Explore the vast range of titles available.

In women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia. In this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing. Between Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79–0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08–1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group. There is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery. National Institute for Health Research Health Technology Assessment Programme.

Tubal ectopic pregnancies can cause substantial morbidity or even death. Current treatment is with methotrexate or surgery. Methotrexate treatment fails in approximately 30% of women who subsequently require rescue surgery. Gefitinib, an epidermal growth factor receptor inhibitor, might improve the effects of methotrexate. We assessed the efficacy of oral gefitinib with methotrexate, versus methotrexate alone, to treat tubal ectopic pregnancy. We performed a multicentre, randomised, double-blind, placebo-controlled trial across 50 UK hospitals. Participants diagnosed with tubal ectopic pregnancy were administered a single dose of intramuscular methotrexate (50 mg/m2) and randomised (1:1 ratio) to 7 days of additional oral gefitinib (250 mg daily) or placebo. The primary outcome, analysed by intention to treat, was surgical intervention to resolve the ectopic pregnancy. Secondary outcomes included time to resolution of ectopic pregnancy and serious adverse events. This trial is registered at the ISRCTN registry, ISCRTN 67795930. Between Nov 2, 2016, and Oct 6, 2021, 328 participants were allocated to methotrexate and gefitinib (n=165) or methotrexate and placebo (n=163). Three participants in the placebo group withdrew. Surgical intervention occurred in 50 (30%) of 165 participants in the gefitinib group and in 47 (29%) of 160 participants in the placebo group (adjusted risk ratio 1·15, 95% CI 0·85 to 1·58; adjusted risk difference –0·01, 95% CI –0·10 to 0·09; p=0·37). Without surgical intervention, median time to resolution was 28·0 days in the gefitinib group and 28·0 days in the placebo group (subdistribution hazard ratio 1·03, 95% CI 0·75 to 1·40). Serious adverse events occurred in five (3%) of 165 participants in the gefitinib group and in six (4%) of 162 participants in the placebo group. Diarrhoea and rash were more common in the gefitinib group. In women with a tubal ectopic pregnancy, adding oral gefitinib to parenteral methotrexate does not offer clinical benefit over methotrexate and increases minor adverse reactions. National Institute of Health Research.

Background Reducing the rate of stillbirth is an international priority. At least half of babies stillborn in high-income countries are small for gestational-age (SGA). The Growth Assessment Protocol (GAP), a complex antenatal intervention that aims to increase the rate of antenatal detection of SGA, was evaluated in the DESiGN type 2 hybrid effectiveness-implementation cluster randomised trial ( n = 13 clusters). In this paper, we present the trial process evaluation. Methods A mixed-methods process evaluation was conducted. Clinical leads and frontline healthcare professionals were interviewed to inform understanding of context (implementing and standard care sites) and GAP implementation (implementing sites). Thematic analysis of interview text used the context and implementation of complex interventions framework to understand acceptability, feasibility, and the impact of context. A review of implementing cluster clinical guidelines, training and maternity records was conducted to assess fidelity, dose and reach. Results Interviews were conducted with 28 clinical leads and 27 frontline healthcare professionals across 11 sites. Staff at implementing sites generally found GAP to be acceptable but raised issues of feasibility, caused by conflicting demands on resource, and variable beliefs among clinical leaders regarding the intervention value. GAP was implemented with variable fidelity (concordance of local guidelines to GAP was high at two sites, moderate at two and low at one site), all sites achieved the target to train > 75% staff using face-to-face methods, but only one site trained > 75% staff using e-learning methods; a median of 84% (range 78–87%) of women were correctly risk stratified at the five implementing sites. Most sites achieved high scores for reach (median 94%, range 62–98% of women had a customised growth chart), but generally, low scores for dose (median 31%, range 8–53% of low-risk women and median 5%, range 0–17% of high-risk women) were monitored for SGA as recommended. Conclusions Implementation of GAP was generally acceptable to staff but with issues of feasibility that are likely to have contributed to variation in implementation strength. Leadership and resourcing are fundamental to effective implementation of clinical service changes, even when such changes are well aligned to policy mandated service-change priorities. Trial registration Primary registry and trial identifying number: ISRCTN 67698474. Registered 02/11/16. https://doi.org/10.1186/ISRCTN67698474 .

Background Stillbirth rates in the United Kingdom (UK) are amongst the highest of all developed nations. The association between small-for-gestational-age (SGA) foetuses and stillbirth is well established, and observational studies suggest that improved antenatal detection of SGA babies may halve the stillbirth rate. The Growth Assessment Protocol (GAP) describes a complex intervention that includes risk assessment for SGA and screening using customised fundal-height growth charts. Increased detection of SGA from the use of GAP has been implicated in the reduction of stillbirth rates by 22%, in observational studies of UK regions where GAP uptake was high. This study will be the first randomised controlled trial examining the clinical efficacy, health economics and implementation of the GAP programme in the antenatal detection of SGA. Methods/design In this randomised controlled trial, clusters comprising a maternity unit (or National Health Service Trust) were randomised to either implementation of the GAP programme, or standard care. The primary outcome is the rate of antenatal ultrasound detection of SGA in infants found to be SGA at birth by both population and customised standards, as this is recognised as being the group with highest risk for perinatal morbidity and mortality. Secondary outcomes include antenatal detection of SGA by population centiles, antenatal detection of SGA by customised centiles, short-term maternal and neonatal outcomes, resource use and economic consequences, and a process evaluation of GAP implementation. Qualitative interviews will be performed to assess facilitators and barriers to implementation of GAP. Discussion This study will be the first to provide data and outcomes from a randomised controlled trial investigating the potential difference between the GAP programme compared to standard care for antenatal ultrasound detection of SGA infants. Accurate information on the performance and service provision requirements of the GAP protocol has the potential to inform national policy decisions on methods to reduce the rate of stillbirth. Trial registration Primary registry and trial identifying number: ISRCTN 67698474 . Registered on 2 November 2016.

A 19-year-old primipara woman was admitted in labour with positive vaginal swab for group B Streptococcus and given benzylpenicillin and ranitidine. She used Entonox for pain relief. She received bupivacaine in the epidural catheter and shortly after developed sensation of foreign body in her throat with muffled voice and isolated angioneurotic oedema of the uvula. She responded well to H1 and H2 histamine blockers and steroids and epinephrine were kept as standby. She recovered well soon after delivery. Penicillin, Entonox or bupivacaine seemed possible cause of the Quincke's disease. Hereditary form was ruled out by normal creatine kinase and reaction to bupivacaine by C1 esterase inhibitor assay. It can be associated with spectrum of anaphylactic reactions and the resuscitation team should be alerted. Airway maintenance should be the primary management strategy. Most cases respond to observation, oxygen therapy and antihistamines with or without steroids. Epinephrine may be required occasionally.

A 19-year-old primipara woman was admitted in labour with positive vaginal swab for group B Streptococcus and given benzylpenicillin and ranitidine. She used Entonox for pain relief. She received bupivacaine in the epidural catheter and shortly after developed sensation of foreign body in her throat with muffled voice and isolated angioneurotic oedema of the uvula. She responded well to H1 and H2 histamine blockers and steroids and epinephrine were kept as standby. She recovered well soon after delivery. Penicillin, Entonox or bupivacaine seemed possible cause of the Quincke's disease. Hereditary form was ruled out by normal creatine kinase and reaction to bupivacaine by C1 esterase inhibitor assay. It can be associated with spectrum of anaphylactic reactions and the resuscitation team should be alerted. Airway maintenance should be the primary management strategy. Most cases respond to observation, oxygen therapy and antihistamines with or without steroids. Epinephrine may be required occasionally.

One of the most pronounced effects of climate change on the world’s oceans is the (generally) poleward movement of species and fishery stocks in response to increasing water temperatures. In some regions, such redistributions are already causing dramatic shifts in marine socioecological systems, profoundly altering ecosystem structure and function, challenging domestic and international fisheries, and impacting on human communities. Such effects are expected to become increasingly widespread as waters continue to warm and species ranges continue to shift. Actions taken over the coming decade (2021–2030) can help us adapt to species redistributions and minimise negative impacts on ecosystems and human communities, achieving a more sustainable future in the face of ecosystem change. We describe key drivers related to climate-driven species redistributions that are likely to have a high impact and influence on whether a sustainable future is achievable by 2030. We posit two different futures—a ‘business as usual’ future and a technically achievable and more sustainable future, aligned with the Sustainable Development Goals. We then identify concrete actions that provide a pathway towards the more sustainable 2030 and that acknowledge and include Indigenous perspectives. Achieving this sustainable future will depend on improved monitoring and detection, and on adaptive, cooperative management to proactively respond to the challenge of species redistribution. We synthesise examples of such actions as the basis of a strategic approach to tackle this global-scale challenge for the benefit of humanity and ecosystems.

Correspondence to Dr Janet E McDonagh, Centre for MSK Research, University of Manchester, Manchester M13 9PT, UK; janet.mcdonagh@manchester.ac.uk We would like to commend the timely review by Dr Odgers and colleagues,1 highlighting the lack of child/caregiver involvement and the need for greater clarity in methodology in studies, eliciting stakeholder priorities for paediatric chronic disease research. The results of this research have been published3 including a recent paper detailing how young people want to be involved in research.4 The research has subsequently informed the involvement strategy for the Barbara Ansell National Network for Adolescent Rheumatology (https://www.bannar.org.uk) to facilitate the future ethical and meaningful involvement of young people at all stages of research. To our knowledge, this is the largest qualitative national study involving young people at all stages of adolescent and young adult development in research priority setting and already has had major impact in the establishment of a national youth advisory panel—Your Rheum.

Background The involvement of people of all ages including young people in research is now widely advocated but prioritisation of research topics is still driven largely by professional agendas. Evidence from adult literature has reported a mismatch between a researcher and patient generated list of research topics. There have been no studies to date exploring the priorities of young people with long term conditions other than in SLE. The study aimed to explore the research priorities of young people across the UK with respect to rheumatic conditions. Methods Focus groups were undertaken with young people aged 11–24 years with rheumatic conditions recruited across the UK via members of the Barbara Ansell National Network for Adolescent Rheumatology BANNAR and relevant national charities. Data was analysed using a Framework approach. Participants discussed their beliefs about what should be researched in: Basic Science; Clinical Medicine; Health Services, Psychosocial, and Public Health. They were then invited to prioritize these areas in terms of how much funding they should receive. Results Thirteen focus groups were held involving 63 participants (18 males: 45 females, mean age 16 years, range 10 to 24) in all four nations of the UK. Young people’s research priorities were influenced by whether they felt research would achieve benefits for all or just some patients and long or short term goals. Another influence was whether participants felt that research areas were already well funded. Across all groups, Basic Science was a key priority and participants felt that psychosocial research should be prioritized more. Health Services Research was a lower priority, as the majority of participants were happy with their care. Clinical medicine was not a high priority as young people were happy with their medication or uncomfortable with trying new ones. Finally, for nearly all groups, Public Health was a low priority. Differences were also observed between the two age groups and across the geographically diverse focus groups. Conclusion Understanding young people’s research priorities is important to develop research that is in tune with their needs. The results highlight the importance of considering the whole age range of adolescence and young adulthood as well as geographical diversity. The findings from this work will inform the future research of the Barbara Ansell National Network for Adolescent Rheumatology BANNAR in the UK.

Background Involving people of all ages in health research is now widely advocated. To date, no studies have explored whether and how young people with chronic rheumatic conditions want to be involved in influencing health research. This study aimed to explore amongst young people with rheumatic conditions, 1) their experiences of research participation and involvement 2) their beliefs about research involvement and 3) beliefs about how young people’s involvement should be organized in the future. Methods Focus groups discussions with young people aged 11–24 years with rheumatic conditions across the UK. Data was analysed using a qualitative Framework approach. Results Thirteen focus groups were held involving 63 participants (45 F: 18 M, mean age 16, range 10 to 24 years) across the UK. All believed that young people had a right to be involved in influencing research and to be consulted by researchers. However, experience of research involvement varied greatly. For many, the current project was the first time they had been involved. Amongst those with experience of research involvement, awareness of what they had been involved in and why was often low. Those who had previously participated in research appeared more positive and confident about influencing research in the future. However, all felt that there were limited opportunities for them to be both research participants and to get involved in research as public contributors. Conclusions These findings suggest that there is an on-going need to both increase awareness of research involvement and participation of young people in rheumatology as well as amongst young people themselves.