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Article ; Online: The Role of TEG Analysis in Patients with COVID-19-Associated Coagulopathy

Jan Hartmann / Alexis Ergang / Dan Mason / Joao D. Dias

Diagnostics, Vol 11, Iss 2, p

A Systematic Review

2021 Volume 172

Abstract: Coronavirus disease 2019 (COVID-19)-associated coagulopathy (CAC), characterized by hypercoagulability and an increased risk of thrombotic complications, is an important consideration in the management of patients with COVID-19. As COVID-19 is a new ... ...

Abstract	Coronavirus disease 2019 (COVID-19)-associated coagulopathy (CAC), characterized by hypercoagulability and an increased risk of thrombotic complications, is an important consideration in the management of patients with COVID-19. As COVID-19 is a new disease, no standard of care for the diagnosis or management of its associated coagulopathy is yet established. Whole blood viscoelastic tests, such as thromboelastography (TEG ® hemostasis analyzer), analyze whole blood to provide a complete overview of the coagulation status. We conducted a systematic review of thromboelastography for management of patients with COVID-19, using MEDLINE (PubMed) and Cochrane databases. TEG ® parameter measurements and clinical outcomes data were extracted for analysis. Our review found 15 publications, with overall results showing thromboelastography can identify and assess a hypercoagulable state in patients with COVID-19. Furthermore, utilization of thromboelastography in this patient population was shown to predict thrombotic complications. The benefits of thromboelastography presented here, in addition to advantages compared with laboratory coagulation tests, position thromboelastography as an important opportunity for optimizing diagnosis of CAC and improving patient management in COVID-19. Given that the benefits of thromboelastography have already been demonstrated in several other clinical applications, we anticipate that clinical data from future studies in patients with COVID-19 will further elucidate the optimal use of thromboelastography in this patient population.
Keywords	blood coagulation ; coronavirus ; COVID-19 ; fibrinolysis ; thromboelastography ; viscoelastic ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Causal effects of maternal circulating amino acids on offspring birthweight

Jian Zhao / Isobel D. Stewart / Denis Baird / Dan Mason / John Wright / Jie Zheng / Tom R. Gaunt / David M. Evans / Rachel M. Freathy / Claudia Langenberg / Nicole M. Warrington / Deborah A. Lawlor / Maria Carolina Borges

EBioMedicine, Vol 88, Iss , Pp 104441- (2023)

a Mendelian randomisation studyResearch in context

2023

Abstract: Summary: Background: Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear. Methods: We explored the effect of maternal ... ...

Abstract	Summary: Background: Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear. Methods: We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10−10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations. Findings: Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (−59 g, 95% CI: −106, −11) and phenylalanine (−25 g, 95% CI: −47, −4) lower offspring birthweight. These findings are supported by sensitivity analyses. Interpretation: Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth. Funding: A full list of funding bodies that contributed to this study can be found under Acknowledgments.
Keywords	Amino acids ; Birthweight ; GWAS ; Mendelian randomisation ; Causal effect ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ethnic differences in kidney function in childhood

Simon D.S. Fraser / Dan Mason / Dagmar Waiblinger / Ho M. Yuen / John Wright / Nisreen A. Alwan / Paul J. Roderick / Richard J.M. Coward / Rafaq Azad / Robin F. Jeffrey / Nida Ziauddeen

Wellcome Open Research, Vol

the Born in Bradford Cohort Renal Study [version 1; peer review: 1 approved, 2 approved with reservations]

2022 Volume 7

Abstract: Background: Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born ... ...

Abstract	Background: Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was mediated by foetal kidney size. Methods: Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure. Results: 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m2 (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m2, 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age. Conclusions: There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty.
Keywords	South Asian ; kidney function ; development ; eng ; Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Born in Bradford’s Better Start (BiBBS) interventional birth cohort study

Wellcome Open Research, Vol

Interim cohort profile [version 2; peer review: 2 approved]

2023 Volume 7

Abstract: Background: The Born in Bradford’s Better Start (BiBBS) interventional birth cohort study was designed as an innovative cohort platform for efficient evaluation of early life interventions delivered through the Better Start Bradford programme. There are ... ...

Abstract	Background: The Born in Bradford’s Better Start (BiBBS) interventional birth cohort study was designed as an innovative cohort platform for efficient evaluation of early life interventions delivered through the Better Start Bradford programme. There are a growing number of interventional cohorts being implemented internationally. This paper provides an interim analysis of BiBBS in order to share learning about the feasibility and value of this method. Methods: Recruitment began in January 2016 and will complete in December 2023 with a target sample of 5,000 pregnancies. An interim analysis was completed for all pregnancies recruited between January 2016 and November 2019 with an expected due date between 1st April 2016 and 8th March 2020. Descriptive statistics were completed on the data. Results: Of 4,823 eligible pregnancies, 2,626 (54%) pregnancies were recruited, resulting in 2,392 mothers and 2,501 children. The sample are representative of the pregnant population (61% Pakistani heritage; 12% White British; 8% other South Asian and 6% Central and Eastern European ethnicity). The majority of participants (84%) live in the lowest decile of the Index of Multiple Deprivation, and many live in vulnerable circumstances. A high proportion (85%) of BiBBS families have engaged in one or more of the Better Start Bradford interventions. Levels of participation varied by the characteristics of the interventions, such as the requirement for active participation and the length of commitment to a programme. Conclusions: We have demonstrated the feasibility of recruiting an interventional cohort that includes seldom heard families from ethnic minority and deprived backgrounds. The high level of uptake of interventions is encouraging for the goal of evaluating the process and outcomes of multiple early life interventions using the innovative interventional cohort approach. BiBBS covers a period before, during and after the coronavirus disease 2019 (COVID-19) pandemic which adds scientific value to the cohort.
Keywords	Interventional cohort ; birth cohort ; early years interventions ; trials within cohorts ; pragmatic randomised controlled trials ; quasi-experimental designs ; eng ; Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	Wellcome
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fine-scale population structure and demographic history of British Pakistanis

Elena Arciero / Sufyan A. Dogra / Daniel S. Malawsky / Massimo Mezzavilla / Theofanis Tsismentzoglou / Qin Qin Huang / Karen A. Hunt / Dan Mason / Saghira Malik Sharif / David A. van Heel / Eamonn Sheridan / John Wright / Neil Small / Shai Carmi / Mark M. Iles / Hilary C. Martin

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 16

Abstract: Little is known about the recent population history or the effects of endogamy on the Pakistani population. Here the authors examine the impact of the biraderi social stratification system on the population structure of individuals of British Pakistani ... ...

Abstract	Little is known about the recent population history or the effects of endogamy on the Pakistani population. Here the authors examine the impact of the biraderi social stratification system on the population structure of individuals of British Pakistani ancestry in the Born in Bradford cohort.
Keywords	Science ; Q
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity

Tom A. Bond / Rebecca C. Richmond / Ville Karhunen / Gabriel Cuellar-Partida / Maria Carolina Borges / Verena Zuber / Alexessander Couto Alves / Dan Mason / Tiffany C. Yang / Marc J. Gunter / Abbas Dehghan / Ioanna Tzoulaki / Sylvain Sebert / David M. Evans / Alex M. Lewin / Paul F. O’Reilly / Deborah A. Lawlor / Marjo-Riitta Järvelin

BMC Medicine, Vol 20, Iss 1, Pp 1-

Mendelian randomisation using polygenic risk scores

2022 Volume 16

Abstract: Abstract Background Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, ...

Abstract	Abstract Background Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal. Methods We undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10–18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs). Results MV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (P difference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size. Conclusions Our results suggest that higher maternal ...
Keywords	Obesity ; BMI ; Pregnancy ; Child ; Maternal ; Offspring ; Medicine ; R
Subject code	150 ; 610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hemorrhagic Resuscitation Guided by Viscoelastography in Far-Forward Combat and Austere Civilian Environments

Journal of Clinical Medicine, Vol 11, Iss 356, p

Goal-Directed Whole-Blood and Blood-Component Therapy Far from the Trauma Center

2022 Volume 356

Abstract: Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in ... ...

Abstract	Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy—especially in austere or challenging environments—is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.
Keywords	viscoelastic testing ; far forward ; austere environment ; resuscitation ; goal-directed therapy ; whole blood ; Medicine ; R
Subject code	629
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Using methylome data to inform exposome-health association studies

Environment International, Vol 138, Iss , Pp - (2020)

An application to the identification of environmental drivers of child body mass index

2020

Abstract: Background: The exposome is defined as encompassing all environmental exposures one undergoes from conception onwards. Challenges of the application of this concept to environmental-health association studies include a possibly high false-positive rate. ... ...

Abstract	Background: The exposome is defined as encompassing all environmental exposures one undergoes from conception onwards. Challenges of the application of this concept to environmental-health association studies include a possibly high false-positive rate. Objectives: We aimed to reduce the dimension of the exposome using information from DNA methylation as a way to more efficiently characterize the relation between exposome and child body mass index (BMI). Methods: Among 1,173 mother–child pairs from HELIX cohort, 216 exposures (“whole exposome”) were characterized. BMI and DNA methylation from immune cells of peripheral blood were assessed in children at age 6–10 years. A priori reduction of the methylome to preselect BMI-relevant CpGs was performed using biological pathways. We then implemented a tailored Meet-in-the-Middle approach to identify from these CpGs candidate mediators in the exposome-BMI association, using univariate linear regression models corrected for multiple testing: this allowed to point out exposures most likely to be associated with BMI (“reduced exposome”). Associations of this reduced exposome with BMI were finally tested. The approach was compared to an agnostic exposome-wide association study (ExWAS) ignoring the methylome. Results: Among the 2284 preselected CpGs (0.6% of the assessed CpGs), 62 were associated with BMI. Four factors (3 postnatal and 1 prenatal) of the exposome were associated with at least one of these CpGs, among which postnatal blood level of copper and PFOS were directly associated with BMI, with respectively positive and negative estimated effects. The agnostic ExWAS identified 18 additional postnatal exposures, including many persistent pollutants, generally unexpectedly associated with decreased BMI. Discussion: Our approach incorporating a priori information identified fewer significant associations than an agnostic approach. We hypothesize that this smaller number corresponds to a higher specificity (and possibly lower sensitivity), compared to the agnostic approach. Indeed, the latter cannot distinguish causal relations from reverse causation, e.g. for persistent compounds stored in fat, whose circulating level is influenced by BMI. Keywords: Biological a priori, Child body mass index – exposome, dimension reduction – DNA methylation, Reverse causality
Keywords	Environmental sciences ; GE1-350
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Maternal iodine status, intrauterine growth, birth outcomes and congenital anomalies in a UK birth cohort

BMC Medicine, Vol 18, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract Background Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth ... ...

Abstract	Abstract Background Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outcomes, finding inconsistent evidence for specific outcomes. Methods Maternal iodine status was estimated from spot urine samples collected at 26–28 weeks’ gestation from 6971 mothers in the Born in Bradford birth cohort. Associations with outcomes were examined for both urinary iodine concentration (UIC) and iodine-to-creatinine ratio (I:Cr). Outcomes assessed included customised birthweight (primary outcome), birthweight, small for gestational age (SGA), low birthweight, head circumference and APGAR score. Results There was a small positive association between I:Cr and birthweight in adjusted analyses. For a typical participant, the predicted birthweight centile at the 25th percentile of I:Cr (59 μg/g) was 2.7 percentage points lower than that at the 75th percentile of I:Cr (121 μg/g) (99% confidence interval (CI) 0.8 to 4.6), birthweight was predicted to be 41 g lower (99% CI 13 to 69) and the predicted probability of SGA was 1.9 percentage points higher (99% CI 0.0 to 3.7). There was no evidence of associations using UIC or other birth outcomes, including stillbirth, preterm birth, ultrasound growth measures or congenital anomalies. Conclusion Lower maternal iodine status was associated with lower birthweight and greater probability of SGA. Whilst small, the effect size for lower iodine on birthweight is comparable to environmental tobacco smoke exposure. Iodine insufficiency is avoidable, and strategies to avoid deficiency in women of reproductive age should be considered. Trial registration ClinicalTrials.gov NCT03552341 . Registered on June 11, 2018.
Keywords	Birthweight ; Iodine ; Pregnancy ; Insufficiency ; SGA ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Associations between air pollution and pediatric eczema, rhinoconjunctivitis and asthma

Environment International, Vol 136, Iss , Pp - (2020)

A meta-analysis of European birth cohorts

2020

Abstract: Background: Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades. Objective: We examined associations of long-term ... ...

Abstract	Background: Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades. Objective: We examined associations of long-term air pollution levels at the home address with pediatric eczema, rhinoconjunctivitis and asthma prevalences in five birth cohorts (BIB, EDEN, GASPII, RHEA and INMA) from seven areas in five European countries. Methods: Current eczema, rhinoconjunctivitis and asthma were assessed in children aged four (N = 6527) and eight years (N = 2489). A multi-morbidity outcome (≥2 conditions versus none) was also defined. Individual outdoor levels of nitrogen dioxide (NO2), nitrogen oxides, mass of particulate matter with an aerodynamic diameter <10 μm (PM10), 10–2.5 μm (PMcoarse) and <2.5 μm (PM2.5), and PM2.5 absorbance were assigned to the birth, four- and eight-year home addresses using highly defined spatial air pollution exposure models. Cohort-specific cross-sectional associations were assessed using logistic regression models adjusted for demographic and environmental covariates and combined in a random effects meta-analysis. Results: The overall prevalence of pediatric eczema, rhinoconjunctivitis and asthma at four years was 15.4%, 5.9% and 12.4%. We found no increase in the prevalence of these outcomes at four or eight years with increasing air pollution exposure. For example, the meta-analysis adjusted odds ratios (95% confidence intervals) for eczema, rhinoconjunctivitis and asthma at four years were 0.94 (0.81, 1.09), 0.90 (0.75, 1.09), and 0.91 (0.74, 1.11), respectively, per 10 μg/m3 increase in NO2 at the birth address, and 1.00 (0.81, 1.23), 0.70 (0.49, 1.00) and 0.88 (0.54, 1.45), respectively, per 5 μg/m3 increase in PM2.5 at the birth address. Discussion: In this large meta-analysis of five birth cohorts, we found no indication of adverse effects of long-term air pollution exposure on the prevalence of current pediatric eczema, rhinoconjunctivitis or ...
Keywords	Environmental sciences ; GE1-350
Subject code	333
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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