Middleton G.,University of Birmingham |
Silcocks P.,University of Liverpool |
Cox T.,University of Liverpool |
Valle J.,University of Manchester |
And 29 more authors.
The Lancet Oncology | Year: 2014
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 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 assigned (1:1:1) to receive either chemotherapy alone, chemotherapy with sequential GV1001 (sequential chemoimmunotherapy), or chemotherapy with concurrent GV1001 (concurrent chemoimmunotherapy). Treatments were allocated with equal probability by means of computer-generated random permuted blocks of sizes 3 and 6 in equal proportion. Chemotherapy included six cycles of gemcitabine (1000 mg/m2, 30 min intravenous infusion, at days 1, 8, and 15) and capecitabine (830 mg/m2 orally twice daily for 21 days, repeated every 28 days). Sequential chemoimmunotherapy included two cycles of combination chemotherapy, then an intradermal lower abdominal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF; 75 μg) and GV1001 (0·56 mg; days 1, 3, and 5, once on weeks 2-4, and six monthly thereafter). Concurrent chemoimmunotherapy included giving GV1001 from the start of chemotherapy with GM-CSF as an adjuvant. The primary endpoint was overall survival; analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN4382138. Findings: The first patient was randomly assigned to treatment on March 29, 2007, and the trial was terminated on March 27, 2011. Of 1572 patients screened, 1062 were randomly assigned to treatment (358 patients were allocated to the chemotherapy group, 350 to the sequential chemoimmunotherapy group, and 354 to the concurrent chemoimmunotherapy group). We recorded 772 deaths; the 290 patients still alive were followed up for a median of 6·0 months (IQR 2·4-12·2). Median overall survival was not significantly different in the chemotherapy group than in the sequential chemoimmunotherapy group (7·9 months [95% CI 7·1-8·8] vs 6·9 months [6·4-7·6]; hazard ratio [HR] 1·19, 98·25% CI 0·97-1·48, p=0·05), or in the concurrent chemoimmunotherapy group (8·4 months [95% CI 7·3-9·7], HR 1·05, 98·25% CI 0·85-1·29, p=0·64; overall log-rank of χ2 2df=4·3; p=0·11). The commonest grade 3-4 toxic effects were neutropenia (68 [19%] patients in the chemotherapy group, 58 [17%] patients in the sequential chemoimmunotherapy group, and 79 [22%] patients in the concurrent chemoimmunotherapy group; fatigue (27 [8%] in the chemotherapy group, 35 [10%] in the sequential chemoimmunotherapy group, and 44 [12%] in the concurrent chemoimmunotherapy group); and pain (34 [9%] patients in the chemotherapy group, 39 [11%] in the sequential chemoimmunotherapy group, and 41 [12%] in the concurrent chemoimmunotherapy group). Interpretation: Adding GV1001 vaccination to chemotherapy did not improve overall survival. New strategies to enhance the immune response effect of telomerase vaccination during chemotherapy are required for clinical efficacy. Funding: Cancer Research UK and KAEL-GemVax. © 2014 Elsevier Ltd.
Agency: Cordis | Branch: H2020 | Program: IA | Phase: FTIPilot-01-2016 | Award Amount: 3.13M | Year: 2017
Medication errors occur daily and form a major burden to society. Medication errors often lead to adverse drug reactions, lengthened hospital stays, increased healthcare costs, and in the most severe cases, increased mortality. Medication errors pose a significant risk to the European population. It is estimated that 4,7 million Europeans are harmed by a medication error every year, which amounts to preventable healthcare costs in excess of 11 billion a year. Strikingly, around 50% of medication errors can be stopped at the patients bedside. MedEye is an innovative medication verification suite that scans, detects and verifies medication at the bedside. MedEye stops medication errors from taking place by verifying medication before it is administered to patients. MedEye has already been tested and validated in three Dutch hospitals with excellent results. In this project, activities will be performed to push MedEye onto the European market and facilitate its deployment on a large scale. MedEye will be integrated with IT systems that serve a major part of European medical centers. Developments will also be performed to enable the sale, deployment and support of MedEye through distributors. Two launching pilots will be performed to establish transnational proof of performance and cost-effectiveness, which will be instrumental in penetrating the European markets. Given the diversity of the European healthcare landscape, a thorough market research will be performed to gear the commercialization strategy towards individual countries. Together, the activities in this project will provide access to the main EU market and facilitate a wide deployment of MedEye throughout Europe.
Taylor R.,Newcastle University |
Taylor R.,The Newcastle upon Tyne Hospitals NHS Foundation Trust |
Batey D.,The Newcastle upon Tyne Hospitals NHS Foundation Trust
Handbook of Retinal Screening in Diabetes: Diagnosis and Management | Year: 2012
Beginning with chapters summarizing the basics of diabetic retinopathy, this updated volume outlines the need for screening, how to screen safely and correctly, and the normal condition of the retina without diabetic retinopathy, all using excellent line and halftone illustrations. The core focus then moves on to examining each different form of retinopathy, all supported by outstanding color retinal photographs illustrating the appearance of the retina at various stages of retinopathy, plus an analysis on the best treatment for each stage. The book ends with chapters providing self-assessment questions of the type that screeners will encounter when gaining their now mandatory retinal screening qualifications, as well as a background information chapter offering advice on related UK, European, and US organizations. A website contains all the full-color retinopathy images from the book, with the option to download these into presentations. © 2012 John Wiley & Sons, Ltd.
Smith L.A.,Medical Research Matters |
Cornelius V.R.,Medical Research Matters |
Plummer C.J.,Freeman Hospital |
Levitt G.,Great Ormond St Hospital for Sick Children NHS Trust |
And 3 more authors.
BMC Cancer | Year: 2010
Background: We conducted a systematic review and meta-analysis to clarify the risk of early and late cardiotoxicity of anthracycline agents in patients treated for breast or ovarian cancer, lymphoma, myeloma or sarcoma.Methods: Randomized controlled trials were sought using comprehensive searches of electronic databases in June 2008. Reference lists of retrieved articles were also scanned for additional articles. Outcomes investigated were early or late clinical and sub-clinical cardiotoxicity. Trial quality was assessed, and data were pooled through meta-analysis where appropriate.Results: Fifty-five published RCTs were included; the majority were on women with advanced breast cancer. A significantly greater risk of clinical cardiotoxicity was found with anthracycline compared with non-anthracycline regimens (OR 5.43 95% confidence interval: 2.34, 12.62), anthracycline versus mitoxantrone (OR 2.88 95% confidence interval: 1.29, 6.44), and bolus versus continuous anthracycline infusions (OR 4.13 95% confidence interval: 1.75, 9.72). Risk of clinical cardiotoxicity was significantly lower with epirubicin versus doxorubicin (OR 0.39 95% confidence interval: 0.20, 0.78), liposomal versus non-liposomal doxorubicin (OR 0.18 95% confidence interval: 0.08, 0.38) and with a concomitant cardioprotective agent (OR 0.21 95% confidence interval: 0.13, 0.33). No statistical heterogeneity was found for these pooled analyses. A similar pattern of results were found for subclinical cardiotoxicity; with risk significantly greater with anthracycline containing regimens and bolus administration; and significantly lower risk with epirubicin, liposomal doxorubicin versus doxorubicin but not epirubicin, and with concomitant use of a cardioprotective agent. Low to moderate statistical heterogeneity was found for two of the five pooled analyses, perhaps due to the different criteria used for reduction in Left Ventricular Ejection Fraction. Meta-analyses of any cardiotoxicity (clinical and subclinical) showed moderate to high statistical heterogeneity for four of five pooled analyses; criteria for any cardiotoxic event differed between studies. Nonetheless the pattern of results was similar to those for clinical or subclinical cardiotoxicity described above.Conclusions: Evidence is not sufficiently robust to support clear evidence-based recommendations on different anthracycline treatment regimens, or for routine use of cardiac protective agents or liposomal formulations. There is a need to improve cardiac monitoring in oncology trials. © 2010 Smith et al; licensee BioMed Central Ltd.
Ding Z.-Y.,Huazhong University of Science and Technology |
Jin G.-N.,Huazhong University of Science and Technology |
Wang W.,Huazhong University of Science and Technology |
Chen W.-X.,Huazhong University of Science and Technology |
And 11 more authors.
Hepatology | Year: 2014
Transcriptional intermediary factor 1 gamma (TIF1γ) may play either a potential tumor-suppressor or -promoter role in cancer. Here we report on a critical role of TIF1γ in the progression of hepatocellular carcinoma (HCC). Reduced expression of TIF1γ was detected in HCC, especially in advanced HCC tissues, compared to adjacent noncancerous tissues. HCC patients with low TIF1γ expression had shorter overall survival times and higher recurrence rates than those with high TIF1γ expression. Reduced TIF1γ expression was an independent and significant risk factor for recurrence and survival after curative resection. In HCC cells, TIF1γ played a dual role: It promoted tumor growth in early-stage HCC, but not in advanced-stage HCC, whereas it inhibited invasion and metastasis in both early- and advanced-stage HCC. Mechanistically, we confirmed that TIF1γ inhibited transforming growth factor-β/ Drosophila mothers against decapentaplegic protein (TGF-β/Smad) signaling through monoubiquitination of Smad4 and suppressed the formation of Smad2/3/4 complex in HCC cells. TGF-β-inducing cytostasis and metastasis were both inhibited by TIF1γ in HCC. We further proved that TIF1γ suppressed cyotstasis-related TGF-β/Smad downstream c-myc down-regulation, as well as p21/cip1 and p15/ink4b up-regulation in early-stage HCC. Meanwhile, TGF-β inducible epithelial-mesenchymal transition and TGF-β/Smad downstream metastatic cascades, including phosphatase and tensin homolog deleted on chromosome ten down-regulation, chemokine (CXC motif) receptor 4 and matrix metalloproteinase 1 induction, and epidermal growth factor receptor- and protein kinase B-signaling transactivation, were inhibited by TIF1γ. In addition, we found that the down-regulation of TIF1γ in HCC was caused by hypermethylation of CpG islands in the TIF1γ promoter, and demonstrated that the combination of TIF1γ and phosphorylated Smad2 was a more powerful predictor of poor prognosis. Conclusion: TIF1γ regulates tumor growth and metastasis through inhibition of TGF-β/Smad signaling and may serve as a novel prognostic biomarker in HCC. (Hepatology 2014;60:1620-1636) © 2014 by the American Association for the Study of Liver Diseases.
Snaith V.J.,The Newcastle upon Tyne Hospitals NHS Foundation Trust |
Hewison J.,University of Leeds |
Steen I.N.,Northumbria University |
Robson S.C.,Northumbria University
BMC Pregnancy and Childbirth | Year: 2014
Background: The number of routine antenatal visits provided to low risk nulliparous women has been reduced in the UK, acknowledging this change in care may result in women being less satisfied with their care and having poorer psychosocial outcomes. The primary aim of the study was to investigate whether the provision of proactive telephone support intervention (TSI) with and without uterine artery Doppler screening (UADS) would reduce the total number of antenatal visits required. A secondary aim was to investigate whether the interventions affected psychological outcomes.Methods: A three-arm randomised controlled trial involving 840 low risk nulliparous women was conducted at a large maternity unit in North East England. All women received antenatal care in line with current UK guidance. Women in the TSI group (T) received calls from a midwife at 28, 33 and 36 weeks and women in the telephone and Doppler group (T + D) received the TSI and additional UADS at 20 weeks' gestation. The main outcome measure was the total number of scheduled and unscheduled antenatal visits received after 20 weeks' gestation.Results: The median number of unscheduled (n = 2.0), scheduled visits (n = 7.0) and mean number of total visits (n = 8.8) were similar in the three groups. The majority (67%) of additional antenatal visits were made to a Maternity Assessment Unit because of commonly occurring pregnancy complications. Additional TSI+/-UADS was not associated with differences in clinical outcomes, levels of anxiety, social support or satisfaction with care. There were challenges to the successful delivery of the telephone support intervention; 59% of women were contacted at 29 and 33 weeks gestation reducing to 52% of women at 37 weeks.Conclusions: Provision of additional telephone support (with or without UADS) in low risk nulliparous women did not reduce the number of unscheduled antenatal visits or reduce anxiety. This study provides a useful insight into the reasons why this client group attend for unscheduled visits.Trial registration: ISRCTN62354584. © 2014 Snaith et al.; licensee BioMed Central Ltd.
Effectiveness of cognitive behavioural therapy (CBT) interventions for anxiety in patients with chronic obstructive pulmonary disease (COPD) undertaken by respiratory nurses: The COPD CBT CARE study: (ISRCTN55206395)
Heslop K.,The Newcastle upon Tyne Hospitals NHS Foundation Trust |
Heslop K.,Northumbria University |
Newton J.,Biomedical Research Center in Ageing and Chronic Disease |
Baker C.,The Newcastle upon Tyne Hospitals NHS Foundation Trust |
And 3 more authors.
BMC Pulmonary Medicine | Year: 2013
Background: Anxiety and depression are common co-morbidities in patients with chronic obstructive pulmonary disease (COPD). Serious implications can result from psychological difficulties in COPD including reduced survival, lower quality of life, and reduced physical and social functioning, increased use of health care resources and are associated with unhealthy behaviours such as smoking. Cognitive behavioural therapy (CBT) is a psychological intervention which is recommended for the treatment of many mental health problems including anxiety and depression. Unfortunately access to trained CBT therapists is limited. The aim of this study is to test the hypothesis that CBT delivered by respiratory nurses is effective in the COPD population. In this paper the design of the Newcastle Chronic Obstructive Pulmonary Disease Cognitive Behavioural Therapy Study (Newcastle COPD CBT Care Study) is described.Methods/Design: This is a prospective open randomised controlled trial comparing CBT with self-help leaflets. The primary outcome measure is the Hospital Anxiety & Depression Scale (HADS) - anxiety subscale. Secondary outcome measures include disease specific quality of life COPD Assessment Tool (CAT), generic quality of life (EQ5D) and HADS-depression subscale. Patients will be followed up at three, six and 12 months following randomisation.Discussion: This is the first randomised controlled trial to evaluate the use of cognitive behavioural therapy undertaken by respiratory nurses. Recruitment has commenced and should be complete by February 2014. Trial registration: Current Controlled Trials, ISRCTN55206395. © 2013 Heslop et al.; licensee BioMed Central Ltd.
Abley C.,The Newcastle upon Tyne Hospitals NHS Foundation Trust
Nursing standard (Royal College of Nursing (Great Britain) : 1987) | Year: 2012
Patient-centred care is a term widely used in health policy and is familiar to staff as a principle or commonly agreed approach to care. However, nursing and multidisciplinary teams often do not agree how it should be provided for older patients. This article outlines three different models of patient-centred care applicable to the care of older people. The article also explores the concept of vulnerability in old age, highlighting differences between the perspectives of older people and those of professionals and how clinical practice can be improved to achieve a more patient-centred approach. The links between patient-centred care and vulnerability in old age are considered along with the implications of this for clinical practice.
McGregor A.,The Newcastle upon Tyne Hospitals NHS Foundation Trust
BMJ case reports | Year: 2012
The authors describe a 28-year-old woman with newly diagnosed acute promyelocytic leukaemia (APL), who developed junctional bradycardia after receiving the molecular-targeted therapy all-trans retinoic acid (ATRA) and the anthracycline-based chemotherapeutic agent idarubicin following sepsis and the APL differentiation syndrome. The patient was asymptomatic of the bradycardia. Electrolytes and cardiac imaging were unremarkable. No other cases have been reported in this context and the mechanisms of the sinus node dysfunction are unclear. The patient achieved normal sinus rhythm after ATRA was withheld. The patient recovered and went on to achieve complete remission after re-starting ATRA and idarubicin.
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust | Date: 2012-06-14
An apparatus for performing haemodialysis on a patient comprises: first blood transfer means (3) for selectively withdrawing blood from a patient and storing it in a first storage portion (5); second blood transfer means (11) for removing filtered blood from a filtration device (7) and storing it in a second storage portion (13); and a fluid measurement system (51a, 51b) for periodically measuring the respective volumes of blood in the first and second storage portions; adding the volume of blood in the first storage portion to the volume of blood in the second storage portion at that time in order to calculate the total volume of blood within the first and second storage portions at that time; and comparing the total measured volumes of blood within the first and second storage portions measured over a predetermined time interval to calculate the volume of fluid removed from the blood during that predetermined time interval.