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Abstract Post COVID-19 condition or long COVID is highly prevalent and often debilitating, with key symptoms including fatigue, breathlessness, and brain fog. There is currently a lack of evidence-based treatments for this highly complex syndrome. There is a need for clinical trial platforms to rapidly evaluate nonpharmacological treatments to support affected individuals with symptom management. We co-produced a mixed methods feasibility study to evaluate a multi-arm digital decentralised clinical trial (DCT) platform to assess non-pharmacological interventions for Long COVID, using pacing interventions as an exemplar. The study demonstrated that the platform was able to successfully e-consent participants, randomise them into one of four intervention arms, capture baseline data, and capture outcomes relevant to a health economic evaluation. The study also highlighted several challenges, including difficulties with recruitment, imposter participants, and high attrition rates. We highlight how these challenges can potentially be mitigated to make a fully powered DCT more feasible.

Abstract Background Sexually transmitted infections (STIs) are a serious public health issue in many countries. Online postal self-sampling (OPSS) is increasingly used to test for STIs, a trend accelerated by the COVID-19 pandemic. There remains limited understanding of how service users experience OPSS and what leads them to access it over clinic-based services, or vice versa. This research seeks to address these gaps, by undertaking a large qualitative study which sits within the ASSIST study, a mixed-methods, realist evaluation of OPSS. Methods Participants were recruited via clinic-based and online sexual health services in three case study areas in England. Purposive sampling was used to over-represent populations disproportionately affected by poor sexual health: young people; people of colour; men who have sex with men; and trans and non-binary people. Semi-structured interviews were analysed using Levesque’s conceptual framework of access to healthcare. Results We interviewed 100 service users. Participants typically became aware of OPSS from sexual health services, the internet or word of mouth. Acceptability of OPSS was facilitated by the perceived privacy it offered over clinic-based services, which some participants found embarrassing to access. OPSS also enabled participants to overcome barriers to reaching clinic-based services, such as a lack of appointment availability, although difficulty obtaining OPSS kits in some areas undermined this. As all services in our case study areas were free to use, affordability did not significantly shape access, although OPSS enabled some participants to avoid costs associated with travelling to clinic-based services. Participants were usually able to engage with OPSS, finding it easy to use and reliable, although blood self-sampling was challenging for most. Participants valued the support offered by clinic-based services beyond STI testing, including the opportunity to access contraception or ask staff questions, and felt this was more appropriate when they had specific concerns about their sexual health, such as STI symptoms. Conclusions Our findings constitute one of the largest qualitative studies to have explored OPSS and offer valuable insights to providers. OPSS shapes access to STI testing in a number of ways, including facilitating access in many circumstances, but users also want to retain access to clinic-based services, particularly for when they believe they need support beyond STI testing.

Background One million people in England and Wales experience sexual violence and abuse each year, with nearly half experiencing serious sexual offences; around 30,000 survivors access sexual assault referral centres. Objectives This research was commissioned by National Institute for Health and Care Research to evaluate access, interventions and care pathways for survivors, especially those provided through sexual assault referral centres. Design, setting, participants The sexual assault referral centres care pathway was investigated through six sub-studies. There were two Cochrane Reviews (4274 participants). Seventy-two providers and 5 survivors were interviewed at eight sites; the children and young people study involved 12 participants from two sexual assault referral centres. A cohort study involving three-wave data collection over 1 year (21 sites; 2602 service users screened, 337 recruited) used a multilevel modelling framework to explore risk factors for burden of post-traumatic stress disorder symptoms at baseline and change at 1 year. We analysed costs and outcomes and conducted a narrative analysis (41 survivors). We worked closely with survivors and prioritised the safety/welfare of participants and researchers. Results Cochrane Reviews identified large effects from psychosocial interventions for post-traumatic stress disorder and depression. Sexual assault referral centres delivered a high-quality frontline service for survivors but groups experiencing domestic abuse and some ethnic and cultural minorities were under-represented. The qualitative research emphasised inter-agency collaboration for survivor benefit. The cohort study identified a risk ‘triad’ of adverse childhood experiences, poor mental health and economic deprivation, which was associated with baseline trauma burden. There were important improvements in trauma symptoms a year later. These improvements were unrelated to different sexual assault referral centre models. Costs and other outcomes were also similar across models. Harmful policing and justice practices/procedures were identified by 25% of participants. In this context, trauma-competent interviewing techniques, regular/timely updates and conveying case decisions with care signalled good practice. Limitations The cohort study lacked a comparison group, reducing confidence in the finding that access to sexual assault referral centres explained the reduction observed in post-traumatic stress disorder. Conclusions and future work Barriers to access call for concerted efforts to implement trauma-informed universal health services. The risk ‘triad’ underscores the value of holistic approaches to care at sexual assault referral centres and timely follow-on care. Poor mental health was the main barrier to service access beyond sexual assault referral centres. The persistence of trauma symptoms a year after accessing sexual assault referral centres signals urgent need for tackling counselling wait-lists, expanding support options and commitment to lifelong care. Multidisciplinary evaluation of sexual assault referral centres for better health provides a foundation for advancing trauma-informed practices in the context of sexual violence and abuse. Study registration This study is registered as ISRCTN30846825 https://doi.org/10.1186/ISRCTN30846825 Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 16/117/04) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 35. See the NIHR Funding and Awards website for further award information. Plain language summary What was the question? Around 30,000 survivors of rape, sexual assault and sexual abuse access sexual assault referral centres in England each year. Sexual assault referral centres provide support, health care and, if people wish, can gather evidence for a criminal investigation. Sexual assault referral centres also open routes to other care/support. We intended to understand the benefits of sexual assault referral centres and ways to improve care. What did we do? We interviewed 72 professionals to understand how they worked together. We followed up 335 survivors over 1 year after visiting a sexual assault referral centre. We gathered the views of 12 children and young people and 41 people from minority and disadvantaged backgrounds. We examined existing research to gather evidence of the benefit of care/support. We worked with survivors to confirm the safety and relevance of our research. What did we find? Participants were positive about sexual assault referral centres and Independent Sexual Violence Advisors, reporting very low harms (1% viewed sexual assault referral centre services as harmful to them). They were also satisfied with charities offering counselling, helplines and advocacy (4% harms). The research gathered mixed feedback about the National Health Service and police, with more harm being reported (15% and 25%, respectively). We found gaps in NHS care for those with complex trauma and long-term mental health problems. Post-traumatic stress disorder affected 70% of participants, with the highest being observed for those with adverse childhood experiences, poor mental health and economic struggles (a risk ‘triad’). Improvements occurred 1 year later, although half of participants still had trauma symptoms. We identified new treatments (e.g. yoga) as potential alternatives to traditional interventions. What does this mean? Sexual assault referral centres offer excellent care to survivors but should be accessible to a wider group of people. Identifying, supporting and careful referral of those with the risk triad mentioned may aid recovery after sexual violence and abuse. The research suggests that the NHS and policing/justice needs to ensure that they provide good care more often. Scientific summary Background Approximately 30,000 victims and survivors of rape, sexual assault and sexual abuse access sexual assault referral centres (SARCs) each year; therefore, there has been an urgent need to assess the experiences of these services. There is also a need to improve options for care; the visibility of and access to SARCs; and collaboration within frontline specialist services to serve people of all ages and genders exposed to sexual assault and rape in England. This research was commissioned by the National Institute for Health and Care Research (NIHR) to evaluate the provision of SARCs. We intended to determine the extent to which SARCs meet the needs of victims and survivors of recent and non-recent sexual violence and abuse, including children, young people and other survivors who may be silenced across different communities in Britain. Objectives The multidisciplinary evaluation of sexual assault referral centres for better health (MESARCH) project addressed a range of research questions, allowing for the evaluation of SARCs and expanding evidence for different services and interventions across SARC care pathways. The questions are as follows: For individuals who have had exposure to sexual violence and abuse, do psychosocial interventions reduce post-traumatic stress disorder (PTSD) and other poor health outcomes? What are providers’ experiences of delivering such psychosocial interventions? What are the experiences of survivors and supporters in accessing such psychosocial interventions? What are the implications of inter-related aspects of SARCs – the everyday work they do, the workforce, the technology and the organisation – for the delivery of SARC services? To what extent are SARCs embedded within the overall response by statutory and voluntary sector organisations to meet the needs of survivors? What are the health and cost trajectories of those who attend SARCs? How can these be compared for different SARC models of service delivery and access to health and Sexual Assault and Abuse Services (SAAS)? What is the effect of different sectors where survivors receive care, including any advantages or disadvantages of accessing post-crisis counselling in the voluntary sector compared with the NHS? What are the experiences of children and young people (CYP) in receiving care and support from SARCs? What do CYP’s recovery journeys look like after receiving support from SARCs? What are the experiences of access to SARCs by survivors with additional vulnerabilities such as chronic mental health problems and survivors from racially and other minoritised populations such as lesbian, gay, bisexual, transgender and/or queer survivors and those with socio-economic deprivation? Methods An innovative focus on patient and public involvement prioritised the safety and welfare of participants and researchers, largely through experts-by-experience embedded across the project lifecycle. A range of mixed-methods was employed: Systematic review, meta-analysis and qualitative evidence synthesis for two Cochrane Reviews For the SARC process evaluation, we mapped out service delivery, undertook thematic analysis of data collected from professionals from a range of SARCs and partners and integrated qualitative data on survivors’ experiences from the cohort study The cohort study interviewed survivors about their health, well-being and service use at baseline, 6 months and 12 months post-SARC. A multilevel modelling framework was used to explore risk factors for PTSD symptoms [Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5)] (primary outcome) at baseline and reduction in symptoms during the subsequent year; and determine whether SARC service models, service experience and participant-level factors influenced the outcome An economic evaluation based on the costs and changes in health-related quality of life, examining cost per quality-adjusted life-year (QALY) gained at 6 and 12 months Thematic analysis was used in the CYP study A life-narrative method with dialogical narrative analysis was applied in a qualitative study embedded within the cohort study to explore access and recovery experiences of racially minoritised survivors or those disadvantaged by other minoritised identities. Settings of studies in the Cochrane Reviews were health (emergency, primary care) and clinical/therapeutic (mental health), medico-legal (similar to SARCs), universities and community (charity-provided services) and most studies were from the USA. For our primary research, our process evaluation study included eight SARC sites and their inward and onwards partners/professionals; the cohort study followed-up survivors attending 21 SARCs; the CYP study was conducted at two SARCs; the qualitative study included cohort participants and a community (non-SARC) setting. Overall, 24 voluntary sector agencies, a local authority and an NHS sexual health clinic referred people into the sub-studies as our main model of recruitment. The study participants included 72 professionals and 5 survivors from service providers in the process evaluation; 2602 adult service users screened for eligibility through SARCs, 337 of whom joined the cohort study; 34 cohort participants and 7 people from the community (qualitative study); and 12 CYP. Two Cochrane Reviews reported on 4274 survivors, 19 family members and 60 providers. Results A comparative analysis of psychosocial interventions with inactive controls in our Cochrane Review suggests a beneficial effect at post-treatment favouring psychosocial interventions in reducing PTSD [standardised mean difference (SMD) −0.83, 95% confidence interval (CI) −1.22 to −0.44; 16 studies, 1130 participants; low‐certainty evidence; large effect size based on Cohen’s d] and depression (SMD −0.82, 95% CI −1.17 to −0.48; 12 studies, 901 participants; low‐certainty evidence; large effect size). The main comparative analysis did not detect unwanted effects from interventions. Our complementary Cochrane Review revealed that interventions helped survivors to better understand trauma and its effects, re-engage in many areas of life and improve interpersonal functioning. ‘Readiness’ was vital for engagement and may be as important as intervention content. Empowering survivors (and supporters) to make decisions about their interventions, for instance, having control over when they start and end interventions, was an important step in recovery. Our process evaluation study showed that SARCs remain an underutilised care pathway for survivors, exacerbated by lack of awareness in the general public, and thus survivors. Routes to SARC care are well-established among police forces, but poorly developed across some other professional groups (e.g. general practitioners [GPs]). Statutory and voluntary sector organisations working in partnership provides enhanced care for survivors, but SARCs and other organisations are hampered by a range of organisational and commissioning structures and processes. Service users joined the cohort study (with a baseline interview) 100 days after they had accessed a SARC (median = 104 days). They met the inclusion criteria of being ≥ 18 years and having sought assistance from a SARC after sexual violence and abuse (index exposure). This abuse was perpetrated by acquaintances (40%), strangers (20%) and partners (25%) and during childhood (13%). Forty-four per cent of the participants accessed a SARC within 10 days of trauma exposure; 38% underwent a forensic medical examination, and 85% had accessed Independent Sexual Violence Advisor (ISVA) care at baseline. Cohort participants were mainly women (90%), belonged to non-minoritised ethnicities (85%), had a mean age of 32 years (range: 18–75 years) and reported a high burden of lifetime trauma [77% indicated four or more adverse childhood experiences (ACEs) and 80% had prior exposure to domestic abuse]. Seventeen per cent of the users faced major daily financial problems. Nearly half of them had pre-existing mental health problems at the point of accessing SARC, and more than half had attempted suicide. Between SARC access and baseline, 56% had been prescribed psychotropic medications and had an average of 20 contacts with health/social/third-sector care [21 contacts at 6 months (a longer timeframe), dropping to 13 at 12 months]. At baseline, 71% of participants had ‘probable PTSD’, decreasing to 55% at 1 year. This reflected an unadjusted mean reduction of 9 points on PCL-5 (95% CI 6.6 to 11, Cohen’s d = 0.53), equating to a clinically important within-group change. One-third of the original cohort was lost to follow-up at 1 year, differing from those retained only on having greater socio-economic deprivation. The study did not detect differences in outcomes at 1 year according to the type of SARC service model (there were four types) they accessed or the location of the ISVA (some ISVAs are part of the SARC team and others are located in the community). There was strong evidence of a positive association between service use and symptom level at baseline, with a one-unit increase in the log of service use count being associated with a 4.5-point higher symptom score at baseline (95% CI 2.6 to 6.4; p < 0.001). For participant-level factors, each additional ACE was associated with a 1.4-point greater score of PTSD symptoms (95% CI 0.8 to 1.9; p < 0.001) and pre-existing mental health problems, with a 7.6-point difference (95% CI 4.0 to 11.1; p < 0.001). Participants with greater financial resources had fewer symptoms than for those with smaller financial resources (p = 0.009). Additionally, there was strong evidence that being unable to work was associated with a 10-point higher baseline score (p < 0.001). For offence-related factors, there was weak evidence that a delay to SARC of more than 10 days was associated with an approximately 4.5-point greater symptom score (p = 0.087), and a similar level of evidence was observed for an association for perpetrator type, where it appears that when the perpetrator was the survivor’s partner/family member, the baseline symptom score was greater. The main predictor of PTSD at 12 months was the baseline score. A high ACE profile doubled the odds of meeting the PTSD diagnostic threshold at baseline, but it reduced to 1.5 at 6 months and was absent at 1 year. SARCs and third-sector agencies achieved consistently high standards of care for survivors across sub-studies, with 50% of participants submitting ratings for these sectors as ≥ 90 on a harm-benefit scale [−100 to 100]. However, harmful responses were much more common in statutory health and justice settings, affecting 15% and 25% of participants, respectively (compared with 1% for SARCs and 4% for the third sector). The children and young people study observed that recovery and healing was influenced by how quickly the CYP accessed support, its content and duration, the location and context of care, how well the services worked together and CYP’s interactions with professionals at SARCs and across sectors. The embedded narrative study identified vital issues around access, as well as risk and recovery, in particular, inequalities arising from chronic mental health, economic disadvantage and family/community-based abuse highly mirroring the risk triad identified in the cohort study. Consistent support for survivors from all professionals and organisations a survivor engages with, ability to move away from the location where abuse has occurred and the opportunity to keep trying different therapies or activities supporting recovery were identified as helpful approaches to the recovery journey. Conclusions Sexual assault referral centres must recognise the high burden of lifetime trauma and chronic mental problems that affect most service users accessing this service. There is evidence that these factors, together with socio-economic status, affect people’s PTSD presentation to a greater degree than aspects of the offence (perpetrator and time since trauma), although these were still important. Different types of SARC and ISVA models did not appear to impinge on trauma symptoms at 1 year, or the way in which survivors experienced care within the SARC and onwards support agencies. Survivor service use was positively related to baseline trauma, which decreased over time, and costs did not differ according to the type of SARC or ISVA service accessed. This emphasises the importance of raising the visibility of SARCs as a care route overall, rather than recommending a specific model of delivery. The SARC pathway may deliver benefits to survivors who report clinically important reductions over time, especially among those with the greatest burden. However, half of the study sample participants remained positive for PTSD at 1 year. Every recovery journey following a sexual assault or abuse is different, and both formal and informal sources of support are important. A consistent trauma-informed societal response to sexual violence is needed. For CYP, early support from SARCs and accessible trauma-informed support throughout adolescence and into adulthood was critical in young people’s recovery. Implications for health care Sexual assault referral centre services deliver a high-quality frontline service for survivors and an effective gateway to health, ISVAs and voluntary sector services. A triad of lifetime traumas, chronic mental health problems and economic deprivation is apparent, which highlights the potential for holistic approaches at SARCs. Enquiring about a wide range of background factors may enhance timely access to appropriate therapies (see our Cochrane Reviews) as well as to social care and advocacy for housing, finances and domestic abuse, as part of the multipronged approach to support recovery and healing among survivors of sexual violence and abuse. Mental health difficulties represented the main barrier to accessing services beyond SARCs, and people affected struggled to consistently access the primary and therapeutic care they needed in the NHS as well as engagement with justice, calling for dedicated ISVA resources with mental health specialism. Inequalities are exacerbated in situations where survivors with relevant resources have the ability to pay for the therapeutic care they need and those without resources do not have the ability to pay and are left waiting. The findings on risk facing racially and other minoritised groups call for concerted efforts to support people to reach care through outreach programmes and campaigns and implement trauma-informed universal health services. Narratives of racial and cultural discrimination by services were not dominant in our qualitative enquiry, but a profound damage was reported when discrimination had occurred. There are vital interconnections between experiences of justice and health outcomes in this context. Harm in police and justice settings was marked, and calls for ongoing efforts to improve communication and other practices by the police in this context are warranted. Our data identified the good practice witnessed, and narratives containing practical measures agencies can take to minimise harms and enhance experiences of justice. We found support for cohesive commissioning strategies that promote a collaborative whole-systems approach to meeting the wide-ranging needs of people after exposure to sexual violence and abuse. The research evidences important improvements in trauma symptoms, but symptoms persisted for many participants at 1 year, supporting calls for tackling wait-lists, enhancing the therapy offering and a commitment to lifelong care for survivors of sexual violence and abuse. Working with survivor stakeholders at all research levels has been demonstrated to enhance feasibility of research and was experienced as empowering by survivor participants; this ethos should be translated into practice settings to diagnose barriers to meeting survivors’ needs and promote services improvement. Future research must focus on expanding evidence for interventions and developing professional interventions for enhancing trauma-informed practice. The MESARCH project identified strengths and urgent gaps in health and justice provision for survivors, and the findings provide a foundation for advancing trauma-informed practices when providing care to and supporting people exposed to the damaging effects of sexual violence and abuse. Study registration This study is registered as ISRCTN30846825 https://doi.org/10.1186/ISRCTN30846825 Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 16/117/04) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 35. See the NIHR Funding and Awards website for further award information.

Background Women’s sexual and reproductive health needs are complex and vary across the life course. They are met by a range of providers, professionals and venues. Provision is not well integrated, with inequalities in access. In some areas of the United Kingdom Women’s Health Hubs have been established to improve provision, experience and outcomes for women, and to address inequalities and reduce costs. These models were established prior to the national implementation of Women’s Health Hubs announced in the English 2022 Women’s Health Strategy. Objective To explore the ‘current state of the art’, mapping the United Kingdom landscape, and studying experiences of delivering and using Women’s Health Hubs across England, defining key features and early markers of success to inform policy and practice. Design A mixed-methods evaluation, comprising three work packages: Mapping the Women’s Health Hub landscape and context and developing a definition of Women’s Health Hubs, informed by an online national survey of Women’s Health Hub leaders, and interviews with regional stakeholders. In-depth evaluation in four hub sites, including interviews with staff and women, focus groups in local communities and documentary analysis. Interviews with national stakeholders and consolidation of findings from work packages 1 and 2. Fieldwork was undertaken from May 2022 to March 2023. The evaluation was initiated prior to the national scale-up of Women’s Health Hubs announced in the 2022 Women’s Health Strategy. Results Most areas of the United Kingdom did not have a Women’s Health Hub. Seventeen active services were identified, established between 2001 and 2022. Women’s Health Hubs were diverse, predominantly GP-led, with different perspectives of the role and definition of a hub. Women using hubs reported positive experiences, finding services caring and convenient. Implementation facilitators included committed, collaborative leaders working across boundaries, sufficient workforce capacity and a supportive policy context. Challenges included access to funding, commissioning, workforce issues, facilities and equipment, stakeholder engagement and wider system integration, priorities and pressures. Leaders were committed to addressing inequalities, but evidence of impact was still emerging. Limitations It was challenging to locate models; therefore, some may have been missed. Data availability limited assessment of impact, including inequalities. Some population groups were not represented in the data, and the evaluation was more provider-oriented. It was not possible to develop a typology of Women’s Health Hubs as planned due to heterogeneity in models. Conclusions Existing Women’s Health Hub models were providing integrated approaches to meet local needs. Many were at an early stage of development. Evidence of system-level impact and costs was still emerging. Women’s Health Hubs may widen inequalities if models are more accessible to advantaged groups. The important role of committed leaders in existing ‘bottom-up’ models may limit scalability and sustainability. Findings suggest that national scale-up will take time and requires funding and that it is necessary to design models according to local needs and resources. In 2023, the Department of Health and Social Care announced funding to establish a Women’s Health Hub in every Integrated Care System in England. Future work Future evaluation should consider system-level impact and costs, explore unintended consequences and test assumptions. Funding This award was funded by the National Institute of Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR135589) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 30. See the NIHR Funding and Awards website for further award information. Plain language summary In the National Health Service, care for women’s health issues such as heavy periods, menopause, contraception and abortion is provided by different services, such as GPs and hospital gynaecology and sexual health clinics. Services are not always joined up and often women find it hard to access care. To improve care, United Kingdom National Health Service teams have set up Women’s Health Hubs. Women’s Health Hubs involve a group of health professionals working together to provide more joined-up community-based services to women throughout their lives. This evaluation aimed to explore why, where and how Women’s Health Hubs have been set up and what they have achieved and to understand staff and patient experiences. The results will be shared with the government and National Health Service as new Women’s Health Hubs are set up. The evaluation included a survey of people who have set up hubs across the United Kingdom and interviews with women’s health leaders in England. In four hubs in England, we talked to local women and staff, and reviewed documents. We found 17 hubs, and most areas of the United Kingdom did not have one. Every hub was different, with different views about how hubs should work. Most were set up to improve access and experiences for women, and reduce pressure on other services. Six hubs had involved women in developing their service but most had not. Hubs offered appointments with health professionals, usually in GP or community clinics. The most common services were for coil fitting, menopause and heavy periods. The set-up of hubs was helped by passionate leaders who involved the right people, and identified funding and time. Challenges included National Health Service pressures and a lack of funding, clinic space and staff. Women who have used hubs report a good experience, with caring and convenient services. More work is needed to understand how hubs can improve care for all women, including unfair differences in care. Scientific summary Background Sexual and reproductive health covers a range of needs and conditions, including contraception, pregnancy and abortion, sexually transmitted infections (STIs), psychosexual services (e.g. counselling for sexual dysfunction), and gynaecological health (e.g. peri-menopause, menopause and menstrual problems) [All-Party Parliamentary Group on Sexual and Reproductive Health. Women’s Lives, Women’s Rights: Strengthening Access to Contraception Beyond the COVID-19 Pandemic (Internet). 2020. www.fsrh.org/documents/womens-lives-womens-rights-full-report/ (accessed 24 October 2023)]. Women’s sexual and reproductive health needs are complex and vary across the life course, and they are met by a variety of providers, venues and professionals. In England, challenges in access, workforce, funding and fragmented commissioning impact on women’s health service provision. In response to these challenges, local teams across the UK established Women’s Health Hubs (WHHs) to improve provision, experiences and outcomes. WHHs aimed to integrate women’s health services more effectively, with a more woman-centred, life-course approach. These emerging models were highlighted as best practice and wider adoption was subsequently recommended as a part of England’s Women’s Health Strategy in 2022. However, there was no agreed definition of a WHH in clinical and policy communities. Hubs were described as not necessarily a ‘place’, but a ‘concept’, and the term was being used differently across services and organisations. In response to WHHs being identified as an important policy topic, in 2022, the National Institute for Health and Care Research (NIHR) asked the BRACE Rapid Evaluation Centre to undertake a rapid evaluation of current hub evidence and practice. Objectives The aim of this evaluation was to explore the ‘current state of the art’ of WHHs, mapping the landscape, studying experiences of delivering and using hub services and defining key features and early markers of success to inform policy and practice. The evaluation explored the following questions: What are WHHs, and is there variation in how stakeholders name and define them? How many WHHs have been established or are in development across the UK, where are they and what are their characteristics, including models of structure, commissioning and delivery? Why have WHHs been implemented, and how are they intended to address health inequalities? What have WHHs achieved to date? How do WHHs achieve this? What are the experiences and perspectives of staff regarding WHH set-up, commissioning, funding, implementation and delivery? What are the experiences and perspectives of women who have used hub services? How are WHHs’ performance, outcomes and costs measured, and how might they be measured in future? Methods This was a mixed-methods evaluation, combining quantitative and qualitative data collection, with data collected at local, regional and national levels. This approach offered both breadth and depth in data collection. The evaluation comprised three work packages (WPs): Mapping the current landscape and context for WHHs, including an online survey of leads from hubs across the UK and interviews with regional stakeholders. Detailed research in four purposively selected exemplar hub sites in England, including interviews with staff and service users, focus groups in local communities and documentary analysis. Bringing together and consolidating findings from WPs 1 and 2 to generate evidence on WHH models, including interviews with national stakeholders. The mapping in WP1 was UK-wide, but the remainder of the work focused on WHHs in England. The England focus was decided collaboratively with a multidisciplinary Stakeholder Group, due to the particularly complex commissioning context in English health and social care systems. In total, interviews with 85 people were conducted: 40 WHH and wider staff, 7 regional stakeholders, 6 national stakeholders and 32 women. Four focus groups were undertaken with women in the local communities served by exemplar hubs. Ten initial scoping interviews undertaken to inform protocol design were included in the analysis. Results There were diverse approaches to implementing WHHs across England, with no standard or ‘typical’ model, and a lack of common language and terminology to describe hubs. A hub can be interpreted as a physical place, but also as a virtual platform (e.g. to triage or offer educational events for women), which can be difficult to understand for some stakeholders, including some women. In collaboration with our evaluation Stakeholder Group, and based on our findings across WPs, we developed a working definition of a WHH that represents a set of common features that were recognised within the community of practitioners as typifying a hub approach: Women’s Health Hubs are based in the community and work at the interface between primary and secondary care and/or voluntary sector and wider. Women’s Health Hubs offer more than a single service (and include the provision of both gynaecological services and contraception) or demonstrate plans to do so. Women’s Health Hubs have more than one organisation involved in the process of service delivery, including in design, commissioning and/or provision of care, beyond simply referring in. This definition should be considered alongside the need for hub design to be tailored to local contexts, needs and resources. As a result, we have not specified which model(s) should be used to implement hubs, which role(s) should lead design/delivery or other details about how the hub is established and resourced. While this offers flexibility to local areas to design a service that meets local needs, there is a risk of creating confusion for women, healthcare professionals and policy-makers regarding what a hub is and should do. This may impact on engagement by these groups and on hub implementation. The heterogeneity in hub models can also hinder evaluation, monitoring and comparison of hub impact. The working definition we have developed can be refined over time in response to evolving evidence and practice. A clear definition can support policy and decision-makers to better understand which models work best for women, including those from groups with greater needs, and which are most effective (including cost-effective). Further refinement of the definition could include standardisation of terminology, for example, to confirm the number and type of services that constitute a 'one-stop shop', and whether the ’spoke’ aspect of a ‘hub-and-spoke’ model must be a physical location or could be virtual. Clear definitions of a hub may also avoid simple rebadging of local services as hubs in response to policy initiatives, without meaningful transformation of care pathways. We identified 17 active WHHs across the UK. This means that most women did not have access to a hub at the time of data collection. Most of the hubs we identified were continuing to evolve and had plans in place to expand their offer and/or geographical reach. Hubs were introduced to meet a range of aims, primarily intending to improve healthcare access, quality and experience. Hub leaders were committed to reducing inequalities and many were implementing strategies to do so but approaches and evidence were still evolving. Hub services were often described as filling the intermediary space between standard primary care and specialist secondary care, although this boundary varied across hubs. Hubs were predominantly clinically led by GPs with a special interest in women’s health, although some were led by other professionals. Often, leadership was not well defined, with unspecified responsibilities and accountabilities, and a blurring of leadership, management and governance boundaries. While many hubs were reported as being one-stop shops, it was rare for them to offer multiple services at the same time and those that did were often opportunistic rather than a planned service offer (e.g. offering a smear test at the same time as fitting a coil). Most hubs operated from multiple venues, often in primary care or community settings. The professionals working to deliver services within hubs varied, and there was no consistent approach to staffing, with different costs associated with the roles deployed. A range of commissioning approaches were in place, often involving collaboration between multiple organisations. Given the challenges in securing funding and overcoming commissioning barriers, hub leaders had developed a range of creative approaches to accessing resources for implementation and delivery. However, these innovative local workarounds may not be suitable for long-term, sustainable scale-up and spread of WHHs. Some hubs had been unable to expand their clinical offer due to pre-existing commissioning barriers. Challenges included moving funding or activity from secondary care gynaecology to WHHs and identifying a long-term solution to enable offer of long-acting reversible contraception (LARC) for both gynaecological and contraceptive reasons in a hub. Resolving these challenges was often described as critical to successful implementation of hubs. In addition to financial resources, some hubs had secured additional expertise and capacity to support implementation, including from other areas of the health system, local authorities and pharmaceutical companies. Development of metrics and the measurement of hub outcomes was evolving and varied between hubs, making comprehensive assessment and comparison difficult. Some hubs had used local data to measure and model population need to inform hub design, and to estimate hub costs and benefits. Available data to quantify hub activity and impact so far were limited, but where reported it indicated that hubs had provided care for many hundreds of women in England. It also indicated that hubs have the potential to reduce waiting times and referral to secondary care gynaecology and increase LARC uptake. Evidence of impact on inequalities was still emerging. Women who participated in the evaluation reported having a positive experience of accessing their local hub and the care they received. However, women using the hub and other local women in the community were generally not familiar with the term ‘women’s health hub’ or did not know that they had received care from a hub, though they welcomed the hub concept. Women also described some challenges in accessing hub services, including difficulties making a GP appointment in order to be referred to the hub. A minority of hubs reported involving women in the design and development of the service. There is scope for greater involvement of women with a range of backgrounds and experiences in WHH development at both a national and local level to ensure that they meet the needs of all women and address inequalities. A number of factors facilitated the implementation and delivery of WHHs. This included leaders (both clinical and non-clinical) who were committed to the hub vision and worked collaboratively across organisational and sector boundaries to design and set up the service. Sufficient workforce capacity and wider policy and strategic support were also important. Implementation challenges included identification of funding and other resources (e.g. facilities equipment, physical space), stakeholder engagement (including allaying concerns regarding negative impacts on other parts of the system), competing priorities and pressures in the healthcare system, and IT issues. The fragmentation of English commissioning arrangements for gynaecology and contraception was a frequently reported barrier. We identified examples of hubs that had overcome some of these barriers to integrate care for women in their area. The creation of Integrated Care Boards (ICBs) in 2022 was seen as a potential route to scale-up hubs nationally. The lack of an ICB leader with responsibility for women’s health (with the exception of maternity) was noted as a challenge. The many competing priorities for ICBs were highlighted as limiting capacity to focus on women’s health. Subsequent to the completion of our evaluation in 2023, additional national funding was announced linked to the Women’s Health Strategy, to support the setting up of a WHH in each ICB in England, along with the appointment of a Women’s Health Champion in every ICB. Hubs had largely been developed bottom up by local professionals, designed to meet the specific needs of the local population. Participants often reflected that a top-down approach to implementing hubs may limit the flexibility to adapt to local needs, context, leadership, workforce and resources. A middle ground between a bottom-up and top-down approach may be required to balance standardisation across hubs (e.g. to have a shared vision and definition) with flexibility to align with local context. Hub establishment was still in the early stages, and it will take time to scale the approach up across the NHS and to ensure long-term sustainability of services, and localities were all at different starting points. The small number of highly diverse hub models in place at the time of this evaluation and varied approaches to measurement meant that it was challenging to assess impact. However, it highlights the opportunity to develop resources to support local systems to design and establish hubs, agree on core definitions and model components, standardise approaches (where appropriate), capture learning/data and test assumptions of different ways of working. Implementation efforts should include exploring and understanding any unintended consequences, a common occurrence when introducing complex changes into health systems. Agreeing some aspects of standardisation (where appropriate), sharing learning and measuring outcomes and impact data can facilitate future and ongoing implementation and evaluation of WHHs, and allow exploration of the relative benefits of different models. This learning can inform further scale-up of and development of WHHs. Conclusions At the start of this evaluation, WHHs were a set of innovative service models spread across the UK, and at the end of the evaluation, they were an explicitly stated policy objective for the Department of Health and Social Care (DHSC). Our findings identified that the few existing WHHs are diverse, and continuously evolving, with many at an early stage of development or delivery, with some employing innovative approaches such as virtual group consultations. The launch of the Women’s Health Strategy, and the associated funding to support hub implementation announced in March 2023, provides an opportunity to expedite the spread of these models. However, the heterogeneity in models and contexts, and the complexity of women’s health care, means that rapid scale-up may be challenging, and substantial commissioning barriers must be overcome. Our findings suggest that implementing models informed by local needs and resources will be necessary, and requires input from women, particularly those who are least well served by current services. We do not yet have clear evidence for the system-level impact or costs of WHHs, and the gathering of consistent data to test assumptions, and measure and learn from WHH achievements, including impacts on inequalities, will enable evaluation of further scale-up. WHHs have the potential to transform women’s access to care, and there is a large community of experts striving to improve women’s health care. The Women’s Health Strategy for England provides a further catalyst to national-level change, alongside the emerging system-level approaches to health improvement driven by ICBs, and wider population interest in women’s health. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research (NIHR award ref: NIHR135589) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 30. See the NIHR Funding and Awards website for further award information.

Background Selected patients with advanced heart failure ineligible for heart transplantation could benefit from left ventricular assist device therapy as ‘destination therapy’. There is evidence of the efficacy of destination therapy; however, it is not currently commissioned within the United Kingdom National Health Service due to the lack of economic evidence. Objective What is the clinical and cost-effectiveness of a left ventricular assist device compared to medical management for patients with advanced heart failure ineligible for heart transplantation (destination therapy)? Methods A systematic review of evidence on the clinical and cost-effectiveness of left ventricular assist devices as destination therapy was undertaken including, where feasible, a network meta-analysis to provide an indirect estimate of the relative effectiveness of currently available left ventricular assist devices compared to medical management. For the systematic reviews, data sources searched (up to 11 January 2022) were Cochrane CENTRAL, MEDLINE and EMBASE via Ovid for primary studies, and Epistemonikos and Cochrane Database of Systematic Reviews for relevant systematic reviews. Trial registers were also searched, along with data and reports from intervention-specific registries. Economic studies were identified in EconLit, CEA registry and the NHS Economic Evaluation Database (NHS EED). The searches were supplemented by checking reference lists of included studies. An economic model (Markov) was developed to estimate the cost-effectiveness of left ventricular assist devices compared to medical management from the United Kingdom National Health Service/personal social service perspective. Deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties. Where possible, all analyses focused on the only currently available left ventricular assist device (HeartMate 3TM, Abbott, Chicago, IL, USA) in the United Kingdom. Results The clinical effectiveness review included 134 studies (240 articles). There were no studies directly comparing HeartMate 3 and medical management (a randomised trial is ongoing). The currently available left ventricular assist device improves patient survival and reduces stroke rates and complications compared to earlier devices and relative to medical management. For example, survival at 24 months is 77% with the HeartMate 3 device compared to 59% with the HeartMate II (MOMENTUM 3 trial). An indirect comparison demonstrated a reduction in mortality compared to medical management [relative risk of death 0.25 (95% confidence interval 0.13 to 0.47); 24 months; this study]. The cost-effectiveness review included 5 cost analyses and 14 economic evaluations covering different generations of devices and with different perspectives. The reported incremental costs per quality-adjusted life-year gained compared to medical management were lower for later generations of devices [as low as £46,207 (2019 prices; United Kingdom perspective; time horizon at least 5 years)]. The economic evaluation used different approaches to obtain the relative effects of current left ventricular assist devices compared to medical management from the United Kingdom National Health Service/personal social service perspective. All gave similar incremental cost-effectiveness ratios of £53,496–58,244 per quality-adjusted life-year gained – lifetime horizon. Model outputs were sensitive to parameter estimates relating to medical management. The findings did not materially differ on exploratory subgroup analyses based on the severity of heart failure. Limitations There was no direct evidence comparing the clinical effectiveness of HeartMate 3 to medical management. Indirect comparisons made were based on limited data from heterogeneous studies regarding the severity of heart failure (Interagency Registry for Mechanically Assisted Circulatory Support score distribution) and possible for survival only. Furthermore, the cost of medical management of advanced heart failure in the United Kingdom is not clear. Conclusions Using cost-effectiveness criteria applied in the United Kingdom, left ventricular assist devices compared to medical management for patients with advanced heart failure ineligible for heart transplant may not be cost-effective. When available, data from the ongoing evaluation of HeartMate 3 compared to medical management can be used to update cost-effectiveness estimates. An audit of the costs of medical management in the United Kingdom is required to further decrease uncertainty in the economic evaluation. Study registration This study is registered as PROSPERO CRD42020158987. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128996) and is published in full in Health Technology Assessment; Vol. 28, No. 38. See the NIHR Funding and Awards website for further award information. Plain language summary The majority of patients with advanced heart failure would be unsuitable for heart transplantation due to their age and comorbidities but selected patients could benefit from a left ventricular assist device. Left ventricular assist device therapy for such patients is known as ‘destination therapy’. This is a long-term therapy that involves implanting a battery-powered pump to support the patient’s heart. The purpose of this project was to collect and assess the research evidence on the effectiveness of left ventricular assist devices when used for destination therapy, and to estimate value for money compared to medical management from the United Kingdom National Health Service/personal social service perspective. This research identified that the currently available left ventricular assist device improves patient survival as well as reducing stroke rates and complications compared to earlier devices and relative to medical management. However, there is uncertainty in the evidence due to the absence of studies directly comparing the current device to medical therapy alone. An ongoing clinical trial is currently assessing this. It also means there is uncertainty about whether left ventricular assist devices could provide value for money as determined currently for the United Kingdom National Health Service. Scientific summary Background Heart failure is a debilitating, progressive syndrome characterised by the inability of the heart to pump blood around the body. Pharmacological treatments are used as first-line treatment but may eventually become less effective and left ventricular assist devices (LVADs) or heart transplant (HT) are considered. LVADs are frequently used as bridge to transplant (BTT) or bridge to candidacy (BTC). However, some patients are ineligible for HT and either continue on medical management (MM) or could have a LVAD implanted as ‘destination therapy’ (DT). LVAD as DT is not currently commissioned within the United Kingdom National Health Service (UK NHS). The costs of LVADs are high, especially when compared to the alternative MM, but may also offer significant benefit in terms of survival. It is important to determine whether LVADs are both clinically and cost-effective as DT to inform decision-making from the UK NHS/personal social service (PSS) perspective on their potential as long-term treatment for advanced heart failure patients ineligible for HT. Aims and objectives What is the clinical and cost-effectiveness of a LVAD compared to MM for advanced heart failure (AHF) patients ineligible for HT (DT)? The specific objectives to address this aim were to undertake: – a systematic review of available evidence on the clinical effectiveness of a LVAD as DT, including a network meta-analysis (NMA) to provide an indirect estimate of the relative effectiveness of currently available LVADs compared to MM; – a systematic review of available economic evidence on the use of a LVAD as DT; and – the development of an economic model to estimate the cost-effectiveness of a LVAD compared to MM from the UK NHS/PSS perspective. Due to the withdrawal of the HeartWare ventricular assist device (HVAD) during the undertaking of this research, the analyses primarily focus on the HeartMate 3™ (Abbott, Chicago, IL, USA) device, the only LVAD available in the UK at this time. Methods Systematic review of clinical effectiveness A systematic review was undertaken of all LVADs as DT and reporting followed the general principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The review was registered on PROSPERO (CRD42020158987). Eligibility criteria Studies of patients over 16 years of age with AHF who received any type of LVAD as DT were included. The review considered all devices, but the analysis focused on the HM3 device due to the recent withdrawal of the HeartWare HVAD (Medtronic, Dublin, Republic of Ireland). Eligible comparators (where relevant) were MM and other LVADs. Outcomes were survival, quality of life (QoL), hospitalisations, major events, complications and functional status. Study designs eligible were any clinical trial (whether randomised, non-randomised or single arm), observational studies (cohort, case-controls and case series) and reports from patient registries [e.g. INTERMACS, International Registry for Mechanically Assisted Circulation (IMACS)]. Studies were eligible if 50 or more DT patients were included. Systematic reviews were included and used to identify any additional potentially relevant primary studies. Searches and study selection Databases were searched from inception to 20 May 2020, with an updated search on 11 January 2022. Databases searched included Cochrane Library (CENTRAL), MEDLINE and EMBASE via Ovid, Epistemonikos, Cochrane Library of Systematic Reviews and World Health Organization (WHO) clinical trials portal (for ongoing studies). There were no restrictions by language or date of publication. Two reviewers independently undertook title and abstract screening and full-text selection via Covidence (Veritas Health Innovation, Melbourne, VIC, Australia). Disagreements were resolved by a third reviewer or consensus and reasons for exclusion were recorded. Risk of bias, data extraction and synthesis Quality assessment and data extraction were completed by one reviewer and checked by a second. Appropriate risk-of-bias tools dependent upon study design were applied. A hierarchical approach to synthesis was undertaken to avoid double-counting of studies with overlapping patient data and to manage the large volume of evidence. Randomised controlled trials (RCTs) and controlled non-randomised trials were considered in the first instance. Registry reports and uncontrolled observational studies were used to supplement findings for all outcomes. Data were tabulated and analysed in a narrative approach by device, and forest plots without summary estimates were presented (and where appropriate the feasibility of meta-analysis was considered). A network meta-analysis was considered for the main outcomes to produce an indirect comparison of the HM3 device (across LVAD generations) to MM, but only carried out for survival. Systematic review of cost-effectiveness A systematic review of the cost-effectiveness of LVADs was carried out utilising the same search strategy, and at the same time as the clinical effectiveness review, with the addition of three further specialist economics database searches in EconLit, Cost-Effectiveness Analysis (CEA) registry and the NHS Economic Evaluation Database (NHS EED). Appropriate risk-of-bias tools were applied and a narrative synthesis was undertaken. Economic evaluation The systematic reviews’ findings were used to inform the development of a cost–utility analysis (CUA), from the NHS/PSS perspective, using a Markov model with a lifetime horizon and 1-month cycles. Along with evidence from the reviews, the model was informed by guidance from clinical specialists, patients and commissioners. All costs used were in 2019 prices, and a discount rate of 3.5% was applied as per the national UK guidelines. To produce the base case, mortality risks for MM and LVAD arms required some assumptions and several methods for estimating the risks were identified. Two of these were primarily utilised: non-comparative net weight estimates and comparative estimates mapped to LVAD data from the recent relevant HM3 trial (MOMENTUM). The analysis was repeated incorporating a small probability of LVAD DT recipients transitioning to HT eligibility. The potential impacts of the severity of heart failure on cost-effectiveness were explored by considering subgroupings of profiles based on the INTERMACS classification. Uncertainty was explored via both deterministic and probabilistic sensitivity analyses, paying specific attention to the life expectancy and ongoing costs. Results Systematic review of clinical effectiveness There were 240 articles from 134 studies included in the clinical effectiveness review (5 randomised trials, 1 non-randomised trial, 86 observational studies, reports from 5 registries, 5 ongoing studies and 32 systematic reviews). Of the six trials that were included, only one of these assessed the HM3 and this was in comparison to the previous generation HeartMate II device (MOMENTUM RCT). The majority of HM3 data comes from this trial, with minimal additional data contributions from registry reports or observational studies of single cohorts. The MOMENTUM study was considered as having some concerns regarding risk of bias; however, this was primarily due to the per-protocol analysis for the DT participants and most other domains were considered low risk. There were 624 DT patients in the MOMENTUM 3 trial in total, with a mean age of 63 [standard deviation (SD) 12], 82.2% male and 52.1% INTERMACS level 3. At the longest follow-up point (24 months) survival was 76.7% in HM3 DT patients compared to 59% in HeartMate II patients. Clear and significant improvements in QoL from baseline were reported at 12 months and maintained at 24 months in the HM3 group; however, this was similar in the HeartMate II group. Major events and complications were present in both groups by the 24-month follow-up. There were eight stroke events per 100 patient-years in the HM3, as well as one pump thrombosis event and 70 bleeding events per 100 patient-years. These were all lower than that of the HeartMate II group. Rehospitalisations were also significantly lower in HM3 patients. While some reports included HM3 patients, there were no HM3 specific data reported in any patient registry reports. One observational study reported that HM3 patients (n = 15) had 0 pump thrombosis events in 24 months of follow-up. While it was not the focus due to withdrawal, survival levels were lower in the HeartWare HVAD trials when compared to the HM3 in the MOMENTUM trial and there were concerns with the stroke rates reported in the evidence. Risk of bias across the included trials varied with all but two studies reporting an overall high risk of bias or with some concerns for at least one outcome. The evidence contained within the remaining trials, observational studies and registry reports mostly relate to devices other than HM3. This evidence is summarised in the main part of this report. Indirect comparison of HeartMate 3 and medical management As there were no studies directly comparing HM3 and MM, indirect comparisons of the trial data were required utilising MM data from the older REMATCH trial (the first RCT comparing the first-generation HeartMate device to MM). Data were available to link through available studies for the survival outcome only. The network meta-analysis demonstrated a reduction in the risk of mortality, relative risk of death of 0.25 [95% confidence interval (CI) 0.13 to 0.47] 24 months, with the HM3 compared to MM. Systematic review of cost-effectiveness There were 19 studies reported in 20 articles included in the cost-effectiveness review: 5 cost analyses and 14 economic evaluations. Nine studies were US-based and four were UK-based. Most of the studies aimed to compare the health and cost outcomes of LVADs with MM. Most economic evaluations (n = 12) used a CUA approach and only two conducted a CEA. Markov-based modelling was applied in eight studies. The perspective, where stated, was the service provider in most studies. Healthcare resource use was usually estimated based on small numbers of patients from a single centre, which resulted in variability. In the studies comparing LVAD with MM for DT patients, the incremental cost per quality-adjusted life-year (QALY) gained estimates ranged between £46,207 and £238,401 in 2019 prices over a time horizon of 5 years or longer and from different perspectives. The overall quality of the studies was considered poor to moderate. Some limitations were limited consideration of uncertainty, insufficient time horizon and lack of consideration of some key complications and cost components. Only one study looked at the impact of disease severity on cost-effectiveness. More recent evaluations tended to have lower estimates of incremental cost-effectiveness, presumably reflecting better clinical outcomes of more recent devices. Two recent studies estimated the cost-effectiveness from a UK perspective, deriving incremental cost-effectiveness ratios of £47,361 and £46,207 per QALY gained for the HeartWare device (device withdrawn in 2021) and the HM3 device, respectively compared to MM. Economic evaluation The economic evaluation found similar results for each base case: Non-comparative net weight estimates approach: LVAD would produce an additional 2.86 QALYs per person, increase life expectancy by 3.73 years and the incremental cost to the NHS would be £152,735 per person. Incremental cost-effectiveness ratio (ICER): £53,496. Comparative estimates mapped to LVAD in MOMENTUM approach: LVAD would produce an additional 2.51 QALYs per person, increase life expectancy by 3.06 years and the incremental cost to the NHS would be £146,275 per person. ICER: £58,244. At a willingness to pay threshold of £50,000 per QALY gained, LVADs would not be considered cost-effective compared to MM for AHF patients ineligible for HT. The same applied when severity weighted ICER estimates based on QALY shortfall methods were used. The deterministic sensitivity analysis showed that inclusion of the probability of becoming eligible for a HT did not change these findings. Furthermore, the findings did not differ in subgroup analyses based on severity of heart failure. Model outputs were most sensitive to estimates related to outpatient costs for both LVAD and MM. Conclusions LVADs have significantly improved over time and the currently available HM3 LVAD is considered clinically effective in patients with end-stage heart failure ineligible for transplant, offering survival of over 75% at 2 years of follow-up with reduced complications and major events in comparison to older devices. However, the device compared to MM may not be considered cost-effective when using methods of defining this for end of life in the UK. Future research Currently, no RCT has been published that compares the HM3 device to MM; however, there is an ongoing trial (SweVAD) comparing the two, which is due to complete final study follow-up in December 2023. This randomised trial, undertaken in Sweden, should allow for relative effects to be determined between the two interventions. This will ultimately enable more robust data to be used to update the current model, rather than relying upon indirect comparisons with wide uncertainty. However, further issues around the true cost of MM are still present due to the lack of recent data on these costs in the UK. An audit of MM costs in DT patients in the UK would address this. Issues also persist in developing reliable subgroup analyses based on severity profiles to aid identification of whether a LVAD is (more) cost-effective for some groups of DT patients. Future trials and other studies should report results by patient severity profiles (e.g. INTERMACS classification), and if registry/observational studies then also by device implanted. Study registration This study is registered as PROSPERO CRD42020158987. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128996) and is published in full in Health Technology Assessment; Vol. 28, No. 38. See the NIHR Funding and Awards website for further award information.

Abstract Background Thoracotomy is considered one of the most painful surgical procedures and can cause debilitating chronic post-surgical pain lasting months or years postoperatively. Aggressive management of acute pain resulting from thoracotomy may reduce the likelihood of developing chronic pain. This trial compares the two most commonly used modes of acute analgesia provision at the time of thoracotomy (thoracic epidural blockade (TEB) and paravertebral blockade (PVB)) in terms of their clinical and cost-effectiveness in preventing chronic post-thoracotomy pain. Methods TOPIC 2 is a multi-centre, open-label, parallel group, superiority, randomised controlled trial, with an internal pilot investigating the use of TEB and PVB in 1026 adult (≥ 18 years old) patients undergoing thoracotomy in up to 20 thoracic centres throughout the UK. Patients (N = 1026) will be randomised in a 1:1 ratio to receive either TEB or PVB. During the first year, the trial will include an integrated QuinteT (Qualitative Research Integrated into Trials) Recruitment Intervention (QRI) with the aim of optimising recruitment and informed consent. The primary outcome is the incidence of chronic post-surgical pain at 6 months post-randomisation defined as ‘worst chest pain over the last week’ equating to a visual analogue score greater than or equal to 40 mm indicating at least a moderate level of pain. Secondary outcomes include acute pain, complications of regional analgesia and surgery, health-related quality of life, mortality and a health economic analysis. Discussion Both TEB and PVB have been demonstrated to be effective in the prevention of acute pain following thoracotomy and nationally practice is divided. Identification of which mode of analgesia is both clinically and cost-effective in preventing chronic post-thoracotomy pain could ameliorate the debilitating effects of chronic pain, improving health-related quality of life, facilitating return to work and caring responsibilities and resulting in a cost saving to the NHS. Trial registration NCT03677856 [ClinicalTrials.gov] registered September 19, 2018. https://clinicaltrials.gov/ct2/show/NCT03677856 . First patient recruited 8 January 2019.

Background: Proficiency in ultrasound usage is quickly becoming an expectation in multiple residency programs: emergency medicine, obstetrics-gynecology, surgery, and internal medicine. There is a lack of affordable training devices for ultrasound training and identification of superficial fluid collections. We sought to develop a model for trainee education in ultrasound usage, identification of superficial fluid collection, aspiration, and incision & drainage (I&D). Materials & methods: Commercially available products were used to develop a novel, low-cost model for ultrasound-guided aspiration and I&D of an abscess. A latex balloon embedded in silicone gel construct simulated a superficial fluid collection when examined with an ultrasound probe and monitor. A 18-gauge needle on a 10-cc syringe were used for aspiration, and a 15-blade disposal scalpel with 0.25″ packing strip used for I&D. Results: Approximately six hours are required to generate 24 individual models of a superficial abscess. Following an initial investment, each model costs less than $1 USD to produce. Compared to commercially available models, this represents a significant savings. This model was utilized during the medical school academic year as a teaching aid for medical students to simulate ultrasound-guided identification, aspiration, and incision and drainage of a superficial abscess. Conclusions: We successfully produced an affordable, low-cost model of a superficial fluid collection for training in ultrasound usage, aspiration, and I&D. The model represents significant savings over commercially available alternatives and can be easily replicated for trainee education.

Abstract Background Bacterial vaginosis is a common and distressing condition for women. Short-term antibiotic treatment is usually clinically effective, but recurrence is common. We assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent bacterial vaginosis. Methods We undertook an open-label, multicentre, parallel group, randomised controlled trial in nineteen UK sexual health clinics and a university health centre. Women aged ≥ 16 years, with current bacterial vaginosis symptoms and a preceding history of bacterial vaginosis, were randomised in a 1:1 ratio using a web-based minimisation algorithm, to 400 mg twice daily oral metronidazole tablets or 5 ml once daily intravaginal lactic acid gel, for 7 days. Masking of participants was not possible. The primary outcome was participant-reported resolution of symptoms within 2 weeks. Secondary outcomes included time to first recurrence of symptoms, number of recurrences and repeat treatments over 6 months and side effects. Results Five hundred and eighteen participants were randomised before the trial was advised to stop recruiting by the Data Monitoring Committee. Primary outcome data were available for 79% (204/259) allocated to metronidazole and 79% (205/259) allocated to lactic acid gel. Resolution of bacterial vaginosis symptoms within 2 weeks was reported in 70% (143/204) receiving metronidazole versus 47% (97/205) receiving lactic acid gel (adjusted risk difference -23·2%; 95% confidence interval -32.3 to -14·0%). In those participants who had initial resolution and for whom 6 month data were available, 51 of 72 (71%) women in the metronidazole group and 32 of 46 women (70%) in the lactic acid gel group had recurrence of symptoms, with median times to first recurrence of 92 and 126 days, respectively. Reported side effects were more common following metronidazole than lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). Conclusions Metronidazole was more effective than lactic acid gel for short-term resolution of bacterial vaginosis symptoms, but recurrence is common following both treatments. Lactic acid gel was associated with fewer reported side effects. Trial registration ISRCTN14161293 , prospectively registered on 18th September 2017.

Abstract Background Diarrhoeal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. We describe a protocol for a cluster randomised trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition. Methods We describe a mixed-methods, parallel group, two-arm, superiority cluster randomised controlled trial with baseline measures. One hundred twenty clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. The community intervention will be focussed around an ideal mother concept involving all community members during campaign days with dramatic arts and pledging, and follow-up home visits. Participants will be mother–child dyads (27 per cluster period) with children aged 6 to 36 months. Data collection will comprise a day of observation and interviews with each participating mother–child pair and will take place at baseline and 4 and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary-food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutrition, child anthropometry, and development scores. A additional structural equation analysis will be conducted to examine the causal relationships between the different outcomes. Qualitative and health economic analyses including process evaluation will be done. Conclusions The trial will provide evidence on the effectiveness of community-based behavioural change interventions designed to reduce the burden of diarrhoeal disease in the under-fives and how effectiveness varies across different contexts. Trial registration ISRCTN14390796. Registration date December 13, 2021

Abstract Background Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women of reproductive age, and it is estimated that up to a third of women will experience it at some point in their lives. BV produces an offensive vaginal odour and it is associated with serious sequelae. The most frequently prescribed treatment for BV in the UK is 7-day oral metronidazole but recurrences are common following it. Dequalinium chloride (Fluomizin©) is an anti-infective, antiseptic agent administered as a vaginal tablet. Small studies have shown this to be an effective alternative to antibiotics as a BV treatment. This trial aims to investigate whether dequalinium is as effective as current antibiotic treatments for the treatment of BV 1 month after treatment start. Methods DEVA is a multi-centre, randomised, open-label, parallel group, non-inferiority trial of dequalinium chloride versus usual care antibiotics for the treatment of BV. Recruitment will take place in 15 GUM clinics in the UK with Leeds Sexual Health also managing remote recruitment via the trial website. Women will be randomised 1:1 to receive dequalinium or usual care antibiotics. The primary outcome is to determine if the proportion of women reporting resolution of BV symptoms 4 weeks after treatment (without the need for additional treatment) is not worse in women treated with dequalinium chloride compared to usual care antibiotics. Questionnaire follow-up will take place 4 and 12 weeks after starting treatment, and remotely recruited patients will also provide a week 4 BV vaginal smear. The sample size is 904. Discussion This trial will provide high-quality evidence on the use of dequalinium chloride as a BV treatment, which could result in patients reducing the number of antibiotics they take. Trial registration ISRCTN ISRCTN91800263. Prospectively registered on 20 January 2020.

Abstract Objectives Some pregnant women are not ready or do not want to quit smoking completely, and currently there is no support provided for these women in the UK. Offering help to reduce smoking could reduce the health risks associated with smoking and increase the limited reach of the NHS Stop Smoking Services (SSS) for pregnant women. This study aimed to design and evaluate a hypothetical intervention aimed at pregnant women who are not yet ready or do not want to quit smoking entirely. Methods A hypothetical intervention, the Reduced Smoking During Pregnancy (RSDP) intervention, was conceptualised based on the best available evidence. The intervention was evaluated, using a decision-analytic model developed for SDP interventions. Two different scenarios, a base-case and a cautious-case were developed, and a cost-utility analysis and return on investment analysis were conducted. The uncertainty around the estimates was assessed, using deterministic and probabilistic sensitivity analyses. Results The RSDP intervention could prevent the loss of 13 foetuses and generate 43 quitters 1 year after delivery per 1000 women. In the lifetime analysis, the intervention was cost-effective in both scenarios, with an incremental cost of £363 (95% CI £29 to £672) and 0.44 (95% CI 0.32 to 0.53) QALYs gained in the base-case. Conclusions The study found that the hypothetical reduction intervention would produce significant health benefits, reduce smoking and be cost-effective. Offering pregnant smokers help to reduce smoking could reduce health inequalities, widen the reach of SSS and improve health. This economic evaluation of a novel, intensive intervention could inform the piloting of such interventions.

We identified and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitro comparisons of the receptor-binding protein with prototypic HeV support that the human monoclonal antibody m102.4 used for postexposure prophylaxis and current equine vaccine will be effective against this variant. An updated quantitative PCR developed for routine surveillance resulted in subsequent case detection. Genetic sequence consistency with virus detected in grey-headed flying foxes suggests the variant circulates at least among this species. Studies are needed to determine infection kinetics, pathogenicity, reservoir-species associations, viral-host coevolution, and spillover dynamics for this virus. Surveillance and biosecurity practices should be updated to acknowledge HeV spillover risk across all regions frequented by flying foxes.

ObjectiveTo provide a summary of the economic and methodological evidence on capturing antimicrobial resistance (AMR) associated costs for curable sexually transmitted infections (STIs). To explore approaches for incorporating the cost of AMR within an economic model evaluating different treatment strategies for gonorrhoea, as a case study.MethodsA systematic review protocol was registered on PROSPERO (CRD42022298232). MEDLINE, EMBASE, CINAHL, Cochrane Library, International Health Technology Assessment Database, National Health Service Economic Evaluation Database, and EconLit databases were searched up to August 2022. Included studies were analysed, quality assessed and findings synthesised narratively. Additionally, an economic evaluation which incorporated AMR was undertaken using a decision tree model and primary data from a randomised clinical trial comparing gentamicin therapy with standard treatment (ceftriaxone). AMR was incorporated into the evaluation using three approaches-integrating the additional costs of treating resistant infections, conducting a threshold analysis, and accounting for the societal cost of resistance for the antibiotic consumed.ResultsTwelve studies were included in the systematic review with the majority focussed on AMR in gonorrhoea. The cost of ceftriaxone resistant gonorrhoea and the cost of ceftriaxone sparing strategies were significant and related to the direct medical costs from persistent gonorrhoea infections, sequelae of untreated infections, gonorrhoea attributable-HIV transmission and AMR testing. However, AMR definition, the collection and incorporation of AMR associated costs, and the perspectives adopted were inconsistent or limited. Using the review findings, different approaches were explored for incorporating AMR into an economic evaluation comparing gentamicin to ceftriaxone for gonorrhoea treatment. Although the initial analysis showed that ceftriaxone was the cheaper treatment, gentamicin became cost-neutral if the clinical efficacy of ceftriaxone reduced from 98% to 92%. By incorporating societal costs of antibiotic use, gentamicin became cost-neutral if the cost of ceftriaxone treatment increased from £4.60 to £8.44 per patient.ConclusionsInclusion of AMR into economic evaluations may substantially influence estimates of cost-effectiveness and affect subsequent treatment recommendations for gonorrhoea and other STIs. However, robust data on the cost of AMR and a standardised approach for conducting economic evaluations for STI treatment which incorporate AMR are lacking, and requires further developmental research.

AimTo explore the characteristics of online STI test users, and assess the frequency and factors associated with subsequent service use following a negative online STI test screen in individuals without symptoms.MethodsOne-year retrospective study of online and clinic STI testing within a large integrated sexual health service (Umbrella in Birmingham and Solihull, England) between January and December 2017. A multivariable analysis of sociodemographic and behavioural characteristics of patients was conducted. Sexual health clinic appointments occurring within 90 days of a negative STI test, in asymptomatic individuals who tested either online or in clinic were determined. Factors associated with online STI testing and subsequent clinic use were determined using generalized estimating equations and reported as odds ratios (OR) with corresponding 95% confidence intervals (CI).Results31 847 online STI test requests and 40 059 clinic attendances incorporating STI testing were included. 79% (25020/31846) of online STI test users and 49% (19672/40059) of clinic STI test takers were asymptomatic. Online STI testing was less utilised (pConclusionsSubsequent clinic attendance amongst online STI test service users with negative test results was infrequent, suggesting that their needs were being met without placing an additional burden on clinic based services. However, unequal use of online services by different patient groups suggests that optimised messaging and the development of online services in partnership with users are required to improve uptake.

BackgroundThe health, social, and economic costs of sexually transmitted infections (STIs) represent a major public health concern. Young people are considered one of the groups most at risk for acquiring and transmitting STIs. Correct and consistent condom use has been shown to be the most effective method for reducing STIs; however, condoms are often not used properly. Evidence shows that brief behavior change interventions that focus on skills, communication, and motivation to acquire safe sex practices should be adopted into routine care to reduce STIs. Funding for sexual health services in England has declined dramatically, so novel ways of reducing clinic attendance are being sought. The home-based intervention strategy (HIS-UK) to promote condom use among young men has shown promise in feasibility and pilot studies by demonstrating high acceptability of the intervention in participant and health professional feedback, including aiding men to find condoms they like and feel more confident when using condoms. ObjectiveThe aim of this study is to determine the effectiveness and cost-effectiveness of HIS-UK when compared to usual condom distribution care among young men. MethodsThe 3 trial arms consisting of “e-HIS” (HIS-UK delivered digitally), “ProHIS” (HIS-UK delivered face-to-face), and control condition (usual National Health Service [NHS] care) will be compared against the following 3 primary outcomes: the extent to which correct and consistent condom use is increased; improvement of condom use experiences (pleasure as well as fit and feel); and decrease in chlamydia test positivity. Eligibility criteria include men aged 16-25 years at risk of STIs through reporting of condom use errors (ie, breakage or slippage) or condomless penile-vaginal or penile-anal intercourse with casual or new sexual partners during the previous 3 months. Prospective participants will be recruited through targeted advertisements and an opportunistic direct approach at selected sexual health and genitourinary medicine services and university-associated health centers and general practitioner practices. Community and educational establishments will be used to further advertise the study and signpost men to recruitment sites. Participants will be randomly allocated to 1 of 3 trial arms. A repeated measures design will assess the parallel arms with baseline and 12 monthly follow-up questionnaires after intervention and 3 chlamydia screening points (baseline, 6, and 12 months). ResultsRecruitment commenced in March 2020. Due to the COVID-19 pandemic, the study was halted and has since reopened for recruitment in Summer 2021. A 30-month recruitment period is planned. ConclusionsIf effective and cost-effective, HIS-UK can be scaled up into routine NHS usual care to reduce both STI transmission in young people and pressure on NHS resources. This intervention may further encourage sexual health services to adopt digital technologies, allowing for them to become more widely available to young people while decreasing health inequalities and fear of stigmatization. Trial RegistrationISRCTN Registry ISRCTN11400820; https://www.isrctn.com/ISRCTN11400820

Abstract Background Smoking during pregnancy (SDP) and the postpartum period has serious health outcomes for the mother and infant. Although some systematic reviews have shown the impact of maternal SDP on particular conditions, a systematic review examining the overall health outcomes has not been published. Hence, this paper aimed to conduct an umbrella review on this issue. Methods A systematic review of systematic reviews (umbrella review) was conducted according to a protocol submitted to PROSPERO ( CRD42018086350 ). CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science, CRD Database and HMIC databases were searched to include all studies published in English by 31 December 2017, except those focusing exclusively on low-income countries. Two researchers conducted the study selection and quality assessment independently. Results The review included 64 studies analysing the relationship between maternal SDP and 46 health conditions. The highest increase in risks was found for sudden infant death syndrome, asthma, stillbirth, low birth weight and obesity amongst infants. The impact of SDP was associated with the number of cigarettes consumed. According to the causal link analysis, five mother-related and ten infant-related conditions had a causal link with SDP. In addition, some studies reported protective impacts of SDP on pre-eclampsia, hyperemesis gravidarum and skin defects on infants. The review identified important gaps in the literature regarding the dose-response association, exposure window, postnatal smoking. Conclusions The review shows that maternal SDP is not only associated with short-term health conditions (e.g. preterm birth, oral clefts) but also some which can have life-long detrimental impacts (e.g. obesity, intellectual impairment). Implications This umbrella review provides a comprehensive analysis of the overall health impacts of SDP. The study findings indicate that while estimating health and cost outcomes of SDP, long-term health impacts should be considered as well as short-term effects since studies not including the long-term outcomes would underestimate the magnitude of the issue. Also, interventions for pregnant women who smoke should consider the impact of reducing smoking due to health benefits on mothers and infants, and not solely cessation.

Abstract Background Effective management of patients with chronic kidney disease (CKD) relies on timely detection of clinical deterioration towards end stage kidney failure. We aimed to design an electronic Patient-Reported Outcome Measure (ePROM) system, which would allow patients with advanced CKD (pre-dialysis) to: (i) remotely self-report their symptoms using a simple and secure online platform; (ii) share the data with the clinical team in real-time via the electronic patient record to help optimise care. We adopted a staged development process which included: a systematic review of PROMs used in CKD; formation of a co-design team; prototype system design/development, user acceptance testing and refinement; finalisation of the system for testing in a pilot/feasibility trial. Results A co-design team was convened, including patients with lived experience of CKD; clinical team members; IT/Informatics experts; academics; and Birmingham Clinical Trials Unit representatives. A prototype system was developed and iterative changes made before finalisation during a series of operational meetings. The system allows patients to remotely self-report their symptoms; provides tailored self-management advice; allows monitoring of real-time patient ePROM data; sends automated notifications to the patient/clinical team in the advent of a severe symptom report; and incorporates longitudinal ePROM symptom data into the electronic patient record. Feasibility of the system will be evaluated as part of the National Institute for Health Research funded RePROM (Renal electronic Patient-Reported Outcome Measure) pilot trial (ISRCTN12669006). Conclusions Routine ePROM collection with real-time feedback has the potential to improve outcomes and reduce health service costs. We have successfully developed a trial-ready ePROM system for advanced CKD, the feasibility of which is currently being explored in a pilot trial. Assuming feasibility is demonstrated, formal evaluation of efficacy will take place in a future multi-centre randomised controlled trial.

Background: Bacterial vaginosis is a common and distressing condition associated with serious comorbidities. Antibiotic treatment is usually clinically effective in the short term, but recurrence is common and side effects can occur. Objectives: The objective is to assess whether or not intravaginal lactic acid gel is clinically effective and cost-effective for treating recurrent bacterial vaginosis compared with oral metronidazole (Flagyl, Sanofi). Design: This was an open-label, multicentre, parallel-arm, randomised (1 : 1) controlled trial. Setting: This took place in one general practice and 19 sexual health centres in the UK. Participants: Women aged ≥ 16 years with bacterial vaginosis symptoms and one or more episode(s) within the past 2 years took part. Interventions: The interventions were 5 ml of intravaginal lactic acid gel taken once daily for 7 days (intervention) or 400-mg oral metronidazole tablets taken twice daily for 7 days (control). Main outcome measures: The primary outcome was the resolution of bacterial vaginosis symptoms 14 days after randomisation. The secondary outcomes were time to first recurrence of symptoms; number of recurrences and treatment courses over 6 months; microbiological resolution on microscopy of vaginal smears at week 2; time to resolution of symptoms; tolerability, adherence and acceptability of the treatment; prevalence of concurrent sexually transmitted infections; quality of life; and cost-effectiveness. Results: Recruitment stopped prior to reaching the target of 1900 participants on recommendation from the Data Monitoring Committee and Trial Steering Committee after a planned review of the results indicated that the research question had been answered. Overall, 518 participants were randomised and primary outcome data were available for 409 participants (79%; 204 in the metronidazole arm, 205 in the lactic acid gel arm). Participant-reported symptom resolution at week 2 was higher with metronidazole (143/204; 70%) than with lactic acid gel (97/205; 47%) (adjusted risk difference –23.2%, 95% confidence interval –32.3% to –14.0%). Recurrence in 6 months in a subset of participants who had initial resolution and were available for follow-up was similar across arms (metronidazole arm: 51/72, 71%; lactic acid gel arm: 32/46, 70%). A higher incidence of some side effects was reported with metronidazole than with lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). At week 2, the average cost per participant with resolved symptoms was £86.94 (metronidazole), compared with £147.00 (lactic acid gel). Some participants preferred using lactic acid gel even if they perceived it to be less effective than metronidazole. Limitations: Loss to follow-up for collection of the primary outcome data was 21% and was similar in both arms. There is a risk of bias owing to missing outcome data at 3 and 6 months post treatment. Conclusions: A higher initial response was seen with metronidazole than with lactic acid gel, but subsequent treatment failure was common with both. Lactic acid gel was less cost-effective than metronidazole. In general, women disliked taking repeated courses of metronidazole and preferred lactic acid gel, even when they were aware that it was less likely to provide symptom resolution. In the absence of effective curative therapy, further evaluation of non-antibiotic treatments to control the symptoms of recurrent bacterial vaginosis is required to improve quality of life for these patients. Further microbiological analysis of vaginal samples would be useful to identify additional factors affecting response to treatment. Trial registration: Current Controlled Trials ISRCTN14161293. 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. 26, No. 2. See the NIHR Journals Library website for further project information.

Abstract Background Bacterial vaginosis (BV) affects 30–50% of women at some time in their lives and is an embarrassing and distressing condition which can be associated with potentially serious comorbidities. Current antibiotic treatments such as metronidazole are effective but can result in side effects, and recurrence is common. This trial aims to investigate whether lactic acid gel is clinically effective and cost effective in the treatment of recurrent BV compared with metronidazole. Methods VITA is an open-label, multicentre, parallel group randomised controlled trial for women with a clinical diagnosis of BV and at least one previous BV episode in the past 2 years. Participants will be randomised 1:1 to intravaginal lactic acid gel 5 ml once daily for 7 days or oral metronidazole tablets 400 mg twice daily for 7 days. All participants will be followed up for 6 months to assess health status and healthcare costs. A subgroup will be interviewed to further explore adherence, tolerability and acceptability of treatment. The estimated sample size is 1900 participants to detect a 6% absolute increase in response rate to 86% in those receiving lactic acid gel. The primary outcome is participant-reported resolution of BV at Week 2. Discussion Results from this trial will help inform UK treatment guidelines for BV and may provide an alternative effective treatment for recurrent episodes of this condition which avoids repeated exposure to antibiotics. Trial registration ISRCTN, ISRCTN14161293. Registered on 8 September 2017.

BackgroundThe Gambia has high rates of under-5 mortality from diarrhoea and pneumonia, peaking during complementary-feeding age. Community-based interventions may reduce complementary-food contamination and disease rates.Methods and findingsA public health intervention using critical control points and motivational drivers, delivered February-April 2015 in The Gambia, was evaluated in a cluster randomised controlled trial at 6- and 32-month follow-up in September-October 2015 and October-December 2017, respectively. After consent for trial participation and baseline data were collected, 30 villages (clusters) were randomly assigned to intervention or control, stratified by population size and geography. The intervention included a community-wide campaign on days 1, 2, 17, and 25, a reminder visit at 5 months, plus informal community-volunteer home visits. It promoted 5 key complementary-food and 1 key drinking-water safety and hygiene behaviours through performing arts, public meetings, and certifications delivered by a team from local health and village structures to all villagers who attended the activities, to which mothers of 6- to 24-month-old children were specifically invited. Control villages received a 1-day campaign on domestic-garden water use. The background characteristics of mother and clusters (villages) were balanced between the trial arms. Outcomes were measured at 6 and 32 months in a random sample of 21-26 mothers per cluster. There were no intervention or research team visits to villages between 6 and 32 months. The primary outcome was a composite outcome of the number of times key complementary-food behaviours were observed as a proportion of the number of opportunities to perform the behaviours during the observation period at 6 months. Secondary outcomes included the rate of each recommended behaviour; microbiological growth from complementary food and drinking water (6 months only); and reported acute respiratory infections, diarrhoea, and diarrhoea hospitalisation. Analysis was by intention-to-treat analysis adjusted by clustering. (Registration: PACTR201410000859336). We found that 394/571 (69%) of mothers with complementary-feeding children in the intervention villages were actively involved in the campaign. No villages withdrew, and there were no changes in the implementation of the intervention. The intervention improved behaviour adoption significantly. For the primary outcome, the rate was 662/4,351(incidence rate [IR] = 0.15) in control villages versus 2,861/4,378 (IR = 0.65) in intervention villages (adjusted incidence rate ratio [aIRR] = 4.44, 95% CI 3.62-5.44, p < 0.001), and at 32 months the aIRR was 1.17 (95% CI 1.07-1.29, p = 0.001). Secondary health outcomes also improved with the intervention: (1) mother-reported diarrhoea at 6 months, with adjusted relative risk (aRR) = 0.39 (95% CI 0.32-0.48, p < 0.001), and at 32 months, with aRR = 0.68 (95% CI 0.48-0.96, p = 0.027); (2) mother-reported diarrhoea hospitalisation at 6 months, with aRR = 0.35 (95% CI 0.19-0.66, p = 0.001), and at 32 months, with aRR = 0.38 (95% CI 0.18-0.80, p = 0.011); and (3) mother-reported acute respiratory tract infections at 6 months, with aRR = 0.67 (95% CI 0.53-0.86, p = 0.001), though at 32 months improvement was not significant (p = 0.200). No adverse events were reported. The main limitations were that only medium to small rural villages were involved. Obtaining laboratory cultures from food at 32 months was not possible, and no stool microorganisms were investigated.ConclusionsWe found that low-cost and culturally embedded behaviour change interventions were acceptable to communities and led to short- and long-term improvements in complementary-food safety and hygiene practices, and reported diarrhoea and acute respiratory tract infections.Trial registrationThe trial was registered on the 17th October 2014 with the Pan African Clinical Trial Registry in South Africa with number (PACTR201410000859336) and 32-month follow-up as an amendment to the trial.

Abstract Background Internationally, tobacco smoking is a leading cause of mortality, morbidity and health inequality. In England, despite increasing awareness about importance of public health interventions to reduce smoking, about 10% of pregnant women are known to be smokers at the time of delivery. There are many systematic reviews investigating the impact of maternal smoking during pregnancy on particular health conditions. Hence, this overview of systematic reviews, which aims to include all health conditions for mother and infant caused by smoking during pregnancy, is timely. Methods CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science, CRD Database (includes DARE, NHSEED and HTA) and HMIC databases will be searched for systematic reviews investigating the effects of smoking during pregnancy. Only reviews written in English and published by 31/12/17 will be included. Studies focussed on low-income countries will be excluded. Study selection and quality assessment will be completed by two reviewers independently. To assess the quality of included studies, the Centre for Reviews and Dissemination checklist for systematic reviews will be utilised. Discussion Existing systematic reviews focus on the impact of smoking during pregnancy on a specific health condition. This review aims to analyse current evidence on the overall health outcomes associated with smoking whilst pregnant by providing an overview of evidence from systematic reviews. Systematic review registration PROSPERO CRD42018086350.

Abstract Background Community-based programmes for children with excess weight are widely available, but few have been developed to meet the needs of culturally diverse populations. We adapted an existing children’s weight management programme, focusing on Pakistani and Bangladeshi communities. We report the evaluation of this programme to assess feasibility of programme delivery, acceptability of the programme to participants from diverse communities, and feasibility of methods to inform a future trial. Methods A cluster-randomised feasibility trial was undertaken in a large UK city. Children’s weight management programmes (n = 24) were randomised to be delivered as the adapted or the standard programme (2:1 ratio). Routine data on participant attendance (n = 243) at the sessions were used to estimate the proportion of families completing the adapted and standard programmes (to indicate programme acceptability). Families planning to attend the programmes were recruited to participate in the feasibility study (n = 92). Outcome data were collected from children and parents at baseline, end of programme, and 6 months post-programme. A subsample (n = 24) of those attending the adapted programme participated in interviews to gain their views of the content and delivery and assess programme acceptability. Feasibility of programme delivery was assessed through observation and consultation with facilitators, and data on costs were collected. Results The proportion of Pakistani and Bangladeshi families and families of all ethnicities completing the adapted programme was similar: 78.8% (95% CI 64.8–88.2%) and 76.3% (95% CI 67.0–83.6%) respectively. OR for completion of adapted vs. standard programme was 2.40 (95% CI 1.32–4.34, p = 0.004). The programme was feasible to deliver with some refinements, and participant interview data showed that the programme was well received. Study participant recruitment was successful, but attrition was high (35% at 6 months). Data collection was mostly feasible, but participant burden was high. Data collection on cost of programme delivery was feasible, but costs to families were more challenging to capture. Conclusions This culturally adapted programme was feasible to deliver and highly acceptable to participants, with increased completion rates compared with the standard programme. Consideration should be given to a future trial to evaluate its clinical and cost-effectiveness. Trial registration ISRCTN81798055, registered: 13/05/2014

Agriculture in California contributes 8% of the state's greenhouse gas (GHG) emissions. To inform the state's policy and program strategy to meet climate targets, we review recent research on practices that can reduce emissions, sequester carbon and provide other co-benefits to producers and the environment across agriculture and rangeland systems. Importantly, the research reviewed here was conducted in California and addresses practices in our specific agricultural, socioeconomic and biophysical environment. Farmland conversion and the dairy and intensive livestock sector are the largest contributors to GHG emissions and offer the greatest opportunities for avoided emissions. We also identify a range of other opportunities including soil and nutrient management, integrated and diversified farming systems, rangeland management, and biomass-based energy generation. Additional research to replicate and quantify the emissions reduction or carbon sequestration potential of these practices will strengthen the evidence base for California climate policy.

Background: Excess weight in children is a continuing health issue. Community-based children’s weight management programmes have had some effect in promoting weight loss. Families from minority ethnic communities are less likely to complete these programmes but, to date, no programmes have been culturally adapted to address this. Objectives: We aimed to (1) culturally adapt an existing weight management programme for children aged 4–11 years and their families to make it more suited to Pakistani and Bangladeshi communities but inclusive of all families and (2) evaluate the adapted programme to assess its feasibility and acceptability, as well as the feasibility of methods, for a future full-scale trial. Design: In phase I, a cultural adaptation of a programme that was informed by formative research and guided by two theoretical frameworks was undertaken and in phase II this adapted programme was delivered in a cluster-randomised feasibility study (for which the clusters were the standard and adapted children’s weight management programmes). Setting: Birmingham: a large, ethnically diverse UK city. Participants: In phase I, Pakistani and Bangladeshi parents of children with excess weight, and, in phase II, children aged 4–11 years who have excess weight and their families. Interventions: A culturally adapted children’s weight management programme, comprising six sessions, which was delivered to children and parents, targeting diet and physical activity and incorporating behaviour change techniques, was developed in phase I and delivered in the intervention arm to 16 groups in phase II. The eight groups in the comparator arm received the standard (unadapted) children’s weight management programme. Main outcome measures: The primary outcome was the proportion of Pakistani and Bangladeshi families completing (attending ≥ 60% of) the adapted programme. Secondary outcomes included the proportion of all families completing the adapted programme, the feasibility of delivery of the programme, the programme’s acceptability to participants, the feasibility of trial processes and the feasibility of collection of outcome and cost data. Results: The proportion of Pakistani and Bangladeshi families and all families completing the adapted programme was 78.8% [95% confidence interval (CI) 64.8% to 88.2%] and 76.3% (95% CI 67.0% to 83.6%), respectively. The programme was feasible to deliver with some refinements and was well received. Ninety-two families participated in outcome data collection. Data collection was mostly feasible, but participant burden was high. Data collection on the cost of programme delivery was feasible, but costs to families were more challenging to capture. There was high attrition over the 6-month follow-up period (35%) and differential attrition in the two study arms (29% and 52% in the intervention and comparator arms, respectively). Limitations: The study was not designed to address the issue of low participant uptake of children’s weight management programmes. The design of a future trial may include individual randomisation and a ‘minimal intervention’ arm, the acceptability of which has not been evaluated in this study. Conclusions: The theoretically informed, culturally adapted children’s weight management programme was highly acceptable to children and families of all ethnicities. Consideration should be given to a future trial to evaluate clinical effectiveness and cost-effectiveness of the adapted programme, but the design of a future trial would need to address the logistics of data collection, participant burden and study attrition. Trial registration: Current Controlled Trials ISRCTN81798055. 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. 23, No. 33. See the NIHR Journals Library website for further project information. Kate Jolly is part-funded by the Collaboration for Leadership in Applied Health Research and Care West Midlands.

Background: Gonorrhoea is a common sexually transmitted infection that can cause pain and discomfort, affect fertility in women and lead to epididymo-orchitis in men. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance reducing its effectiveness. Gentamicin is a potential alternative treatment requiring further evaluation. Objectives: To assess the clinical effectiveness and cost-effectiveness of gentamicin as an alternative treatment to ceftriaxone in the treatment of gonorrhoea. Design: A multicentre, parallel-group, blinded, non-inferiority randomised controlled trial. Setting: Fourteen sexual health clinics in England. Participants: Adults aged 16–70 years with a diagnosis of uncomplicated, untreated genital, pharyngeal or rectal gonorrhoea based on a positive Gram-stained smear on microscopy or a positive nucleic acid amplification test (NAAT). Randomisation and blinding: Participants were randomised using a secure web-based system, stratified by clinic. Participants, investigators and research staff assessing participants were blinded to treatment allocation. Interventions: Allocation was to either 240 mg of gentamicin (intervention) or 500 mg of ceftriaxone (standard treatment), both administered as a single intramuscular injection. All participants also received 1 g of oral azithromycin. Main outcome measure: The primary outcome measure was clearance of Neisseria gonorrhoeae at all infected sites, confirmed by a negative Aptima Combo 2® (Hologic Inc., Marlborough, MA, USA) NAAT, at 2 weeks post treatment. Results: We randomised 720 participants, of whom 81% were men. There were 358 participants in the gentamicin group and 362 in the ceftriaxone group; 292 (82%) and 306 (85%) participants, respectively, were included in the primary analysis. Non-inferiority of gentamicin to ceftriaxone could not be demonstrated [adjusted risk difference for microbiological clearance –6.4%, 95% confidence interval (CI) –10.4% to –2.4%]. Clearance of genital infection was similar in the two groups, at 94% in the gentamicin group and 98% in the ceftriaxone group, but clearance of pharyngeal infection and rectal infection was lower in the gentamicin group (80% vs. 96% and 90% vs. 98%, respectively). Reported pain at the injection site was higher for gentamicin than for ceftriaxone. The side-effect profiles were comparable between the groups. Only one serious adverse event was reported and this was deemed not to be related to the trial medication. The economic analysis found that treatment with gentamicin is not cost neutral compared with standard care, with average patient treatment costs higher for those allocated to gentamicin (£13.90, 95% CI £2.47 to £37.34) than to ceftriaxone (£6.72, 95% CI £1.36 to £17.84). Limitations: Loss to follow-up was 17% but was similar in both treatment arms. Twelve per cent of participants had a negative NAAT for gonorrhoea at their baseline visit but this was balanced between treatment groups and unlikely to have biased the trial results. Conclusions: The trial was unable to demonstrate non-inferiority of gentamicin compared with ceftriaxone in the clearance of gonorrhoea at all infected sites. Clearance at pharyngeal and rectal sites was lower for participants allocated to gentamicin than for those allocated to ceftriaxone, but was similar for genital sites in both groups. Gentamicin was associated with more severe injection site pain. However, both gentamicin and ceftriaxone appeared to be well tolerated. Future work: Exploration of the genetic determinants of antibiotic resistance in N. gonorrhoeae will help to identify accurate markers of decreased susceptibility. Greater understanding of the immune response to infection can assist gonococcal vaccine development. Trial registration: Current Controlled Trials ISRCTN51783227. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 20. See the NIHR Journals Library website for further project information.

Background: Caesarean section is associated with blood loss and maternal morbidity. Excessive blood loss requires transfusion of donor (allogeneic) blood, which is a finite resource. Cell salvage returns blood lost during surgery to the mother. It may avoid the need for donor blood transfusion, but reliable evidence of its effects is lacking. Objectives: To determine if routine use of cell salvage during caesarean section in mothers at risk of haemorrhage reduces the rates of blood transfusion and postpartum maternal morbidity, and is cost-effective, in comparison with standard practice without routine salvage use. Design: Individually randomised controlled, multicentre trial with cost-effectiveness analysis. Treatment was not blinded. Setting: A total of 26 UK obstetric units. Participants: Out of 3054 women recruited between June 2013 and April 2016, we randomly assigned 3028 women at risk of haemorrhage to cell salvage or routine care. Randomisation was stratified using random permuted blocks of variable sizes. Of these, 1672 had emergency and 1356 had elective caesareans. We excluded women for whom cell salvage or donor blood transfusion was contraindicated. Interventions: Cell salvage (intervention) versus routine care without salvage (control). In the intervention group, salvage was set up in 95.6% of the women and, of these, 50.8% had salvaged blood returned. In the control group, 3.9% had salvage deployed. Main outcome measures: Primary – donor blood transfusion. Secondary – units of donor blood transfused, time to mobilisation, length of hospitalisation, mean fall in haemoglobin, fetomaternal haemorrhage (FMH) measured by Kleihauer–Betke test, and maternal fatigue. Analyses were adjusted for stratification factors and other factors that were believed to be prognostic a priori. Cost-effectiveness outcomes – costs of resources and service provision taking the UK NHS perspective. Results: We analysed 1498 and 1492 participants in the intervention and control groups, respectively. Overall, the transfusion rate was 2.5% in the intervention group and 3.5% in the control group [adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42 to 1.01; p = 0.056]. In a planned subgroup analysis, the transfusion rate was 3.0% in the intervention group and 4.6% in the control group among emergency caesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 1.8% in the intervention group and 2.2% in the control group among elective caesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46, suggesting that the difference in effect between subgroups was not statistically significant). Secondary outcomes did not differ between groups, except for FMH, which was higher under salvage in rhesus D (RhD)-negative women with RhD-positive babies (25.6% vs. 10.5%, adjusted OR 5.63, 95% CI 1.43 to 22.14; p = 0.013). No case of amniotic fluid embolism was observed. The additional cost of routine cell salvage during caesarean was estimated, on average, at £8110 per donor blood transfusion avoided. Conclusions: The modest evidence for an effect of routine use of cell salvage during caesarean section on rates of donor blood transfusion was associated with increased FMH, which emphasises the need for adherence to guidance on anti-D prophylaxis. We are unable to comment on long-term antibody sensitisation effects. Based on the findings of this trial, cell salvage is unlikely to be considered cost-effective. Future work: Research into risk of alloimmunisation among women exposed to cell salvage is needed. Trial registration: Current Controlled Trials ISRCTN66118656. 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. 22, No. 2. See the NIHR Journals Library website for further project information.

Background: Diet- and physical activity-based interventions in pregnancy have the potential to alter maternal and child outcomes. Objectives: To assess whether or not the effects of diet and lifestyle interventions vary in subgroups of women, based on maternal body mass index (BMI), age, parity, Caucasian ethnicity and underlying medical condition(s), by undertaking an individual patient data (IPD) meta-analysis. We also evaluated the association of gestational weight gain (GWG) with adverse pregnancy outcomes and assessed the cost-effectiveness of the interventions. Data sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment database were searched from October 2013 to March 2015 (to update a previous search). Review methods: Researchers from the International Weight Management in Pregnancy Collaborative Network shared the primary data. For each intervention type and outcome, we performed a two-step IPD random-effects meta-analysis, for all women (except underweight) combined and for each subgroup of interest, to obtain summary estimates of effects and 95% confidence intervals (CIs), and synthesised the differences in effects between subgroups. In the first stage, we fitted a linear regression adjusted for baseline (for continuous outcomes) or a logistic regression model (for binary outcomes) in each study separately; estimates were combined across studies using random-effects meta-analysis models. We quantified the relationship between weight gain and complications, and undertook a decision-analytic model-based economic evaluation to assess the cost-effectiveness of the interventions. Results: Diet and lifestyle interventions reduced GWG by an average of 0.70 kg (95% CI –0.92 to –0.48 kg; 33 studies, 9320 women). The effects on composite maternal outcome [summary odds ratio (OR) 0.90, 95% CI 0.79 to 1.03; 24 studies, 8852 women] and composite fetal/neonatal outcome (summary OR 0.94, 95% CI 0.83 to 1.08; 18 studies, 7981 women) were not significant. The effect did not vary with baseline BMI, age, ethnicity, parity or underlying medical conditions for GWG, and composite maternal and fetal outcomes. Lifestyle interventions reduce Caesarean sections (OR 0.91, 95% CI 0.83 to 0.99), but not other individual maternal outcomes such as gestational diabetes mellitus (OR 0.89, 95% CI 0.72 to 1.10), pre-eclampsia or pregnancy-induced hypertension (OR 0.95, 95% CI 0.78 to 1.16) and preterm birth (OR 0.94, 95% CI 0.78 to 1.13). There was no significant effect on fetal outcomes. The interventions were not cost-effective. GWG, including adherence to the Institute of Medicine-recommended targets, was not associated with a reduction in complications. Predictors of GWG were maternal age (summary estimate –0.10 kg, 95% CI –0.14 to –0.06 kg) and multiparity (summary estimate –0.73 kg, 95% CI –1.24 to –0.23 kg). Limitations: The findings were limited by the lack of standardisation in the components of intervention, residual heterogeneity in effects across studies for most analyses and the unavailability of IPD in some studies. Conclusion: Diet and lifestyle interventions in pregnancy are clinically effective in reducing GWG irrespective of risk factors, with no effects on composite maternal and fetal outcomes. Future work: The differential effects of lifestyle interventions on individual pregnancy outcomes need evaluation. Study registration: This study is registered as PROSPERO CRD42013003804. Funding: The National Institute for Health Research Health Technology Assessment programme.

Management of the vineyard floor affects soil and crop productivity, as well as runoff and sediment that leave the vineyard. In Monterey County, weed control is typically conducted in a 4-foot-wide area under the vines, while cover crops are planted in the middles between vine rows. This 5-year multidisciplinary study in a low rainfall vineyard evaluated the impact of weed control strategies (cultivation, pre-emergence and post-emergence herbicides) in the vine rows, factorially arranged with three cover-crop treatments in the middles. We studied soil compaction, moisture and runoff; vine and soil nutrition; soil microbial biomass and mycorrhizae; and grape yield and quality. The late-maturing 'Trios 102' triticale used more water during the vine growing season than the earlier maturing 'Merced' rye. Cover crops increased organic matter and microbial biomass in the middles and reduced sediment loss. Weed control treatments did not affect crop yield or soil nutritional and microbiological parameters, but cultivation increased soil compaction at 4 to 7 inches deep. Weed control strategies and cover crops must be chosen carefully to maximize benefits and minimize negative environmental impacts.

Vegetable growers have been experimenting with reduced tillage practices to increase soil organic matter, limit compaction, and reduce fuel and labor costs. We studied soil properties of different tillage practices and compared deep minimum tillage (chiseling and ripping) with shallow minimum tillage for lettuce on a farm in the Salinas Valley. We found that periodic deep minimum tillage is recommended for long-term retention of semipermanent, raised beds in lettuce production. Over a period of several years, deep minimum tillage increased lettuce yield and decreased symptoms of lettuce drop disease, as compared with shallow minimum tillage. Continuous shallow minimum tillage, despite a trend toward higher active and total organic matter in the surface layer of soil, is best used with intermittent deeper tillage to avoid disease and yield losses.

Although cover crops contribute many benefits to organic and conventional agricultural systems, they may play a significant role in the epidemiology of soil-borne diseases. A 2-year study shows that Sclerotinia minor, which causes lettuce drop disease, is a pathogen of phacelia, lana woollypod vetch and Austrian winter pea cover crops. Greenhouse and field inoculations failed to result in S. minor infections of oilseed radish, barley and fava bean cover crops. It appears these three cover crops can be safely incorporated into lettuce rotations without increasing the occurrence of lettuce drop.

The large amounts of soil nitrate that can accumulate in annual row crop production during the winter fallow period can leach during winter storms and spring irrigation. In Monterey County, 48% of the wells in the upper unconfined aquifer exceed the public health drinking water standard of 10 ppm of nitrate-N. Nonleguminous cover crops, planted during the winter fallow and incorporated in early spring using reduced tillage equipment to maintain intact beds, have been found to reduce nitrate leaching without disrupting cropping schedules.