Metformin for endometrial hyperplasia.

BACKGROUND: Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets that are currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. A levonorgestrel intrauterine device may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown, in some human studies, to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. This is an update of a review first published in 2017. OBJECTIVES: To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, PubMed, Embase, Google Scholar, OpenGrey, LILACS, and two trials registers from inception to 5 September 2022. We searched the bibliographies of all relevant studies, and contacted experts in the field for any additional trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo, no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data from included studies, assessed the risk of bias in the included studies, and assessed the certainty of the evidence for each outcome. We resolved disagreements by discussion or by deferring to a third review author. When study details were missing, review authors contacted the study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. MAIN RESULTS: We included seven RCTs, in which a total of 387 women took part. In the comparison, Metformin plus megestrol versus megestrol alone, we rated the certainty of the evidence as low for the outcome, regression of endometrial hyperplasia. We rated the quality of the evidence as very low for the rest of the outcomes, in all three comparisons. Although there was a low risk of selection bias, there was a high risk of bias in the blinding of personnel and outcome assessment (performance bias and detection bias) in many studies. This update identified four new RCTs and six ongoing RCTs. Metformin versus megestrol We are uncertain whether metformin increases the regression of endometrial hyperplasia towards normal histology over megestrol (odds ratio (OR) 4.89, 95% confidence interval (CI) 1.56 to 15.32; P = 0.006; 2 RCTs, 83 participants; I² = 7%; very low-certainty evidence). This evidence suggests that if the rate of regression with megestrol is 61%, the rate of regression with metformin would be between 71% and 96%. It is unresolved whether metformin results in different rates of abnormal uterine bleeding or hysterectomy compared to megestrol. No study in this comparison reported progression of hyperplasia to endometrial cancer, recurrence of endometrial hyperplasia, health-related quality of life, or adverse effects during treatment. Metformin plus megestrol versus megestrol monotherapy The combination of metformin and megestrol may enhance the regression of endometrial hyperplasia towards normal histology more than megestrol alone (OR 3.27, 95% CI 1.65 to 6.51; P = 0.0007; 4 RCTs, 258 participants; I² = 0%, low-certainty evidence). This suggests that if the rate of regression with megestrol monotherapy is 54%, the rate of regression with the addition of metformin would be between 66% and 84%. In one study, 3/8 (37.5%) of participants who took metformin had nausea that settled without further treatment. It is unresolved whether the combination of metformin and megestrol results in different rates of recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, or hysterectomy compared to megestrol monotherapy. No study in this comparison reported abnormal uterine bleeding, or health-related quality of life. Metformin plus levonorgestrel (intrauterine system) versus levonorgestrel (intrauterine system) monotherapy We are uncertain whether there is a difference between groups in the regression of endometrial hyperplasia towards normal histology (OR 0.29, 95% CI 0.01 to 7.56; 1 RCT, 46 participants; very low-certainty evidence). This evidence suggests that if the rate of regression with levonorgestrel monotherapy is 96%, the rate of regression with the addition of metformin would be between 73% and 100%. It is unresolved whether the combination of metformin and levonorgestrel results in different rates of abnormal uterine bleeding, hysterectomy, or the development of adverse effects during treatment compared to levonorgestrel monotherapy. No study in this comparison reported recurrence of endometrial hyperplasia, progression of hyperplasia to endometrial cancer, or health-related quality of life. AUTHORS' CONCLUSIONS: Review authors found insufficient evidence to either support or refute the use of metformin, specifically megestrol acetate, given alone or in combination with standard therapy, for the treatment of women with endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials, yielding long-term outcome data are still needed to address this clinical question.

A common curriculum in obstetrics and gynecology for medical students globally.

OBJECTIVE: Global variations in women's health outcomes, increased international migration, and an increase in the number of medical schools underpin the need for global standardization in obstetrics and gynecology curricula for medical students. However, there are currently no recommendations regarding the content of a common curriculum. The aim of this project was to agree the objectives for a common curriculum in obstetrics and gynecology for medical students globally. METHODS: The curriculum was developed and agreed by an international taskforce of obstetricians and gynecologists. Published curricula for medical students in a variety of regions globally were reviewed and discussed, and the objectives for a common curriculum in obstetrics and gynecology for medical students were agreed by consensus. RESULTS: The content of the proposed curriculum is classified into three domains: clinical skills, professional behaviors, and knowledge. The recommended curriculum covers health conditions that affect women globally in different social and cultural contexts, and addresses important global health issues of relevance to obstetrics and gynecology. CONCLUSION: The methods and outcomes of a project by an international taskforce of obstetricians and gynecologists to develop a common curriculum in obstetrics and gynecology for medical students globally are presented. More work is required to identify ways in which the curriculum may be adapted to a minimum essential required curriculum in times of man-made or natural disasters. Achieving these will facilitate the intended long-term aims of this curriculum, to improve women's health outcomes globally.

Evaluating an obstetrics and gynecology teaching program for medical students incorporating simulation-based education underpinned by cognitive load theory.

Although there have been previous publications on curriculum innovations in teaching O&G to medical students, especially utilizing simulation-based education, there have been none, as far as we know, incorporating and evaluating the outcomes using cognitive load theory. The aim of this article was to describe the introduction, implementation, and evaluation of an innovative teaching program in O&G, incorporating simulation-based education, underpinned by cognitive load theory. Cognitive load is defined as the amount of information a working memory can hold at any one time and incorporates three types of cognitive load-intrinsic, extraneous, and germane. To optimize learning, educators are encouraged to manage intrinsic cognitive load, minimize extraneous cognitive load, and promote germane cognitive load. In these sessions, students were encouraged to prepare in advance of each session with recommended reading materials; to limit intrinsic cognitive load and promote germane cognitive load, faculty were advised ahead of each session to manage intrinsic cognitive load, an open-book MCQ practice session aimed to reduce anxiety, promote psychological safety, and minimize extraneous cognitive load. For the simulation sessions, the faculty initially demonstrated the role-play situation or clinical skill first, to manage intrinsic cognitive load and reduce extraneous cognitive load. The results of the evaluation showed that the students perceived that they invested relatively low mental effort in understanding the topics, theories, concepts, and definitions discussed during the sessions. There was a low extraneous cognitive load. Measures of germane cognitive load or self-perceived learning were high. The primary message is that we believe this teaching program is a model that other medical schools globally might want to consider adopting, to evaluate and justify innovations in the teaching of O&G to medical students. The secondary message is that evaluation of innovations to teaching and facilitation of learning using cognitive load theory is one way to contribute to the high-quality training of competent future healthcare workers required to provide the highest standard of care to women who are crucial to the overall health and wellbeing of a nation.

Prevalence and Diagnosis of PCOS Using Electronic Health Records: A Scoping Review and a Database Analysis.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. It increases the risk of type 2 diabetes, cardiovascular disease, endometrial cancer, infertility, gestational diabetes, preeclampsia, and preterm birth. Accurately identifying predictors of these health risks is crucial. Electronic health records (EHRs) offer an affordable approach, however, the validity and reliability of EHRs for PCOS diagnosis are unclear. A scoping review of the literature on the prevalence and reliability of the diagnosis of PCOS using EHRs was performed. An analysis of the feasibility of obtaining diagnostic variables from a PCOS patient database was also carried out. Eight studies met the criteria. The prevalence of PCOS ranged from 0.27% to 5.8%. Reliability varied, with one study reporting a sensitivity of 50% and a specificity of 29%. Another study found a 74.4% agreement between international classification of disease (ICD) codes and clinical criteria. The database analysis found only 13.7%, 8%, and 7.5% of women had all the necessary variables for an objective diagnosis of PCOS using the Rotterdam, National Institutes of Health (NIH), and Androgen Excess and PCOS Society (AEPCOS) criteria, respectively. Using EHRs results in an underestimation of PCOS prevalence compared to other diagnostic criteria, and many women identified may not meet the complete diagnostic criteria. These findings have implications for future research studies on PCOS prevalence and related health risks.

Deciphering the Role of Insulin-Like Growth Factor 1 in Endometrial Cancer in Patients With Polycystic Ovary Syndrome: Protocol for a Methodological Approach Using Cell Culture Experiments.

BACKGROUND: Endometrial cancer (EC) is the most common gynecological cancer in women globally. It is linked to increasing obesity rates and longer life spans. The molecular mechanisms leading to EC are unclear; however, women with polycystic ovary syndrome (PCOS) have a 3- to 5-fold increased EC risk. According to a pilot study conducted in the United Kingdom, insulin-like growth factor-1 (IGF-1) gene and protein were raised in the endometrium and blood of women with EC and PCOS, compared with those without PCOS (controls). Therefore, raised serum IGF-1 levels may contribute to an increased EC risk in women with PCOS, but it is necessary to test this hypothesis since not all studies have demonstrated this association. OBJECTIVE: This study aims to investigate the role of IGF-1 in mediating EC risk in PCOS. This will be achieved by evaluating the proliferative effects of PCOS serum, IGF-1, and IGF-1 antagonist on human endometrial cancer 1-A and 1-B cell lines, with a comparison to controls (using serum from women without PCOS and cell culture media). The study will also identify differentially expressed genes and pathways activated by various treatments. METHODS: We intend to recruit 20 women with PCOS and 20 women without PCOS for this cross-sectional study. All experiments will be carried out 4 times to ensure consistency. We will perform transcriptomic and phosphoproteomic profiling to identify differentially expressed genes and phosphoproteins between different treatments using RNA sequencing and phosphoproteomics. We will also perform bioinformatics pathway analysis to identify whether any unique collection of genes or phosphoproteins explains increased EC risk in PCOS. The primary outcome measure will be the cell proliferation (growth) difference measured by cell index values. Our protocol stands out due to its unique approach; no previous study has used this approach to investigate the oncogenic effect of serum from women with PCOS. Additionally, no previous study has considered the differential mutations of genes related to the insulin signaling pathway across various types of human EC cell lines and the potential impact of these variations on their experimental findings. RESULTS: Participants are currently being recruited. It is expected that preliminary findings suitable for analysis and publication will be available by the summer of 2024. CONCLUSIONS: Although we currently do not have any results to report, sharing our protocol at this stage will aid in research collaboration, provide an opportunity for early feedback, and help reduce duplication of effort by other research groups. The findings of our study will have broader implications. A deeper understanding of the mechanisms underlying the regulation of the IGF system in PCOS and EC will improve our ability to develop effective treatment modalities for EC and will be a vital step toward reducing EC in women globally. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48127.

Transcriptomic analysis identifies four novel receptors potentially linking endometrial cancer with polycystic ovary syndrome and generates a transcriptomic atlas.

Polycystic Ovary Syndrome (PCOS) is associated with a 3 to 4-fold increased risk of endometrial cancer (EC), but molecular mechanisms are unclear. Upregulation of the IGF1 gene in PCOS endometrium may increase EC risk, but this is uncertain. We aimed to investigate links between EC and PCOS, by analysing publicly available transcriptomic data. The NCBI Gene Expression Omnibus was used to identify relevant studies. Differentially expressed genes (DEGs) were identified and analysed using Metascape to identify pathways of interest. PCOS DEGs that encode proteins secreted into blood were identified using the Human Protein Atlas blood protein database. EC DEGs that are cellular receptors were identified using EcoTyper. These were intersected to identify which EC receptors interact with PCOS secreted proteins. Seven receptors were identified in EC but only PTPRF, ITGA2, ITGA3 and ITGB4 genes were expressed on epithelial cells. Pathway enrichment of these genes showed that the major and common pathway involved was that of the PI3K-AKT signalling pathway which was consistent with a link between PCOS and EC. However, IGF1 was down regulated in PCOS and EC. These findings hold significant promise for improving our understanding of mechanistic pathways leading to EC in PCOS.

Obesity and female infertility.

Infertility is a significant global health issue, with a negative impact on people's wellbeing and human rights. Despite the longstanding association between obesity and infertility, there remains uncertainty, about the precise mechanisms underpinning this association and best management strategies. In this article, we aimed to address these uncertainties by reviewing the recent literature, and focusing on studies which evaluated live birth rates. We found that just over half of the studies, investigating the relationship between preconception maternal weight and live birth rates found an inverse correlation. There was, however, insufficient evidence, that preconception maternal lifestyle or pharmacological interventions in obese women with infertility, resulted in improved live birth rates. The implications for clinical practice and future research are highlighted. For example, the need to consider some flexibility in applying strict preconception body mass index targets, limiting access to fertility treatment, and a need for large clinical trials of new pharmacological options and bariatric surgery.

Prevalence of Polycystic Ovary Syndrome amongst Females Aged between 15 and 45 Years at a Major Women's Hospital in Dubai, United Arab Emirates.

Objective criteria have been scarce in published data on the occurrence of polycystic ovary syndrome (PCOS) in the United Arab Emirates (UAE). It is crucial that we enhance our comprehension of PCOS prevalence in the UAE to inform key stakeholders about the disease's burden and enable comparisons with other nations. This research aimed to examine the PCOS prevalence at a large academic tertiary centre in Dubai, UAE, called Latifa Women and Children's Hospital. We performed a cross-sectional study by reviewing the electronic medical records of patients accessing care between 2017 and 2022 (5 years). By utilizing the international classification of diseases codes (ICD-10), we discovered a period prevalence of PCOS of 1.6% among 64,722 women aged between 15 and 45 years. It is worth noting that the estimated annual point prevalence rose from 1.19% in 2020 (at the beginning of the COVID19 pandemic) to 2.72% in 2022 (after the start of the COVID-19 pandemic). Therefore, the odds ratio of the risk of a PCOS diagnosis in 2022 compared to 2020 was 2.28. The majority of the women diagnosed with PCOS in this study had an ICD-10 code of E28.2. Women with PCOS were younger than the controls, less likely to be pregnant, and had a higher body mass index and systolic and diastolic blood pressure. This is the most extensive research to date examining PCOS prevalence in the UAE, and it emphasizes the significance of this condition. It is crucial to prioritize PCOS to prevent morbidity and mortality from reproductive and long-term health consequences, including infertility, type 2 diabetes and endometrial cancer, which is presently the most frequent gynecological cancer in the UAE.

A literature review and proposed framework for a core curriculum in obstetrics and gynecology for medical students globally.

BACKGROUND: There have been challenges in deciding the curricular content in obstetrics and gynecology (Ob/Gyn) for medical students because the core knowledge, competencies, and duration of Ob/Gyn clerkships, varies widely by country. OBJECTIVES: To investigate current recommendations for Ob/Gyn curricula for medical students globally, in a rapid review of the literature and websites of a selection of medical schools. SEARCH STRATEGY: A targeted search of selected databases (PubMed and Google Scholar) using relevant key words and a search of university websites. SELECTION CRITERIA: Studies that applied to medical or undergraduate students in Ob/Gyn. DATA COLLECTION AND ANALYSIS: A standardized extraction form on Microsoft excel to extract and chart data. MAIN RESULTS: We identified recommendations from national professional bodies (Royal College of Obstetricians and Gynaecologists, Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Association of Professors of Gynecology and Obstetrics, and the Turkish-National Core Curriculum), and descriptions from five university websites. We also identified additional objectives, including teaching on intimate partner violence, health priorities in low- and middle-income countries, and a variation in practical skills recommended. CONCLUSIONS: Fitting all the recommended curricula content into medical student Ob/Gyn clerkships is a challenge. A framework to address this, for consideration by the International Federation of Gynaecology and Obstetrics and other stakeholders, is proposed in which priority is given to topics related to emergency Ob/Gyn, history taking, and examination of the pregnant and non-pregnant patient.

Polycystic Ovarian Syndrome (PCOS): Does the Challenge End at Conception?

Polycystic ovary syndrome (PCOS) is a prevalent condition that not only has the potential to impede conception but also represents the most common endocrine dysfunction in fertile women. It is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome's risks. Undoubtedly, the impact of PCOS on infertility has attracted most of the attention of healthcare providers and investigators. However, there is growing evidence that even after conception is achieved, PCOS predisposes the parturient to several adverse pregnancy outcomes including a high risk of pregnancy-induced hypertension, spontaneous abortion, gestational diabetes, preeclampsia, and preterm birth, which increase the risks of stillbirth and neonatal death. Fetal growth abnormalities may also be more common, but the relationship is less well defined. This narrative review aims to summarize current knowledge regarding these conditions as they interplay with PCOS and concludes that although there appears to be an increase in these complications during the pregnancy of women with PCOS, there is a need for further research to clarify the possible confounding impact of obesity. Implications for clinical practice and future research are outlined.

A scoping review of the literature on the impact of the COVID-19 quarantine on the psychological wellbeing of medical students.

BACKGROUND: The goal of this study was to identify the nature and extent of the available published research on the impact of social isolation, on the psychological wellbeing of medical students, who had to quarantine due to the COVID-19 pandemic. METHODS: Design. Scoping review. SEARCH STRATEGY: The PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews), guideline, was used to structure this study. A search strategy was carried out across six bibliographic databases. PubMed, Embase, ERIC, Scopus, Cochrane Database of Systematic Reviews and Web of Science. The following search terms were used, "medical student*" AND "impact" AND "quarantine" AND "COVID-19". Searches were initially confined to articles published (excluding conference abstracts) between 1 January 2019- 21 August 2021 but updated in September 2022 with the original search terms expanded to include "isolation" or "lockdown" as well as "quarantine" and the period of search extended to 21 August 2022. A search of secondary references was conducted. Data from the selected studies were extracted, and the following variables recorded; first author and year of publication, country of study, study design, sample size, participants, mode of analysing impact of quarantine from COVID-19 on mental health and results of the studies. RESULTS: A total of 223 articles were identified in the original search in 2021 and 387 articles, in the updated search in 2022. Following the exclusion of duplicates and application of the agreed inclusion and exclusion criteria, 31 full-text articles were identified for the final review, most of which were cross sectional studies. Sample sizes ranged from 13 to 4193 students and most studies used a variety of self-administered questionnaires to measure psychological wellbeing. Overall, 26 of the 31 articles showed that quarantine had a negative impact on the psychological well-being of medical students. However, two studies showed no impact, and three studies showed an improvement. CONCLUSION: The evidence is growing. Quarantine because of the COVID-19 pandemic may have had a negative impact on the psychological wellbeing of medical students, but this is not certain. There is therefore a need for more studies to further evaluate this research question.

Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota.

Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the 'Human Microbiome Project' in 2016. We obtained 200 articles by inputting keywords such as 'gut microbiome', 'gut microbiota', 'gut dysbiosis', 'PCOS', and 'endometrial cancer' into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.

Vibrational Biospectroscopy: An Alternative Approach to Endometrial Cancer Diagnosis and Screening.

Endometrial cancer (EC) is the sixth most common cancer and the fourth leading cause of death among women worldwide. Early detection and treatment are associated with a favourable prognosis and reduction in mortality. Unlike other common cancers, however, screening strategies lack the required sensitivity, specificity and accuracy to be successfully implemented in clinical practice and current diagnostic approaches are invasive, costly and time consuming. Such limitations highlight the unmet need to develop diagnostic and screening alternatives for EC, which should be accurate, rapid, minimally invasive and cost-effective. Vibrational spectroscopic techniques, Mid-Infrared Absorption Spectroscopy and Raman, exploit the atomic vibrational absorption induced by interaction of light and a biological sample, to generate a unique spectral response: a "biochemical fingerprint". These are non-destructive techniques and, combined with multivariate statistical analysis, have been shown over the last decade to provide discrimination between cancerous and healthy samples, demonstrating a promising role in both cancer screening and diagnosis. The aim of this review is to collate available evidence, in order to provide insight into the present status of the application of vibrational biospectroscopy in endometrial cancer diagnosis and screening, and to assess future prospects.

Coenzyme A Restriction as a Factor Underlying Pre-Eclampsia with Polycystic Ovary Syndrome as a Risk Factor.

Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why polycystic ovary syndrome is a risk factor and what might be done to treat and reduce the risk of disease.

Impact of New Clinical Policies during the COVID-19 Pandemic on Clinical Incidents and Complaints at a UK Teaching Hospital.

BACKGROUND: To investigate any associations between new clinical policies implemented because of the COVID-19 pandemic and harm to patients. METHODS: Retrospective data collection of incidents and complaints reported through Datix®, and the Patient Advice and Liaison Service (PALS), respectively. The setting was the Family Health division in a University teaching hospital in the UK. Primary and secondary outcome measures included: the proportion of incidents reported on Datix® from 23 March 2020 to 29 May 2020, compared to the period from 23 March 2019 to 29 May 2019. COVID-19 related incidents and complaints and association with newly published guidelines or pathways from 23 March 2020 to 29 May 2020 were investigated. RESULTS: There was no significant difference in the proportion of overall patient activity resulting in incidents reported on Datix in 2020 (2.08%) compared to 2019 (2.09%), with 98% resulting in no/low harm in 2020. Three incident categories had increases in relative proportions of incidents including the terms "COVID" or "Corona" compared to incidents that did not: "Child death", "delay/failure to treatment and procedure" and "information governance". One of the child deaths was a miscarriage and we were unable to link the second child death to a change in clinical policy at this stage. We were only able to link two COVID-19 associated incidents with a pathway or procedural change (one to the Children's Emergency Department admission pathway and the second to the introduction of virtual antenatal clinics). Eighteen complaints related to COVID-19 were logged. However, at this stage, we are unable to link any of these to a published change in clinical policy. CONCLUSIONS: New policies introduced in the division, during the COVID-19 pandemic were associated with similar rates of clinical incidents, when compared with the previous year. There were only two COVID-19-related incidents clearly related to a change in pathways and procedures. Continued surveillance and improved metrics for monitoring the impact of changes to pathways and procedures should be sought with the sustained presence of COVID-19 in clinical areas.

Lipidomic Biomarkers in Polycystic Ovary Syndrome and Endometrial Cancer.

Women with polycystic ovary syndrome (PCOS) are more likely to develop endometrial cancer (EC). The molecular mechanisms which increase the risk of EC in PCOS are unclear. Derangements in lipid metabolism are associated with EC, but there have been no studies, investigating if this might increase the risk of EC in PCOS. This was a cross-sectional study of 102 women in three groups of 34 (PCOS, EC and controls) at Nottingham University Hospital, UK. All participants had clinical assessments, followed by obtaining plasma and endometrial tissue samples. Lipidomic analyses were performed using liquid chromatography (LC) coupled with high resolution mass spectrometry (HRMS) and the obtained lipid datasets were screened using standard software and databases. Using multivariate data analysis, there were no common markers found for EC and PCOS. However, on univariate analyses, both PCOS and EC endometrial tissue samples showed a significant decrease in monoacylglycerol 24:0 and capric acid compared to controls. Further studies are required to validate these findings and investigate the potential role of monoacylglycerol 24:0 and capric acid in the link between PCOS with EC.

The student is key: A realist review of educational interventions to develop analytical and non-analytical clinical reasoning ability.

OBJECTIVES: Clinical reasoning refers to the cognitive processes used by individuals as they formulate a diagnosis or treatment plan. Clinical reasoning is dependent on formal and experiential knowledge. Developing the ability to acquire and recall knowledge effectively for both analytical and non-analytical cognitive processing has patient safety implications. This realist review examines the way educational interventions develop analytical and non-analytical reasoning ability in undergraduate education. A realist review is theory-driven, seeking not only to identify if an intervention works, but also understand the reasons why, for whom, and in what circumstances. The aim of this study is to develop understanding about the way educational interventions develop effective analytical and non-analytical clinical reasoning ability, when they do, for whom and in what circumstances. METHODS: Literature from a scoping search, combined with expert opinion and researcher experience was synthesised to generate an initial programme theory (IPT). Four databases were searched and articles relevant to the developing theory were selected as appropriate. Factors affecting educational outcomes at the individual student, teacher and wider organisational levels were investigated in order to further refine the IPT. RESULTS: A total of 28 papers contributed to the overall programme theory. The review predominantly identified evidence of mechanisms for interventions at the individual student level. Key student level factors influencing the effectiveness of interventions included an individual's self-confidence, self-efficacy and pre-existing level of knowledge. These contexts influenced a variety of educational interventions, impacting both positively and negatively on educational outcomes. CONCLUSIONS: Development of analytical and non-analytical clinical reasoning ability requires activities that enhance knowledge acquisition and recall alongside the accumulation of clinical experience and opportunities to practise reasoning in real or simulated clinical environments. However, factors such as pre-existing knowledge and self-confidence influence their effectiveness, especially amongst individuals with 'low knowledge.' Promoting non-analytical reasoning once novices acquire more clinical knowledge is important for the development of clinical reasoning in undergraduate education.

Emotional Well-Being, Cognitive Load and Academic Attainment.

This article was migrated. The article was marked as recommended. This opinion piece examines some of the literature on the impact of emotional wellbeing on cognitive load and the impact this might have on educational attainment. It discusses cognitive load theory and outlines a brief history of its evolution to our current understanding. The literature on the degree to which negative emotions contribute to cognitive load is explored, followed by the association between cognitive load and educational attainment in the context of cognitive load theory. The article concludes by making a case for increased awareness, highlighting the need for more empirical research and briefly examining the role of some potential interventions to optimise cognitive load in the context of emotional wellbeing and their potential impact on educational attainment.