Management of postpartum haemorrhage: from research into practice, a narrative review of the literature and the Cardiff experience

Postpartum haemorrhage (PPH) is caused by obstetric complications but may be exacerbated by haemostatic impairment. In a ten year programme of research we have established that haemostatic impairment is uncommon in moderate PPH and that fibrinogen falls earlier than other coagulation factors. Laboratory Clauss fibrinogen and the point of care surrogate measure of fibrinogen (Fibtem® A5 measured on the ROTEM® machine) are predictive biomarkers for progression from early to severe PPH, the need for blood transfusion and invasive procedures to control haemorrhage. Fibrinogen replacement is not required in PPH unless the plasma level falls below 2 g/L or the Fibtem A5 is below 12mm. Deficiencies of coagulation factors other than fibrinogen are uncommon even during severe PPH, and ROTEM monitoring can inform withholding FFP safely in most women. In the absence of placental abruption, clinically significant thrombocytopenia is uncommon unless the platelet count is low before the bleed started, or very large bleeds (>5000 mL) occur. Measuring blood loss is feasible in routine practice during PPH and is more accurate than estimation. These research findings have been collated to design an ongoing quality improvement programme for all maternity units in Wales called OBS Cymru (Wales) (The Obstetric Bleeding Strategy for Wales)

Managing the coagulopathy of postpartum hemorrhage: an evolving role for viscoelastic hemostatic assays

Postpartum hemorrhage (PPH) is usually caused by obstetrical complications but may be exacerbated by hemostatic impairment. Standard laboratory tests of coagulation often take too long to become available to inform treatment in a rapidly changing clinical situation. The role of point-of-care viscoelastic hemostatic assays (VHAs) in monitoring hemostatic impairment and guiding procoagulant blood product replacement during PPH is evolving, although these technologies are not available in most maternity units. We have used VHAs during PPH in our institution for the last 8 years and have developed a simple algorithm to direct blood component replacement. VHAs are useful for reassuring clinicians that hemostasis is adequate and that procoagulant blood products are not required and an obstetrical cause for bleeding needs to be sought. VHAs can be used to detect hypofibrinogenemia due to dilution or acute obstetrical coagulopathy and to guide fibrinogen replacement. The role of VHAs in guiding fresh frozen plasma infusion is less clear, but normal results suggest that fresh frozen plasma is not required. In this review, we describe 3 cases of postpartum hemorrhage to illustrate different hemostatic scenarios and discuss the controversies and evidence gaps related to each case

Are we asking the right questions? Working with the LGBTQ+ community to prioritise healthcare research themes.

BackgroundConversations about research priorities with members of the public are rarely designed specifically to include people who identify as Lesbian, Gay, Bisexual, Transgender and Queer (LGBTQ+) and are not researchers.MethodsGenerally, to address this gap, and specifically, to inform future research for CLS, we carried out a rapid review of published research priority sets covering LGBTQ+ topics, and an online workshop to prioritise identified themes.ResultsRapid review: results. The rapid review identified 18 LGBTQ+ research priority sets. Some focussed on specific populations such as women or men, younger or older people or people living within families. Five addressed transgender and gender non- conforming populations. All of the research priority sets originated from English-speaking, high and middle-income countries (UK, US, Canada, and Australia), and date from 2016 onwards. Prioritization approaches were wide-ranging from personal commentary to expert workshops and surveys. Participants involved in setting priorities mostly included research academics, health practitioners and advocacy organisations, two studies involved LGBTQ+ public in their process. Research priorities identified in this review were then grouped into themes which were prioritised during the workshop. Workshop: results. For the workshop, participants were recruited using local (Cambridge, UK) LGBTQ+ networks and a national advert to a public involvement in research matching website to take part in an online discussion workshop. Those that took part were offered payment for their time in preparing for the workshop and taking part. Participants personal priorities and experiences contributed to a consensus development process and a final ranked list of seven research themes and participants' experiences of healthcare, mental health advocacy, care homes, caring responsibilities, schools and family units added additional context.ConclusionsFrom the workshop the three research themes prioritised were: healthcare services delivery, prevention, and particular challenges / intersectionality of multiple challenges for people identifying as LGBTQ+. Research themes interconnected in many ways and this was demonstrated by the comments from workshop participants. This paper offers insights into why these priorities were important from participants' perspectives and detail about how to run an inclusive and respectful public involvement research exercise. On a practical level these themes will directly inform future research direction for CLS

Post-AGB stars with hot circumstellar dust: binarity of the low-amplitude pulsators

While the first binary post-AGB stars were serendipitously discovered, the distinct characteristics of their Spectral Energy Distribution (SED) allowed us to launch a more systematic search for binaries. We selected post-AGB objects which show a broad dust excess often starting already at H or K, pointing to the presence of a gravitationally bound dusty disc in the system. We started a very extensive multi-wavelength study of those systems and here we report on our radial velocity and photometric monitoring results for six stars of early F type, which are pulsators of small amplitude. To determine the radial velocity of low signal-to-noise time-series, we constructed dedicated auto-correlation masks. The radial velocity variations were subjected to detailed analysis to differentiate between pulsational variability and variability due to orbital motion. Finally orbital minimalisation was performed to constrain the orbital elements. All of the six objects are binaries, with orbital periods ranging from 120 to 1800 days. Five systems have non-circular orbits. The mass functions range from 0.004 to 0.57 solar mass and the companions are likely unevolved objects of (very) low initial mass. We argue that these binaries must have been subject to severe binary interaction when the primary was a cool supergiant. Although the origin of the circumstellar disc is not well understood, the disc is generally believed to be formed during this strong interaction phase. The eccentric orbits of these highly evolved objects remain poorly understood. With the measured orbits and mass functions we conclude that the circumbinary discs seem to have a major impact on the evolution of a significant fraction of binary systems.Comment: 13 pages, 15 figures, accepted for Astronomy and Astrophysic

What is different about living alone with cancer in older age? A qualitative study of experiences and preferences for care

Background: Increasing numbers of older patients with advanced cancer live alone but there is little research on how well health services meet their needs. The aim of this study was to compare the experiences and future preferences for care between two groups of older people with cancer in their last year of life; those who live alone, and those who live with co-resident carers. Methods: In-depth qualitative interviews were conducted with 32 people aged between 70 and 95 years who were living with cancer. They were recruited from general practices and hospice day care, when the responsible health professional answered no to the question, of whether they would be surprised if the patient died within twelve months. Twenty participants lived alone. Interviews were recorded and transcribed and the data analysed using a Framework approach, focussing on the differences and commonalities between the two groups. Results: Many experiences were common to all participants, but had broader consequences for people who lived alone. Five themes are presented from the data: a perception that it is a disadvantage to live alone as a patient, the importance of relational continuity with health professionals, informal appraisal of care, place of care and future plans. People who lived alone perceived emotional and practical barriers to accessing care, and many shared an anxiety that they would have to move into a care home. Participants were concerned with remaining life, and all who lived alone had made plans for death but not for dying. Uncertainty of timescales and a desire to wait until they knew that death was imminent were some of the reasons given for not planning for future care needs. Conclusions: Older people who live alone with cancer have emotional and practical concerns that are overlooked by their professional carers. Discussion and planning for the future, along with continuity in primary care may hold the key to enhancing end-of-life care for this group of patients

The effect of timing and frequency of push notifications on usage of a smartphone-based stress management intervention: An exploratory trial

Push notifications offer a promising strategy for enhancing engagement with smartphone-based health interventions. Intelligent sensor-driven machine learning models may improve the timeliness of notifications by adapting delivery to a user's current context (e.g. location). This exploratory mixed-methods study examined the potential impact of timing and frequency on notification response and usage of Healthy Mind, a smartphone-based stress management intervention. 77 participants were randomised to use one of three versions of Healthy Mind that provided: intelligent notifications; daily notifications within pre-defined time frames; or occasional notifications within pre-defined time frames. Notification response and Healthy Mind usage were automatically recorded. Telephone interviews explored participants' experiences of using Healthy Mind. Participants in the intelligent and daily conditions viewed (d = .47, .44 respectively) and actioned (d = .50, .43 respectively) more notifications compared to the occasional group. Notification group had no meaningful effects on percentage of notifications viewed or usage of Healthy Mind. No meaningful differences were indicated between the intelligent and non-intelligent groups. Our findings suggest that frequent notifications may encourage greater exposure to intervention content without deterring engagement, but adaptive tailoring of notification timing does not always enhance their use. Hypotheses generated from this study require testing in future work. Trial registration number: ISRCTN67177737 © 2017 Morrison et al

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant