Building a Weight of Evidence to Prevent Cancer in Later Life

Background: Obesity is the largest preventable risk factor for cancer in the UK after smoking. Being overweight as an adult is linked to 13 types of cancer, and overweight children are more likely to become overweight adults. Routine data shows that around one in three children leave primary school in the UK (aged 12) overweight or obese, with the children from the most deprived communities twice as likely to be so. Cancer Research UK is campaigning for restrictions on the marketing of foods high in salt sugar and fat (HFSS foods) to children as part of a comprehensive population level strategy to prevent obesity-related cancers in the future. Aim: To undertake a mixed methods program of research aimed at building a body of evidence to directly inform policy to address childhood obesity. Methods: Individual studies included: a national cross-sectional survey to investigate obesity and cancer awareness in the UK adult population; a modeling study to predict future obesity-related cancer cases; and qualitative and quantitative studies to explore obesity-linked behaviors and exposure to HFSS marketing in children. A narrative synthesis of results from individual studies was conducted to identify key themes and develop recommendations for policy. Results: Cancer was not at the forefront of people's minds when thinking about obesity, with only 26% of UK adults reporting (unprompted) awareness of the link. However, results from modeling identified that the projected impact of obesity on cancer is high: if current trends continue it will lead to a further 670,000 cases in the UK over the next 20 years. Qualitative research identified a high awareness of junk food marketing in children aged 8-19. This influenced their behavior using a variety of persuasive marketing techniques, including catchy slogans and jingles, celebrity endorsements or by referencing youth culture. Logistic regression modeling associated commercial TV screen time with an increased risk of high junk food consumption (OR 1.8, P = 0.002). Furthermore, recalling one extra broadcast advert predicted a significant increase in HFSS consumption, approximately 18,000 extra calories/person/year. Conclusion: These linked studies have informed Cancer Research UK's campaign on obesity, and results have been used to inform work with the media, coalition building and influencing. Findings that HFSS food marketing influenced children's consumption behaviors were published on the charity's lobbying day in parliament where the research was discussed with almost 170 members of parliament. To achieve further HFSS marketing restrictions, research evidence is essential to making the case for policy change and this approach from a large UK cancer charity could inform similar efforts in other countries.

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No Association between Prenatal Viral Infection and Depression in Later Life—A Long-Term Cohort Study of 6152 Subjects

The Canadian Journal of Psychiatry ◽

10.1177/070674370905400809 ◽

2009 ◽

Vol 54 (8) ◽

pp. 565-570 ◽

Cited By ~ 25

Author(s):

Dong Pang ◽

Saddaf Syed ◽

Paul Fine ◽

Peter B Jones

Keyword(s):

Viral Infection ◽

Primary Care Physicians ◽

Viral Infections ◽

Later Life ◽

International Classification Of Diseases ◽

In Utero ◽

Matched Pair ◽

Increased Risk ◽

Uk National Health Service ◽

The Uk

Objective: Previous studies have suggested a role for prenatal viral infections in the etiology of schizophrenia; however, little is known about depression. We examined whether in-utero viral infections result in increased risk of depression in later life. Method: We identified a cohort ( n = 3076) born between 1946 and 1980, whose mothers suffered known viral infections in pregnancy. Subjects were individually matched by birthdate, sex, and area of birth to another cohort ( n = 3076) from the UK National Health Service Central Register (NHSCR). These 2 cohorts, one exposed to viruses prenatally, the other not known to have been exposed, were then followed-up to June 1996 by sending a morbidity questionnaire to their primary care physicians. This included specific items on affective disorders, schizophrenia, mental handicap (mental retardation), epilepsy, as well as other central nervous system disorders and specified physical illness, all coded according to the International Classification of Diseases, Ninth Edition. Death certificates were supplied by the NHSCR. A method for matched-pair cohort data calculated the relative risk and 95% confidence intervals for depression in the exposed and unexposed cohorts by varying type of viral exposure. Results: The response to the questionnaire was high (85%). There was no overall increased risk for depression associated with viral exposure; a narrow confidence interval surrounded unity (RR = 1.0, 95% CI 0.8 to 1.2); effects for individual viral exposures were all scattered around unity. Conclusions: The results provide no support for the hypothesis that in-utero exposure to viral infection is associated with risk of subsequent nonpsychotic affective disorder. Further analyses on schizophrenia, bipolar disorder, and mental illness other than depression are required.

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Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank

Journal of Medical Genetics ◽

10.1136/jmedgenet-2018-105477 ◽

2018 ◽

Vol 56 (3) ◽

pp. 131-138 ◽

Cited By ~ 34

Author(s):

Karen Crawford ◽

Matthew Bracher-Smith ◽

David Owen ◽

Kimberley M Kendall ◽

Elliott Rees ◽

...

Keyword(s):

Later Life ◽

Uk Biobank ◽

Medical Outcomes ◽

Neurodevelopmental Outcomes ◽

Increased Risk ◽

Array Quality ◽

Pathogenic Cnvs ◽

The Uk ◽

Genomic Disorders ◽

Rate Threshold

BackgroundGenomic CNVs increase the risk for early-onset neurodevelopmental disorders, but their impact on medical outcomes in later life is still poorly understood. The UK Biobank allows us to study the medical consequences of CNVs in middle and old age in half a million well-phenotyped adults.MethodsWe analysed all Biobank participants for the presence of 54 CNVs associated with genomic disorders or clinical phenotypes, including their reciprocal deletions or duplications. After array quality control and exclusion of first-degree relatives, we compared 381 452 participants of white British or Irish origin who carried no CNVs with carriers of each of the 54 CNVs (ranging from 5 to 2843 persons). We used logistic regression analysis to estimate the risk of developing 58 common medical phenotypes (3132 comparisons).Results and conclusionsMany of the CNVs have profound effects on medical health and mortality, even in people who have largely escaped early neurodevelopmental outcomes. Forty-six CNV–phenotype associations were significant at a false discovery rate threshold of 0.1, all in the direction of increased risk. Known medical consequences of CNVs were confirmed, but most identified associations are novel. Deletions at 16p11.2 and 16p12.1 had the largest numbers of significantly associated phenotypes (seven each). Diabetes, hypertension, obesity and renal failure were affected by the highest numbers of CNVs. Our work should inform clinicians in planning and managing the medical care of CNV carriers.

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Medical consequences of pathogenic CNVs in adults: Analysis of the UK Biobank

10.1101/264077 ◽

2018 ◽

Author(s):

Karen Crawford ◽

Matthew Bracher-Smith ◽

Kimberley M Kendall ◽

Elliott Rees ◽

Antonio F Pardiñas ◽

...

Keyword(s):

Statistical Significance ◽

Copy Number Variants ◽

Later Life ◽

Uk Biobank ◽

Bonferroni Correction ◽

Medical Outcomes ◽

Neurodevelopmental Outcomes ◽

Minimal Impact ◽

Increased Risk ◽

The Uk

AbstractBackgroundGenomic copy number variants (CNVs) increase risk for early-onset neurodevelopmental disorders but their impact on medical outcomes in later life is poorly understood. The UK Biobank, with half a million well-phenotyped adults, presents an opportunity to study the medical consequences of CNV in middle and old age.MethodsWe called 54 CNVs associated with clinical phenotypes or genomic disorders, including their reciprocal deletions or duplications, in all Biobank participants. We used logistic regression analysis to test CNVs for associations with 58 common medical phenotypes.FindingsCNV carriers had an increased risk of developing 37 of the 58 phenotypes at nominal levels of statistical significance, with 19 associations surviving Bonferroni correction (p<8·6×10−4). Tests of each of the 54 CNVs for association with each of the 58 phenotypes identified 18 associations that survived Bonferroni correction (p<1·6×10−5) and a further 57 that were associated at a false discovery rate (FDR) threshold of 0·1. Thirteen CNVs had three or more significant associations at FDR=0·1, with the largest number of phenotypes (N=15) found for deletions at 16p11·2. The most common CNVs (frequency 0·5-0·7%) have no or minimal impact on medical outcomes in adults.InterpretationSome of the 54 tested CNVs have profound effects on physical health, even in people who have largely escaped early neurodevelopmental outcomes. Our work provides clinicians with a morbidity map of potential outcomes among carriers of these CNVs.FundingMRC UK, Wellcome Trust UK

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The Role of Revascularisation in Patients Undergoing Non-cardiac Surgery

Interventional Cardiology Review ◽

10.15420/icr.2010.5.1.104 ◽

2010 ◽

Vol 5 (1) ◽

pp. 104

Author(s):

Daniel S Menees ◽

Eric R Bates ◽

◽

Keyword(s):

Cardiac Surgery ◽

Prediction Models ◽

Cardiovascular Complications ◽

Weight Of Evidence ◽

Beta Blockade ◽

Cardiac Morbidity ◽

Increased Risk ◽

Reduction Strategies ◽

Artery Disease ◽

Risk Reduction Strategies

Coronary artery disease (CAD) affects millions of US citizens. As the population ages, an increasing number of people with CAD are undergoing non-cardiac surgery and face significant peri-operative cardiac morbidity and mortality. Risk-prediction models can be used to help identify those patients at increased risk of peri-operative cardiovascular complications. Risk-reduction strategies utilising pharmacotherapy with beta blockade and statins have shown the most promise. Importantly, the benefit of prophylactic coronary revascularisation has not been demonstrated. The weight of evidence suggests reserving either percutaneous or surgical revascularisation in the pre-operative setting for those patients who would otherwise meet independent revascularisation criteria.

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Long term alterations of growth after antenatal steroids in preterm twin pregnancies

Journal of Perinatal Medicine ◽

10.1515/jpm-2020-0204 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Thorsten Braun ◽

Vivien Filleböck ◽

Boris Metze ◽

Christoph Bührer ◽

Andreas Plagemann ◽

...

Keyword(s):

Early Childhood ◽

Disease Risk ◽

Later Life ◽

Ponderal Index ◽

Childhood Growth ◽

Antenatal Steroids ◽

Increased Risk ◽

Infancy And Early Childhood ◽

Twin Pregnancies

AbstractObjectivesTo compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth.MethodsA retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children’s examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years.ResultsOverall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%.ConclusionsANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease.SynopsisFirst-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk.

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Socioeconomic Inequalities and Ethnicity Are Associated with a Positive COVID-19 Test among Cancer Patients in the UK Biobank Cohort

Cancers ◽

10.3390/cancers13071514 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1514

Author(s):

Shing Fung Lee ◽

Maja Nikšić ◽

Bernard Rachet ◽

Maria-Jose Sanchez ◽

Miguel Angel Luque-Fernandez

Keyword(s):

Cancer Patients ◽

Socioeconomic Inequalities ◽

Uk Biobank ◽

Incident Cancer ◽

Increased Risk ◽

Exposure Variable ◽

Independent Risk Factors ◽

The Uk ◽

Deprived Areas

We explored the role of socioeconomic inequalities in COVID-19 incidence among cancer patients during the first wave of the pandemic. We conducted a case-control study within the UK Biobank cohort linked to the COVID-19 tests results available from 16 March 2020 until 23 August 2020. The main exposure variable was socioeconomic status, assessed using the Townsend Deprivation Index. Among 18,917 participants with an incident malignancy in the UK Biobank cohort, 89 tested positive for COVID-19. The overall COVID-19 incidence was 4.7 cases per 1000 incident cancer patients (95%CI 3.8–5.8). Compared with the least deprived cancer patients, those living in the most deprived areas had an almost three times higher risk of testing positive (RR 2.6, 95%CI 1.1–5.8). Other independent risk factors were ethnic minority background, obesity, unemployment, smoking, and being diagnosed with a haematological cancer for less than five years. A consistent pattern of socioeconomic inequalities in COVID-19 among incident cancer patients in the UK highlights the need to prioritise the cancer patients living in the most deprived areas in vaccination planning. This socio-demographic profiling of vulnerable cancer patients at increased risk of infection can inform prevention strategies and policy improvements for the coming pandemic waves.

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Association between early bronchiolitis and the development of childhood asthma: a meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-043956 ◽

2021 ◽

Vol 11 (5) ◽

pp. e043956

Author(s):

Guizuo Wang ◽

Dong Han ◽

Zhengdong Jiang ◽

Manxiang Li ◽

Shumei Yang ◽

...

Keyword(s):

Early Life ◽

Fixed Effects ◽

Late Onset ◽

Meta Analysis ◽

Later Life ◽

Analysis Data ◽

Fixed Effects Model ◽

Case Control Studies ◽

Increased Risk ◽

Registration Number

ObjectiveEarly life bronchiolitis has been hypothesised to be associated with the subsequent risk of persistent wheezing or asthma. However, the link remains controversial. The objective of our study was to evaluate the association between bronchiolitis before 2 years of age and the late-onset wheezing/asthma.DesignSystematic review and meta-analysis.MethodsPubMed, Embase and Web of Science databases were systematically searched for studies published between 1955 and January 2020. Meanwhile, we also checked through the reference lists of relevant articles to see whether these references included reports of other studies that might be eligible for the review. Cohort and case–control studies assessing the association between early-life bronchiolitis and late-onset wheezing/asthma were included in this meta-analysis. Data were extracted by two independent reviewers. Results were pooled using a random-effects model or fixed-effects model according to the heterogeneity among studies.Results32 original articles with 292 844 participants, which met the criteria, were included in this meta-analysis. Bronchiolitis before 2 years of age was associated with an increased risk of subsequent wheezing/asthma (relative risk=2.46, 95% CI 2.14 to 2.82, p<0.001). After categorising studies into different groups based on age at the end of follow-up, geographical region and study quality, the association still remained significant.ConclusionsThe meta-analysis indicates an association between bronchiolitis before 2 years of age and the wheezing/asthma in later life. Well-designed and highly standardised prospective studies that better address bias due to potential confounding factors are needed to validate the risk identified in our meta-analysis.PROSPERO registration numberCRD42018089453.

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Paediatric rotavirus vaccination, coeliac disease and type 1 diabetes in children: a population-based cohort study

BMC Medicine ◽

10.1186/s12916-021-02017-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Thomas Inns ◽

Kate M. Fleming ◽

Miren Iturriza-Gomara ◽

Daniel Hungerford

Keyword(s):

Type 1 Diabetes ◽

Cohort Study ◽

Coeliac Disease ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Rotavirus Vaccine ◽

Rotavirus Vaccination ◽

Increased Risk ◽

The Uk

Abstract Background Rotavirus infection has been proposed as a risk factor for coeliac disease (CD) and type 1 diabetes (T1D). The UK introduced infant rotavirus vaccination in 2013. We have previously shown that rotavirus vaccination can have beneficial off-target effects on syndromes, such as hospitalised seizures. We therefore investigated whether rotavirus vaccination prevents CD and T1D in the UK. Methods A cohort study of children born between 2010 and 2015 was conducted using primary care records from the Clinical Practice Research Datalink. Children were followed up from 6 months to 7 years old, with censoring for outcome, death or leaving the practice. CD was defined as diagnosis of CD or the prescription of gluten-free goods. T1D was defined as a T1D diagnosis. The exposure was rotavirus vaccination, defined as one or more doses. Mixed-effects Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs). Models were adjusted for potential confounders and included random intercepts for general practices. Results There were 880,629 children in the cohort (48.8% female). A total of 343,113 (39.0%) participants received rotavirus vaccine; among those born after the introduction of rotavirus vaccination, 93.4% were vaccinated. Study participants contributed 4,388,355 person-years, with median follow-up 5.66 person-years. There were 1657 CD cases, an incidence of 38.0 cases per 100,000 person-years. Compared with unvaccinated children, the adjusted HR for a CD was 1.05 (95% CI 0.86–1.28) for vaccinated children. Females had a 40% higher hazard than males. T1D was recorded for 733 participants, an incidence of 17.1 cases per 100,000 person-years. In adjusted analysis, rotavirus vaccination was not associated with risk of T1D (HR = 0.89, 95% CI 0.68–1.19). Conclusions Rotavirus vaccination has reduced diarrhoeal disease morbidity and mortality substantial since licencing in 2006. Our finding from this large cohort study did not provide evidence that rotavirus vaccination prevents CD or T1D, nor is it associated with increased risk, delivering further evidence of rotavirus vaccine safety.

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Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

Journal of Clinical Medicine ◽

10.3390/jcm10040835 ◽

2021 ◽

Vol 10 (4) ◽

pp. 835

Author(s):

Manoja P. Herath ◽

Jeffrey M. Beckett ◽

Andrew P. Hills ◽

Nuala M. Byrne ◽

Kiran D. K. Ahuja

Keyword(s):

Diabetes Mellitus ◽

Adipose Tissue ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Fat Mass ◽

Metabolic Disorders ◽

Later Life ◽

Therapeutic Interventions ◽

Increased Risk ◽

The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

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Prescribing Trends of Anticholinergic Drugs Between 1989 and 2017: A UK Biobank Study

Innovation in Aging ◽

10.1093/geroni/igaa057.675 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 209-209

Author(s):

Jure Mur ◽

Simon Cox ◽

Riccardo Marioni ◽

Tom Russ ◽

Graciela Muniz Terrera

Keyword(s):

Prescription Drugs ◽

Anticholinergic Drug ◽

Later Life ◽

Anticholinergic Drugs ◽

Uk Biobank ◽

Linear Estimate ◽

Cross Sectional ◽

Increased Risk ◽

Prescribing Trends ◽

Anticholinergic Burden

Abstract Prescription drugs with anticholinergic properties are commonly prescribed and negatively impact physical performance, cognitive function, and increase the risk of falls and dementia. The prevalence of anticholinergic drugs is high in later life, when there is an increased risk of adverse drug effects. Recent, in-depth longitudinal analyses of specifically anticholinergic prescribing in Europe is lacking. Prescriptions for the UK-Biobank participants (n=222,122) were ascertained from primary care electronic patient records. We assigned anticholinergic activity to each drug by using a composite score. We used linear regression to study the association between current anticholinergic burden and time period, explore secular trends in anticholinergic use, and various demographic factors. We further explored the results in the context of different classes of prescriptions drugs. 74 distinct drugs in the sample (1.1%) had anticholinergic effects. An individual’s overall anticholinergic burden increased nonlinearly (linear estimate=0.474, quadratic estimate = 0.094, both p<2.2x10-16) between 1989 (mean=0.09, σ=0.009) and 2000 (mean=0.22, σ=0.006) and increased nonlinearly (linear estimate=0.282, quadratic estimate=0.074, both p<2.2x10-16) from 2000 to 2016 (mean=0.27, σ=0.009). The proportion of patients prescribed at least one anticholinergic drug per month increased from 6.1% to 16.7% from 1989 to 2000 and increased to 18.6% by 2016. When adjusted for sex and polypharmacy, age was negatively associated with recent cross-sectional anticholinergic burden (estimate=-0.042, p<2.2x10-16). Our results demonstrate an increase in prescribing of anticholinergic drugs over the past 30 years and indicate contemporary deprescribing of anticholinergic drugs in the later decades of life.

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