Key mechanisms by which post-ICU activities can improve in-ICU care: results of the international THRIVE collaboratives

Objective: To identify the key mechanisms that clinicians perceive improve care in the intensive care unit (ICU), as a result of their involvement in post-ICU programs. Methods: Qualitative inquiry via focus groups and interviews with members of the Society of Critical Care Medicine’s THRIVE collaborative sites (follow-up clinics and peer support). Framework analysis was used to synthesize and interpret the data. Results: Five key mechanisms were identified as drivers of improvement back into the ICU: (1) identifying otherwise unseen targets for ICU quality improvement or education programs—new ideas for quality improvement were generated and greater attention paid to detail in clinical care. (2) Creating a new role for survivors in the ICU—former patients and family members adopted an advocacy or peer volunteer role. (3) Inviting critical care providers to the post-ICU program to educate, sensitize, and motivate them—clinician peers and trainees were invited to attend as a helpful learning strategy to gain insights into post-ICU care requirements. (4) Changing clinician’s own understanding of patient experience—there appeared to be a direct individual benefit from working in post-ICU programs. (5) Improving morale and meaningfulness of ICU work—this was achieved by closing the feedback loop to ICU clinicians regarding patient and family outcomes. Conclusions: The follow-up of patients and families in post-ICU care settings is perceived to improve care within the ICU via five key mechanisms. Further research is required in this novel area

Enablers and Barriers to Implementing ICU Follow-Up Clinics and Peer Support Groups Following Critical Illness: The Thrive Collaboratives

OBJECTIVES: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. DESIGN: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. SETTING: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. SUBJECTS: Clinicians from 21 sites. MEASUREMENT AND MAIN RESULTS: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. CONCLUSIONS: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles

Exploring evidence-policy linkages in health research plans: A case study from six countries

The complex evidence-policy interface in low and middle income country settings is receiving increasing attention. Future Health Systems (FHS): Innovations for Equity, is a research consortium conducting health systems explorations in six Asian and African countries: Bangladesh, India, China, Afghanistan, Uganda, and Nigeria. The cross-country research consortium provides a unique opportunity to explore the research-policy interface. Three key activities were undertaken during the initial phase of this five-year project. First, key considerations in strengthening evidence-policy linkages in health system research were developed by FHS researchers through workshops and electronic communications. Four key considerations in strengthening evidence-policy linkages are postulated: development context; research characteristics; decision-making processes; and stakeholder engagement. Second, these four considerations were applied to research proposals in each of the six countries to highlight features in the research plans that potentially strengthen the research-policy interface and opportunities for improvement. Finally, the utility of the approach for setting research priorities in health policy and systems research was reflected upon. These three activities yielded interesting findings. First, developmental consideration with four dimensions – poverty, vulnerabilities, capabilities, and health shocks – provides an entry point in examining research-policy interfaces in the six settings. Second, research plans focused upon on the ground realities in specific countries strengthens the interface. Third, focusing on research prioritized by decision-makers, within a politicized health arena, enhances chances of research influencing action. Lastly, early and continued engagement of multiple stakeholders, from local to national levels, is conducive to enhanced communication at the interface. The approach described has four main utilities: first, systematic analyses of research proposals using key considerations ensure such issues are incorporated into research proposals; second, the exact meaning, significance, and inter-relatedness of these considerations can be explored within the research itself; third, cross-country learning can be enhanced; and finally, translation of evidence into action may be facilitated. Health systems research proposals in low and middle income countries should include reflection on transferring research findings into policy. Such deliberations may be informed by employing the four key considerations suggested in this paper in analyzing research proposals

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Exploring health systems research and its influence on policy processes in low income countries

<p>Abstract</p> <p>Background</p> <p>The interface between research and policymaking in low-income countries is highly complex. The ability of health systems research to influence policy processes in such settings face numerous challenges. Successful analysis of the research-policy interface in these settings requires understanding of contextual factors as well as key influences on the interface. <it>Future Health Systems (FHS): Innovations for Equity </it>is a consortium conducting research in six countries in Asia and Africa. One of the three cross-country research themes of the consortium is analysis of the relationship between research (evidence) and policy making, especially their impact on the poor; insights gained in the initial conceptual phase of FHS activities can inform the global knowledge pool on this subject.</p> <p>Discussion</p> <p>This paper provides a review of the research-policy interface in low-income countries and proposes a conceptual framework, followed by directions for empirical approaches. First, four developmental perspectives are considered: social institutional factors; virtual versus grassroots realities; science-society relationships; and construction of social arrangements. Building on these developmental perspectives three research-policy interface entry points are identified: 1. Recognizing policy as complex processes; 2. Engaging key stakeholders: decision-makers, providers, scientists, and communities; and 3. Enhancing accountability. A conceptual framework with three entry points to the research-policy interface – policy processes; stakeholder interests, values, and power; and accountability – within a context provided by four developmental perspectives is proposed. Potential empirical approaches to the research-policy interface are then reviewed. Finally, the value of such innovative empirical analysis is considered.</p> <p>Conclusion</p> <p>The purpose of this paper is to provide the background, conceptual framework, and key research directions for empirical activities focused on the research-policy interface in low income settings. The interface can be strengthened through such analysis leading to potential improvements in population health in low-income settings. Health system development cognizant of the myriad factors at the research-policy interface can form the basis for innovative future health systems.</p

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms