ORCID Profile
0000-0001-9572-7293
Current Organisations
RWTH Aachen University Clinic
,
Bradford Institute for Health Research
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Publisher: Public Library of Science (PLoS)
Date: 19-05-2022
DOI: 10.1371/JOURNAL.PMED.1003981
Abstract: Type 2 diabetes (T2D) is highly prevalent in British South Asians, yet they are underrepresented in research. Genes & Health (G& H) is a large, population study of British Pakistanis and Bangladeshis (BPB) comprising genomic and routine health data. We assessed the extent to which genetic risk for T2D is shared between BPB and European populations (EUR). We then investigated whether the integration of a polygenic risk score (PRS) for T2D with an existing risk tool (QDiabetes) could improve prediction of incident disease and the characterisation of disease subtypes. In this observational cohort study, we assessed whether common genetic loci associated with T2D in EUR in iduals were replicated in 22,490 BPB in iduals in G& H. We replicated fewer loci in G& H ( n = 76/338, 22%) than would be expected given power if all EUR-ascertained loci were transferable ( n = 101, 30% p = 0.001). Of the 27 transferable loci that were powered to interrogate this, only 9 showed evidence of shared causal variants. We constructed a T2D PRS and combined it with a clinical risk instrument (QDiabetes) in a novel, integrated risk tool (IRT) to assess risk of incident diabetes. To assess model performance, we compared categorical net reclassification index (NRI) versus QDiabetes alone. In 13,648 patients free from T2D followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval (CI): 2.0% to 4.4%). IRT performed best in reclassification of in iduals aged less than 40 years deemed low risk by QDiabetes alone (NRI 5.6%, 95% CI 3.6% to 7.6%), who tended to be free from comorbidities and slim. After adjustment for QDiabetes score, PRS was independently associated with progression to T2D after gestational diabetes (hazard ratio (HR) per SD of PRS 1.23, 95% CI 1.05 to 1.42, p = 0.028). Using cluster analysis of clinical features at diabetes diagnosis, we replicated previously reported disease subgroups, including Mild Age-Related, Mild Obesity-related, and Insulin-Resistant Diabetes, and showed that PRS distribution differs between subgroups ( p = 0.002). Integrating PRS in this cluster analysis revealed a Probable Severe Insulin Deficient Diabetes (pSIDD) subgroup, despite the absence of clinical measures of insulin secretion or resistance. We also observed differences in rates of progression to micro- and macrovascular complications between subgroups after adjustment for confounders. Study limitations include the absence of an external replication cohort and the potential biases arising from missing or incorrect routine health data. Our analysis of the transferability of T2D loci between EUR and BPB indicates the need for larger, multiancestry studies to better characterise the genetic contribution to disease and its varied aetiology. We show that a T2D PRS optimised for this high-risk BPB population has potential clinical application in BPB, improving the identification of T2D risk (especially in the young) on top of an established clinical risk algorithm and aiding identification of subgroups at diagnosis, which may help future efforts to stratify care and treatment of the disease.
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.JACI.2012.07.053
Abstract: Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent ersistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.
Publisher: Public Library of Science (PLoS)
Date: 11-02-2019
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: European Respiratory Society (ERS)
Date: 07-2017
DOI: 10.1183/23120541.00150-2016
Abstract: While there is evidence for variations in prevalence rates of childhood wheeze and asthma between countries, longitudinal, in idual-level data are needed to understand these differences. The aim of this study was to examine variations in prevalence rates of childhood asthma, wheeze and wheeze with asthma in Europe. We analysed datasets from 10 MeDALL (Mechanisms of the Development of ALLergy) cohorts in eight countries, representing 26 663 children, to calculate prevalence rates of wheeze and asthma by child age and wheeze with asthma at age 4 years. Harmonised variables included outcomes parent-reported wheeze and parent-reported doctor-diagnosed asthma, and covariates maternal education, parental smoking, pets, parental asthma, doctor-diagnosed allergic rhinitis, doctor-diagnosed eczema and wheeze severity. At age 4 years, asthma prevalence varied from 1.72% in Germany to 13.48% in England and the prevalence of wheeze varied from 9.82% in Greece to 55.37% in Spain. Adjusted estimates of the proportion of 4-year-old children with wheeze diagnosed with asthma remained highest in England (38.14%, 95% CI 31.38–44.90%) and lowest in Spain (15.94%, 95% CI 6.16–25.71%). The large differences in prevalence rates of asthma, wheeze and wheeze with asthma at age 4 years between European cohorts may indicate that childhood asthma is more readily diagnosed in some countries while going unrecognised elsewhere.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2014
Publisher: Wiley
Date: 24-01-2011
DOI: 10.1111/J.1398-9995.2010.02534.X
Abstract: The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.
Publisher: Public Library of Science (PLoS)
Date: 18-08-2020
Publisher: BMJ
Date: 15-03-2012
Publisher: Wiley
Date: 29-07-2016
Publisher: Elsevier BV
Date: 02-2017
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.JACI.2016.12.940
Abstract: Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL EU FP7-CP-IP project no: 261357 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Wiley
Date: 12-2016
Publisher: Wiley
Date: 20-02-2017
Publisher: Wiley
Date: 13-09-2015
DOI: 10.1111/ALL.12686
Abstract: Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
Publisher: International Global Health Society
Date: 12-2019
Publisher: American Association for the Advancement of Science (AAAS)
Date: 22-04-2016
Abstract: On average, most people's genomes contain approximately 100 completely nonfunctional genes. These loss-of-function (LOF) mutations tend to be rare and/or occur only as a single copy within in iduals. Narasimhan et al. investigated LOF in a Pakistani population with high levels of consanguinity. Examining LOF alleles that were identical by descent, they found, as expected, an absence of homozygote LOF for certain protein-coding genes. However, they also identified many homozygote LOF alleles with no apparent deleterious phenotype, including some that were expected to confer genetic disease. Indeed, one family had lost the recombination-associated gene PRDM9 . Science , this issue p. 474
Publisher: Oxford University Press (OUP)
Date: 20-06-2014
DOI: 10.1136/POSTGRADMEDJ-2013-132333
Abstract: Mentorship has been identified as a beneficial practice for doctors and may be particularly valuable for newly appointed consultants. It is associated with a number of potential clinical and non-clinical gains, such as enhanced job satisfaction and well-being. Despite strong support, many formalised schemes fail to launch or gain momentum. Research to date has largely focused on the gains associated with mentorship but has lacked study of the factors that facilitate uptake and maintenance of mentoring relationships by physicians. To explore perceptions of mentorship, the extent to which UK doctors appear to value mentorship and factors that may contribute to its successful use. Qualitative, descriptive, multi-centre study. 30 doctors including registrars, those newly appointed to consultant grade, senior doctors and medical leaders from nine hospitals in the north of England. Semistructured in idual interviews were undertaken between August and December 2013. Findings revealed a demand for mentorship for new consultants, with widely recognised benefits associated with its use. Several factors were identified as critical to successful mentorship relationships, including consistent understanding and expectations of mentorship between mentee and mentor, positive prior experiences, a suitable match between mentee and mentor, making time for people to act as mentors and the ensuring that mentors can meet a erse and changing set of needs. Mentorship for newly appointed consultants is valued, but current models of mentorship may suffer from rigid structures, mismatched expectations of participants and the absence of a culture of mentorship from training into practice. A social network approach, in which doctors have the opportunity to engage with a range of mentors through informal and naturally occurring relationships, may be one way to encourage successful and sustained mentoring relationships among doctors. An organisational culture in which mentorship is permitted and is the norm may enable such approaches to be widely adopted.
Publisher: Elsevier BV
Date: 10-2023
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for John Wright.