The IGNITE network: a model for genomic medicine implementation and research.

BACKGROUND: Patients, clinicians, researchers and payers are seeking to understand the value of using genomic information (as reflected by genotyping, sequencing, family history or other data) to inform clinical decision-making. However, challenges exist to widespread clinical implementation of genomic medicine, a prerequisite for developing evidence of its real-world utility. METHODS: To address these challenges, the National Institutes of Health-funded IGNITE (Implementing GeNomics In pracTicE; www.ignite-genomics.org ) Network, comprised of six projects and a coordinating center, was established in 2013 to support the development, investigation and dissemination of genomic medicine practice models that seamlessly integrate genomic data into the electronic health record and that deploy tools for point of care decision making. IGNITE site projects are aligned in their purpose of testing these models, but individual projects vary in scope and design, including exploring genetic markers for disease risk prediction and prevention, developing tools for using family history data, incorporating pharmacogenomic data into clinical care, refining disease diagnosis using sequence-based mutation discovery, and creating novel educational approaches. RESULTS: This paper describes the IGNITE Network and member projects, including network structure, collaborative initiatives, clinical decision support strategies, methods for return of genomic test results, and educational initiatives for patients and providers. Clinical and outcomes data from individual sites and network-wide projects are anticipated to begin being published over the next few years. CONCLUSIONS: The IGNITE Network is an innovative series of projects and pilot demonstrations aiming to enhance translation of validated actionable genomic information into clinical settings and develop and use measures of outcome in response to genome-based clinical interventions using a pragmatic framework to provide early data and proofs of concept on the utility of these interventions. Through these efforts and collaboration with other stakeholders, IGNITE is poised to have a significant impact on the acceleration of genomic information into medical practice.

Neurology and psychiatry: waking up to opportunities of sleep. State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

Characterization and optimization of experimental variables within a reproducible bladder encrustation model and in vitro evaluation of the efficacy of urease inhibitors for the prevention of medical device-related encrustation

This study presents a reproducible, cost-effective in vitro encrustation model and, furthermore, describes the effects of components of the artificial urine and the presence of agents that modify the action of urease on encrustation on commercially available ureteral stents. The encrustation model involved the use of small-volume reactors (700 mL) containing artificial urine and employing an orbital incubator (at 37 degrees C) to ensure controlled stirring. The artificial urine contained sources of calcium and magnesium (both as chlorides), albumin and urease. Alteration of the ratio (% w/w) of calcium salt to magnesium salt affected the mass of encrustation, with the greatest encrustation noted whenever magnesium was excluded from the artificial urine. Increasing the concentration of albumin, designed to mimic the presence of protein in urine, significantly decreased the mass of both calcium and magnesium encrustation until a plateau was observed. Finally, exclusion of urease from the artificial urine significantly reduced encrustation due to the indirect effects of this enzyme on pH. Inclusion of the urease inhibitor, acetohydroxamic acid, or urease substrates (methylurea or ethylurea) into the artificial medium markedly reduced encrustation on ureteral stents. In conclusion, this study has described the design of a reproducible, cost-effective in vitro encrustation model. Encrustation was markedly reduced on biomaterials by the inclusion of agents that modify the action of urease. These agents may, therefore, offer a novel clinical approach to the control of encrustation on urological medical devices. (c) 2005 Wiley Periodicals, Inc.

Non-invasive in vivo imaging in small animal research

Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET), bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advantages and limitations to current imaging technology are discussed and the issues concerning small animal care during imaging are highlighted.

Characterization of the physicochemical, antimicrobial, and drug release properties of thermoresponsive hydrogel copolymers designed for medical device applications

In this study, a series of hydrogels was synthesized by free radical polymerization, namely poly(2-(hydroxyethyl) methacrylate) (pHEMA), poly(4-(hydroxybutyl)methacrylate) (pHBMA), poly(6-(hydroxyhexyl)methacrylate) (pHHMA), and copolymers composed of N-isopropylacrylamide (NIPAA), methacrylic acid (MA), NIPAA, and the above monomers. The surface, mechanical, and swelling properties (at 20 and 37 degrees C, pH 6) of the polymers were determined using dynamic contact angle analysis, tensile analysis, and thermogravimetry, respectively. The T-g and lower critical solution temperatures (LCST) were determined using modulated DSC and oscillatory rheometry, respectively. Drug loading of the hydrogels with chlorhexidine diacetate was performed by immersion in a drug solution at 20 degrees C (

Research ethics committees: values and power in higher education

The rise of research governance structures in universities has created huge disquiet amongst academic researchers. The unquestioning adoption of a medical model of ethical review based upon positivist methodological assumptions has created for many a mismatch between their own ongoing ethical research practice and the process of obtaining clearance from Research Ethics Committees (REC). This paper examines the issues that have contributed to dissatisfaction with the ethical review model that is prevalent within the modern university. Using examples from the authors’ own experiences, the dynamics of values, interests and power in research governance is examined from multiple perspectives including that of REC member and applicant; lecturer/student supervisor; researcher; and
university administrator. The paper reveals a rift between the values and objectives of the key players in research governance within the modern university and concludes by asking whether differences can be resolved so that a collaborative approach to ethical review may be incorporated into a renewed academic research culture. It is suggested that the alternative is increasing alienation from anything to do with ‘ethics’, with potentially serious consequences for the ethical standards of social research.

Conceptualizing a transformative research agenda

Transformative consumer researchers seek to enhance consumer well-being by tackling some of the more difficult and intractable social problems and getting the results into the hands of stakeholders who can apply the research findings. Although traditional research approaches offer a viable path for doing research seeking positive social change, alternative research approaches exist that are uniquely suited to the challenges of Transformative Consumer Research. This article examines the standard research process from the perspective of a transformative research agenda to highlight steps in the process that can be better adapted and suggests innovations inspired from other translational research programs.

Identifying research priorities in long term care homes

Concerns about the quality of care in long term care (LTC) homes range from inadequate daily care to understaffing and insufficient funding. LTC decision makers are challenged to keep up with the changing demographics of residents admitted to LTC who have increasingly complex care needs. Decisions regarding LTC policies and procedures need to be informed by research that identifies the most effective and efficient care practices.This study solicited feedback from LTC decision makers in Ontario, Canada, regarding research priorities to guide improvement in the quality of care in LTC homes. Representatives from 134 LTC homes responded (53.6% response rate). Nine thematic areas of research were identified: delivery of care; staffing; organization and structure of homes; funding; indicators, standards, policies, and procedures; managing difficult behaviors; education; safety; and infectious disease control. It is anticipated that these themes will steer research down a path that is responsive to the information needs of practitioners in LTC homes. © 2012 American Medical Directors Association, Inc.

Agreement between self-report and medical records on signs and symptoms of respiratory illness

Background: Information on patient symptoms can be obtained by patient self-report or medical records review. Both methods have limitations. Aims: To assess the agreement between self-report and documentation in the medical records of signs/symptoms of respiratory illness (fever, cough, runny nose, sore throat, headache, sinus problems, muscle aches, fatigue, earache, and chills). Methods: Respondents were 176 research participants in the Hutterite Influenza Prevention Study during the 2008-2009 influenza season with information about the presence or absence of signs/symptoms from both self-report and primary care medical records. Results: Compared with medical records, lower proportions of self-reported fever, sore throat, earache, cough, and sinus problems were found. Total agreements between self-report and medical report of symptoms ranged from 61% (for sore throat) to 88% (for muscle aches and earache), with kappa estimates varying from 0.05 (for chills) to 0.41 (for cough) and 0.51 (for earache). Negative agreement was considerably higher (from 68% for sore throat to 93% for muscle aches and earache) than positive agreement (from 13% for chills to 58% for earache) for each symptom except cough where positive agreement (77%) was higher than negative agreement (64%). Agreements varied by age group. We found better agreement for earache (kappa=0.62) and lower agreements for headache, sinus problems, muscle aches, fatigue, and chills in older children (aged =5 years) and adults. Conclusions: Agreements were variable depending on the specific symptom. Contrary to research in other patient populations which suggests that clinicians report fewer symptoms than patients, we found that the medical record captured more symptoms than selfreport. Symptom agreement and disagreement may be affected by the perspectives of the person experiencing them, the observer, the symptoms themselves, measurement error, the setting in which the symptoms were observed and recorded, and the broader community and cultural context of patients. © 2012 Primary Care Respiratory Society UK. All rights reserved.