Endocrinology and diabetes
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 neuro-developmental 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.
De-prescribing in elderly people with diabetes
Older adults with diabetes are at risk of developing a similar spectrum of macrovascular and microvascular complications as their younger counterparts with diabetes. However, the intensity of glycaemic control needed in older people needs to be less stringent as they tend to be at high risk for polypharmacy and falls. There is currently a work programme on the safe de-prescribing in elderly people with diabetes and other multi-morbidities. Working with their supervisors, the ACF will lead the epidemiological aspect of the work programme. The post holder will have a unique opportunity to use CPRD in collaboration with a large network of researchers across the unit to explore the epidemiology of safe de-prescribing in elderly people with diabetes and cardio-metabolic conditions. The Leicester Diabetes Research Centre has recently obtained Gold access to the CPRD which grants access to linkage to HES to provide greater insight into cardiovascular outcomes. The post holder will be provided training in one or more of the following areas:
Big Data training: (Professor Kamlesh Khunti): The ACF will be trained to code and analyse large, linked datasets. The post holder will then explore the epidemiology of de-prescribing of diabetes and cardio-metabolic medication and the relationship of this to the quality of life of these patients.
Pragmatic trial: The ACF will work along an expert group of researchers to conduct a pragmatic cluster randomised trial on the safe de-prescribing of diabetes and cardio-metabolic medications in the elderly population from the over 200 network of practices in Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) hosted by University of Surrey.
Synchronisation of lifestyle interventions with circadian rhythm to optimize metabolic health
Mammalian endogenous circadian timing systems originate in internal oscillators or biological clocks. These circadian rhythms need to be entrained to environmental cues to cope with food availability, light exposure or predatorial risks. The circadian rhythm also regulates a host of metabolic processes through central and peripheral mechanisms. The advent of modern industrialised societies has created a 24 hour society where many individuals’ exhibit circadian rhythms that are out of phase with their imposed daily schedule. The new term of ‘‘social jet-lag’’ has been used to describe this phenomenon. This disruption is enhanced by inter-individual variability in temporal preferences of the population which vary from the extreme morning (‘‘lark’’) type to the extreme nocturnal (‘‘owl’’) type; these behavioural manifestations of the circadian rhythm have been termed “chronotypes”. Living a lifestyle that is out of phase with individual chronotyopes is now recognised to initiate metabolic dysfunction and is a major risk factor for type 2 diabetes.
The ACF will be to undertake a series of studies to test whether synchronising lifestyle interventions with circadian rhythm can restore metabolic health in those with dysglycaemia.
The project will involve a series of supervised laboratory trials and free-living interventions to test the extent to which lifestyles that are out of phase with chronotype are associated with dysglycaemia and type 2 diabetes and whether metabolic health can subsequently be restored through targeted interventions matching exercise training and dietary intake to key period within individual circadian rhythms. In addition, the fellowship will undertake a systematic review assessing the current state of the evidence.
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.
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.