Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Predictors and rates of PTSD, depression and anxiety in UK frontline health and social care workers during COVID-19

Background: Studies have shown that working in frontline healthcare roles during epidemics and pandemics was associated with PTSD, depression, anxiety, and other mental health disorders. Objectives: The objectives of this study were to identify demographic, work-related and other predictors for clinically significant PTSD, depression, and anxiety during the COVID-19 pandemic in UK frontline health and social care workers (HSCWs), and to compare rates of distress across different groups of HCSWs working in different roles and settings. Methods: A convenience sample (n = 1194) of frontline UK HCSWs completed an online survey during the first wave of the pandemic (27 May – 23 July 2020). Participants worked in UK hospitals, nursing or care homes and other community settings. PTSD was assessed using the International Trauma Questionnaire (ITQ); Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9); Anxiety was assessed using the Generalized Anxiety Disorder Scale (GAD-7). Results: Nearly 58% of respondents met the threshold for a clinically significant disorder (PTSD = 22%; anxiety = 47%; depression = 47%), and symptom levels were high across occupational groups and settings. Logistic regression analyses found that participants who were concerned about infecting others, who could not talk with their managers if there were not coping, who reported feeling stigmatized and who had not had reliable access to personal protective equipment (PPE) were more likely to meet criteria for a clinically significant mental disorder. Being redeployed during the pandemic, and having had COVID were associated with higher odds for PTSD. Higher household income was associated with reduced odds for a mental disorder. Conclusions: This study identified predictors of clinically significant distress during COVID-19 and highlights the need for reliable access to PPE and further investigation of barriers to communication between managers and staff

Distribution of ascariasis, trichuriasis and hookworm infections in Ogun State, Southwestern Nigeria.

BackgroundAscariasis, Trichuriasis and Hookworm infections poses a considerable public health burden in Sub-Saharan Africa, and a sound understanding of their spatial distribution facilitates to better target control interventions. This study, therefore, assessed the prevalence of the trio, and mapped their spatial distribution in the 20 administrative regions of Ogun State, Nigeria.MethodsParasitological surveys were carried out in 1,499 households across 33 spatially selected communities. Fresh stool samples were collected from 1,027 consenting participants and processed using ether concentration method. The locations of the communities were georeferenced using a GPS device while demographic data were obtained using a standardized form. Data were analysed using SPSS software and visualizations and plotting maps were made in ArcGIS software.ResultsFindings showed that 19 of the 20 regions were endemic for one or more kind of the three infections, with an aggregated prevalence of 17.2%. Ascariasis was the most frequently observed parasitic infection in 28 communities with a prevalence of 13.6%, followed by hookworm infections with a prevalence of 4.6% while Trichuriasis was the least encountered with a prevalence of 1.7%. The spatial distribution of infections ranges between 5.3-49.2% across the regions. The highest and lowest distribution of overall helminth infections was recorded in Egbado South and Egbado North respectively. Nine regions had infection status between 20.0%-49.2%, while 10 regions had infection status between 5.3%-15.8%.ConclusionThis study provides epidemiological data on the prevalence and spatial distribution of ascariasis, trichuriasis and hookworm infections which will add to the baseline data and guide the public health officers in providing appropriate control strategies in the endemic communities