The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink

PURPOSE: Pre-clinical studies suggest that oral anticoagulant agents, such as warfarin, may inhibit metastases and potentially prolong survival in cancer patients. However, few population-based studies have examined the association between warfarin use and cancer-specific mortality.

METHODS: Using prescribing, cause of death, and cancer registration data from the UK Clinical Practice Research Datalink, four population-based cohorts were constructed, comprising breast, colorectal, lung, and prostate cancer patients diagnosed between 1 January 1998, and the 31 December 2010. Comparing pre-diagnostic warfarin users to non-users, multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality.

RESULTS: Overall, 16,525 breast, 12,902 colorectal, 12,296 lung, and 12,772 prostate cancers were included. Pre-diagnostic warfarin use ranged from 2.4 to 4.7 %. There was little evidence of any strong association between warfarin use pre-diagnosis and cancer-specific mortality in prostate (adjusted HR 1.03, 95 % CI 0.84-1.26), lung (adjusted HR 1.06, 95 % CI 0.96-1.16), breast (adjusted HR 0.81, 95 % CI 0.62-1.07), or colorectal (adjusted HR 0.88, 95 % CI 0.77-1.01) cancer patients. Dose-response analyses did not reveal consistent evidence of reductions in users of warfarin defined by the number of prescriptions used and daily defined doses.

CONCLUSIONS: There was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.

Post-diagnostic oral bisphosphonate use and colorectal cancer mortality: a population-based cohort study within the UK Clinical Practice Research Datalink

Background:We conducted the first study to investigate post-diagnostic oral bisphosphonates use and colorectal cancer-specific mortality.

Methods:Colorectal cancer patients were identified from the National Cancer Data Repository (1998–2007) and linked to the UK Clinical Practice Research Datalink, providing prescription records, and Office of National Statistics mortality data. Time-dependent Cox regression models investigated colorectal cancer-specific mortality in post-diagnostic bisphosphonate users.

Results:Overall, in 4791 colorectal cancer patients, there was no evidence of an association between bisphosphonate use and colorectal cancer-specific mortality (adjusted hazard ratio=1.11; 95% confidence interval 0.80, 1.54) or with drug frequency or type.

Conclusions:In this novel population-based cohort study, post-diagnostic bisphosphonate use was not associated with longer rates of colorectal cancer survival.

Paediatricians' opinions of microneedle-mediated monitoring: a key stage in the translation of microneedle technology from laboratory into clinical practice

Microneedle (MN) arrays could offer an alternative method to traditional drug delivery and blood sampling methods. However, acceptance among key end-users is critical for new technologies to succeed. MNs have been advocated for use in children and so, paediatricians are key potential end-users. However, the opinions of paediatricians on MN use have been previously unexplored. The aim of this study was to investigate the views of UK paediatricians on the use of MN technology within neonatal and paediatric care. An online survey was developed and distributed among UK paediatricians to gain their opinions of MN technology and its use in the neonatal and paediatric care settings, particularly for MN-mediated monitoring. A total of 145 responses were obtained, with a completion response rate of 13.7 %. Respondents believed an alternative monitoring technique to blood sampling in children was required. Furthermore, 83 % of paediatricians believed there was a particular need in premature neonates. Overall, this potential end-user group approved of the MN technology and a MN-mediated monitoring approach. Minimal pain and the perceived ease of use were important elements in gaining favour. Concerns included the need for confirmation of correct application and the potential for skin irritation. The findings of this study provide an initial indication of MN acceptability among a key potential end-user group. Furthermore, the concerns identified present a challenge to those working within the MN field to provide solutions to further improve this technology. The work strengthens the rationale behind MN technology and facilitates the translation of MN technology from lab bench into the clinical setting.

β-Blocker usage and colorectal cancer mortality:a nested case-control study in the UK Clinical Practice Research Datalink cohort

BACKGROUND: Epidemiological and laboratory studies suggest that β-blockers may reduce cancer progression in various cancer sites. The aim of this study was to conduct the first epidemiological investigation of the effect of post-diagnostic β-blocker usage on colorectal cancer-specific mortality in a large population-based colorectal cancer patient cohort.

PATIENTS AND METHODS: A nested case-control analysis was conducted within a cohort of 4794 colorectal cancer patients diagnosed between 1998 and 2007. Patients were identified from the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with a colorectal cancer- specific death (data from the Office of National Statistics death registration system) were matched to five controls. Conditional logistic regression was applied to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) according to β-blocker usage (data from GP-prescribing records).

RESULTS: Post-diagnostic β-blocker use was identified in 21.4% of 1559 colorectal cancer-specific deaths and 23.7% of their 7531 matched controls, with little evidence of an association (OR = 0.89 95% CI 0.78-1.02). Similar associations were found when analysing drug frequency, β-blocker type or specific drugs such as propranolol. There was some evidence of a weak reduction in all-cause mortality in β-blocker users (adjusted OR = 0.88; 95% CI 0.77-1.00; P = 0.04) which was in part due to the marked effect of atenolol on cardiovascular mortality (adjusted OR = 0.62; 95% CI 0.40-0.97; P = 0.04).

CONCLUSIONS: In this novel, large UK population-based cohort of colorectal cancer patients, there was no evidence of an association between post-diagnostic β-blocker use and colorectal cancer-specific mortality.

CLINICAL TRIALS NUMBER: NCT00888797.

(223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice

Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases. This article reviews the different radionuclide-based approaches for targeting bone metastases, with an emphasis on (223)Ra, and key elements of the underlying radiobiology of these that will impact their clinical effectiveness. Consideration is given to the remaining unknowns of both the basic radiobiological and applied clinical effects of (223)Ra as targets for future research.

How can we use systematic reviews to inform clinical practice?

Aims/purpose: Systematic reviews provide the highest quality evidence and inform clinical practice. For patient benefit, it is imperative that nurses keep abreast of evidence-based practice. This presentation highlights where to find systematic reviews and how the information presented can be used to inform care.
Presentation description: Clinical research is increasing at an incredible rate. In the clinical trials database alone, more than 2000 new studies are registered/month and this does not include qualitative studies that do not require registration. Keeping abreast of current evidence can not only be a time consuming process, but can be problematic when studies produce conflicting results. Systematic reviews can be useful for summarizing the increasing amount of knowledge that is gained from scientific papers. In addition, combining individual studies in a meta-analysis increases statistical power, resulting in more precise effect estimates. This presentation draws upon a few systematic reviews relevant to ICU nursing practice, highlights their findings and demonstrates how the information can be used to inform translation of evidence into practice. Additionally, although these reviews include steps to minimize bias, nurses should be aware of some of the biases that may reduce confidence in the findings.
Conclusion: Systematic reviews can be useful tools for informing evidence based practice, although careful interpretation is necessary for understanding their relevance to local practice.

Focused molecular analysis of small cell lung cancer: feasibility in routine clinical practice.

Background: There is an urgent need to identify molecular signatures in small cell lung cancer (SCLC) that may select patients who are likely to respond to molecularly targeted therapies. In this study, we investigate the feasibility of undertaking focused molecular analyses on routine diagnostic biopsies in patients with SCLC.

Methods: A series of histopathologically confirmed formalin-fixed, paraffin-embedded SCLC specimens were analysed for epidermal growth factor receptors (EGFR), KRAS, NRAS and BRAF mutations, ALK gene rearrangements and MET amplification. EGFR and KRAS mutation testing was evaluated using real time polymerase chain reaction (RT-PCR cobas®), BRAF and NRAS mutations using multiplex PCR and capillary electrophoresis-single strand conformation analysis, and ALK and MET aberrations with fluorescent in situ hybridization. All genetic aberrations detected were validated independently.

Results: A total of 105 patients diagnosed with SCLC between July 1990 and September 2006 were included. 60 (57 %) patients had suitable tumour tissue for molecular testing. 25 patients were successfully evaluated for all six pre-defined molecular aberrations. Eleven patients failed all molecular analysis. No mutations in EGFR, KRAS and NRAS were detected, and no ALK gene rearrangements or MET gene amplifications were identified. A V600E substitution in BRAF was detected in a Caucasian male smoker diagnosed with SCLC with squamoid and glandular features.

Conclusion: The paucity of patients with sufficient tumour tissue, quality of DNA extracted and low frequency of aberrations detected indicate that alternative molecular characterisation approaches are necessary, such as the use of circulating plasma DNA in patients with SCLC.

IMPLEMENTING BACK PAIN TREATMENT PATHWAYS IN CLINICAL PRACTICE: QUALITATATIVE ANALYSIS OF STAKEHOLDER PERCEPTIONS

Background
Evidence-based practice advocates utilising best current research evidence, while reflecting patient preference and clinical expertise in decision making. Successfully incorporating this evidence into practice is a complex process. Based on recommendations of existing guidelines and systematic evidence reviews conducted using the GRADE approach, treatment pathways for common spinal pain disorders were developed.

Aims
The aim of this study was to identify important potential facilitators to the integration of these pathways into routine clinical practice.

Methods
A 22 person stakeholder group consisting of patient representatives, clinicians, researchers and members of relevant clinical interest groups took part in a series of moderated focus groups, followed up with individual, semi-structured interviews. Data were analysed using content analysis.

Results
Participants identified a number of issues which were categorized into broad themes. Common facilitators to implementation included continual education and synthesis of research evidence which is reflective of everyday practice; as well as the use of clear, unambiguous messages in recommendations. Meeting additional training needs in new or extended areas of practice was also recognized as an important factor. Different stakeholders identified specific areas which could be associated with successful uptake. Patients frequently defined early involvement in a shared decision making process as important. Clinicians identified case based examples and information on important prognostic indicators as useful tools to aiding decisions.

Conclusion
A number of potential implementation strategies were identified. Further work will examine the impact of these and other important factors on the integration of evidence-based treatment recommendations into clinical practice.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery.

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice.

Management of Hyperphosphataemia in Chronic Kidney Disease:Summary of National Institute for Health and Clinical Excellence (NICE) Guideline

Bone disease and ectopic calcification are the two main consequences of hyperphosphataemia of chronic kidney disease (CKD). Observational studies have demonstrated that hyperphosphataemia in CKD is associated with increased mortality. Furthermore, the use of phosphate binders in dialysis patients is associated with significantly lower mortality. The UK Renal Registry data show significant underachievement of phosphate targets in dialysis patients. It is believed to be due to wide variation in how management interventions are used. The National Institute for Health and Clinical Excellence (NICE) has developed a guideline on the management of hyperphosphataemia in CKD. This is based on the evidence currently available using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This review outlines the recommendations including research recommendations and discusses methodology, rationale and challenges faced in developing this guideline and the health economic model used to assess the cost-effectiveness of different phosphate binders. © 2013 S. Karger AG, Basel.

Learning, development, and support needs of community palliative care clinical nurse specialists

Background: The palliative care clinical nurse specialist (PC-CNS) is a core member of the specialist palliative care team. According to professional policy, the role has four specific components: clinical practice, education, research, and leadership and management. Little is known about how to support staff in this role. Aim: The aim of this study was to explore what learning, development, and support PC-CNSs in one hospice need to enable them to fulfil all components of their role. Design: Using a descriptive exploratory approach, semi-structured interviews were undertaken with a purposive sample of community PC-CNSs from a hospice in Northern Ireland. Interviews were audio-recorded, transcribed verbatim, and thematically analysed. Findings: Seventeen interviews were analysed and three themes identified: influence of organisational culture, influence of the individual, and learning and development solutions. Conclusions: Participants reported that the PC-CNS role was stressful. They identified that the organisational culture and indeed individuals themselves influenced the learning and development support available to help them fulfil the four components of the role. Working relationships and stability within teams affected how supported individuals felt and had implications for managers in meeting the needs of staff while balancing the needs of the service.