Unsettling the treatment imperative? Chemotherapy decision-making in the wake of genomic techniques.

Social scientists have argued that a treatment imperative shapes experiences of biomedicine. This is evident within oncology, where discourses of hope are tempered by persistent fears surrounding cancer. It is within this context that genomic decision-making tools are entering routine care. These may indicate that a treatment is not appropriate for a particular disease profile. We draw on qualitative interviews and observations centred on gene expression profiling to consider the implications of this technique for the treatment imperative in early breast cancer. Influenced by sociological perspectives on medical technologies, we discuss how fallibilities of established tools have forged a space for the introduction of genomic testing into chemotherapy decision-making. We demonstrate how high expectations shaped patients' interpretations of this tool as facilitating the 'right' treatment choice. We then unpick these accounts, highlighting the complex relationship between gene expression profiling and treatment decision-making. We argue that anticipations for genomic testing to provide certainty in treatment choice must account for the sociocultural and organisational contexts in which it is used, including the powerful entwinement of chemotherapy and cancer. Our research has implications for sociological perspectives on treatment decision-making and clinical expectations for genomic medicine to resolve the 'problem' of overtreatment.

Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.

Background: Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation. Methods: We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine. Results: Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated. Conclusions: Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.

Hyperexcitability in young iPSC-derived C9ORF72 mutant motor neurons is associated with increased intracellular calcium release.

A large hexanucleotide repeat expansion in the C9ORF72 gene is the most prevalent cause of amyotrophic lateral sclerosis (ALS). To better understand neuronal dysfunction during ALS progression, we studied motor neuron (MN) cultures derived from iPSC lines generated from C9ORF72 (C9) expansion carriers and unaffected controls. C9 and control MN cultures showed comparable mRNA levels for MN markers SMI-32, HB9 and ISL1 and similar MN yields (> 50% TUJ1/SMI-32 double-positive MNs). Using whole-cell patch clamp we showed that C9-MNs have normal membrane capacitance, resistance and resting potential. However, immature (day 40) C9-MNs exhibited a hyperexcitable phenotype concurrent with increased release of calcium (Ca2+) from internal stores, but with no changes to NaV and KV currents. Interestingly, this was a transient phenotype. By day 47, maturing C9-MNs demonstrated normal electrophysiological activity, displaying only subtle alterations on mitochondrial Ca2+ release. Together, these findings suggest the potential importance of a developmental component to C9ORF72-related ALS.

Selective vulnerability of tripartite synapses in amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. Separate lines of evidence suggest that synapses and astrocytes play a role in the pathological mechanisms underlying ALS. Given that astrocytes make specialised contacts with some synapses, called tripartite synapses, we hypothesise that tripartite synapses could act as the fulcrum of disease in ALS. To test this hypothesis, we have performed an extensive microscopy-based investigation of synapses and tripartite synapses in the spinal cord of ALS model mice and post-mortem human tissue from ALS cases. We reveal widescale synaptic changes at the early symptomatic stages of the SOD1G93a mouse model. Super-resolution microscopy reveals that large complex postsynaptic structures are lost in ALS mice. Most surprisingly, tripartite synapses are selectively lost, while non-tripartite synapses remain in equal number to healthy controls. Finally, we also observe a similar selective loss of tripartite synapses in human post-mortem ALS spinal cords. From these data we conclude that tripartite synaptopathy is a key hallmark of ALS.

Implementation of a novel ultrasound training programme for midwives in Malawi: A mixed methods evaluation using the RE-AIM framework.

Introduction: Despite recommendation that all women receive an ultrasound in pregnancy prior to 24 weeks', this remains unavailable to many women in low-income countries where trained practitioners are scarce. Although many programmes have demonstrated efficacy, few have achieved longterm sustainability, with a lack of information about how best to implement such programmes. This mixed-methods study aimed to evaluate the implementation of a novel education package to teach ultrasound-naive midwives in Malawi basic obstetric ultrasound, assessing its impact in the context of the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework. Methods: The study ran across six sites in Malawi between October 2020 and June 2021, encompassing three phases; pre-implementation, implementation and post-implementation. Twenty nine midwives underwent a bespoke education package with matched pre and post course surveys assessed their knowledge, attitudes and confidence and "hands on" assessments evaluating practical skills. Training evaluation forms and in-depth interviews explored their satisfaction with the package, with repeat assessment and remote image review evaluating maintenance of skills. Results: 28/29 midwives completed the training, with significant increases in knowledge, confidence and practical skills. Adherence to the education package varied, however many changes to the proposed methodology were adaptive and appeared to facilitate the efficacy of the programme. Unfortunately, despite reporting approval regarding the training itself, satisfaction regarding supervision and follow up was mixed, reflecting the difficulties encountered with providing ongoing in-person and remote support. Conclusion: This programme was successful in improving trainees' knowledge, confidence and skill in performing basic obstetric ultrasound, largely on account of an adaptive approach to implementation. The maintenance of ongoing support was challenging, reflected by trainee dissatisfaction. By evaluating the success of this education package based on its implementation and not just its efficacy, we have generated new insights into the barriers to sustainable upscale, specifically those surrounding maintenance.

Accessing targeted therapies for cancer: self and collective advocacy alongside and beyond mainstream cancer charities.

As precision oncology has evolved, patients and their families have become more involved in efforts to access these treatments via fundraising and campaigning that take place outside of the larger cancer charities. In this paper, we explore the solidarities, networks, and emotional work of the UK-based access advocates, drawing on the stories of nine advocates, which included interviews and content analyses of their social media posts and coverage of their case in news, commentary, and fundraising websites. We consider the emotional and knowledge work of building networks that spanned consumerist and activist agendas, forged individual and collective goals, and orientations toward the public, private, and third sectors as part of securing support and access. Through these various practices, the actors we have studied cultivated personal advantage and solidarities with other patients and advocates, and in so doing engaged in self and collective advocacy alongside and beyond mainstream cancer charities.

Exploring ethnic minority women's experiences of maternity care during the SARS-CoV-2 pandemic: a qualitative study.

OBJECTIVE: To explore the experiences of pregnancy, childbirth, antenatal and postnatal care in women belonging to ethnic minorities and to identify any specific challenges that these women faced during the SARS-CoV-2 pandemic. DESIGN: This was a qualitative study using semistructured interviews of pregnant women or those who were 6 weeks postnatal from Black, Asian and minority ethnic backgrounds. The study included 16 women in a predominantly urban Scottish health board area. RESULTS: The finding are presented in four themes: 'communication', 'interactions with healthcare professionals', 'racism' and 'the pandemic effect'. Each theme had relevant subthemes. 'Communication' encompassed respect, accent bias, language barrier and cultural dissonance; 'interactions with healthcare professionals': continuity of care, empathy, informed decision making and dissonance with other healthcare systems; 'racism' was deemed to be institutional, interpersonal or internalised; and 'the pandemic effect' consisted of isolation, psychological impact and barriers to access of care. CONCLUSIONS: This study provides insight into the specific challenges faced by ethnic minority women in pregnancy, which intersect with the unique problems posed by the ongoing SARS-CoV-2 pandemic to potentially widen existing ethnic disparities in maternal outcomes and experiences of maternity care.

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.

Diagnostic layering: Patient accounts of breast cancer classification in the molecular era.

Social scientific work has considered the promise of genomic medicine to transform healthcare by personalising treatment. However, little qualitative research attends to already well-established molecular techniques in routine care. In this article we consider women's experiences of routine breast cancer diagnosis in the UK NHS. We attend to patient accounts of the techniques used to subtype breast cancer and guide individual treatment. We introduce the concept of 'diagnostic layering' to make sense of how the range of clinical techniques used to classify breast cancer shape patient experiences of diagnosis. The process of diagnostic layering, whereby various levels of diagnostic information are received by patients over time, can render diagnosis as incomplete and subject to change. In the example of early breast cancer, progressive layers of diagnostic information are closely tied to chemotherapy recommendations. In recent years a genomic test, gene expression profiling, has become introduced into routine care. Because gene expression profiling could indicate a treatment recommendation where standard tools had failed, the technique could represent a 'final layer' of diagnosis for some patients. However, the test could also invalidate previous understandings of the cancer, require additional interpretation and further prolong the diagnostic process. This research contributes to the sociology of diagnosis by outlining how practices of cancer subtyping shape patient experiences of breast cancer. We add to social scientific work attending to the complexities of molecular and genomic techniques by considering the blurring of diagnostic and therapeutic activities from a patient perspective.

What makes AI 'intelligent' and 'caring'? Exploring affect and relationality across three sites of intelligence and care.

This paper scrutinises how AI and robotic technologies are transforming the relationships between people and machines in new affective, embodied and relational ways. Through investigating what it means to exist as human 'in relation' to AI across health and care contexts, we aim to make three main contributions. (1) We start by highlighting the complexities of philosophical issues surrounding the concepts of "artificial intelligence" and "ethical machines." (2) We outline some potential challenges and opportunities that the creation of such technologies may bring in the health and care settings. We focus on AI applications that interface with health and care via examples where AI is explicitly designed as an 'augmenting' technology that can overcome human bodily and cognitive as well as socio-economic constraints. We focus on three dimensions of 'intelligence' - physical, interpretive, and emotional - using the examples of robotic surgery, digital pathology, and robot caregivers, respectively. Through investigating these areas, we interrogate the social context and implications of human-technology interaction in the interrelational sphere of care practice. (3) We argue, in conclusion, that there is a need for an interdisciplinary mode of theorising 'intelligence' as relational and affective in ways that can accommodate the fragmentation of both conceptual and material boundaries between human and AI, and human and machine. Our aim in investigating these sociological, philosophical and ethical questions is primarily to explore the relationship between affect, relationality and 'intelligence,' the intersection and integration of 'human' and 'artificial' intelligence, through an examination of how AI is used across different dimensions of intelligence. This allows us to scrutinise how 'intelligence' is ultimately conveyed, understood and (technologically or algorithmically) configured in practice through emerging relationships that go beyond the conceptual divisions between humans and machines, and humans vis-à-vis artificial intelligence-based technologies.

Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis.

BACKGROUND: Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix. METHODS AND FINDINGS: We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55-1.38], p = 0.54). The primary neonatal outcome-a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery-was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54-1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50-1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses. CONCLUSIONS: These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out. TRIAL REGISTRATION: ISRCTN Registry ISRCTN 02235181. ClinicalTrials.gov NCT02235181.

Towards a feminist philosophy of engagements in health-related research.

Engagement with publics, patients, and stakeholders is an important part of the health research environment today,and different modalities of 'engaged' health research have proliferated in recent years. Yet, th ere is no consensus on what, exactly, 'engaging' means, what it should look like, and what the aims, justifications, or motivations for it should be. In this paper, we set out what we see as important, outstanding challenges around the practice and theory of engaging and consider the tensions and possibilities that the diverse landscape of engaging evokes. We examine the roots, present modalities and institutional frameworks that have been erected around engaging, including how they shape and delimit how engagements are framed, enacted, and justified. We inspect the related issue of knowledge production within and through engagements, addressing whether engagements can, or should, be framed as knowledge producing activities. We then unpack the question of how engagements are or could be valued and evaluated, emphasising the plural ways in which 'value' can be conceptualised and generated. We conclude by calling for a philosophy of engagements that can capture the diversity of related practices, concepts and justifications around engagements, and account for the plurality of knowledges and value that engagements engender, while remaining flexible and attentive to the structural conditions under which engagements occur. Such philosophy should be a feminist one, informed by feminist epistemological and methodological approaches to equitable modes of research participation, knowledge production, and valuing. Especially, translating feminist tools of reflexivity and positionalityinto the sphere of engagements can enable a synergy of empirical, epistemic and normative considerations in developing accounts of engaging in both theory and praxis. Modestly, here, we hope to carve out the starting points for this work.

Neurobiological limits and the somatic significance of love: Caregivers' engagements with neuroscience in Scottish parenting programmes.

While parents have long received guidance on how to raise children, a relatively new element of this involves explicit references to infant brain development, drawing on brain scans and neuroscientific knowledge. Sometimes called 'brain-based parenting', this has been criticised from within sociological and policy circles alike. However, the engagement of parents themselves with neuroscientific concepts is far less researched. Drawing on 22 interviews with parents/carers of children (mostly aged 0-7) living in Scotland, this article examines how they account for their (non-)use of concepts and understandings relating to neuroscience. Three normative tropes were salient: information about children's processing speed, evidence about deprived Romanian orphans in the 1990s, and ideas relating to whether or not children should 'self-settle' when falling asleep. We interrogate how parents reflexively weigh and judge such understandings and ideas. In some cases, neuroscientific knowledge was enrolled by parents in ways that supported biologically reductionist models of childhood agency. This reductionism commonly had generative effects, enjoining new care practices and producing particular parent and infant subjectivities. Notably, parents do not uncritically adopt or accept (sometimes reductionist) neurobiological and/or psychological knowledge; rather, they reflect on whether and when it is applicable to and relevant for raising their children. Thus, our respondents draw on everyday epistemologies of parenting to negotiate brain-based understandings of infant development and behaviour, and invest meaning in these in ways that cannot be fully anticipated (or appreciated) within straightforward celebrations or critiques of the content of parenting programmes drawing on neuropsychological ideas.

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.

Cell Therapies for Spinal Cord Injury: Trends and Challenges of Current Clinical Trials.

Cell therapies have the potential to revolutionize the treatment of spinal cord injury. Basic research has progressed significantly in recent years, with a plethora of cell types now reaching early-phase human clinical trials, offering new strategies to repair the spinal cord. However, despite initial enthusiasm for preclinical and early-phase clinical trials, there has been a notable hiatus in the translation of cell therapies to routine clinical practice. Here, we review cell therapies that have reached clinical trials for spinal cord injury, providing a snapshot of all registered human trials and a summary of all published studies. Of registered trials, the majority have used autologous cells and approximately a third have been government funded, a third industry sponsored, and a third funded by university or healthcare systems. A total of 37 cell therapy trials have been published, primarily using stem cells, although a smaller number have used Schwann cells or olfactory ensheathing cells. Significant challenges remain for cell therapy trials in this area, including achieving stringent regulatory standards, ensuring appropriately powered efficacy trials, and establishing sustainable long-term funding. However, cell therapies hold great promise for human spinal cord repair and future trials must continue to capitalize on the exciting developments emerging from preclinical studies.

Accomplishing an adaptive clinical trial for cancer: Valuation practices and care work across the laboratory and the clinic.

A new generation of adaptive, multi-arm clinical trials has been developed in cancer research including those offering experimental treatments to patients based on the genomic analysis of their cancer. Depending on the molecular changes found in patients' cancer cells, it is anticipated that targeted and personalised therapies will be made available for those who have reached the end of standard treatment options, potentially extending survival time. Results from these trials are also expected to advance genomic knowledge for patients in the future. Drawing on data from a qualitative study of one such trial in the UK, comprising observations of out-patient clinic appointments, out-patient biopsy procedures, laboratory work, and interviews with practitioners, this paper explores how the clinical and research value of one such trial was accomplished in everyday practice by focussing on the work of clinical trials and laboratory staff across recruitment, laboratory analysis, and results management. In the face of numerous potential set-backs, disappointments and failure, we explore how practitioners worked to balance the need to meet established measures of value such as numbers of patients recruited into the trial, alongside cultivating the value of positive affects for patients by managing their expectations and emotions. This care work was performed primarily by practitioners whose roles have historically been devalued in healthcare practice and yet, as we show, were critical to this process. We conclude by arguing that as complex multi-arm adaptive trials become more commonplace, we need to attend to, and render visible, the dynamic and care-full valuation practices of backstage practitioners through which experimental biomedicine is accomplished, and in doing so show that care both achieves clinical and research value, and is also a series of practices and processes that tends to tissue, patients and staff in the context of ever-present possibility of failure.

Exploring Patient Experience of Chest Pain Before and After Implementation of an Early Rule-Out Pathway for Myocardial Infarction: A Qualitative Study.

STUDY OBJECTIVE: High-sensitivity cardiac troponin assays enable myocardial infarction to be excluded in the emergency department (ED). As part of a prospective clinical trial, we explore how introducing an early rule-out pathway may affect patient experience of chest pain. METHODS: In a qualitative study, participants presenting to the ED with suspected acute coronary syndrome, and for whom the diagnosis of myocardial infarction was excluded, were interviewed before (n=23) or after (n=26) implementation of an early rule-out pathway. Preimplementation, diagnosis of myocardial infarction was excluded on serial troponin testing requiring admission to the hospital. Postimplementation, diagnosis could be excluded in the ED, enabling direct patient discharge. Semistructured interviews exploring the patients' illness experience were conducted approximately 1 week postdischarge, transcribed verbatim, and analyzed thematically. Themes emerging pre- and postimplementation are described. RESULTS: Common themes emerged across both pathways: participants commonly sought health care advice before presenting to the ED; a discordance may exist between the objective interpretation of troponin results by clinicians and the patients' experience of illness; and pretest information, trust in the clinician, and active listening may enhance reassurance gained from negative test results. Other themes related to the care pathway were that routine care procedures appeared to be a source of frustration for participants requiring hospital admission, and patients assessed with the early rule-out pathway appeared less likely to appraise their future health status. CONCLUSION: The early rule-out of myocardial infarction may be enhanced by recognition of patient out-of-hospital experience and improved communication surrounding reassurance and future cardiovascular health goals.

Diagnosing uncertainty, producing neonatal abstinence syndrome.

The use of alcohol and other drugs during pregnancy is understood to be an important public health problem. One way in which this problem is expressed and responded to is via the identification and treatment of neonatal abstinence syndrome (NAS). In this article, we demonstrate how the processes of anticipating, identifying and responding to NAS are characterised by significant uncertainty among parents and health and social care practitioners. We draw on interviews with 16 parents who had recently had a baby at risk of NAS, and multidisciplinary focus groups with 27 health and social care professionals, held in Scotland, UK. NAS, and drug use in pregnancy, is a fraught and complex arena. Parents in the UK who use opioids risk losing custody of children, and must navigate a high degree of surveillance, governance and marginalisation. We suggest that considering NAS as a social diagnosis, further informed by Mol's political ontology of 'multiple' bodies/diseases, may help to produce clinical and social responses to uncertainty which avoid, rather than promote, further marginalisation of parents who use drugs. One such response is to develop a culture of relationship-based care which empowers both service providers and service users to challenge existing practice and decision-making.