scholarly journals Successful incorporation of a genetic risk prediction research platform into routine newborn screening

2021 ◽  
Author(s):  
Owen M Bendor-Samuel ◽  
Tabitha Wishlade ◽  
Louise Willis ◽  
Parvinder Aley ◽  
Edward Choi ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Genetic Risk ◽  
Screening Programme ◽  
Genomic Medicine ◽  
Genetic Research ◽  
Population Based ◽  
Clinical Genetic ◽  
Screening Programs ◽  
Increased Risk ◽  
The Uk

ABSTRACTAn increasing number of diseases can be offered treatments that are transformative if administered in a timely manner. However, many of these diseases are currently not included in the newborn screening programs because they lack sensitive and specific metabolic biomarkers, and detection of children at increased risk relies on genetic methods. Type 1 diabetes (T1D) constitutes a potential example of such disease.Between April 2018 and November 2020, over 15500 babies were enrolled into ‘INGR1D’ (Investigating Genetic Risk for T1D), a research study to identify newborns with an increased genetic risk of T1D. This project, performed as part of a T1D primary prevention study (the Primary Oral Insulin Trial, POInT), has helped to pioneer the integration of genetic screening into the NHS Newborn Blood Spot Screening Programme (NBSSP) for consenting mothers, without affecting the screening pathway. The use of prospective consent to perform personalised genetic testing on samples obtained through the routine NBSSP represents a novel mechanism for clinical genetic research in the UK and provides a model for further population based genetic studies in the newborn.This project builds on the UK’s role as a world leader in genomic medicine, e.g. through its inception and completion of the 100 000 Genomes Project, and its subsequent ambition to map 5 million further genomes over the next 5 years.Our aim is therefore to describe the methodology used by INGR1D as a way to demonstrate how a successful research and clinical trial tool can be integrated into a national screening programme, with the potential for the tool to be developed to incorporate multiple diseases with genetic markers without altering the screening pathway.

scholarly journals Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project

2020 ◽  
Author(s):  
Gerard C. Millen ◽  
Roland Arnold ◽  
Jean-Baptiste Cazier ◽  
Helen Curley ◽  
Richard G. Feltbower ◽  
...  
Keyword(s):  
Severe Infection ◽  
Paediatric Population ◽  
Population Based ◽  
Children With Cancer ◽  
The United Kingdom ◽  
Increased Risk ◽  
Polymerase Chain ◽  
The Uk ◽  
Active Care ◽  
Care Support

Abstract Background Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK. Methods Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital. Results Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%. Conclusions Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.

scholarly journals Increased risk of all‐cause mortality associated with domperidone use in Parkinson's patients: a population‐based cohort study in the UK

2018 ◽  
Vol 84 (11) ◽  
pp. 2551-2561 ◽  
Author(s):  
Marina Simeonova ◽  
Frank Vries ◽  
Sander Pouwels ◽  
Johanna H. M. Driessen ◽  
Hubert G.M. Leufkens ◽  
...  
Keyword(s):  
Cohort Study ◽  
Population Based ◽  
Increased Risk ◽  
All Cause Mortality ◽  
The Uk

Cervical cancer screening programme

2019 ◽  
Vol 13 (11) ◽  
pp. 526-533
Author(s):  
Ian Peate
Keyword(s):  
Cervical Cancer ◽  
Cancer Screening ◽  
Cervical Cancer Screening ◽  
Screening Programme ◽  
Cervical Screening ◽  
Signs And Symptoms ◽  
Increased Risk ◽  
Cancer Screening Programme ◽  
Cervical Cancer Screening Programme ◽  
The Uk

Screening for cervical cancer saves lives. This article provides an overview of cervical screening programmes offered by the NHS. All four countries in the UK provide a cervical cancer screening programme. Cervical screening identifies apparently healthy women who may be at increased risk of a disease or condition; this then provides an opportunity for earlier treatment or better informed decisions. In some instances, the healthcare assistant and assistant practitioner (HCA and AP) may be needed in order to provide assistance with the screening procedure, offering the woman physical and psychological support. This article offers the reader an overview of the cervix, along with a brief description of signs and symptoms of cervical cancer.

scholarly journals Altered Cortical Brain Structure and Increased Risk for Disease Seen Decades After Perinatal Exposure to Maternal Smoking: A Study of 9000 Adults in the UK Biobank

2019 ◽  
Vol 29 (12) ◽  
pp. 5217-5233 ◽  
Author(s):  
Lauren E Salminen ◽  
Rand R Wilcox ◽  
Alyssa H Zhu ◽  
Brandalyn C Riedel ◽  
Christopher R K Ching ◽  
...  
Keyword(s):  
Brain Structure ◽  
Brain Mri ◽  
Population Based ◽  
Smoke Exposure ◽  
Sensitivity Analyses ◽  
Uk Biobank ◽  
Increased Risk ◽  
Increase Risk ◽  
Sensory Cortices ◽  
The Uk

Abstract Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44–80) who were exposed (n = 2510) or unexposed (n = 6079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volumes. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE−) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n = 109, unexposed, n = 315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

scholarly journals Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mary Ward ◽  
Catherine F. Hughes ◽  
J. J. Strain ◽  
Rosie Reilly ◽  
Conal Cunningham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Risk ◽  
Antihypertensive Treatment ◽  
Methylenetetrahydrofolate Reductase ◽  
Randomised Trial ◽  
Population Based ◽  
Nutrition Survey ◽  
Increased Risk ◽  
The Impact ◽  
Riboflavin Status

Abstract Background Genome-wide and clinical studies have linked the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) with hypertension, whilst limited evidence shows that intervention with riboflavin (i.e. the MTHFR co-factor) can lower blood pressure (BP) in hypertensive patients with the variant MTHFR 677TT genotype. We investigated the impact of this common polymorphism on BP throughout adulthood and hypothesised that riboflavin status would modulate the genetic risk of hypertension. Methods Observational data on 6076 adults of 18–102 years were drawn from the Joint Irish Nutrigenomics Organisation project, comprising the Trinity-Ulster Department of Agriculture (TUDA; volunteer sample) and the National Adult Nutrition Survey (NANS; population-based sample) cohorts. Participants were recruited from the Republic of Ireland and Northern Ireland (UK) in 2008–2012 using standardised methods. Results The variant MTHFR 677TT genotype was identified in 12% of adults. From 18 to 70 years, this genotype was associated with an increased risk of hypertension (i.e. systolic BP ≥ 140 and/or a diastolic BP ≥ 90 mmHg): odds ratio (OR) 1.42, 95% confidence interval (CI) 1.07 to 1.90; P = 0.016, after adjustment for antihypertensive drug use and other significant factors, namely, age, male sex, BMI, alcohol and total cholesterol. Low or deficient biomarker status of riboflavin (observed in 30.2% and 30.0% of participants, respectively) exacerbated the genetic risk of hypertension, with a 3-fold increased risk for the TT genotype in combination with deficient riboflavin status (OR 3.00, 95% CI, 1.34–6.68; P = 0.007) relative to the CC genotype combined with normal riboflavin status. Up to 65 years, we observed poorer BP control rates on antihypertensive treatment in participants with the TT genotype (30%) compared to those without this variant, CT (37%) and CC (45%) genotypes (P < 0.027). Conclusions The MTHFR 677TT genotype is associated with higher BP independently of homocysteine and predisposes adults to an increased risk of hypertension and poorer BP control with antihypertensive treatment, whilst better riboflavin status is associated with a reduced genetic risk. Riboflavin intervention may thus offer a personalised approach to prevent the onset of hypertension in adults with the TT genotype; however, this requires confirmation in a randomised trial in non-hypertensive adults.

Screening for Type 1 Diabetes Risk in Newborns: The Freder1k Pilot Study in Saxony*

2017 ◽  
Vol 50 (01) ◽  
pp. 44-49 ◽  
Author(s):  
Angela Hommel ◽  
Florian Haupt ◽  
Petrina Delivani ◽  
Christiane Winkler ◽  
Marina Stopsack ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Testing ◽  
Pilot Study ◽  
Newborn Screening ◽  
Early Stage ◽  
Diabetes Risk ◽  
Screening Programs ◽  
Increased Risk

AbstractAn increased risk for type 1 diabetes can be identified using genetic and immune markers. The Freder1k study introduces genetic testing for type 1 diabetes risk within the context of the newborn screening in order to identify newborns with a high risk to develop type 1 diabetes for follow-up testing of early stage type 1 diabetes and for primary prevention trials. Consent for research-based genetic testing of type 1 diabetes risk is obtained with newborn screening. Increased risk is assessed using three single nucleotide polymorphisms for HLA DRB1*03 (DR3), HLA DRB1*04 (DR4), HLA DQB1*0302 (DQ8) alleles, and defined as 1. an HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype or 2. an HLA DR4-DQ8 haplotype and a first-degree family history of type 1 diabetes. Families of infants with increased risk are asked to participate in follow-up visits at infant age 6 months, 2 years, and 4 years for autoantibody testing and early diagnosis of type 1 diabetes. After 8 months, the screening rate has reached 181 per week, with 63% coverage of newborns within Freder1k-clinics and 24% of all registered births in Saxony. Of 4178 screened, 2.6% were identified to have an increased risk, and around 80% of eligible infants were recruited to follow-up. Psychological assessment of eligible families is ongoing with none of 31 families demonstrating signs of excessive burden associated with knowledge of type 1 diabetes risk. This pilot study has shown that it is feasible to perform genetic risk testing for childhood disease within the context of newborn screening programs.

The principles of a national diabetic eye screening programme

2020 ◽  
pp. 111-122
Author(s):  
Paul Galsworthy
Keyword(s):  
Public Health ◽  
Young Person ◽  
Population Based ◽  
National Standards ◽  
Evidence Based ◽  
Independent Evidence ◽  
Eye Screening ◽  
Increased Risk ◽  
Diabetic Eye Screening ◽  
The Uk

Screening identifies apparently healthy people who may be at increased risk of a disease or condition, enabling earlier treatment or better-informed decisions. The NHS diabetic eye screening (DES) programme is one of the young person and adult NHS population screening programmes in the UK. The UK National Screening Committee (UK NSC), which makes independent, evidence-based recommendations to ministers in the four UK nations about the 11 population-based screening programmes. Public Health England (PHE)—Screening Quality Assurance Service (SQAS) ensures programmes are safe and effective by ensuring national standards are met.

Tuberculosis in healthcare workers, Scotland

2017 ◽  
Vol 62 (3) ◽  
pp. 101-103 ◽  
Author(s):  
Kevin G Pollock ◽  
Eisin McDonald ◽  
Alison Smith-Palmer ◽  
Fiona Johnston ◽  
Syed Ahmed
Keyword(s):  
Incidence Rate ◽  
Healthcare Workers ◽  
Latent Tuberculosis Infection ◽  
Screening Programme ◽  
Latent Tuberculosis ◽  
Mycobacterial Infection ◽  
Population Based ◽  
Tuberculosis Infection ◽  
The Mean ◽  
The Uk

In an attempt to explore healthcare worker acquisition of tuberculosis infection, we conducted population-based surveillance of all cases recorded as healthcare workers reported to Enhanced Surveillance of Mycobacterial Infection from 2000 to 2015. Over the study period, the mean incidence rate of tuberculosis among all healthcare workers was 15.4 per 100,000 healthcare workers. However, the incidence rate of tuberculosis amongst those healthcare workers born outside the UK was 164.8 per 100,000 compared with 5.0 per 100,000 UK-born healthcare workers. Fifty-seven per cent of all non-UK-born healthcare workers were diagnosed within five years of their arrival in the UK and would have been new entrants to the NHS. An effective new entrant occupational health screening programme for latent tuberculosis infection may have prevented some of these active cases of infection.

scholarly journals Polygenic prediction of breast cancer: comparison of genetic predictors and implications for screening

2018 ◽  
Author(s):  
Kristi Läll ◽  
Maarja Lepamets ◽  
Marili Palover ◽  
Tõnu Esko ◽  
Andres Metspalu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Population Based ◽  
Risk Scores ◽  
Full Potential ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genetic Risk Scores ◽  
The Uk

AbstractBackgroundPublished genetic risk scores for breast cancer (BC) so far have been based on a relatively small number of markers and are not necessarily using the full potential of large-scale Genome-Wide Association Studies. This study aims to identify an efficient polygenic predictor for BC based on best available evidence and to assess its potential for personalized risk prediction and screening strategies.MethodsFour different genetic risk scores (two already published and two newly developed) and their combinations (metaGRS) are compared in the subsets of two population-based biobank cohorts: the UK Biobank (UKBB, 3157 BC cases, 43,827 controls) and Estonian Biobank (EstBB, 317 prevalent and 308 incident BC cases in 32,557 women). In addition, correlations between different genetic risk scores and their associations with BC risk factors are studied in both cohorts.ResultsThe metaGRS that combines two genetic risk scores (metaGRS2 - based on 75 and 898 Single Nucleotide Polymorphisms, respectively) has the strongest association with prevalent BC status in both cohorts. One standard deviation difference in the metaGRS2 corresponds to an Odds Ratio = 1.6 (95% CI 1.54 to 1.66, p = 9.7*10-135) in the UK Biobank and accounting for family history marginally attenuates the effect (Odds Ratio = 1.58, 95% CI 1.53 to 1.64, p = 9.1*10-129). In the EstBB cohort, the hazard ratio of incident BC for the women in the top 5% of the metaGRS2 compared to women in the lowest 50% is 4.2 (95% CI 2.8 to 6.2, p = 8.1*10-13). The different GRSs are only moderately correlated with each other and are associated with different known predictors of BC. The classification of genetic risk for the same individual may vary considerably depending on the chosen GRS.ConclusionsWe have shown that metaGRS2 that combines on the effects of more than 900 SNPs provides best predictive ability for breast cancer in two different population-based cohorts. The strength of the effect of metaGRS2 indicates that the GRS could potentially be used to develop more efficient strategies for breast cancer screening for genotyped women.

scholarly journals Gout, rheumatoid arthritis and the risk of death from COVID-19: an analysis of the UK Biobank

2020 ◽  
Author(s):  
Ruth K Topless ◽  
Amanda Phipps-Green ◽  
Megan Leask ◽  
Nicola Dalbeth ◽  
Lisa K Stamp ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Population Based ◽  
Data Sets ◽  
Uk Biobank ◽  
Control Cohort ◽  
Risk Of Death ◽  
Increased Risk ◽  
Adjusted Logistic Regression ◽  
The Uk

AbstractObjectiveTo assess whether gout and / or rheumatoid arthritis (RA) are risk factors for coronavirus disease 19 (COVID-19) diagnosis. To assess whether gout and / or RA are risk factors for death from COVID-19.MethodsWe used data from the UK Biobank. Multivariate-adjusted logistic regression was employed in the following analyses. Analysis A: to test for association between gout or RA and COVID-19 diagnosis in a population-based cohort (n=473,139). Analysis B: to test for association between gout or RA and death from COVID-19 in a case-control cohort of people who died or survived with COVID-19 (n=2,073). Analysis C: to test for association with gout or RA and death from COVID-19 in a population-based cohort (n=473,139)ResultsNeither RA nor gout associated with COVID-19 diagnosis in analysis A, nor did RA or gout associate with risk of death in the COVID-19-diagnosed group in analysis B. However RA associated with risk of death from COVID-19 using the population-based cohort in analysis C independent of comorbidities and other measured risk factors (OR=1.8 [95% CI 1.2 ; 2.7]). Gout was not associated with death from COVID-19 in the same population-based analysis (OR=1.2 [95% CI 0.9 ; 1.7]).ConclusionsRA and gout are not risk factors for COVID-19-diagnosis. However RA, but not gout, is a risk factor for death from COVID-19 in a population-based analysis using the UK Biobank. These findings require replication in larger data sets that also allow inclusion of a wider range of factors.Key messagesWhat is already known?Information on the risk of death from COVID-19 for people with gout and rheumatoid arthritis is scarce.What does this study add?In a population-based analysis there is an increased risk of death by COVID-19 for people with rheumatoid arthritis independent of co-morbidities, but not gout.The findings need to be replicated in other datasets where the influence of therapies for RA can be tested.How might this impact on clinical practice?Improved clinical management and treatment for RA patients with COVID-19.

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