Publications

Publication: BMC Medicine

Burgoine, T., Monsivais, P., Sharp, S., Forouhi, N. and Wareham, N.

15 February 2021

Characteristics of the built environment, such as neighbourhood fast-food outlet exposure, are increasingly recognised as risk factors for unhealthy diet and obesity. Obesity also has a genetic component, with common genetic variants explaining a substantial proportion of population-level obesity susceptibility. However, it is not known whether and to what extent associations between fast-food outlet exposure and body weight are modified by genetic predisposition to obesity.

We used data from the Fenland Study, a population-based sample of 12,435 UK adults (mean age 48.6 years). We derived a genetic risk score associated with BMI (BMI-GRS) from 96 BMI-associated single nucleotide polymorphisms. Neighbourhood fast-food exposure was defined as quartiles of counts of outlets around the home address. We used multivariable regression models to estimate the associations of each exposure, independently and in combination, with measured BMI, overweight and obesity, and investigated interactions.

We found independent associations between BMI-GRS and risk of overweight (RR = 1.34, 95% CI 1.23–1.47) and obesity (RR = 1.73, 95% CI 1.55–1.93), and between fast-food outlet exposure and risk of obesity (highest vs lowest quartile RR = 1.58, 95% CI 1.21–2.05). There was no evidence of an interaction of fast-food outlet exposure and genetic risk on BMI (P = 0.09), risk of overweight (P = 0.51), or risk of obesity (P = 0.27). The combination of higher BMI-GRS and highest fast-food outlet exposure was associated with 2.70 (95% CI 1.99–3.66) times greater risk of obesity.

Our study demonstrated independent associations of both genetic obesity risk and neighbourhood fast-food outlet exposure with adiposity. These important drivers of the obesity epidemic have to date been studied in isolation. Neighbourhood fast-food outlet exposure remains a potential target of policy intervention to prevent obesity and promote the public’s health.

Publication: Geriatrics

Christopher N. Osuafor, Catriona Davidson, Alistair J. Mackett, Marie Goujon, Lelane Van Der Poel, Vince Taylor, Jacobus Preller, Robert J. B. Goudie and Victoria L. Keevil

1 February 2021

Summary

In an observational study, researchers in Cambridge investigated the clinical features and inpatient trajectories of older adults hospitalised with COVID-19 and explore relationships with frailty.

Publication: The Lancet

Kathryn Beardsall, Lynn Thomson, Catherine Guy, Isabel Iglesias-Platas, Prof Mirjam M van Weissenbruch, Simon Bond, et al

9 February 2021

Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants.

Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care.

This international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6–10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life.

Between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis.

Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6–10 mmol/L glucose concentration target range. More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group. There were no serious adverse events related to the use of the device or episodes of infection.

Real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes.

Publication: Osteoporosis International 

A.M. Constable, D. Vlachopoulos, A.R. Barker, S.A. Moore, S. Soininen, E.A. Haapala, J. Väistö, K. Westgate, S. Brage, A. Mahonen &  T.A. Lakka

5 February 2021

Summary

It is unclear how physical activity intensity and vitamin D status are related to bone health in prepubertal children. We found positive associations between vitamin D status and moderate-to-vigorous physical activity with bone in boys and girls. This highlights the importance of lifestyle factors for skeletal health prepuberty.

Publication: Stroke AHA

Eric L. Harshfield, Marios K. Georgakis, Rainer Malik, Martin Dichgans, Hugh S. Markus

4 February 2021

Summary

Assessing whether modifiable risk factors are causally associated with stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data.

Here the research team evaluated whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal risk factors for ischemic stroke and its subtypes and hemorrhagic stroke.

They performed 2-sample and multivariable Mendelian randomization to assess the causal effect of 12 lifestyle factors on risk of stroke and whether these effects are independent.

Genetically predicted years of education was inversely associated with ischemic, large artery, and small vessel stroke, and intracerebral hemorrhage.

Genetically predicted smoking, body mass index, and waist-hip ratio were associated with ischemic and large artery stroke. The effects of education, body mass index, and smoking on ischemic stroke were independent.

These findings support the hypothesis that reduced education and increased smoking and obesity increase risk of ischemic, large artery, and small vessel stroke, suggesting that lifestyle modifications addressing these risk factors will reduce stroke risk.

Publication: Clinical Kidney Journal

Toby J L Humphrey, Glen James, Eric T Wittbrodt, Donna Zarzuela, Thomas F Hiemstra

30 January 2021

Summary:

In an observational study analysing data from over 430,000 patients, those who had their RAASi – blood pressure medications – interrupted or stopped, were found to have worse outcomes than those who continued with their treatment.

The patients who had medication interruptions or discontinuated were more likely to be hospitalised, to have a cardiac arrest or develop kidney damage than those who continued on their RAASi medications throughout the study.

This study highlights that the potential risks for and against RAASi treatment interruption or discontinuation be very carefully considered in patients for whom guideline-recommended RAAS inhibitor therapy is indicated.

Publication: Communications Biology

E Allara, S Kaptoge, AM Wood, AS Butterworth, J Danesh, E Di Angelantonio et al

3 February 2021

Iron is essential for many biological functions and iron deficiency and overload have major health implications.

Here the researchers performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin, total iron binding capacity, iron and transferrin saturation.

They identified 46 novel loci affecting iron homeostasis and showed an association of five of these loci with IDA, a major clinical entity that hitherto has not been studied thoroughly from a genetic point of view.

This study reveals a substantial catalog of possible iron regulatory genes, awaiting further inquiry to fully elucidate their functional role.

Publication: Translational Psychiatry

Kanen JW, Arntz FE, Yellowlees R, Cardinal RN, Price A, Christmas DM, Apergis-Schoute AM, Sahakian BJ, Robbins TW

1 February 2021

Serotonin is involved in a wide range of mental capacities essential for navigating the social world, including emotion and impulse control. Much recent work on serotonin and social functioning has focused on decision-making. Here researchers investigated the influence of serotonin on human emotional reactions to social conflict. They used a novel computerised task that required mentally simulating social situations involving unjust harm and found that depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-enhanced emotional responses to the scenarios in a large sample of 73 healthy volunteers, and interacted with individual differences in trait personality to produce distinctive human emotions.

Whereas guilt was preferentially elevated in highly empathic participants, annoyance was potentiated in those high in trait psychopathy, with medium to large effect sizes. The findings show how individual differences in personality, when combined with fluctuations of serotonin, may produce diverse emotional phenotypes. This has implications for understanding vulnerability to psychopathology, determining who may be more sensitive to serotonin-modulating treatments, and casts new light on the functions of serotonin in emotional processing.

Publication: The Lancet Infectious Diseases

Luke W Meredith, William L Hamilton, Ben Warne, Charlotte J Houldcroft, Myra Hosmillo, Aminu S Jahun, Martin D Curran, Surendra Parmar, Laura G Caller, Sarah L Caddy, Fahad A Khokhar, Anna Yakovleva, Grant Hall, Theresa Feltwell, Sally Forrest, Sushmita Sridhar, Michael P Weekes, Prof Stephen Baker, Nicholas Brown, Elinor Moore, Ashley Popay, Iain Roddick, Mark Reacher, Theodore Gouliouris, Prof Sharon J Peacock, Prof Gordon Dougan, M Estée Török, Prof Ian Goodfellow.

14 July 2020

Summary:

Cambridge researchers have shown how rapid genome sequencing of virus samples and enhanced testing of hospital staff can help to identify clusters of healthcare-associated COVID-19 infections. Read the full news article.

Publication: MedRxiV

Christopher J. R. Illingworth, ProfileWilliam L. Hamilton,  ProfileChris Jackson, Ashley Popay, Luke Meredith, Charlotte J. Houldcroft, Myra Hosmillo, Aminu Jahun, Matthew Routledge, Ben Warne, Laura Caller, Sarah Caddy, Anna Yakovleva, Grant Hall, Fahad A. Khokhar, Theresa Feltwell, Malte L. Pinckert, Iliana Georgana, Yasmin Chaudhry, Martin Curran, Surendra Parmar, Dominic Sparkes, Lucy Rivett, Nick K. Jones, Sushmita Sridhar, Sally Forrest, Tom Dymond, Kayleigh Grainger, Chris Workman, Effrossyni Gkrania-Klotsas, Nicholas M. Brown, Michael P. Weekes, Stephen Baker, Sharon J. Peacock, Theodore Gouliouris, Ian Goodfellow, Daniela de Angelis, M. Estée Török

27 October 2020

Summary:

A new software tool will help doctors identify where cases of COVID-19 were caused by transmission within a hospital, helping them to prevent further spread of the disease.

The new software package, A2B-Covid, combines knowledge about infection dynamics, data describing the movements of individuals, and genome sequence data to assess whether or not coronavirus has been transmitted between people in the hospital environment.

Publication: JAMA

Eric L. Harshfield, Lisa Pennells, Joseph, Schwartz, Peter Willeit, Stephen Kaptoge, Steven Bell, Jonathan A. Shaffer, Thomas Bolton, Sarah Spackman, Sylvia Wassertheil-Smoller, Frank Kee, Philippe Amouyel, Steven J. Shea, Lewis H. Kuller,  Jussi Kauhanen,  E. M. van Zutphen, Dan G. Blazer, Harlan Krumholz, Paul J. Nietert, Daan Kromhout, MD19; Gail Laughlin, Lisa Berkman, Robert B. Wallace, Leon A. Simons, Elaine M. Dennison, Elizabeth L. M. Barr,  Haakon E. Meyer, Angela M. Wood, John Danesh, Emanuele Di Angelantonio, Karina W. Davidson

15 December 2020

Summary

People who experience symptoms of depression are more likely to go on to develop heart disease or suffer a stroke than those who report good mental health.

Researchers analysed the health records of over half a million people, with no prior history of heart and circulatory disease, who were enrolled to two different studies.

Upon joining the studies, participants were given a score based on questionnaires assessing their mood and any symptoms of depression that they had experienced over the previous one to two weeks.

Over 10, researchers have found that those in the highest scoring group, and with most severe symptoms of depression, were more likely to have since developed heart disease or to have had a stroke, compared to people with the lowest scores.

Publication: Neurology

Marios K. Georgakis, Eric L. Harshfield, Rainer Malik, Nora Franceschini, Claudia Langenberg, Nicholas J. Wareham, Hugh S. Markus, Martin Dichgans

25 January 2021

The researchers employed Mendelian randomization to explore the effects of genetic predisposition to type 2 diabetes (T2D), hyperglycemia, insulin resistance, and pancreatic β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes.

This study supports causal effects of T2D and hyperglycemia on large artery and small vessel stroke. Genetically predicted insulin resistance and β-cell dysfunction are associated with large artery and small vessel stroke; this may have implications for antidiabetic treatments targeting these mechanisms.

Publication: Medrxiv

Laura Bergamaschi, Federica Mescia, Lorinda Turner, Aimee Hanson, Prasanti Kotagiri, Benjamin J. Dunmore, Helene Ruffieux, Aloka De Sa, Oisin Huhn, Mark R. Wills, Stephen Baker, Rainer Doffinger, Gordon Dougan, Anne Elmer, Ian G Goodfellow, Ravindra K. Gupta, Myra Hosmillo, Kelvin Hunter, Nathalie Kingston, Paul J. Lehner, Nicholas J. Matheson, Jeremy K. Nicholson, Anna M. Petrunkina, Sylvia Richardson, Caroline Saunders, James E.D. Thaventhiran, Erik J. M. Toonen, Michael P. Weekes, Mark Toshner, Christoph Hess, John R. Bradley, Paul A. Lyons, Kenneth G.C. Smith

15 January 2021

Summary

It may be possible to predict which patients will go on to develop severe or long-term COVID symptoms (sometimes known as ‘long COVID’).

Cambridge researchers looked at blood samples taken regularly over three months from more than 200 people, ranging from COVID-19 patients who were severely ill and needed ventilation to asymptomatic NHS staff who had tested positive for the virus but showed no symptoms.

The immune systems in patients who were the sickest showed early evidence of an abnormal inflammatory response, leading to a flood of immune cells which damaged healthy cells as well as the virus. Finding inflammation early in the blood samples and at the point of diagnosis could help doctors to identify and predict patients who will develop severe COVID-19.

The results have been released as a pre-print, read the full news story.

Publication: Critical Care

Publication: PLOS Medicine

Alexandros A. Moraitis, Norman Shreeve, Ulla Sovio, Peter Brocklehurst, Alexander E. P. Heazell, Jim G. Thornton, Stephen C. Robson, Aris Papageorghiou, Gordon C. Smith 

13 October 2020

Summary:

Delivering a large baby (usually defined as above 4Kg or 90th birth weight centile) has been associated with complications such shoulder dystocia – after the vaginal delivery of the head, the baby’s shoulder gets stuck behind the mother’s pubic bone. This could lead to the baby with fractured bones and lack of oxygen during the delivery. There may be then a potential need for emergency caesarean section and neonatal unit admission.

Predicting the delivery of a large baby can be difficult and there is currently no standard screening programme to predict these complications.

Screening more than 100,000 patients, Cambridge researchers found that offering a scan to all women at 36 weeks could increase the detection of delivering a large baby and the prediction was more effective for very large babies (above 4.5Kg). However, the screening could not identify shoulder dystocia to the same effect or enough evidence to predict which babies could have other complications.

More evidence is needed on the benefit of introducing another ultrasound for all women, to help identify any potential problems before labour as well as predict large babies.

Publication: PLOS Medicine

Julieta Galante, Claire Friedrich, Anna F Dawson, Marta Modrego-Alarcón, Pia Gebbing, Irene Delgado-Suárez, Radhika Gupta, Lydia Dean, Tim Dalgleish, Ian R White, Peter B Jones 

11 January 2021

Summary:

Many randomised controlled trials (RCTs) have been conducted around the world to assess whether in-person mindfulness training can improve mental health and wellbeing, but the results are often varied.

Researchers led a systematic review and meta-analysis to examine the published data from the RCTs. This approach allows them to bring together existing – and often contradictory or under-powered – studies to provide more robust conclusions.

The team identified 136 RCTs on mindfulness training for mental health promotion in community settings. These trials included 11,605 participants aged 18 to 73 years from 29 countries, more than three-quarters (77%) of whom were women.

The researchers found that in most community settings, compared with doing nothing, mindfulness reduces anxiety, depression and stress, and increases wellbeing. However, the data suggested that in more than one in 20 trials settings, mindfulness-based programmes may not improve anxiety and depression. Read the full press release

Publication: EBioMedicine

Olga L, van Diepen J, Bobeldijk-Pastorova I, Gross G, Prentice P, Snowden S et al.

7 January 2021

Altered lipid metabolism in early life has been associated with subsequent weight gain and predicting this could aid in obesity prevention and risk management. Here, a lipidomic approach was used to identify circulating markers for future obesity risk in translational murine models and validate in a human infant cohort.

From murine models to human setting, the ratios of circulating lipid species indicating key desaturase activities in lipid metabolism were associated with subsequent body size increase, providing a potential tool to predict early life weight gain.

Publication: AHA Journals - Hypertension

Dipender Gill, Alan C. Cameron, Stephen Burgess, Xue Li, Daniel J. Doherty, Ville Karhunen, Azmil H. Abdul-Rahim, Martin Taylor-Rowan, Verena Zuber, Philip S. Tsao, Derek Klarin, Evangelos Evangelou, Paul Elliott, Scott M. Damrauer, Terence J. Quinn, Abbas Dehghan, Evropi Theodoratou, Jesse Dawson, Ioanna Tzoulaki

28 December 2020

Summary:

Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, researchers performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials.

Publication: Science Direct

Michael J. Sweeting, John Marshall, Matthew Glover, Akhtar Nasim, Matthew J. Bown

25 December 2020

The National Health Service Abdominal Aortic Aneurysm Screening Programme has been shown to be highly cost-effective. Recently, the prevalence of screen-detected abdominal aortic aneurysm (AAA) has fallen. If this trend continues, the cost-effectiveness of AAA screening is threatened.

One option to improve program cost-effectiveness is to extend the length of time between surveillance scans for men who are found to have AAA at screening. The potential safety and cost savings associated with such a change are unknown.

Extending the length of time between surveillance scans for men with screen-detected AAA in the Abdominal Aortic Aneurysm Screening Programme, especially for those with smaller AAAs, reduces the incremental cost per quality-adjusted life-year of the program. This is associated with a small increase in the number of adverse clinical events in the overall population of men invited for screening.

It is unclear whether the benefit of cost saving from refining surveillance strategies justifies the increased harms associated with such a change in clinical practice. Furthermore, realizing the benefits of minimized surveillance strategies for individual screening units may be difficult owing to the regional structure of the AAA screening workforce.

This study aimed to investigate the safety and cost-effectiveness of lengthening the time between surveillance ultrasound scans in the UK Abdominal Aortic Aneurysm (AAA) Screening Programme.

A discrete event simulation model was used to evaluate the cost-effectiveness of AAA screening for men aged 65, comparing current surveillance intervals to 6 alternative surveillance interval strategies that lengthened the time between surveillance scans for 1 or more AAA size categories. The model considered clinical events and costs incurred over a 30-year time horizon and the cost per quality-adjusted life year (QALY). The model adopted the National Health Service perspective and discounted future costs and benefits at 3.5%.

Compared with current practice, alternative surveillance strategies resulted in up to a 4% reduction in the number of elective AAA repairs but with an increase of up to 1.6% in the number of AAA ruptures and AAA-related deaths. Alternative strategies resulted in a small reduction in QALYs compared to current practice but with reduced costs. Two strategies that lengthened surveillance intervals in only very small AAAs (3.0-3.9 cm) provided, at a cost-effectiveness threshold of £20 000 per QALY, the highest positive incremental net benefit. There was negligible chance that current practice is the most cost-effective strategy at any threshold below £40,000 per QALY.

Lengthening surveillance intervals in the UK Abdominal Aortic Aneurysm Screening Programme, especially for small AAA, can marginally reduce the incremental cost per QALY of the program. Nevertheless, whether the cost savings from refining surveillance strategies justifies a change in clinical practice is unclear.

Publication: BMJ Open

Saman Khalatbari-Soltani, Pedro Marques-Vidal, Fumiaki Imamura, G. Forouhi

22 December 2020

Summary:

In an international study, with researchers from Cambridge and Switzerland, researchers reviewed a Mediterranean-style diet to see if it may lower the risk of developing fatty liver disease.

Fatty liver, defined as fat accumulation of more than 5% of liver volume, is common especially among obese and diabetic individuals. Fatty liver is the first stage for non-alcoholic fatty liver disease (NAFLD), which is a major cause of liver disease worldwide, and may also predispose to higher risk of cardiovascular diseases.

The Mediterranean diet is thought to be beneficial but research was limited to people with established fatty liver disease. Researchers

In 2288 study participants without NAFLD at baseline, when we assessed their dietary habits and scaled their levels of adherence to the well-established Mediterranean diet. After an average of 5.3-years of follow-up in the study, we tested for the presence of fatty liver disease based on two indices called “fatty liver index” and “NAFLD score”.

Results showed that those who adhered more to the Mediterranean diet had lower risk of developing new-onset fatty liver disease based on fatty liver index.