Hidden systems in primary care cancer detection: an embedded qualitative intervention development study.

BACKGROUND: UK cancer mortality is worse than in many other high-income countries, partly because of diagnostic delays in primary care. AIM: To understand beliefs and behaviours of GPs, and systems of general practice teams, to inform the Think Cancer! intervention development. DESIGN AND SETTING: An embedded qualitative study guided by behaviour change models (COM-B [Capability, Opportunity, Motivation - Behaviour] and theoretical domains framework [TDF]) in primary care in Wales, UK. METHOD: Twenty qualitative, semi-structured telephone interviews with GPs were undertaken and four face-to-face focus groups held with practice teams. Framework analysis was used and results were mapped to multiple, overlapping components of COM-B and TDF. RESULTS: Three themes illustrate complex, multilevel referral considerations facing GPs and practice teams; external influences and constraints; and the role of practice systems and culture. Tensions emerged between individual considerations of GPs (Capability and Motivation) and context-dependent external pressures (Opportunity). Detecting cancer was guided not only by external requirements, but also by motivational factors GPs described as part of their cancer diagnostics process. External influences on the diagnosis process often resulted from the primary-secondary care interface and social pressures. GPs adapted their behaviour to deal with this disconnect. Positive practice culture and supportive practice-based systems ameliorated these tensions and complexity. CONCLUSION: By exploring individual GP behaviours together with practice systems and culture we contribute new understanding about how cancer diagnosis operates in primary care and how delays can be improved. We highlight commonly overlooked dynamics and tensions that are experienced by GPs as a tension between individual decision making (Capability and Motivation) and external considerations, such as pressures in secondary care (Opportunity).

Realistic numerical simulations of diffusion tensor cardiovascular magnetic resonance: The effects of perfusion and membrane permeability.

PURPOSE: To study the sensitivity of diffusion tensor cardiovascular magnetic resonance (DT-CMR) to microvascular perfusion and changes in cell permeability. METHODS: Monte Carlo (MC) random walk simulations in the myocardium have been performed to simulate self-diffusion of water molecules in histology-based media with varying extracellular volume fraction (ECV) and permeable membranes. The effect of microvascular perfusion on simulations of the DT-CMR signal has been incorporated by adding the contribution of particles traveling through an anisotropic capillary network to the diffusion signal. The simulations have been performed considering three pulse sequences with clinical gradient strengths: monopolar stimulated echo acquisition mode (STEAM), monopolar pulsed-gradient spin echo (PGSE), and second-order motion-compensated spin echo (MCSE). RESULTS: Reducing ECV intensifies the diffusion restriction and incorporating membrane permeability reduces the anisotropy of the diffusion tensor. Widening the intercapillary velocity distribution results in increased measured diffusion along the cardiomyocytes long axis when the capillary networks are anisotropic. Perfusion amplifies the mean diffusivity for STEAM while the opposite is observed for short diffusion encoding time sequences (PGSE and MCSE). CONCLUSION: The effect of perfusion on the measured diffusion tensor is reduced using an increased reference b-value. Our results pave the way for characterization of the response of DT-CMR to microstructural changes underlying cardiac pathology and highlight the higher sensitivity of STEAM to permeability and microvascular circulation due to its longer diffusion encoding time.

Development of the HT&Me intervention to support women with breast cancer to adhere to adjuvant endocrine therapy and improve quality of life.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Approximately 80% of breast cancers are oestrogen receptor positive (ER+). Patients treated surgically are usually recommended adjuvant endocrine therapy (AET) for 5-10 years. AET significantly reduces recurrence, but up to 50% of women do not take it as prescribed. OBJECTIVE: To co-design and develop an intervention to support AET adherence and improve health-related quality-of-life (QoL) in women with breast cancer. METHODS: Design and development of the HT&Me intervention took a person-based approach and was guided by the Medical Research Council framework for complex interventions, based on evidence and underpinned by theory. Literature reviews, behavioural analysis, and extensive key stakeholder involvement informed 'guiding principles' and the intervention logic model. Using co-design principles, a prototype intervention was developed and refined. RESULTS: The blended tailored HT&Me intervention supports women to self-manage their AET. It comprises initial and follow-up consultations with a trained nurse, supported with an animation video, a web-app and ongoing motivational 'nudge' messages. It addresses perceptual (e.g. doubts about necessity, treatment concerns) and practical (e.g. forgetting) barriers to adherence and provides information, support and behaviour change techniques to improve QoL. Iterative patient feedback maximised feasibility, acceptability, and likelihood of maintaining adherence; health professional feedback maximised likelihood of scalability. CONCLUSIONS: HT&Me has been systematically and rigorously developed to promote AET adherence and improve QoL, and is complemented with a logic model documenting hypothesized mechanisms of action. An ongoing feasibility trial will inform a future randomised control trial of effectiveness and cost-effectiveness.

Earlier cancer diagnosis in primary care: a feasibility economic analysis of ThinkCancer!

BACKGROUND: UK cancer survival rates are much lower compared with other high-income countries. In primary care, there are opportunities for GPs and other healthcare professionals to act more quickly in response to presented symptoms that might represent cancer. ThinkCancer! is a complex behaviour change intervention aimed at primary care practice teams to improve the timely diagnosis of cancer. AIM: To explore the costs of delivering the ThinkCancer! intervention to expedite cancer diagnosis in primary care. DESIGN & SETTING: Feasibility economic analysis using a micro-costing approach, which was undertaken in 19 general practices in Wales, UK. METHOD: From an NHS perspective, micro-costing methodology was used to determine whether it was feasible to gather sufficient economic data to cost the ThinkCancer! INTERVENTION: Owing to the COVID-19 pandemic, ThinkCancer! was mainly delivered remotely online in a digital format. Budget impact analysis (BIA) and sensitivity analysis were conducted to explore the costs of face-to-face delivery of the ThinkCancer! intervention as intended pre-COVID-19. RESULTS: The total costs of delivering the ThinkCancer! intervention across 19 general practices in Wales was £25 030, with an average cost per practice of £1317 (standard deviation [SD]: 578.2). Findings from the BIA indicated a total cost of £34 630 for face-to-face delivery. CONCLUSION: Data collection methods were successful in gathering sufficient health economics data to cost the ThinkCancer! INTERVENTION: Results of this feasibility study will be used to inform a future definitive economic evaluation alongside a pragmatic randomised controlled trial (RCT).

Random walk diffusion simulations in semi-permeable layered media with varying diffusivity.

In this paper we present random walk based solutions to diffusion in semi-permeable layered media with varying diffusivity. We propose a novel transit model for solving the interaction of random walkers with a membrane. This hybrid model is based on treating the membrane permeability and the step change in diffusion coefficient as two interactions separated by an infinitesimally small layer. By conducting an extensive analytical flux analysis, the performance of our hybrid model is compared with a commonly used membrane transit model (reference model). Numerical simulations demonstrate the limitations of the reference model in dealing with step changes in diffusivity and show the capability of the hybrid model to overcome this limitation and to offer substantial gains in computational efficiency. The suitability of both random walk transit models for the application to simulations of diffusion tensor cardiovascular magnetic resonance (DT-CMR) imaging is assessed in a histology-based domain relevant to DT-CMR. In order to demonstrate the usefulness of the new hybrid model for other possible applications, we also consider a larger range of permeabilities beyond those commonly found in biological tissues.

Development of a cardiovascular magnetic resonance-compatible large animal isolated heart model for direct comparison of beating and arrested hearts.

Cardiac motion results in image artefacts and quantification errors in many cardiovascular magnetic resonance (CMR) techniques, including microstructural assessment using diffusion tensor cardiovascular magnetic resonance (DT-CMR). Here, we develop a CMR-compatible isolated perfused porcine heart model that allows comparison of data obtained in beating and arrested states. Ten porcine hearts (8/10 for protocol optimisation) were harvested using a donor heart retrieval protocol and transported to the remote CMR facility. Langendorff perfusion in a 3D-printed chamber and perfusion circuit re-established contraction. Hearts were imaged using cine, parametric mapping and STEAM DT-CMR at cardiac phases with the minimum and maximum wall thickness. High potassium and lithium perfusates were then used to arrest the heart in a slack and contracted state, respectively. Imaging was repeated in both arrested states. After imaging, tissue was removed for subsequent histology in a location matched to the DT-CMR data using fiducial markers. Regular sustained contraction was successfully established in six out of 10 hearts, including the final five hearts. Imaging was performed in four hearts and one underwent the full protocol, including colocalised histology. The image quality was good and there was good agreement between DT-CMR data in equivalent beating and arrested states. Despite the use of autologous blood and dextran within the perfusate, T2 mapping results, DT-CMR measures and an increase in mass were consistent with development of myocardial oedema, resulting in failure to achieve a true diastolic-like state. A contiguous stack of 313 5-µm histological sections at and a 100-µm thick section showing cell morphology on 3D fluorescent confocal microscopy colocalised to DT-CMR data were obtained. A CMR-compatible isolated perfused beating heart setup for large animal hearts allows direct comparisons of beating and arrested heart data with subsequent colocalised histology, without the need for onsite preclinical facilities.

Assessing Changes in Airflow and Energy Loss in a Progressive Tracheal Compression Before and After Surgical Correction.

The energy needed to drive airflow through the trachea normally constitutes a minor component of the work of breathing. However, with progressive tracheal compression, patient subjective symptoms can include severe breathing difficulties. Many patients suffer multiple respiratory co-morbidities and so it is important to assess compression effects when evaluating the need for surgery. This work describes the use of computational prediction to determine airflow resistance in compressed tracheal geometries reconstructed from a series of CT scans. Using energy flux analysis, the regions that contribute the most to airway resistance during inhalation are identified. The principal such region is where flow emerging from the zone of maximum constriction undergoes breakup and turbulent mixing. Secondary regions are also found below the tongue base and around the glottis, with overall airway resistance scaling nearly quadratically with flow rate. Since the anatomical extent of the imaged airway varied between scans-as commonly occurs with clinical data and when assessing reported differences between research studies-the effect of sub-glottic inflow truncation is considered. Analysis shows truncation alters the location of jet breakup and weakly influences the pattern of pressure recovery. Tests also show that placing a simple artificial glottis in the inflow to a truncated model can replicate patterns of energy loss in more extensive models, suggesting a means to assess sensitivity to domain truncation in tracheal airflow simulations.

Novel insights into in-vivo diffusion tensor cardiovascular magnetic resonance using computational modeling and a histology-based virtual microstructure.

PURPOSE: To develop histology-informed simulations of diffusion tensor cardiovascular magnetic resonance (DT-CMR) for typical in-vivo pulse sequences and determine their sensitivity to changes in extra-cellular space (ECS) and other microstructural parameters. METHODS: We synthesised the DT-CMR signal from Monte Carlo random walk simulations. The virtual tissue was based on porcine histology. The cells were thickened and then shrunk to modify ECS. We also created idealised geometries using cuboids in regular arrangement, matching the extra-cellular volume fraction (ECV) of 16-40%. The simulated voxel size was 2.8 × 2.8 × 8.0 mm3 for pulse sequences covering short and long diffusion times: Stejskal-Tanner pulsed-gradient spin echo, second-order motion-compensated spin echo, and stimulated echo acquisition mode (STEAM), with clinically available gradient strengths. RESULTS: The primary diffusion tensor eigenvalue increases linearly with ECV at a similar rate for all simulated geometries. Mean diffusivity (MD) varies linearly, too, but is higher for the substrates with more uniformly distributed ECS. Fractional anisotropy (FA) for the histology-based geometry is higher than the idealised geometry with low sensitivity to ECV, except for the long mixing time of the STEAM sequence. Varying the intra-cellular diffusivity (DIC ) results in large changes of MD and FA. Varying extra-cellular diffusivity or using stronger gradients has minor effects on FA. Uncertainties of the primary eigenvector orientation are reduced using STEAM. CONCLUSIONS: We found that the distribution of ECS has a measurable impact on DT-CMR parameters. The observed sensitivity of MD and FA to ECV and DIC has potentially interesting applications for interpreting in-vivo DT-CMR parameters.

Talking about human papillomavirus and cancer: protocol for a patient-centred study to develop scripted consultations.

INTRODUCTION: Persistent infection with sexually transmitted, high-risk human papillomavirus (HPV) types is the cause of all cervical cancers and some anogenital and oropharyngeal cancers. HPV is an extremely common asymptomatic infection but little known and poorly understood by the public. Patients with HPV-related cancers have new and challenging information needs due to the complex natural history of HPV and the stigma of sexual transmission. They may ask questions that are outside the remit of the traditional cancer consultation, and there is a lack of guidance on how to counsel them. This study aims to fulfil that need by developing and testing cancer site-specific scripted consultations. METHODS AND ANALYSIS: A synthesis of findings generated from previous work, a systematic review of information-based interventions for patients with HPV-related cancers, and interviews with cancer clinicians will provide the evidence base underpinning provisional messages. These will be explored in three phases of face-to-face interviews with 75-90 purposively selected patients recruited in cancer clinics to: (1) select and prioritise the most salient messages, (2) phrase the messages appropriately in plain English and, (3) test their acceptability and usefulness. Phases 1 and 2 will draw on card-sorting methods used in website design. In phase three, we will create cancer site-specific versions of the script and test them using cognitive interviewing techniques. ETHICS AND DISSEMINATION: The study has received ethical approval. Findings will be published in a peer-reviewed journal. The final product will be cancer-specific scripted consultations, most likely in the form of a two-sided information sheet with the most important messages to be conveyed in a consultation on one side, and frequently asked questions for later reading on the reverse. However, they will also be appropriate and readily adaptable to web-based uses.