Braganza J.M.,Royal Infirmary |
Lee S.H.,Royal Infirmary |
McCloy R.F.,Lancashire Teaching Hospitals |
McMahon M.J.,University of Leeds
The Lancet | Year: 2011
Chronic pancreatitis is a progressive fibroinflammatory disease that exists in large-duct (often with intraductal calculi) or small-duct form. In many patients this disease results from a complex mix of environmental (eg, alcohol, cigarettes, and occupational chemicals) and genetic factors (eg, mutation in a trypsin-controlling gene or the cystic fibrosis transmembrane conductance regulator); a few patients have hereditary or autoimmune disease. Pain in the form of recurrent attacks of pancreatitis (representing paralysis of apical exocytosis in acinar cells) or constant and disabling pain is usually the main symptom. Management of the pain is mainly empirical, involving potent analgesics, duct drainage by endoscopic or surgical means, and partial or total pancreatectomy. However, steroids rapidly reduce symptoms in patients with autoimmune pancreatitis, and micronutrient therapy to correct electrophilic stress is emerging as a promising treatment in the other patients. Steatorrhoea, diabetes, local complications, and psychosocial issues associated with the disease are additional therapeutic challenges. © 2011 Elsevier Ltd.
Fowler S.J.,University of Manchester |
Fowler S.J.,Lancashire Teaching Hospitals |
Basanta-Sanchez M.,University of Manchester |
Xu Y.,University of Manchester |
And 3 more authors.
Thorax | Year: 2015
Background Healthcare associated infections, including ventilator associated pneumonia, are difficult to diagnose and treat, and are associated with significant morbidity, mortality and cost. We aimed to demonstrate proof of concept that breath volatile profiles were associated with the presence of clinically relevant pathogens in the lower respiratory tract. Methods Patients with sterile brain injury requiring intubation and ventilation on the intensive care unit were eligible for inclusion. Serial clinical and breath data were obtained three times a week, from admission up to a maximum of 10 days. Bronchial lavage for semiquantitative culture was collected immediately prior to breath sampling. Breath samples were collected in triplicate for off-line analysis by thermal-desorption/gas chromatography/time-of-flight mass spectrometry. Breath data were recorded as retention time/mass ion pairs, and analysed ( pathogen present vs absent) by ANOVA-mean centre principal component analysis. Results Samples were collected from 46 patients (mean (SD) age 49 (19) years; 27 male). The dominant factors affecting breath sample analysis were the individual breath profile and duration of intubation. When these were taken into account, clear separation was seen between breath profiles at each time point by the presence/absence of pathogens. Loadings plots identified consistent metabolite peaks contributing to this separation at each time point. Conclusions Breath volatile analysis is able to classify breath profiles of patients with and without significant pathogen load in the lower respiratory tract. If validated in independent cohorts, these findings could lead to development of rapid non-invasive point-ofcare surveillance systems and diagnostics for lower respiratory tract infection in the intensive care unit.
Bhalme M.,St James's Hospital |
Sharma A.,Lancashire Teaching Hospitals |
Keld R.,Leigh NHS Foundation Trust |
Willert R.,University of Manchester |
Campbell S.,University of Manchester
European Journal of Gastroenterology and Hepatology | Year: 2013
BACKGROUND: Adalimumab (ADA) is a subcutaneous anti-tumour necrosis factor (anti-TNF) agent, effective in inducing and maintaining remission in Crohn's disease (CD). Unlike Infliximab (IFX), ADA dosing is not weight adjusted and dose frequency is based on clinical response. AIM: To determine whether obesity is a risk factor for early loss of response (LOR) to anti-TNF treatment and whether weight-adjusted anti-TNF treatment is favourable. MATERIALS AND METHODS: A hospital database of CD patients receiving anti-TNF treatment was analyzed retrospectively. The relationship between time to LOR and BMI was examined by Kaplan-Meier (KM) survival curves and a Cox proportional hazards model. RESULTS: ADA patients: Of the 54 patients (46 BMI<30 and 8 BMI≥30), KM estimation indicated a significantly shorter time to dose escalation in the BMI of at least 30 (χ=6.117, P=0.01). The Cox proportional hazards model showed that an increased hazard of LOR to ADA is related to increases in BMI (P=0.04). IFX patients: Of the 76 patients (62 BMI<30 and 14 BMI≥30), KM estimation showed that the differences in survival curves were not significant (χ=1.933, P=0.16) for the BMI groups. This was supported by the Cox proportional hazard model (P=0.36). CONCLUSION: BMI appears to be important in predicting ADA efficacy (LOR) in CD. IFX appears to overcome this reduction of efficacy in obese patients. A prospective study evaluating the effect of weight on anti-TNF drug response and serum drug levels is warranted. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Clark R.L.,Lancashire Teaching Hospitals |
Bowling F.L.,University of Manchester |
Fergus Jepson,Lancashire Teaching Hospitals |
Rajbhandari S.,Lancashire Teaching Hospitals
Pain | Year: 2013
There is a commonly held belief that diabetic amputees experience less phantom limb pain than nondiabetic amputees because of the effects of diabetic peripheral neuropathy; however, evidence to verify this claim is scarce. In this study, a customised postal questionnaire was used to examine the effects of diabetes on the prevalence, characteristics, and intensity of phantom limb pain (PLP) and phantom sensations (PS) in a representative group of lower-limb amputees. Participants were divided into those who had self-reported diabetes (DM group) and those who did not (ND group). Participants with diabetes were further divided into those with long-duration diabetes (>10 years) and those with short-duration diabetes. Two hundred questionnaires were sent, from which 102 responses were received. The overall prevalence of PLP was 85.6% and there was no significant difference between the DM group (82.0%) and the ND group (89.4%) (P = 0.391). There was also no difference in the prevalence of PS: DM group (66.0%), ND group (70.2%) (P = 0.665). The characteristics of the pain were very similar in both groups, with sharp/stabbing pain being most common. Using a 0-10 visual analogue scale, the average intensity of PLP was 3.89 (±0.40) for the DM group and 4.38 (±0.41) for the ND group, which was not a statistically significant difference (P = 0.402). Length of time since diagnosis of diabetes showed no correlation with average PLP intensity. Our findings suggest that there is no large difference in the prevalence, characteristics, or intensity of PLP when comparing diabetic and nondiabetic amputees, though a larger adjusted comparison would be valuable. © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Gore R.B.,University of Manchester |
Gore R.B.,Lancashire Teaching Hospitals
Current Opinion in Pulmonary Medicine | Year: 2010
Purpose of review: Recent work demonstrates that patients with refractory asthma are likely to be sensitized to environmental fungi and that specific antifungal treatments may be of benefit to this group. Recent findings: The relationships among fungal sensitization, exposure and asthma severity are imperfectly understood. Exposure to environmental fungi occurs ubiquitously and there is emerging evidence that internal airways colonization could be a source of ongoing exposure. Antifungal treatments appear to improve asthma-related quality of life. Such treatments are generally well tolerated but there are potential side-effects. The mechanisms behind the clinical improvements are not yet fully established. Summary: Antifungal treatments are used in some centres for patients with refractory asthma. Further research needs to explore the questions of patient selection, optimum duration of therapy and the prediction and management of azole-corticosteroid drug interactions. Advances in our understanding of the fungal molecular allergome and in our understanding of the allergic importance of small hyphal fragments may help to more precisely define the relationships among fungal sensitization, exposure and asthma severity. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Bahl A.,University of Bristol |
Masson S.,University of Bristol |
Birtle A.,Lancashire Teaching Hospitals |
Chowdhury S.,Guys and St Thomas NHS Foundation Trust |
de Bono J.,The Institute of Cancer Research and Royal Marsden NHS Foundation Trust
Cancer Treatment Reviews | Year: 2014
Standard first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) is docetaxel plus prednisone; however, patients will usually experience disease progression during or after docetaxel treatment due to inherent or acquired resistance. Before 2010, second-line options for mCRPC were limited. However, cabazitaxel, abiraterone acetate and enzalutamide have since been approved for patients with mCRPC whose disease has progressed during or after receiving docetaxel, based on the Phase III trials TROPIC, COU-AA-301 and AFFIRM. In all three trials, an overall survival benefit (primary endpoint) was seen in the experimental arm compared with the control arm: 15.1 vs. 12.7. months for cabazitaxel plus prednisone compared with mitoxantrone plus prednisone in TROPIC (hazard ratio [HR] 0.70; P<. 0.0001); 14.8 vs. 10.9. months for abiraterone acetateplus prednisone compared with placebo plus prednisone in COU-AA-301 (HR 0.65; P<. 0.001); and 18.4 vs. 13.6. months for enzalutamide compared with placebo alone in AFFIRM (0.63; P<. 0.001). However, differences in patient populations, comparators, and selection and/or definition of secondary endpoints make it difficult to draw direct cross-trial comparisons. Radium-223 dichloride has also been approved for patients with mCRPC with metastases to bone but not other organs. To date, no comparative trials or sequencing studies with newer agents have been performed. Without such data, treatment decisions must be based on evaluation of the existing evidence. This commentary compares and contrasts study designs and key data from each of these Phase III trials, and also discusses recent and ongoing clinical trials with new agents in the first- and second-line settings in mCRPC. © 2013 The Authors.
Nwosu A.C.,University of Liverpool |
Debattista M.,Lancashire Teaching Hospitals |
Rooney C.,The Christie NHS Foundation Trust |
Mason S.,University of Liverpool
BMJ Supportive and Palliative Care | Year: 2015
Background: Social media describes technological applications which are used to exchange information in a virtual environment. The use of social media is increasing, in professional and social contexts, on a variety of platforms such as Twitter; however, the scope and breadth of its use to discuss end-of-life care has not previously been reported. Aims: To determine the frequency, sentiment and trend of Twitter 'tweets' containing palliative care-related identifiers (hashtags) and/or phrases sent by users over a 2-year period. Methods: A 2-year retrospective analysis of Twitter posts (tweets), between the 1 August 2011 to 31 July 2013, using a social media analytics tool: TopsyPro. Thirteen search terms were identified and analysed for tweet volume, frequency, sentiment and acceleration. Results: A total of 683.5K tweets containing a combination of 13 palliative care terms were analysed. The tweet volume for all terms increased by 62.3%between 2011-2012 (262.5K) and 2012-2013 (421K). The most popular terms include 'end-of-life' (210K), #hpm (114K) and 'palliative care' (93.8K). Sentiment was high with 89%of tweets rated more positive than all other tweets sent on Twitter during this period. The term 'Liverpool Care Pathway' experienced the highest percentage increase in tweets (55% increase) reaching a peak in July 2013. Conclusions: A lot of discussion about palliative care is taking place on Twitter, and the majority of this is positive. Social media presents a novel opportunity for engagement and ongoing dialogue with public and professional groups.
Bezecny P.,Lancashire Teaching Hospitals
Medical Oncology | Year: 2014
Epigenetic mechanisms are increasingly recognized as a major factor contributing to pathogenesis of cancer including glioblastoma, the most common and most malignant primary brain tumour in adults. Enzymatic modifications of histone proteins regulating gene expression are being exploited for therapeutic drug targeting. Over the last decade, numerous studies have shown promising results with histone deacetylase (HDAC) inhibitors in various malignancies. This article provides a brief overview of mechanism of anti-cancer effect and pharmacology of HDAC inhibitors and summarizes results from pre-clinical and clinical studies in glioblastoma. It analyses experience with HDAC inhibitors as single agents as well as in combination with targeted agents, cytotoxic chemotherapy and radiotherapy. Hallmark features of glioblastoma, such as uncontrolled cellular proliferation, invasion, angiogenesis and resistance to apoptosis, have been shown to be targeted by HDAC inhibitors in experiments with glioblastoma cell lines. Vorinostat is the most advanced HDAC inhibitor that entered clinical trials in glioblastoma, showing activity in recurrent disease. Multiple phase II trials with vorinostat in combination with targeted agents, temozolomide and radiotherapy are currently recruiting. While the results from pre-clinical studies are encouraging, early clinical trials showed only modest benefit and the value of HDAC inhibitors for clinical practice will need to be confirmed in larger prospective trials. Further research in epigenetic mechanisms driving glioblastoma pathogenesis and identification of molecular subtypes of glioblastoma is needed. This will hopefully lead to better selection of patients who will benefit from treatment with HDAC inhibitors. © Springer Science+Business Media 2014.
McKenzie L.H.,Lancaster University |
Simpson J.,Lancaster University |
Stewart M.,Lancashire Teaching Hospitals
Psychology, Health and Medicine | Year: 2010
In addition to the physical benefits, another important objective of coronary artery bypass graft (CABG) surgery is improvement of health-related quality of life. The aim of this systematic review is to provide an overview of the literature relating to the pre-operative prediction of post-operative depression and anxiety in individuals who have undergone CABG surgery. Forty-six studies were identified through a literature search of electronic databases conducted using explicit inclusion and exclusion criteria. The study characteristics, methodological features, and psychometric and clinical outcomes were summarised in a systematic manner. Collective appraisal of the studies indicated that symptoms of depression and anxiety exhibited after CABG surgery are best predicted by pre-operative measures of functioning in that area. Papers were inconclusive with respect to the predictive qualities of gender and age. Further research is required to clarify the predictive values of these and other factors, including pre-morbid ill health and socio-economic status. The findings of this review indicate a range of pre-operative predictors of post-operative depression and anxiety in patients with CABG. Chief among these are pre-operative depression and anxiety. These findings have clinical implications concerning the importance of pre and post-operative psychological assessment and intervention for individuals at risk of poor psychological recovery.
Spencer C.,Lancashire Teaching Hospitals |
Orr D.,Lancashire Teaching Hospitals |
Hallam S.,Lancashire Teaching Hospitals |
Tillmanns E.,Lancashire Teaching Hospitals
Journal of Hospital Infection | Year: 2013
Routine daily bathing of intensive care (ICU) patients with topical chlorhexidine reduces meticillin-resistant Staphylococcus aureus (MRSA) acquisition. The aim of this study was to investigate whether repeated five-day cycles of daily topical octenidine could result in a similar effect. This was a two-year retrospective, uncontrolled study in a mixed medical and surgical ICU/high dependency unit, demonstrating a 76% reduction in MRSA acquisition but no significant reduction in all ICU-acquired bacteraemias. Chlorhexidine use is increasing but resistance is being reported. This pilot study found a similar reduction in MRSA acquisition with octenidine as an alternative to chlorhexidine. Further study is required to establish causality. © 2012 The Healthcare Infection Society.