (ICU) stay are at risk of developing symptoms of anxiety, depression and Post-Traumatic Stress Disorder (PTSD). Coping strategies used by family members may play an important role in the severity of some of these symptoms. OBJECTIVES: The primary aim of this study was to describe coping strategies used by family members of ECMO-treated patients during ICU admission and recovery period. The secondary aim was to explore the course of the symptoms anxiety, depression, PTSD, and Health Related Quality Of Life (HRQOL) over time. METHODS: In this single-center prospective longitudinal study, validated questionnaires were used to measure coping strategies, symptoms of anxiety, depression and PTSD, and HRQOL in family members of ECMO-treated patients directly after the start of ECMO and at one and six months after the start of ECMO. RESULTS: Family members (n = 26) mainly used problem-focused coping strategies. Symptoms of anxiety appeared to be most present during treatment but decreased over time, as did symptoms of depression and PTSD. HRQOL was severely affected, especially in the mental domain, and did not improve over time. CONCLUSION: In family members of ECMO-treated patients, problem-focused coping mechanisms were most prominent. Psychological functioning was impaired on admission but improved over time, although a mild reaction to stress remained.

Perceived Training of Junior Speed Skaters versus the Coach's Intention: Does a Mismatch Relate to Perceived Stress and Recovery?

The aim of this observational study was to examine the differences between training variables as intended by coaches and perceived by junior speed skaters and to explore how these relate to changes in stress and recovery. During a 4-week preparatory period, intended and perceived training intensity (RPE) and duration (min) were monitored for 2 coaches and their 23 speed skaters, respectively. The training load was calculated by multiplying RPE by duration. Changes in perceived stress and recovery were measured using RESTQ-sport questionnaires before and after 4 weeks. Results included 438 intended training sessions and 378 executed sessions of 14 speed skaters. A moderately higher intended (52:37 h) versus perceived duration (45:16 h) was found, as skaters performed fewer training sessions than anticipated (four sessions). Perceived training load was lower than intended for speed skating sessions (-532 ± 545 AU) and strength sessions (-1276 ± 530 AU) due to lower RPE scores for skating (-0.6 ± 0.7) or shorter and fewer training sessions for strength (-04:13 ± 02:06 hh:mm). All training and RESTQ-sport parameters showed large inter-individual variations. Differences between intended-perceived training variables showed large positive correlations with changes in RESTQ-sport, i.e., for the subscale's success (r = 0.568), physical recovery (r = 0.575), self-regulation (r = 0.598), and personal accomplishment (r = 0.589). To conclude, speed skaters that approach or exceed the coach's intended training variables demonstrated an increased perception of success, physical recovery, self-regulation, and personal accomplishment.

Facilitators and barriers for the implementation of exercise are medicine in routine clinical care in Dutch university medical centres: a mixed methodology study on clinicians' perceptions.

OBJECTIVES: Despite the many proven advantages of a physically active lifestyle in patient populations, prescription of exercise is currently not widely implemented in routine clinical practice. The aims of this study were twofold: (1) to assess perceptions of clinicians on the current practice of exercise is medicine (E=M) prescription in two Dutch university medical centres and (2) to determine their perceived barriers and facilitators for the implementation of E=M in routine clinical care in Dutch university medical centres. DESIGN: A mixed methodologies study, using both online questionnaires and semi-structured interviews. SETTING: Dutch university medical centres. PARTICIPANTS: Clinicians working within the departments of medical oncology, orthopaedics and rehabilitation medicine of two university medical centres. RESULTS: Forty-five clinicians (response rate of 51%) completed the questionnaire, and 19 clinicians were interviewed. The results showed that even though clinicians had a positive attitude towards prescribing E=M, only a few reported to regularly prescribe E=M to their patients. The 52 identified facilitators and barriers for implementation of E=M were categorised into four main themes: (1) beliefs toward the implementation of E=M (eg, clinicians knowledge and skills, and social support), (2) factors related to the patient perspective (eg, patient priorities or motivation), (3) factors related to the referral options (eg, knowledge of and trust in local referral options) and (4) practical considerations when implementing E=M (eg, time constraints). CONCLUSIONS: Our study showed that even though many clinicians have a positive attitude toward an active lifestyle, many are not prescribing E=M on a regular basis. In order for clinicians to effectively implement E=M, strategies should focus on increasing clinicians E=M referral skills, improving clinicians knowledge of E=M referral options and develop a support system to ensure that E=M is high on the priority list of clinicians.

Reduction of artefacts caused by hip implants in CT-based attenuation-corrected PET images using 2-D interpolation of a virtual sinogram on an irregular grid.

PURPOSE: Metallic prosthetic replacements, such as hip or knee implants, are known to cause strong streaking artefacts in CT images. These artefacts likely induce over- or underestimation of the activity concentration near the metallic implants when applying CT-based attenuation correction of positron emission tomography (PET) images. Since this degrades the diagnostic quality of the images, metal artefact reduction (MAR) prior to attenuation correction is required. METHODS: The proposed MAR method, referred to as virtual sinogram-based technique, replaces the projection bins of the sinogram that are influenced by metallic implants by a 2-D Clough-Tocher cubic interpolation scheme performed in an irregular grid, called Delaunay triangulated grid. To assess the performance of the proposed method, a physical phantom and 30 clinical PET/CT studies including hip prostheses were used. The results were compared to the method implemented on the Siemens Biograph mCT PET/CT scanner. RESULTS: Both phantom and clinical studies revealed that the proposed method performs equally well as the Siemens MAR method in the regions corresponding to bright streaking artefacts and the artefact-free regions. However, in regions corresponding to dark streaking artefacts, the Siemens method does not seem to appropriately correct the tracer uptake while the proposed method consistently increased the uptake in the underestimated regions, thus bringing it to the expected level. This observation is corroborated by the experimental phantom study which demonstrates that the proposed method approaches the true activity concentration more closely. CONCLUSION: The proposed MAR method allows more accurate CT-based attenuation correction of PET images and prevents misinterpretation of tracer uptake, which might be biased owing to the propagation of bright and dark streaking artefacts from CT images to the PET data following the attenuation correction procedure.

Total 18F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour.

PURPOSE: Positron emission tomography (PET) using 6-[18F]fluoro-L-dihydroxyphenylalanine (18F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. 18F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total 18F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. METHODS: Seventy-seven consecutive carcinoid patients who underwent an 18F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on 18F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. RESULTS: All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. 18F-dopa PET detected 979 lesions. SUVmax on 18F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r=0.51) and urinary and plasma 5-HIAA (r=0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. CONCLUSION: Tumour load per patient measured with 18F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity.

Repeatability of two semi-automatic artificial intelligence approaches for tumor segmentation in PET.

BACKGROUND: Positron emission tomography (PET) is routinely used for cancer staging and treatment follow-up. Metabolic active tumor volume (MATV) as well as total MATV (TMATV-including primary tumor, lymph nodes and metastasis) and/or total lesion glycolysis derived from PET images have been identified as prognostic factor or for the evaluation of treatment efficacy in cancer patients. To this end, a segmentation approach with high precision and repeatability is important. However, the implementation of a repeatable and accurate segmentation algorithm remains an ongoing challenge. METHODS: In this study, we compare two semi-automatic artificial intelligence (AI)-based segmentation methods with conventional semi-automatic segmentation approaches in terms of repeatability. One segmentation approach is based on a textural feature (TF) segmentation approach designed for accurate and repeatable segmentation of primary tumors and metastasis. Moreover, a convolutional neural network (CNN) is trained. The algorithms are trained, validated and tested using a lung cancer PET dataset. The segmentation accuracy of both segmentation approaches is compared using the Jaccard coefficient (JC). Additionally, the approaches are externally tested on a fully independent test-retest dataset. The repeatability of the methods is compared with those of two majority vote (MV2, MV3) approaches, 41%SUVMAX, and a SUV > 4 segmentation (SUV4). Repeatability is assessed with test-retest coefficients (TRT%) and intraclass correlation coefficient (ICC). An ICC > 0.9 was regarded as representing excellent repeatability. RESULTS: The accuracy of the segmentations with the reference segmentation was good (JC median TF: 0.7, CNN: 0.73). Both segmentation approaches outperformed most other conventional segmentation methods in terms of test-retest coefficient (TRT% mean: TF: 13.0%, CNN: 13.9%, MV2: 14.1%, MV3: 28.1%, 41%SUVMAX: 28.1%, SUV4: 18.1%) and ICC (TF: 0.98, MV2: 0.97, CNN: 0.99, MV3: 0.73, SUV4: 0.81, and 41%SUVMAX: 0.68). CONCLUSION: The semi-automatic AI-based segmentation approaches used in this study provided better repeatability than conventional segmentation approaches. Moreover, both algorithms lead to accurate segmentations for both primary tumors as well as metastasis and are therefore good candidates for PET tumor segmentation.

Managing Load to Optimize Well-Being and Recovery During Short-Term Match Congestion in Elite Basketball.

In elite basketball, players are exposed to intensified competition periods when participating in both national and international competitions. How coaches manage training between matches and in reference to match scheduling for a full season is not yet known. PURPOSE: First, to compare load during short-term match congestion (ie, ≥2-match weeks) with regular competition (ie, 1-match weeks) in elite male professional basketball players. Second, to determine changes in well-being, recovery, neuromuscular performance, and injuries and illnesses between short-term match congestion and regular competition. METHODS: Sixteen basketball players (age 24.8 [2.0] y, height 195.8 [7.5] cm, weight 94.8 [14.0] kg, body fat 11.9% [5.0%], VO2max 51.9 [5.3] mL·kg-1·min-1) were monitored during a full season. Session rating of perceived exertion (s-RPE) was obtained, and load was calculated (s-RPE × duration) for each training session or match. Perceived well-being (fatigue, sleep quality, general muscle soreness, stress levels, and mood) and total quality of recovery were assessed each training day. Countermovement jump height was measured, and a list of injuries and illnesses was collected weekly using the adapted Oslo Sports Trauma Research Center Questionnaire on Health Problems. RESULTS: Total load (training sessions and matches; P < .001) and training load (P < .001) were significantly lower for ≥2-match weeks. Significantly higher well-being (P = .01) and less fatigue (P = .001) were found during ≥2-match weeks compared with 1-match weeks. CONCLUSION: Total load and training load were lower during short-term match congestion compared with regular competition. Furthermore, better well-being and less fatigue were demonstrated within short-term match congestion. This might indicate that coaches tend to overcompensate training load in intensified competition.

PET segmentation of bulky tumors: Strategies and workflows to improve inter-observer variability.

BACKGROUND: PET-based tumor delineation is an error prone and labor intensive part of image analysis. Especially for patients with advanced disease showing bulky tumor FDG load, segmentations are challenging. Reducing the amount of user-interaction in the segmentation might help to facilitate segmentation tasks especially when labeling bulky and complex tumors. Therefore, this study reports on segmentation workflows/strategies that may reduce the inter-observer variability for large tumors with complex shapes with different levels of user-interaction. METHODS: Twenty PET images of bulky tumors were delineated independently by six observers using four strategies: (I) manual, (II) interactive threshold-based, (III) interactive threshold-based segmentation with the additional presentation of the PET-gradient image and (IV) the selection of the most reasonable result out of four established semi-automatic segmentation algorithms (Select-the-best approach). The segmentations were compared using Jaccard coefficients (JC) and percentage volume differences. To obtain a reference standard, a majority vote (MV) segmentation was calculated including all segmentations of experienced observers. Performed and MV segmentations were compared regarding positive predictive value (PPV), sensitivity (SE), and percentage volume differences. RESULTS: The results show that with decreasing user-interaction the inter-observer variability decreases. JC values and percentage volume differences of Select-the-best and a workflow including gradient information were significantly better than the measurements of the other segmentation strategies (p-value<0.01). Interactive threshold-based and manual segmentations also result in significant lower and more variable PPV/SE values when compared with the MV segmentation. CONCLUSIONS: FDG PET segmentations of bulky tumors using strategies with lower user-interaction showed less inter-observer variability. None of the methods led to good results in all cases, but use of either the gradient or the Select-the-best workflow did outperform the other strategies tested and may be a good candidate for fast and reliable labeling of bulky and heterogeneous tumors.

Implementing Individually Tailored Prescription of Physical Activity in Routine Clinical Care: Protocol of the Physicians Implement Exercise = Medicine (PIE=M) Development and Implementation Project.

BACKGROUND: The prescription of physical activity (PA) in clinical care has been advocated worldwide. This "exercise is medicine" (E=M) concept can be used to prevent, manage, and cure various lifestyle-related chronic diseases. Due to several challenges, E=M is not yet routinely implemented in clinical care. OBJECTIVE: This paper describes the rationale and design of the Physicians Implement Exercise = Medicine (PIE=M) study, which aims to facilitate the implementation of E=M in hospital care. METHODS: PIE=M consists of 3 interrelated work packages. First, levels and determinants of PA in different patient and healthy populations will be investigated using existing cohort data. The current implementation status, facilitators, and barriers of E=M will also be investigated using a mixed-methods approach among clinicians of participating departments from 2 diverse university medical centers (both located in a city, but one serving an urban population and one serving a more rural population). Implementation strategies will be connected to these barriers and facilitators using a systematic implementation mapping approach. Second, a generic E=M tool will be developed that will provide tailored PA prescription and referral. Requirements for this tool will be investigated among clinicians and department managers. The tool will be developed using an iterative design process in which all stakeholders reflect on the design of the E=M tool. Third, we will pilot-implement the set of implementation strategies, including the E=M tool, to test its feasibility in routine care of clinicians in these 2 university medical centers. An extensive learning process evaluation will be performed among clinicians, department managers, lifestyle coaches, and patients using a mixed-methods design based on the RE-AIM framework. RESULTS: This project was approved and funded by the Dutch grant provider ZonMW in April 2018. The project started in September 2018 and continues until December 2020 (depending on the course of the COVID-19 crisis). All data from the first work package have been collected and analyzed and are expected to be published in 2021. Results of the second work package are described. The manuscript is expected to be published in 2021. The third work package is currently being conducted in clinical practice in 4 departments of 2 university medical hospitals among clinicians, lifestyle coaches, hospital managers, and patients. Results are expected to be published in 2021. CONCLUSIONS: The PIE=M project addresses the potential of providing patients with PA advice to prevent and manage chronic disease, improve recovery, and enable healthy ageing by developing E=M implementation strategies, including an E=M tool, in routine clinical care. The PIE=M project will result in a blueprint of implementation strategies, including an E=M screening and referral tool, which aims to improve E=M referral by clinicians to improve patients' health, while minimizing the burden on clinicians.

Development and characterization of clinical-grade 89Zr-trastuzumab for HER2/neu immunoPET imaging.

UNLABELLED: The anti-human epidermal growth factor receptor 2 (HER2/neu) antibody trastuzumab is administered to patients with HER2/neu-overexpressing breast cancer. Whole-body noninvasive HER2/neu scintigraphy could help to assess and quantify the HER2/neu expression of all lesions, including nonaccessible metastases. The aims of this study were to develop clinical-grade radiolabeled trastuzumab for clinical HER2/neu immunoPET scintigraphy, to improve diagnostic imaging, to guide antibody-based therapy, and to support early antibody development. The PET radiopharmaceutical (89)Zr-trastuzumab was compared with the SPECT tracer (111)In-trastuzumab, which we have tested in the clinic already. METHODS: Trastuzumab was labeled with (89)Zr and (for comparison) with (111)In. The minimal dose of trastuzumab required for optimal small-animal PET imaging and biodistribution was determined with human HER2/neu-positive or -negative tumor xenograft-bearing mice. RESULTS: Trastuzumab was efficiently radiolabeled with (89)Zr at a high radiochemical purity and specific activity. The antigen-binding capacity was preserved, and the radiopharmaceutical proved to be stable for up to 7 d in solvent and human serum. Of the tested protein doses, the minimal dose of trastuzumab (100 microg) proved to be optimal for imaging. The comparative biodistribution study showed a higher level of (89)Zr-trastuzumab in HER2/neu-positive tumors than in HER2/neu-negative tumors, especially at day 6 (33.4 +/- 7.6 [mean +/- SEM] vs. 7.1 +/- 0.7 percentage injected dose per gram of tissue). There were good correlations between the small-animal PET images and the biodistribution data and between (89)Zr-trastuzumab and (111)In-trastuzumab uptake in tumors (R(2) = 0.972). CONCLUSION: Clinical-grade (89)Zr-trastuzumab showed high and HER2/neu-specific tumor uptake at a good resolution.

Steroid hormones affect binding of the sigma ligand 11C-SA4503 in tumour cells and tumour-bearing rats.

PURPOSE: Sigma receptors are implicated in memory and cognitive functions, drug addiction, depression and schizophrenia. In addition, sigma receptors are strongly overexpressed in many tumours. Although the natural ligands are still unknown, steroid hormones are potential candidates. Here, we examined changes in binding of the sigma-1 agonist (11)C-SA4503 in C6 glioma cells and in living rats after modification of endogenous steroid levels. METHODS: (11)C-SA4503 binding was assessed in C6 monolayers by gamma counting and in anaesthetized rats by microPET scanning. C6 cells were either repeatedly washed and incubated in steroid-free medium or exposed to five kinds of exogenous steroids (1 h or 5 min before tracer addition, respectively). Tumour-bearing male rats were repeatedly treated with pentobarbital (a condition known to result in reduction of endogenous steroid levels) or injected with progesterone. RESULTS: Binding of (11)C-SA4503 to C6 cells was increased (approximately 50%) upon removal and decreased (approximately 60%) upon addition of steroid hormones (rank order of potency: progesterone > allopregnanolone = testosterone = androstanolone > dehydroepiandrosterone-3-sulphate, IC(50) progesterone 33 nM). Intraperitoneally administered progesterone reduced tumour uptake and tumour-to-muscle contrast (36%). Repeated treatment of animals with pentobarbital increased the PET standardized uptake value of (11)C-SA4503 in tumour (16%) and brain (27%), whereas the kinetics of blood pool radioactivity was unaffected. CONCLUSIONS: The binding of (11)C-SA4503 is sensitive to steroid competition. Since not only increases but also decreases of steroid levels affect ligand binding, a considerable fraction of the sigma-1 receptor population in cultured tumour cells or tumour-bearing animals is normally occupied by endogenous steroids.

RaCaT: An open source and easy to use radiomics calculator tool.

PURPOSE: The widely known field 'Radiomics' aims to provide an extensive image based phenotyping of e.g. tumors using a wide variety of feature values extracted from medical images. Therefore, it is of utmost importance that feature values calculated by different institutes follow the same feature definitions. For this purpose, the imaging biomarker standardization initiative (IBSI) provides detailed mathematical feature descriptions, as well as (mathematical) test phantoms and corresponding reference feature values. We present here an easy to use radiomic feature calculator, RaCaT, which provides the calculation of a large number of radiomic features for all kind of medical images which are in compliance with the standard. METHODS: The calculator is implemented in C++ and comes as a standalone executable. Therefore, it can be easily integrated in any programming language, but can also be called from the command line. No programming skills are required to use the calculator. The software architecture is highly modularized so that it is easily extendible. The user can also download the source code, adapt it if needed and build the calculator from source. The calculated feature values are compliant with the ones provided by the IBSI standard. Source code, example files for the software configuration, and documentation can be found online on GitHub (https://github.com/ellipfaehlerUMCG/RaCat). RESULTS: The comparison with the standard values shows that all calculated features as well as image preprocessing steps, comply with the IBSI standard. The performance is also demonstrated on clinical examples. CONCLUSIONS: The authors successfully implemented an easy to use Radiomics calculator that can be called from any programming language or from the command line. Image preprocessing and feature settings and calculations can be adjusted by the user.