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Background The Medical Certificate of Stillbirth (MCS) records data about a baby’s death after 24 weeks of gestation but before birth. Major errors that could alter interpretation of the MCS were widespread in two UK-based regional studies. Methods A multicentre evaluation was conducted, examining MCS issued 1 January 2018 to 31 December 2018 in 76 UK obstetric units. A systematic case-note review of stillbirths was conducted by Obstetric and Gynaecology trainees, generating individual ‘ideal MCSs’ and comparing these to the actual MCS issued. Anonymized central data analysis described rates and types of error, agreement and factors associated with major errors. Results There were 1120 MCSs suitable for assessment, with 126 additional submitted data sets unsuitable for accuracy analysis (total 1246 cases). Gestational age demonstrated ‘substantial’ agreement [K = 0.73 (95% CI 0.70–0.76)]. Primary cause of death (COD) showed ‘fair’ agreement [K = 0.26 (95% CI 0.24–0.29)]. Major errors [696/1120; 62.1% (95% CI 59.3–64.9%)] included certificates issued for fetal demise at Conclusion This study demonstrates widespread major errors in MCS completion across the UK. MCS should only be completed following structured case-note review, with particular attention on the fetal growth trajectory.

IntroductionA journal club (JC) is a commonly used medical educational tool. Videoconferencing technology can facilitate the delivery of JCs, however, there remains no evidence on the role of web-based virtual JCs in promoting the acquisition and retention of medical knowledge. The Web-Ed trial aims to evaluate the educational benefits, feasibility and acceptability of web-based virtual JCs compared with traditional face-to-face ones.Methods and analysisWeb-Ed is a multicentre pragmatic parallel-group randomised trial across teaching hospitals within the UK National Health Service (NHS). We will enrol qualified doctors or medical students who are >18 years old, proficient in English and able to use online videoconferencing software. Block randomisation will be used to allocate participants in 1:1 ratio to either intervention group. Both groups will be presented with the same educational material and follow a standardised JC structure hosted by nominated moderators and medical faculty members.The primary outcome is the difference in participants’ knowledge acquisition and retention 7 days after the JCs evaluated using standardised multiple-choice questions. We will report secondarily on the feasibility and acceptability of the JCs using Likert scale questionnaires. Assuming a 30% drop-out rate, we aim to enrol 75 participants to detect a 20% improvement in knowledge acquisition at 80% power and 5% significance. We will report using mean difference or risk ratio with 95% CIs and assess significance using parametric/non-parametric testing. Where relevant, we will adjust for predetermined characteristics (age, grade of training and session duration) using multivariate regression analyses.Ethics and disseminationWeb-Ed was designed by doctors in training to address their learning needs and evaluate the preferred mode of learning. The trial results will be published in peer-reviewed journals and presented at relevant scientific conferences. The trial has been approved by the NHS Health Regulation Authority (21/HRA/3361).Trial registration numberISRCTN18036769.

The World Health Organisation has defined infertility as the inability to become pregnant after 12 months of regular unprotected vaginal sexual intercourse. Primary infertility refers to couples that have never conceived, whereas secondary infertility refers to couples that have failed to conceive despite previous pregnancy. In the general population, 80% of couples are expected to be able to conceive within a year and 90% by the end of 2 years. With the rising trend for increasing maternal age at time of first pregnancy and the obesity epidemic, the incidence of infertility is likely to increase. Couples unable to conceive will seek help and advice from their GP. Infertility is highly emotive, and patients and their partners subject to investigation and management for infertility are likely to experience anxiety. Although primarily managed in secondary care, a robust understanding of investigation and treatment options for infertility can enable GPs to educate and support patients, as well as manage expectations.

Obesity and hyperinsulinemia are known risk factors for endometrial cancer, yet thebiological pathways underlying this relationship are incompletely understood. Thisstudy investigated protein expression in endometrial cancer and benign tissue andits correlation with obesity and insulin resistance.One hundred and seven women undergoing hysterectomy for endometrial canceror benign conditions provided a fasting blood sample and endometrial tissue. Weperformed proteomic expression according to body mass index, insulin resistance,and serum marker levels. We used linear regression and independentttest for statis-tical analysis. Proteomic data from 560 endometrial cancer cases from The CancerGenome Atlas (TCGA) databank were used to assess reproducibility of results.One hundred and twenty seven proteins were significantly differentially expressedbetween 66 cancer and 26 benign patients. Protein expression involved in cellcycle progression, impacting cytoskeletal dynamics (PAK1) and cell survival (Rab25), were most significantly altered. Obese women with cancer had increasedPRAS40_pT246; a downstream marker of increased PI3K-AKT signaling. Obesewomen without cancer had increased mitogenic and antiapoptotic signaling byway of upregulation of Mcl-1, DUSP4, and Insulin Receptor-b.This exploratory study identified a number of candidate proteins specific to endo-metrioid endometrial cancer and benign endometrial tissues. Obesity and insulinresistance in women with benign endometrium leads to specific upregulation ofproteins involved in insulin and driver oncogenic signaling pathways such as thePI3K-AKT-mTOR and growth factor signaling pathways which are mitogenic andalso disruptive to metabolism. (Translational Research 2020; 000:1 16)

BackgroundObesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery.MethodsVaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery.ResultsThe bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of aLactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillusspp., andGardnerella- spp. depleted) VMB, compared with non-obese subjects (pDialisterspecies (pAnaerococcus vaginalis(p=0.021), andPrevotella timonensis(p=0.020) and decreased relative abundance ofLactobacillus crispatus(p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α and TNFα levels were all higher among obese women, however, only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery; however, 75% of these women remained obese at 6 months. Prior to surgery, there was no relationship between body mass index (BMI) and VMB structure; however, post-surgery women with aLactobacillus-dominant VMB had a significantly lower BMI than those with a high diversity VMB.ConclusionsObese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB; however, those with the greatest weight loss 6-month post-surgery are most likely to have aLactobacillus-dominant VMB.

Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11–1.20), body mass index (BMI) (RR ≥ 30 kg/m2 versus normal 1.27, 95% CI 1.17–1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69–0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia&mdash, the early recognition of which may allow fertility sparing management and cancer prevention.

We performed a systematic review and meta-analysis to explore the optimum management strategy for women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/mild dyskaryosis) cytological abnormalities at primary screening in the absence of HPV DNA test. We searched MEDLINE, EMBASE and CENTRAL and included randomised controlled trials comparing immediate colposcopy to cytological surveillance in women with ASCUS/LSIL. The outcomes of interest were occurrence of different histological grades of cervical intraepithelial neoplasia (CIN) and default rates during follow-up. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect model and with inverse variance weighting. Interstudy heterogeneity was assessed using I2 statistics. Six RCTs were included. Immediate colposcopy significantly increased detection of unimportant abnormalities as opposed to repeat cytology (koilocytosis: 32 vs. 21%, RR: 1.49, 95% CI = 1.17–1.90); CIN1: 21 vs. 8%, RR: 2.58, 95% CI = 1.69–3.94). Although immediate colposcopy detected CIN2, CIN2+, and CIN3+ earlier than cytology, the differences were no longer observed at 24 months (CIN3+: 10.3 vs.11.9%, RR: 1.02, 95% CI = 0.53–1.97), with significant interstudy heterogeneity (p

Although many risk factors could have causal association with endometrial cancer, they are also prone to residual confounding or other biases which could lead to over- or underestimation. This umbrella review evaluates the strength and validity of evidence pertaining risk factors for endometrial cancer. Systematic reviews or meta-analyses of observational studies evaluating the association between non-genetic risk factors and risk of developing or dying from endometrial cancer were identified from inception to April 2018 using PubMed, the Cochrane database and manual reference screening. Evidence was graded strong, highly suggestive, suggestive or weak based on statistical significance of random-effects summary estimate, largest study included, number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings. We identified 171 meta-analyses investigating associations between 53 risk factors and endometrial cancer incidence and mortality. Risk factors were categorised: anthropometric indices, dietary intake, physical activity, medical conditions, hormonal therapy use, biochemical markers, gynaecological history and smoking. Of 127 meta-analyses including cohort studies, three associations were graded with strong evidence. Body mass index and waist-to-hip ratio were associated with increased cancer risk in premenopausal women (RR per 5 kg/m

Biospectroscopy has the potential to investigate and characterise biological samples and could, therefore, be utilised to diagnose various diseases in a clinical environment. An important consideration in spectrochemical studies is the cost-effectiveness of the substrate used to support the sample, as high expense would limit their translation into clinic. In this paper, the performance of low-cost aluminium (Al) foil substrates was compared with the commonly used low-emissivity (low-E) slides. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy was used to analyse blood plasma and serum samples from women with endometrial cancer and healthy controls. The two populations were differentiated using principal component analysis with support vector machines (PCA-SVM) with 100% sensitivity in plasma samples (endometrial cancer=70; healthy controls=15) using both Al foil and low-E slides as substrates. The same sensitivity results (100%) were achieved for serum samples (endometrial cancer=60; healthy controls=15). Specificity was found higher using Al foil (90%) in comparison to low-E slides (85%) and lower using Al foil (70%) in comparison to low-E slides in serum samples. The establishment of Al foil as low-cost and highly-performing substrate would pave the way for large-scale, multi-centre studies and potentially for routine clinical use.

We performed a systematic review and meta-analysis to explore the optimum management strategy for women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/mild dyskaryosis) cytological abnormalities at primary screening in the absence of HPV DNA test. We searched MEDLINE, EMBASE and CENTRAL and included randomised controlled trials comparing immediate colposcopy to cytological surveillance in women with ASCUS/LSIL. The outcomes of interest were occurrence of different histological grades of cervical intraepithelial neoplasia (CIN) and default rates during follow-up. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect model and with inverse variance weighting. Interstudy heterogeneity was assessed using I

5596 Background: Symptoms of endometrial cancer often appear in early stages, thus a diagnosis, based on microscopic histological examination of endometrial tissue, can be given relatively on time. However, this procedure interferes subjective interpretation allowing human error, while screening of the asymptomatic population is not widely performed because of the high cost of the available tests (e.g. transvaginal ultrasound) and the relative invasiveness [biopsy or dilation and curettage (D+C)]. Consequently, there is a widespread need to develop inexpensive, non-invasive techniques that would accurately diagnose endometrial cancer, as well as classify the different subtypes. Spectrochemical methods generate a signature fingerprint of biological material in the form of spectra. Unlike immunological methods, which detect only one molecule at a time, the spectra obtained from a clinical sample represent all the molecular constituents within that sample, including proteins, lipids and carbohydrates; this provides a holistic picture of the sample. Previous studies have confirmed spectroscopy’s ability to diagnose gynecologic cancers in blood. Methods: Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy was used to analyse blood plasma and serum from 71 women with endometrial cancer and 18 age-matched healthy controls; classification algorithms were then applied to extract the underlying biological information. Results: Principal component analysis followed by support vector machine (PCA-SVM) diagnosed endometrial cancer with 100% accuracy in plasma and 95% in serum. Discrimination between the different subtypes [endometrioid adenocarcinoma (n = 43) vs carcinosarcoma (n = 14)] was achieved with 98.33% accuracy in both plasma and serum. The spectral regions responsible for discrimination were attributed to protein and lipid alterations. Conclusions: Our preliminary results suggest an accurate and objective diagnostic tool for endometrial cancer with blood testing, allowing therefore thoughts for a potential screening test in high risk populations. Future work will include higher number of normal cases and different subtypes and grades.