Tissue classification for laparoscopic image understanding based on multispectral texture analysis.

Intraoperative tissue classification is one of the prerequisites for providing context-aware visualization in computer-assisted minimally invasive surgeries. As many anatomical structures are difficult to differentiate in conventional RGB medical images, we propose a classification method based on multispectral image patches. In a comprehensive ex vivo study through statistical analysis, we show that (1) multispectral imaging data are superior to RGB data for organ tissue classification when used in conjunction with widely applied feature descriptors and (2) combining the tissue texture with the reflectance spectrum improves the classification performance. The classifier reaches an accuracy of 98.4% on our dataset. Multispectral tissue analysis could thus evolve as a key enabling technique in computer-assisted laparoscopy

Reporting errors, incidence and risk factors for postpartum haemorrhage and progression to severe PPH:a prospective observational study

OBJECTIVE: To quantify reporting errors, measure incidence of postpartum haemorrhage (PPH) and define risk factors for PPH (≥500 ml) and progression to severe PPH (≥1500 ml). DESIGN: Prospective observational study. SETTING: Two UK maternity services. POPULATION: Women giving birth between 1 August 2008 and 31 July 2009 (n = 10 213). METHODS: Weighted sampling with sequential adjustment by multivariate analysis. MAIN OUTCOME MEASURES: Incidence and risk factors for PPH and progression to severe PPH. RESULTS: Errors in transcribing blood volume were frequent (14%) with evidence of threshold preference and avoidance. The incidences of PPH ≥500, ≥1500 and ≥2500 ml were 33.7% (95% CI 31.2–36.2), 3.9% (95% CI 3.3–4.6) and 0.8% (95% CI 0.6–1.0). New independent risk factors predicting PPH ≥ 500 ml included Black African ethnicity (adjusted odds ratio [aOR] 1.77, 95% CI 1.31–2.39) and assisted conception (aOR 2.93, 95% CI 1.30–6.59). Modelling demonstrated how prepregnancy- and pregnancy-acquired factors may be mediated through intrapartum events, including caesarean section, elective (aOR 24.4, 95% CI 5.53–108.00) or emergency (aOR 40.5, 95% CI 16.30–101.00), and retained placenta (aOR 21.3, 95% CI 8.31–54.7). New risk factors were identified for progression to severe PPH, including index of multiple deprivation (education, skills and training) (aOR 1.75, 95% CI 1.11–2.74), multiparity without caesarean section (aOR 1.65, 95% CI 1.20–2.28) and administration of steroids for fetal reasons (aOR 2.00, 95% CI 1.24–3.22). CONCLUSIONS: Sequential, interacting, traditional and new risk factors explain the highest rates of PPH and severe PPH reported to date

Feasibility and design of a trial regarding the optimal mode of delivery for preterm birth: the CASSAVA multiple methods study

BACKGROUND: Around 60,000 babies are born preterm (prior to 37 weeks' gestation) each year in the UK. There is little evidence on the optimal birth mode (vaginal or caesarean section). OBJECTIVE: The overall aim of the CASSAVA project was to determine if a trial to define the optimal mode of preterm birth could be carried out and, if so, determine what sort of trial could be conducted and how it could best be performed. We aimed to determine the specific groups of preterm women and babies for whom there are uncertainties about the best planned mode of birth, and if there would be willingness to recruit to, and participate in, a randomised trial to address some, but not all, of these uncertainties. This project was conducted in response to a Heath Technology Assessment programme commissioning call (17/22 'Mode of delivery for preterm infants'). METHODS: We conducted clinician and patient surveys (n = 224 and n = 379, respectively) to identify current practice and opinion, and a consensus survey and Delphi workshop (n = 76 and n = 22 participants, respectively) to inform the design of a hypothetical clinical trial. The protocol for this clinical trial/vignette was used in telephone interviews with clinicians (n = 24) and in focus groups with potential participants (n = 13). RESULTS: Planned sample size and data saturation was achieved for all groups except for focus groups with participants, as this had to be curtailed because of the COVID-19 pandemic and data saturation was not achieved. There was broad agreement from parents and health-care professionals that a trial is needed. The clinician survey demonstrated a variety of practice and opinion. The parent survey suggested that women and their families generally preferred vaginal birth at later gestations and caesarean section for preterm infants. The interactive workshop and Delphi consensus process confirmed the need for more evidence (hence the case for a trial) and provided rich information on what a future trial should entail. It was agreed that any trial should address the areas with most uncertainty, including the management of women at 26-32 weeks' gestation, with either spontaneous preterm labour (cephalic presentation) or where preterm birth was medically indicated. Clear themes around the challenges inherent in conducting any trial emerged, including the concept of equipoise itself. Specific issues were as follows: different clinicians and participants would be in equipoise for each clinical scenario, effective conduct of the trial would require appropriate resources and expertise within the hospital conducting the trial, potential participants would welcome information on the trial well before the onset of labour and minority ethnic groups would require tailored approaches. CONCLUSION: Given the lack of evidence and the variation of practice and opinion in this area, and having listened to clinicians and potential participants, we conclude that a trial should be conducted and the outlined challenges resolved. FUTURE WORK: The CASSAVA project could be used to inform the design of a randomised trial and indicates how such a trial could be carried out. Any future trial would benefit from a pilot with qualitative input and a study within a trial to inform optimal recruitment. LIMITATIONS: Certainty that a trial could be conducted can be determined only when it is attempted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12295730. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 61. See the NIHR Journals Library website for further project information

Open randomised trial of the (Arabin) pessary to prevent preterm birth in twin pregnancy with health economics and acceptability: STOPPIT-2-a study protocol.

INTRODUCTION: The STOPPIT-2 study aims to determine the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix, about which there is current uncertainty. STOPPIT-2 will resolve uncertainty around effectiveness for women with a twin pregnancy and a cervical length of 35 mm or less, define adverse effects, ascertain acceptability and estimate National Health Service costs and savings. METHODS: STOPPIT-2 is a pragmatic multicentre open-label randomised controlled trial. Consenting women with twin pregnancy will have an transvaginal ultrasound scan of their cervical length performed between 18+0 and 20+6 weeks' gestation by an accredited practitioner: women with a cervical length of ≤35 mm will be eligible for inclusion in the treatment phase of the study. The intervention by the insertion of the Arabin cervical pessary will be compared with standard treatment (no pessary).The primary outcomes are (obstetric) spontaneous onset of labour for the mother leading to delivery before 34 weeks' gestation and (neonatal) a composite of specific adverse outcomes or death occurring up to the end of the first 4 weeks after the estimated date of delivery to either or both babies.We plan to recruit 500 women in the treatment phase of the study. Assuming a treatment effect of 0.6, and background rates of 35% and 18%, respectively, for each of the primary outcomes, our study has 85% power to detect a difference between the intervention and the control groups. ANALYSIS: Data will be analysed on the intention-to-treat principle. ETHICS: STOPPIT-2 was approved by the South East Scotland Ethics Committee 02 on 29 August 2014, reference number 14/SS/1031 IRAS ID 159610. DISSEMINATION: Peer reviewed journals, presentations at national and international scientific meetings. TRIAL REGISTRATION NUMBER: ISRCTN98835694 and NCT02235181

Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

BACKGROUND: Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. METHODS: Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. RESULTS: One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. CONCLUSIONS: The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. REGISTRATION: This review was registered on PROSPERO as CRD42020177714

Defining abnormal fetal growth and perinatal risk—population or customized standards?

In January's Guest Editorial, Sarah Stock and Jenny Myers discuss approaches to fetal and neonatal growth assessment

Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis

BACKGROUND: Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix. METHODS AND FINDINGS: We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55-1.38], p = 0.54). The primary neonatal outcome-a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery-was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54-1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50-1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses. CONCLUSIONS: These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out. TRIAL REGISTRATION: ISRCTN Registry ISRCTN 02235181. ClinicalTrials.gov NCT02235181

Quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 1: Individual participant data meta-analysis and health economic analysis.

INTRODUCTION: The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (qfFN) concentration, in combination with clinical risk factors. METHODS AND ANALYSIS: The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts) which quantifies fFN in a vaginal swab. In part 1 of the study, we will develop and internally validate a prognostic model using an individual participant data (IPD) meta-analysis of existing studies containing women with symptoms of preterm labour alongside fFN measurements and pregnancy outcome. An economic analysis will be undertaken to assess potential cost-effectiveness of the qfFN prognostic model. The primary endpoint will be the ability of the prognostic model to rule out spontaneous preterm birth within 7 days. Six eligible studies were identified by systematic review of the literature and five agreed to provide their IPD (n=5 studies, 1783 women and 139 events of preterm delivery within 7 days of testing). ETHICS AND DISSEMINATION: The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). PROSPERO REGISTRATION NUMBER: CRD42015027590. VERSION: Protocol version 2, date 1 November 2016

Study protocol: quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 2, UK Prospective Cohort Study.

INTRODUCTION: The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (fFN) concentration, in combination with clinical risk factors. METHODS AND ANALYSIS: The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts, USA) which quantifies fFN in a vaginal swab. In QUIDS part 2, we will perform a prospective cohort study in at least eight UK consultant-led maternity units, in women with symptoms of preterm labour at 22+0 to 34+6 weeks gestation to externally validate a prognostic model developed in QUIDS part 1. The effects of quantitative fFN on anxiety will be assessed, and acceptability of the test and prognostic model will be evaluated in a subgroup of women and clinicians (n=30). The sample size is 1600 women (with estimated 96-192 events of preterm delivery within 7 days of testing). Clinicians will be informed of the qualitative fFN result (positive/negative) but be blinded to quantitative fFN result. Research midwives will collect outcome data from the maternal and neonatal clinical records. The final validated prognostic model will be presented as a mobile or web-based application. ETHICS AND DISSEMINATION: The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). VERSION: Protocol V.2, Date 1 November 2016. TRIAL REGISTRATION NUMBER: ISRCTN 41598423andCPMS: 31277

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record