Quantifying the effects of risk-stratified breast cancer screening when delivered in real time as routine practice versus usual screening: the BC-Predict non-randomised controlled study (NCT04359420).

BACKGROUND: Risk stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) could provide a better balance of benefits and harms. We developed BC-Predict, to offer women when invited to the NHSBSP, which collects standard risk factor information; mammographic density; and in a sub-sample, a Polygenic Risk Score (PRS). METHODS: Risk prediction was estimated primarily from self-reported questionnaires and mammographic density using the Tyrer-Cuzick risk model. Women eligible for NHSBSP were recruited. BC-Predict produced risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5-<8% 10-year) to have appointments to discuss prevention and additional screening. RESULTS: Overall uptake of BC-Predict in screening attendees was 16.9% with 2472 consenting to the study; 76.8% of those received risk feedback within the 8-week timeframe. Recruitment was 63.2% with an onsite recruiter and paper questionnaire compared to <10% with BC-Predict only (P < 0.0001). Risk appointment attendance was highest for those at high risk (40.6%); 77.5% of those opted for preventive medication. DISCUSSION: We have shown that a real-time offer of breast cancer risk information (including both mammographic density and PRS) is feasible and can be delivered in reasonable time, although uptake requires personal contact. Preventive medication uptake in women newly identified at high risk is high and could improve the cost-effectiveness of risk stratification. TRIAL REGISTRATION: Retrospectively registered with clinicaltrials.gov (NCT04359420).

What are the benefits and harms of risk stratified screening as part of the NHS breast screening Programme? Study protocol for a multi-site non-randomised comparison of BC-predict versus usual screening (NCT04359420).

BACKGROUND: In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict produces risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5 to < 8% 10-year) to have discussion of prevention and early detection options at Family History, Risk and Prevention Clinics. Despite the promise of systems such as BC-Predict, there are still too many uncertainties for a fully-powered definitive trial to be appropriate or ethical. The present research aims to identify these key uncertainties regarding the feasibility of integrating BC-Predict into the NHSBSP. Key objectives of the present research are to quantify important potential benefits and harms, and identify key drivers of the relative cost-effectiveness of embedding BC-Predict into NHSBSP. METHODS: A non-randomised fully counterbalanced study design will be used, to include approximately equal numbers of women offered NHSBSP (n = 18,700) and BC-Predict (n = 18,700) from selected screening sites (n = 7). In the initial 8-month time period, women eligible for NHSBSP will be offered BC-Predict in four screening sites. Three screening sites will offer women usual NHSBSP. In the following 8-months the study sites offering usual NHSBSP switch to BC-Predict and vice versa. Key potential benefits including uptake of risk consultations, chemoprevention and additional screening will be obtained for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires, with embedded qualitative process analysis. A decision-analytic model-based cost-effectiveness analysis will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHSBSP. DISCUSSION: We will assess the feasibility of integrating BC-Predict into the NHSBSP, and identify the main uncertainties for a definitive evaluation of the clinical and cost-effectiveness of BC-Predict. TRIAL REGISTRATION: Retrospectively registered with clinicaltrials.gov (NCT04359420).

Goal-directed and goal-less imitation in autism spectrum disorder.

To investigate how people with Autism are affected by the presence of goals during imitation, we conducted a study to measure movement kinematics and eye movements during the imitation of goal-directed and goal-less hand movements. Our results showed that a control group imitated changes in movement kinematics and increased the level that they tracked the hand with their eyes, in the goal-less compared to goal-direction condition. In contrast, the ASD group exhibited more goal-directed eye movements, and failed to modulate the observed movement kinematics successfully in either condition. These results increase the evidence for impaired goal-less imitation in ASD, and suggest that there is a reliance on goal-directed strategies for imitation in ASD, even in the absence of visual goals.

The influence of goals on movement kinematics during imitation.

This study took a quantitative approach to investigate movement kinematics during the imitation of goal-directed and non-goal directed movements. Motion tracking equipment was used to record the hand movements of 15 healthy participants during an imitation task involving aiming movements that varied in speed. We predicted that movement kinematics would be most similar to the observed movements in the non-goal condition, as a result of direct visuomotor mapping of the action, and least similar in the goal-directed condition because more importance would be given to the end goal. We also predicted that precues (prior information about the movement) would increase imitation accuracy in the non-goal condition by reducing cognitive demand, and that precues would reduce accuracy in the goal-directed condition, as less attention would be paid to the movement. Results showed that imitation was modulated by the speed of the observed action in the non-goal condition only. Contrary to predictions, precues did not improve imitation in the non-goal condition or improve imitation accuracy in the goal-directed condition. These results demonstrate that visuomotor mapping is favoured in non-goal imitation, regardless of prior information, and that accurate imitation of movement detail is compromised by the presence of goals. Such differences in movement kinematics indicate that different processes mediate the imitation of non-goal and goal-directed actions.