Supporting General Practitioners and people withhypertension to maximise medication use to control bloodpressure: the contribution of Collective Intelligence to thedevelopment of the ‘Maximising Adherence, MinimisingInertia’ (MIAMI) intervention

Background: Hypertension remains one of the most important modifiable risk factors for stroke and heart disease. Anti-hypertensive medications are effective, but are often not used to maximum benefit. Sub-optimal dosing by prescribers and challenges with medication-taking for patients remain barriers to effective blood pressure control. Objectives: We aimed to systematically develop a theory-based complex intervention to support General Practitioners (GPs) and people with hypertension to maximise medication use to control blood pressure. Methods: We used the three-phase Behaviour Change Wheel (BCW) as the overarching intervention development framework. Collective Intelligence methodology was used to operationalise the stakeholder input to Phases 2 and 3 of the BCW. This took the form of a Collective Intelligence workshop with 19 stakeholders from diverse backgrounds including lived experience, general practice, nursing, pharmacy and health psychology. Techniques such as barrier identification, idea-writing and scenario-based design were used to generate possible intervention options. Intervention options were then selected and refined using the Acceptability, Practicability, Effectiveness, Affordability, Side-effects and Equity (APEASE) criteria and guidance from the MIAMI Public and Patient Involvement Panel. Results: The finalised MIAMI intervention consists of both GP and patient supports. GP supports include a 30-minute online training, information booklet and consultation guide (drop-down menu) embedded within the patient electronic health system. Patient supports include a pre-consultation plan, website, and a structured GP consultation with results from an Ambulatory Blood Pressure Monitor and urine chemical adherence test. The intervention components have been mapped to the intervention functions of the BCW and Behaviour Change Technique Ontology. Conclusion: Collective Intelligence offered a novel method to operationalise stakeholder input to Phases 2 and 3 of the BCW. The MIAMI intervention is now at pilot evaluation stage

Supporting General Practitioners and people withhypertension to maximise medication use to control bloodpressure: the contribution of Collective Intelligence to thedevelopment of the ‘Maximising Adherence, MinimisingInertia’ (MIAMI) intervention

Background: Hypertension remains one of the most important modifiable risk factors for stroke and heart disease. Anti-hypertensive medications are effective, but are often not used to maximum benefit. Sub-optimal dosing by prescribers and challenges with medication-taking for patients remain barriers to effective blood pressure control. Objectives: We aimed to systematically develop a theory-based complex intervention to support General Practitioners (GPs) and people with hypertension to maximise medication use to control blood pressure. Methods: We used the three-phase Behaviour Change Wheel (BCW) as the overarching intervention development framework. Collective Intelligence methodology was used to operationalise the stakeholder input to Phases 2 and 3 of the BCW. This took the form of a Collective Intelligence workshop with 19 stakeholders from diverse backgrounds including lived experience, general practice, nursing, pharmacy and health psychology. Techniques such as barrier identification, idea-writing and scenario-based design were used to generate possible intervention options. Intervention options were then selected and refined using the Acceptability, Practicability, Effectiveness, Affordability, Side-effects and Equity (APEASE) criteria and guidance from the MIAMI Public and Patient Involvement Panel. Results: The finalised MIAMI intervention consists of both GP and patient supports. GP supports include a 30-minute online training, information booklet and consultation guide (drop-down menu) embedded within the patient electronic health system. Patient supports include a pre-consultation plan, website, and a structured GP consultation with results from an Ambulatory Blood Pressure Monitor and urine chemical adherence test. The intervention components have been mapped to the intervention functions of the BCW and Behaviour Change Technique Ontology. Conclusion: Collective Intelligence offered a novel method to operationalise stakeholder input to Phases 2 and 3 of the BCW. The MIAMI intervention is now at pilot evaluation stage.Additional author: Gerard J Mollo

vCJD risk in the Republic of Ireland

BACKGROUND: The Republic of Ireland has the second highest incidence of BSE worldwide. Only a single case of vCJD has been identified to date. METHODS: We estimate the total future number of clinical cases of vCJD using an established mathematical model, and based on infectivity of bovine tissue calculated from UK data and on the relative exposure to BSE contaminated meat. RESULTS: We estimate 1 future clinical case (95% CI 0 – 15) of vCJD in the Republic of Ireland. Irish exposure is from BSE infected indigenous beef products and from imported UK beef products. Additionally, 2.5% of the Irish population was exposed to UK beef through residing in the UK during the 'at-risk' period. The relative proportion of risk attributable to each of these three exposures individually is 2:2:1 respectively. CONCLUSIONS: The low numbers of future vCJD cases estimated in this study is reassuring for the Irish population and for other countries with a similar level of BSE exposure

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Using collective intelligence methods to improve government data infrastructures and promote the use of complex data: the example of the Northern Ireland longitudinal study

BackgroundThis paper discusses how collective intelligence (CI) methods can be implemented to improve government data infrastructures, not only to support understanding and primary use of complex national data but also to increase the dissemination and secondary impact of research based on these data. The case study uses the Northern Ireland Longitudinal Study (NILS), a member of the UK family of census/administrative data longitudinal studies (UKLS).MethodsA stakeholder-engaged CI approach was applied to inform the transformation of the NILS Research Support Unit (RSU) infrastructure to support researchers in their use of government data, including collaborative decision-making and better dissemination of research outputs.ResultsWe provide an overview of NILS RSU infrastructure design changes that have been implemented to date, focusing on a website redesign to meet user information requirements and the formation of better working partnerships between data users and providers within the Northern Ireland data landscape. We also discuss the key challenges faced by the design team during this project of transformation.ConclusionOur primary objective to improve government data infrastructure and to increase dissemination and the impact of research based on data was a complex and multifaceted challenge due to the number of stakeholders involved and their often conflicting perspectives. Results from this CI approach have been pivotal in highlighting how NILS RSU can work collaboratively with users to maximize the potential of this data, in terms of forming multidisciplinary networks to ensure the research is utilized in policy and in the literature and providing academic support and resources to attract new researchers.<br/

Factors Influencing the Application of a Biopsychosocial Perspective in Clinical Judgement of Chronic Pain: Interactive Management with Medical Students

Background: Though there is wide support for the application of biopsychosocial perspectives in clinical judgement of chronic pain cases, such perspectives are often overlooked due to either inadequate training or attitudes favoring a biomedical approach. Recent research has indicated that despite such explanations, both established general practitioners (GP) and medical students account for some psychosocial factors when making clinical judgements regarding chronic pain cases, but report not being likely to apply these in real-world, clinical settings due to numerous factors, including available time with patients. Thus, it is evident that a greater understanding of clinical judgement-making processes and the factors that affect application of these processes is required, particularly regarding chronic pain.Objectives: The aims of the current study were to investigate medical students’ conceptualizations of the factors that influence application of a biopsychosocial approach to clinical judgement-making incases of chronic pain using interactive management (IM), model the relationships among these factors, and make recommendations to chronic pain treatment policy in light of the findings.Study Design: The current study used IM to identify and model factors that influence the application of a biopsychosocial approach to clinical judgement-making in cases of chronic pain, based on medical students’ conceptualizations of these factors.Setting: Two university classrooms.Methods: IM is a systems thinking and action mapping strategy used to aid groups in developing outcomes regarding complex issues, through integrating contributions from individuals with diverse views, backgrounds, and perspectives. IM commonly utilizes the nominal group technique and interpretive structural modeling, which in this context were employed to help medical students identify, clarify, and model influences on the application of biopsychosocial perspectives in treating chronic pain patients.Results: Results of IM group work revealed 7 core biopsychosocial approach application categories: GP attitudes, cost, GP knowledge, time, patient-doctor relationship, biomedical factors. and patient perception. GP attitudes was the most critical driver of all other competencies in the system, with cost and GP knowledge revealed as secondary drivers.Limitations: Potential differences in level of prior biopsychosocial perspective knowledge across participants and a potentially small sample size (though consistent with past research and appropriate for an exploratory study of this nature – for purposes of achieving the depth and richness of the deliberation and qualitative insights revealed by participants using the IM methodology).Conclusions: Results from this study may be used to both recommend further research on the identified factors influencing application of biopsychosocial perspectives in treatment of chronic pain and support amendment to extant health care policy, particularly with respect to cost, GP attitudes, and knowledge. Though this research claims neither that the influences identified are the only influences on biopsychosocial application, nor the order of their importance, the research does contribute to an ongoing effort to better understand the factors that influence doctors in their treatment of chronic pain