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Hammond E.M.,University of Oxford | Asselin M.-C.,Wolfson Molecular Imaging Center | Forster D.,Wolfson Molecular Imaging Center | O'Connor J.P.B.,Institute of Population Health | And 2 more authors.
Clinical Oncology | Year: 2014

Hypoxia was identified as a microenvironmental component of solid tumours over 60 years ago and was immediately recognised as a potential barrier to therapy through the reliance of radiotherapy on oxygen to elicit maximal cytotoxicity. Over the last two decades both clinical and experimental studies have markedly enhanced our understanding of how hypoxia influences cellular behaviour and therapy response. Furthermore, they have confirmed early assumptions that low oxygenation status in tumours is an exploitable target in cancer therapy. Generally such approaches will be more beneficial to patients with hypoxic tumours, necessitating the use of biomarkers that reflect oxygenation status. Tissue biomarkers have shown utility in many studies. Further significant advances have been made in the non-invasive measurement of tumour hypoxia with positron emission tomography, magnetic resonance imaging and other imaging modalities. Here, we describe the complexities of defining and measuring tumour hypoxia and highlight the therapeutic approaches to combat it. © 2014 The Royal College of Radiologists.

Whiting P.,University of Bristol | Whiting P.,National Health Research Institute | Whiting P.,Kleijnen Systematic Reviews Ltd | Savovic J.,University of Bristol | And 11 more authors.
Journal of Clinical Epidemiology | Year: 2016

Objective To develop ROBIS, a new tool for assessing the risk of bias in systematic reviews (rather than in primary studies). Study Design and Setting We used four-stage approach to develop ROBIS: define the scope, review the evidence base, hold a face-to-face meeting, and refine the tool through piloting. Results ROBIS is currently aimed at four broad categories of reviews mainly within health care settings: interventions, diagnosis, prognosis, and etiology. The target audience of ROBIS is primarily guideline developers, authors of overviews of systematic reviews ("reviews of reviews"), and review authors who might want to assess or avoid risk of bias in their reviews. The tool is completed in three phases: (1) assess relevance (optional), (2) identify concerns with the review process, and (3) judge risk of bias. Phase 2 covers four domains through which bias may be introduced into a systematic review: study eligibility criteria; identification and selection of studies; data collection and study appraisal; and synthesis and findings. Phase 3 assesses the overall risk of bias in the interpretation of review findings and whether this considered limitations identified in any of the phase 2 domains. Signaling questions are included to help judge concerns with the review process (phase 2) and the overall risk of bias in the review (phase 3); these questions flag aspects of review design related to the potential for bias and aim to help assessors judge risk of bias in the review process, results, and conclusions. Conclusions ROBIS is the first rigorously developed tool designed specifically to assess the risk of bias in systematic reviews. © 2016 The Authors. Published by Elsevier Inc.

El-Gohary M.,University of Southampton | Hay A.D.,University of Bristol | Coventry P.,Institute of Population Health | Coventry P.,University of Manchester | And 3 more authors.
Family Practice | Year: 2013

Background: Cough associated with acute respiratory tract infection (RTI) is one of the most common problems managed in primary care. Despite minimal evidence for the use of antibiotics, they continue to be prescribed at great cost and are a significant cause of emerging bacterial resistance. Objectives: To carry out a systematic review of randomized controlled trials to evaluate the effect of corticosteroid therapy in otherwise-healthy adults with acute RTI. Methods: Seven electronic databases and five ongoing trial registers were searched. Studies were eligible if they compared the use of any corticosteroid treatment against a control group in adults with an acute (<3 weeks) or subacute (<8 weeks) cough associated with an RTI but no asthma. Primary outcomes were differences in mean cough and other symptom scores. Secondary outcomes included adverse effects, subsequent diagnosis of asthma and patient satisfaction. Results: Four trials (335 participants) investigating the effects of inhaled corticosteroids were identified. None investigated the use of oral corticosteroids. Results were mixed, with two reporting equivalence and two reporting benefits for mean cough score (P = 0.012) and cough frequency (P = 0.047). One reported additional benefits in non-smokers. Adverse events were rare and there were no data on patient satisfaction or the subsequent diagnosis of asthma. Most trials were of unclear risk of bias. Study outcomes were too heterogeneous to meta-analyse. Conclusions: There is insufficient evidence to recommend the routine use of inhaled corticosteroids for acute RTI in adults. However, some trials have shown benefits, suggesting the need for further high-quality, adequately powered trials. © The Author 2013.

Morrison A.P.,University of Manchester | Turkington D.,Northumbria University | Pyle M.,University of Manchester | Spencer H.,Northumbria University | And 15 more authors.
The Lancet | Year: 2014

Background Antipsychotic drugs are usually the first line of treatment for schizophrenia; however, many patients refuse or discontinue their pharmacological treatment. We aimed to establish whether cognitive therapy was effective in reducing psychiatric symptoms in people with schizophrenia spectrum disorders who had chosen not to take antipsychotic drugs. Methods We did a single-blind randomised controlled trial at two UK centres between Feb 15, 2010, and May 30, 2013. Participants aged 16-65 years with schizophrenia spectrum disorders, who had chosen not to take antipsychotic drugs for psychosis, were randomly assigned (1:1), by a computerised system with permuted block sizes of four or six, to receive cognitive therapy plus treatment as usual, or treatment as usual alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. Our primary outcome was total score on the positive and negative syndrome scale (PANSS), which we assessed at baseline, and at months 3, 6, 9, 12, 15, and 18. Analysis was by intention to treat, with an ANCOVA model adjusted for site, age, sex, and baseline symptoms. This study is registered as an International Standard Randomised Controlled Trial, number 29607432. Findings 74 individuals were randomly assigned to receive either cognitive therapy plus treatment as usual (n=37), or treatment as usual alone (n=37). Mean PANSS total scores were consistently lower in the cognitive therapy group than in the treatment as usual group, with an estimated between-group effect size of -6·52 (95% CI -10·79 to -2·25; p=0·003). We recorded eight serious adverse events: two in patients in the cognitive therapy group (one attempted overdose and one patient presenting risk to others, both after therapy), and six in those in the treatment as usual group (two deaths, both of which were deemed unrelated to trial participation or mental health; three compulsory admissions to hospital for treatment under the mental health act; and one attempted overdose). Interpretation Cognitive therapy significantly reduced psychiatric symptoms and seems to be a safe and acceptable alternative for people with schizophrenia spectrum disorders who have chosen not to take antipsychotic drugs. Evidence-based treatments should be available to these individuals. A larger, definitive trial is needed. Copyright © Chatterjee et al.

Meehan S.,University of Nottingham | Beck C.R.,University of Nottingham | Mair-Jenkins J.,Institute of Population Health | Leonardi-Bee J.,University of Nottingham | Puleston R.,University of Nottingham
Pediatrics | Year: 2014

BACKGROUND AND OBJECTIVES: Despite numerous studies reporting an elevated risk of infant mortality among women who are obese, the magnitude of the association is unclear. A systematic review and metaanalysis was undertaken to assess the association between maternal overweight or obesity and infant mortality. METHODS: Four health care databases and gray literature sources were searched and screened against the protocol eligibility criteria. Observational studies reporting on the relationship between maternal overweight and obesity and infant mortality were included. Data extraction and risk of bias assessments were performed. RESULTS: Twenty-four records were included from 783 screened. Obese mothers (BMI ≥30) had greater odds of having an infant death (odds ratio 1.42; 95% confidence interval, 1.24-1.63; P <.001; 11 studies); these odds were greatest for the most obese (BMI >35) (odds ratio 2.03; 95% confidence interval, 1.61-2.56; P <.001; 3 studies). CONCLUSIONS: Our results suggest that the odds of having an infant death are greater for obese mothers and that this risk may increase with greater maternal BMI or weight; however, residual confounding may explain these findings. Given the rising prevalence of maternal obesity, additional high-quality epidemiologic studies to elucidate the actual influence of elevated maternal mass or weight on infant mortality are needed. If a causal link is determined and the biological basis explained, public health strategies to address the issue of maternal obesity will be needed. Copyright © 2014 by the American Academy of Pediatrics.

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