Demand for mental health support has exerted unprecedented pressure on statutory services. Innovative solutions such as Green or Nature-Based Social Prescribing (NBSP) programmes may help address unmet need, improve access to personalised treatment, and support the sustainable delivery of primary services within a prevention model of population health. We piloted an innovative health economics-informed Social Return on Investment (SROI) analysis and forecast of a ‘Making Well’ therapeutic craft and horticulture programme for mental health between October 2021 and March 2022. Quantitative and qualitative outcome data were collected from participants with mild-to-moderate mental health conditions at baseline and nine-weeks follow-up using a range of validated measures, including the Short Warwick–Edinburgh Mental Well-being Scale, ICEpop CAPability measure for Adults (ICECAP-A), General Self-Efficacy Scale (GSES), and a bespoke Client Service Receipt Inventory (CSRI). The acceptability and feasibility of these measures were explored. Results indicate that the Making Well programme generated well-being-related social value in the range of British Pound Sterling (GBP) GBP 3.30 to GBP 4.70 for every GBP 1 invested. Our initial pilot forecast suggests that the programme has the potential to generate GBP 5.40 to GBP 7.70 for every GBP 1 invested as the programme is developed and delivered over a 12-month period. Despite the small sample size and lack of a control group, our results contribute to the evidence-base for the effectiveness and social return on investment of NBSP as a therapeutic intervention for improving health and well-being and provides an example of the use of health economic well-being outcome measures such as ICECAP-A and CSRIs in social value analysis. Combining SROI evaluation and forecast methodologies with validated quantitative outcome measures used in the field of health economics can provide valuable social cost–benefit evidence to decision-makers.

Background: Nature Based Social Prescribing (NBSP) is a means of connecting people with non-clinical, nature-based community-led interventions delivered by 3rd sector organisations using local community assets. NBSP can support well-being and help alleviate pressure on mental health services addressing local health and wellbeing needs. This research used a mixed-method Social Return on Investment (SROI) evaluation of a six-month pilot ‘Making Well’ NBSP programme to support individuals with chronic mental health conditions in Wales. Charitable organisations and 3rd sector community organisations deliver socially prescribed programmes within local communities heavily rely on public funding to support their activity. This SROI evaluation incorporated a forecast for The Fathom Trust, an emerging Wales-based charity to demonstrate financial transparency to demonstrate efficiency and effective to ensure long-term sustainable creation of social value and public health outcomes. Methods: The ’Making Well’ programme costs were estimated in consultation with The Fathom Trust and well-being benefits and their monetary value were based on a recent SROI evaluation of a six-month Making Well programme pilot. The projected 20% overheads, including governance, programme development, staff training and fund-raising costs, were incorporated to reflect sustainable costs as the charity develops and more accurately estimate the future social value expected to be generated. The ‘Making Well’ project delivered two separate programmes between October 2021 and April 2022. Data was collected from participants (n=12) at baseline and eight-week follow-up along with interviews to collect in-depth data on individuals lived experience of participating in the programme. The ‘Making Well’ programme costs were estimated and financial proxies from the HACT Social Value (SV) bank were applied to identified benefits. Results: The estimated cost of ‘Making Well’ programme inputs were £1,312 per participant and the net value of well-being benefits were £4,313 to £6,130 per participant, giving a range of SVR’s between £3.30 to £4.70 for every £1 invested in this NBSP intervention. The SROI forecast provides a three-year projection of the annual social value created and the estimated forecast cost of programme inputs was £797 per participant. The net value of well-being benefits was £4,313 to £6,130 per participant, giving a range of social value ratios between £5.40 to £7.70 for every £1 invested. Significant wellbeing outcomes reported by participants included achieving higher self-confidence, increased feelings of social connection, and improved mental health. Conclusions: The SROI results demonstrate that the ‘Making Well’ programme is an effective NBSP intervention for supporting people with enduring mild to moderate mental health conditions. This SROI contributes to emerging evidence on the use of community assets and NBSP in generating a return on investment and positive social value. SROI forecasting for socially prescribed interventions delivered by local community assets, such as The Fathom Trust, can help organisations demonstrate transparent and effective investment of public funds and support optimal future social value creation and long-term public health outcomes.

There is growing interest in green social prescribing and connecting with nature-based activities to promote social cohesion along with improving levels of health, wealth and well-being. The Outdoor Partnership is a third sector organisation based in North Wales offering nature based social prescribing interventions. Individuals experiencing poor mental health and wellbeing are referred from GPs, community mental health services, and third sector organisations to the ‘Opening the Doors to the Outdoors’ (ODO) programme which is a 12-week outdoor walking and climbing green prescribing intervention. The purpose of the ODO programme is to provide a supportive environment to increase levels of physical activity among participants leading to improvements in overall health and mental wellbeing while promoting socialisation among peers. In this evaluation of a preventative green social prescribing intervention, a mixed method social return on investment (SROI) approach used quantitative and qualitative data from ODO participants. Data collection took place from April 2022–November 2022. Mental wellbeing data was collected at baseline and at 12 weeks using the Short Warwick Edinburgh Mental Wellbeing Scale, a social trust question, an overall health question, and the International Physical Activity Questionnaire- short form. Baseline and follow-up data was available for 52 ODO participants. Results indicate that for every £1 invested in the ODO programme, social values ranging from £4.90 to £5.36 were generated.

Abstract Keywords: Social Return on Investment, Social cost-benefit analysis, Lifestyle coaching, mental health, wellbeing, social prescribing Introduction The NHS is experiencing increased pressures due to an ageing population and rising health inequalities. GPs spend almost a fifth of their patient facing time addressing non-medical problems such as social isolation, financial struggles, and bereavement. Recent research suggests that holistic approaches linking social care to primary care may be cost-effective in supporting patients. Social Prescribing (SP) is an approach which could help individuals by sign posting and referral to non-clinical services, which can promote improvements in mental health and wellbeing, building resilience using community assets. The EmotionMind Dynamic (EMD) is a lifestyle coaching programme that supports individuals suffering from anxiety or depression referred from the health and social care sectors. EMD offers a unique, non-clinical mixed-modality approach combining coaching, mentoring, counselling skills, teaching and mindfulness. EMD is an adaptable, guided self-help tool that can be used as a preventative, supportive or reactive measure for improving mental health and wellbeing. Methods SROI methodology will be used to evaluate the EMD service. The aim of the SROI analysis is to develop a programme-level theory of change to establish how inputs (e.g. costs, staffing) are converted into outputs (e.g. numbers of clients seen), and subsequently into outcomes that matter to clients impacted by EMD coaching (e.g. improved mental wellbeing). Fifty participants will be recruited including clients who have completed the EMD programme and new clients participating in the online blended learning format. Face-to-face and blended learning formats will offer six sessions over a three-month period. A mixed-method approach will collect quantitative and qualitative from questionnaires and interviews. Outcomes will measure improvements in mental wellbeing and self-efficacy. Wellbeing valuation will be applied to quantify and value outcomes. Social value ratios will be generated from two value sets, one from the Social Value Bank and the other from the Short Warwick Edinburgh Mental Wellbeing Scale. Article Summary Strengths and limitations of this study The first study to undertake an SROI analysis on lifestyle coaching to improve mental wellbeing resilience Applies a mixed-method approach using both quantitative and qualitative data, using valid and reliable outcome measures Researchers working with the same data may arrive at different SROI ratios The matching of outcomes from proposed study data with the most appropriate SVB value will depend on the research team's discretion and agreement. This could potentially introduce researcher bias and the likelihood that potential estimates of social value generated could be upward-biased

Accelerate: the Welsh Health Innovation and Technology Accelerator.

BackgroundThe COVID-19 pandemic has created excess weighting lists to access Mental Health Services in the UK (Stats Wales, 2021). It is important to find effective solutions to alleviate the pressures that Mental Health services experience. The NHS Five Year Forward View encourages the development of new social prescribing empowerment-based interventions to supplement existing mental health programmes (Mental Health Taskforce, 2016). The EmotionMind Dynamic (EMD) is a lifestyle coaching programme that supports individuals suffering from anxiety or depression referred from the health and social care sectors. EMD offers a unique, non-clinical mixed-modality approach combining coaching, mentoring, counselling skills, teaching and mindfulness. MethodsSocial Return On Investment (SROI) methodology is applied to evaluate the EMD service. The aim of the SROI analysis is to develop a programme-level theory of change to establish how inputs (e.g. costs, staffing) are converted into outputs (e.g. numbers of clients seen), and subsequently into outcomes that matter to clients impacted by EMD service (e.g. improved mental wellbeing). Wellbeing valuation will quantify and value outcomes using two value sets. The SROI mixed-method approach collects quantitative and qualitative data from questionnaires and interviews with former face-to-face EMD clients as well a new clients, undertaking the online blended learning programme. FindingsInitial results indicate that the social prescribing face-to-face EMD programme generated positive social value ratios ranging from £9 to £23 for every £1 invested. In addition, the General Self-Efficacy Scale (GSES) which measures participant’s self-reported self-efficacy and confidence indicated that the face-to-face EMD participants experienced improved mental wellbeing and resilience as a result of participating in the EMD lifestyle coaching programme. Sensitivity analyses was conducted with Social Value Bank (SVB) figures for improved confidence and confirmed assumptions that former EMD clients experienced positive mental wellbeing improvements as a result of undertaking the lifestyle coaching programme. ConclusionsThis is the first study to undertake an SROI analysis of a social prescribing lifestyle coaching programme aimed at improving mental wellbeing and resilience. Phase one of this novel SROI study of the face-to-face EMD clients indicates that the EMD lifestyle coaching programme has the potential to generate positive social value ratios. Phase two analysis of the online EMD blended learning programme will compare the effectiveness of the two lifestyle coaching formats: face to face and the online blended format to improve mental wellbeing and self-efficacy by participating in this innovative lifestyle coaching programme.

Psychiatric conditions affect a large proportion of the population. High heritability estimates have been reported for commonly diagnosed conditions, suggesting both environmental factors and genetic variation significantly contribute to the chance of psychiatric outcomes. Despite growing interest in the provision and receipt of genetic counseling services for these conditions, such specialized interventions are not routinely available in most healthcare systems, including in the United Kingdom (UK). This study examined the attitudes of fourteen National Health Service employed genetic counselors and clinical geneticists, from seven regional genetic centers, toward offering psychiatric genetic counseling (PGC) in the UK. A qualitative methodology was adopted and individual semi-structured interviews were conducted either by telephone or face-to-face, audio recorded, transcribed in full and analyzed using thematic analysis. Participants' attitudes were organized under three themes: "Demand," "Readiness to Provide Support," and "Patient Experience." Participants cited key informational and resource needs which included increased workforce capacity, access to further psychological support for patients and more knowledge about the following: specific genes involved, available genetic testing, recurrence/occurrence risk figures, clinical manifestations, diagnostic criteria, patient concerns associated with the impact of psychiatric conditions and interpersonal skills. While some participants appreciated the value of PGC, some reported apprehension and raised concerns around a lack of available genetic testing, the perceived utility of current management options, and a potential negative psychological impact of PGC. This study identified important barriers to the delivery of PGC in the UK by genetics healthcare practitioners. Our findings highlight the importance of a collaborative, multidisciplinary approach to delivering this intervention and the need for additional training. Further research is required to better understand demand for, nature of, and barriers to provision of PGC in the UK, particularly in terms of genetic counselors' perceptions of their role.

22q11.2 DS is characterised by its variability, rarity and variety of features ranging from congenital heart conditions to psychiatric and behavioural issues. As a result, health information–seeking behaviour is different from other more common conditions. An exploratory study was carried out to understand how parents access information and support, and how that information is shared. Qualitative interviews were carried out with families and support group representatives, and thematic analysis was applied. Four main themes emerged from our findings: perceptions of clinical expertise, parent empowerment, support group activities and community building via an Internet platform. Our thematic analysis enabled the construction of a possible model of information-seeking behaviour in parents and carers of children with 22q11.2 DS. We discuss the model and how the understanding of how information is shared and gathered can aid in clinical practice.

Background: The diagnosis of developmental disorders is being transformed by advances in whole genome technologies. However, continuing uncertainties about the individual risks and potential severity of psychiatric impacts attributed to causal genomic variants limits the availability of comprehensive family-oriented information. In addition, there is insufficient evidence about how the parents of children with developmental disorders comprehend the facts and implications of their diagnosis through genetic counselling, nor how they gather developmental and mental health information to guide their understanding. Methods: Parents of children (aged 0–17 years) referred to paediatric genetics services completed an anonymous online 46-item survey about: (i) the experience of attending services to receive their child’s genetic diagnosis, and (ii) the availability, quality and helpfulness of information about psychiatric and neurodevelopmental conditions associated with genomic disorders. Findings: Two-hundred and eighty-six families (199 UK and 87 USA) completed the survey. One-in-three UK and one-in-five US respondents were dissatisfied with how their child’s genetic diagnosis was communicated. Satisfaction was predicted by face-to-face communication (odds ratio 2·91 [95% CI 1·43–5·94]; p= 0·003); results being presented by genetics specialists (2·97 [1·41–6·26]; p =0·004); receiving clear explanations (5·14 [2·58– 10·26]; p <0·001); receiving support (2·99 [1·21–7·36], p =0·017); and male gender of the tested child (2·56 [1·28–5·14]; p =0·008). Compared to health-related information on developmental delay or intellectual disability, parents were more likely to obtain information about psychiatric manifestations from non-professional lay sources than from clinical specialists ( p <0·001). This was particularly evident for families in the UK compared to the USA ( p <0·001). Parents considered information from rare disorder support groups to be more helpful than from genetics specialists (odds ratio 11·0 [95% CI 5·08–86·75]; p <0·001), or paediatricians (11·0 [1·42–85·20]; p =0·006), or internet sites (15·5 [3·71–64·77]; p <0·001), which in turn proved more helpful than information provided by geneticists (2·5 [1·44–4·31]; p =0·001). Interpretation: Psychiatric comorbidity is a common feature of rare genomic disorders, but the paucity of suitable information available from clinical specialists suggests families are not optimally informed about these challenges. Wider implementation of genomic testing in general medicine should include adequate training in genetic counselling to ensure best practice in communicating and explaining complex test results supported by comprehensive, family-oriented information. Funding: The Waterloo Foundation: Changing Minds Programme (506296); The Medical Research Council (MRC) Research Grant: Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (MR/N022572/1).

Background To describe the long-term mortality of a complete national cohort of acute coronary syndrome (ACS) patients enrolled in 2002, to compare this with a national age, sex and Maori ethnicity matched population, and to assess the influence of baseline factors on the 12-year mortality. Methods We reviewed 721 patients with a discharge diagnosis of an ACS who were enrolled in the first New Zealand ACS audit group cohort over 14 days in May 2002. We matched the cohort to the national mortality database using each patient's unique national identity number. Results Over a median follow-up of 12.7 years of 721 patients discharged with an ACS, overall mortality was 52%: ST-elevation myocardial infarction (STEMI) (58%), non-ST-elevation myocardial infarction (NSTEMI) (61%) and unstable angina pectoris (UAP) (42%) patients, p < 0.0001. In an age-adjusted survival model, males had a 29% increased mortality rate compared to females with a hazard ratio of 1.29 (95% CI 1.04, 1.61, p = 0.019). Over 12 years there were 339 (47%) deaths, compared to 284 (39%) deaths observed in the matched population. The standardised mortality ratio for patients admitted with an ACS in New Zealand is 1.3 (95% CI 1.2, 1.5) with eight patients per 100 not surviving to 12 years compared to this matched population. Conclusion The high mortality rate in this ACS cohort is a stark reminder of the prognostic implications of a presentation with an ACS. It emphasises the on-going need for optimal management of these patients throughout every stage of their initial treatment and subsequent on-going care.

DNA-binding proteins utilise different recognition mechanisms to locate their DNA targets. Some proteins recognise specific nucleotide sequences, while many DNA repair proteins interact with specific (often bent) DNA structures. While sequence-specific DNA binding mechanisms have been studied extensively, structure-specific mechanisms remain unclear. Here, we study structure-specific DNA recognition by examining the structure and dynamics of DNA polymerase I (Pol) substrates both alone and in Pol-DNA complexes. Using a rigid-body docking approach based on a network of 73 distance restraints collected using single-molecule FRET, we determined a novel solution structure of the singlenucleotide-gapped DNA-Pol binary complex. The structure was highly consistent with previous crystal structures with regards to the downstream primer-template DNA substrate; further, our structure showed a previously unobserved sharp bend (~120°) in the DNA substrate; we also showed that this pronounced bending of the substrate is present in living bacteria. All-atom molecular dynamics simulations and single-molecule quenching assays revealed that 4-5 nt of downstream gap-proximal DNA are unwound in the binary complex. Coarsegrained simulations on free gapped substrates reproduced our experimental FRET values with remarkable accuracy (<ΔFRET> = -0.0025 across 34 independent distances) and revealed that the one-nucleotide-gapped DNA frequently adopted highly bent conformations similar to those in the Pol-bound state (ΔG < 4 kT); such conformations were much less accessible to nicked (> 7 kT) or duplex (>> 10 kT) DNA. Our results suggest a mechanism by which Pol and other structure-specific DNA-binding proteins locate their DNA targets through sensing of the conformational dynamics of DNA substrates. Significance Statement Most genetic processes, including DNA replication, repair and transcription, rely on DNA-binding proteins locating specific sites on DNA; some sites contain a specific sequence, whereas others present a specific structure. While sequence-specific recognition has a clear physical basis, structure-specific recognition mechanisms remain obscure. Here, we use single-molecule FRET and computer simulations to show that the conformational dynamics of an important repair intermediate (1nt-gapped DNA) act as central recognition signals for structure-specific binding by DNA polymerase I (Pol). Our conclusion is strongly supported by a novel solution structure of the Pol-DNA complex wherein the gapped-DNA is significantly bent. Our iterative approach combining precise single-molecule measurements with molecular modelling is general and can elucidate the structure and dynamics for many large biomachines.

A key question in the function of DNA-processing enzymes is their mechanism for rapid location and binding of target sites in DNA. DNA polymerase I (Pol) is involved in high-fidelity DNA replication and repair, and must recognize gapped and flapped DNA substrates. Due to their transient and dynamic nature, the structures of these complexes and the recognition mechanism by which they are formed are largely unknown. Combining single-molecule Förster Resonance Energy Transfer (smFRET) with dye-position modelling, we can obtain absolute distance measurements with angstrom precision. We have used 120 such distances in a rigid-body docking approach to determine the structure of the single-nucleotide-gapped DNA-Pol binary complex, and that of the gapped-DNA substrate alone. In the complex structure, the DNA substrate exhibits a 120-degree bend. The upstream DNA is channeled into the Pol active site, and its position is in excellent agreement (RMSD < 3 Å) with the position of short DNA fragments seen in crystal structures of Pol. The downstream DNA is partially melted and held in close proximity to F771, a residue important for strand displacement. The structure of the gapped-DNA substrate alone adopts a 20-degree bend and a twist. Our coarse-grained simulations show short excursions of the substrate to partially kinked conformations not accessible to duplex DNA. Together, these data are consistent with a two-step model whereby Pol recognizes and binds a partially kinked conformation of gapped DNA, which then further rearranges to the fully bent state seen in the complex structure. Finally, using our method of internalization by electroporation, we have observed single-molecule FRET signals corresponding to unbound and Pol-bound gapped DNA in live bacteria, confirming the physiological relevance of the proposed substrate and complex structures and the recognition mechanism.

DNA polymerase I Klenow Fragment (Pol) adopts multiple conformations during high-fidelity DNA replication and repair, many of which have not been resolved by conventional techniques because of their transient and dynamic nature. Early in the DNA repair process, Pol must recognise and bind a one-nucleotide-gapped DNA substrate. Both the structure of this complex and the recognition mechanism by which it is formed are currently unknown. After demonstrating the sub-angstrom accuracy of our distance measurements using duplex DNA standards, we present a single-molecule FRET-restrained structural model of the DNA-Pol complex and show that binding of the gapped-DNA is consistent with a conformational-selection mechanism. Experiments on donor-acceptor-labelled gapped-DNA alone showed it adopted a low-FRET (unkinked) and a higher-FRET (kinked) conformation. Increasing concentrations of Pol stabilised the higher-FRET conformer, whilst also leading to the appearance of a third state, attributed to binding of a second Pol. We selected the DNA-Pol binary species from this dynamic equilibrium for structural characterization, obtaining >30 DNA-DNA and DNA-Pol distances, sufficient to restrain a unique molecular model of the complex (a structure which has not been resolved by NMR or crystallography). In this structure, the DNA exhibits a ∼90 degree bend which is likely important for both the search for the site of polymerization and for subsequent catalysis. To further investigate the Pol-DNA binding mechanism we developed a protein induced fluorescence enhancement (PIFE)-FRET coupled assay, which reported simultaneously on the DNA conformation and the presence of the Pol. This assay showed that all bound DNAs were kinked. Taken together, these data are consistent with a conformational-selection mechanism, in which the gapped-DNA substrate is recognised in its kinked state. This mechanism contrasts with experiments on the nucleotide binding, which we show to proceed via an induced-fit mechanism.

INTRODUCTION:It is frequent for news items to lead to a short lived temporary increase in interest in a particular health related service, however it is rare for this to have a long lasting effect. In 2013, in the UK in particular, there has been unprecedented publicity in hereditary breast cancer, with Angelina Jolie's decision to have genetic testing for the BRCA1 gene and subsequently undergo risk reducing mastectomy (RRM), and a pre-release of the NICE guidelines on familial breast cancer in January and their final release on 26th June. The release of NICE guidelines created a lot of publicity over the potential for use of chemoprevention using tamoxifen or raloxifene. However, the longest lasting news story was the release of details of film actress Angelina Jolie's genetic test and surgery.METHODS:To assess the potential effects of the 'Angelina Jolie' effect, referral data specific to breast cancer family history was obtained from around the UK for the years 2012 and 2013. A consortium of over 30 breast cancer family history clinics that have contributed to two research studies on early breast surveillance were asked to participate as well as 10 genetics centres. Monthly referrals to each service were collated and increases from 2012 to 2013 assessed.RESULTS:Data from 12 family history clinics and 9 regional genetics services showed a rise in referrals from May 2013 onwards. Referrals were nearly 2.5 fold in June and July 2013 from 1,981 (2012) to 4,847 (2013) and remained at around two-fold to October 2013. Demand for BRCA1/2 testing almost doubled and there were also many more enquiries for risk reducing mastectomy. Internal review shows that there was no increase in inappropriate referrals.CONCLUSIONS:The Angelina Jolie effect has been long lasting and global, and appears to have increased referrals to centres appropriately.

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