Obstetrics and gynaecology
Long term metabolic and cardiovascular health using UK primary care data [the Clinical Practice Research Datalink (CPRD)]
This project is a retrospective cohort study using UK primary care data [the Clinical Practice Research Datalink (CPRD)], to explore maternal and neonatal outcomes in women with anaemia during pregnancy. Globally, about 50% of severe maternal outcomes including maternal deaths and near-miss complications are attributed to anaemia. Maternal anaemia is associated with a range of adverse pregnancy outcomes, including fetal losses, neonatal deaths, pre-term births, small for gestational age, low birth weight and neurodevelopmental problems. Women with anaemia in pregnancy are less likely to endure the effects of extreme blood loss in child birth, and are more likely to succumb to infection/sepsis, fatigue and depression in the antenatal and postnatal periods. Adverse effects of maternal anaemia often exacerbate in the postpartum stage and are associated with lactation failure. Finally, maternal anaemia is associated with long term maternal and fetal metabolic and cardiovascular morbidity and mortality. This project proposes identifying all pregnancies with maternal anaemia from 2000 to 2018 within CPRD along with a comparison group of time-matched non-anaemic controls. Both short and long-term maternal and fetal outcomes will be compared between the two cohorts and a secondary analysis stratifying by severity of anaemia will also be undertaken.
Development of minimally invasive test to identify womb cancer
Postmenopausal bleeding (PMB) is the most common presenting symptom of endometrial cancer (EC) however, less than 10% of women with PMB will have EC or pre-cancer (complex atypical hyperplasia, CAH). As a result tens of thousands of women each year in the UK are referred to secondary care for investigation of PMB, typically by a hysteroscopy in order to visualise the endometrium and perform a biopsy. A hysteroscopy is an invasive, typically painful and expensive procedure that is not without risk. Public patient involvement (PPI) work conducted in women diagnosed with EC found that women unanimously reported that they found a hysteroscopy very uncomfortable and that a blood or vaginal swab/smear test would be preferable. The aim of this study is to identify a molecular marker that could accurately detect EC/CAH on a vaginal smear or swab test, thereby enabling women with an abnormality to be identified quickly and women without an abnormality to be reassured, and potentially avoid a hysteroscopy. The study will enable skills in clinical study management and recruitment, qualitative research techniques as well as laboratory skills and data analysis.
Urine exosome profiling in women who develop proteinuria in pregnancy
Development of proteinuria in pregnancy is multifactorial and can significantly impact maternal and fetal health. It may be isolate or associated with high blood pressure (pre-eclampsia) or chronic kidney disease. Investigation of underlying cause is complicated in pregnancy by the relative difficulty of performing a renal biopsy and therefore diagnostic and prognostic biomarkers are needed to help risk stratify women and identify those at greatest risk of complications and most likely to benefit from intervention. The ACF/PhD will comprise three components:
- Part 1: Undertake a cross sectional study using urine from healthy pregnant women and pregnant women who develop proteinuria- purify the urine exosomes and perform next generation sequencing for mRNA and microRNA content and LC-MS/MS to identify associated proteins and identify exosomal mRNAs/miRs/proteins associated with proteinuria
- Part 2: Validate findings from the Part 1 biomarker discovery study with a second set of samples. Perform bioinformatic and laboratory analyses to determine potential cells of origin of the exosomes and biological function.
- Part 3: Undertake a prospective longitudinal study to examine changes in excretion of identified proteinuria-specific exosomal mRNA/miR/proteins during pregnancy in unselected cases and relate these to development of proteinuria, maternal and fetal outcomes.
During the ACF we would expect the trainee to collect pilot data to support a PhD proposal to cover definitive Part 2 and 3 studies.
Role of robotic assist surgery in gynaecology
Gynaecology has always been at the forefront of minimally invasive surgery (MIS) development and as a result MIS is an integral part of everyday surgical practice. More recently robotic-assisted surgery (RA) has become established as an alternative to straight-stick (SS) laparoscopy in gynaecology. Financial cost is primary barrier to widespread RA use however with newer robotic platforms being introduced this may change in the future. The clinical impact of better visualisation, tremor reduction and increased dexterity that are reported with RA in the gynaecology population need further investigation in order to objectively determine the benefits and aid optimum case selection.
University of Leicester is working with Loughborough University on surgeon ergonomics and RA and has an established dry lab for movement capture and monitoring. The ACF will work with the clinical and engineering teams investigating effect of patient characteristics on surgeon ergonomics. The proposed research would complement this work by looking more closely at patient physiology during RA. The study will enable skills in clinical study management and recruitment, qualitative and quantitative research techniques as well as data analysis.
Determining the clinically relevant anatomy to teach UG medical students
Human anatomy has been a core component of undergraduate medical education for many years, and while it continues to be a key theme, the depth of anatomy taught has seen a steady decline. The need for a solid foundation of anatomical knowledge, while more readily appreciated as essential for those pursuing surgical careers, is important for any practicing clinician. Clearly, which areas of anatomy are most relevant will vary depending on the postgraduate speciality. With ever increasing pressures on space within the UG curriculum, there is obvious priority to ensuring what is taught best enables students to meet the demands of the breadth of future clinical practice.
While the GMC do not currently stipulate specific outcomes for the level of anatomy within the UG medical curriculum, the future introduction of the UK Medical Licensing Assessment will likely lead to efforts to better establish ILOs for the basic sciences, as a whole. In 2016, in response to the lack of consensus and guidance on the appropriate level of anatomy, the Anatomical Society defined a core regional anatomy syllabus of 156 ILOs, which were to help curriculum planners determine the clinically relevant anatomy to teach UG medical students. The proposed ILOs were determined by a Delphi panel of experts, which included surgeons, radiologists and anatomists.
The first step of the project will involve a series of focus groups and surveys with a variety of early clinical trainees from medicine, surgery and primary care. The purpose of this will be to identify whether there are elements of the 156 identified ILOs that represent a base of anatomical knowledge common across a breadth of specialities (surgical and non-surgical). The second step will be to explore how well they perceive (by self-report) to have retained knowledge of those areas of anatomy (identified in the first step of the project).
The findings from this project will help to better define areas of anatomy that are seen as most important, relevant and common to a breadth of clinical specialities. Further work/projects could explore how this anatomy could be prioritised or given greater attention within the UG medical curriculum, or early postgraduate period and whether there are any interventions that can be applied to improve retention of knowledge in those areas.
Significant weight loss through dietary restriction to reduce endometrial malignancy risk (Diet to Reduce Endo Risk)
There is a rise in the incidence of endometrial cancer (EC) attributed in part to rising obesity levels. New strategies for prevention are required, particularly for women who wish to preserve fertility. Obesity plays a major role in development of endometrioid EC, through a chronic state of hyperestrogenaemia, insulin resistance and inflammation.
Endometrial cancer is preventable with weight loss in women who are overweight.
This project will work with women identified as at risk by the UHL Endometrial Cancer Services. Currently at this stage women are given advice about losing weight to reduce risk and are signposted to existing weight management services, or offered hysterectomy.
The ACF will pilot an alternative approach to weight loss using an effective energy restrictive diet, which has not been used in this population at this time. Applying a low energy diet (LED) (~800kcal) in the window between risk identification and planned hysterectomy.
We will examine feasibility and acceptability of applying this approach for a future trial, and quantifying associated changes in endometrial pathology.