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The use of tranexamic acid for postpartum hemorrhage has entered obstetric practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during caesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error appear to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard; and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug error mortality.

Background There is an absence of clinically relevant epidemiological data in regional Australia pertaining to haematological malignancies. Aim To determine the incidence and geographical variation of haematological malignancies in North Queensland using a clinically appropriate disease classification. Methods Retrospective, observational study of individual patient data records of all adults diagnosed with a haematological malignancy between 2005-2014 and residing within The Townsville Hospital Haematology catchment region. We report descriptive summaries, incidence rates and incidence-rate ratios of haematologic malignancies by geographic regions. Results 1581 haematological malignancies (69% lymphoid, 31% myeloid) were diagnosed over the 10-year study period. Descriptive data is presented for 58 major subtypes as per the WHO diagnostic classification of tumours of haematopoietic and lymphoid tissues. The overall median age at diagnosis was 66 years with a male predominance (60%). We demonstrate a temporal increase in the incidence of haematologic malignancies over the study period. We observed geographical variations in the age-standardised incidence rates per 100,000 ranging from 0.5 to 233.5. Our data suggests an increased incidence rate ratio for haematological malignancies in some postcodes within the Mackay area compared to other regions. Conclusion This study successfully reports on the incidence of haematological malignancies in regional Queensland using a clinically meaningful diagnostic classification system and identifies potential geographic hotspots. We advocate for such contemporary, comprehensive, and clinically meaningful epidemiological data reporting of blood cancer diagnoses in wider Australia. Such an approach will have significant implications toward developing appropriate data-driven management strategies and public health responses for haematological malignancies. This article is protected by copyright. All rights reserved.

Key content Continuing financial constraints on the UK’s National Health Service means the need for clinicians to provide high-quality care in a cost-effective way has never been greater. While the medical education system equips doctors with skills to provide safe clinical care, it should also provide an understanding of healthcare costs and cost-effectiveness analysis. Value-based care is becoming a key paradigm in women’s health services, where clinicians must employ strategies for delivering value, rationalising costs and capitalising on the use of emerging technologies. The calculation of value of an intervention for providers and service users may differ; care must be taken to ensure this concept is adapted for, and not imposed on healthcare systems. Engaging trainees in systems transformation and embedding the concepts of ‘do no financial harm’ are essential to ensure sustainable healthcare services. Learning Objectives To understand the principles of value-based health care. To highlight the importance of adopting ‘cost-conscious’ care within daily clinical practice. To learn the differences between ‘cost’, ‘charge’, ‘price’ and ‘reimbursement. To encourage developing value-based competencies for future medical workforce through utilising out of programme placements and digital resources. Ethical Issues The ethical obligation of clinicians to consider cost may encompass justice and equity. However, the impact of practicing value-based health care is yet to be evaluated.

Recently, fertility services have started resuming since COVID-19 was declared a pandemic, but there remains significant uncertainty in the way this care will be delivered in the United Kingdom. The objective of our study was to explore the impact of COVID-19 on individuals using fertility services in the United Kingdom. The study was conducted in two phases between May 2020 and July 2020: an online questionnaire involving 1212 participants and subsequent individual semi-structured telephone interviews with 15 participants. Through thematic analysis, we learned from the questionnaire findings that 74% of individuals identified as White British, 21% as Black and Minority Ethnic (BAME) and 2.6% as male. Ninety-six per cent of individuals from the questionnaire explained that COVID-19 had a ‘negative impact’ on their fertility treatment, namely ‘delay in care’. Eighty-two per cent of participants discussed concerns about the ‘uncertainty’ they felt about fertility services; these included the ‘unknown impact of COVID-19 on pregnancy outcomes’, the ‘unknown impact on general gynaecology services’ and the ‘unknown impact of COVID-19 on fertility success’. Through semi-structured telephone interviews with 15 participants, we learned about the ‘cultural pressures’ individuals from BAME backgrounds faced in relation to care. Participants were mindful about the ‘pressures on the service’ when reopening, and therefore ‘advancing maternal age’, ‘socio-economic background’ and ‘previous unsuccessful fertility treatment’ were the main factors individuals considered important when ‘prioritising’ fertility care. Our findings can be used by fertility service providers to appreciate the patient perspective when considering the reopening of fertility services nationally and internationally. Lay summary The impact of COVID-19 on patients seeking or undergoing fertility treatment is not entirely known. Many patients have had their treatment postponed during the pandemic. As fertility services begin to recommence, it is important to understand how the pandemic has affected this group of patients. In addition, it is vital to appreciate and understand the patient’s voice in order to ensure services take into account the patients’ concerns as they begin to offer certain fertility treatments. Our study was conducted in two phases and involved an online questionnaire and individual interviews with people. We found that people were worried about services restarting and how care would be prioritised. People also discussed some of the perceived barriers to seeking fertility healthcare. Our findings highlight the importance of understanding the patient’s voice when recommencing fertility services.

Dyspareunia is defined as recurrent or persistent genital pain associated with sexual intercourse. It is a symptom that can have a significant impact on women's health, relationships and quality of life. There are multiple different causes for it, including both organic and psychosexual components. Despite the high prevalence of sexual pain, estimated to between 3 and 18% worldwide, few guidelines exist for its evaluation and management. Adequate assessment requires a comprehensive sexual history, a systematic and thorough examination of the lower genital tract to rule out anatomical causes and an exploration of potential psychosexual causes. Further investigations may include swabs and a pelvic ultrasound scan. In some cases, a diagnostic laparoscopy may be required if there is evidence of endometriosis or utero-vaginal pathology that does not respond to conservative management. This article considers the diagnosis and investigation of women complaining of dyspareunia.

Objectives There are limited case series reporting the impact on women affected by coronavirus during pregnancy. In women affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the case fatality rate appears higher in those affected in pregnancy compared with non-pregnant women. We conducted a rapid review to guide health policy and management of women affected by COVID-19 during pregnancy, which was used to develop the Royal College of Obstetricians and Gynaecologists' (RCOG) guidelines on COVID-19 infection in pregnancy. Methods Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies and randomized controlled trials describing women affected by coronavirus in pregnancy. Data were extracted from relevant papers. This review has been used to develop guidelines with representatives of the Royal College of Paediatrics and Child Health (RCPCH) and RCOG who provided expert consensus on areas in which data were lacking. Results From 9965 search results in PubMed and 600 in MedRxiv, 21 relevant studies, all of which were case reports or case series, were identified. From reports of 32 women to date affected by COVID-19 in pregnancy, delivering 30 babies (one set of twins, three ongoing pregnancies), seven (22%) were asymptomatic and two (6%) were admitted to the intensive care unit (ICU), one of whom remained on extracorporeal membrane oxygenation. No maternal deaths have been reported to date. Delivery was by Cesarean section in 27 cases and by vaginal delivery in two, and 15 (47%) delivered preterm. There was one stillbirth and one neonatal death. In 25 babies, no cases of vertical transmission were reported; 15 were reported as being tested with reverse transcription polymerase chain reaction after delivery. Case fatality rates for SARS and MERS were 15% and 27%, respectively. SARS was associated with miscarriage or intrauterine death in five cases, and fetal growth restriction was noted in two ongoing pregnancies affected by SARS in the third trimester. Conclusions Serious morbidity occurred in 2/32 women with COVID-19, both of whom required ICU care. Compared with SARS and MERS, COVID-19 appears less lethal, acknowledging the limited number of cases reported to date and that one woman remains in a critical condition. Preterm delivery affected 47% of women hospitalized with COVID-19, which may put considerable pressure on neonatal services if the UK's reasonable worst-case scenario of 80% of the population being affected is realized. Based on this review, RCOG, in consultation with RCPCH, developed guidance for delivery and neonatal care in pregnancies affected by COVID-19, which recommends that delivery mode be determined primarily by obstetric indication and recommends against routine separation of affected mothers and their babies. We hope that this review will be helpful for maternity and neonatal services planning their response to COVID-19. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

ObjectivesTo describe the severity of maternal infection when the Omicron SARS-CoV-2 variant was dominant (15/12/21-14/01/22) and compare outcomes among groups with different vaccination status.DesignProspective cohort studySettingUK consultant-led maternity unitsParticipantsPregnant women hospitalised with a positive SARS-CoV-2 PCR test up to 7 days prior to admission and/or during admission up to 2 days after giving birth.Main outcome measuresSymptomatic or asymptomatic infection. Vaccination status. Severity of maternal infection (moderate or severe infection according to modified WHO criteria). Mode of birth and perinatal outcomes.ResultsOut of 1561 women admitted to hospital with SARS-CoV-2 infection, 449 (28.8%) were symptomatic. Among symptomatic women admitted, 86 (19.2%) had moderate to severe infection; 51 (11.4%) had pneumonia on imaging, 62 (14.3%) received respiratory support, and 19 (4.2%) were admitted to the intensive care unit (ICU). Three women died (0.7%). Vaccination status was known for 383 symptomatic women (85.3%) women; 249 (65.0%) were unvaccinated, 45 (11.7%) had received one vaccine dose, 76 (19.8%) had received two doses and 13 (3.4%) had received three doses. 59/249 (23.7%) unvaccinated women had moderate to severe infection, compared to 10/45 (22.2%) who had one dose, 9/76 (11.8%) who had two doses and 0/13 (0%) who had three doses. Among the 19 symptomatic women admitted to ICU, 14 (73.7%) were unvaccinated, 3 (15.8%) had received one dose, 1 (5.3%) had received two doses, 0 (0%) had received 3 doses and 1 (5.3%) had unknown vaccination status.ConclusionThe risk of severe respiratory disease amongst unvaccinated pregnant women admitted with symptomatic SARS-CoV-2 infection during the Omicron dominance period was comparable to that observed during the period the wildtype variant was dominant. Most women with severe disease were unvaccinated. Vaccine coverage among pregnant women admitted with SARS-CoV-2 was low compared to the overall pregnancy population and very low compared to the general population. Ongoing action to prioritise and advocate for vaccine uptake in pregnancy is essential.SUMMARY BOXWhat is already known on this topicIn non-pregnant adults, growing evidence indicates a lower risk of severe respiratory disease with the Omicron SARS-CoV-2 Variant of Concern (VOC).Pregnant women admitted during the periods in which the Alpha and Delta VOC were dominant were at increased risk of moderate to severe SARS-CoV-2 infection compared to the period when the original wildtype infection was dominant.Most women admitted to hospital with symptomatic SARS-CoV-2 infection have been unvaccinated.What this study addsOne in four women who had received no vaccine or a single dose had moderate to severe infection, compared with one in eight women who had received two doses and no women who had received three dosesThe proportional rate of moderate to severe infection in unvaccinated pregnant women during the Omicron dominance period is similar to the rate observed during the wildtype dominance periodOne in eight symptomatic admitted pregnant women needed respiratory support during the period when Omicron was dominant

Introduction There is a lack of population level data on risk factors and impact of severe COVID-19 in pregnancy. The aims of this study were to determine the characteristics, and maternal and perinatal outcomes associated with severe COVID-19 in pregnancy compared with those with mild and moderate COVID-19 and to explore the impact of timing of birth. Material and methods This was a secondary analysis of a national, prospective cohort study. All pregnant women admitted to hospital in the UK with symptomatic SARS-CoV-2 from March 1, 2020 to October 31, 2021 were included. The severity of maternal infection (need for high flow or invasive ventilation, intensive care admission or died), pregnancy and perinatal outcomes, and the impact of timing of birth were analyzed using multivariable logistic regression. Results Of 4436 pregnant women, 13.9% (n = 616) had severe infection. Women with severe infection were more likely to be aged ≥30 years (adjusted odds ratio [aOR] aged 30–39 1.48, 95% confidence interval [CI] 1.20–1.83), be overweight or obese (aOR 1.73, 95% CI 1.34–2.25 and aOR 2.52 95% CI 1.97–3.23, respectively), be of mixed ethnicity (aOR 1.93, 95% CI 1.17–3.21) or have gestational diabetes (aOR 1.43, 95% CI 1.09–1.87) compared with those with mild or moderate infection. Women with severe infection were more likely to have a pre-labor cesarean birth (aOR 8.84, 95% CI 6.61–11.83), a very or extreme preterm birth (28–31+ weeks’ gestation, aOR 18.97, 95% CI 7.78–14.85; Conclusions Severe COVID-19 in pregnancy increases the risk of adverse outcomes. Information to promote uptake of vaccination should specifically target those at greatest risk of severe outcomes. Decisions about timing of birth should be informed by multidisciplinary team discussion; however, our data suggest that women with severe infection who do not require early delivery have mostly good outcomes but that those with severe infection at term may warrant rapid delivery.

Acquired haemophagocytic lymphohistiocytosis (aHLH) is a rare and often fatal process of uncontrolled cytokine release driven by the inability of natural killer cells to eliminate infected or malignant cells. Herein, we report two cases of aHLH complicated by bleeding secondary to coagulopathy due to hypofibrinogenaemia and thrombocytopenia despite appropriate correction with blood products. These cases highlight the effect coagulopathy and thrombocytopenia can have on patient outcomes when trying to confirm and manage the underlying process driving aHLH.

Exposure to coastal flooding is increasing due to growing population and economic activity. These developments go hand-in-hand with a loss and deterioration of ecosystems. Ironically, these ecosystems can play a buffering role in reducing flood hazard. The ability of ecosystems to contribute to reducing coastal flooding has been emphasized in multiple studies. However, the role of ecosystems in hybrid coastal protection (i.e. a combination of ecosystems and levees) has been poorly quantified at a global scale. Here, we evaluate the use of coastal vegetation, mangroves, and marshes fronting levees to reduce global coastal protection costs, by accounting for wave-vegetation interaction.The research is carried out by combining earth observation data and hydrodynamic modelling. We show that incooperating vegetation in hybrid coastal protection results in more sustainable and financially attractive coastal protection strategies. If vegetated foreshore levee systems were established along populated coastlines susceptible to flooding, the required levee crest height could be considerably reduced. This would result in a reduction of 320 (range: 107-961) billion USD2005 Power Purchasing Parity (PPP) in investments, of which 67.5 (range: 22.5- 202) billion USD2005 PPP in urban areas for a 1 in 100-year flood protection level., Nearly one-third of the global coastline is vegetated. Incorporating these vegetation belts in coastal protection strategies would result in more sustainable and financially-attractive designs to mitigate the impacts of extreme coastal storms.

Cadiz Bay is a shallow mesotidal lagoon with extensive populations of the seagrass Cymodocea nodosa at intertidal and shallow subtidal elevations. This work aims to understand the mechanisms behind the resilience of this species to gradual sea level rise by studying its acclimation capacity to depth along the shallow littoral, and therefore, to gradual variations in the light environment. To address this objective, these populations have been monitored seasonally over a 10 year period, representing the longest seasonal database available in the literature for this species. The monitoring included populations at 0.4, − 0.08 and − 0.5 m LAT. The results show that C. nodosa has a strong seasonality for demographic and shoot dynamic properties – with longer shoots and larger growth in summer (high temperature) than in winter (low temperature), but also some losses. Moreover, shoots have different leaf morphometry depending on depth, with small and dense shoots in the intertidal areas (0.4 m) and sparse large shoots in the subtidal ones (− 0.08 and 0.5 m). These differences in morphometry and shoot dynamic properties, combined with the differences in shoot density, explain the lack of differences in meadow production balance (i.e. meadow growth – meadow losses) between the intertidal (0.4 m) and the deepest population (− 0.5 m), supporting the long term resilience of Cymodocea nodosa in Cadiz Bay. This study contributes to the understanding of the mechanisms behind seagrass stability and resilience, which is particularly important towards predicting the effects of climate change on these key coastal ecosystems, and also highlights the value of continuous long-term monitoring efforts to evaluate seagrass trajectories. info:eu-repo/semantics/publishedVersion

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BackgroundIn the UK, the Alpha variant of SARS-CoV-2 became dominant in late 2020, rapidly succeeded by the Delta variant in May 2021. The aim of this study was to compare the impact of these variants on severity of maternal infection and perinatal outcomes within the time-periods in which they predominated.MethodsThis national, prospective cohort study collated data on hospitalised pregnant women with symptoms of confirmed SARS-CoV-2 infection and compared the severity of infection and perinatal outcomes across the Wildtype (01/03/20-30/11/20), Alpha (01/12/20-15/05/21) and Delta dominant periods (16/05/21-11/07/21), using multivariable logistic regression.FindingsOf 3371 pregnant women, the proportion that experienced moderate to severe infection significantly increased between Wildtype and Alpha periods (24.4% vs. 35.8%; aOR1.75 95%CI 1.48-2.06), and between Alpha and Delta periods (35.8% vs. 45.0%; aOR1.53, 95%CI 1.07-2.17). Compared to the Wildtype period, symptomatic women admitted in the Alpha period were more likely to require respiratory support (27.2% vs. 20.3%, aOR1.39, 95%CI 1.13-1.78), have pneumonia (27.5% vs. 19.1%, aOR1.65, 95%CI 1.38-1.98) and be admitted to intensive care (11.3% vs. 7.7%, aOR1.61, 95%CI 1.24-2.10). Women admitted during the Delta period had further increased risk of pneumonia (36.8% vs. 27.5%, aOR1.64 95%CI 1.14-2.35). No fully vaccinated pregnant women were admitted between 01/02/2021 when vaccination data collection commenced and 11/07/2021. The proportion of women receiving pharmacological therapies for SARS-CoV-2 management was low, even in those critically ill.InterpretationSARS-CoV-2 infection during Alpha and Delta dominant periods was associated with more severe infection and worse pregnancy outcomes compared to the Wildtype infection, which itself increased risk compared to women without SARS-CoV-2 infection.1 Clinicians need to be aware and implement COVID-specific therapies in keeping with national guidance. Urgent action to tackle vaccine misinformation and policy change to prioritise uptake in pregnancy is essential.FundingNational Institute for Health Research HS&DR Programme (11/46/12).

The humanised recombinant monoclonal antibody natalizumab (Tysabri), is a selective antagonist of the α4 subunit of the leukocyte adhesion molecule integrin, VLA-3. Blockade of VLA-3 leads to inhibition of immune cell transmigration into target organs, notably the intestinal lining and central nervous system.1,2 Natalizumab is approved to treat relapsing-remitting Multiple Sclerosis (RRMS) in the US and Europe, and Crohn’s Disease in the US. Following approval in 2004, natalizumab was withdrawn in 2005 due to 3 reported cases of progressive multifocal leukoencephalopathy (PML). In 2006, it re-entered the market with additional monitoring requirements.

Objective: To gain insight into the areas that impact women with endometriosis. Design: A qualitative content analysis of an online survey. Setting: Online questionnaire via Endometriosis UK. Population: Women diagnosed with endometriosis of any age range. Methods: Free-text online questionnaire through Endometriosis UK completed by women. Results were analysed using NVivo version 9, qualitative analysis software. The software creates links between common words (codes), and these links allow data to be placed in nodes (called themes) which are then developed into categories. Content analysis was used to understand this data. Main outcome measures Impact of endometriosis on women’s lives. Results: In total, 1872 questionnaires were returned but not everyone was able to identify ten separate features that affected them. As such, 1872 women provided at least one area that affected them, 1800 provided two areas, 1770 provided three areas and 1600 provided four areas. The results show that the main areas of concern for these women were pain (53%), heavy menstrual bleeding (11%), low mood (8%) and the perceived lack of understanding displayed by other people (7%). Other important factors were fertility concerns, impact on employment, problems with the medical team and uncertainty. These then impacted on their daily life whereby some women felt “guilty” for not ‘being a normal mother’. A key term that resonated was that endometriosis is an “invisible disease”. Conclusion: This analysis provides us with insight into the complex psycho-social factors that interact with bio-physical symptoms. Further research is required in sub-population groups such as teenagers and ethnic minority women to explore any differences in impact and how care can be guided accordingly.

OBJECTIVE To determine the safety and efficacy of a standardized bilateral abdominal sacrocolpopexy using polyvinylidene fluoride mesh 1-year post-operatively. METHODS In a retrospective observational study of women undergoing bilateral abdominal sacrocolpo/cervicopexy between July 2013 and October 2016 at the Norfolk and Norwich University Hospital, Norwich, UK, patients were assessed 1 year post-operatively using the International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS). RESULTS The study involved 100 women, 93 of whom were followed up 1 year post-operatively. The primary outcome was apical prolapse rate, of which there were none. Eight women had anterior and four had posterior wall prolapses; four women required vaginal repairs. Eleven women complained of urinary stress incontinence (six worsening and five de novo) and five had subsequent tension-free vaginal tape procedures. One woman had urethral pain and one had mesh exposure into the vagina. Pre-operatively, mean ICIQ-VS score was 27.87 (standard deviation [SD] 6.8), and at 1 year post-operatively it was 5.82 (SD 3.8). Impact on quality of life score dropped by 83.4%, from 8.35 (SD 2.1) to 1.39 (SD 1.1). CONCLUSION The modified technique used in the present study retained the advantages of traditional sacrocolpopexy, but required smaller volumes of mesh. We found it to be safe and effective with excellent patient satisfaction at 1 year, and providing a promising treatment option for patients suffering from apical prolapse.