Protocol for electroporating and isolating murine (sub)ventricular zone cells for single-nuclei omics.

In vivo genetic modification of neural stem cells is necessary to model the origins and pathogenesis of neurological disorders. Electroporation is a technique that applies a transient electrical field to direct charged molecules into living cells to genetically modify the mouse brain. Here, we provide a protocol to electroporate the neural stem cells surrounding the neonatal ventricles. We describe subsequent steps to isolate and prepare nuclei from the cells and their cellular progeny for single-nuclei omics. For complete details on the use and execution of this protocol, please refer to Riley et al.1.

"They are saying it's high, but I think it's quite low": exploring cardiovascular disease risk communication in NHS health checks through video-stimulated recall interviews with patients - a qualitative study.

BACKGROUND: NHS Health Check (NHSHC) is a national cardiovascular disease (CVD) risk identification and management programme. However, evidence suggests a limited understanding of the most used metric to communicate CVD risk with patients (10-year percentage risk). This study used novel application of video-stimulated recall interviews to understand patient perceptions and understanding of CVD risk following an NHSHC that used one of two different CVD risk calculators. METHODS: Qualitative, semi-structured video-stimulated recall interviews were conducted with patients (n = 40) who had attended an NHSHC using either the QRISK2 10-year risk calculator (n = 19) or JBS3 lifetime CVD risk calculator (n = 21). Interviews were transcribed and analysed using reflexive thematic analysis. RESULTS: Analysis resulted in the development of four themes: variability in understanding, relief about personal risk, perceived changeability of CVD risk, and positive impact of visual displays. The first three themes were evident across the two patient groups, regardless of risk calculator; the latter related to JBS3 only. Patients felt relieved about their CVD risk, yet there were differences in understanding between calculators. Heart age within JBS3 prompted more accessible risk appraisal, yet mixed understanding was evident for both calculators. Event-free survival age also resulted in misunderstanding. QRISK2 patients tended to question the ability for CVD risk to change, while risk manipulation through JBS3 facilitated this understanding. Displaying information visually also appeared to enhance understanding. CONCLUSIONS: Effective communication of CVD risk within NHSHC remains challenging, and lifetime risk metrics still lead to mixed levels of understanding in patients. However, visual presentation of information, alongside risk manipulation during NHSHCs can help to increase understanding and prompt risk-reducing lifestyle changes. TRIAL REGISTRATION: ISRCTN10443908. Registered 7th February 2017.

Tsc2 coordinates neuroprogenitor differentiation.

Neural stem cells (NSCs) of the ventricular-subventricular zone (V-SVZ) generate numerous cell types. The uncoupling of mRNA transcript availability and translation occurs during the progression from stem to differentiated states. The mTORC1 kinase pathway acutely controls proteins that regulate mRNA translation. Inhibiting mTORC1 during differentiation is hypothesized to be critical for brain development since somatic mutations of mTORC1 regulators perturb brain architecture. Inactivating mutations of TSC1 or TSC2 genes cause tuberous sclerosis complex (TSC). TSC patients have growths near the striatum and ventricles. Here, it is demonstrated that V-SVZ NSC Tsc2 inactivation causes striatal hamartomas. Tsc2 removal altered translation factors, translatomes, and translational efficiency. Single nuclei RNA sequencing following in vivo loss of Tsc2 revealed changes in NSC activation states. The inability to decouple mRNA transcript availability and translation delayed differentiation leading to the retention of immature phenotypes in hamartomas. Taken together, Tsc2 is required for translational repression and differentiation.

The Impact and Perception of England's Web-Based Heart Age Test of Cardiovascular Disease Risk: Mixed Methods Study.

BACKGROUND: It is well documented that individuals struggle to understand cardiovascular disease (CVD) percentage risk scores, which led to the development of heart age as a means of communicating risk. Developed for clinical use, its application in raising public awareness of heart health as part of a self-directed digital test has not been considered previously. OBJECTIVE: This study aimed to understand who accesses England's heart age test (HAT) and its effect on user perception, knowledge, and understanding of CVD risk; future behavior intentions; and potential engagement with primary care services. METHODS: There were 3 sources of data: routinely gathered data on all individuals accessing the HAT (February 2015 to June 2020); web-based survey, distributed between January 2021 and March 2021; and interviews with a subsample of survey respondents (February 2021 to March 2021). Data were used to describe the test user population and explore knowledge and understanding of CVD risk, confidence in interpreting and controlling CVD risk, and effect on future behavior intentions and potential engagement with primary care. Interviews were analyzed using reflexive thematic analysis. RESULTS: Between February 2015 and June 2020, the HAT was completed approximately 5 million times, with more completions by men (2,682,544/4,898,532, 54.76%), those aged between 50 to 59 years (1,334,195/4,898,532, 27.24%), those from White ethnic background (3,972,293/4,898,532, 81.09%), and those living in the least deprived 20% of areas (707,747/4,898,532, 14.45%). The study concluded with 819 survey responses and 33 semistructured interviews. Participants stated that they understood the meaning of high estimated heart age and self-reported at least some improvement in the understanding and confidence in understanding and controlling CVD risk. Negative emotional responses were provoked among users when estimated heart age did not equate to their previous risk perceptions. The limited information needed to complete it or the production of a result when physiological risk factor information was missing (ie, blood pressure and cholesterol level) led some users to question the credibility of the test. However, most participants who were interviewed mentioned that they would recommend or had already recommended the test to others, would use it again in the future, and would be more likely to take up the offer of a National Health Service Health Check and self-reported that they had made or intended to make changes to their health behavior or felt encouraged to continue to make changes to their health behavior. CONCLUSIONS: England's web-based HAT has engaged large number of people in their heart health. Improvements to England's HAT, noted in this paper, may enhance user satisfaction and prevent confusion. Future studies to understand the long-term benefit of the test on behavioral outcomes are warranted.

Tsc2 shapes olfactory bulb granule cell molecular and morphological characteristics.

Tuberous Sclerosis Complex (TSC) is a neurodevelopmental disorder caused by mutations that inactivate TSC1 or TSC2. Hamartin and tuberin are encoded by TSC1 and TSC2 which form a GTPase activating protein heteromer that inhibits the Rheb GTPase from activating a growth promoting protein kinase called mammalian target of rapamycin (mTOR). Growths and lesions occur in the ventricular-subventricular zone (V-SVZ), cortex, olfactory tract, and olfactory bulbs (OB) in TSC. A leading hypothesis is that mutations in inhibitory neural progenitor cells cause brain growths in TSC. OB granule cells (GCs) are GABAergic inhibitory neurons that are generated through infancy by inhibitory progenitor cells along the V-SVZ. Removal of Tsc1 from mouse OB GCs creates cellular phenotypes seen in TSC lesions. However, the role of Tsc2 in OB GC maturation requires clarification. Here, it is demonstrated that conditional loss of Tsc2 alters GC development. A mosaic model of TSC was created by performing neonatal CRE recombinase electroporation into inhibitory V-SVZ progenitors yielded clusters of ectopic cytomegalic neurons with hyperactive mTOR complex 1 (mTORC1) in homozygous Tsc2 mutant but not heterozygous or wild type mice. Similarly, homozygous Tsc2 mutant GC morphology was altered at postnatal days 30 and 60. Tsc2 mutant GCs had hypertrophic dendritic arbors that were established by postnatal day 30. In contrast, loss of Tsc2 from mature GCs had negligible effects on mTORC1, soma size, and dendrite arborization. OB transcriptome profiling revealed a network of significantly differentially expressed genes following loss of Tsc2 during development that altered neural circuitry. These results demonstrate that Tsc2 has a critical role in regulating neural development and shapes inhibitory GC molecular and morphological characteristics.

Using social media for patient and public involvement and engagement in health research: The process and impact of a closed Facebook group.

BACKGROUND: As part of a multifaceted approach to patient and public involvement and engagement (PPIE), alongside traditional methods, a closed Facebook group was established to facilitate PPIE feedback on various aspects of a project that used video-recording to examine risk communication in NHS Health Checks between June 2017 and July 2019. OBJECTIVE: To explore the process and impact of conducting PPIE through a closed Facebook group and to identify the associated benefits and challenges. METHODS: Supported by reflections and information from project meetings used to document how this engagement informed the project, we describe the creation and maintenance of the Facebook Group and how feedback from the group members was obtained. Facebook data were used to investigate levels and types of engagement in the closed Facebook group. We reflect on the challenges of using this method of engaging the public in health research. RESULTS: A total of 289 people joined the 'Risk Communication of Cardiovascular disease in NHS Health Checks' PPIE closed Facebook group. They provided feedback, which was used to inform aspects of the study, including participant-facing documents, recruitment, camera position and how the methodology being used (video-recorded Health Checks and follow-up interviews) would be received by the public. DISCUSSION: Using a closed Facebook group to facilitate PPIE offered a flexible approach for both researchers and participants, enabled a more inclusive method to PPIE (compared with traditional methods) and allowed rapid feedback. Challenges included maintaining the group, which was more labour intensive than anticipated and managing members' expectations. Suggestions for best practice include clear communication about the purpose of the group, assigning a group co-ordinator to be the main point of contact for the group, and a research team who can dedicate the time necessary to maintain the group. CONCLUSION: The use of a closed Facebook group can facilitate effective PPIE. Its flexibility can be beneficial for researchers, patients and public who wish to engage in the research process. Dedicated time for sustained group engagement is important. PATIENT OR PUBLIC CONTRIBUTION: Patient representatives were engaged with the development of the research described in this paper and a patient representative reviewed the manuscript.

Alcohol and physical activity screening in the National Health Service Health Check programme: Comparison of medical records and actual practice.

Objectives: National data for the National Health Service (NHS) Health Check programme (in England), collected by University College London, Public Health England and NHS Digital, found that physical activity and alcohol was recorded in just 64.5% and 38.3% of patient records, respectively. We examined video recorded NHS Health Checks from the RIsk COmmunication in NHS Health Check study (collected 2018-19) to explore alcohol and physical activity measurement, comparing recorded and actual activity. Study design: Observational study. Methods: Anonymised medical records and transcripts of 130 video-recorded NHS Health Checks from 12 general practices were compared to understand use of alcohol (Alcohol Use Disorders Identification Test, Alcohol Use Disorders Identification Test-Concise, Fast Alcohol Screening Test) and physical activity (General Practitioner Physical Activity Questionnaire) measures. Results: Findings showed considerable discrepancies between how alcohol measurement was recorded in the patient's medical record and how it was assessed in practice. Equally, practitioners completed or partially completed AUDIT in fewer than half of patients who were perceived to be eligible for further screening. There was more consistency in physical activity assessment. Omitted questions, related to physical activity, were largely around work-related physical activity. Conclusions: Overall, inconsistent use of recommended tools for screening alcohol and physical activity in NHS Health Check suggests that some practitioners do not follow recommended national guidance. Omission of certain questions led to missed opportunities for practitioners to discuss alcohol consumption, particularly with those who reported apparently excessive alcohol consumption (>14 units per week). Interviews with NHS Health Check practitioners may help to understand barriers to following recommended practice and identify areas for improvement. Classification: Restricted.

Cardiovascular disease risk communication in NHS Health Checks using QRISK®2 and JBS3 risk calculators: the RICO qualitative and quantitative study.

BACKGROUND: The NHS Health Check is a national cardiovascular disease prevention programme. There is a lack of evidence on how health checks are conducted, how cardiovascular disease risk is communicated to foster risk-reducing intentions or behaviour, and the impact on communication of using different cardiovascular disease risk calculators. OBJECTIVES: RIsk COmmunication in Health Check (RICO) study aimed to explore practitioner and patient understanding of cardiovascular disease risk, the associated advice or treatment offered by the practitioner, and the response of the patients in health checks supported by either the QRISK®2 or the JBS3 lifetime risk calculator. DESIGN: This was a qualitative study with quantitative process evaluation. SETTING: Twelve general practices in the West Midlands of England, stratified on deprivation of the local area (bottom 50% vs. top 50%), and with matched pairs randomly allocated to use QRISK2 or JBS3 during health checks. PARTICIPANTS: A total of 173 patients eligible for NHS Health Check and 15 practitioners. INTERVENTIONS: The health check was delivered using either the QRISK2 10-year risk calculator (usual practice) or the JBS3 lifetime risk calculator, with heart age, event-free survival age and risk score manipulation (intervention). RESULTS: Video-recorded health checks were analysed quantitatively (n = 173; JBS3, n = 100; QRISK2, n = 73) and qualitatively (n = 128; n = 64 per group), and video-stimulated recall interviews were undertaken with 40 patients and 15 practitioners, with 10 in-depth case studies. The duration of the health check varied (6.8-38 minutes), but most health checks were short (60% lasting < 20 minutes), with little cardiovascular disease risk discussion (average < 2 minutes). The use of JBS3 was associated with more cardiovascular disease risk discussion and fewer practitioner-dominated consultations than the use of QRISK2. Heart age and visual representations of risk, as used in JBS3, appeared to be better understood by patients than 10-year risk (QRISK2) and, as a result, the use of JBS3 was more likely to lead to discussion of risk factors and their management. Event-free survival age was not well understood by practitioners or patients. However, a lack of effective cardiovascular disease risk discussion in both groups increased the likelihood of a maladaptive coping response (i.e. no risk-reducing behaviour change). In both groups, practitioners often missed opportunities to check patient understanding and to tailor information on cardiovascular disease risk and its management during health checks, confirming apparent practitioner verbal dominance. LIMITATIONS: The main limitations were under-recruitment in some general practices and the resulting imbalance between groups. CONCLUSIONS: Communication of cardiovascular disease risk during health checks was brief, particularly when using QRISK2. Patient understanding of and responses to cardiovascular disease risk information were limited. Practitioners need to better engage patients in discussion of and action-planning for their cardiovascular disease risk to reduce misunderstandings. The use of heart age, visual representation of risk and risk score manipulation was generally seen to be a useful way of doing this. Future work could focus on more fundamental issues of practitioner training and time allocation within health check consultations. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10443908. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 50. See the NIHR Journals Library website for further project information.

In England, NHS Health Checks aim to prevent cardiovascular diseases, such as heart attack and stroke. Health checks are conducted in primary care by a health-care assistant or practice nurse, who should measure the patient's risk of cardiovascular disease before advising them on how to reduce their risk. Cardiovascular disease risk is measured using a cardiovascular disease risk calculator. These calculators use various patient characteristics (e.g. age, sex, blood pressure and cholesterol) to predict how likely patients are to have a heart attack or stroke in the future. The aim of this study was to compare how practitioners explain cardiovascular disease risk to patients during health checks when using two risk calculators: QRISK^®2, which measures the risk of heart attack or stroke over the next 10 years (current usual practice), and JBS3 (a newer risk calculator), which gives this risk across the lifetime, is more interactive and has various visual displays of risk. We were interested to see if using JBS3 in health checks would lead to better practitioner and patient understanding of cardiovascular disease risk and result in patients intending to change, or actually changing, their behaviour to reduce their cardiovascular disease risk (compared with QRISK2). Health checks were video-recorded: 73 using QRISK2 and 100 using JBS3. Patients and members of the public advised on the study design, methods and management. Most consultations lasted < 20 minutes, with most time spent discussing the causes of cardiovascular disease. There was evidence that, compared with health checks using JBS3, those using QRISK2 led to less discussion of risk and practitioners speaking far more than patients. Sixty-four health checks from each risk calculator group were examined in depth. Opportunities to check whether or not patients understood the cardiovascular disease risk information and to encourage ways to lower risk were missed, making it less likely that patients would change their behaviour. The way that risk is presented by JBS3 seems to be more easily understood by patients than that presented by QRISK2. Nineteen patients in the QRISK2 group and 21 patients in the JBS3 group were interviewed 4 weeks after the consultation, and the practitioners were interviewed after they had completed all of their health checks. Patients found it difficult to understand and remember what they had been told about their cardiovascular disease risk during their health check. Their understanding and motivation to change behaviour appeared to be higher when they were visually shown how behaviour changes could lower their risk. Practitioners sometimes misunderstood risk and used patients' reactions to judge whether or not they understood, rather than asking them. Our findings should help to improve how cardiovascular disease risk is communicated during health checks in future, through simple changes to the consultations (e.g. using aspects of JBS3) and by highlighting a gap in practitioners' training.

Cardiovascular disease risk communication in NHS Health Checks: a qualitative video-stimulated recall interview study with practitioners.

BACKGROUND: NHS Health Check (NHSHC) is a national programme to identify and manage cardiovascular disease (CVD) risk. Practitioners delivering the programme should be competent in discussing CVD risk, but there is evidence of limited understanding of the recommended 10-year percentage CVD risk scores. Lifetime CVD risk calculators might improve understanding and communication of risk. AIM: To explore practitioner understanding, perceptions, and experiences of CVD risk communication in NHSHCs when using two different CVD risk calculators. DESIGN & SETTING: Qualitative video-stimulated recall (VSR) study with NHSHC practitioners in the West Midlands. METHOD: VSR interviews were conducted with practitioners who delivered NHSHCs using either the QRISK2 10-year risk calculator (n = 7) or JBS3 lifetime CVD risk calculator (n = 8). Data were analysed using reflexive thematic analysis. RESULTS: In total, nine healthcare assistants (HCAs) and six general practice nurses (GPNs) were interviewed. There was limited understanding and confidence of 10-year risk, which was used to guide clinical decisions through determining low-, medium-, or high-risk thresholds, rather than as a risk communication tool. Potential benefits of some JBS3 functions were evident, particularly heart age, risk manipulation, and visual presentation of risk. CONCLUSION: There is a gap between the expectation and reality of practitioners' understanding, competencies, and training in CVD risk communication for NHSHCs. Practitioners would welcome heart age and risk manipulation functions of JBS3 to promote patient understanding of CVD risk, but there is a more fundamental need for practitioner training in CVD risk communication.

A qualitative exploration of two risk calculators using video-recorded NHS health check consultations.

BACKGROUND: The aim of the study was to explore practitioner-patient interactions and patient responses when using QRISK®2 or JBS3 cardiovascular disease (CVD) risk calculators. Data were from video-recorded NHS Health Check (NHSHC) consultations captured as part of the UK RIsk COmmunication (RICO) study; a qualitative study of video-recorded NHSHC consultations from 12 general practices in the West Midlands, UK. Participants were those eligible for NHSHC based on national criteria (40-74 years old, no existing diagnoses for cardiovascular-related conditions, not on statins), and practitioners, who delivered the NHSHC. METHOD: NHSHCs were video-recorded. One hundred twenty-eight consultations were transcribed and analysed using deductive thematic analysis and coded using a template based around Protection Motivation Theory. RESULTS: Key themes used to frame the analysis were Cognitive Appraisal (Threat Appraisal, and Coping Appraisal), and Coping Modes (Adaptive, and Maladaptive). Analysis showed little evidence of CVD risk communication, particularly in consultations using QRISK®2. Practitioners often missed opportunities to check patient understanding and encourage risk- reducing behaviour, regardless of the risk calculator used resulting in practitioner verbal dominance. JBS3 appeared to better promote opportunities to initiate risk-factor discussion, and Heart Age and visual representation of risk were more easily understood and impactful than 10-year percentage risk. However, a lack of effective CVD risk discussion in both risk calculator groups increased the likelihood of a maladaptive coping response. CONCLUSIONS: The analysis demonstrates the importance of effective, shared practitioner-patient discussion to enable adaptive coping responses to CVD risk information, and highlights a need for effective and evidence-based practitioner training. TRIAL REGISTRATION: ISRCTN ISRCTN10443908 . Registered 7th February 2017.

Quantitative examination of video-recorded NHS Health Checks: comparison of the use of QRISK2 versus JBS3 cardiovascular risk calculators.

OBJECTIVES: Quantitatively examine the content of National Health Service Health Check (NHSHC), patient-practitioner communication balance and differences when using QRISK2 versus JBS3 cardiovascular disease (CVD) risk calculators. DESIGN: RIsk COmmunication in NHSHC was a qualitative study with quantitative process evaluation, comparing NHSHC using QRISK2 or JBS3. We present data from the quantitative process evaluation. SETTING AND PARTICIPANTS: Twelve general practices in the West Midlands (England) conducted NHSHC using JBS3 or QRISK2 (6/group). Patients were eligible for NHSHC based on national criteria (aged 40-74, no existing cardiovascular-related diagnoses, not taking statins). Recruitment was stratified by patients' age, gender and ethnicity. METHODS: Video recordings of NHSHC were coded, second-by-second, to quantify who was speaking and what was being discussed. Outcomes included consultation duration, practitioner verbal dominance (ratio of practitioner:patient speaking time (pr:pt ratio)) and proportion of time discussing CVD risk, risk factors and risk management. RESULTS: 173 video-recorded NHSHC were analysed (73 QRISK, 100 JBS3). The sample was 51% women, 83% white British, with approximately equal proportions across age groups. NHSHC duration varied greatly (6.8-38.0 min). Most (60%) lasted less than 20 min. On average, CVD risk was discussed for less than 2 min (9.06%±4.30% of consultation time). There were indications that, compared with NHSHC using JBS3, those with QRISK2 involved less CVD risk discussion (JBS3 M=10.24%, CI: 8.01-12.48 vs QRISK2 M=7.44%, CI: 5.29-9.58) and were more verbally dominated by practitioners (pr:pt ratio JBS3 M=3.21%, CI: 2.44-3.97 vs QRISK2=2.35%, CI: 1.89-2.81). The largest proportion of NHSHC time was spent discussing causal risk factors (M=37.54%, CI: 32.92-42.17). CONCLUSIONS: There was wide variation in NHSHC duration. Many were short and practitioner-dominated, with little time discussing CVD risk. JBS3 appears to extend CVD risk discussion and patient contribution. Qualitative examination of how it is used is necessary to fully understand the potential benefits of these differences. TRIAL REGISTRATION NUMBER: ISRCTN10443908.

Randomised controlled trial comparing uptake of NHS Health Check in response to standard letters, risk-personalised letters and telephone invitations.

BACKGROUND: NHS Health Check is a primary prevention programme offering cardiovascular disease (CVD) risk assessment to adults in England aged 40-74. Uptake remains a challenge and invitation method is a strong predictor of uptake. There is evidence of low uptake when using invitation letters. Telephone invitations might increase uptake, but are not widely used. We explored the potential to improve uptake through personalising letters to patient's CVD risk, and to compare this with generic letters and telephone invitations. METHODS: HEalth Check TRial (HECTR) was a three-arm randomised controlled trial in nine general practices in Staffordshire (UK). Eligible patients were randomised to be invited to a NHS Health Check using one of three methods: standard letter (control); telephone invitation; letter personalised to the patient's CVD risk. The primary outcome was attendance/non-attendance. Data were collected on a range of patient- and practice-level factors (e.g., patient socio-demographics, CVD risk, practice size, Health Checks outside usual working hours). Multi-level logistic regression estimated the marginal effects to explore whether invitation method predicted attendance. Invitation costs were collated from practices to estimate cost benefit. RESULTS: In total, 4614 patients were included in analysis (mean age 50.2 ± 8.0 yr.; 52.4% female). Compared with patients invited by standard letter (30.9%), uptake was significantly higher in those invited by telephone (47.6%, P < .001), but not personalised letter (31.3%, p = .812). In multi-level analysis, compared with the standard letter arm, likelihood of attendance was 18 percentage points higher in the telephone arm and 4 percentage points higher in the personalised letter arm. The effect of telephone calls appeared strongest in patients who were younger and had lower CVD risk. We estimated per 1000 patients invited, risk-personalised letters could result in 40 additional attended Health Checks (at no extra cost) and telephone invitations could result in 180 additional Health Checks at an additional cost of £240. CONCLUSIONS: Telephone invitations should be advocated to address the substantial deficit between current and required levels of NHS uptake, and could be targeted at younger and lower CVD risk adults. Risk-personalised letters should be explored further in a larger sample of high risk individuals. TRIAL REGISTRATION: Registration number: ISRCTN15840751 date of registration: 24/10/2017.

A qualitative study of cardiovascular disease risk communication in NHS Health Check using different risk calculators: protocol for the RIsk COmmunication in NHS Health Check (RICO) study.

BACKGROUND: NHS Health Check is a national cardiovascular disease (CVD) risk assessment programme for 40-74 year olds in England, in which practitioners should assess and communicate CVD risk, supported by appropriate risk-management advice and goal-setting. This requires effective communication, to equip patients with knowledge and intention to act. Currently, the QRISK®2 10-year CVD risk score is most common way in which CVD risk is estimated. Newer tools, such as JBS3, allow manipulation of risk factors and can demonstrate the impact of positive actions. However, the use, and relative value, of these tools within CVD risk communication is unknown. We will explore practitioner and patient CVD risk perceptions when using QRISK®2 or JBS3, the associated advice or treatment offered by the practitioner, and patients' responses. METHODS: RIsk COmmunication in NHS Health Check (RICO) is a qualitative study with quantitative process evaluation. Twelve general practices in the West Midlands of England will be randomised to one of two groups: usual practice, in which practitioners use QRISK®2 to assess and communicate CVD risk; intervention, in which practitioners use JBS3. Twenty Health Checks per practice will be video-recorded (n = 240, 120 per group), with patients stratified by age, gender and ethnicity. Post-Health Check, video-stimulated recall (VSR) interviews will be conducted with 48 patients (n = 24 per group) and all practitioners (n = 12-18), using video excerpts to enhance participant recall/reflection. Patient medical record reviews will detect health-protective actions in the first 12-weeks following a Health Check (e.g., lifestyle referrals, statin prescription). Risk communication, patient response and intentions for health-protective behaviours in each group will be explored through thematic analysis of video-recorded Health Checks (using Protection Motivation Theory as a framework) and VSR interviews. Process evaluation will include between-group comparisons of quantitatively coded Health Check content and post-Health Check patient outcomes. Finally, 10 patients with the most positive intentions or behaviours will be selected for case study analysis (using all data sources). DISCUSSION: This study will produce novel insights about the utility of QRISK®2 and JBS3 to promote patient and practitioner understanding and perception of CVD risk and associated implications for patient intentions with respect to health-protective behaviours (and underlying mechanisms). Recommendations for practice will be developed. TRIAL REGISTRATION: ISRCTN ISRCTN10443908 . Registered 7th February 2017.

Uptake of NHS health check: issues in monitoring.

Within the NHS health check (NHSHC) programme, there is evidence of marked inconsistencies and challenges in practice-level self-reporting of uptake. Consequently, we explored the perceptions of those involved in commissioning of NHSHC to better understand the implications for local and national monitoring and evaluation of programme uptake. Semi-structured, one-to-one, telephone interviews (n=15) were conducted with NHSHC commissioners and leads, and were analysed using inductive thematic analysis. NHSHC data were often collected from practices using online extraction systems but many still relied on self-reported data. Performance targets and indicators used to monitor and feedback to general practices varied between localities. Participants reported a number of issues when collecting and reporting data for NHSHC, namely because of opportunistic checks. Owing to the perceived inaccuracies in reporting, there was concern about the credibility and relevance of national uptake figures. The general practice extraction service will be important to fully understand uptake of NHSHC.

qSOFA, SIRS and NEWS for predicting inhospital mortality and ICU admission in emergency admissions treated as sepsis.

BACKGROUND: The third international consensus definition for sepsis recommended use of a new prognostic tool, the quick Sequential Organ Failure Assessment (qSOFA), based on its ability to predict inhospital mortality and prolonged intensive care unit (ICU) stay in patients with suspected infection. While several studies have compared the prognostic accuracy of qSOFA to the Systemic Inflammatory Response Syndrome (SIRS) criteria in suspected sepsis, few have compared qSOFA and SIRS to the widely used National Early Warning Score (NEWS). METHODS: This was a retrospective cohort study carried out in a UK tertiary centre. The study population comprised emergency admissions in whom sepsis was suspected and treated. The accuracy for predicting inhospital mortality and ICU admission was calculated and compared for qSOFA, SIRS and NEWS. RESULTS: Among 1818 patients, 53 were admitted to ICU (3%) and 265 died in hospital (15%). For predicting inhospital mortality, the area under the receiver operating characteristics curve for NEWS (0.65, 95% CI 0.61 to 0.68) was similar to qSOFA (0.62, 95% CI 0.59 to 0.66) (test for difference, P=0.18) and superior to SIRS (P<0.001), which was not predictive. The sensitivity of NEWS≥5 (74%, 95% CI 68% to 79%) was similar to SIRS≥2 (80%, 95% CI 74% to 84%) and higher than qSOFA≥2 (37%, 95% CI 31% to 43%). The specificity of NEWS≥5 (43%, 95% CI 41% to 46%) was higher than SIRS≥2 (21%, 95% CI 19% to 23%) and lower than qSOFA≥2 (79%, 95% CI 77% to 81%). The negative predictive value was 88% (86%-90%) for qSOFA, 86% (82%-89%) for SIRS and 91% (88%-93%) for NEWS. Results were similar for the secondary outcome of ICU admission. CONCLUSION: NEWS has equivalent or superior value for most test characteristics relative to SIRS and qSOFA, calling into question the rationale of adopting qSOFA in institutions where NEWS is already in use.