A sub-µs accuracy GPS alternative using electrical transmission grids as precision timing networks.

It is widely recognised that over-reliance on GNSS (e.g GPS) for time synchronisation represents an acute threat to modern society, and a diversity of alternatives are required to mitigate the threat of an outage. This paper proposes a GNSS alternative using time dissemination over national scale transmission or distribution networks. The method utilises the same frequency bandwidth and coupling technology as established power line carrier technology in conjunction with modern chirp Spread Spectrum modulation. The basis of the method is the transmission of a time synchronised chirp from a central substation, coupled into the aerial modes of the transmission line. During GNSS operation, all substations can estimate the time of flight by correlating the received chirp with a time-synchronised local copy. During GNSS outage, time sychronisation to the central substation is maintained by correcting for the precalculated time of flight. It is shown that recent advances in chirp spread spectrum allow for a computationally efficient algorithm with the capacity to compute hundreds of thousand of chirp correlations every second, facilitating timing accuracy which satisfies the majority of smart grid applications. ATP-EMTP simulations of the method on large transmission networks demonstrate sub-µs timing accuracy even in the presence of low SNR and impulsive noise. An FPGA prototype demonstrates experimentally sub-µs accuracy for time dissemination over a distance of 700 m. Averaging over time is shown to facilitate satisfactory performance down to - 20 dB , which could extend the range of the system to a national scale and a time dissemination network invulnerable to wireless spoofing and jamming attack vectors.

Health economics-informed planning of psychiatric care: A primer and curriculum framework for psychiatrists.

OBJECTIVE: Contemporary medical education lacks a strong focus on health economics which guides major decisions in private and public health services. We briefly outline the rationale, guiding principles, main analytic methods, and a suggested framework for health economics education in psychiatry. CONCLUSIONS: Health economics aims to improve the efficiency of healthcare. Some analytic methods can be harnessed by psychiatrists to better plan clinical care. Health economic methods will also assist psychiatrists in translating their expertise and clinical priorities more effectively to policy-makers, governments, and private insurers motivated by economic reasoning.

Supply and demand - a health economic perspective on the Australian hospital and elective surgery crisis.

The COVID-19 pandemic has contributed to longstanding structural shortfalls in the supply of healthcare services in high-income countries, including Australia. These impacts are reflected in Australian public hospital key performance indicators for acute care, elective surgery and hospital exit block. The challenges occur in the context of increased demand following the suspension of a range of healthcare services during the pandemic. The main supply challenge is suitable numbers of skilled healthcare workers. Rebalancing of supply and demand in healthcare is challenging, but needs to be achieved.

Accurate calculations of out-of-pocket costs for mental healthcare consultations.

What is known about the topic? When assessing real growth in costs, it is important to adjust for inflation through indexation to the Consumer Price Index (CPI). The change in prices or costs over time can be calculated in constant currency amounts by adjusting by a ratio of the CPI in the year of interest to the CPI in the baseline year. What does this paper add? Rosenberg et al. (2022) did not calculate out-of-pocket costs in constant currency, which does not give an accurate estimation of costs adjusted for inflation. What are the implications for practitioners? We calculated examples to illustrate the impact of such adjustments, which substantially impact the results of the study.

Planned delivery for pre-eclampsia between 34 and 37 weeks of gestation: the PHOENIX RCT.

BACKGROUND: In women with late preterm pre-eclampsia (i.e. at 34+0 to 36+6 weeks' gestation), the optimal delivery time is unclear because limitation of maternal-fetal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether or not planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of perinatal or infant outcomes, compared with expectant management, in women with late preterm pre-eclampsia. METHODS: We undertook an individually randomised, triple non-masked controlled trial in 46 maternity units across England and Wales, with an embedded health economic evaluation, comparing planned delivery and expectant management (usual care) in women with late preterm pre-eclampsia. The co-primary maternal outcome was a maternal morbidity composite or recorded systolic blood pressure of ≥ 160 mmHg (superiority hypothesis). The co-primary short-term perinatal outcome was a composite of perinatal deaths or neonatal unit admission (non-inferiority hypothesis). Analyses were by intention to treat, with an additional per-protocol analysis for the perinatal outcome. The primary 2-year infant neurodevelopmental outcome was measured using the PARCA-R (Parent Report of Children's Abilities-Revised) composite score. The planned sample size of the trial was 900 women; the trial is now completed. We undertook two linked substudies. RESULTS: Between 29 September 2014 and 10 December 2018, 901 women were recruited; 450 women [448 women (two withdrew consent) and 471 infants] were allocated to planned delivery and 451 women (451 women and 475 infants) were allocated to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group [289 (65%) women] than in the expectant management group [338 (75%) women] (adjusted relative risk 0.86, 95% confidence interval 0.79 to 0.94; p = 0.0005). The incidence of the co-primary perinatal outcome was significantly higher in the planned delivery group [196 (42%) infants] than in the expectant management group [159 (34%) infants] (adjusted relative risk 1.26, 95% confidence interval 1.08 to 1.47; p = 0.0034), but indicators of neonatal morbidity were similar in both groups. At 2-year follow-up, the mean PARCA-R scores were 89.5 points (standard deviation 18.2 points) for the planned delivery group (290 infants) and 91.9 points (standard deviation 18.4 points) for the expectant management group (256 infants), both within the normal developmental range (adjusted mean difference -2.4 points, 95% confidence interval -5.4 to 0.5 points; non-inferiority p = 0.147). Planned delivery was significantly cost-saving (-£2711, 95% confidence interval -£4840 to -£637) compared with expectant management. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group. CONCLUSION: In women with late preterm pre-eclampsia, planned delivery reduces short-term maternal morbidity compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater short-term neonatal morbidity (such as need for respiratory support). At 2-year follow-up, around 60% of parents reported follow-up scores. Average infant development was within the normal range for both groups; the small between-group mean difference in PARCA-R scores is unlikely to be clinically important. Planned delivery was significantly cost-saving to the health service. These findings should be discussed with women with late preterm pre-eclampsia to allow shared decision-making on timing of delivery. LIMITATIONS: Limitations of the trial include the challenges of finding a perinatal outcome that adequately represented the potential risks of both groups and a maternal outcome that reflects the multiorgan manifestations of pre-eclampsia. The incidences of maternal and perinatal primary outcomes were higher than anticipated on the basis of previous studies, but this did not limit interpretation of the analysis. The trial was limited by a higher loss to follow-up rate than expected, meaning that the extent and direction of bias in outcomes (between responders and non-responders) is uncertain. A longer follow-up period (e.g. up to 5 years) would have enabled us to provide further evidence on long-term infant outcomes, but this runs the risk of greater attrition and increased expense. FUTURE WORK: We identified a number of further questions that could be prioritised through a formal scoping process, including uncertainties around disease-modifying interventions, prognostic factors, longer-term follow-up, the perspectives of women and their families, meta-analysis with other studies, effect of a similar intervention in other health-care settings, and clinical effectiveness and cost-effectiveness of other related policies around neonatal unit admission in late preterm birth. TRIAL REGISTRATION: The trial was prospectively registered as ISRCTN01879376. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in Health Technology Assessment. See the NIHR Journals Library website for further project information.

Economic Considerations in COVID-19 Vaccine Hesitancy and Refusal: A Survey of the Literature.

The COVID-19 global pandemic has triggered one of the greatest economic shocks in a century. Effective COVID-19 vaccines have been developed, but a proportion of people either are hesitant or refuse to be vaccinated, facilitated by a global misinformation campaign. If 'herd immunity' cannot be achieved, there is potential not only for ongoing surges in infection, but also for development of new strains of the virus that could evade vaccines and precipitate further health and economic crises. We review the economics of vaccination and of vaccine hesitancy and refusal, and their potential effects on the recovery from the COVID-19 pandemic.

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.

The socioeconomic gradient in mortality from ovarian, cervical, and endometrial cancer in Australian women, 2001-2018: A population-based study.

BACKGROUND: Socio-economic (SE) status is closely linked to health status and the mechanisms of this association are complex. One important adverse effect of SE disadvantage is vulnerability to cancer and cancer is a major cause of morbidity and mortality in Australia. AIMS: We aimed to estimate the effect of SE status on mortality rates from ovarian, cervical, and endometrial cancer. MATERIALS AND METHODS: National mortality data were obtained from the Australian Bureau of Statistics (ABS) for the calendar years from 2001 to 2018, inclusive. Individual deaths were grouped by the ABS Index of Relative Socio-economic Advantage and Disadvantage. Population data were obtained to provided denominators allowing calculation of mortality rates (deaths per 100 000 women aged 30-79 years). Statistical analyses performed included tabulating point-estimates of mortality rates and their changes over time and modelling the trends of rates using maximum likelihood method. RESULTS: Age-standardised mortality rates for ovarian and cervical cancer fell over the study period but increased for endometrial cancer. There was clear evidence of a SE gradient in the mortality rate for all three cancers. This SE gradient increased over the study period for ovarian and cervical cancer but remained unchanged for endometrial cancer. CONCLUSIONS: Women at greater SE disadvantage have higher rates of death from the commonest gynaecological cancers and this gradient has not reduced over the last two decades. After the COVID-19 pandemic efforts must be redoubled to ensure that Australians already at risk of ill health do not face even greater risks because of their circumstances.

Formalin-Fixed Paraffin-Embedded (FFPE) samples are not a beneficial replacement for frozen tissues in fetal membrane microbiota research.

Formalin-Fixed Paraffin-Embedded (FFPE) tissues are routinely collected, archived, and used for clinical diagnosis, including maternal and neonatal health. Applying FFPE samples to microbiota research would be beneficial to reduce preparation, storage and costs associated with limited available frozen samples. This research aims to understand if FFPE fetal membrane samples are comparable to frozen tissues, which are the current gold standard for DNA microbiota analysis. Extracted DNA from nine matched paired patients were sequenced by Illumina sequencing of the V4 16S rRNA gene region. This included duplicate frozen amnion and chorion fetal membrane rolls or FFPE combined amniochorionic samples. Negative controls of surrounding wax blocks and DNA extraction reagents were processed alongside samples using identical methods. DNA quality and quantity was assessed by NanoDrop, agarose gel electrophoresis and Bioanalyzer. Decontam and SourceTracker were integrated into microbiota analysis to identify the presence of contaminating sources. The bacterial profile and nine genera differed between FFPE and frozen fetal membranes. There were no differences in bacterial profiles between FFPE samples and corresponding wax negative controls, with 49% of bacteria in FFPE fetal membrane samples matched to the source origin of paraffin wax, and 40% originating from DNA extraction reagent sources. FFPE samples displayed high fragmentation and low quantity of extracted DNA compared to frozen samples. The microbiota of FFPE fetal membrane samples is influenced by processing methods, with the inability to differentiate between the microbiota of the tissue sample and the surrounding wax block. Illumina sequencing results of FFPE and frozen fetal membrane samples should not be compared using the methods employed here. Variation could be influenced by limitations including storage time, DNA extraction and purification methods. To utilise FFPE fetal membrane samples in microbiota research then contamination prevention and detection methods must be included into optimised and standardised protocols, with recommendations presented here.

Strategies for Peptide-Mediated Cargo Delivery to Human Smooth Muscle Cells.

Diseases involving dysfunction of smooth muscle cells present a major health and socioeconomic burden, and have remained stubbornly resistant to standard therapeutic strategies. Examples include many cardiovascular diseases and spontaneous preterm birth, a complication affecting up to 11% of all pregnancies worldwide. This fuels the continued search for new drug delivery strategies to treat these conditions. The use of cell penetrating peptides (CPPs) for this purpose remains a promising, if as yet unrealized, avenue to explore. In part, this may relate to a paucity of studies investigating the application of CPPs as drug delivery vectors to human smooth muscle cells and tissues. We have sought to address this knowledge gap by reporting methods for examining the uptake of different CPP-cargo vectors to human uterine and vascular smooth muscle cells. In particular, we report here (a) that four different CPP-fluorophore conjugates, spanning masses of 1309-3435 Da, and net charges of +2 to +7, can be delivered to human isolated uterine smooth muscle cells without inducing cell toxicity; (b) that the cargo delivered by such CPPs can be fluorescent moieties and/or biologically active peptides; (c) that CPP delivery in a short time frame to native smooth muscle cells in human tissues ex vivo can be achieved. Further exploration of CPPs as tools to facilitate targeted drug delivery to native human smooth muscle tissues will assist in improving our understanding of scientific mechanisms underlying major diseases involving smooth muscle dysfunction as well as facilitating therapeutic investigations.

A pedunculated small bowel gastrointestinal stromal tumour (GIST) masquerading as an ovarian tumour.

While gastro-intestinal stromal tumours (GIST) are the most common non-epithelial neoplasms of the gastrointestinal tract, 10% occur externally. Symptomatology is therefore broad, dependent on location. A 42-year-old female presented to the Emergency Department after 12 hours of severe right lower abdominal, preceded by vague pain over two weeks. Imaging revealed a right-sided 7.5 × 5.8 × 5.6 cm ovarian cystic lesion, suspicious for torsion. Laparoscopically, the lesion was densely adherent to small and large bowel, and she was proceeded to resection of an assumed primary ovarian neoplasm. Histopathology revealed an infarcted epithelioid GIST, high-grade with clear margins (stage pT3). There are only 24 cases of GISTs pre-operatively mistaken for gynaecological neoplasms. Additionally, there are reports of GISTs metastasizing to ovaries. Both computed tomography and ultrasound are non-specific, including hypo- and hyperechoic features. In all published cases, imaging was not able to identify presumed gynaecological neoplasms as GISTS. Differential diagnoses for pelvic masses should include non-gynaecological tumours.

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.

A silent burden-prolapse, incontinence, and infertility in Australian Aboriginal and Torres Strait Islander women: A systematic search and narrative review.

BACKGROUND: Pelvic organ prolapse (POP), urinary incontinence, and infertility are all prevalent conditions associated with considerable reduction in quality of life. As a group, Aboriginal and Torres Strait Islander women may be at higher risk of these conditions, but studies are scarce. OBJECTIVE: To review the literature pertaining to the epidemiology, diagnosis, and management of these conditions in Indigenous Australian women. SEARCH STRATEGY: Medline, Embase, and Scopus were searched for articles published between 1980 and 2021 pertaining to these conditions in Indigenous Australian women. SELECTION CRITERIA: Studies that did not directly address the epidemiology, diagnosis, and management of these conditions were excluded. MAIN RESULTS: It was possible to identify only 11 papers dealing with these conditions in Indigenous Australian women. Only one dealt with POP and was a retrospective audit of a health outreach program in the Northern Territory concluding that there was significant underreporting of the condition. Five papers dealt with urinary incontinence and, again, described significant underreporting and poor referral pathways. Five papers reported small studies about infertility, one reporting poor engagement from clinical directors. CONCLUSION: It was concluded that despite the importance of these conditions, there is almost no body of research and this is an urgent national problem.

Aspirin non-adherence in pregnant women at risk of preeclampsia (ANA): a qualitative study.

BACKGROUND: Antenatal adherence to aspirin prophylaxis is key to reducing the occurrence of a major pregnancy complication: pre-eclampsia (PE). Up to 75% of pregnant women at increased risk of pre-eclampsia do not take aspirin as prescribed. Little research has been done to understand the psychological determinants of aspirin adherence in pregnancy. This qualitative study aimed to explore barriers and facilitators to aspirin adherence in women at increased risk of PE using version 2 of Theoretical Domains Framework (TDF). METHODS: Fourteen women from the North-East of England who declared various levels of non-adherence to aspirin (0-5 of 7 prescribed tablets/week) were interviewed 4-18 months after delivery, using the TDF as a guide. Semi-structured interviews were digitally recorded and transcribed verbatim. A thematic framework analysis was used. RESULTS: Women exhibited both intentional and unintentional non-adherence and faced multiple barriers at a personal and environmental level. They struggled to initiate, implement and persist in taking medication as prescribed. Women expressed inadequate knowledge about PE and aspirin; they struggled to identify as 'medication takers' and relate to the risk factors for PE as identified by the midwife. Significant barriers within the health-care environment were identified; women had difficulties obtaining medication and perceived conflict amongst health care professionals regarding medication safety. CONCLUSION: A combination of inadequate knowledge, lack of identification with the risk factors and beliefs about consequences of taking medication were interlinked with other domains, such as environmental context and resonate with the Necessity-Concerns Framework.

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.

Informational needs related to aspirin prophylactic therapy amongst pregnant women at risk of preeclampsia - A qualitative study.

OBJECTIVE: Despite being key to reducing the occurrence of pre-eclampsia in high-risk women, adherence to aspirin prophylaxis is low, reflecting multifactorial challenges faced by pregnant women. It is therefore important to understand the barriers and facilitators of aspirin adherence in pregnancy. This sub-analysis of a qualitative study conducted to better understand barriers and facilitators of aspirin adherence was set to describe informational needs related to aspirin use in pregnancy. STUDY DESIGN: A qualitative study was conducted with 14 postnatal women from North-East of England, who declared various levels of non-adherence to aspirin (0-5/7 prescribed). A thematic framework analysis of semi-structured interviews was used. OUTCOME MEASURES: Emerging themes associated with informational needs about aspirin use in pregnancy. RESULTS: Main themes identified a) Informational needs, b) Nature of the information seeking behaviour (active vs passive), c) Sources of information, d) Preferred format of information, e) Partners seeking knowledge. Not all women actively seek information; some choose not to pursue it as they find thinking of hypothetical risks disturbing. When information is accessed, women use a wide range of informational resources from scientific articles and National Health Services website to social media sources and word-of-mouth. Women admit that reading leaflets can be difficult, preferring to receive information in interactive ways. Although partners seek information about risks and risk reduction strategies, they are often not included in conversations with health care professionals. CONCLUSION: New interactive and accessible informational resources are needed to engage pregnant women and their partners in aspirin prophylactic therapy.

The connected patient project: moving towards a population-based primary health care research registry.

BACKGROUND: The NHS pledges to give all patients access to clinical research. In England, 32% of General Practices are research active and only 14% of patients engage in research. This project aimed to evaluate consent-for-contact and communication in primary care patients. METHODS: An explanatory mixed methods study of patients and staff within a single general practice. The study included all patients over the age of 18 years, and excluded those on the palliative care register and those unable to give informed consent. The questionnaire asked recipients to indicate their preferred contact method and data-sharing permissions with three organisations: NHS, Universities and Commercial Companies. Survey recipients and staff were invited to take part in a semi-structured interview. Interviews explored project acceptability, feasibility and reasoning behind choices made. Statistical data were triangulated with interview data. RESULTS: The target patient population was 4678, 24% (n = 1148) responded. Seven hundred and three gave permission for at least one of the organisations to contact them. Older people were more likely to respond than young people, (p < 0.001). There was a trend for more women than men to give permissions however, in the 70 years plus age group this was reversed. Short message service was the preferred method of communication (48% n = 330), but those aged 70 years and over, preferred letter (p = 0.001). Interviews suggested patients felt the project was primarily about improving communication and secondly access to research. Patients trusted the NHS and university researchers. Staff interviewees found the project was less onerous than expected. Barriers to wider rollout included workload and the fragmented nature of NHS digital systems. CONCLUSIONS: A registry of patients was established; however, the response rate of 24% needs increasing before wider adoption. Health promotion and chronic disease-based research may recruit better when based in primary health care. Older demographics would be more likely to volunteer for research. NHS and academic researchers are trusted, commercial organisations less so. The move to digitalise communication methods has the potential to marginalise older women. Findings were used to drive forward two novel developments: a consent registry (Research+Me) and a federation-wide participant identification process.

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.