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The purpose of this paper is to explain and establish a link between social-psychological and biological explanations of self-efficacy theory. Specifically, the paper uses a hypothetical rock climbing program to illustrate how a practitioner could enhance the four sources of self-efficacious beliefs (enactive attainment, vicarious experience, verbal persuasion, and physiological state), in a way that would increase the likelihood of releasing four risk/reward brain chemicals (dopamine, serotonin, oxytocin, and endorphin) while decreasing the likelihood of releasing the stress hormone cortisol. By understanding and applying self-efficacy theory at the social-psychological and biological levels--a process called vertical integration--practitioners could improve program implementation and evaluation, thereby enhancing the overall outcomes of their programs. Furthermore, adoption of a vertically integrated self-efficacy theory could help bridge the research--practice gap.

The complexity of head and neck cancers (HNC) mandates a multidisciplinary approach and radiation therapy (RT) plays a critical role in the optimal management of patients with HNC, either as frontline or adjuvant treatment postoperatively. The advent of both definitive and post-operative RT has significantly improved the outcomes of patients with HNC. Herein, we discuss the role of postoperative RT in different subtypes of HNC, its side effects, and the importance of surveillance. The treatment regions discussed in this paper are the oral cavity, nasopharynx, paranasal sinus cavity, oropharynx, larynx and hypopharynx. Multiple studies that demonstrate the importance of definitive and/or postoperative RT, which led to an improved outlook of survival for HNC patients will be discussed.

Objective: To report neurodevelopment at age 5.5 years according to developmental delay screening with the Ages & Stages Questionnaire (ASQ) in late infancy in preterm-born children., Design: Population-based cohort study, EPIPAGE-2., Setting: France, 2011-2017., Participants: 2504 children born at 24-26, 27-31 and 32-34 weeks, free of cerebral palsy, deafness or blindness at 2 years' corrected age., Main Outcome Measures: Moderate/severe, mild or no disability at age 5.5 years using gross and fine motor, sensory, cognitive and behavioural evaluations. Results of the ASQ completed between 22 and 26 months' corrected age described as positive screening or not., Results: Among 2504 participants, 38.3% had ASQ positive screening. The probability of having moderate/severe or mild disability was higher for children with ASQ positive versus negative screening: 14.2% vs 7.0%, adjusted OR 2.5 (95% CI 1.8 to 3.4), and 37.6% vs 29.7%, adjusted OR 1.5 (1.2 to 1.9). For children with ASQ positive screening, the probability of having neurodevelopmental disabilities at age 5.5 years was associated with the number of domain scores below threshold, very low gestational age and severe neonatal morbidities. For children with ASQ negative screening, this probability was increased for boys and children born small-for-gestational age. For both groups, maternal level of education was strongly associated with outcomes., Conclusion: In preterm-born children, ASQ screening at 2 years' corrected age was associated with neurodevelopmental disabilities at age 5.5 years. However, other factors should be considered when interpreting the ASQ data to draw further follow-up., Trial Registration Number: 2016-A00333-48., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC)., Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss., Results: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1., Conclusions: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: Symptom-triggered testing for ovarian cancer was introduced to the UK whereby symptomatic women undergo an ultrasound scan and serum CA125, and are referred to hospital within 2 weeks if these are abnormal. The potential value of symptom-triggered testing in the detection of early-stage disease or low tumor burden remains unclear in women with high grade serous ovarian cancer. In this descriptive study, we report on the International Federation of Gynecology and Obstetrics (FIGO) stage, disease distribution, and complete cytoreduction rates in women presenting via the fast-track pathway and who were diagnosed with high grade serous ovarian cancer., Methods: We analyzed the dataset from Refining Ovarian Cancer Test accuracy Scores (ROCkeTS), a single-arm prospective diagnostic test accuracy study recruiting from 24 hospitals in the UK. The aim of ROCkeTS is to validate risk prediction models in symptomatic women. We undertook an opportunistic analysis for women recruited between June 2015 to July 2022 and who were diagnosed with high grade serous ovarian cancer via the fast-track pathway. Women presenting with symptoms suspicious for ovarian cancer receive a CA125 blood test and an ultrasound scan if the CA125 level is abnormal. If either of these is abnormal, women are referred to secondary care within 2 weeks. Histology details were available on all women who underwent surgery or biopsy within 3 months of recruitment. Women who did not undergo surgery or biopsy at 3 months were followed up for 12 months as per the national guidelines in the UK. In this descriptive study, we report on patient demographics (age and menopausal status), WHO performance status, FIGO stage at diagnosis, disease distribution (low/pelvic confined, moderate/extending to mid-abdomen, high/extending to upper abdomen) and complete cytoreduction rates in women who underwent surgery., Results: Of 1741 participants recruited via the fast-track pathway, 119 (6.8%) were diagnosed with high grade serous ovarian cancer. The median age was 63 years (range 32-89). Of these, 112 (94.1%) patients had a performance status of 0 and 1, 30 (25.2%) were diagnosed with stages I/II, and the disease distribution was low-to-moderate in 77 (64.7%). Complete and optimal cytoreduction were achieved in 73 (61.3%) and 18 (15.1%). The extent of disease was low in 43 of 119 (36.1%), moderate in 34 of 119 (28.6%), high in 32 of 119 (26.9%), and not available in 10 of 119 (8.4%). Nearly two thirds, that is 78 of 119 (65.5%) women with high grade serous ovarian cancer, underwent primary debulking surgery, 36 of 119 (30.3%) received neoadjuvant chemotherapy followed by interval debulking surgery, and 5 of 119 (4.2%) women did not undergo surgery., Conclusion: Our results demonstrate that one in four women identified with high grade serous ovarian cancer through the fast-track pathway following symptom-triggered testing was diagnosed with early-stage disease. Symptom-triggered testing may help identify women with a low disease burden, potentially contributing to high complete cytoreduction rates., Competing Interests: Competing interests: SS has received honoraria from AstraZeneca, GSK, Mercke, Immunogen and research funding from AoA diagnostics. UM had stock ownership awarded by University College London (UCL) between until October 2021 in Abcodia, which holds the license for ROCA. She has received grants and AGM has been funded by grants from the Medical Research Council (MRC), Cancer Research UK, National Institute for Health Research (NIHR) and The Eve Appeal. UM has also received grants from UK Innovate and National Health and Medical Research Council (NHMRC), Australia and salary support from UCL Hospital Biomedical Research Centre. UM and AGM report funded research collaborations with industry - iLOF (intelligent Lab on Fiber), RNA Guardian, Micronoma, Mercy BioAnalytics and academics - Cambridge University, QIMR Berghofer Medical Research Institute, Imperial College London, University of Innsbruck and Dana Farber USA. UM holds patent number EP10178345.4 for Breast Cancer Diagnostics. AGM is a member of ACED Gynaecological Cancer Working Group and is ACED Co-Director Research Domain Trials. All other authors report no conflict of interest., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Women who suffer an early pregnancy loss require specific clinical care, aftercare, and ongoing support. In the UK, the clinical management of early pregnancy complications, including loss is provided mainly through specialist Early Pregnancy Assessment Units. The COVID-19 pandemic fundamentally changed the way in which maternity and gynaecological care was delivered, as health systems moved to rapidly reconfigure and re-organise services, aiming to reduce the risk and spread of SARS-CoV-2 infection. PUDDLES is an international collaboration investigating the pandemic's impact on care for people who suffered a perinatal bereavement. Presented here are initial qualitative findings undertaken with UK-based women who suffered early pregnancy losses during the pandemic, about how they navigated the healthcare system and its restrictions, and how they were supported., Methods: In-keeping with a qualitative research design, in-depth semi-structured interviews were undertaken with an opportunity sample of women (N = 32) who suffered any early pregnancy loss during the COVID-19 pandemic. Data were analysed using a template analysis to understand women's access to services, care, and networks of support, during the pandemic following their pregnancy loss. The thematic template was based on findings from parents who had suffered a late-miscarriage, stillbirth, or neonatal death in the UK, during the pandemic., Results: All women had experienced reconfigured maternity and early pregnancy services. Data supported themes of: 1) COVID-19 Restrictions as Impractical & Impersonal; 2) Alone, with Only Staff to Support Them; 3) Reduction in Service Provision Leading to Perceived Devaluation in Care; and 4) Seeking Their Own Support. Results suggest access to early pregnancy loss services was reduced and pandemic-related restrictions were often impractical (i.e., restrictions added to burden of accessing or receiving care). Women often reported being isolated and, concerningly, aspects of early pregnancy loss services were reported as sub-optimal., Conclusions: These findings provide important insight for the recovery and rebuilding of health services in the post-pandemic period and help us prepare for providing a higher standard of care in the future and through any other health system shocks. Conclusions made can inform future policy and planning to ensure best possible support for women who experience early pregnancy loss., (© 2024. The Author(s).)

Active inflammatory arthritis in pregnancy is associated with an increased risk of adverse pregnancy outcomes. Treatment of active inflammation and maintenance of low disease activity with medication reduces these risks. Therapeutic decisions on disease-modifying antirheumatic drugs (DMARDs) in pregnancy are complicated by safety concerns, which have led to inappropriate withdrawal of treatment and consequential harm to mother and fetus. Studies of inflammatory arthritis in pregnancy have consistently shown minimal safety concerns with the use of biological DMARDs and an increased risk of disease flare with discontinuation of biological DMARDs. It is our opinion that during pregnancy, the benefits of disease control with biological DMARDs, when required in addition to conventional synthetic DMARDs, outweigh the risks. In this Series paper, we review the reasons for reconsideration of equipoise and propose an agenda for future research to optimise the use of biological DMARDs in inflammatory arthritis during pregnancy., Competing Interests: Declaration of interests IG has received grants from Union Chimique Belge (UCB), honoraria from MGP as a coauthor on an educational review article in 2020, and speaker fees from UCB, and has participated in advisory boards for UCB. IT has received speaker fees from UCB. CN-P has received speaker fees from UCB and participated in advisory boards for UCB. CT has received honoraria to provide an online lecture in a related area in 2022 and to be coauthor on an educational review article in 2020 (from MGP), and has acted as an expert witness for obstetric cases in the UK. SD has received speaker and consulting fees from UCB. NF has received consulting fees from ALK, Sanofi Aventis, Gideon Richter, Abbot, Galderma, AstraZeneca, Ipsen, Vertex, Thea, Novo Nordisk, Aimmune, and Ipsen; speaker fees from Abbott Singapore; and has participated in advisory boards for Orion. RJEMD has received grants paid to his department from the Dutch Arthritis Association, ZonMw, UCB, and Galapagos; consulting fees from Galapagos and UCB; and speaker fees from UCB, Roche, AbbVie, Genzyme, Novartis, AstraZeneca, and Eli Lilly; and has participated in advisory boards for Galapagos and UCB. MEBC has received grants and consulting fees from GSK and UCB and has participated in advisory boards for MotherToBaby. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A 165 ) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A 165 (1 × 10 10 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A 165 increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A 165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A 165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A 165 normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR., (© 2024. The Author(s).)

A questionnaire-based study was jointly organised by European Board and College of Obstetrics and Gynaecology and European Society of Contraception to evaluate the current status as regards access and quality of care regarding contraception, abortion care, and pre-conceptional counselling and care among the 26 European countries. There are considerable variations among these countries as regards the provision of contraceptive services and abortion care. There is ample room for improvement through European training and education programs. However, the most important difference is the absence of a comprehensive network of healthcare providers in various countries to deliver these services at different points of access. There is notable absence of educational programs and instructional materials tailored specifically for nurses and midwives in several countries. This deficiency impedes the professional development and skills enhancement of these healthcare professionals, potentially compromising the quality of healthcare services provided to women in these countries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Male factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy., Objective: We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis., Methods: We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI)., Results: We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78-3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23-4.62), tamoxifen (SMD - 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD - 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44-2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo., Conclusion: There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men., Prospero: CRD42023430179., (© 2024. The Author(s).)

Background: Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT "Stitch, Pessary, or Progesterone Randomised Trial" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy., Methods and Findings: SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks' gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks' gestation. Secondary outcomes included PTB <34 weeks', <30 weeks', and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14+0 and 23+6 weeks' gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) -0.7% [-12.1 to 10.7], cerclage versus progesterone RD 6.2% [-5.0 to 17.0], and progesterone versus pessary RD -6.9% [-17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic., Conclusions: In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapies would be reasonable clinical management. These results can be used as a counselling tool for clinicians when managing women with a short cervix., Trial Registration: EU Clinical Trials register. EudraCT Number: 2015-000456-15, clinicaltrialsregister.eu., ISRCTN Registry: ISRCTN13364447, isrctn.com., Competing Interests: AS is a member of PLOS Medicine’s editorial board. The authors have declared that no other competing interests exist., (Copyright: © 2024 Hezelgrave et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To evaluate the accuracy of combined models of maternal biophysical factors, ultrasound, and biochemical markers for predicting stillbirths., Methods: A retrospective cohort study of pregnant women undergoing first-trimester pre-eclampsia screening at 11-13 gestational weeks was conducted. Maternal characteristics and history, mean arterial pressure (MAP) measurement, uterine artery pulsatility index (UtA-PI) ultrasound, maternal ophthalmic peak ratio Doppler, and placental growth factor (PlGF) serum were collected during the visit. Stillbirth was classified as placental dysfunction-related when it occurred with pre-eclampsia or birth weight <10th percentile. Combined prediction models were developed from significant variables in stillbirths, placental dysfunction-related, and controls. We used the area under the receiver-operating-characteristics curve (AUC), sensitivity, and specificity based on a specific cutoff to evaluate the model's predictive performance by measuring the capacity to distinguish between stillbirths and live births., Results: There were 13 (0.79%) cases of stillbirth in 1643 women included in the analysis. The combination of maternal factors, MAP, UtA-PI, and PlGF, significantly contributed to the prediction of stillbirth. This model was a good predictor for all (including controls) types of stillbirth (AUC 0.879, 95% CI: 0.799-0.959, sensitivity of 99.3%, specificity of 38.5%), and an excellent predictor for placental dysfunction-related stillbirth (AUC 0.984, 95% CI: 0.960-1.000, sensitivity of 98.5, specificity of 85.7)., Conclusion: Screening at 11-13 weeks' gestation by combining maternal factors, MAP, UtA-PI, and PlGF, can predict a high proportion of stillbirths. Our model has good accuracy for predicting stillbirths, predominantly placental dysfunction-related stillbirths., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Introduction: Intra-abdominal drains are often placed in emergency gastrointestinal surgery procedures with the aim to prevent the formation of intra-abdominal collections (IAC) and aid in their early detection. However, the evidence for this is debated. This scoping review aims to evaluate the current evidence for their use in this setting., Methods: A literature search was performed using MEDLINE via PubMed, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. Primary studies published between January 2000 and September 2023 that assessed intra-abdominal drain placement and post-operative IAC formation in emergency gastrointestinal surgery were included., Results: A total of 26 articles were identified. There was no strong evidence to suggest that prophylactic intra-abdominal drain placement influences the formation of IAC in emergency gastrointestinal procedures. There was a suggestion that drain placement may increase the rate of surgical site infection and length of hospital stay. However, current studies on the topic are of poor quality and high risk of bias., Conclusion: The undifferentiated use of drains in emergency gastrointestinal surgery should not be encouraged. Drain placement should be specific to the clinical context. Higher quality research is warranted to better understand the influence drain placement has on post-operative outcomes., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age-related disease. Ninety-eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24-86 years). We used nonlinear and penalized regression to model CA and time to all-cause mortality. We examined associations of four new and two previously published metabolomic age models, with aging risk factors and phenotypes. Within the UK Biobank (N ≈102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type-2 diabetes mellitus, cancer, dementia, and chronic obstructive pulmonary disease), and all-cause mortality. Seven-fold cross-validated Pearson's r between metabolomic age models and CA ranged between 0.47 and 0.65 in the training cohort set (mean absolute error: 8-9 years). Metabolomic age models, adjusted for CA, were associated with C-reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with CA were modest (r = 0.29-0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06/metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objective: To create a sensorised surgical glove that can accurately identify obstetric anal sphincter injury to facilitate timely repair, reduce complications and aid training., Design: Proof-of-concept., Setting: Laboratory., Sample: Pig models., Methods: Flexible triboelectric pressure/force sensors were mounted onto the fingertips of a routine surgical glove. The sensors produce a current when rubbed on materials of different characteristics which can be analysed. A per rectum examination was performed on the intact sphincter of pig cadavers, analogous to routine examination for obstetric anal sphincter injuries postpartum. An anal sphincter defect was created by cutting through the vaginal mucosa and into the external anal sphincter using a scalpel. The sphincter was then re-examined. Data and signals were interpreted., Main Outcome Measures: Sensitivity and specificity of the glove in detecting anal sphincter injury., Results: In all, 200 examinations were performed. The sensors detected anal sphincter injuries in a pig model with sensitivities between 98% and 100% and a specificity of 100%. The current produced when examining an intact sphincter and sphincter with a defect was significantly different (p < 0.001)., Conclusion: In this preliminary study, the sensorised glove accurately detected anal sphincter injury in a pig model. Future plans include its clinical translation, starting with an in-human study on postpartum women, to determine whether it can accurately detect different types of obstetric anal sphincter injury in vivo., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Introduction: This study aims to investigate probe motion during full mid-trimester anomaly scans., Methods: We undertook a prospective, observational study of obstetric sonographers at a UK University Teaching Hospital. We collected prospectively full-length video recordings of routine second-trimester anomaly scans synchronized with probe trajectory tracking data during the scan. Videos were reviewed and trajectories analyzed using duration, path metrics (path length, velocity, acceleration, jerk, and volume) and angular metrics (spectral arc, angular area, angular velocity, angular acceleration, and angular jerk). These trajectories were then compared according to the participant level of expertise, fetal presentation, and patient BMI., Results: A total of 17 anomaly scans were recorded. The average velocity of the probe was 12.9 ± 3.4 mm/s for the consultants versus 24.6 ± 5.7 mm/s for the fellows (p = 0.02), the average acceleration 170.4 ± 26.3 mm/s 2 versus 328.9 ± 62.7 mm/s 2 (p = 0.02), and the average jerk 7491.7 ± 1056.1 mm/s 3 versus 14944.1 ± 3146.3 mm/s 3 (p = 0.02), the working volume 9.10 6  ± 4.10 6 mm 3 versus 29.10 6  ± 11.10 6 mm 3 (p = 0.03), respectively. The angular metrics were not significantly different according to the participant level of expertise, the fetal presentation, or to patients BMI., Conclusion: Some differences in the probe path metrics (velocity, acceleration, jerk and working volume) were noticed according to operator's level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Due to increasing life expectancy, women spend a significant part of their lives in menopause. Women with a history of endometriosis are more likely to become menopausal at an early age due to bilateral oophorectomy or repeated ovarian surgery. In addition, some medical therapies used for endometriosis, such as gonadotropin releasing hormone agonists or progestins reduce bone mineral density. Furthermore, women with endometriosis have a higher background risk of cardiovascular disorders and hypercholesterolemia. Hence, it is important to recommend the use of hormone replacement therapy (HRT) to these women when they become menopausal, at least until the age of natural menopause. Although based on limited data, there is a possibility of reactivation of symptoms of endometriosis or its lesions, and a theoretical possibility of malignant transformation, although this remains unproven. Therefore, women should be advised in the light of this information before starting HRT after the age of natural menopause and are asked to seek help if they experience symptoms that may indicate these changes. Estrogen only HRT should be avoided and combined HRT preparations should be recommended, even after a hysterectomy., Competing Interests: Conflict of Interest: No conflict of interest is declared by the authors., (Copyright© 2024 The Author. Published by Galenos Publishing House on behalf of Turkish-German Gynecological Association. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 (CC BY-NC-ND) International License.)

Although the central role of adequate blood flow and oxygen delivery is known, the lack of optimized imaging modalities to study placental structure has impeded our understanding of its vascular function. Magnetic resonance imaging is increasingly being applied in this field, but gaps in knowledge remain, and further methodological developments are needed. In particular, the ability to distinguish maternal from fetal placental perfusion and the understanding of how individual placental lobules are functioning are lacking. The potential clinical benefits of developing noninvasive tools for the in vivo assessment of blood flow and oxygenation, two key determinants of placental function, are tremendous. Here, we summarize a number of structural and functional magnetic resonance imaging techniques that have been developed and applied in animal models and studies of human pregnancy over the past decade. We discuss the potential applications and limitations of these approaches. Their combination provides a novel source of contrast to allow analysis of placental structure and function at the level of the lobule. We outline the physiological mechanisms of placental T2 and T2* decay and devise a model of how tissue composition affects the observed relaxation properties. We apply this modeling to longitudinal magnetic resonance imaging data obtained from a preclinical pregnant nonhuman primate model to provide initial proof-of-concept data for this methodology, which quantifies oxygen transfer and placental structure across and between lobules. This method has the potential to improve our understanding and clinical management of placental insufficiency once validation in a larger nonhuman primate cohort is complete., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Introduction: Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4., Methods and Analysis: BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1-5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in COL1A1 or COL1A2 can be included in the trial.Each subject receives four intravenous doses of 3×10 6 /kg BOOST cells at 4 month intervals, with 48 (doses 1-2) or 24 (doses 3-4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally.The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover., Ethics and Dissemination: The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals., Trial Registration Numbers: EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482., Competing Interests: Competing interests: ALD is a consultant for Esperare Foundation for a clinical trial unrelated to this work. CG, LW-J and MW are cofounders and coowners of BOOST Pharma ApS founded in 2020. OS is a scientific advisor for BOOST Pharma ApS., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To determine whether obstetric outcomes differ between women with endometriosis and those without, where all women undergo first-trimester screening for endometriosis., Design: A prospective observational cohort study., Setting: The Early Pregnancy Unit at University College London Hospital, United Kingdom., Patients: Women with a live pregnancy progressing beyond 12 weeks' gestation and concurrent endometriosis (n = 110) or no endometriosis (n = 393)., Intervention: All women underwent a pelvic ultrasound examination in early pregnancy to examine for the presence of endometriosis and uterine abnormalities., Main Outcome Measures: The primary outcome of interest was preterm birth, defined as delivery before 37 completed weeks' gestation. Secondary outcomes included late miscarriage, antepartum hemorrhage, placental site disorders, gestational diabetes, hypertensive disorders of pregnancy, neonates small for gestational age, mode of delivery, intrapartum sepsis, postpartum hemorrhage, and admission to the neonatal unit., Results: Women with a diagnosis of endometriosis did not have statistically significantly higher odds of preterm delivery (adjusted odds ratio [aOR] 1.85 [95% confidence interval {CI} 0.50-6.90]), but they did have higher odds of postpartum hemorrhage during cesarean section (aOR 3.64 [95% CI 2.07-6.35]) and admission of their newborn infant to the neonatal unit (aOR 3.24 [95% CI 1.08-9.73]). Women with persistent or recurrent deep endometriosis after surgery also had higher odds of placental site disorders (aOR 8.65 [95% CI 1.17-63.71]) and intrapartum sepsis (aOR 3.47 [95% CI 1.02-11.75])., Conclusion: We observed that women with endometriosis do not have higher odds of preterm delivery, irrespective of their disease subtype. However, they do have higher odds of postpartum hemorrhage during the cesarean section and newborn admission to the neonatal unit., Competing Interests: Declaration of Interests E.M.R.B. reported serving as a senior council member of the British Society of Gynaecological Endoscopy. J.K. reported receiving lecture fees from The Slovenian Medical Association and serving as the vice president of the Slovene Association of Gynaecologists and Obstetricians. N.T. has nothing to disclose. L.D.B. has nothing to disclose. F.T. has nothing to disclose. M.H. reported serving as a senior council member of the British Society of Gynaecological Endoscopy and receiving consulting fees to their institution and funding for attendance at the World Endometriosis Congress from Theramex in relation to fibroid management. A.D. has nothing to disclose. D.J. has nothing to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Introduction: Unplanned pregnancies are associated with increased risks. Despite this, they are currently not routinely detected during antenatal care. This study evaluates the implementation of the London Measure of Unplanned Pregnancy (LMUP) - a validated measure of pregnancy planning - into antenatal care at University College London Hospital, Homerton Hospital, and St Thomas' Hospital, England, 2019-2023., Methods: We conducted a mixed methods evaluation of the pilot. Uptake and acceptability were measured using anonymized data with non-completion of the LMUP as a proxy measure of acceptability overall. We conducted focus groups with midwives, and one-to-one interviews with women, to explore their thoughts of asking, or being asked the LMUP, which we analyzed with a Framework Analysis., Results: Asking the LMUP at antenatal appointments is feasible and acceptable to women and midwives, and the LMUP performed as expected. Advantages of asking the LMUP, highlighted by participants, include providing additional support and personalizing care. Midwives' concerns about judgment were unsubstantiated; women with unplanned pregnancies valued such discussions., Conclusions: These findings support the implementation of the LMUP in routine antenatal care and show how it can provide valuable insights into the circumstances of women's pregnancies. This can be used to help midwives personalize care, and potentially reduce adverse outcomes and subsequent unplanned pregnancy. Integration of the LMUP into the Maternity Services Data Set will establish national data collection of a validated measure of unplanned pregnancy and enable analysis of the prevalence, factors, and implications of unplanned pregnancies across subpopulations and over time to inform implementation., Competing Interests: The authors have each completed and submitted an ICMJE form for Disclosure of Potential Conflicts of Interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. J. Hall and C. Stewart report that Dama Health made payments to their institution for research consultancy relating to contraception research. H. Duncan reports that she has a leadership/fiduciary role in the coalition of academic experts and public health professionals of the UK Preconception Partnership and in the Ministerial taskforce for supporting with evidence and data from a civil service perspective of the Maternity Disparities Taskforce. She also reports substantive employment in The Office for Health Improvement and Disparities at the Department of Health and Social Care. J. Hall reports that travel and accommodation costs to attend an Annual Scientific Meeting in June 2023, were covered by the Faculty of Sexual and Reproductive Health; the NIHR Advanced Fellowship funds her salary and this research; she participates in the Data Safety Monitoring Board of ALERT; and she is a member without payment of the NHS England Maternity Transformation Programme, Public Health and Prevention Advisory Group and the Faculty of Sexual and Reproductive Health Research Group. H. Lovell reports that she has received a personal research development award from the NIHR Doctoral Clinical Academic Research Fellowship (Grant number 302860)., (© 2024 Hall J.A. et al.)

Background: Better use of healthcare systems data, collected as part of interactions between patients and the healthcare system, could transform planning and conduct of randomised controlled trials. Multiple challenges to widespread use include whether healthcare systems data captures sufficiently well the data traditionally captured on case report forms. "Data Utility Comparison Studies" (DUCkS) assess the utility of healthcare systems data for RCTs by comparison to data collected by the trial. Despite their importance, there are few published UK examples of DUCkS., Methods-And-Results: Building from ongoing and selected recent examples of UK-led DUCkS in the literature, we set out experience-based considerations for the conduct of future DUCkS. Developed through informal iterative discussions in many forums, considerations are offered for planning, protocol development, data, analysis and reporting, with comparisons at "patient-level" or "trial-level", depending on the item of interest and trial status., Discussion: DUCkS could be a valuable tool in assessing where healthcare systems data can be used for trials and in which trial teams can play a leading role. There is a pressing need for trials to be more efficient in their delivery and research waste must be reduced. Trials have been making inconsistent use of healthcare systems data, not least because of an absence of evidence of utility. DUCkS can also help to identify challenges in using healthcare systems data, such as linkage (access and timing) and data quality. We encourage trial teams to incorporate and report DUCkS in trials and funders and data providers to support them., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CB is now employed at Insitro, South San Francisco, CA. Insitro had no involvement in the design or implementation of the work presented here., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the baseline symptom burden(SB) experienced by patients(pts) with recurrent ovarian cancer(ROC) prior and associations with progression free survival (PFS) and overall survival (OS)., Methods: We analysed baseline SB reported by pts. with platinum resistant/refractory ROC (PRR-ROC) or potentially‑platinum sensitive ROC receiving their third or greater line of chemotherapy (PPS-ROC≥3) enrolled in the Gynecologic Cancer InterGroup - Symptom Benefit Study (GCIG-SBS) using the Measure of Ovarian Symptoms and Treatment concerns (MOST). The severity of baseline symptoms was correlated with PFS and OS., Results: The 948 pts. reported substantial baseline SB. Almost 80% reported mild to severe pain, and 75% abdominal symptoms. Shortness of breath was reported by 60% and 90% reported fatigue. About 50% reported moderate to severe anxiety, and 35% moderate to severe depression. Most (89%) reported 1 or more symptoms as moderate or severe, 59% scored 6 or more symptoms moderate or severe, and 46% scored 9 or more symptoms as moderate or severe. Higher SB was associated with significantly shortened PFS and OS; five symptoms had OS hazard ratios larger than 2 for both moderate and severe symptom cut-offs (trouble eating, vomiting, indigestion, loss of appetite, and nausea; p < 0.001)., Conclusion: Pts with ROC reported high SB prior to starting palliative chemotherapy, similar among PRR-ROC and PPS-ROC≥3. High SB was strongly associated with early progression and death. SB should be actively managed and used to stratify patients in clinical trials. Clinical trials should measure and report symptom burden and the impact of treatment on symptom control., Competing Interests: Conflict of interest statement FR acknowledges travel grant from Pfizer. Y-CL acknowledges institutional research grant from Beigene, honoraria from Astra Zeneca for educational event and received honoraria from GSK for participation in advisory board. MF acknowledges institutional grants from Astra Zeneca, Beigene, Novartis; received honoraria from Astra Zeneca, GSK, MSD; consulting fees from Astra Zeneca, Novartis, GSK, Incyclix. JL acknowledges grants from Astra Zeneca, MSD/Merck; advisory board for Astra Zeneca, Clovis Oncology, GSK, Artios Pharma, MSD/Merck, VBL Therapeutics, BMS, Nuvation, Ellipses, Immagene, Incyte, Immunogen; educational events for Astra Zeneca, MSD/Merck, GSK, Eisai, Neopharm, and data safety monitoring board for Mersana. AO acknowledges data safety monitoring board for Morphosys, Astra Zeneca, BMS, and uncompensated leadership role for Ozmosis Research where he is CEO and Board member. FH acknowledges grants from GSK, Astra Zeneca, MSD, PharmaMar, Immunogen, consulting fees from Immunogen, MSD, Astra Zeneca; honoraria from GSK, Astra Zeneca, MSD, Pharma Mar; and has been on data safety monitoring boards for MSD, GSK and Astra Zeneca. JB acknowledges grants from Tesaro, Eisai, Immunogen, Karyopharm. MS acknowledges institutional grants from Astellas, Amgen, Astra Zeneca, Bionomics, BMS, Celgene, Medivation, Merck, Sharp and Dohme, Pfizer, Roche and Sanofi. MK, RO, EA-L, FJ, M-CK, YY, DB and AL declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Respiratory syncytial virus (RSV) causes a severe respiratory condition, bronchiolitis, in infants but not in adults. Bronchiolitis is characterised by neutrophilic infiltration in the airways, but whether neutrophils enhance recovery from infection or contribute to its pathology remains unknown., Methods: We used a novel in-vitro model to compare term umbilical cord blood (infant) (n=17 donors) and adult neutrophils (n=15 donors) during migration across RSV-infected differentiated human nasal airway epithelial cells (AECs) in a basolateral to apical direction., Results: Greater numbers of infant neutrophils (mean (95% CI)) (336 684 (242 352 to 431 015)) migrated across RSV-infected AECs to the apical compartment (equivalent to the airway lumen) compared with adult neutrophils (56 586 (24 954 to 88 218)) (p<0.0001). Having reached the apical compartment of infected AECs, much greater numbers of infant neutrophils (140 787 (103 117 to 178 456)) became apoptotic compared with adult (5853 (444 to 11 261)) (p=0.002). Infant neutrophils displayed much greater expression of CD11b, CD64, neutrophil elastase (NE) and myeloperoxidase (MPO) than adult neutrophils at baseline and at all points of migration. However, as adult neutrophils migrated, expression of CD11b, CD64, NE and MPO became greater than at baseline., Discussion: The high proportion of infant neutrophils migrating across RSV-infected AECs correlates with the neutrophilic infiltrate seen in infants with severe RSV bronchiolitis, with large numbers undergoing apoptosis, which may represent a protective mechanism during infection. Compared with adult neutrophils, infant neutrophils already have high expression of surface markers before contact with AECs or migration, with less capacity to increase further in response to RSV infection or migration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To evaluate the clinical effectiveness of long acting progestogens compared with the combined oral contraceptive pill in preventing recurrence of endometriosis related pain., Design: The PRE-EMPT (preventing recurrence of endometriosis) pragmatic, parallel group, open label, randomised controlled trial., Setting: 34 UK hospitals., Participants: 405 women of reproductive age undergoing conservative surgery for endometriosis., Interventions: Participants were randomised in a 1:1 ratio using a secure internet facility to a long acting progestogen (depot medroxyprogesterone acetate or levonorgestrel releasing intrauterine system) or the combined oral contraceptive pill., Main Outcome Measures: The primary outcome was pain measured three years after randomisation using the pain domain of the Endometriosis Health Profile 30 (EHP-30) questionnaire. Secondary outcomes (evaluated at six months, one, two, and three years) included the four core and six modular domains of the EHP-30, and treatment failure (further therapeutic surgery or second line medical treatment)., Results: 405 women were randomised to receive a long acting progestogen (n=205) or combined oral contraceptive pill (n=200). At three years, there was no difference in pain scores between the groups (adjusted mean difference -0.8, 95% confidence interval -5.7 to 4.2, P=0.76), which had improved by around 40% in both groups compared with preoperative values (an average of 24 and 23 points for long acting progestogen and combined oral contraceptive pill groups, respectively). Most of the other domains of the EHP-30 also showed improvement at all time points compared with preoperative scores, without evidence of any differences between groups. Women randomised to a long acting progestogen underwent fewer surgical procedures or second line treatments compared with those randomised to the combined oral contraceptive pill group (73 v 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00)., Conclusions: Postoperative prescription of a long acting progestogen or the combined oral contraceptive pill results in similar levels of improvement in endometriosis related pain at three years, with both groups showing around a 40% improvement compared with preoperative levels. While women can be reassured that both options are effective, the reduced risk of repeat surgery for endometriosis and hysterectomy might make long acting reversible progestogens preferable for some., Trial Registration: ISRCTN registry ISRCTN97865475., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research for the submitted work. SB declares receiving fees from Merck and Ferring. AWH declares receiving fees from Theramex. TJC declares receiving fees from Bayer and was president of the British Society of Gynaecological Endoscopy during the study. ES declares receiving fees from Hologic, Medtronic, Karl Storz, Intuitive, and Artrex. All other authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Placental mediated pregnancy complications (PMPC) are common, often recurring, and pose a significant health risk to mother and fetus. Evidence suggests that the hypercoagulable state associated with many PMPC, could reflect reduced expression of Annexin 5 (ANXA5), a naturally occurring anticoagulant protein in placental tissue. The ANXA5 M2 haplotype is a genetic variant, which results in reduced expression of ANXA5 protein. M2 haplotype carrier couples may therefore be at increased risk of PMPC. Evidence regarding the effectiveness of anticoagulation to prevent PMPC is inconsistent. Furthermore, studies have not selected or stratified for M2 haplotype carriers, in whom there is a predisposition to hypercoagulability, to assess the effectiveness of anticoagulation, which may vary from those without the M2 haplotype., Objectives and Rationale: The aim of this study was to systematically review the current evidence to assess whether anticoagulant treatment improves pregnancy outcomes in couples positive for M2 haplotype., Search Methods: The review was registered on PROSPERO (CRD42022343943). A comprehensive literature search was performed using MEDLINE, Embase and Cochrane collaboration databases from inception to January 2023. Two reviewers assessed the articles for eligibility and extracted the data simultaneously. Primary outcome was successful pregnancy and live birth. Secondary outcomes included PMPC (implantation failure, miscarriage, pre-eclampsia, preterm birth and fetal growth restriction)., Outcomes: From a pool of 410 references, 10 were selected for full text review, of which three studies (a post hoc analysis of a randomised controlled trial, cohort study and a case report) were included in this review. Included studies comprised of 223 individuals, 129 of whom who received anticoagulation treatment after testing positive for M2 haplotype. The studies collectively showed an improvement in pregnancy outcomes in M2 haplotype positive individuals however, given the heterogeneity of studies, it was not possible to conduct a meta-analysis and draw firm conclusions., Wider Implications: Current evidence is limited, such that the value of screening couples for the M2 haplotype to select or stratify for treatment with prophylactic anticoagulation remains unknown. Thus, further studies including well designed, large, multi-centre randomised controlled trials are required to assess whether anticoagulation treatment will be effective in improving pregnancy outcomes in M2 haplotype couples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Research has shown that many babies who die in neonatal units could have been potential tissue and/or organ donors. Despite the existence of guidelines supporting its implementation, the incidence of neonatal donation remains rare in the United Kingdom., Aim: The aim of this audit was to retrospectively determine potential eligibility for neonatal tissue and/or organ donation referral in infants who died in a single UK tertiary-level neonatal unit between 2012 and 2021. Cause of death and documentation of any discussions held regarding referral for donation were also explored., Study Design: An audit was undertaken to identify all neonatal deaths at a single tertiary-level NICU in London from 2012-2021. Infants who retrospectively could have been referred as potential tissue and/or organ donors were identified using current NHS Blood and Transplant inclusion and exclusion criteria., Results and Conclusion: A significant missed potential for neonatal tissue and/or organ donation referrals was identified, which is likely not just limited to the unit audited. Causes of death were as expected for a tertiary level neonatal unit and centre for therapeutic cooling of babies born with hypoxic perinatal brain injuries. Only one documented conversation was found regarding neonatal donation., Relevance to Clinical Practice: To enable conversations regarding neonatal donation to become a routine part of end-of-life care discussions with families as appropriate, good links between neonatal healthcare professionals and Specialist Nurses in Organ Donation need to be established. This will facilitate the referral of all suitable neonates as potential donors and ensure that neonatal staff feel supported to care for babies identified as potential donors., (© 2023 British Association of Critical Care Nurses.)

Objectives: To assess the utility of Art & Craft - a new, hands-on course on Advanced Rotational Techniques and safe Caesarean biRth at Advanced/Full dilation Training aimed at senior Obstetrics trainees. The aims were to assess whether it improved confidence and skills in rotational vaginal birth, impacted fetal head at caesarean, and ultrasound for fetal position., Study Design: With ethical approval, pre- and post- course questionnaires and post- course interviews of attendees were conducted. A pre course questionnaire was emailed 1 week before the course. Attendees were asked to rate their confidence levels in performing vaginal examination and ultrasound assessment of fetal position, rotational ventouse, manual rotation, Kielland's rotational forceps, and disimpaction of the fetal head during second stage caesarean on a scale of 1 to 5. 1 = not confident at all and 5 = very confident. A post-course questionnaire with the same questions was emailed 3 days after. p values for differences in scores were calculated using the Wilcoxon signed rank test using Stata/MP 18 software., Results: 32 trainees attended the course. 28 questionnaires were available for analysis. The majority 39 % were middle grade (ST3-ST5) level. Initial confidence was very low for rotational forceps (median 1/5). After attending the course and practical stations, respondents' confidence levels increased significantly (p < 0.05) across all domains; vaginal examination from 4 to 5, ultrasound for fetal position, rotational ventouse, and manual rotation from 3 to 5, disimpaction from 4 to 4.5, and Kielland's rotational forceps from 1 to 4. Nine participated in post course interviews, which were thematically analysed. Participants expressed that the course gave them the opportunity to ask specific questions from experts to improve their confidence. A barrier to learning new methods was highlighted in that it is difficult to receive practical training in Kielland's, resulting in low confidence., Conclusion: A practical, hands-on course on complex operative birth significantly increases trainee confidence levels in vaginal examination, ultrasound for fetal position, disimpaction, and techniques for rotational vaginal birth. The evaluation highlights that continued education and practise is required, even when trainees are senior. Evaluation of clinical outcomes after training is needed; and planned., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)