Papers by Chris Winchester
Open Pharma one-page summary
On June 15, 2020, current and prospective Members and Supporters of Open Pharma and a group of Ad... more On June 15, 2020, current and prospective Members and Supporters of Open Pharma and a group of Advisers met for a virtual roundtable meeting to discuss US perspectives on open access and the reach of the Open Pharma position statement, the ways in which patients access and discover medical research, how the use of an ORCID iD can build research trust and accountability, and the value of plain language summaries and preprints.
Research Integrity and Peer Review
Background Structured, systematic methods to formulate consensus recommendations, such as the Del... more Background Structured, systematic methods to formulate consensus recommendations, such as the Delphi process or nominal group technique, among others, provide the opportunity to harness the knowledge of experts to support clinical decision making in areas of uncertainty. They are widely used in biomedical research, in particular where disease characteristics or resource limitations mean that high-quality evidence generation is difficult. However, poor reporting of methods used to reach a consensus – for example, not clearly explaining the definition of consensus, or not stating how consensus group panellists were selected – can potentially undermine confidence in this type of research and hinder reproducibility. Our objective is therefore to systematically develop a reporting guideline to help the biomedical research and clinical practice community describe the methods or techniques used to reach consensus in a complete, transparent, and consistent manner. Methods The ACCORD (ACcura...
Medical Writing, 2018
Can we predict neo-adjuvant therapy response in patients with osteosarcoma? O steosarcoma (OS) is... more Can we predict neo-adjuvant therapy response in patients with osteosarcoma? O steosarcoma (OS) is a malignant primary tumor of bone affecting adolescents and young adults. There are few if any molecular markers to predict its behavior and prognosis. In our study we investigated the relationship of expression of different molecular markers in osteosarcoma tumors before treatment to pathologic necrotic response after neo-adjuvant chemotherapy. In summary, deletion of RB1 (72%), gain of RUNX2 (68%), deletion of TP53 (52%), deletion 18q23 (48%) by molecular studies and p16-negative by IHC (38%) were common findings. Most abnormalities, particularly RB1 and TP53 deletions and RUNX2 gain, did not correlate with chemotherapy response. IHC p16-negative status correlated strongly with failed chemotherapy response (15/40). Alterations of 18q correlated slightly with poor response (p=0.0796). Poor response cases included 3 cases with deletion of 18q23, 3 cases with LOH for 18q23 and 1 case with copy gain (trisomy 18). Comparison of 18q genomic abnormalities in cases with a favorable versus poor response suggested a smallest region of overlap for a negative factor at 18q23. In conclusion we identified complex genotypes in the OS samples with frequent occurrence of previously identified biomarkers such as deletion RB1, deletion TP53, deletion 18q23 and gain of RUNX2. Comparison of genomic findings to p16negative status and chemotherapy response revealed p16-negative status to be the best overall indicator of a poor chemotherapy response, with the poorest responders being both p16 negative and altered for 18q23. Additional studies are warranted to validate these findings and further characterize the role of CDKN2A and other factors that influence response to therapy in osteosarcoma patients.
During Open Access Week 2020, Open Pharma launched a set of educational slides that can be used i... more During Open Access Week 2020, Open Pharma launched a set of educational slides that can be used in conversations and engagements advocating for open access and the open science movement.<br>
General practice and primary care, 2019
Objective: We evaluated compliance of recent narrative systematic reviews with the preferred repo... more Objective: We evaluated compliance of recent narrative systematic reviews with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidance. Research design and methods: We searched EMBASE and MEDLINE databases on 21-September-2017, for English-language records with a print publication date of 01-June-2017, for "systematic review" (in the title field) and terms relating to drug therapy (in the subject field). Case studies, conference reports, letters, surveys, errata, editorials, and meta-analyses were excluded. A manual screen excluded protocols and reports providing statistical analysis. Articles were scored for fulfilment of PRISMA checklist items for the objectives, methods (information sources, search, study selection), and results (study selection, study characteristics), and whether they reference PRISMA. Results: Of the 99 abstracts identified, 46 (46.5%) were selected for analysis. Reasons for exclusion were: not drug related (n ¼ 35), statistical analysis conducted (n ¼ 10), protocol (n ¼ 7), and not in English (n ¼ 1). Twenty-seven (58.7%) publications did not fully adhere to our set of PRISMA items. More than 82% of publications appropriately reported on objectives, information sources, and study selection (methods) items, whereas 76.1% and 50.0% reported study selection (results) and search items, respectively. Publications citing PRISMA (n ¼ 28; 60.8%) tended to report on more items with the exception of search criteria. Conclusions: Just over half of these recent publications described as systematic reviews did not follow PRISMA criteria, despite referencing them. These findings suggest a need for improvement in performing systematic reviews and/or reporting how they were conducted. Such improvements may lead to greater confidence in the findings of systematic reviews.
Experimental Hematology, 1999
We previously demonstrated that lysis of tumor cells that express Hsp70, the highly stress-induci... more We previously demonstrated that lysis of tumor cells that express Hsp70, the highly stress-inducible member of the HSP70 family, on their plasma membrane is mediated by natural killer (NK) cells. Here, we studied the effects of different proteins of the HSP70 family in combination with interleukin 2 (IL-2) on the proliferation and cytotoxic activity of human NK cells in vitro. Proliferation of NK cells was significantly enhanced by human recombinant Hsp70 (rHsp70) and to a lesser extent by rHsp70homC, the recombinant C-terminal peptidebinding domain derived from Hsp70hom, but not by the constitutive Hsc70 or DnaK, the Escherichia coli analogue of human Hsp70. Even rHsp70 protein alone moderately enhances proliferation and cytolytic activity of NK cells, thus indicating that the stimulatory effect is not strictly dependent on IL-2. NK cells stimulated with rHsp70 protein also exhibit an increased secretion of interferon ␥ (IFN-␥ ). The phenotypic characterization of NK cells with specificity for Hsp70expressing tumor cells revealed a CD16 dim /CD56 bright and increased CD57 and CD94 expression. The cytolytic activity of NK cells also was significantly reduced when a CD94-specific antibody or rHsp70 was added directly before the cytotoxicity assay, whereas other antibodies directed against CD57 and major histocompatibility complex class I molecules or Hsp70 proteins, including Hsc70 and DnaK, did not affect the NKmediated killing. However, long-term incubation of NK cells with rHsp70 protein enhances not only the proliferative but also the cytolytic response against Hsp70-expressing tumor cells. Our results indicate that the C-terminal domain of Hsp70 protein affects not only the proliferative but also the cytolytic activity of a phenotypically distinct NK cell population with specificity for Hsp70-expressing tumor cells.
Question 2: At which congresses did e-posters receive the most attention? Question 4: What is the... more Question 2: At which congresses did e-posters receive the most attention? Question 4: What is the geographical spread of individuals accessing the Shire Congress Posters platform? Conclusions USA 40.4% UK 24.1% Countries where individuals were located at the time when they accessed the Shire Congress Posters platform
Chest, Oct 1, 2009
More prospective studies are needed to assess the predictors of benefit for PR in patients with I... more More prospective studies are needed to assess the predictors of benefit for PR in patients with ILD (and COPD) that are hypothesis driven as opposed to data driven. Unfortunately, this study does not provide strong enough evidence to support prescribing PR for patients with ILD based on their characteristics such as baseline values for 6MWD.
Gut, 2013
To update the findings of the 2005 systematic review of population-based studies assessing the ep... more To update the findings of the 2005 systematic review of population-based studies assessing the epidemiology of gastro-oesophageal reflux disease (GERD). PubMed and Embase were screened for new references using the original search strings. Studies were required to be population-based, to include ≥ 200 individuals, to have response rates ≥ 50% and recall periods &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;12 months. GERD was defined as heartburn and/or regurgitation on at least 1 day a week, or according to the Montreal definition, or diagnosed by a clinician. Temporal and geographic trends in disease prevalence were examined using a Poisson regression model. 16 studies of GERD epidemiology published since the original review were found to be suitable for inclusion (15 reporting prevalence and one reporting incidence), and were added to the 13 prevalence and two incidence studies found previously. The range of GERD prevalence estimates was 18.1%-27.8% in North America, 8.8%-25.9% in Europe, 2.5%-7.8% in East Asia, 8.7%-33.1% in the Middle East, 11.6% in Australia and 23.0% in South America. Incidence per 1000 person-years was approximately 5 in the overall UK and US populations, and 0.84 in paediatric patients aged 1-17 years in the UK. Evidence suggests an increase in GERD prevalence since 1995 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), particularly in North America and East Asia. GERD is prevalent worldwide, and disease burden may be increasing. Prevalence estimates show considerable geographic variation, but only East Asia shows estimates consistently lower than 10%.
BACKGROUND • Real world evidence (RWE) studies are becoming increasingly important throughout the... more BACKGROUND • Real world evidence (RWE) studies are becoming increasingly important throughout the life cycle of a medicine. They are less well known, however, than randomized controlled trials (RCTs), which are often referred to as the 'gold standard' of evidence. • Our aim is to describe the pattern of knowledge of RWE in our industry, starting with a survey of ISMPP members.
BACKGROUND • Real world evidence (RWE) studies are becoming increasingly important throughout the... more BACKGROUND • Real world evidence (RWE) studies are becoming increasingly important throughout the life cycle of a medicine. They are less well known, however, than randomized controlled trials (RCTs), which are often referred to as the 'gold standard' of evidence. • Our aim is to describe the pattern of knowledge of RWE in our industry, starting with a survey of ISMPP members.
Integrative Medicine Research
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Papers by Chris Winchester