Claire Keeble
University of Leeds, Biostatistics, Post-Doc
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Research Interests: Medicine, Multivariate Analysis, Endometrial Cancer, Humans, Internal Medicine, and 15 moreFemale, Aged, Middle Aged, Neutrophils, Adult, Proportional hazards model, Retrospective Studies, Prognosis, Age Factors, Lymphocytes, Neoplasm staging, Blood platelets, Lymphocyte, Endometrial neoplasms, and hazard ratio
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ABSTRACT With the introduction of national guidelines for ultrasound screening it might be assumed that there is agreement in the key features required in assessing image quality. The aim of this study was to determine whether it is... more
ABSTRACT With the introduction of national guidelines for ultrasound screening it might be assumed that there is agreement in the key features required in assessing image quality. The aim of this study was to determine whether it is possible that personal preferences may influence what is regarded as an acceptable image. Two image sets, one vascular and one obstetric, were taken to the British Medical Ultrasound Society ‘Ultrasound 2012’ conference for delegates to rate whether images were acceptable or not. Data collection took place on days one and two, with the results presented on day three of the conference. Images from a variety of ultrasound machines were used and ranked in order of the odds of producing an acceptable image using logistic regression. Agreement between observers was investigated and three images per person were repeated to look at agreement within observers. Audience feedback was used to record the reasons why images were regarded as acceptable or not. Eighty-two participants reviewed each of the two image sets. The machine rankings revealed that some machines were up to 12 times more likely to produce an acceptable image than other machines. Agreement amongst experts or non-experts was found, but disagreement between the subgroups of experts and non-experts. Agreement within observers was around 80% and similar results were found in each of the image sets. Despite image quality assessment, personal preferences and expertise may still affect judgement, and guidelines may not ensure agreement.
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Background & aims: Iodine is important for thyroid function during pregnancy to support fetal growth, but studies of maternal iodine status and birth outcomes are conflicting. We aimed to quantify the association between iodine status and... more
Background & aims: Iodine is important for thyroid function during pregnancy to support fetal growth, but studies of maternal iodine status and birth outcomes are conflicting. We aimed to quantify the association between iodine status and birth outcomes, including potential threshold effects using nonlinear dose–response curves. Methods: We systematically searched Medline and Embase to 10 October 2022 for relevant cohort studies. We conducted random-effects meta-analyses of urinary iodine concentration (UIC), iodine:creatinine ratio (I:Cr), and iodide intake for associations with birth weight, birth weight centile, small for gestational age (SGA), preterm delivery, and other birth outcomes. Study quality was assessed using the Newcastle-Ottawa scale. Results: Meta-analyses were conducted on 23 cohorts with 42269 participants. Birth weight was similar between UIC ≥ 150 μg/L and <150 μg/L (difference = 30 g, 95% CI −22 to 83, p = 0.3, n = 13, I2 = 89%) with no evidence of linear tr...
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Introduction We assessed the association of arterial access site with clinical outcomes following PPCI in a large consecutive patient-series. Methods Demographic, clinical, and 30 day follow up data for all patients undergoing PPCI... more
Introduction We assessed the association of arterial access site with clinical outcomes following PPCI in a large consecutive patient-series. Methods Demographic, clinical, and 30 day follow up data for all patients undergoing PPCI between 1–1–2009 and 31–12–2011, and 1–1–2013 and 31–12–2013, in Leeds General Infirmary, were collected prospectively. All arterial access sites were recorded. Cross-overs were analysed by initial arterial access site. Patients presenting with cardiogenic shock and/or cardiac arrest were excluded. Clinical endpoints were 30 day MACE (total mortality and major bleeding. Multivariable analysis was performed with Cox proportional hazards models adjusting for major cardiovascular risk factors. Results 4056 patients underwent PPCI during this period (464 excluded due to cardiogenic shock and/or cardiac arrest). Data for 30 day bleeding and MACE were available for 3381 (94.2%) patients. 111 patients crossed over from radial to femoral access, and 102 patients ...
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Additional file 1.
Additional file 1: Table S1. Details of socioeconomic position categories and maternal education levels. Table S2. Details of model covariates, sample exclusions, sensitivity analyses and subgroup analyses for each of the different... more
Additional file 1: Table S1. Details of socioeconomic position categories and maternal education levels. Table S2. Details of model covariates, sample exclusions, sensitivity analyses and subgroup analyses for each of the different outcomes. Table S3. Pairwise correlations between each of the growth measures. Table S4. Predicted estimates (continuous outcomes) and percent at the threshold (binary outcomes) (99% CIs) at the 25th, 50th and 75th centiles of iodine concentration and p-overall* for 'average' participants†. Figure S1. A directed acyclic graph used to identify confounders and competing exposures in the association between maternal iodine concentration and birth or pregnancy outcomes. Figure S2. Flow chart of participant inclusions and exclusions. Figure S3. Estimated APGAR score at 1 minute and percent with congenital anomalies, using imputed datasets for the full sample. Figure S4. Estimated biparietal diameter, femur length and abdominal circumference, from ultra...
Objectives The neutrophil–lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous... more
Objectives The neutrophil–lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous melanoma and how this biomarker changed over time with the recurrence of disease. Methods This multicentre cohort study describes patients treated for Stage I–III cutaneous melanoma over 10 years. The baseline NLR was measured immediately prior to surgery and again at the time of discharge or disease recurrence. The odds ratios (OR) for sentinel node involvement are estimated using mixed-effects logistic regression. The risk of recurrence is estimated using multivariable Cox regression. Results Overall 1489 individuals were included. The mean baseline NLR was higher in patients with palpable nodal disease compared to those with microscopic nodal or localised disease (2.8 versus 2.4 and 2.3, respectively; p
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In the peripheral blood, the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) change in response to malignancy. These biomarkers are associated with adverse outcomes in numerous cancers, but the evidence is limited in... more
In the peripheral blood, the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) change in response to malignancy. These biomarkers are associated with adverse outcomes in numerous cancers, but the evidence is limited in relation to melanoma. This study sought to investigate the association between these biomarkers and survival in Stages I-III cutaneous melanoma. This multicenter cohort study investigated a consecutive series of patients who underwent wide excision of biopsy-proven cutaneous melanoma and sentinel lymph node biopsy during a 10-year period. The baseline NLR and PLR were calculated immediately before sentinel lymph node biopsy. Adjusted hazard ratios (HRs) for overall and melanoma-specific survival were generated. Overall, 1351 patients were included in the study. During surveillance, 184 of these patients died (14%), with 141 of the deaths (77%) attributable to melanoma. Worse overall survival was associated with a baseline NLR lower than 2.5 [HR 2.2...
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Understanding the factors associated with participation is key in addressing the problem of declining participation rates in epidemiological studies. This review aims to summarise factors affecting participation rates in articles... more
Understanding the factors associated with participation is key in addressing the problem of declining participation rates in epidemiological studies. This review aims to summarise factors affecting participation rates in articles published during the last nine years, to compare with previous findings to determine whether the research focus for non-participation has changed and whether the findings have been consistent over time. Web of Science was used to search titles of English articles from 2007–2015 for a range of synonymous words concerning participation rates. A predefined inclusion criteria was used to determine whether the resulting articles referred to participation in the context of study enrolment. Factors associated with participation were extracted from included articles. The search returned 626 articles, of which 162 satisfied the inclusion criteria. Compared with pre-2007, participant characteristics generally remained unchanged, but were topic-dependent. An increased...
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Background Directed acyclic graphs (DAGs) are an increasingly popular approach for identifying confounding variables that require conditioning when estimating causal effects. This review examined the use of DAGs in applied health research... more
Background Directed acyclic graphs (DAGs) are an increasingly popular approach for identifying confounding variables that require conditioning when estimating causal effects. This review examined the use of DAGs in applied health research to inform recommendations for improving their transparency and utility in future research. Methods Original health research articles published during 1999–2017 mentioning ‘directed acyclic graphs’ (or similar) or citing DAGitty were identified from Scopus, Web of Science, Medline and Embase. Data were extracted on the reporting of: estimands, DAGs and adjustment sets, alongside the characteristics of each article’s largest DAG. Results A total of 234 articles were identified that reported using DAGs. A fifth (n = 48, 21%) reported their target estimand(s) and half (n = 115, 48%) reported the adjustment set(s) implied by their DAG(s). Two-thirds of the articles (n = 144, 62%) made at least one DAG available. DAGs varied in size but averaged 12 nodes...
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Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Iodine requirements increase in pregnancy, but many women in regions without salt iodization have insufficient intakes. We explored... more
Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Iodine requirements increase in pregnancy, but many women in regions without salt iodization have insufficient intakes. We explored associations between iodide intake and urinary iodine concentration (UIC), urinary iodine/creatinine ratio (I/Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. A total of 246 pregnant women aged 18–40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter at around 12, 26 and 36 weeks’ gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24 h recalls. During pregnancy, median (IQR) dietary iodide intake was 101 µg/day (54, 142), with 42% from dairy and 9% from wh...
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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... more
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 ...
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BACKGROUND: Directed acyclic graphs (DAGs) are an increasingly popular approach for identifying confounding variables that require adjustment when estimating causal effects. This review examined the use of DAGs in applied health research... more
BACKGROUND: Directed acyclic graphs (DAGs) are an increasingly popular approach for identifying confounding variables that require adjustment when estimating causal effects. This review examined the use of DAGs in applied health research to inform recommendations for improving their transparency and utility in future research. METHODS: Original health research articles published during 1999-2017 mentioning "directed acyclic graphs" or similar or citing DAGitty were identified from Scopus, Web of Science, Medline, and Embase. Data were extracted on the reporting of: estimands, DAGs, and adjustment sets, alongside the characteristics of each article's largest DAG. RESULTS: A total of 234 articles were identified that reported using DAGs. A fifth (n=48, 21%) reported their target estimand(s) and half (n=115, 48%) reported the adjustment set(s) implied by their DAG(s). Two-thirds of the articles (n=144, 62%) made at least one DAG available. Diagrams varied in size but aver...
BackgroundThere is a paucity of real-world outcome data comparing clopidogrel, prasugrel and ticagrelor in primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). We sought to assess the... more
BackgroundThere is a paucity of real-world outcome data comparing clopidogrel, prasugrel and ticagrelor in primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI). We sought to assess the association of choice of oral P2Y12-receptor inhibitor with clinical outcomes following PPCI for STEMI in a large consecutive patient series.MethodsDemographic, procedural and 12-month outcome data were prospectively collected for all patients undergoing PPCI in Leeds, UK, between 01 January 2009 and 31 December 2011, and 01 January 2013 and 31 December 2013. Clinical endpoints were 30-day and 12-month all-cause mortality, recurrent MI and 30-day HORIZONS-major bleeding. Logistic regression analyses were undertaken to adjust for confounding factors.ResultsPrasugrel (n=1244) was associated with lower adjusted 30-day (OR 0.53 (0.34–0.85)) and 12-month (OR 0.55 (0.38–0.78)) mortality, and 12-month MI (OR 0.63 (0.42–0.94)) compared with clopidogrel (n=16...
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Severe iodine deficiency in mothers is known to impair foetal development. Pregnant women in the UK may be iodine insufficient, but recent assessments of iodine status are limited. This study assessed maternal urinary iodine... more
Severe iodine deficiency in mothers is known to impair foetal development. Pregnant women in the UK may be iodine insufficient, but recent assessments of iodine status are limited. This study assessed maternal urinary iodine concentrations (UIC) and birth outcomes in three UK cities. Spot urines were collected from 541 women in London, Manchester and Leeds from 2004–2008 as part of the Screening for Pregnancy End points (SCOPE) study. UIC at 15 and 20 weeks’ gestation was estimated using inductively coupled plasma-mass spectrometry (ICP-MS). Associations were estimated between iodine status (UIC and iodine-to-creatinine ratio) and birth weight, birth weight centile (primary outcome), small for gestational age (SGA) and spontaneous preterm birth. Median UIC was highest in Manchester (139 μg/L, 95% confidence intervals (CI): 126, 158) and London (130 μg/L, 95% CI: 114, 177) and lowest in Leeds (116 μg/L, 95% CI: 99, 135), but the proportion with UIC <50 µg/L was <20% in all thre...
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Case-control studies are used in epidemiology to try to uncover the causes of diseases, but are a retrospective study design known to suffer from non-participation and recall bias, which may explain their decreased popularity in recent... more
Case-control studies are used in epidemiology to try to uncover the causes of diseases, but are a retrospective study design known to suffer from non-participation and recall bias, which may explain their decreased popularity in recent years. Traditional analyses report usually only the odds ratio for given exposures and the binary disease status. Chain event graphs are a graphical representation of a statistical model derived from event trees which have been developed in artificial intelligence and statistics, and only recently introduced to the epidemiology literature. They are a modern Bayesian technique which enable prior knowledge to be incorporated into the data analysis using the agglomerative hierarchical clustering algorithm, used to form a suitable chain event graph. Additionally, they can account for missing data and be used to explore missingness mechanisms. Here we adapt the chain event graph framework to suit scenarios often encountered in case-control studies, to stre...
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Female sex and South Asian race have been associated with poor clinical outcomes following primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) but remain understudied in large... more
Female sex and South Asian race have been associated with poor clinical outcomes following primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) but remain understudied in large real-world series. We therefore investigated the association of sex and race with clinical outcomes following PPCI. We conducted a prospective study of all patients undergoing PPCI for STEMI between January 2009 and December 2011 at a large UK cardiac centre. Clinical characteristics and outcomes were compared according to sex and race using Chi-square test, independent samples Student's t-test and Mann-Whitney U-test. Primary and secondary outcomes were 12-month major adverse cardiovascular events (MACEs) - defined as all-cause mortality, myocardial infarction and unplanned revascularization, analysed using Cox proportional hazard models adjusting for cardiovascular risk factors. Three thousand and forty-nine patients were included. Women ( n=826) were ...
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Objectives The neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous... more
Objectives The neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous melanoma and how this biomarker changed over time with the recurrence of disease. Methods This multicentre cohort study describes patients treated for Stage I-III cutaneous melanoma over 10 years. The baseline NLR was measured immediately prior to surgery and again at the time of discharge or disease recurrence. The odds ratios (OR) for sentinel node involvement are estimated using mixed-effects logistic regression. The risk of recurrence is estimated using multivariable Cox regression. Results Overall 1489 individuals were included. The mean baseline NLR was higher in patients with palpable nodal disease compared to those with microscopic nodal or localised disease (2.8 versus 2.4 and 2.3, respectively; p < 0.001). A baseline NLR ≥ 2.3 was associated with 30% higher odds of microscopic metastatic melanoma in the sentinel lymph node [adjusted OR 1.3 (95% CI 1.3, 1.3)]. Following surgery, 253 patients (18.7%) developed recurrent melanoma during surveillance although there was no statistically significant association between the baseline NLR and the risk of recurrence [adjusted HR 0.9 (0.7, 1.1)]. Conclusion The NLR is associated with the volume of melanoma at presentation and may predict occult sentinel lymph metastases. Further prospective work is required to investigate how NLR may be modelled against other clinicopathological variables to predict outcomes and to understand the temporal changes in NLR following surgery for melanoma. Keywords Neutrophil-lymphocyte ratio · Platelet-lymphocyte ratio · Lymphocyte-monocyte ratio · Cutaneous melanoma · Recurrence · Biomarker Abbreviations CI Confidence interval FBC Full blood count HR Hazard ratio IQR Interquartile range NLR Neutrophil lymphocyte ratio OR Odds ratio SLN Sentinel lymph node WLE Wider local excision
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Research Interests: Biomarkers and Melanoma
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Chain event graphs are a graphical representation of a statistical model derived from event trees, previously applied to cohort studies but not to case-control studies. We apply the chain event graph framework to a Yorkshire case-control... more
Chain event graphs are a graphical representation of a statistical model derived from event trees, previously applied to cohort studies but not to case-control studies. We apply the chain event graph framework to a Yorkshire case-control study of childhood type I diabetes, to examine four exposure variables associated with the mother, three of which are fully observed (her school-leaving-age, amniocenteses during pregnancy and delivery type) and one with missing values (her rhesus factor), while incorporating previous type I diabetes knowledge. We conclude that the unknown rhesus factor values are likely to be missing not at random, and are mainly rhesus positive. The mother's school-leaving-age and rhesus factor are not associated with the diabetes status of the child, whereas having at least one amniocentesis and, to a lesser extent, delivering by cesarean are, with the combination of both procedures further increasing the probability of diabetes. This application of chain eve...
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The aim of this research was to quantify the reduction in radiation dose facilitated by image processing alone for percutaneous coronary intervention (PCI) patient angiograms, without reducing the perceived image quality required to... more
The aim of this research was to quantify the reduction in radiation dose facilitated by image processing alone for percutaneous coronary intervention (PCI) patient angiograms, without reducing the perceived image quality required to confidently make a diagnosis. Incremental amounts of image noise were added to five PCI angiograms, simulating the angiogram as having been acquired at corresponding lower dose levels (10-89% dose reduction). 16 observers with relevant experience scored the image quality of these angiograms in 3 states-with no image processing and with 2 different modern image processing algorithms applied. These algorithms are used on state-of-the-art and previous generation cardiac interventional X-ray systems. Ordinal regression allowing for random effects and the delta method were used to quantify the dose reduction possible by the processing algorithms, for equivalent image quality scores. Observers rated the quality of the images processed with the state-of-the-art...
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Type 2 diabetes mellitus prevalence is growing globally, and the leading cause of mortality in these patients is cardiovascular disease. Epigenetic mechanisms such as microRNAs (miRs) and DNA methylation may contribute to complications of... more
Type 2 diabetes mellitus prevalence is growing globally, and the leading cause of mortality in these patients is cardiovascular disease. Epigenetic mechanisms such as microRNAs (miRs) and DNA methylation may contribute to complications of type 2 diabetes mellitus. We discovered an aberrant type 2 diabetes mellitus-smooth muscle cell phenotype driven by persistent up-regulation of miR-145. This study aimed to determine whether elevated expression was due to changes in methylation at the miR-145 promoter. Smooth muscle cells were cultured from saphenous veins of 22 non-diabetic and 22 type 2 diabetes mellitus donors. DNA was extracted, bisulphite treated and pyrosequencing used to interrogate methylation at 11 CpG sites within the miR-145 promoter. Inter-patient variation was high irrespective of type 2 diabetes mellitus. Differential methylation trends were apparent between non-diabetic and type 2 diabetes mellitus-smooth muscle cells at most sites but were not statistically signific...
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ABSTRACT Studies into participation bias have examined participation trends, where it occurs, the factors affecting it, and methods to try to reduce it. However, some authors only discuss participation bias at the end of the study, some... more
ABSTRACT Studies into participation bias have examined participation trends, where it occurs, the factors affecting it, and methods to try to reduce it. However, some authors only discuss participation bias at the end of the study, some acknowledge it and apply a method to try to reduce it, while others ignore it or dismiss it as negligible. Issues of three high-impact epidemiology journals were examined; 81 articles were read and reviewed for potential participation bias. Categories were used to classify the approach taken to participation bias and the results recorded. Of the 81 articles considered, 42 (51%) were eligible and could have suffered from participation bias. It was found that 57% of these articles ignored the effects of participation bias, while 17% only considered it briefly in the discussion. Few articles (22%) attempted to reduce the participation bias, with over half of these using unsuitable methods (55%). This review highlights how participation bias is often not considered and hence the conclusions drawn from these studies may not be correct.