Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: A pilot study

<p>Abstract</p> <p>Background</p> <p>Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE.</p> <p>Methods</p> <p>30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab.</p> <p>Results</p> <p>Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (<it>p </it>= 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (<it>p </it>= 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE.</p> <p>Conclusions</p> <p>IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation at week 14.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00049322">NCT00049322</a>.</p

A multi-stakeholder approach to the co-production of the research agenda for medicines optimisation

© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence (http://creativecommons.org/licenses/by/4.0/), and indicate if changes were made.BACKGROUND: Up to 50% of medicines are not used as intended, resulting in poor health and economic outcomes. Medicines optimisation is 'a person-centred approach to safe and effective medicines use, to ensure people obtain the best possible outcomes from their medicines'. The purpose of this exercise was to co-produce a prioritised research agenda for medicines optimisation using a multi-stakeholder (patient, researcher, public and health professionals) approach. METHODS: A three-stage, multiple method process was used including: generation of preliminary research questions (Stage 1) using a modified Nominal Group Technique; electronic consultation and ranking with a wider multi-stakeholder group (Stage 2); a face-to-face, one-day consensus meeting involving representatives from all stakeholder groups (Stage 3). RESULTS: In total, 92 research questions were identified during Stages 1 and 2 and ranked in order of priority during stage 3. Questions were categorised into four areas: 'Patient Concerns' [e.g. is there a shared decision (with patients) about using each medicine?], 'Polypharmacy' [e.g. how to design health services to cope with the challenge of multiple medicines use?], 'Non-Medical Prescribing' [e.g. how can the contribution of non-medical prescribers be optimised in primary care?], and 'Deprescribing' [e.g. what support is needed by prescribers to deprescribe?]. A significant number of the 92 questions were generated by Patient and Public Involvement representatives, which demonstrates the importance of including this stakeholder group when identifying research priorities. CONCLUSIONS: A wide range of research questions was generated reflecting concerns which affect patients, practitioners, the health service, as well the ethical and philosophical aspects of the prescribing and deprescribing of medicines. These questions should be used to set future research agendas and funding commissions.Peer reviewedFinal Published versio

New Concerns for Neurocognitive Function during Deep Space Exposures to Chronic, Low Dose-Rate, Neutron Radiation.

As NASA prepares for a mission to Mars, concerns regarding the health risks associated with deep space radiation exposure have emerged. Until now, the impacts of such exposures have only been studied in animals after acute exposures, using dose rates ∼1.5×105 higher than those actually encountered in space. Using a new, low dose-rate neutron irradiation facility, we have uncovered that realistic, low dose-rate exposures produce serious neurocognitive complications associated with impaired neurotransmission. Chronic (6 month) low-dose (18 cGy) and dose rate (1 mGy/d) exposures of mice to a mixed field of neutrons and photons result in diminished hippocampal neuronal excitability and disrupted hippocampal and cortical long-term potentiation. Furthermore, mice displayed severe impairments in learning and memory, and the emergence of distress behaviors. Behavioral analyses showed an alarming increase in risk associated with these realistic simulations, revealing for the first time, some unexpected potential problems associated with deep space travel on all levels of neurological function

Identifying enablers and barriers to individually tailored prescribing: a survey of healthcare professionals in the UK.

BACKGROUND: Many people now take multiple medications on a long-term basis to manage health conditions. Optimising the benefit of such polypharmacy requires tailoring of medicines use to the needs and circumstances of individuals. However, professionals report barriers to achieving this in practice. In this study, we examined health professionals' perceptions of enablers and barriers to delivering individually tailored prescribing. METHODS: Normalisation Process Theory (NPT) informed an on-line survey of health professionals' views of enablers and barriers to implementation of Individually Tailored Prescribing (ITP) of medicines. Links to the survey were sent out through known professional networks using a convenience/snowball sampling approach. Survey questions sought to identify perceptions of supports/barriers for ITP within the four domains of work described by NPT: sense making, engagement, action and monitoring. Analysis followed the framework approach developed in our previous work. RESULTS: Four hundred and nineteen responses were included in the final analysis (67.3% female, 32.7% male; 52.7% nurse prescribers, 19.8% pharmacists and 21.8% GPs). Almost half (44.9%) were experienced practitioners (16+ years in practice); around one third reported already routinely offering ITP to their patients. GPs were the group least likely to recognise this as consistent usual practice. Findings revealed general support for the principles of ITP but significant variation and inconsistency in understanding and implementation in practice. Our findings reveal four key implications for practice: the need to raise understanding of ITP as a legitimate part of professional practice; to prioritise the work of ITP within the range of individual professional activity; to improve the consistency of training and support for interpretive practice; and to review the impact of formal and informal monitoring processes on practice. CONCLUSION: The findings will inform the ongoing development of our new complex intervention (PRIME Prescribing) to support the individual tailoring of medicines needed to address problematic polypharmacy

Sorghum Genome Sequencing by Methylation Filtration

Sorghum bicolor is a close relative of maize and is a staple crop in Africa and much of the developing world because of its superior tolerance of arid growth conditions. We have generated sequence from the hypomethylated portion of the sorghum genome by applying methylation filtration (MF) technology. The evidence suggests that 96% of the genes have been sequence tagged, with an average coverage of 65% across their length. Remarkably, this level of gene discovery was accomplished after generating a raw coverage of less than 300 megabases of the 735-megabase genome. MF preferentially captures exons and introns, promoters, microRNAs, and simple sequence repeats, and minimizes interspersed repeats, thus providing a robust view of the functional parts of the genome. The sorghum MF sequence set is beneficial to research on sorghum and is also a powerful resource for comparative genomics among the grasses and across the entire plant kingdom. Thousands of hypothetical gene predictions in rice and Arabidopsis are supported by the sorghum dataset, and genomic similarities highlight evolutionarily conserved regions that will lead to a better understanding of rice and Arabidopsis

Effect of educational outreach on general practice prescribing of antibiotics and antidepressants: a two-year randomised controlled trial

Objective. Prescribing of broad spectrum antibiotics and antidepressants in general practice often does not accord with guidelines. The aim was to determine the effectiveness of educational outreach in improving the prescribing of selected antibiotics and antidepressants, and whether the effect is sustained for two years. Design. Single blind randomized trial. Setting. Twenty-eight general practices in Leicestershire, England. Intervention. Educational outreach visits were undertaken, tailored to barriers to change, 14 practices receiving visits for reducing selected antibiotics and 14 for improving antidepressant prescribing. Main outcome measures. Number of items prescribed per 1000 registered patients for amoxicillin with clavulanic acid (co-amoxiclav) and quinolone antibiotics, and average daily quantities per 1000 patients for lofepramine and fluoxetine antidepressants, measured at the practice level for six-month periods over two years. Results. There was no effect on the prescribing of co-amoxiclav, quinolones, or fluoxetine, but prescribing of lofepramine increased in accordance with the guidelines. The increase persisted throughout two years of follow-up. Conclusion. A simple, group-level educational outreach intervention, designed to take account of identified barriers to change, can have a modest but sustained effect on prescribing levels. However, outreach is not always effective. The context in which change in prescribing practice is being sought, the views of prescribers concerning the value of the drug, or other unrecognised barriers to change may influence the effectiveness of outreach

Conducting a critical interpretive synthesis of the literature on access to healthcare by vulnerable groups

BACKGROUND: Conventional systematic review techniques have limitations when the aim of a review is to construct a critical analysis of a complex body of literature. This article offers a reflexive account of an attempt to conduct an interpretive review of the literature on access to healthcare by vulnerable groups in the UK METHODS: This project involved the development and use of the method of Critical Interpretive Synthesis (CIS). This approach is sensitised to the processes of conventional systematic review methodology and draws on recent advances in methods for interpretive synthesis. RESULTS: Many analyses of equity of access have rested on measures of utilisation of health services, but these are problematic both methodologically and conceptually. A more useful means of understanding access is offered by the synthetic construct of candidacy. Candidacy describes how people's eligibility for healthcare is determined between themselves and health services. It is a continually negotiated property of individuals, subject to multiple influences arising both from people and their social contexts and from macro-level influences on allocation of resources and configuration of services. Health services are continually constituting and seeking to define the appropriate objects of medical attention and intervention, while at the same time people are engaged in constituting and defining what they understand to be the appropriate objects of medical attention and intervention. Access represents a dynamic interplay between these simultaneous, iterative and mutually reinforcing processes. By attending to how vulnerabilities arise in relation to candidacy, the phenomenon of access can be better understood, and more appropriate recommendations made for policy, practice and future research. DISCUSSION: By innovating with existing methods for interpretive synthesis, it was possible to produce not only new methods for conducting what we have termed critical interpretive synthesis, but also a new theoretical conceptualisation of access to healthcare. This theoretical account of access is distinct from models already extant in the literature, and is the result of combining diverse constructs and evidence into a coherent whole. Both the method and the model should be evaluated in other contexts

Why do patients want to have their blood tested? A qualitative study of patient expectations in general practice

BACKGROUND: General practitioners often take their impression of patients' expectations into account in their decision to have blood tests done. It is commonly recommended to involve patients in decision-making during consultations. The study aimed to obtain detailed information on patients' expectations about blood tests. METHODS: Qualitative study among patients in waiting rooms of general practices. Each patient was presented with a short questionnaire about their preferences in terms of diagnostics. Patients who would like blood tests to be done were interviewed. RESULTS: Fifty-seven (26%) of the 224 respondents wanted blood tests. Twenty-two were interviewed. Patients overestimated the qualities of blood tests. Favourable test results were regarded as proof of good health. Patients regarded blood tests as a useful instrument to screen for serious disorders, and were confirmed in this belief by people in their social environment and by the media. Many patients expected their GP to take an active test ordering approach, though some indicated that they might be convinced if their GP proposed a wait-and-see policy. CONCLUSIONS: GPs' perceptions about patient expectations seem justified: patients appear to have high hopes for testing as a diagnostic tool. They expect diagnostic certainty without mistakes and a proof of good health. The question is whether it would be desirable to remove patients' misconceptions, allowing them to participate in policy decisions on the basis of sound information, or whether it would be better to leave the misconceptions uncontested, in order to retain the 'magic' of additional tests and reassure patients. We expect that clarifying the precise nature of patients' expectations by the GP may be helpful in creating a diagnostic strategy that satisfies both patients and GPs. GPs will have to balance the benefits of reassuring their patients by means of blood tests which may be unnecessary against the benefits of avoiding unnecessary tests. Further research is needed into the effects of different types of patient information and the effects of testing on satisfaction and anxiety

Researching complex interventions in health: the state of the art

CITATION: Craig, P., et al. 2016. Researching complex interventions in health : the state of the art. BMC Health Services Research, 16:101, doi:10.1186/s12913-016-1274-0.The original publication is available at https://bmchealthservres.biomedcentral.comENGLISH SUMMARY : Keynote presentationsPublishers' Versio

Designing an intervention to help people with colorectal adenomas reduce their intake of red and processed meat and increase their levels of physical activity: a qualitative study

Background: most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients' preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial.Methods: patients aged 60-74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared.Results: two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population.Conclusion: this study has demonstrated the difficulties involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to individuals, the lack of knowledge about the aetiology of colon cancer and the lack of motivation to change behaviour are critical factors