Advancing the Collaboration Between Imaging and Radiation Oncology.

The fusion of cutting-edge imaging technologies with radiation therapy (RT) has catalyzed transformative breakthroughs in cancer treatment in recent decades. It is critical for us to review our achievements and preview into the next phase for future synergy between imaging and RT. This paper serves as a review and preview for fostering collaboration between these two domains in the forthcoming decade. Firstly, it delineates ten prospective directions ranging from technological innovations to leveraging imaging data in RT planning, execution, and preclinical research. Secondly, it presents major directions for infrastructure and team development in facilitating interdisciplinary synergy and clinical translation. We envision a future where seamless integration of imaging technologies into RT will not only meet the demands of RT but also unlock novel functionalities, enhancing accuracy, efficiency, safety, and ultimately, the standard of care for patients worldwide.

Protocol for a randomized clinical trial of strength at home parents: A trauma informed parenting intervention for veterans.

Background: Post-traumatic stress disorder (PTSD) is highly prevalent in veterans and associated with impairments in family functioning, including parenting. There is a bidirectional relationship between PTSD and familial functioning such that impaired functioning is related to increases in trauma-related symptoms, and vice versa. Despite this known bidirectional association, there is currently no trauma-informed parenting intervention available for veterans within the Department of Veterans Affairs (VA). Strength at Home - Parents (SAHP) is an 8-session telehealth delivered psychotherapy group that aims to improve parenting behaviors and overall parent-child and family functioning among U.S. military veterans with PTSD symptoms. This paper describes the methods of an individually randomized group therapy trial to test the efficacy of SAHP compared to a VA treatment as usual control condition.Methods are reported using SPIRIT guidelines. Methods: One hundred and ninety veterans with elevated PTSD symptoms and parent-child functioning problems will be randomly assigned to the SAHP intervention or a treatment-as-usual control group. Outcomes are measured at 4 timepoints including baseline. The primary outcome is parenting stress. We will also examine changes in parenting behaviors, whether treatment gains are maintained over time, and will conduct an exploratory analysis to examine results separately by gender. Secondary outcomes include symptoms of PTSD and depression, family functioning, and child psychosocial functioning. Conclusion: Study findings will determine the efficacy of SAHP, an intervention developed for ease of use and implementation within the VA to improve parenting stress and parenting behaviors in veterans with elevated PTSD symptoms and parenting difficulties.

Implementing Plan of the Day for Cervical Cancer: A Comparison of Target Volume Generation Methods.

Purpose: Owing to substantial interfraction motion in cervical cancer, plan-of-the-day (PotD) adaptive radiation therapy may be of benefit to patients. Implementation is limited by uncertainty over how to generate the planning target volumes (PTVs). We compared published methods on our own patients. Methods and Materials: Forty patients each had 3 planning scans with variable bladder filling and daily cone beam computed tomographies (cone beam CTs) during radiation therapy; 5 to 11 cone beam CTs were selected to represent interfraction motion. Clinical target volumes (CTVs) and organs at risk were contoured following EMBRACE-II guidelines. A literature search identified 30 adaptive and nonadaptive solutions to PTV generation, which we applied to our patients. PTV sizes and mean coverage of the daily CTV were determined. For 11 patients, the clinically implemented, subjectively edited plan library was also investigated. Results: Eleven studies assessed 15 PotD strategies against nonadaptive comparators on a median of 14 patients (range, 9-23). Some PotD approaches applied margin recipes to the CTV on each planning scan, some modeled the CTV against bladder volume, and others applied incremental isotropic margins to the CTV with a single planning scan. Generally, coverage improved as PTV size increased. The fixed isotropic margin required to provide 100% coverage of all patients was 44 mm, with a mean PTV size of 3316 cm3. The PotD strategy with the best coverage was a 2-plan library formed by modeling the CTV against bladder volume with extrapolation; it provided 98% mean coverage with 1419-cm3 mean PTV size. A 3-plan library consisting of the CTV on each planning scan with 10-mm margin provided 96% mean coverage with 1346-cm3 mean PTV size. The clinically implemented solution that employed subjective extrapolation had mean 100% coverage and 1282-cm3 PTV size on the 11-patient subset. Coverage provided by the best nonadaptive strategies was not statistically superior to the best PotD strategy (P = .13), but PTVs were larger (P = .02). Conclusions: We identified a modeled 2-plan method and a simple 3-plan method, both of which provided excellent coverage with small PTVs compared with nonadaptive strategies.

Simulation of ultrasound backscatter coefficient measurement using the finite element method.

Ultrasound backscatter coefficient (BSC) measurement is a method for assessing tissue morphology that can inform on pathologies such as cancer. The BSC measurement is, however, limited by the accuracy with which the investigator can normalise their results to account for frequency dependent effects of diffraction and attenuation whilst performing such measurements. We propose a simulation-based approach to investigate the potential sources of error in assessing the BSC. Presented is a tool for the 2D Finite Element (FE) simulation mimicking a BSC measurement using the planar reflector substitution method in reduced dimensionality. The results of this are verified against new derivations of BSC equations also in reduced dimensionality. These new derivations allow computation of BSC estimates based on the scattering from a 2D scattering area, a line reference reflector and a theoretical value for the BSC of a 2D distribution of scatterers. This 2D model was designed to generate lightweight simulations that allow rapid investigation of the factors associated with BSC measurement, allowing the investigator to generate large data sets in relatively short time scales. Under the conditions for an incoherent scattering medium, the simulations produced BSC estimates within 6% of the theoretical value calculated from the simulation domain, a result reproduced across a range of source f-numbers. This value of error compares well to both estimated errors from other simulation based approaches and to physical experiments. The mathematical and simulation models described here provide a theoretical and experimental framework for continued investigation into factors affecting the accuracy of BSC measurements.

Comparing the healthy development of youth Australian Rules Footballers across talent development and community settings.

Objectives: This study aimed to compare talent development athletes to community-level athletes in Australian Rules Football across various markers of healthy youth development. Methods: Survey data were collected from 363 youth athletes (126 women, 232 men, 5 not reported; Mage=18.69 years, SDage=2.62 years, age range 16-25 years) playing Australian Rules Football at a talent development (recruited from Australian Football League Talent Pathway, n=220) or community (n=143) level. Measures included markers of physical health (eg, general health, risk-taking behaviours), psychological and emotional well-being (eg, mental health symptoms, life satisfaction), family and social relationships (eg, social support, relationship status), educational and occupational attainment/engagement (eg, career satisfaction, education), ethical behaviour (eg, moral self-image), civic engagement, life skills (eg, self-mastery, coping), and demographics. Results: Based on regression models, relative to community-level athletes, talent development athletes reported better physical health (d=0.51), lower injury rates (OR=0.50) and less problematic drug use (d=-0.46). Talent development athletes also reported better psychological and emotional well-being, evidenced by lower stress (d=-0.30), higher life satisfaction (d=0.47) and less problematic gambling (d=-0.34). Additionally, talent development athletes reported higher family support (d=0.49), lower likelihood of poor educational outcomes (less than expected educational stage; OR=0.37), lower intention to complete less than year 12 education (OR=0.18), higher career satisfaction (d=0.42), higher self-mastery (d=0.37) and higher perfectionistic striving (d=0.59). Conclusion: Findings demonstrate markers of healthier development within talent development athletes relative to community athlete peers. Investment in community-level sports may be warranted to improve healthy development. However, further causal evidence is required.

Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment: Identification of metabolic correlates of fatigue.

OBJECTIVE: In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR symptoms in the metabolite signatures of peripheral blood from patients with PMR or the related disease, giant cell arteritis (GCA). METHODS: Nuclear magnetic resonance spectroscopy was performed on serum from 40 patients with untreated PMR, 84 with new-onset confirmed GCA, and 53 with suspected GCA who later were clinically confirmed non-GCA, and 39 age-matched controls. Further samples from PMR patients were taken one and six months into glucocorticoid therapy to explore relationship of metabolites to persistent fatigue. 100 metabolites were identified using Chenomx and statistical analysis performed in SIMCA-P to examine the relationship between metabolic profiles and, disease, GC treatment or symptoms. RESULTS: The metabolite signature of patients with PMR and GCA differed from that of age-matched non-inflammatory controls (R2 > 0.7). There was a smaller separation between patients with clinically confirmed GCA and those with suspected GCA who later were clinically confirmed non-GCA (R2 = 0.135). In PMR, metabolite signatures were further altered with glucocorticoid treatment (R2 = 0.42) but did not return to that seen in controls. Metabolites correlated with CRP, pain, stiffness, and fatigue (R2 ≥ 0.39). CRP, pain, and stiffness declined with treatment and were associated with 3-hydroxybutyrate and acetoacetate, but fatigue did not. Metabolites differentiated patients with high and low fatigue both before and after treatment (R2 > 0.9). Low serum glutamine was predictive of high fatigue at both time points (0.79-fold change). CONCLUSION: PMR and GCA alter the metabolite signature. In PMR, this is further altered by glucocorticoid therapy. Treatment-induced metabolite changes were linked to measures of inflammation (CRP, pain and stiffness), but not to fatigue. Furthermore, metabolite signatures distinguished patients with high or low fatigue.

Predicting cervical cancer target motion using a multivariate regression model to enable patient selection for adaptive external beam radiotherapy.

Background and purpose: Interfraction motion during cervical cancer radiotherapy is substantial in some patients, minimal in others. Non-adaptive plans may miss the target and/or unnecessarily irradiate normal tissue. Adaptive radiotherapy leads to superior dose-volume metrics but is resource-intensive. The aim of this study was to predict target motion, enabling patient selection and efficient resource allocation. Materials and methods: Forty cervical cancer patients had CT with full-bladder (CT-FB) and empty-bladder (CT-EB) at planning, and daily cone-beam CTs (CBCTs). The low-risk clinical target volume (CTVLR) was contoured. Mean coverage of the daily CTVLR by the CT-FB CTVLR was calculated for each patient. Eighty-three investigated variables included measures of organ geometry, patient, tumour and treatment characteristics. Models were trained on 29 patients (171 fractions). The Two-CT multivariate model could use all available data. The Single-CT multivariate model excluded data from the CT-EB. A univariate model was trained using the distance moved by the uterine fundus tip between CTs, the only method of patient selection found in published cervix plan-of-the-day studies. Models were tested on 11 patients (68 fractions). Accuracy in predicting mean coverage was reported as mean absolute error (MAE), mean squared error (MSE) and R2. Results: The Two-CT model was based upon rectal volume, dice similarity coefficient between CT-FB and CT-EB CTVLR, and uterine thickness. The Single-CT model was based upon rectal volume, uterine thickness and tumour size. Both performed better than the univariate model in predicting mean coverage (MAE 7 %, 7 % and 8 %; MSE 82 %2, 65 %2, 110 %2; R2 0.2, 0.4, -0.1). Conclusion: Uterocervix motion is complex and multifactorial. We present two multivariate models which predicted motion with reasonable accuracy using pre-treatment information, and outperformed the only published method.

Patient decision aids for aortic stenosis and chronic coronary artery disease: a systematic review and meta-analysis.

AIMS: Shared decision-making is recommended for patients considering treatment options for severe aortic stenosis (AS) and chronic coronary artery disease (CAD). This review aims to systematically identify and assess patient decision aids (PtDAs) for chronic CAD and AS and evaluate the international evidence on their effectiveness for improving the quality of decision-making. METHODS AND RESULTS: Five databases (Cochrane, CINAHL, Embase, MEDLINE, and PsycInfo), clinical trial registers, and 30 PtDA repositories/websites were searched from 2006 to March 2023. Screening, data extraction, and quality assessments were completed independently by multiple reviewers. Meta-analyses were conducted using Stata statistical software. Eleven AS and 10 CAD PtDAs were identified; seven were less than 5 years old. Over half of the PtDAs were web based and the remainder paper based. One AS and two CAD PtDAs fully/partially achieved international PtDA quality criteria. Ten studies were included in the review; four reported on the development/evaluation of AS PtDAs and six on CAD PtDAs. Most studies were conducted in the USA with White, well-educated, English-speaking participants. No studies fulfilled all quality criteria for reporting PtDA development and evaluation. Meta-analyses found that PtDAs significantly increased patient knowledge compared with 'usual care' (mean difference: 0.620; 95% confidence interval 0.396-0.845, P < 0.001) but did not change decisional conflict. CONCLUSION: Patients who use PtDAs when considering treatments for AS or chronic CAD are likely to be better informed than those who do not. Existing PtDAs may not meet the needs of people with low health literacy levels as they are rarely involved in their development. REGISTRATION: PROSPERO: CRD42021264700.

Evaluation of Vector-Enabled Xenosurveillance in Rural Guatemala.

Surveillance methods that permit rapid detection of circulating pathogens in low-resource settings are desperately needed. In this study, we evaluated a mosquito bloodmeal-based surveillance method ("xenosurveillance") in rural Guatemala. Twenty households from two villages (Los Encuentros and Chiquirines) in rural southwest Guatemala were enrolled and underwent weekly prospective surveillance from August 2019 to December 2019 (16 weeks). When febrile illness was reported in a household, recently blood-fed mosquitoes were collected from within dwellings and blood samples taken from each member of the household. Mosquitoes were identified to species and blood sources identified by sequencing. Shotgun metagenomic sequencing was used to identify circulating viruses. Culex pipiens (60.9%) and Aedes aegypti (18.6%) were the most abundant mosquitoes collected. Bloodmeal sources were most commonly human (32.6%) and chicken (31.6%), with various other mammal and avian hosts detected. Several mosquito-specific viruses were detected, including Culex orthophasma virus. Human pathogens were not detected. Therefore, xenosurveillance may require more intensive sampling to detect human pathogens in Guatemala and ecologically similar localities in Central America.

Colorado tick fever virus: a review of historical literature and research emphasis for a modern era.

Colorado tick fever virus is an understudied tick-borne virus of medical importance that is primarily transmitted in the western United States and southwestern Canada. The virus is the type species of the genus Coltivirus (Spinareoviridae) and consists of 12 segments that remain largely uncharacterized. Patterns of viral distribution are driven by the presence of the primary vector, the Rocky Mountain wood tick, Dermacentor andersoni. Infection prevalence in D. andersoni can range from 3% to 58% across the geographic distribution of the tick. Infection in humans can be severe and often presents with fever relapses but is rarely fatal. Here, we review the literature from primary characterizations in the early 20th century to current virus/vector research being conducted and identify vacancies in current research.

Trends in use of intraosseous and intravenous access in out-of-hospital cardiac arrest across English ambulance services: A registry-based, cohort study.

INTRODUCTION: The optimum route for drug administration in cardiac arrest is unclear. Recent data suggest that use of the intraosseous route may be increasing. This study aimed to explore changes over time in use of the intraosseous and intravenous drug routes in out-of-hospital cardiac arrest in England. METHODS: We extracted data from the UK Out-of-Hospital Cardiac Arrest Outcomes registry. We included adult out-of-hospital cardiac arrest patients between 2015-2020 who were treated by an English Emergency Medical Service that submitted vascular access route data to the registry. The primary outcome was any use of the intraosseous route during cardiac arrest. We used logistic regression models to describe the association between time (calendar month) and intraosseous use. RESULTS: We identified 75,343 adults in cardiac arrest treated by seven Emergency Medical Service systems between January 2015 and December 2020. The median age was 72 years, 64% were male and 23% presented in a shockable rhythm. Over the study period, the percentage of patients receiving intraosseous access increased from 22.8% in 2015 to 42.5% in 2020. For each study-month, the odds of receiving any intraosseous access increased by 1.019 (95% confidence interval 1.019 to 1.020, p < 0.001). This observed effect was consistent across sensitivity analyses. We observed a corresponding decrease in use of intravenous access. CONCLUSION: In England, the use of intraosseous access in out-of-hospital cardiac arrest has progressively increased over time. There is an urgent need for randomised controlled trials to evaluate the clinical effectiveness of the different vascular access routes in cardiac arrest.

Multidisciplinary paper on patient blood management in cardiothoracic surgery in the UK: perspectives on practice during COVID-19.

The coronavirus (COVID-19) pandemic disrupted all surgical specialties significantly and exerted additional pressures on the overburdened United Kingdom (UK) National Health Service. Healthcare professionals in the UK have had to adapt their practice. In particular, surgeons have faced organisational and technical challenges treating patients who carried higher risks, were more urgent and could not wait for prehabilitation or optimisation before their intervention. Furthermore, there were implications for blood transfusion with uncertain patterns of demand, reductions in donations and loss of crucial staff because of sickness and public health restrictions. Previous guidelines have attempted to address the control of bleeding and its consequences after cardiothoracic surgery, but there have been no targeted recommendations in light of the recent COVID-19 challenges. In this context, and with a focus on the perioperative period, an expert multidisciplinary Task Force reviewed the impact of bleeding in cardiothoracic surgery, explored different aspects of patient blood management with a focus on the use of haemostats as adjuncts to conventional surgical techniques and proposed best practice recommendations in the UK.

Evaluation of Performance Tradeoffs When Using Mechanically Swept 1-D Linear Arrays for 3-D DCE-US.

Dynamic contrast-enhanced ultrasound imaging (DCE-US) may be used to characterize tumor vascular perfusion using metrics derived from time-amplitude curves (TACs). The 3-D DCE-US enables generation of 3-D parametric maps of TAC metrics that may inform on how perfusion varies across the entire tumor. The aim of this work was to understand the effect of low temporal sampling (i.e., < 1 Hz) typical of 3-D imaging using a swept 1-D array transducer on the evaluation of TAC metrics and the effect of transducer motion in combination with flow on 3-D parametric maps generated using both plane wave imaging (PWI) (seven angles) and focused imaging (FI). Correlation maps were introduced to evaluate the spatial blurring of TAC metrics. A research ultrasound scanner and a pulse-inversion algorithm were used to obtain DCE-US. The 2-D (frame rate 10 Hz) and 3-D (volume rate 0.4 Hz) images were acquired of a simple wall-less vessel phantom (flow phantom) and a cartridge phantom. Volumetric imaging provided similar TACs to that of the higher 2-D sampling rate. Varying sweep speed and acceleration/deceleration had little influence on the 3-D TAC compared to 2-D for both FI and PWI. Sweeping motion and limited temporal sampling (0.4 Hz) did not change the spatial correlation of TAC metrics measured using FI, whereas a small increase in correlation across the cartridge phantom was observed for PWI. This was attributed to grating lobe artifacts, broad beam spatial blurring, and incoherent compounding caused by motion. Increased correlation will reduce the spatial resolution with which inhomogeneity of vascular perfusion can be mapped supporting the choice of FI for DCE-US.

Elevated fullness and bloating as correlates of eating pathology: Implications for screening.

A minority of individuals with eating disorders report being asked about their eating by health care professionals; delayed detection of eating disorders may contribute to poorer outcomes. The current study investigated common meal-related gastrointestinal symptoms (i.e., elevated fullness and bloating) as correlates of eating pathology that may be more readily disclosed to health professionals and indicate the need to assess for eating pathology. The current study also tested the hypothesis that elevated fullness and bloating are more strongly linked to eating pathology among those with higher body dissatisfaction. 281 university students (70.1% female, 84.3% white) completed gastrointestinal symptom and eating pathology assessments. Elevated fullness and bloating were each associated with increased purging, restrictive eating behaviors, and likelihood of having an eating disorder. Elevated fullness and bloating were more strongly linked to purging and probable eating disorder diagnosis with higher, relative to lower, body dissatisfaction. However, body dissatisfaction did not moderate the relationship between gastrointestinal symptoms and restrictive eating behaviors. Results indicate that elevated fullness and bloating are correlates of eating pathology. Healthcare professionals should consider and/or assess for eating pathology when elevated fullness and bloating are reported; further assessment of body dissatisfaction may be helpful in identifying purging behaviors.

Carpe Diem: Making the Most of Plan-of-the-Day for Cervical Cancer Radiation Therapy.

PURPOSE: Radiation therapy is the key treatment for locally advanced cervical cancer. Organ motion presents a challenge to accurate targeting of external beam radiation therapy. The plan-of-the-day (PotD) adaptive approach is therefore an attractive option. We present our experience and the procedural steps required to implement PotD for cervix cancer. METHODS AND MATERIALS: We reviewed relevant studies on organ motion and adaptive radiation therapy identified through a literature search and cross referencing. These included 10 dosimetric and 3 quality of life studies directly assessing the PotD approach to radiation therapy in cervix cancer. RESULTS: Studies show improvements in target coverage and reduction of dose received by normal tissues and suggest improved toxicity. Clinical implementation of PotD has been slow because of a number of difficulties and uncertainties, which we discuss with the aim of helping teams to implement PotD at their center. CONCLUSIONS: The PotD approach improves dosimetry and may improve toxicity. We describe a framework to assist with practical implementation.

Preclinical Three-Dimensional Vibrational Shear Wave Elastography for Mapping of Tumour Biomechanical Properties In Vivo.

Preclinical investigation of the biomechanical properties of tissues and their treatment-induced changes are essential to support drug-discovery, clinical translation of biomarkers of treatment response, and studies of mechanobiology. Here we describe the first use of preclinical 3D elastography to map the shear wave speed (cs), which is related to tissue stiffness, in vivo and demonstrate the ability of our novel 3D vibrational shear wave elastography (3D-VSWE) system to detect tumour response to a therapeutic challenge. We investigate the use of one or two vibrational sources at vibrational frequencies of 700, 1000 and 1200 Hz. The within-subject coefficients of variation of our system were found to be excellent for 700 and 1000 Hz and 5.4 and 6.2%, respectively. The relative change in cs measured with our 3D-VSWE upon treatment with an anti-vascular therapy ZD6126 in two tumour xenografts reflected changes in tumour necrosis. U-87 MG drug vs vehicle: Δcs = −24.7 ± 2.5 % vs 7.5 ± 7.1%, (p = 0.002) and MDA-MB-231 drug vs vehicle: Δcs = −12.3 ± 2.7 % vs 4.5 ± 4.7%, (p = 0.02). Our system enables rapid (<5 min were required for a scan length of 15 mm and three vibrational frequencies) 3D mapping of quantitative tumour viscoelastic properties in vivo, allowing exploration of regional heterogeneity within tumours and speedy recovery of animals from anaesthesia so that longitudinal studies (e.g., during tumour growth or following treatment) may be conducted frequently.

Efficacy of interval exercise training to improve vascular health in sedentary postmenopausal females.

BACKGROUND: Menopause represents a turning point where vascular damage begins to outweigh reparative processes, leading to increased cardiovascular disease (CVD) risk. Exercise training reduces CVD risk in postmenopausal females via improvements in traditional risk factors and direct changes to the vasculature. We assessed the effect of moderate (MODERATE-IT) versus heavy (HEAVY-IT) intensity interval exercise training upon markers of cardiovascular health and vascular repair in postmenopausal females. METHODS: Twenty-seven healthy postmenopausal females (56 ± 4 yr) were assigned to 12 weeks of either MODERATE-IT or HEAVY-IT, twice per week. MODERATE-IT consisted of 10s work, and 10s active recovery repeated for 30 min. HEAVY-IT comprised 30s work, and 30s active recovery repeated for 21 ± 2 min. Endothelial function (flow-mediated dilation), arterial stiffness (pulse wave velocity), and V̇O2peak were assessed pre-training and post-training. Blood samples were obtained pre-training and post-training for enumeration of circulating angiogenic cells (CACs), culture of CACs, and lipoprotein profile. RESULTS: V̇O2peak increased 2.4 ± 2.8 ml/kg/min following HEAVY-IT only (p < 0.05). Brachial blood pressure and endothelial function were unchanged with exercise training (p > 0.05). Peripheral pulse wave velocity reduced 8% with exercise training, irrespective of intensity (p < 0.05). Exercise training had no effect on lipoprotein profile or endothelin-1 (p > 0.05). CAC adhesion to vascular smooth muscle cells (VSMC) increased 30 min post plating following MODERATE-IT only (p < 0.05). CONCLUSIONS: HEAVY-IT was more effective at increasing V̇O2peak in postmenopausal females. The ability of CACs to adhere to VSMC improved following MODERATE-IT but not HEAVY-IT. Interval training had the same effect on endothelial function (no change) and arterial stiffness (reduced), regardless of exercise intensity.

Development and user-testing of a digital patient decision aid to facilitate shared decision-making for people with stable angina.

BACKGROUND: Research shows that people with stable angina need decision support when considering elective treatments. Initial treatment is with medicines but patients may gain further benefit with invasive percutaneous coronary intervention (PCI). Choosing between these treatments can be challenging for patients because both confer similar benefits but have different risks. Patient decision aids (PtDAs) are evidence-based interventions that support shared decision-making (SDM) when making healthcare decisions. This study aimed to develop and user-test a digital patient decision aid (CONNECT) to facilitate SDM for people with stable angina considering invasive treatment with elective PCI. METHODS: A multi-phase study was conducted to develop and test CONNECT (COroNary aNgioplasty dECision Tool) using approaches recommended by the International Patient Decision Aid Standards Collaboration: (i) Steering Group assembled, (ii) review of clinical guidance, (iii) co-design workshops with patients and cardiology health professionals, (iv) first prototype developed and 'alpha' tested (semi-structured cognitive interviews and 12-item acceptability questionnaire) with patients, cardiologists and cardiac nurses, recruited from two hospitals in Northern England, and (v) final PtDA refined following iterative user-feedback. Quantitative data were analysed descriptively and qualitative data from the interviews analysed using deductive content analysis. RESULTS: CONNECT was developed and user-tested with 34 patients and 29 cardiology health professionals. Findings showed that CONNECT was generally acceptable, usable, comprehensible, and desirable. Participants suggested that CONNECT had the potential to improve care quality by personalising consultations and facilitating SDM and informed consent. Patient safety may be improved as CONNECT includes questions about symptom burden which can identify asymptomatic patients unlikely to benefit from PCI, as well as those who may need to be fast tracked because of worsening symptoms. CONCLUSIONS: CONNECT is the first digital PtDA for people with stable angina considering elective PCI, developed in the UK using recommended processes and fulfilling international quality criteria. CONNECT shows promise as an approach to facilitate SDM and should be evaluated in a clinical trial. Further work is required to standardise the provision of probabilistic risk information for people considering elective PCI and to understand how CONNECT can be accessible to underserved communities.

Safety study of Rift Valley Fever human vaccine candidate (DDVax) in mosquitoes.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen with significant human and veterinary health consequences that periodically emerges in epizootics. RVFV causes fetal loss and death in ruminants and in humans can lead to liver and renal disease, delayed-onset encephalitis, retinitis, and in some cases severe haemorrhagic fever. A live attenuated vaccine candidate (DDVax), was developed by the deletion of the virulence factors NSs and NSm from a clinical isolate, ZH501, and has proven safe and immunogenic in rodents, pregnant sheep and non-human primates. Deletion of NSm also severely restricted mosquito midgut infection and inhibited vector-borne transmission. To demonstrate environmental safety, this study investigated the replication, dissemination and transmission efficiency of DDVax in mosquitoes following oral exposure compared to RVFV strains MP-12 and ZH501. Infection and dissemination profiles were also measured in mosquitoes 7 days after they fed on goats inoculated with DDvax or MP-12. We hypothesized that DDVax would infect mosquitoes at significantly lower rates than other RVFV strains and, due to lack of NSm, be transmission incompetent. Exposure of Ae. aegypti and Cx. tarsalis to 8 log10 plaque forming units (PFU)/ml DDVax by artificial bloodmeal resulted in significantly reduced DDVax infection rates in mosquito bodies compared to controls. Plaque assays indicated negligible transmission of infectious DDVax in Cx. tarsalis saliva (1/140 sampled) and none in Ae. aegypti saliva (0/120). Serum from goats inoculated with DDVax or MP-12 did not harbour detectable infectious virus by plaque assay at 1, 2 or 3 days post-inoculation. Infectious virus was, however, recovered from Aedes and Culex bodies that fed on goats vaccinated with MP-12 (13.8% and 4.6%, respectively), but strikingly, DDvax-positive mosquito bodies were greatly reduced (4%, and 0%, respectively). Furthermore, DDVax did not disseminate to legs/wings in any of the goat-fed mosquitoes. Collectively, these results are consistent with a beneficial environmental safety profile.