Extending the scope of pooled analyses of individual patient biomarker data from heterogeneous laboratory platforms and cohorts using merging algorithms

Background: A common challenge in medicine, exemplified in the analysis of biomarker data, is that large studies are needed for sufficient statistical power. Often, this may only be achievable by aggregating multiple cohorts. However, different studies may use disparate platforms for laboratory analysis, which can hinder merging. Methods: Using circulating placental growth factor (PIGF), a potential biomarker for hypertensive disorders of pregnancy (HDP) such as preeclampsia, as an example, we investigated how such issues can be overcome by inter-platform standardization and merging algorithms. We studied 16,462 pregnancies from 22 study cohorts. PIGF measurements (gestational age >= 20 weeks) analyzed on one of four platforms: R & Systems, Alere (R) Triage, Roche (R) Elecsys or Abbott (R) Architect, were available for 13,429 women. Two merging algorithms, using Z-Score and Multiple of Median transformations, were applied. Results: Best reference curves (BRC), based on merged, transformed PIGF measurements in uncomplicated pregnancy across six gestational age groups, were estimated. Identification of HDP by these PIGF-BRCS was compared to that of platform-specific curves. Conclusions: We demonstrate the feasibility of merging PIGF concentrations from different analytical platforms. Overall BRC identification of HDP performed at least as well as platform-specific curves. Our method can be extended to any set of biomarkers obtained from different laboratory platforms in any field. Merged biomarker data from multiple studies will improve statistical power and enlarge our understanding of the pathophysiology and management of medical syndromes. (C) 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.Peer reviewe

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome

Study Question What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary Answer International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What Is Known Already Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study Design, Size, Duration International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/Materials, Setting, Methods Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main Results and the Role of Chance The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; ii) reducing unnecessary testing; iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, Reasons for Caution Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider Implications of the Findings The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. Study Funding/Competing Interest(S) The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREEII criteria and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Residential Identity and Perceptions of Reclaimed Water: A Case Study of Greater Reno-Sparks, Nevada

This thesis examines the intersection between local identity and reclaimed water preferences in the greater Reno-Sparks area of northern Nevada. This case study uses data from a 2018 survey of residents in a rapidly growing community located in a water scarce region. Specifically, this research explores the relationship between residential identity and willingness to drink potable reclaimed water. Many regions experiencing water scarcity throughout the world have explored the option of reclaiming wastewater to supplement the potable drinking water supplies, which is also known as “potable reuse”. In Nevada, updated regulations in 2017 allow for planned potable reuse. However, past case studies of other unsuccessful attempts to implement a potable reuse projects demonstrate the necessity of public acceptance and understanding their preferences and beliefs surrounding the alternative water resource. Similar surveys have been completed in many other areas to gauge public opinion of reclaimed water for a variety of applications, including drinking water. The innovation of this thesis is twofold. First, this is the first project surveying public perception of reclaimed water in the greater Reno-Sparks area. Second, this is the first known study to analyze the influence of residential identity on perceptions of reclaimed water. Using data from a survey mailed to a sample of residents (n=474) in spring 2018, a mixed method approach is employed to examine if self-identification as a rural, urban, or suburban resident influences reclaimed water preferences and overall water management and resource preferences in the Reno-Sparks area. The findings reveal suburban respondents were significantly more likely to support reclaimed water for a variety of applications, including drinking water

Reclaiming Suburbia: Differences in Local Identity and Public Perceptions of Potable Water Reuse

Urban water managers are increasingly interested in incorporating reclaimed water into drinking supplies, particularly in rapidly growing arid and semi-arid urban areas, such as the western United States. Northern Nevada is one location that is considering augmenting drinking water supplies with reclaimed water, a practice that is known as planned potable water reuse. Potable water reuse can expand water supply and reduce wastewater disposal. However, past studies have shown that the introduction of potable reclaimed water can be controversial and requires an understanding of public perceptions of the resource prior to implementation. This study explores the factors that influence whether or not respondents in northern Nevada express willingness to drink reclaimed water. We pay specific attention to the degree to which self-identification as an urban, suburban, or rural resident influences how people consider using treated wastewater for both potable and non-potable purposes. To address this, we conducted a survey to assess community perceptions of reclaimed water use and applications in northern Nevada in the spring of 2018. We find that years spent living in the home and a respondent being female are negative and significant predictors of being willing to drink reclaimed water, while having heard of reclaimed water before and self-identification as a suburban resident are positive and significant predictors. As the region becomes more developed, particularly in its growing suburbs, it is essential to understand the nature of the interests and concerns regarding water resources and the expanded use of reclaimed water

What can we learn from interventions that aim to increase policy-makers’ capacity to use research? A realist scoping review

Abstract Background Health policy-making can benefit from more effective use of research. In many policy settings there is scope to increase capacity for using research individually and organisationally, but little is known about what strategies work best in which circumstances. This review addresses the question: What causal mechanisms can best explain the observed outcomes of interventions that aim to increase policy-makers’ capacity to use research in their work? Methods Articles were identified from three available reviews and two databases (PAIS and WoS; 1999–2016). Using a realist approach, articles were reviewed for information about contexts, outcomes (including process effects) and possible causal mechanisms. Strategy + Context + Mechanism = Outcomes (SCMO) configurations were developed, drawing on theory and findings from other studies to develop tentative hypotheses that might be applicable across a range of intervention sites. Results We found 22 studies that spanned 18 countries. There were two dominant design strategies (needs-based tailoring and multi-component design) and 18 intervention strategies targeting four domains of capacity, namely access to research, skills improvement, systems improvement and interaction. Many potential mechanisms were identified as well as some enduring contextual characteristics that all interventions should consider. The evidence was variable, but the SCMO analysis suggested that tailored interactive workshops supported by goal-focused mentoring, and genuine collaboration, seem particularly promising. Systems supports and platforms for cross-sector collaboration are likely to play crucial roles. Gaps in the literature are discussed. Conclusion This exploratory review tentatively posits causal mechanisms that might explain how intervention strategies work in different contexts to build capacity for using research in policy-making

Knowledge mobilisation for chronic disease prevention: the case of the Australian Prevention Partnership Centre

Abstract Background Cross-sectoral, multidisciplinary partnership research is considered one of the most effective means of facilitating research-informed policy and practice, particularly for addressing complex problems such as chronic disease. Successful research partnerships tend to be underpinned by a range of features that enable knowledge mobilisation (KMb), seeking to connect academic researchers with decision-makers and practitioners to improve the nature, quality and use of research. This paper contributes to the growing discourse on partnership approaches by illustrating how knowledge mobilisation strategies are operationalised within the Australian Prevention Partnership Centre (the Centre), a national collaboration of academics, policy-makers and practitioners established to develop systems approaches for the prevention of lifestyle-related chronic diseases. Methods We undertook interviews with key academics, policy, and practice partners and funding representatives at the mid-point of the Centre’s initial 5-year funding cycle. We aimed to explore how the Centre is functioning in practice, to develop a conceptual model of KMb within the Centre for use in further evaluation, and to identify ways of strengthening our approach to partnership research. Inductive and deductive thematic analysis was used to identify the key mechanisms underpinning the Centre’s KMb approach. Results Six key mechanisms appeared to facilitate KMb within our Centre, namely Engagement, Partnerships, Co-production, Capacity and Skills, Knowledge Integration, and Adaptive Learning and Improvement. We developed a conceptual model that articulated these mechanisms in relation to the structures and processes that support them, as well as the Centre’s goals. Findings also informed adaptations designed to strengthen the Centre. Conclusions Findings provide insights into the practical realities of operationalising KMb strategies within a research partnership. Overall, the centre is perceived to be progressing towards its KMb goals, but challenges include stakeholders from different settings understanding each other’s contexts and working together effectively, and ensuring knowledge generated across different projects within the Centre is integrated into a more comprehensive understanding of chronic disease prevention policy and practice. Our conceptual model is now informing ongoing developmental evaluation activities within the Centre, where it is being tested and refined

Additional file 2: of What can we learn from interventions that aim to increase policy-makers’ capacity to use research? A realist scoping review

Overview of included studies. (PDF 389 kb

Additional file 1: of What can we learn from interventions that aim to increase policy-makers’ capacity to use research? A realist scoping review

Review characteristics and search strategy. (DOCX 38 kb

Measurement of sST2 is comparable to PlGF in the diagnosis of early-onset pre-eclampsia

A diagnostic test to confirm pre-eclampsia would be beneficial for the clinical management of the syndrome. The Triage PlGF test is able to confirm pre-eclampsia with high accuracy, with the greatest efficacy at <35 weeks gestation. We recently found that the anti-inflammatory protein sST2 is elevated in the plasma of pre-eclamptic women compared to normal controls. Here sST2 and PlGF are compared in early-onset and late-onset pre-eclamptic women. sST2 was found to be an equally good diagnostic tool for early-onset (sST2 AUC 0.944 versus PlGF AUC 0.995; not significant) but not late-onset disease. © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved