Assessment of Autoregulation of the Cerebral Circulation during Acute Lung Injury in a Neonatal Porcine Model.

In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen consumption and extraction is not well understood in term infants with ALI. We examined hemodynamics, cerebral autoregulation and fractional oxygen extraction, as measured by near-infrared spectroscopy (NIRS) and blood gases, in a neonatal porcine oleic acid injury model of moderate ALI. We hypothesized that in ALI animals, cerebral oxygen extraction would be increased to a greater degree than kidney or gut oxygen extraction as indicative of the brain's adaptive efforts to increase cerebral oxygen extraction at the expense of splanchnic end organs. Fifteen anesthetized, ventilated 5-day-old neonatal piglets were divided into moderate lung injury by treatment with oleic acid or control (sham injection). The degree of lung injury was quantified at baseline and after establishment of ALI by blood gases, ventilation parameters and calculated oxygenation deficit, hemodynamic indices by echocardiography and lung injury score by ultrasound. PaCO2 was maintained constant during ventilation. Cerebral, renal and gut oxygenation was determined by NIRS during stepwise decreases in inspired oxygen from 50% to 21%, correlated with PaO2 and PvO2; changes in fractional oxygen extraction (ΔFOE) were calculated from NIRS and from regional blood gas samples. The proportion of cerebral autoregulation impairment attributable to blood pressure, and to hypoxemia, was calculated from autoregulation nomograms. ALI manifested as hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance and increased resistance, and marked increase in lung ultrasound score. Brain, gut and renal NIRS, obtained from probes placed over the anterior skull, central abdomen and flank, respectively, correlated with concurrent SVC (brain) or IVC (gut, renal) PvO2 and SvO2. Cerebral autoregulation was impaired after ALI as a function of blood pressure at all FiO2 steps, but predominantly by hypoxemia at FiO2 < 40%. Cerebral ΔFOE was higher in ALI animals at all FiO2 steps. We conclude that in an animal model of neonatal ALI, cerebrovascular blood flow regulation is primarily dependent on oxygenation. There is not a defined oxygenation threshold below which cerebral autoregulation is impaired in ALI. Cerebral oxygen extraction is enhanced in ALI, reflecting compensation for exhausted cerebral autoregulation due to the degree of hypoxemia and/or hypotension, thereby protecting against tissue hypoxia.

Emesis in pregnancy - a qualitative study on trial recruitment failure from the EMPOWER internal pilot.

BACKGROUND: As part of the internal pilot of the EMPOWER trial investigating the second-line antiemetic therapies in severe emesis in pregnancy ( https://www.isrctn.com/ISRCTN16924692 ), a qualitative study of women's views was carried out, to improve our understanding of why women did, or did not, consent to participation in the trial. Interviews were also conducted with site research staff, to broaden our analysis and explore other factors affecting recruitment. METHODS: The sample comprised women who accepted or declined trial participation (n=21) and site research staff (n=22). A structured topic guide was used, in four email interviews and 17 telephone interviews with women, and semi-structured telephone interviews were carried out with staff. Of the women interviewed, seven had declined trial participation, and of the staff interviewed, 16 were research midwives/research nurses and six were principal investigators. All transcripts were checked for accuracy, anonymised and entered into NVIVO12 for indexing and retrieval. Data was analysed using a reflexive thematic analytic approach. In total, 72 codes were generated from the thematic analysis, and 36 from each sample group. RESULTS: Three key themes based on all the interviews were (a) the diversity of recruitment pathways and boundaries of care, (b) the impact of trial complexity on recruitment and staff morale and (c) the ethics of caring for a patient with emesis. Ethical issues discussed included the use of double dummy and time to treat, particularly those suffering severely from the effects of nausea and vomiting. To illustrate these themes, staff perspectives are given more prominence. CONCLUSIONS: The main reason the trial was stopped related to the high proportion of women ineligible for recruitment due to prior treatment with study drug(s) because of unanticipated changes in clinical practice. The qualitative results also demonstrate the impact of the trial on women and staff and highlight how the diversity of referral pathways, boundaries of care and the complexity of the trial and protocol resulted in additional barriers to successful trial recruitment. Qualitative work in pilot and feasibility studies of a clinical trial is recommended, to evaluate whether recruitment strategies remain viable in unanticipated contexts. TRIAL REGISTRATION: Trial registration number ISRCTN16924692 . Date: 08/01/2018.

Ondansetron and metoclopramide as second-line antiemetics in women with nausea and vomiting in pregnancy: the EMPOWER pilot factorial RCT.

BACKGROUND: Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. OBJECTIVES: To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. DESIGN: This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. PARTICIPANTS: Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. INTERVENTIONS: Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. MAIN OUTCOME MEASURES: The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. RESULTS: Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. LIMITATIONS: The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. CONCLUSIONS: The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. 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. 63. See the NIHR Journals Library website for further project information.

Nausea and vomiting in pregnancy cause physical and emotional distress, and up to 30% of affected women require medical treatment. Guidelines on the use of anti-sickness drugs exist, but evidence is limited about which drugs work the best. The EMPOWER (EMesis in Pregnancy ­ Ondansetron With mEtoClopRamide) trial aimed to compare the clinical effectiveness and cost-effectiveness of two anti-sickness drugs [metoclopramide (metoclopramide hydrochloride, Actavis UK Ltd, Barnstable, UK; IV Ratiopharm GmbH, Ulm, Germany) and ondansetron (ondansetron hydrochloride dehydrate, Wockhardt UK Ltd, Wrexham, UK; IV Hameln Pharma plus GmbH, Hameln)] for the treatment of nausea and vomiting in pregnancy. Women who were < 17 weeks pregnant with severe nausea and vomiting who attended hospital because their first anti-sickness drug had failed to improve their symptoms were asked to take part in the trial. Participants received fluids and, with consent, were randomly allocated to one of four groups: (1) metoclopramide and dummy ondansetron, (2) ondansetron and dummy metoclopramide, (3) metoclopramide and ondansetron or (4) double dummy. Trial drugs were administered into a vein and then by tablet for 10 days. On advice from sufferers, the trial focused on treatment failure, but other outcomes, including drug side effects, costs and pregnancy outcome, were collected. The trial was unable to recruit enough women and, therefore, did not progress. Nearly 600 women at 11 hospitals were screened, of whom 122 (21%) were eligible and 33 were recruited. The main reason for ineligibility (68%) was prior use of trial drug (mostly ondansetron). Overall, 15 out of 30 evaluable women experienced treatment failure. Interviews with 21 women who were approached about the trial and 22 research staff identified complex hurdles to and enablers of recruitment. The main hurdles were the requirements of the study protocol in relation to guidelines on anti-sickness drugs and the diversity of pathways to care. The role of research staff was a key enabler. The trial was too small to draw useful conclusions and it highlights the challenges of conducting complex studies on sick pregnant women. Subsequent concerns about the safety of ondansetron highlight the need for further studies to help inform women and the NHS about the best care for nausea and vomiting in pregnancy.

How is high quality research evidence used in everyday decisions about induction of labour between pregnant women and maternity care professionals? An exploratory study.

OBJECTIVE: To explore the use of high quality research evidence in women's and maternity care professionals' decisions about induction of labour (IOL). METHODS: A qualitative study underpinned by a social constructionist framework, using semi-structured interviews and generative thematic analysis. SETTING: A large tertiary referral maternity unit in northern England in 2013/14. PARTICIPANTS: 22 randomly selected health care professionals involved in maternity care (midwives, obstetricians, maternity service managers), and 16 postnatal women, 3-8 weeks post-delivery, who were offered IOL in their most recent pregnancy. FINDINGS: Three themes were identified in the data; (1) the value of different forms of knowledge, (2) accessing and sharing knowledge, and (3) constrained pathways and default choices. Findings echo other evidence in suggesting that women do not feel informed about IOL or that they have choices about the procedure. This study illuminates potential explanatory factors by considering the complex context within which IOL is discussed and offered (e.g. presentation of IOL as routine rather than a choice, care pathways that make declining IOL appear undesirable, blanket use of clinical guidelines without consideration of individual circumstances and preferences). KEY CONCLUSIONS: This study suggests that organisational, social, and professional factors conspire towards a culture where (a) IOL has become understood as a routine part of maternity care rather than an intervention to make an informed choice about, (b) several factors contribute to demotivate women and health care practitioners from seeking to understand the evidence base regarding induction, and (c) health care professionals can find themselves ill-equipped to discuss the relative risks and benefits of IOL and its alternatives. IMPLICATIONS FOR PRACTICE: It is important that IOL is recognised as an optional intervention and is not presented to women as a routine part of maternity care. When IOL is offered it should be accompanied by an evidence informed discussion about the options available to support informed decision making. Health care professionals should be supported to understand the evidence base and our findings suggest that any attempt to facilitate this needs to acknowledge and tackle complex organisational, social and professional influences that contribute to current care practices.

Lung ultrasound predicts histological lung injury in a neonatal model of acute respiratory distress syndrome.

RATIONALE: Point-of-care ultrasound (POCUS) is used to evaluate pulmonary edema in adults with acute respiratory distress syndrome (ARDS). Its use has not been validated in neonatal models. OBJECTIVES: We compared an in vivo lung ultrasound score against clinical and histological markers of acute lung injury, in a neonatal animal model, hypothesizing that POCUS would sensitively diagnose early acute lung injury in neonates and discern its severity. METHODS: Fifteen anesthetized, ventilated 3-day-old neonatal piglets were divided into controls, moderate lung injury, or severe lung injury by graded treatment with oleic acid. Degree of lung injury was quantified at baseline, immediately after oleic acid administration, and 1 hour after the evolution of acute lung injury, by blood gases, ventilation parameters and calculated oxygenation deficit; hemodynamic indices by echocardiography, and lung ultrasound obtained in an 8-region grid of anterior and posterior zones, semi-quantitatively analyzed by a blinded observer. Lungs were inflation-fixed postmortem at last mean airway pressure, for histological assessment. RESULTS: Acute lung injury manifested in oleic acid-treated groups as dose-dependent capillary leak causing intravascular depletion and cardiac failure, hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance, and resistance. Ultrasound scores of anterior regions distinguished moderate from severe injury; scores in posterior regions reached maximum values immediately after lung injury. POCUS score correlated with calculated intrapulmonary shunt fraction (R2 = .65) and with histological injury score (R2 = .61), P < .01. CONCLUSION: We conclude that POCUS may be valuable in neonates for early quantification of acute lung injury or ARDS; and that nondependent ultrasound regions clearly distinguish severity of pulmonary edema.

'I couldn't say the words': communicative bodies and spaces in parents' encounters with nonsuicidal self-injury.

There is a growing recognition that nonsuicidal self-injury commonly incorporates communicative and interactional dimensions. But regardless of whether we approach self-injury within the terms of deliberate interpersonal communication, it is undeniably something that conveys a significant impact into the social and communicative field between people. As such, it is something that can be approached and analysed as communicative in this more general sense. In this paper, we draw on 13 in-depth qualitative interviews with the parents of people who self-injure, conducted for a larger pilot study, to explore some of these more general communicative processes, spaces and impacts associated with self-injury. By providing a phenomenologically informed examination of parents' experiences, we argue that self-injury is in fact a richly communicative phenomenon, albeit one that cannot be adequately mapped using the traditional sender-receiver communication paradigm. To provide a more nuanced mapping, we look beyond this paradigm to include more subtle, ambiguous, pre-reflexive and bodily forms of communication. Indeed, self-injury offers a particularly powerful case study with which to think through a more complex model of communication, one that connects the interpersonal, intersubjective and intercorporeal levels, and that, as such, is more appropriate to the sociologies of everyday life and embodiment.

The social life of self-injury: exploring the communicative dimension of a very personal practice.

This article makes the case for a sociological focus on the communicative, relational and interactional dimensions of nonsuicidal self-injury. While current research tends to be dominated by highly individual and intrapsychic models, it is increasingly observed that such models leave a social dimension to the practice unexplained. A burgeoning sociological literature has begun to address this paradox of the social in self-injury; however, we argue that the role of the social must be considered beyond the issues of aetiology, social learning and social construal/construction that are typically covered in this literature. Specifically, we argue that, since the lived meanings of self-injury directly implicate the interactional along with the intrapsychic, a more systematic focus on the role of social relations and social communication is vital. To illustrate this conceptual argument and embed it in the lived experiences of self-injury, we draw on two case studies taken from pilot research conducted by the authors. The more thoroughly sociological approach to self-injury that we present here offers an important compliment to the existing evidence base by reframing the absent presence of social communication contained within it, and suggesting important future directions for research.

Pregnancy decisions after fetal or perinatal death: systematic review of qualitative research.

OBJECTIVES: To synthesise the findings of qualitative research exploring parents' experiences, views and decisions about becoming pregnant following a perinatal death or fetal loss. DESIGN: Systematic review and meta-synthesis of qualitative research. DATA SOURCES: Medline, Web of Science, CINAHL, PsycINFO, ASSIA, Embase, PUBMED, Scopus and Google Scholar. ELIGIBILITY CRITERIA: Nine electronic databases were searched using predefined search terms. Articles published in English, in peer-reviewed journals, using qualitative methods to explore the experiences and attitudes of bereaved parents following perinatal or fetal loss, were included. DATA EXTRACTION AND SYNTHESIS: Qualitative data relating to first-order and second-order constructs were extracted and synthesised across studies using a thematic analysis. RESULTS: 15 studies were included. Four descriptive themes and 10 subthemes were identified. The descriptive themes were: deciding about subsequent pregnancy, diversity of reactions to the event, social network influences, and planning or timing of subsequent pregnancy. The decision to become pregnant after death is complex and varies between individuals and sometimes within couples. Decisions are often made quickly, in the immediate aftermath of a pregnancy loss, but may evolve over time. Bereaved parents may feel isolated from social networks. CONCLUSIONS: There is an opportunity to support parents to prepare for a pregnancy after a fetal or perinatal loss, and conversations may be welcomed at an early stage. Health professionals may play an important role providing support lacking from usual social networks. PROSPERO REGISTRATION NUMBER: CRD42018112839.

MRI in the diagnosis of fetal developmental brain abnormalities: the MERIDIAN diagnostic accuracy study.

BACKGROUND: Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately. OBJECTIVES: To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality. DESIGN: A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy. SETTING: Sixteen UK fetal medicine centres. PARTICIPANTS: Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks' gestation) with a suspected brain abnormality detected on ultrasonography. INTERVENTIONS: Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician. MAIN OUTCOME MEASURES: Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2-3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken. RESULTS: The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18-23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed. CONCLUSIONS: iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27626961. 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. 49. See the NIHR Journals Library website for further project information.

Ultrasonography is routine in pregnancy to check that the baby's brain is developing as expected. However, no medical test is perfect and ultrasonography may miss some brain abnormalities, may get some brain abnormalities wrong or may diagnose an abnormality that is not really present. Magnetic resonance imaging (MRI) may help clarify difficult cases during pregnancy. We wanted to find out if MRI was better than ultrasonography alone in making an accurate diagnosis. We recruited pregnant women whose ultrasound scan, performed by an expert, suggested that their baby had a brain abnormality, and referred them for a MRI scan. The results of the two tests were compared with each other and to the final outcome of the pregnancy. Our results showed that using MRI in addition to ultrasonography improved the accuracy of the diagnosis in about one in four pregnancies. It changed the prediction of how the baby would develop in at least one in five cases. In many cases, the pregnancy was managed differently because of the MRI result. The MRI was acceptable to women, with 95% saying that they would have MRI again in a similar situation. Neither MRI nor ultrasonography accurately identified children who went on to have delayed development at the age of 2­3 years, but MRI was better than ultrasonography at ruling out developmental problems at this age. The MRI cost more than ultrasonography alone; therefore, whether or not it is worthwhile depends on the value placed on the decisions that changed as a result of its use.

A Review of Clinical Poster Presentations at the Sixth Biennial Pediatric Anesthesia Neurodevelopment Assessment (PANDA) Symposium.

Clinical researchers studying the long-term neurocognitive effects of anesthetic and sedative agents on children continue to struggle with identifying a phenotype for anesthetic neurotoxicity, the window of vulnerability, and the toxicity threshold in terms of concentration and duration. The Sixth Biennial Pediatric Anesthesia Neurodevelopment Assessment (PANDA) symposium at Columbia University included a moderated poster presentation session where 4 investigators presented their latest contributions to the landscape of clinical anesthetic neurotoxicity research. A lack of standardization in the design of clinical studies in terms of age at exposure, duration and type of exposure, and outcome measures assessed were highlighted by all the investigators. Suggestions for the future direction of clinical trials included the implementation of more consistent study parameters and the employment of standardized neurocognitive testing and imaging before and after exposure to general anesthesia. Presentations covered a broad range of topics including the valid translation of preclinical studies to human subjects, the quantification of real-world exposures to anesthetic and sedative medications, and possible alternatives to these exposures.

"He looks gorgeous" - iuMR images and the transforming of foetal and parental identities.

The MERIDIAN study examined whether in-utero MRI (iuMRI) improves the accuracy of diagnosis of foetal brain abnormalities, when used as an adjunct to ultrasound anomaly scanning. A diagnostic iuMRI differs from routine ultrasound screening because of its infrequent use and scanning procedure. Nested within this trial, this sociological study explored the acceptability of iuMRI as a technology and its contribution to parental decision-making. Our sociological interpretation of the role of iuMR images in prenatal diagnosis draws on narrative interviews with women (and some partners) who underwent MRI imaging at three different centres. Overall, participants found iuMRI helpful in decision-making because it either confirmed or disconfirmed previous results, or provided additional information. Expectant couples experienced the iuMR imaging process as informative, but also as having emotive and practical value. Our paper extends the existing sociological literature on antenatal testing and visualising the foetus, by using iuMR diagnostic imaging to further explore the concept of the unborn entity. Our data suggest that alongside the iuMR images, the 'parental gaze' and accompanying commentary are used by parents to construct and transform foetal and parental identities despite ongoing uncertainties about, and shifting social contexts to their pregnancy.

Constructions of Decision Making for Risk-Reducing Mastectomy.

This research article explores constructions of the decision-making process for risk-reducing mastectomy and considers the consequent role and responsibility of clinical psychologists. Using a Foucauldian discourse analysis approach, three online newspaper articles, five online forums, and four semi-structured interviews were analyzed. Seven discursive constructions are identified and discussed within three broader discourses of mental illness, risk, and embodied selves. Primary conclusions highlight the role for clinical psychologists and health professionals to incorporate the multiple social and political factors involved in discourses that shape decision making. The role of power is critically considered and there is a need for further analysis of "talk" among health professionals.

A survey of health professionals' views on acceptable gestational age and termination of pregnancy for fetal anomaly.

Termination of pregnancy for fetal anomaly is legal in the UK with no upper limit, if two doctors, in good faith, agree "there is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped". This is Clause E of the Human Fertlisation and Embryology Act. The most commonly sighted Clause is C, which states "the pregnancy has not exceeded its twenty-fourth week and that the continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the pregnant woman". This study aimed to investigate health professionals' views on gestational age and acceptable termination of pregnancy for fetal anomaly (TOPFA). We undertook a questionnaire survey of UK health professionals working in fetal medicine, obstetrics and gynaecology and neonatology. A study pack consisting of a self-completion questionnaire, an invitation letter, participant information sheet, and a stamped addressed return envelope, were sent to health professionals. We used four fetal anomalies as case study examples in the questionnaire: isolated cleft lip, hypoplastic left heart, spina bifida and trisomy 21. These anomalies were chosen as they differed in terms of the type of anomaly, the type of impairment, and the perceived severity. Forty-one study packs were returned. For anomalies deemed less serious, later gestational ages were an important consideration when deciding acceptable TOPFA. The prognosis of an anomaly was considered an important factor in deciding whether a TOPFA was acceptable alongside gestational age. Clause C of the current UK legislation, which allows a legal termination prior to 24 weeks gestational age if continuing with the pregnancy would impact the mental health of the mother, was deemed a reasonable option for termination when parents are requesting a TOPFA. For each case study example, health professionals responded that TOPFA at '25 weeks and over' was acceptable (cleft lip n = 1; hypoplastic left heart n = 19; spina bifida n = 13 and Trisomy 21 n = 10). Professionals also distinguished between their personal and professional views. These findings offer new insight into how gestational age considerations influence professionals' conceptualisation of acceptable TOPFA.

Negotiating acceptable termination of pregnancy for non-lethal fetal anomaly: a qualitative study of professional perspectives.

OBJECTIVE: This study aims to explore the perspectives of professionals around the issue of termination of pregnancy for non-lethal fetal anomaly (TOPFA). METHODS: Semi-structured interviews were undertaken with medical professionals (14 consultants in fetal medicine, obstetrics, neonatology and paediatrics) and social care professionals (nine individuals with roles supporting people living with impairment) from the Northeast of England. Analysis adopted an inductive thematic approach facilitated by NVivo. RESULTS: The overarching theme to emerge from the interview data was of professionals, medical and social care, wanting to present an acceptable self-image of their views on TOPFA. Professionals' values on 'fixing', pain and 'normality' influenced what aspects of moral acceptability they gave priority to in terms of their standpoint and, in turn, their conceptualisations of acceptable TOPFA. Thus, if a termination could be defended morally, including negotiation of several key issues (including 'fixing', perceptions of pain and normality), then participants conceptualised TOPFA as an acceptable pregnancy outcome. CONCLUSION: Despite different professional experiences, these professional groups were able to negotiate their way through difficult terrain to conceptualise TOPFA as a morally acceptable principle. While professionals have different moral thresholds, no one argued for a restriction of the current legislation. The data suggest that social care professionals also look at the wider social context of a person with an impairment when discussing their views regarding TOPFA. Medical professionals focus more on the individual impairment when discussing their views on TOPFA.

MRI for Fetal Developmental Brain Abnormalities: Perspectives From the Pregnant Patient.

Ultrasound is routinely used as a prenatal screening and diagnostic tool but has limitations. Some anomalies in the developing fetal brain can be difficult to detect, and in utero magnetic resonance imaging (iuMRI) is increasingly used as an adjunct to ultrasound. However, understandings of patient perspectives of iuMRI technology are still developing. Our qualitative study of 41 mothers who experienced iuMRI was embedded in a diagnostic accuracy trial and aimed to inform policy recommendations that might stem from the clinical findings. Our analysis suggests that iuMRI is seen as useful, offering valuable additional information and helping women make decisions about care options at a difficult time. However, patients' experiences demonstrated the uncertainty and anxiety associated with the prenatal diagnosis (PND) process relating to brain anomalies including the challenges of their embodied contributions. Our findings suggest more could be done to reduce the impact on pregnant women during an already difficult, anxious period.

Use of MRI in the diagnosis of fetal brain abnormalities in utero (MERIDIAN): a multicentre, prospective cohort study.

BACKGROUND: In-utero MRI (iuMRI) has shown promise as an adjunct to ultrasound but the comparative diagnostic performance has been poorly defined. We aimed to assess whether the diagnostic accuracy and confidence of the prenatal diagnosis of fetal brain abnormalities is improved with iuMRI and assess the clinical impact and patient acceptability of iuMRI. METHODS: We did a multicentre, prospective, cohort study in the UK, at 16 fetal medicine centres, of pregnant women aged 16 years or older whose fetus had a brain abnormality detected by ultrasound at a gestational age of 18 weeks or more, had no contraindications to iuMRI, and consented to enter the study. Women carrying a fetus suspected of having a brain anomaly on ultrasound had iuMRI done within 14 days of ultrasound. The findings were reviewed by two independent panels and used to estimate diagnostic accuracy and confidence by comparison with outcome diagnoses. Changes in diagnosis, prognosis, and clinical management brought about by iuMRI and patient acceptability were assessed. FINDINGS: Participants were recruited between July 29, 2011, and Aug 31, 2014. The cohort was subdivided by gestation into the 18 weeks to less than 24 weeks fetus cohort (n=369) and into the 24 weeks or older fetus cohort (n=201). Diagnostic accuracy was improved by 23% (95% CI 18-27) in the 18 weeks to less than 24 weeks group and 29% (23-36) in the 24 weeks and older group (p<0·0001 for both groups). The overall diagnostic accuracy was 68% for ultrasound and 93% for iuMRI (difference 25%, 95% CI 21-29). Dominant diagnoses were reported with high confidence on ultrasound in 465 (82%) of 570 cases compared with 544 (95%) of 570 cases on iuMRI. IuMRI provided additional diagnostic information in 387 (49%) of 783 cases, changed prognostic information in at least 157 (20%), and led to changes in clinical management in more than one in three cases. IuMRI also had high patient acceptability with at least 95% of women saying they would have an iuMRI study if a future pregnancy were complicated by a fetal brain abnormality. INTERPRETATION: iuMRI improves diagnostic accuracy and confidence for fetal brain anomalies and leads to management changes in a high proportion of cases. This finding, along with the high patient acceptability, leads us to propose that any fetus with a suspected brain abnormality on ultrasound should have iuMRI to better inform counselling and management decisions. FUNDING: National Institute for Health Research Health Technology Assessment programme.

Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC) have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC) can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n=6) to intravenous oleic acid (OA) injury, ventilation and hMSC infusion, while the controls (n=5) had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1h after the administration of OA. The animals were monitored for additional 4h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB), a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p=0.04). There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p=0.063). There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term.

Mothers' perspectives on the perinatal loss of a co-twin: a qualitative study.

BACKGROUND: There is a growing body of literature exploring the emotional impact of perinatal loss upon parents but only limited research focussing specifically on the views and experiences of parents who have experienced a loss from a twin or higher order pregnancy. We undertook a qualitative study to provide an in-depth understanding of the experiences of mothers who have had a loss from a twin pregnancy and subsequently continued visiting hospital whilst their surviving twin was cared for. METHODS: A qualitative study involving semi-structured interviews. Mothers were recruited from a Neonatal Intensive Care Unit and Fetal Medicine department. Fourteen interviews were carried out with mothers who had experienced a loss in pregnancy or the neonatal period and had a surviving twin on the neonatal unit. Data were analysed using a generative thematic approach. RESULTS: The analysis identified three key themes in the accounts mothers gave of their experiences: the status of 'special'; the importance of trust; and control and empowerment. Where the surviving co-twin remained in hospital for many weeks, mothers described the emotional support of health professionals as crucial to their wellbeing. Few mothers sought formal bereavement support, instead they kept their grief 'on hold' in order to support their surviving baby. Due to the trauma of their loss, mothers reflected that they had been unable to make informed decisions, in particular in relation to the funeral of their deceased baby. CONCLUSIONS: Our study highlighted that there are a specific set of issues for mothers who have lost a baby from a twin pregnancy. Relatively small changes to practice however, made a significant difference to wellbeing during their time in hospital with a surviving twin. Findings from this research will provide insight into the needs of bereaved mothers, will inform healthcare planning and the development of care packages.

Mephedrone inhalation causes pneumomediastinum.

A 17-year-old male patient presented to A&E with swelling on the right side of his neck, extending to below the clavicle, associated with neck pain and dysphonia. On examination, subcutaneous supraclavicular and chest wall emphysema was noted. Clinical observations and bloods were normal. A chest X-ray and subsequent CT of the thorax showed evidence of pneumomediastinum and subcutaneous emphysema. The patient denied any history of trauma but admitted to inhalation of mephedrone 3 days previously. The patient was discussed with the regional cardiothoracic unit who advised conservative management. He was treated prophylactically with antibiotics and was initially kept nil by mouth, but diet was introduced 24 h later. He remained well, his dysphonia resolved and his subcutaneous emphysema improved. He was discharged after 3 days. He has not attended any formal follow-up but was well when contacted by phone.