Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine

The ability of the bioreductive drugs AQ4N and tirapazamine to enhance the anti-tumour effect of cyclophosphamide was assessed in three murine tumour models. In male BDF mice implanted with the T50/80 mammary carcinoma, AQ4N (50–150 mg kg−1) in combination with cyclophosphamide (100 mg kg−1) produced an effect equivalent to a single 200 mg kg−1dose of cyclophosphamide. Tirapazamine (25 mg kg−1) in combination with cyclophosphamide (100 mg kg−1) produced an effect equivalent to a single 150 mg kg−1dose of cyclophosphamide. In C3H mice implanted with the SCCVII or RIF-1 tumours, enhancement of tumour cell killing was found with both drugs in combination with cyclophosphamide (50–200 mg kg−1); AQ4N (50–200 mg kg−1) produced a more effective combination than tirapazamine (12.5–50 mg kg−1). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kg−1) 6 h prior to cyclophosphamide (100 mg kg−1) resulted in no additional toxicity towards bone marrow cells compared to that caused by cyclophosphamide alone. In conclusion, AQ4N gave a superior anti-tumour effect compared to tirapazamine when administered with a single dose of cyclophosphamide (100 mg kg−1). © 2000 Cancer Research Campaig

Acceptability and feasibility of peer assisted supervision and support for intervention practitioners: a Q-methodology evaluation

Evidence-based interventions often include quality improvement methods to support fidelity and improve client outcomes. Clinical supervision is promoted as an effective way of developing practitioner confidence and competence in delivery; however, supervision is often inconsistent and embedded in hierarchical line management structures that may limit the opportunity for reflective learning. The Peer Assisted Supervision and Support (PASS) supervision model uses peer relationships to promote the self-regulatory capacity of practitioners to improve intervention delivery. The aim of the present study was to assess the acceptability and feasibility of PASS amongst parenting intervention practitioners. A Q-methodology approach was used to generate data and 30 practitioners volunteered to participate in the study. Data were analyzed and interpreted using standard Q-methodology procedures and by-person factor analysis yielded three factors. There was consensus that PASS was acceptable. Participants shared the view that PASS facilitated an environment of support where negative aspects of interpersonal relationships that might develop in supervision were not evident. Two factors represented the viewpoint that PASS was also a feasible model of supervision. However, the third factor was comprised of practitioners who reported that PASS could be time consuming and difficult to fit into existing work demands. There were differences across the three factors in the extent to which practitioners considered PASS impacted on their intervention delivery. The findings highlight the importance of organizational mechanisms that support practitioner engagement in supervision

Scientific advice and public policy: expert advisers’ and policymakers’ discourses on boundary work

This article reports on considerable variety and diversity among discourses on their own jobs of boundary workers of several major Dutch institutes for science-based policy advice. Except for enlightenment, all types of boundary arrangements/work in the Wittrock-typology (Social knowledge and public policy: eight models of interaction. In: Wagner P (ed) Social sciences and modern states: national experiences and theoretical crossroads. Cambridge University Press, Cambridge, 1991) do occur. ‘Divergers’ experience a gap between science and politics/policymaking; and it is their self-evident task to act as a bridge. They spread over four discourses: ‘rational facilitators’, ‘knowledge brokers’, ‘megapolicy strategists’, and ‘policy analysts’. Others aspire to ‘convergence’; they believe science and politics ought to be natural allies in preparing collective decisions. But ‘policy advisors’ excepted, ‘postnormalists’ and ‘deliberative proceduralists’ find this very hard to achieve

Who knows best? A Q methodology study to explore perspectives of professional stakeholders and community participants on health in low-income communities

Abstract Background Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. Methods Q methodology was used to identify and describe the shared perspectives (‘subjectivities’) that exist on i) why health is worse in low-income communities (‘Causes’) and ii) the ways that health could be improved in these same communities (‘Solutions’). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements – 34 ‘Causes’ and 39 ‘Solutions’ – onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. ‘Causes’ and ‘Solutions’ were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. Results Analysis produced three factor solutions for both the ‘Causes’ and ‘Solutions’. Broadly summarised these accounts for ‘Causes’ are: i) ‘Unfair Society’, ii) ‘Dependent, workless and lazy’, iii) ‘Intergenerational hardships’ and for ‘Solutions’: i) ‘Empower communities’, ii) ‘Paternalism’, iii) ‘Redistribution’. No professionals defined (i.e. had a significant association with one factor only) the ‘Causes’ factor ‘Dependent, workless and lazy’ and the ‘Solutions’ factor ‘Paternalism’. No community participants defined the ‘Solutions’ factor ‘Redistribution’. The direction of correlations between the two sets of factor solutions – ‘Causes’ and ‘Solutions’ – appear to be intuitive, given the accounts identified. Conclusions Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on

What motivates senior clinicians to teach medical students?

BACKGROUND: This study was designed to assess the motivations of senior medical clinicians to teach medical students. This understanding could improve the recruitment and retention of important clinical teachers. METHODS: The study group was 101 senior medical clinicians registered on a teaching list for a medical school teaching hospital (The Canberra Hospital, ACT, Australia). Their motivations to teach medical students were assessed applying Q methodology. RESULTS: Of the 75 participants, 18 (24%) were female and 57 (76%) were male. The age distribution was as follows: 30–40 years = 16 participants (21.3%), 41–55 years = 46 participants (61.3%) and >55 years = 13 participants (17.3%). Most participants (n = 48, 64%) were staff specialists and 27 (36%) were visiting medical officers. Half of the participants were internists (n = 39, 52%), 12 (16%) were surgeons, and 24 (32%) were other sub-specialists. Of the 26 senior clinicians that did not participate, two were women; 15 were visiting medical officers and 11 were staff specialists; 16 were internists, 9 were surgeons and there was one other sub-specialist. The majority of these non-participating clinicians fell in the 41–55 year age group. The participating clinicians were moderately homogenous in their responses. Factor analysis produced 4 factors: one summarising positive motivations for teaching and three capturing impediments for teaching. The main factors influencing motivation to teach medical students were intrinsic issues such as altruism, intellectual satisfaction, personal skills and truth seeking. The reasons for not teaching included no strong involvement in course design, a heavy clinical load or feeling it was a waste of time. CONCLUSION: This study provides some insights into factors that may be utilised in the design of teaching programs that meet teacher motivations and ultimately enhance the effectiveness of the medical teaching workforce

The predictive and prognostic value of tumour necrosis in muscle invasive bladder cancer patients receiving radiotherapy with or without chemotherapy in the BC2001 trial (CRUK/01/004)

Background: Severe chronic hypoxia is associated with tumour necrosis. In patients with muscle invasive bladder cancer (MIBC), necrosis is prognostic for survival following surgery or radiotherapy and predicts benefit from hypoxia modification of radiotherapy. Adding mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy to radiotherapy improved locoregional control (LRC) compared to radiotherapy alone in the BC2001 trial. We hypothesised that tumour necrosis would not predict benefit for the addition of MMC and 5-FU to radiotherapy, but would be prognostic. Methods: Diagnostic tumour samples were available from 230 BC2001 patients. Tumour necrosis was scored on whole-tissue sections as absent or present, and its predictive and prognostic significance explored using Cox proportional hazards models. Survival estimates were obtained by Kaplan–Meier methods. Results: Tumour necrosis was present in 88/230 (38%) samples. Two-year LRC estimates were 71% (95% CI 61–79%) for the MMC/5-FU chemoradiotherapy group and 49% (95% CI 38–59%) for the radiotherapy alone group. When analysed by tumour necrosis status, the adjusted hazard ratios (HR) for MMC/5-FU vs. no chemotherapy were 0.46 (95% CI: 0.12–0.99; P=0.05, necrosis present) and 0.55 (95% CI: 0.31–0.98; P=0.04, necrosis absent). Multivariable analysis of prognosis for LRC by the presence vs. absence of necrosis yielded a HR=0.89 (95% CI 0.55–1.44, P=0.65). There was no significant association for necrosis as a predictive or prognostic factor with respect to overall survival. Conclusions: Tumour necrosis was neither predictive nor prognostic, and therefore MMC/5-FU is an appropriate radiotherapy-sensitising treatment in MIBC independent of necrosis status

A Q-methodology study of flare help-seeking behaviours and different experiences of daily life in rheumatoid arthritis

© 2014 Lin et al.; licensee BioMed Central Ltd. Background: Previous studies have not addressed rheumatoid arthritis (RA) patients' help-seeking behaviours for RA flares, and only one small qualitative study has addressed how patients experience daily life on current treatment regimes. Thus, this study aims to identify clusters of opinion related to RA patients' experiences of daily life on current treatments, and their help-seeking behaviours for RA flares. Methods: Using Q-methodology (a methodology using qualitative and quantitative methods to sort people according to subjective experience), two separate studies were conducted with the same sample of RA patients (mean age 55, 73% female). Thirty participants sorted 39 statements about daily life (Q-study 1) and 29 participants separately sorted 23 statements about flare help-seeking (Q-study 2). Data were examined using Q-factor analysis. Results: Daily life with RA (Q-study 1): Three factors relating to the experience of living with RA were extracted and explained. Patients belonging to Factor A (mean age 62, 86% female) use effective self-management techniques to control the daily impact of RA. Those in Factor B (mean age 55, 75% male) struggle to self-manage and cope. Whilst patients in Factor C (mean age 42, 100% female) prioritise life responsibilities over their RA, reporting less impact. Flare help-seeking (Q-study 2): Two factors explaining the experience of flare help-seeking (unrelated to the factors from Q-study 1) were extracted and explained. Factor X (68.8% on biologics) reported seeking help quickly, believing the medical team is there to help. Factor Y (0% on biologics) delay help-seeking, concerned about wasting the rheumatologist's time, believing they should manage alone. All participants agreed they sought help due to intense pain and persistent, unmanageable symptoms. Conclusions: Patients with different characteristics appear to manage RA life in different ways and men may struggle more than women. Whilst all patients are prompted to seek help by persistent, unmanageable symptoms, some delay help-seeking. Further research is needed to quantify the severity of daily symptoms, the level of symptoms needed for patients to define themselves as in flare and to understand the support needs of RA men

Bootstrapping Q Methodology to Improve the Understanding of Human Perspectives.

Q is a semi-qualitative methodology to identify typologies of perspectives. It is appropriate to address questions concerning diverse viewpoints, plurality of discourses, or participation processes across disciplines. Perspectives are interpreted based on rankings of a set of statements. These rankings are analysed using multivariate data reduction techniques in order to find similarities between respondents. Discussing the analytical process and looking for progress in Q methodology is becoming increasingly relevant. While its use is growing in social, health and environmental studies, the analytical process has received little attention in the last decades and it has not benefited from recent statistical and computational advances. Specifically, the standard procedure provides overall and arguably simplistic variability measures for perspectives and none of these measures are associated to individual statements, on which the interpretation is based. This paper presents an innovative approach of bootstrapping Q to obtain additional and more detailed measures of variability, which helps researchers understand better their data and the perspectives therein. This approach provides measures of variability that are specific to each statement and perspective, and additional measures that indicate the degree of certainty with which each respondent relates to each perspective. This supplementary information may add or subtract strength to particular arguments used to describe the perspectives. We illustrate and show the usefulness of this approach with an empirical example. The paper provides full details for other researchers to implement the bootstrap in Q studies with any data collection design

Acceptability of a Positive Parenting Programme on a Mother and Baby Unit: Q-Methodology with Staff

The Baby Triple P Positive Parenting Programme, a new addition to the established Triple P programmes, is currently being considered for a trial in a Mother and Baby Unit with the aim of exploring its benefits to mothers presenting with severe mental illness. The aim of the current study was to investigate staff views of the acceptability and feasibility of a parenting programme such as the Baby Triple P Positive Parenting Programme in a Mother and Baby Unit. Q-methodology, using an 88-item Q-sort, was employed to explore the opinions of 16 staff working in a Mother and Baby Unit in the North West of England. Results obtained from the Q-sort analysis identified two distinct factors: (1) staff qualified acceptance and (2) systemic approach/systemic results. Preliminary findings indicate that staff perceived Baby Triple P to be an acceptable and feasible intervention for the Mother and Baby Unit setting and that mothers on the unit would be open and receptive to the programme. Further research is required to expand these findings and assess the potential for this type of intervention to be used more widely across a number of Mother and Baby Unit settings