ORCID Profile
0000-0003-4440-574X
Current Organisation
University of Oxford
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Publisher: Elsevier BV
Date: 09-2017
Publisher: Springer Science and Business Media LLC
Date: 30-03-2008
DOI: 10.1038/NG.111
Abstract: To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.
Publisher: Springer Science and Business Media LLC
Date: 14-10-2007
DOI: 10.1038/NG.2007.18
Abstract: To identify risk variants for colorectal cancer (CRC), we conducted a genome-wide association study, genotyping 550,163 tag SNPs in 940 in iduals with familial colorectal tumor (627 CRC, 313 advanced adenomas) and 965 controls. We evaluated selected SNPs in three replication s le sets (7,473 cases, 5,984 controls) and identified three SNPs in SMAD7 (involved in TGF-beta and Wnt signaling) associated with CRC. Across the four s le sets, the association between rs4939827 and CRC was highly statistically significant (P(trend) = 1.0 x 10(-12)).
Publisher: National Institute for Health and Care Research
Date: 09-2009
DOI: 10.3310/HTA13420
Abstract: To determine the accuracy, acceptability and cost-effectiveness of polymerase chain reaction (PCR) and optical immunoassay (OIA) rapid tests for maternal group B streptococcal (GBS) colonisation at labour. A test accuracy study was used to determine the accuracy of rapid tests for GBS colonisation of women in labour. Acceptability of testing to participants was evaluated through a questionnaire administered after delivery, and acceptability to staff through focus groups. A decision-analytic model was constructed to assess the cost-effectiveness of various screening strategies. Two large obstetric units in the UK. Women booked for delivery at the participating units other than those electing for a Caesarean delivery. Vaginal and rectal swabs were obtained at the onset of labour and the results of vaginal and rectal PCR and OIA (index) tests were compared with the reference standard of enriched culture of combined vaginal and rectal swabs. The accuracy of the index tests, the relative accuracies of tests on vaginal and rectal swabs and whether test accuracy varied according to the presence or absence of maternal risk factors. PCR was significantly more accurate than OIA for the detection of maternal GBS colonisation. Combined vaginal or rectal swab index tests were more sensitive than either test considered in idually [combined swab sensitivity for PCR 84% (95% CI 79-88%) vaginal swab 58% (52-64%) rectal swab 71% (66-76%)]. The highest sensitivity for PCR came at the cost of lower specificity [combined specificity 87% (95% CI 85-89%) vaginal swab 92% (90-94%) rectal swab 92% (90-93%)]. The sensitivity and specificity of rapid tests varied according to the presence or absence of maternal risk factors, but not consistently. PCR results were determinants of neonatal GBS colonisation, but maternal risk factors were not. Overall levels of acceptability for rapid testing amongst participants were high. Vaginal swabs were more acceptable than rectal swabs. South Asian women were least likely to have participated in the study and were less happy with the s ling procedure and with the prospect of rapid testing as part of routine care. Midwives were generally positive towards rapid testing but had concerns that it might lead to overtreatment and unnecessary interference in births. Modelling analysis revealed that the most cost-effective strategy was to provide routine intravenous antibiotic prophylaxis (IAP) to all women without screening. Removing this strategy, which is unlikely to be acceptable to most women and midwives, resulted in screening, based on a culture test at 35-37 weeks' gestation, with the provision of antibiotics to all women who screened positive being most cost-effective, assuming that all women in premature labour would receive IAP. The results were sensitive to very small increases in costs and changes in other assumptions. Screening using a rapid test was not cost-effective based on its current sensitivity, specificity and cost. Neither rapid test was sufficiently accurate to recommend it for routine use in clinical practice. IAP directed by screening with enriched culture at 35-37 weeks' gestation is likely to be the most acceptable cost-effective strategy, although it is premature to suggest the implementation of this strategy at present.
Publisher: Oxford University Press (OUP)
Date: 27-08-2008
DOI: 10.1093/HMG/DDN267
Abstract: The common single-nucleotide polymorphism (SNP) rs3802842 at 11q23.1 has recently been reported to be associated with risk of colorectal cancer (CRC). To examine this association in detail we genotyped rs3802842 in eight independent case-control series comprising a total of 10 638 cases and 10 457 healthy in iduals. A significant association between the C allele of rs3802842 and CRC risk was found (per allele OR = 1.17 95% confidence interval [CI]: 1.12-1.22 P = 1.08 x 10(-12)) with the risk allele more frequent in rectal than colonic disease (P = 0.02). In combination with 8q21, 8q24, 10p14, 11q, 15q13.3 and 18q21 variants, the risk of CRC increases with an increasing numbers of variant alleles for the six loci (OR(per allele) = 1.19 95% CI: 1.15-1.23 P(trend) = 7.4 x 10(-24)). Using the data from our genome-wide association study of CRC, LD mapping and imputation, we were able to refine the location of the causal locus to a 60 kb region and screened for coding changes. The absence of exonic mutations in any of the transcripts (FLJ45803, LOC120376, C11orf53 and POU2AF1) mapping to this region makes the association likely to be a consequence of non-coding effects on gene expression.
Publisher: Elsevier BV
Date: 09-2000
Publisher: Elsevier BV
Date: 10-2003
Publisher: Wiley
Date: 12-06-2007
DOI: 10.1111/J.1471-0528.2007.01382.X
Abstract: The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting. A multicentre randomised controlled trial (RCT). Fetal medicine units. Pregnant women with singleton, male fetus with isolated lower urinary tract obstruction (LUTO). Following ultrasound diagnosis of LUTO in a male fetus and exclusion of other structural and chromosomal anomalies, participation in the trial will be discussed with the mother and written information given. Consent for participation in the trial will be taken and the mother randomised via the internet to either insertion of a vesicoamniotic shunt or expectant management. During pregnancy, both groups will be followed with regular ultrasound scans looking at viability, renal measurements and amniotic fluid volume. Following delivery, babies will be followed up by paediatric nephrologists/urologists at 4-6 weeks, 12 months and 3 and 5 years to assess renal function via serum creatinine, renal ultrasound and need for dialysis/transplant. The main outcome measures will be perinatal mortality rates and renal function at 4-6 weeks and 12 months measured via serum creatinine, renal ultrasound and need for dialysis/transplant. Wellbeing of Women. ESTIMATED COMPLETION DATE: September 2010. TRIAL ALGORITHM: [flowchart: see text].
Publisher: Springer Science and Business Media LLC
Date: 08-07-2007
DOI: 10.1038/NG2085
Abstract: Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 x 10(-7), allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected in iduals and 3,752 controls 1,901 affected in iduals and 1,079 controls 1,072 affected in iduals and 415 controls) and replicated the association, providing P = 1.27 x 10(-14) (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 in iduals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34 P = 6.89 x 10(-5)). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.
Publisher: Elsevier BV
Date: 06-2012
Publisher: Wiley
Date: 13-10-2010
DOI: 10.1111/J.1471-0528.2010.02725.X
Abstract: To assess the accuracy and acceptability of polymerase chain reaction (PCR) and optical immunoassay (OIA) tests for the detection of maternal group B streptococcus (GBS) colonisation during labour, comparing their performance with the current UK policy of risk factor-based screening. Diagnostic test accuracy study. Fourteen hundred women in labour at two large UK maternity units provided vaginal and rectal swabs for testing. The PCR and OIA index tests were compared with the reference standard of selective enriched culture, assessed blind to index tests. Factors influencing neonatal GBS colonisation were assessed using multiple logistic regression, adjusting for antibiotic use. The acceptability of testing to participants was evaluated through a structured questionnaire administered after delivery. The sensitivity and specificity of PCR, OIA and risk factor-based screening. Maternal GBS colonisation was 21% (19-24%) by combined vaginal and rectal swab enriched culture. PCR test of either vaginal or rectal swabs was more sensitive (84% [79-88%] versus 72% [65-77%]) and specific (87% [85-89%] versus 57% [53-60%]) than OIA (P < 0.001), and far more sensitive (84 versus 30% [25-35%]) and specific (87 versus 80% [77-82%]) than risk factor-based screening (P < 0.001). Maternal antibiotics (odds ratio, 0.22 [0.07-0.62] P = 0.004) and a positive PCR test (odds ratio, 29.4 [15.8-54.8] P < 0.001) were strongly related to neonatal GBS colonisation, whereas risk factors were not (odds ratio, 1.44 [0.80-2.62] P = 0.2). Intrapartum PCR screening is a more accurate predictor of maternal and neonatal GBS colonisation than is OIA or risk factor-based screening, and is acceptable to women.
Publisher: Massachusetts Medical Society
Date: 12-11-2009
Publisher: National Institute for Health and Care Research
Date: 03-2021
DOI: 10.3310/HTA25190
Abstract: Assistive technology and telecare have been promoted to manage the risks associated with independent living for people with dementia, but there is limited evidence of their effectiveness. This trial aimed to establish whether or not assistive technology and telecare assessments and interventions extend the time that people with dementia can continue to live independently at home and whether or not they are cost-effective. Caregiver burden, the quality of life of caregivers and of people with dementia and whether or not assistive technology and telecare reduce safety risks were also investigated. This was a pragmatic, randomised controlled trial. Blinding was not undertaken as it was not feasible to do so. All consenting participants were included in an intention-to-treat analysis. This trial was set in 12 councils in England with adult social services responsibilities. Participants were people with dementia living in the community who had an identified need that might benefit from assistive technology and telecare. Participants were randomly assigned to receive either assistive technology and telecare recommended by a health or social care professional to meet their assessed needs (a full assistive technology and telecare package) or a pendant alarm, non-monitored smoke and carbon monoxide detectors and a key safe (a basic assistive technology and telecare package). The primary outcomes were time to admission to care and cost-effectiveness. Secondary outcomes assessed caregivers using the 10-item Center for Epidemiological Studies Depression Scale, the State–Trait Anxiety Inventory 6-item scale and the Zarit Burden Interview. Of 495 participants, 248 were randomised to receive full assistive technology and telecare and 247 received the limited control. Comparing the assistive technology and telecare group with the control group, the hazard ratio for institutionalisation was 0.76 (95% confidence interval 0.58 to 1.01 p = 0.054). After adjusting for an imbalance in the baseline activities of daily living score between trial arms, the hazard ratio was 0.84 (95% confidence interval 0.63 to 1.12 p = 0.20). At 104 weeks, there were no significant differences between groups in health and social care resource use costs (intervention group – control group difference: mean –£909, 95% confidence interval –£5336 to £3345) or in societal costs (intervention group – control group difference: mean –£3545 95% confidence interval –£13,914 to £6581). At 104 weeks, based on quality-adjusted life-years derived from the participant-rated EuroQol-5 Dimensions questionnaire, the intervention group had 0.105 (95% confidence interval –0.204 to –0.007) fewer quality-adjusted life-years than the control group. The number of quality-adjusted life-years derived from the proxy-rated EuroQol-5 Dimensions questionnaire did not differ between groups. Caregiver outcomes did not differ between groups over 24 weeks. Compliance with the assigned trial arm was variable, as was the quality of assistive technology and telecare needs assessments. Attrition from assessments led to data loss additional to that attributable to care home admission and censoring events. A full package of assistive technology and telecare did not increase the length of time that participants with dementia remained in the community, and nor did it decrease caregiver burden, depression or anxiety, relative to a basic package of assistive technology and telecare. Use of the full assistive technology and telecare package did not increase participants’ health and social care or societal costs. Quality-adjusted life-years based on participants’ EuroQol-5 Dimensions questionnaire responses were reduced in the intervention group compared with the control group groups did not differ in the number of quality-adjusted life-years based on the proxy-rated EuroQol-5 Dimensions questionnaire. Future work could examine whether or not improved assessment that is more personalised to an in idual is beneficial. Current Controlled Trials ISRCTN86537017. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 19. See the NIHR Journals Library website for further project information.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.EJVS.2013.07.020
Abstract: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. ISRCTN21144362.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Richard Gray.