The Arabin pessary to prevent preterm birth in women with a twin pregnancy and a short cervix: the STOPPIT 2 RCT.

BACKGROUND: Preterm birth is common in twins and accounts for significant mortality and morbidity. There are no effective preventative treatments. Some studies have suggested that, in twin pregnancy complicated by a short cervix, the Arabin pessary, which fits around the cervix and can be inserted as an outpatient procedure, reduces preterm birth and prevents neonatal morbidity. OBJECTIVE: STOPPIT 2 aimed to evaluate the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix. DESIGN: STOPPIT 2 was a pragmatic, open label, multicentre randomised controlled trial with two treatment group - the Arabin pessary plus standard care (intervention) and standard care alone (control). Participants were initially recruited into the screening phase of the study, when cervical length was measured. Women with a measured cervical length of ≤ 35 mm were then recruited into the treatment phase of the study. An economic evaluation considered cost-effectiveness and a qualitative substudy explored the experiences of participants and clinicians. SETTING: Antenatal clinics in the UK and elsewhere in Europe. PARTICIPANTS: Women with twin pregnancy at < 21 weeks' gestation with known chorionicity and gestation established by scan at ≤ 16 weeks' gestation. INTERVENTIONS: Ultrasound scan to establish cervical length. Women with a cervical length of ≤ 35 mm at 18+ 0-20+ 6 weeks' gestation were randomised to standard care or Arabin pessary plus standard care. Randomisation was performed by computer and accessed through a web-based browser. MAIN OUTCOME MEASURES: Obstetric - all births before 34+ 0 weeks' gestation following the spontaneous onset of labour; and neonatal - composite of adverse outcomes, including stillbirth or neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis or proven sepsis, all measured up to 28 days after the expected date of delivery. RESULTS: A total of 2228 participants were recruited to the screening phase, of whom 2170 received a scan and 503 were randomised: 250 to Arabin pessary and 253 to standard care alone. The rate of the primary obstetric outcome was 18.4% (46/250) in the intervention group and 20.6% (52/253) in the control group (adjusted odds ratio 0.87, 95% confidence interval 0.55 to 1.38; p = 0.54). The rate of the primary neonatal outcome was 13.4% (67/500) and 15.0% (76/506) in the intervention group and control group, respectively (adjusted odds ratio 0.86, 95% confidence interval 0.54 to 1.36; p = 0.52). The pessary was largely well tolerated and clinicians found insertion and removal 'easy' or 'fairly easy' in the majority of instances. The simple costs analysis showed that pessary treatment is no more costly than standard care. LIMITATIONS: There was the possibility of a type II error around smaller than anticipated benefit. CONCLUSIONS: In this study, the Arabin pessary did not reduce preterm birth or adverse neonatal outcomes in women with a twin pregnancy and a short cervix. The pessary either is ineffective at reducing preterm birth or has an effect size of < 0.4. FUTURE WORK: Women with twin pregnancy remain at risk of preterm birth; work is required to find treatments for this. TRIAL REGISTRATION: Current Controlled Trials ISRCTN98835694 and ClinicalTrials.gov NCT02235181. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 44. See the NIHR Journals Library website for further project information.

Women who are pregnant with twins have a much higher risk of going into labour early and having an early (preterm) birth than women who are pregnant with only one baby. For this reason, babies who are twins are much more likely to die or to have serious health complications in the first months of life. Although we know that women with twin pregnancy are at risk, there are no treatments that are recommended to prevent early births. Some studies have suggested that the Arabin pessary can help. The Arabin pessary is a silicone ring that fits around the cervix (neck of the womb). The pessary can be put in place in a clinic without any need for an anaesthetic. Some studies have suggested that the Arabin pessary helps and others have suggested that it does not. It appears to be most helpful when the cervix (neck of the womb) is already shortening. Shortening of the neck of the womb is a sign that early birth is even more likely. We asked women with twin pregnancy to take part in STOPPIT 2. Women who agreed had an ultrasound scan of the neck of the womb, which measured its length. Those with a short cervix were randomised to be offered the Arabin pessary (in addition to standard care) or standard care alone. This allocation was carried out 'at random' by a computer. We followed women up until the end of their pregnancy and collected information on the babies' health after birth. We found that the Arabin pessary did not reduce the risk of an early birth; nor did it reduce the risk of health complications for the baby. We conclude that the Arabin pessary should not be used for this purpose.

Public involvement in the governance of population-level biomedical research: unresolved questions and future directions.

Population-level biomedical research offers new opportunities to improve population health, but also raises new challenges to traditional systems of research governance and ethical oversight. Partly in response to these challenges, various models of public involvement in research are being introduced. Yet, the ways in which public involvement should meet governance challenges are not well understood. We conducted a qualitative study with 36 experts and stakeholders using the World Café method to identify key governance challenges and explore how public involvement can meet these challenges. This brief report discusses four cross-cutting themes from the study: the need to move beyond individual consent; issues in benefit and data sharing; the challenge of delineating and understanding publics; and the goal of clarifying justifications for public involvement. The report aims to provide a starting point for making sense of the relationship between public involvement and the governance of population-level biomedical research, showing connections, potential solutions and issues arising at their intersection. We suggest that, in population-level biomedical research, there is a pressing need for a shift away from conventional governance frameworks focused on the individual and towards a focus on collectives, as well as to foreground ethical issues around social justice and develop ways to address cultural diversity, value pluralism and competing stakeholder interests. There are many unresolved questions around how this shift could be realised, but these unresolved questions should form the basis for developing justificatory accounts and frameworks for suitable collective models of public involvement in population-level biomedical research governance.

Living with and beyond cancer with comorbid illness: a qualitative systematic review and evidence synthesis.

PURPOSE: To identify the qualitative evidence on the experience of cancer and comorbid illness from the perspective of patients, carers and health care professionals to identify psycho-social support needs, experience of health care, and to highlight areas where more research is needed. METHODS: A qualitative systematic review following PRISMA guidance. Relevant research databases were searched using an exhaustive list of search terms. Two reviewers independently screened titles and abstracts and discussed variations. Included articles were subject to quality appraisal before data extraction of article characteristics and findings. Thomas and Harden's thematic synthesis of extracted findings was undertaken. RESULTS: Thirty-one articles were included in the review, covering a range of cancer types and comorbid conditions; with varying time since cancer diagnosis and apparent severity of disease for both cancer and other conditions. The majority of studies were published after 2010 and in high income countries. Few studies focused exclusively on the experience of living with comorbid conditions alongside cancer; such that evidence was limited. Key themes identified included the interaction between cancer and comorbid conditions, symptom experience, illness identities and ageing, self-management and the role of primary and secondary care. CONCLUSIONS: In addition to a better understanding of the complex experience of cancer and comorbidity, the review will combine with research prioritisation work with consumers to inform an interview study with the defined patient group. IMPLICATIONS FOR CANCER SURVIVORS: Expanding this evidence base will help to illuminate developing models of cancer patient-centred follow-up care for the large proportion of patients with comorbid conditions.

Open randomised trial of the (Arabin) pessary to prevent preterm birth in twin pregnancy with health economics and acceptability: STOPPIT-2-a study protocol.

INTRODUCTION: The STOPPIT-2 study aims to determine the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix, about which there is current uncertainty. STOPPIT-2 will resolve uncertainty around effectiveness for women with a twin pregnancy and a cervical length of 35 mm or less, define adverse effects, ascertain acceptability and estimate National Health Service costs and savings. METHODS: STOPPIT-2 is a pragmatic multicentre open-label randomised controlled trial. Consenting women with twin pregnancy will have an transvaginal ultrasound scan of their cervical length performed between 18+0 and 20+6 weeks' gestation by an accredited practitioner: women with a cervical length of ≤35 mm will be eligible for inclusion in the treatment phase of the study. The intervention by the insertion of the Arabin cervical pessary will be compared with standard treatment (no pessary).The primary outcomes are (obstetric) spontaneous onset of labour for the mother leading to delivery before 34 weeks' gestation and (neonatal) a composite of specific adverse outcomes or death occurring up to the end of the first 4 weeks after the estimated date of delivery to either or both babies.We plan to recruit 500 women in the treatment phase of the study. Assuming a treatment effect of 0.6, and background rates of 35% and 18%, respectively, for each of the primary outcomes, our study has 85% power to detect a difference between the intervention and the control groups. ANALYSIS: Data will be analysed on the intention-to-treat principle. ETHICS: STOPPIT-2 was approved by the South East Scotland Ethics Committee 02 on 29 August 2014, reference number 14/SS/1031 IRAS ID 159610. DISSEMINATION: Peer reviewed journals, presentations at national and international scientific meetings. TRIAL REGISTRATION NUMBER: ISRCTN98835694 and NCT02235181.

Creating a climate that catalyses healthcare innovation in the United Kingdom - learning lessons from international innovators.

BACKGROUND: The United Kingdom (UK) lags behind other high-income countries in relation to technological innovation in healthcare. In order to inform UK strategy on how to catalyse innovation, we sought to understand what national strategies can help to promote a climate for innovation in healthcare settings by extracting lessons for the UK from international innovators. METHODS: We undertook a series of qualitative semi-structured interviews with senior international innovators from a range of health related policy, care/service delivery, commercial and academic backgrounds. Thematic analysis helped to explore how different stakeholder groups could facilitate/inhibit innovation at individual, organisational, and wider societal levels. RESULTS: We conducted 14 interviews and found that a conducive climate for healthcare innovation comprised of national/regional strategies stimulating commercial competition, promoting public/private relationships, and providing central direction (e.g. incentives for adoption and regulation through standards) without being restrictive. Organisational attitudes with a willingness to experiment and to take risks were also seen as important, but a bottom-up approach to innovation, based on the identification of clinical need, was seen as a crucial first step to construct relevant national policies. CONCLUSIONS: There is now a need to create mechanisms through which frontline National Health Service staff in relation can raise ideas/concerns and suggest opportunities for improvement, and then build national innovation environments that seek to address these needs. This should be accompanied by creating competitive health technology markets to stimulate a commercial environment that attracts high-quality health information technology experts and innovators working in partnership with staff and patients.

Health-Related Quality of Life for individuals with hepatitis C: A narrative review.

BACKGROUND: The assessment of Health-Related Quality of Life (HRQoL) in hepatitis C (HCV) infected individuals continues to gain importance. However, rarely do reviews of this literature consider quantitative and qualitative accounts of HRQoL collectively, which only allows partial insight into the topic. This narrative review aims to address this gap in the literature. METHODS: Literature searches were conducted using seven databases with two separate search strategies, and results assessed for eligibility using specific inclusion/exclusion criteria; a data extraction sheet was used to identify the dominant themes for each research paradigm which were then distilled to key findings to construct the narrative. RESULTS: Quantitative investigation reveals a low HRQoL in individuals with HCV due to a complex multifactorial cause. During treatment for HCV, a further transient reduction is observed, followed by improvement if a sustained virological response is achieved. Qualitative data provide a recognisable voice to the everyday challenges experienced by individuals with HCV including insights into diagnosis and stigmatisation, contextualising how a reduced HRQoL is experienced day-to-day. Methodological limitations of these findings are then discussed. Much of the quantitative data has little relevance to current substance users as they are excluded from most trials, and appraisal of the qualitative literature reveals a marked difference in the lived experience of HCV infected current substance users and that of other HCV groups. CONCLUSION: Concurrent analysis of quantitative and qualitative paradigms provides a deeper understanding of the true burden of HCV illness on HRQoL. Greater utilisation of qualitative research within international clinical guidelines is likely to be of benefit in identifying relevant HRQoL outcomes for substance users.

Children's perspectives on how parents protect them from secondhand smoke in their homes and cars in socioeconomically contrasting communities: a qualitative study.

INTRODUCTION: Children are particularly vulnerable to the health effects of secondhand smoke (SHS) and are mainly exposed in the home and the car. Reducing children's SHS exposure is a tobacco control goal, yet few studies have explored children's perspectives on SHS. This study examines children's accounts of the strategies family members employ to protect them from SHS and is the first to examine how these may be constrained or facilitated in communities with contrasting smoking prevalence rates. METHODS: Individual, paired, and group interviews using topic guides and visual stimulus methods were conducted with 38 children aged 10-15 years who lived in 2 Scottish communities of contrasting socioeconomic status and had a close family member who smoked. Transcripts were analyzed thematically. RESULTS: Parents were reported to employ spatial and dispersal measures to reduce children's SHS exposure in homes and cars. Smoking was restricted to certain rooms and to times when those considered more vulnerable were absent. Less distance between smokers and children and more smoking in the home were reported in the disadvantaged community, reflecting less space within homes and greater parental smoking. Participants expressed strong negative views about smoking in cars and the perceived ineffectiveness of dispersal measures in this context. CONCLUSIONS: Although there was general awareness that SHS exposure was potentially harmful, SHS in the home was considered safe by some participants if certain conditions were met, particularly by those from the disadvantaged area. The implications of these findings for tobacco control programs and media campaigns, particularly those targeted at disadvantaged groups, are discussed.

Children's resistance to parents' smoking in the home and car: a qualitative study.

BACKGROUND AND AIMS: Reducing second-hand smoke exposure in the home is a key tobacco control goal, yet few studies have explored children's views and experiences of this. This study aimed to explore children's accounts of family members' smoking in the home and car and the impact of their socio-economic circumstances. DESIGN: Individual and friendship group interviews using topic guides and visual stimulus methods. SETTING: Two communities in Edinburgh, Scotland, one socio-economically advantaged, one socio-economically disadvantaged. PARTICIPANTS: Thirty-eight children aged 10-15 years who had a close family member who smoked. MEASUREMENTS: Focus group and interview topic guides. FINDINGS: Participants in both communities expressed a strong dislike of family members' smoking and concern about the potential impact on the smoker's health. Participants described overt and covert acts of resistance, including challenging relatives about their smoking, expressing disgust and concern, hiding or destroying cigarettes. Some acts were carried out in collusion with a non-smoking parent and/or sibling. Resistant acts were constrained by expectations of negative responses, which appeared to increase with age, wider social norms around smoking and whether or not the young person smoked. CONCLUSIONS: Some children and young people in the United Kingdom, irrespective of socio-economic status, may actively oppose parents' smoking in the home and car, although their influence may be limited by their position in the family and social norms.

Action to achieve smoke-free homes: an exploration of experts' views.

BACKGROUND: Smoking in the home is the major cause of exposure to second-hand smoke in children in the UK, particularly those living in low income households which have fewer restrictions on smoking in the home. Reducing children's exposure to second-hand smoke is an important public health and inequalities issue. Drawing on findings from a qualitative Scottish study, this paper identifies key issues and challenges that need to be considered when developing action to promote smoke-free homes at the national and local level. METHODS: Two panels of tobacco control experts (local and national) from Scotland considered the implications of the findings from a qualitative study of smokers and non-smokers (who were interviewed about smoking in the home), for future action on reducing smoking in the home. RESULTS: Several key themes emerged through the expert panel discussions. These related to: improving knowledge about SHS among carers and professionals; the goal and approach of future interventions (incremental/harm reduction or total restrictions); the complexity of the interventions; and issues around protecting children. CONCLUSION: The expert panels were very aware of the sensitivities around the boundary between the 'private' home and public health interventions; but also the lack of evidence on the relative effectiveness of specific individual and community approaches on increasing restrictions on smoking in the home. Future action on smoke-free homes needs to consider and address these complexities. In particular health professionals and other key stakeholders need appropriate training on the issues around smoking in the home and how to address these, as well as for more research to evaluate interventions and develop a more robust evidence base to inform effective action on this issue.

Tackling community concerns about commercialisation and genetic research: a modest interdisciplinary proposal.

In recent years, there has been a rise in the creation of DNA databases promising a range of health benefits to individuals and populations. This development has been accompanied by an interest in, and concern for the ethical, legal and social aspects of such collections. In terms of policy solutions, much of the focus of these debates has been on issues of consent, confidentiality and research governance. However, there are broader concerns, such as those associated with commercialisation, which cannot be adequately addressed by these foci. In this article, we focus on the health-wealth benefits that DNA databases promise by considering the views of 10 focus groups on Generation Scotland, Scotland's first national genetic database. As in previous studies, our qualitative research on public/s and stakeholders' views of DNA databases show the prospect of utilising donated samples and information derived for wealth-related ends (i.e. for private profit), irrespective of whether there is an associated health-related benefit, arouses considerable reaction. While health-wealth benefits are not mutually exclusive ideals, the tendency has been to cast 'public' benefits as exclusively health-related, while 'private' commercial benefits for funders and/or researchers are held out as a necessary pay-off. We argue for a less polarised approach that reconsiders what is meant by 'public benefits' and questions the exclusivity of commercial interests. We believe accommodation can be achieved via the mobilisation of a grass roots solution known as 'benefit-sharing' or a 'profit pay-off'. We propose a sociologically informed model that has a pragmatic, legal framework, which responds seriously to public concerns.

Contrasting lives, contrasting views? Understandings of health inequalities from children in differing social circumstances.

Children's differing socio-economic, cultural and familial circumstances and experiences are part of the pathways implicated in health and illness in adulthood. However, in the existing, mainly survey based, work children's own voices tend to be absent and adult-defined data about health and illness accumulated. Little is known about the social and cultural processes, in children's very different childhoods, which underpin and ultimately constitute these epidemiological findings. This paper reports findings from a qualitative study examining the socio-economic and cultural contexts of children's lifestyles and the production of inequalities in health, carried out in a large Scottish city. Two rounds of semi-structured interviews, using a range of child-friendly techniques (photographs, drawings, vignettes), were carried out with 35 girls and boys aged 9-12 years living in two contrasting but contiguous areas, one relatively advantaged and one relatively disadvantaged. Thirty of their parents were also interviewed and community profiling and observational work undertaken. Children and parents described often starkly contrasting lives and opportunities, regularly involving material differences. However, children appeared to locate inequalities as much in relationships and social life as in material concerns; in this their direct experiences of relationships and unfairness were central to their making sense of inequality and its impact on health. Although children from both areas highlighted several different inequalities, including those related to material resources, they also spoke of the importance of control over their life world; of care and love particularly from parents; of friendship and acceptance by their peer group. Many children challenged straightforward causal explanations for future ill-health, privileging some explanations, such as psychological or lifestyle factors. The accounts of children from both areas displayed considerable resilience to and downplaying of the effects of both relationship and material inequalities; also showing how familial and personal challenges, such as bullying, divorce, learning difficulties, cut across structurally based differences.