Precision Public Health for the Era of Precision Medicine Khoury, Muin J., MD, PhD; Iademarco, Michael F., MD, MPH; Riley, William T., PhD
American journal of preventive medicine,
03/2016, Letnik:
50, Številka:
3
Journal Article
Pragmatic measures are important to facilitate implementation and dissemination, address stakeholder issues, and drive quality improvement. This paper proposes necessary and recommended criteria for ...pragmatic measures, provides examples of projects to develop and identify such measures, addresses potential concerns about these recommendations, and identifies areas for future research and application. Key criteria for pragmatic measures include importance to stakeholders in addition to researchers, low burden, broad applicability, sensitivity to change, and being actionable. Examples of pragmatic measures are provided, including ones for different settings (e.g., primary care, hospital) and levels (e.g., individual, practitioner, setting) that illustrate approaches to produce broad-scale dissemination and the development of brief, standardized measures for use in pragmatic studies. There is an important need for pragmatic measures to facilitate pragmatic research, guide quality improvement, and inform progress on public health goals, but few examples are currently available. Development and evaluation of pragmatic measures and metrics would provide useful resources to advance science, policy, and practice.
The authors report on the development and calibration of item banks for depression, anxiety, and anger as part of the Patient-Reported Outcomes Measurement Information System (PROMIS®). Comprehensive ...literature searches yielded an initial bank of 1,404 items from 305 instruments. After qualitative item analysis (including focus groups and cognitive interviewing), 168 items (56 for each construct) were written in a first person, past tense format with a 7-day time frame and five response options reflecting frequency. The calibration sample included nearly 15,000 respondents. Final banks of 28, 29, and 29 items were calibrated for depression, anxiety, and anger, respectively, using item response theory. Test information curves showed that the PROMIS item banks provided more information than conventional measures in a range of severity from approximately −1 to +3 standard deviations (with higher scores indicating greater distress). Short forms consisting of seven to eight items provided information comparable to legacy measures containing more items.
Prior research has shown a serious lack of research transparency resulting from the failure to publish study results in a timely manner. The National Institutes of Health (NIH) has increased its use ...of publication rate and time to publication as metrics for grant productivity. In this study, we analyze the publications associated with all R01 and U01 grants funded from 2008 through 2014, providing sufficient time for these grants to publish their findings, and identify predictors of time to publication based on a number of variables, including if a grant was coded as a behavioral and social sciences research (BSSR) grant or not. Overall, 2.4% of the 27,016 R01 and U01 grants did not have a publication associated with the grant within 60 months of the project start date, and this rate of zero publications was higher for BSSR grants (4.6%) than for non-BSSR grants (1.9%). Mean time in months to first publication was 15.2 months, longer for BSSR grants (22.4 months) than non-BSSR grants (13.6 months). Survival curves showed a more rapid reduction of risk to publish from non-BSSR vs BSSR grants. Cox regression models showed that human research (vs. animal, neither, or both) and clinical trials research (vs. not) are the strongest predictors of time to publication and failure to publish, but even after accounting for these and other predictors, BSSR grants continued to show longer times to first publication and greater risk of no publications than non-BSSR grants. These findings indicate that even with liberal criteria for publication (any publication associated with a grant), a small percentage of R01 and U01 grantees fail to publish in a timely manner, and that a number of factors, including human research, clinical trial research, child research, not being an early stage investigator, and conducting behavioral and social sciences research increase the risk of time to first publication.
A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and ...acute myocardial infarction. A therapeutic ideal--relative to cell transplantation--would be to stimulate a resident source, thus avoiding the caveats of limited graft survival, restricted homing to the site of injury and host immune rejection. Here we demonstrate in mice that the adult heart contains a resident stem or progenitor cell population, which has the potential to contribute bona fide terminally differentiated cardiomyocytes after myocardial infarction. We reveal a novel genetic label of the activated adult progenitors via re-expression of a key embryonic epicardial gene, Wilm's tumour 1 (Wt1), through priming by thymosin β4, a peptide previously shown to restore vascular potential to adult epicardium-derived progenitor cells with injury. Cumulative evidence indicates an epicardial origin of the progenitor population, and embryonic reprogramming results in the mobilization of this population and concomitant differentiation to give rise to de novo cardiomyocytes. Cell transplantation confirmed a progenitor source and chromosome painting of labelled donor cells revealed transdifferentiation to a myocyte fate in the absence of cell fusion. Derived cardiomyocytes are shown here to structurally and functionally integrate with resident muscle; as such, stimulation of this adult progenitor pool represents a significant step towards resident-cell-based therapy in human ischaemic heart disease.
The National Institutes of Health Office of Behavioral and Social Sciences Research (OBSSR) recently released its strategic plan for 2017-2021. This plan focuses on three equally important strategic ...priorities: 1) improve the synergy of basic and applied behavioral and social sciences research, 2) enhance and promote the research infrastructure, methods, and measures needed to support a more cumulative and integrated approach to behavioral and social sciences research, and 3) facilitate the adoption of behavioral and social sciences research findings in health research and in practice. This commentary focuses on scientific priority two and future directions in measurement science, technology, data infrastructure, behavioral ontologies, and big data methods and analytics that have the potential to transform the behavioral and social sciences into more cumulative, data rich sciences that more efficiently build on prior research.
This paper addresses the rapid pace of change in the technologies that support digital interventions; the complexity of the health problems they aim to address; and the adaptation of scientific ...methods to accommodate the volume, velocity, and variety of data and interventions possible from these technologies. Information, communication, and computing technologies are now part of every societal domain and support essentially every facet of human activity. Ubiquitous computing, a vision articulated fewer than 30 years ago, has now arrived. Simultaneously, there is a global crisis in health through the combination of lifestyle and age-related chronic disease and multiple comorbidities. Computationally intensive health behavior interventions may be one of the most powerful methods to reduce the consequences of this crisis, but new methods are needed for health research and practice, and evidence is needed to support their widespread use.
The challenges are many, including a reluctance to abandon timeworn theories and models of health behavior—and health interventions more broadly—that emerged in an era of self-reported data; medical models of prevention, diagnosis, and treatment; and scientific methods grounded in sparse and expensive data. There are also many challenges inherent in demonstrating that newer approaches are, indeed, effective. Potential solutions may be found in leveraging methods of research that have been shown to be successful in other domains, particularly engineering. A more “agile science” may be needed that streamlines the methods through which elements of health interventions are shown to work or not, and to more rapidly deploy and iteratively improve those that do. There is much to do to advance the issues discussed in this paper, and the papers in this theme issue. It remains an open question whether interventions based in these new models and methods are, in fact, equally if not more efficacious as what is available currently. Economic analyses of these new approaches are needed because assumptions of net worth compared to other approaches are just that, assumptions. Human-centered design research is needed to ensure that users ultimately benefit. Finally, a translational research agenda will be needed, as the status quo will likely be resistant to change.
Creative use of new mobile and wearable health information and sensing technologies (mHealth) has the potential to reduce the cost of health care and improve well-being in numerous ways. These ...applications are being developed in a variety of domains, but rigorous research is needed to examine the potential, as well as the challenges, of utilizing mobile technologies to improve health outcomes. Currently, evidence is sparse for the efficacy of mHealth. Although these technologies may be appealing and seemingly innocuous, research is needed to assess when, where, and for whom mHealth devices, apps, and systems are efficacious. In order to outline an approach to evidence generation in the field of mHealth that would ensure research is conducted on a rigorous empirical and theoretic foundation, on August 16, 2011, researchers gathered for the mHealth Evidence Workshop at NIH. The current paper presents the results of the workshop. Although the discussions at the meeting were cross-cutting, the areas covered can be categorized broadly into three areas: (1) evaluating assessments; (2) evaluating interventions; and (3) reshaping evidence generation using mHealth. This paper brings these concepts together to describe current evaluation standards, discuss future possibilities, and set a grand goal for the emerging field of mHealth research.
Health services, economics, and outcomes research (referred to as health economics research hereinafter) is one of the interdisciplinary sciences that the National Institutes of Health (NIH) supports ...in order to pursue its overall mission to improve health. In 2015, NIH guidance was published to clarify the type of health economics research that NIH would continue to fund. This analysis aimed to determine if there were changes in the number of health economics applications received and funded by NIH after the release of the guidance. Health economics applications submitted to NIH both before and after publication of the guidance were identified using a machine learning approach with input from subject matter experts. Application and funding trends were examined by fiscal year, method of application (solicited vs. unsolicited), and activity code. This study found that application and funding rates of health economics research were decreasing prior to guidance. Following publication of this guidance, the application and funding rate of health economics applications increased.
Heart Regeneration in the Mexican Cavefish Stockdale, William T.; Lemieux, Madeleine E.; Killen, Abigail C. ...
Cell reports (Cambridge),
11/2018, Letnik:
25, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Although Astyanax mexicanus surface fish regenerate their hearts after injury, their Pachón cave-dwelling counterparts cannot and, instead, form a permanent fibrotic scar, similar to the human heart. ...Myocardial proliferation peaks at similar levels in both surface fish and Pachón 1 week after injury. However, in Pachón, this peak coincides with a strong scarring and immune response, and ultimately, cavefish cardiomyocytes fail to replace the scar. We identified lrrc10 to be upregulated in surface fish compared with Pachón after injury. Similar to cavefish, knockout of lrrc10 in zebrafish impairs heart regeneration without affecting wound cardiomyocyte proliferation. Furthermore, using quantitative trait locus (QTL) analysis, we have linked the degree of heart regeneration to three loci in the genome, identifying candidate genes fundamental to the difference between scarring and regeneration. Our study provides evidence that successful heart regeneration entails a delicate interplay between cardiomyocyte proliferation and scarring.
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•Astyanax mexicanus surface fish regenerate their hearts, but Pachón cavefish cannot•Successful regeneration is a delicate interplay between proliferation and scarring•lrrc10 is required for heart regeneration•Using QTL analysis, we have identified three genomic loci linked to heart regeneration
Stockdale et al. identify the Mexican cavefish as a model for heart regeneration research. This model provides an opportunity for direct comparison of natural regeneration versus scarring within a single species. Furthermore, they have identified key genomic regions regulating heart regeneration using an unbiased quantitative trait loci analysis approach.
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