Do men regret prostate biopsy: Results from the PiCTure study

Abstract Background Understanding men\u2019s experience of prostate biopsy is important as the procedure is common, invasive and carries potential risks. The psychological aspects of prostate biopsy have been somewhat neglected. The aim of this study was to explore the level of regret experienced by men after prostate biopsy and identify any associated factors. Methods Men attending four clinics in Republic of Ireland and two in Northern Ireland were given a questionnaire to explore their experience of prostate biopsy. Regret was measured on a Likert scale asking men how much they agreed with the statement \u201cIt [the biopsy] is something I regret.\u201d Results Three hundred thirty-five men responded to the survey. The mean age was 63\ua0years (SD \ub17\ua0years). Three quarters of respondents (76%) were married or co-habiting, and (75%) finished education at primary or secondary school level. For just over two thirds of men (70%) their recent biopsy represented their first ever prostate biopsy. Approximately one third of men reported a diagnosis of cancer, one third a negative biopsy result, and the remaining third did not know their result. Two thirds of men reported intermediate or high health anxiety. 5.1% of men agreed or strongly agreed that they regretted the biopsy. Conclusions Level of regret was low overall. Health anxiety was the only significant predictor of regret, with men with higher anxiety reporting higher levels of regret than men with low anxiety (OR\u2009=\u20093.04, 95% CI 1.58, 5.84). Men with high health anxiety may especially benefit from careful counselling before and after prostate biopsy

Visual Function Questionnaire as an outcome measure for homonymous hemianopia: subscales and supplementary questions, analysis from the VISION trial

Background: We conduct supplementary analyses of the NEI VFQ-25 data to evaluate where changes occurred within subscales of the NEI VFQ-25 leading to change in the composite scores between the three treatment arms, and evaluate the NEI VFQ-25 with and without the Neuro 10 supplement. Methods: A prospective, multicentre, parallel, single-blind, three-arm RCT of fourteen UK acute stroke units was conducted. Stroke survivors with homonymous hemianopia were recruited. Interventions included: Fresnel prisms for minimum 2 h, 5 days/week over 6-weeks (Arm a), Visual search training for minimum 30 min, 5 days/week over 6-weeks (Arm b) and standard care-information only (Arm c). Primary and secondary outcomes (including NEI VFQ-25 data) were measured at baseline, 6, 12 and 26 weeks after randomisation. Results: Eighty seven patients were recruited (69% male; mean age (SD) equal to 69 (12) years). At 26 weeks, outcomes for 24, 24 and 22 patients, respectively, were compared to baseline. NEI VFQ-25 (with and without Neuro 10) responses improved from baseline to 26 weeks with visual search training compared to Fresnel prisms and standard care. In subscale analysis, the most impacted across all treatment arms was ‘driving’ whilst the least impacted were ‘colour vision’ and ‘ocular pain’. Conclusions: Composite scores differed systematically for the NEI VFQ-25 (Neuro 10) versus NEI VFQ-25 at all time points. For subscale scores, descriptive statistics suggest clinically relevant improvement in distance activities and vision-specific dependency subscales for NEI VFQ-25 scores in the visual search treatment arm. Trial Registration: Current Controlled Trials ISRCTN05956042

Exploring the costs and outcomes of sexually transmitted infection (STI) screening interventions targeting men in football club settings: preliminary cost-consequence analysis of the SPORTSMART pilot randomised controlled trial

Background: The objective of this study was to compare the costs and outcomes of two sexually transmitted infection (STI) screening interventions targeted at men in football club settings in England, including screening promoted by team captains. Methods: A comparison of costs and outcomes was undertaken alongside a pilot cluster randomised control trial involving three trial arms: (1) captain-led and poster STI screening promotion; (2) sexual health advisor-led and poster STI screening promotion and (3) poster-only STI screening promotion (control/comparator). For all study arms, resource use and cost data were collected prospectively. Results: There was considerable variation in uptake rates between clubs, but results were broadly comparable across study arms with 50% of men accepting the screening offer in the captain-led arm, 67% in the sexual health advisor-led arm and 61% in the poster-only control arm. The overall costs associated with the intervention arms were similar. The average cost per player tested was comparable, with the average cost per player tested for the captain-led promotion estimated to be £88.99 compared with £88.33 for the sexual health advisor-led promotion and £81.87 for the poster-only (control) arm. Conclusions: Costs and outcomes were similar across intervention arms. The target sample size was not achieved, and we found a greater than anticipated variability between clubs in the acceptability of screening, which limited our ability to estimate acceptability for intervention arms. Further evidence is needed about the public health benefits associated with screening interventions in non-clinical settings so that their cost-effectiveness can be fully evaluated

Clinicians’ experiences of discontinuing routine hip precautions following total hip replacement surgery: a qualitative analysis

PurposeHip precautions are routinely provided in the UK, despite evidence suggesting that they are no longer needed. A change in practice was introduced into an orthopaedic service whereby the provision of routine hip precautions was discontinued for selected individuals receiving a primary total hip replacement. The change involved implementing a new regime of “no precautions” which was facilitated using a number of key strategies. The aim of this study was to explore the experiences of clinicians associated with the change in practice.Material and methodsIndividual semi-structured interviews were conducted with clinicians who had experience of delivering both hip precautions and no hip precaution regimes. Data were analysed thematically.ResultsTen orthopaedic staff (two senior occupational therapists, one occupational therapy support worker, three senior physiotherapists, two surgeons, and two senior nurses) were interviewed. Three main themes were identified: changes experienced, perceptions of the new regime, and challenges experienced.ConclusionSeveral barriers and facilitators to the successful changeover were identified. Successful strategies in changing practice included assigning “Hip Champions”, staff education and targeted training. It is proposed that holding multidisciplinary education and training would be the ideal model. Implications for rehabilitation - Key strategies for changing practice were educating staff and providing targeted training.- Multidisciplinary training might prevent discrepancies in the advice given to patients.- Appointing “Hip Champions” provided clear role models and enabled new clinical behaviours to be enforced

Do men regret prostate biopsy: results from the PiCTure study

Background: Understanding men’s experience of prostate biopsy is important as the procedure is common, invasive and carries potential risks. The psychological aspects of prostate biopsy have been somewhat neglected. The aim of this study was to explore the level of regret experienced by men after prostate biopsy and identify any associated factors. Methods: Men attending four clinics in Republic of Ireland and two in Northern Ireland were given a questionnaire to explore their experience of prostate biopsy. Regret was measured on a Likert scale asking men how much they agreed with the statement “It [the biopsy] is something I regret.” Results: Three hundred thirty-five men responded to the survey. The mean age was 63 years (SD ±7 years). Three quarters of respondents (76%) were married or co-habiting, and (75%) finished education at primary or secondary school level. For just over two thirds of men (70%) their recent biopsy represented their first ever prostate biopsy. Approximately one third of men reported a diagnosis of cancer, one third a negative biopsy result, and the remaining third did not know their result. Two thirds of men reported intermediate or high health anxiety. 5.1% of men agreed or strongly agreed that they regretted the biopsy. Conclusions: Level of regret was low overall. Health anxiety was the only significant predictor of regret, with men with higher anxiety reporting higher levels of regret than men with low anxiety (OR = 3.04, 95% CI 1.58, 5.84). Men with high health anxiety may especially benefit from careful counselling before and after prostate biopsy

TP53 mutant MDM2-amplified cell lines selected for resistance to MDM2-p53 binding antagonists retain sensitivity to ionizing radiation

Non-genotoxic reactivation of the p53 pathway by MDM2-p53 binding antagonists is an attractive treatment strategy for wild-type TP53 cancers. To determine how resistance to MDM2/p53 binding antagonists might develop, SJSA-1 and NGP cells were exposed to growth inhibitory concentrations of chemically distinct MDM2 inhibitors, Nutlin-3 and MI-63, and clonal resistant cell lines generated. The p53 mediated responses of parental and resistant cell lines were compared. In contrast to the parental cell lines, p53 activation by Nutlin-3, MI-63 or ionizing radiation was not observed in either the SJSA-1 or the NGP derived cell lines. An identical TP53 mutation was subsequently identified in both of the SJSA-1 resistant lines, whilst one out of three identified mutations was common to both NGP derived lines. Mutation specific PCR revealed these mutations were present in parental SJSA-1 and NGP cell populations at a low frequency. Despite cross-resistance to a broad panel of MDM2/p53 binding antagonists, these MDM2-amplified and TP53 mutant cell lines remained sensitive to ionizing radiation (IR). These results indicate that MDM2/p53 binding antagonists will select for p53 mutations present in tumours at a low frequency at diagnosis, leading to resistance, but such tumours may nevertheless remain responsive to alternative therapies, including IR

Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib

This work was supported by five grants to Sonia Laín: Vetenskapsrådet (VR) 521-2014-3341, Cancerfonden (Swedish Cancer Society) 150393, CAN 2014/702, Association for International Cancer Research (AICR) 130086, Barncancerfonden (Swedish Childhood Cancer Foundation) TJ-2014-0038, Barncancerfonden (Swedish Childhood Cancer Foundation) PR-2014-0038; two grants to Ravi Bhatia: Leukemia and Lymphoma Society (LLS) 6137-14 and NIH R01 CA95684; one grant to David P Lane: Vetenskapsrådet (VR) 538-2013-8807; one grant to Marcus J G W Ladds: Karolinska Institute KID Doctoral Student Funding; one grant to Gergana Popova: Karolinska Institutet KID Doctoral Student Funding; two grants to Nicholas J Westwood: Cancer Research UK C21383 and Cancer Research UK A6950; two grants to Gerald McInerney: Vetenskapsrådet (VR) 621-2014-4718 and Cancerfonden (Swedish Cancer Society) 150393, CAN 2015/751; and four grants to Emmet McCormack: Kreftforeningen 182735, Kreftforeningen 732200, Halse Vest 911884, Halse Vest 911789.Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules. Additionally, we evaluate the contribution of this tertiary amine to the elimination of proliferating melanoma cells in culture. We also demonstrate that the presence of the tertiary amine is sufficient to lead to death of tumour cells arrested in G1 phase following vemurafenib treatment. We conclude that blockage of autophagic flux by tenovins is necessary to eliminate melanoma cells that survive B-Raf inhibition and achieve total tumour cell kill and that autophagy blockage can be achieved at a lower concentration than by chloroquine. This observation is of great relevance as relapse and resistance are frequently observed in cancer patients treated with B-Raf inhibitors.Publisher PDFPeer reviewe

Development of an occupational advice intervention for patients undergoing lower limb arthroplasty (the OPAL study)

Background: There are an increasing number of patients of working age undergoing hip and knee replacements. Currently there is variation in the advice and support given about sickness absence, recovery to usual activities and return to work after these procedures. Earlier, sustainable, return to work improves the health of patients and benefits their employers and society. An intervention that encourages and supports early recovery to usual activities, including work, has the potential to reduce the health and socioeconomic burden of hip and knee replacements. Methods/design: A two-phase research programme delivered over 27 months will be used to develop and subsequently test the feasibility of an occupational advice intervention to facilitate return to work and usual activities in patients undergoing lower limb arthroplasty. The 2 phases will incorporate a six-stage intervention mapping process: Phase 1: Intervention mapping stages 1–3: 1 Needs assessment (including rapid evidence synthesis, prospective cohort analysis and structured stakeholder interviews) 2 Identification of intended outcomes and performance objectives 3 Selection of theory-based methods and practical strategies Phase 2: Intervention mapping stages 4–6: 4 Development of components and materials for the occupational advice intervention using a modified Delphi process 5 Adoption and implementation of the intervention 6 Evaluation and feasibility testing The study will be undertaken in four National Health Service (NHS) hospitals in the United Kingdom and two Higher Education Institution. Discussion: OPAL (Occupational advice for Patients undergoing Arthroplasty of the Lower limb) aims to develop an occupational advice intervention to support early recovery to usual activities including work, which is tailored to the requirements of patients undergoing hip and knee replacements. The developed intervention will then be assessed with a specific focus on evaluating its feasibility as a potential trial intervention to improve speed of recovery to usual activities including work

Cost-effectiveness of financial incentives to promote adherence to depot antipsychotic medication: economic evaluation of a cluster-randomised controlled trial

Background: Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. Methods: Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of ‘good’ adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). Findings: Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4 533, £5 730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8 020, £14 000). The extra cost per patient of achieving 'good' adherence was £2 950 (CI -£19 400, £27 800). Probability of cost-effectiveness exceeded 97.5%at willingness-to-pay values of £14 000 for a 20% increase in adherence and £27 800 for good adherence. Interpretation: Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention. Trial Registration: ISRCTN.com 7776928