Trevor F Cox

• PhD
• University of Liverpool

Background The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness an...

Background The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of 1) the exercise prehabilitation programme on psychological health; and 2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and...

Background Alkaptonuria (AKU) is present from birth, yet clinical effects are considered to appear later in life. Morbidity of AKU, considered irreversible, is secondary to ochronosis. Age of ochronosis onset is not clearly known. Nitisinone profoundly lowers homogentisic acid (HGA), the metabolic defect in AKU. Nitisinone also arrests ochronosis a...

[This corrects the article DOI: 10.1186/s41512-016-0001-y.].

Objective and background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapies. Methods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as w...

BackgroundROC (receiver operating characteristic) curve analysis is well established for assessing how well a marker is capable of discriminating between individuals who experience disease onset and individuals who do not. The classical (standard) approach of ROC curve analysis considers event (disease) status and marker value for an individual as...

Background: Erlotinib is an EGFR tyrosine kinase inhibitor that has shown a significant but only marginally improved median overall survival when combined with gemcitabine in patients with locally advanced and metastatic pancreatic cancer. Vandetanib is a novel tyrosine kinase inhibitor of VEGFR2, RET, and EGFR, all of which are in involved in the...

Background: In the UK, the majority of diagnostic upper gastrointestinal (UGI) endoscopies are a result of direct-to-test referral from the primary care physician. The diagnostic yield of these tests is relatively low, and the burden high on endoscopy services. Dual-focus magnification, high-definition endoscopy is expected to improve detection an...

Joris de Groot, Christiana Naaktgeboren, Hans Reitsma, Carl Moons Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands Correspondence: Joris de Groot (j.degroot-17@umcutrecht.nl) A major contributor to the rising problem of overdiagnosis, with the subsequent risk of overtreatment, is t...

Interpretation of principal components is difficult due to their weights (loadings, coefficients) being of various sizes. Whereas very small weights or very large weights can give clear indication of the importance of particular variables, weights that are neither large nor small (‘grey area’ weights) are problematical. This is a particular problem...

Background: Vandetanib is a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, rearranged during transfection (RET), and epidermal growth factor receptor, all of which are in involved in the pathogenesis of pancreatic cancer. We investigated the clinical efficacy of vandetanib in patients with advanced pancreatic canc...

Background: Hydration in advanced cancer is a controversial area; however, current hydration assessments methods are poorly developed. Bioelectrical impedance vector analysis (BIVA) is an accurate hydration tool; however its application in advanced cancer has not been explored. This study used BIVA to evaluate hydration status in advanced cancer t...

Background: Diabetes mellitus is frequently observed in pancreatic cancer patients and is both a risk factor and an early manifestation of the disease. Methods: We analysed the prognostic impact of diabetes on the outcome of pancreatic cancer following resection and adjuvant chemotherapy using individual patient data from three European Study Gr...

Background and aim: Adenoma detection rate (ADR) is the most important quality indicator for screening colonoscopy, due to its association with colorectal cancer outcomes. As a result, a number of techniques and technologies have been proposed that have the potential to improve ADR. The aim of this study was to assess the potential impact of new-g...

Background and aims The role of GATA factors in cancer has gained increasing attention recently, but the function of GATA6 in pancreatic ductal adenocarcinoma (PDAC) is controversial. GATA6 is amplified in a subset of tumours and was proposed to be oncogenic, but high GATA6 levels are found in well-differentiated tumours and are associated with bet...

Background and aims The role of GATA factors in cancer has gained increasing attention recently, but the function of GATA6 in pancreatic ductal adenocarcinoma (PDAC) is controversial. GATA6 is amplified in a subset of tumours and was proposed to be oncogenic, but high GATA6 levels are found in well-differentiated tumours and are associated with bet...

Introduction Adenoma detection rate (ADR) is the most important quality indicator for screening colonoscopy, due to its association with colorectal cancer outcomes. As a result a number of techniques and technologies have been proposed that have the potential to improved ADR. The aim of this study was to assess the potential impact of the new gener...

Background Preclinical studies suggest that chemotherapy may enhance the immune response against pancreatic cancer. Methods The levels of granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) and the associated inflammatory marker C-reactive protein (CRP) were assessed in 38 patients receiving gemcitabine and capecitab...

This paper introduces a new simple divergence measure between two survival distributions. For two groups of patients, the divergence measure between their associated survival distributions is based on the integral of the absolute difference in probabilities that a patient from one group dies at time t and a patient from the other group survives bey...

Background & aims: GALAD and BALAD-2 are statistical models for estimating the likelihood of the presence of hepatocellular carcinoma (HCC) in individual patients with chronic liver disease and the survival of patients with HCC, respectively. Both models use objective measures, particularly the serum markers α-fetoprotein (AFP), AFP-L3, and des-γ-...

The standard treatment pathway for locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Neoadjuvant CRT has been shown to decrease physical fitness, and this decrease is associated with increased post-operative morbidity. Exercise training can stimulate skeletal muscle adaptations such as increased mitochondria...

The standard treatment pathway for locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Neoadjuvant CRT has been shown to decrease physical fitness, and this decrease is associated with increased post-operative morbidity. Exercise training can stimulate skeletal muscle adaptations such as increased mitochondria...

Principal components analysis is a much used and practical technique for analysing multivariate data, finding a particular set of linear compounds of the variables under consideration, such that covariances between all pairs are 0. An alternative view is that when the variables are considered as axes in a Cartesian coordinate system, then principal...

Objectives: Pancreatic intraductal papillary mucinous neoplasias (IPMNs) represent 25% of all cystic neoplasms and are precursor lesions for pancreatic ductal adenocarcinoma. This study aims to identify the best imaging modality for detecting malignant transformation in IPMN, the sensitivity and specificity of risk features on imaging, and the use...

Purpose: Identification of serum biomarkers enabling earlier diagnosis of pancreatic ductal adenocarcinoma (PDAC) could improve outcome. Serum protein profiles in patients with pre-clinical disease and at diagnosis were investigated. Experimental design: Serum from cases up to 4 years prior to PDAC diagnosis and controls (UKCTOCS,n=174) were stu...

Introduction: Identification of serum biomarkers enabling earlier diagnosis of pancreatic ductal adenocarcinoma (PDAC) could improve outcome. Aims: Serum protein profiles in patients with pre-clinical disease and at diagnosis were investigated. Patients & methods: Serum from cases up to 4 years prior to diagnosis of PDAC and controls enrolled on...

Alkaptonuria (AKU) is an ultrarare autosomal recessive disorder resulting from a deficiency of homogentisate 1,2 dioxygenase (HGD), an enzyme involved in the catabolism of phenylalanine and tyrosine. Loss of HGD function prevents metabolism of homogentisic acid (HGA), leading to increased levels of plasma HGA and urinary excretion. Excess HGA becom...

Introduction: Alkaptonuria (OMIM 203500) is an iconic autosomal recessive disease present at birth. The clinical effects are due to high circulating homogentisic acid (HGA) and high urine HGA. Oxidative conversion of circulating HGA to pigment is termed ochronosis, a process that alters tissues, resulting in the classical clinical consequences of t...

Pancreatic cancer is the fifth most common cause of cancer death. Only 10%-15% of patients are suitable for surgical resection. The role of adjuvant therapy has been evaluated in randomized controlled trials. There is a clearly demonstrated survival advantage of adjuvant 5-fluorouracil plus folinic acid (5-FU/FA; ESPAC-1) or gemcitabine (CONKO-001)...

Alkaptonuria (AKU) is a serious genetic disease due to a defect in tyrosine metabolism, leading to increased serum levels of homogentisic acid (HGA). Nitisinone decreases HGA in AKU, but the concentration-response relationship has not been previously reported. To determine the relationship between serum concentrations of nitisinone and the effect o...

Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an internation...

Individuals from hereditary pancreatitis (HP) and familial pancreatic cancer (FPC) kindreds are at increased risk of developing pancreatic cancer. Premalignant molecular changes may be detected in pancreatic juice collected by endoscopic retrograde cholangiopancreatography (ERCP). The objective was to determine the risk of post-ERCP pancreatitis (P...

The Cox proportional hazards model is widely used in the analysis of medical data either for survival or time to a particular event. Factors and continuous covariates can be easily incorporated into the model and hazard ratios calculated. The model can however be distorted when extreme value observations occur within a continuous covariate and the...

Unlabelled: Circulating intercellular adhesion molecule-1 (ICAM-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been widely proposed as potential diagnostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). We report on serum protein levels prior to clinical presentation of pancreatic cancer. Serum ICAM-1 and TIMP-1 were measur...

This is the protocol for a review and there is no abstract. The objectives are as follows: A systematic review of the available evidence, both published and unpublished, on the management of localised and locally advanced pancreatic cancer is planned. The interventions to be evaluated are chemotherapy and radiotherapy, in the adjuvant (for localise...

Background: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer. Methods: TeloVac was a three-group, open-label, randomised phase 3 trial. We recruited patients from 51 UK hospitals. Eligible pat...

Background We investigated whether combinations of serum cytokines, used with logistic disease predictor models, could facilitate the detection of pancreatic ductal adenocarcinoma (PDAC). Methods The serum levels of 27 cytokines were measured in 241 subjects, 127 with PDAC, 49 with chronic pancreatitis, 20 with benign biliary obstruction and 45 he...

Background: The Japanese ‘BALAD' model offers the first objective, biomarker-based, tool for assessment of prognosis in hepatocellular carcinoma, but relies on dichotomisation of the constituent data, has not been externally validated, and cannot be applied to the individual patients. Methods: In this Japanese/UK collaboration, we replicated the o...

Although focus is placed on achieving patient preference to die at home, ensuring the provision of good quality care and family support is equally important. To assess quality of care and family support, as perceived by bereaved relatives, using 'Care Of the Dying Evaluation' (CODE), a 40-item validated post-bereavement questionnaire based on key c...

Background As well as facilitating patients’ wish to die at home, evaluating quality of care in this setting is essential. Postbereavement surveys with family members represent one assessment method. ‘Care Of the Dying Evaluation’ (CODE) is a 40-item self-completion postbereavement questionnaire, based on the key components of best practice for car...

UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS). Considerable variation in practice exists due to a lack of expertise, technical difficulties and other, as yet ill-defined features. This retrospective multi-centre study aims to determine...

Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma, but the optimal duration and time to initiate chemotherapy is unknown. Patients with pancreatic ductal adenocarcinoma treated within the international, phase III, European Study Group for Pancreatic Cancer-3 (version 2) study were included if they h...

METHODS: TeloVac was a three-group, open-label, randomised phase 3 trial. We recruited patients from 51 UK hospitals. Eligible patients were treatment naive, aged older than 18 years, with locally advanced or metastatic pancreatic ductal adenocarcinoma, and Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assig...

Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were class...

We explore the possibility of incorporating historical information, which may take the form of data from previous trials, summary information or information derived from expert opinion into the design of phase II clinical trials with a time-to-event endpoint. We model the survival data by means of the Piecewise Exponential Model and introduce a met...

Alkaptonuria (AKU) is an orphan inherited homogentisate dioxygenase enzyme deficiency resulting in accumulation of homogentisic acid (HGA). HGA is converted to a black pigment polymer known as ochronosis that causes tissue damage affecting many tissues including joints and heart, with significant poor quality of life. The DevelopAKUre project is a...

PP-plots for survival distributions are considered where one survival distribution is plotted against the other. This is seen as another way of visualizing the nature of the relationship between the two survival distributions along with typical Kaplan-Meier plots. For three survival distributions, the PPP-plot is introduced where the survival distr...

Background: Hepatocellular carcinoma is a common complication of chronic liver disease (CLD), and is conventionally diagnosed by radiological means. We aimed to build a statistical model that could determine the risk of hepatocellular carcinoma in individual patients with CLD using objective measures, particularly serological tumor markers. Methods...

Evaluating Care and Health Outcomes-for the Dying (ECHO-D) is a post-bereavement questionnaire that assesses quality of care for the dying and is linked with the Liverpool Care Pathway for the Dying Patient (LCP). To further assess the validity and reliability of the ECHO-D, namely the construct validity, internal consistency, and test-retest relia...

Fludarabine plus cyclophosphamide (FC) is the chemotherapy backbone of modern chronic lymphocytic leukemia (CLL) treatment. CYP2B6 is a polymorphic cytochrome P450 isoform that converts cyclophosphamide to its active form. This study investigated the possible impact of genetic variation in CYP2B6 on response to FC chemotherapy in CLL. Available DNA...

On-site source data verification is a common and expensive activity, with little evidence that it is worthwhile. Central statistical monitoring (CSM) is a cheaper alternative, where data checks are performed by the coordinating centre, avoiding the need to visit all sites. Several publications have suggested methods for CSM; however, few have descr...

Background: The Liverpool Care Pathway for the Dying Patient (LCP) aims to transfer hospice principles of care for dying patients to other health-care sectors. This post-bereavement survey explored the LCP's effectiveness in improving quality of care for cancer patients. Methods: Postal self-completion questionnaires were sent to 778 next-of-kin t...

Background: The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance. Methods: Isobaric tags for relative and absolute quantification were u...

Introduction: Patients with severe acute pancreatitis are at risk of candidal infections carrying the potential risk of an increase in mortality. Since early diagnosis is problematic, several clinical risk scores have been developed to identify patients at risk. Such patients may benefit from prophylactic antifungal therapy while those patients wh...

Source data verification (SDV) is a resource intensive method of quality assurance frequently used in clinical trials. There is no empirical evidence to suggest that SDV would impact on comparative treatment effect results from a clinical trial. Data discrepancies and comparative treatment effects obtained following 100% SDV were compared to those...

In Reply: The ESPAC-3 periampullary cancer trial demonstrated a significant survival benefit for adjuvant chemotherapy, adjusting for prognostic variables. Dr Overman and colleagues have suggested a central pathology review to be more certain about the origin of the primary tumor in the patients enrolled in the trial. Such a review was not possible...

Pancreatic cancer is a challenging malignancy to treat, as less than one-fifth of diagnosed cases are resectable, surgery is complex and postoperative recovery slow, treated patients tend to relapse and overall survival rates are low. It is one of the leading causes of cancer-related mortality. Adjuvant therapy has been employed in resectable disea...

Patients with periampullary adenocarcinomas undergo the same resectional surgery as that of patients with pancreatic ductal adenocarcinoma. Although adjuvant chemotherapy has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas. To determine whether adjuvant chemotherapy...

Pancreatic resection for cancer may produce pancreatic exocrine insufficiency (PEI), which is poorly understood. This study examined the coefficient of fat absorption (CFA), symptoms, quality of life (QoL) and the accuracy of faecal elastase-1 (FE-1) measurement to predict PEI. Forty patients were analysed following resection for pancreatic maligna...

Wide use has been made of multidimensional scaling (MDS) techniques since the pioneering papers of Shepard and Kruskal. In the main, dissimilarities used in the various MDS techniques are derived for pairs of objects or stimuli. This is termed 2-way, 1-mode data, meaning pairs of objects within a single set are considered. Some MDS techniques are d...

Increased circulating homogentisic acid in body fluids occurs in alkaptonuria (AKU) due to lack of enzyme homogentisate dioxygenase leading in turn to conversion of HGA to a pigmented melanin-like polymer, known as ochronosis. The tissue damage in AKU is due to ochronosis. A potential treatment, a drug called nitisinone, to decrease formation of HG...

Alkaptonuria (AKU) is due to excessive homogentisic acid accumulation in body fluids due to lack of enzyme homogentisate dioxygenase leading in turn to varied clinical manifestations mainly by a process of conversion of HGA to a polymeric melanin-like pigment known as ochronosis. A potential treatment, a drug called nitisinone, to decrease formatio...

LBA4006 Background: The effect of adjuvant treatment on overall survival (OS) of resected ampullary adenocarcinoma is not known. The aim was to compare the survival effect of adjuvant chemotherapy compared to observation (OBS) after resection and within the chemotherapy group to compare 5-fluorouracil/folinic acid (5-FU/FA) against gemcitabine (GEM...

To determine the effect of toothpaste concentration on enamel and dentine wear in vitro and to model the effects of toothpaste abrasion upon dilution during toothbrushing in vivo. Polished human enamel/dentine specimens were indented with a Knoop diamond and the enamel-dentine junction profiled. Specimens were brushed for 1200s with toothpastes wit...

The aims of this study were to evaluate the effects of a novel silica-based blue covarine whitening toothpaste on the colour of anterior restoration materials. Restoration materials (three glass ionomers, three resin composites) were cast into disks (10 mm diameter, 2 mm thick) using cylindrical moulds. Specimens were immersed in pooled whole saliv...

To evaluate the effects of a 6% hydrogen peroxide tooth whitener, Xtra White, on sound human enamel microhardness in vitro after an extended and exaggerated simulated 8 weeks of product use. Polished human enamel specimens were prepared and baseline microhardness and color measurements determined. The enamel specimens were exposed to a fluoride-con...

To determine the protective nature of pellicle towards toothpaste abrasion. The enamel region of human enamel-dentine blocks was indented with a Knoop diamond and the profile across the enamel-dentine junction was measured. Blocks were either exposed to deionised water or placed onto intra-oral appliances and worn in the mouth to produce in situ pe...

To determine the enamel abrasivity of three whitening toothpastes and a silica toothpaste and to measure the brushing forces used. Polished human enamel blocks were indented with a Knoop diamond and attached to dentures of adult volunteers. The blocks were brushed ex vivo, twice per day with either a whitening toothpaste containing Perlite (White S...

Suppose dissimilarity data have been collected on a set of n objects or individuals, where there is a value of dissimilarity measured for each pair.The dissimilarity measure used might be a subjective judgement made by a judge, where for example a teacher subjectively scores the strength of friendship between pairs of pupils in her class, or, as an...

Objectives: To measure the delivery of active ingredients of a new oral health toothpaste with zinc citrate trihydrate/triclosan and containing α-tocopherol acetate (vitamin E) and sunflower oil (vitamin F) and compare its anti-plaque/anti-ginigvitis efficacy to that of a clinically proven control toothpaste.Methods: The new toothpaste contained 0....

Objectives: To measure delivery of vitamin E acetate and sunflower oil (as triolein) to gums after use of a fluoridated toothpaste with 0.1% vitamin E acetate, 0.5% sunflower oil and a gum-health active system (0.3% triclosan (TCN) and 0.75% zinc citrate trihydrate) compared to a control fluoridated toothpaste containing zinc citrate trihydrate and...