Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK Clinical Practice Research Datalink

INTRODUCTION: Recent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients.

METHODS: A cohort of newly diagnosed breast cancer patients (1998 to 2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis).

RESULTS: After breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy.

CONCLUSIONS: Overall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.

General practice-recorded depression and antidepressant use in young people with newly diagnosed Type 1 diabetes: a cohort study using the Clinical Practice Research Datalink

Aims - To investigate whether young people with Type 1 diabetes have an increased rate of depression andantidepressant use and whether their risk varies by age group, time from diabetes diagnosis, calendar period ofdiagnosis or complications status. Methods - A cohort of incident cases of patients with Type 1 diabetes diagnosed before 35 years of age (n = 5548) wasidentified within the Clinical Practice Research Datalink and individually age and sex matched with up to two controlsubjects without diabetes (n = 10 657). Patients with depression were identified through general practice-recordeddepression codes and antidepressant prescriptions. Cox regression models gave hazard ratios for depression in peoplewith Type 1 diabetes compared with control subjects. Results - People with Type 1 diabetes were twice as likely to have a record of antidepressant use and generalpractice-diagnosed depression as their matched control subjects (hazard ratio 2.08, 95% CI 1.73–2.50, P < 0.001).These associations varied by time from diagnosis, with marked increases observed within the first 5 years of diagnosis(hazard ratio 2.14, 95% CI 1.51–3.03, P < 0.001), and by age at diabetes diagnosis, with excesses noted even in the 10-to 19-year age group (hazard ratio 1.45, 95% CI 1.06–1.98, P = 0.02). Conclusions - This population-based study shows that people with Type 1 diabetes have higher rates of generalpractice-recorded depression and antidepressant use. The excess is present within 5 years of diabetes diagnosis,suggesting psychological input for patients is warranted in the early years of their condition.

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.

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.

Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

The Family Model - A transgenerational approach to mental health in families: personal, clinical, educational, research, systems and policy perspectives

The Family Model – A transgenerational approach to mental health in families This workshop will provide an overview on The Family Model (TFM) and its use in promoting and facilitating a trans­generational family focus in Mental Health services, over the past 10­ - 15 years. Each of the speakers will address a different perspective, including service user/consumer, clinical practice, education & training, research and policy. Adrian Falkov (chair) will provide an overview of TFM to set the scene and a ‘policy to practice’ perspective, based on use of TFM in Australia. Author: Heide Lloyd. The Family Model ­ A personal (consumer/patient) perspective | United Kingdom Heide will provide a description of her experiences as a child, adult, parent & grandparent, using TFM as the structure around which to ‘weave’ her story and demonstrate how TFM has assisted her in understanding the impact of symptoms on her & family and how she has used it in her management of symptoms and recovery (personal perspective). The Family Model ­ Education & training perspective ­ Marie Diggins | United Kingdom PhD Bente Weimand | Norway Authors: ­ Marie Diggins | United Kingdom PhD Bente Weimand | Norway This combined (UK & Norwegian) presentation will cover historical background to TFM and its use in eLearning (the Social Care Institute for Excellence)and a number of other UK initiatives, together with a description of the postgraduate masters course at the University Oslo/Akershus, using TFM. The Family Model ­ A research perspective PhD Anne Grant | Northern Ireland Author: PhD Anne Grant | Ireland Anne Grant will describe how she used TFM as the theoretical framework for her PhD looking at family focused (nursing) practice in Ireland. The Family Model ­ A service systems perspective ­ Mary Donaghy | Northern Ireland Authors: PhD Adrian Falkov | Australia ­ Mary Donaghy | N Ireland Mary Donaghy will discuss how TFM has been used to support & facilitate a cross service ‘whole of system’ change program in Belfast (NI) to achieve improved family focused practice. She will demonstrate its utility in achieving a broader approach to service design, delivery and evaluation.