69 research outputs found
Factors influencing participation in randomised clinical trials among patients with early Barrett's neoplasia: a multicentre interview study
OBJECTIVES: Strong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett's neoplasia. This paper aims to identify factors influencing patients' participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy. DESIGN: A semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes. SETTING: Interview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted. PARTICIPANTS: We interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined. RESULTS: Four themes were identified centred around interviewees' decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant-recruiter relationship; (2) participants' views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants' perceptions of surgical risks versus less invasive treatments. CONCLUSION: We identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett's-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials
Acetic acid guided biopsies in Barrettâs surveillance for neoplasia detection versus non-targeted biopsies (Seattle protocol):a feasibility study for a randomised tandem endoscopy trial. The ABBA study.
Background and study aims - Barrettâs esophagus is a potentially pre-cancerous condition, affecting 375,000 people in the UK. Patients receive a 2-yearly endoscopy to detect cancerous changes, as early detection and treatment results in better outcomes. Current treatment requires random mapping biopsies along the length of Barrettâs, in addition to biopsy of visible abnormalities. As only 13 % of precancerous changes appear as visible nodules or abnormalities, areas of dysplasia are often missed. Acetic acid chromoendoscopy (AAC) has been shown to improve detection of pre-cancerous and cancerous tissue in observational studies, but no randomized controlled trials (RCTs) have been performed to date. Patients and methods - A âtandemâ endoscopy cross-overdesign. Participants will be randomized to endoscopy usingmapping biopsies or AAC, in which dilute acetic acid issprayed onto the surface of the esophagus, highlighting tissuethrough an whitening reaction and enhancing visibilityof areas with cellular changes for biopsy. After 4 to 10weeks, participants will undergo a repeat endoscopy, usingthe second method. Rates of recruitment and retention willbe assessed, in addition to the estimated dysplasia detectionrate, effectiveness of the endoscopist training program,and rates of adverse events (AEs). Qualitative interviewswill explore participant and endoscopist acceptabilityof study design and delivery, and the acceptability ofswitching endoscopic techniques for Barrett's surveillance. Results - Endoscopistsâ ability to diagnose dysplasia in Barrettâsesophagus can be improved. AAC may offer a simple,universally applicable, easily-acquired technique to improvedetection, affording patients earlier diagnosis and treatment,reducing endoscopy time and pathology costs. TheABBA study will determine whether a crossover âtandemâendoscopy design is feasible and acceptable to patientsand clinicians and gather outcome data to power a definitivetrial
Acetic acid guided biopsies in Barrettâs surveillance for neoplasia detection versus non-targeted biopsies (Seattle protocol):a feasibility study for a randomised tandem endoscopy trial. The ABBA study.
<div><p>MiRNAs function in post-transcriptional regulation of gene expression and play very important roles in plant development. <i>Lonicera japonica</i> is one of the important medicinal plants in China. However, few studies on the discovery of conserved and novel miRNAs from <i>L</i>. <i>japonica</i> were reported. In this study, we employed deep sequencing technology to identify miRNAs in leaf and flower tissues of <i>L</i>. <i>japonica</i>. A total of 22.97 million clean reads from flower and leaf tissues were obtained, which generated 146 conserved miRNAs distributed in 20 families and 110 novel miRNAs. Accordingly, 72 differentially expressed miRNAs (Pâ¤0.001) between leaves and flowers and their potential target genes were identified and validated. The qRT-PCR validation showed that majority of the differentially expressed miRNAs showed significant tissue-specific expression in <i>L</i>. <i>japonica</i>. Furthermore, the miRNA-mRNA and mRNA-mRNA regulatory networks were constructed using Cytoscape software. Taken together, this study identified a large number of miRNAs and target genes in <i>L</i>. <i>japonica</i>, which not only provides the first global miRNA expression profiles, but also sheds light on functional genomics research on <i>L</i>. <i>japonica</i> in the future.</p></div
A first-in-human phase I study to determine the maximum tolerated dose of the oral Src/ABL inhibitor AZD0424
BACKGROUND: Src is involved in cancer invasion and metastasis. AZD0424, an oral inhibitor of Src and ABL1, has shown evidence of anti-tumour activity in pre-clinical studies. METHODS: A phase Ia, dose escalation study was performed to assess the safety of continuous oral dosing with AZD0424 in advanced solid tumours. Secondary objectives included investigation of AZD0424 pharmacokinetics, effect on Src activity using markers of bone turnover, and anti-tumour activity. RESULTS: 41 patients were treated; 34 received AZD0424 once-daily at doses ranging from 5âmg to 150âmg, and 7 received 40âmg bi-daily 41.5% of patients experienced at least one AZD0424-related adverse event that was Grade 3-5 in severity, with patients treated at doses above 60âmg per day experiencing multiple treatment-related toxicities. The most commonly observed AZD0424-related adverse events were nausea, fatigue, anorexia and alopecia. Cmaxand AUC increased linearly with dose and the meanÂąstandard deviation t1/2was 8.4Âą2.8âh. Clear evidence of Src target inhibition was seen at doses ⊞20âmg per day. No responses were observed and 7 patients (17.1%) achieved stable disease lasting 6 weeks or more. CONCLUSIONS: AZD0424 displayed no evidence of efficacy as monotherapy despite a clear pharmacodynamic effect. Further evaluation of AZD0424 monotherapy in patients with solid tumours is not recommended
'Country life'? Rurality, folk music and 'Show of Hands'
This paper examines the contribution of folk music to understanding the dynamic, fluid and multi-experiential nature of the countryside. Drawing from literature on the geographies of music, it examines the work of 'Show of Hands', a contemporary folk band from Devon in England. Three areas are studied. First, the paper examines the musical style of Show of Hands in order to explore how hybridised, yet distinctive, styles of music emerge in particular places. Second, it demonstrates how Show of Hands' hybrid musical style has become closely associated with the Southwest of England. Finally, within these spatial and hybrid contexts, attention is given to the ways in which their music represents the 'everyday lives of the rural'. Taken together these themes assess the relevance of music in the understanding of rurality as hybrid space. Š 2008 Elsevier Ltd. All rights reserved
Team Sport Risk Exposure Framework-2 (TS-REF-2) to identify sports activities and contacts at increased SARS-CoV-2 transmission risk during the COVID-19 pandemic.
The Team Sports Risk Exposure Framework (TS-REF) was developed in July 2020 by experts in sports medicine, virology, sports science and public health to facilitate the safe return of sport during the COVID-19 pandemic. The TS-REF was developed at the time when the outdoor transmission risk of SARS-CoV-2 during sport was unknown. The TS-REF has been adopted by Public Health England and the UK Government (Department for Digital, Culture, Media and Sport), for use within both elite and community sports, to both determine the risk of SARS-CoV-2 transmission during specific sporting activities (eg, rugby tackle), and to identify and isolate increased risk contacts during sport. The TS-REF classified increased risk contacts as player-to-player interactions âwithin 1 m, directly face to face, for 3 or more secondsâ
Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping⢠to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial
Background Up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping⢠(DCMâ˘) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM⢠is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM⢠in the UK is urgently needed. Methods/design A pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCMâ˘) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. Discussion The protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. Trial registration Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015
The effects of problem-oriented policing on crime and disorder
Problem-oriented Policing (POP) was first introduced by Herman Goldstein in 1979. The
approach was one of a series of responses to a crisis in effectiveness and legitimacy in
policing that emerged in the 1970s and 1980s. Goldstein argued that police were not
being effective in preventing and controlling crime because they had become too focused
on the âmeansâ of policing and had neglected the âgoalsâ of preventing and controlling
crime and other community problems. Goldstein argued that the unit of analysis in
policing must become the âproblemâ rather than calls or crime incidents as was the case
during that period. POP has had tremendous impact on American policing, and is now
one of the most widely implemented policing strategies in the US.
To synthesize the extant problem-oriented policing evaluation literature and assess the
effects of problem-oriented policing on crime and disorder
Eligible studies had to meet three criteria: (1) the SARA model was used for a problemoriented
policing intervention; (2) a comparison group was included; (3) at least one
crime or disorder outcome was reported with sufficient data to generate an effect size.
The unit of analysis could be people or places.
Several strategies were used to perform an exhaustive search for literature fitting the
eligibility criteria. First, a keyword search was performed on an array of online abstract
databases. Second, we reviewed the bibliographies of past reviews of problem-oriented
policing. Third, we performed forward searches for works that have cited seminal
problem-oriented policing studies. Fourth, we performed hand searches of leading
journals in the field. Fifth, we searched the publications of several research and
professional agencies. Sixth, after finishing the above searches we e-mailed the list of
studies meeting our eligibility criteria to leading policing scholars knowledgeable in the
area of problem-oriented policing to ensure we had not missed any relevant studies.
For our ten eligible studies, we provide both a narrative review of effectiveness and a
meta-analysis. For the meta-analysis, we coded all primary outcomes of the eligible
studies and we report the mean effect size (for studies with more than one primary
outcome, we averaged effects to create a mean), the largest effect, and the smallest effect.
Because of the heterogeneity of our studies, we used a random effects model.
Based on our meta-analysis, overall problem-oriented policing has a modest but
statistically significant impact on reducing crime and disorder. Our results are consistent
when examining both experimental and quasi-experimental studies.
Conclusions:
We conclude that problem-oriented policing is effective in reducing crime and disorder,
although the effect is fairly modest. We urge caution in interpreting these results because
of the small number of methodologically rigorous studies on POP and the diversity of
problems and responses used in our eligible studies
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