PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Muin J Khoury - Top 30 Publications

Human Genome Sequencing at the Population Scale: A Primer on High-Throughput DNA Sequencing and Analysis.

Most human diseases have underlying genetic causes. To better understand the impact of genes on disease and its implications for medicine and public health, researchers have pursued methods for determining the sequences of individual genes, then all genes, and now complete human genomes. Massively parallel high-throughput sequencing technology, where DNA is sheared into smaller pieces, sequenced, and then computationally reordered and analyzed, enables fast and affordable sequencing of full human genomes. As the price of sequencing continues to decline, more and more individuals are having their genomes sequenced. This may facilitate better population-level disease subtyping and characterization, as well as individual-level diagnosis and personalized treatment and prevention plans. In this review, we describe several massively parallel high-throughput DNA sequencing technologies and their associated strengths, limitations, and error modes, with a focus on applications in epidemiologic research and precision medicine. We detail the methods used to computationally process and interpret sequence data to inform medical or preventative action.

Editorial: Emergence of Gene-Environment Interaction Analysis in Epidemiologic Research.

Trends in utilization and costs of BRCA testing among women aged 18-64 years in the United States, 2003-2014.

PurposeWe examined 12-year trends in BRCA testing rates and costs in the context of clinical guidelines, national policies, and other factors.MethodsWe estimated trends in BRCA testing rates and costs from 2003 to 2014 for women aged 18-64 years using private claims data and publicly reported revenues from the primary BRCA testing provider.ResultsThe percentage of women with zero out-of-pocket payments for BRCA testing increased during 2013-2014, after 7 years of general decline, coinciding with a clarification of Affordable Care Act coverage of BRCA genetic testing. Beginning in 2007, family history accounted for an increasing proportion of women with BRCA tests compared with personal history, coinciding with BRCA testing guidelines for primary care settings and direct-to-consumer advertising campaigns. During 2013-2014, BRCA testing rates based on claims grew at a faster rate than revenues, following 3 years of similar growth, consistent with increased marketplace competition. In 2013, BRCA testing rates based on claims increased 57%, compared with 11% average annual increases over the preceding 3 years, coinciding with celebrity publicity.ConclusionThe observed trends in BRCA testing rates and costs are consistent with possible effects of several factors, including the Affordable Care Act, clinical guidelines and celebrity publicity.GENETICS in MEDICINE advance online publication, 21 September 2017; doi:10.1038/gim.2017.118.

BRCA Genetic Testing and Receipt of Preventive Interventions Among Women Aged 18-64 Years with Employer-Sponsored Health Insurance in Nonmetropolitan and Metropolitan Areas - United States, 2009-2014.

Genetic testing for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations can identify women at increased risk for breast and ovarian cancer. These testing results can be used to select preventive interventions and guide treatment. Differences between nonmetropolitan and metropolitan populations in rates of BRCA testing and receipt of preventive interventions after testing have not previously been examined.

A proposed approach to accelerate evidence generation for genomic-based technologies in the context of a learning health system.

Genomic technologies should demonstrate analytical and clinical validity and clinical utility prior to wider adoption in clinical practice. However, the question of clinical utility remains unanswered for many genomic technologies. In this paper, we propose three building blocks for rapid generation of evidence on clinical utility of promising genomic technologies that underpin clinical and policy decisions. We define promising genomic tests as those that have proven analytical and clinical validity. First, risk-sharing agreements could be implemented between payers and manufacturers to enable temporary coverage that would help incorporate promising technologies into routine clinical care. Second, existing data networks, such as the Sentinel Initiative and the National Patient-Centered Clinical Research Network (PCORnet) could be leveraged, augmented with genomic information to track the use of genomic technologies and monitor clinical outcomes in millions of people. Third, endorsement and engagement from key stakeholders will be needed to establish this collaborative model for rapid evidence generation; all stakeholders will benefit from better information regarding the clinical utility of these technologies. This collaborative model can create a multipurpose and reusable national resource that generates knowledge from data gathered as part of routine care to drive evidence-based clinical practice and health system changes.GENETICS in MEDICINE advance online publication, 10 August 2017; doi:10.1038/gim.2017.122.

Cascade Screening for Familial Hypercholesterolemia and the Use of Genetic Testing.

No Shortcuts on the Long Road to Evidence-Based Genomic Medicine.

Making genomic medicine evidence-based and patient-centered: a structured review and landscape analysis of comparative effectiveness research.

Comparative effectiveness research (CER) in genomic medicine (GM) measures the clinical utility of using genomic information to guide clinical care in comparison to appropriate alternatives. We summarized findings of high-quality systematic reviews that compared the analytic and clinical validity and clinical utility of GM tests. We focused on clinical utility findings to summarize CER-derived evidence about GM and identify evidence gaps and future research needs. We abstracted key elements of study design, GM interventions, results, and study quality ratings from 21 systematic reviews published in 2010 through 2015. More than half (N = 13) of the reviews were of cancer-related tests. All reviews identified potentially important clinical applications of the GM interventions, but most had significant methodological weaknesses that largely precluded any conclusions about clinical utility. Twelve reviews discussed the importance of patient-centered outcomes, although few described evidence about the impact of genomic medicine on these outcomes. In summary, we found a very limited body of evidence about the effect of using genomic tests on health outcomes and many evidence gaps for CER to address.Genet Med advance online publication 13 April 2017.

Utilization of genetic tests: analysis of gene-specific billing in Medicare claims data.

We examined the utilization of precision medicine tests among Medicare beneficiaries through analysis of gene-specific tier 1 and 2 billing codes developed by the American Medical Association in 2012.

Evaluating Precision Medicine's Ability to Improve Population Health-Reply.

The current state of implementation science in genomic medicine: opportunities for improvement.

The objective of this study was to identify trends and gaps in the field of implementation science in genomic medicine.

Trends in published meta-analyses in cancer research, 2008-2013.

In order to capture trends in the contribution of epidemiology to cancer research, we describe an online meta-analysis database resource for cancer clinical and population research and illustrate trends and descriptive detail of cancer meta-analyses from 2008 through 2013. A total of 4,686 cancer meta-analyses met our inclusion criteria. During this 6-year period, a fivefold increase was observed in the yearly number of meta-analyses. Fifty-six percent of meta-analyses concerned observational studies, mostly of cancer risk, more than half of which were genetic studies. The major cancer sites were breast, colorectal, and digestive. This online database for Cancer Genomics and Epidemiology Navigator will be continuously updated to allow investigators to quickly navigate the meta-analyses emerging from cancer epidemiology studies and cancer clinical trials.

CDC Grand Rounds: Family History and Genomics as Tools for Cancer Prevention and Control.

Although many efforts in cancer prevention and control have routinely focused on behavioral risk factors, such as tobacco use, or on the early detection of cancer, such as colorectal cancer screening, advances in genetic testing have created new opportunities for cancer prevention through evaluation of family history and identification of cancer-causing inherited mutations. Through the collection and evaluation of a family cancer history by a trained health care provider, patients and families at increased risk for a hereditary cancer syndrome can be identified, referred for genetic counseling and testing, and make informed decisions about options for cancer risk reduction (1). Although hereditary cancers make up a small proportion of all cancers, the number of affected persons can be large, and the level of risk among affected persons is high. Two hereditary cancer syndromes for which public health professionals have worked to reduce the burden of morbidity and mortality are hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome.

Population-Based Precision Cancer Screening: A Symposium on Evidence, Epidemiology, and Next Steps.

Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled "Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps". The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial. Cancer Epidemiol Biomarkers Prev; 25(11); 1449-55. ©2016 AACR.

The need for a next-generation public health response to rare diseases.

Epidemiology matters: peering inside the "black box" in economic evaluations of genetic testing.

Will Precision Medicine Improve Population Health?

The Cancer Epidemiology Descriptive Cohort Database: A Tool to Support Population-Based Interdisciplinary Research.

We report on the establishment of a web-based Cancer Epidemiology Descriptive Cohort Database (CEDCD). The CEDCD's goals are to enhance awareness of resources, facilitate interdisciplinary research collaborations, and support existing cohorts for the study of cancer-related outcomes.

A knowledge base for tracking the impact of genomics on population health.

We created an online knowledge base (the Public Health Genomics Knowledge Base (PHGKB)) to provide systematically curated and updated information that bridges population-based research on genomics with clinical and public health applications.

Convergence of Implementation Science, Precision Medicine, and the Learning Health Care System: A New Model for Biomedical Research.

Implementation of the 21-gene recurrence score test in the United States in 2011.

We examined hospital use of the 21-gene breast cancer test in the United States. We report state-level differences in utilization and propose a model for predicting implementation of guideline-recommended genomic testing.

From genomic medicine to precision medicine: highlights of 2015.

Reproducible Research Practices and Transparency across the Biomedical Literature.

There is a growing movement to encourage reproducibility and transparency practices in the scientific community, including public access to raw data and protocols, the conduct of replication studies, systematic integration of evidence in systematic reviews, and the documentation of funding and potential conflicts of interest. In this survey, we assessed the current status of reproducibility and transparency addressing these indicators in a random sample of 441 biomedical journal articles published in 2000-2014. Only one study provided a full protocol and none made all raw data directly available. Replication studies were rare (n = 4), and only 16 studies had their data included in a subsequent systematic review or meta-analysis. The majority of studies did not mention anything about funding or conflicts of interest. The percentage of articles with no statement of conflict decreased substantially between 2000 and 2014 (94.4% in 2000 to 34.6% in 2014); the percentage of articles reporting statements of conflicts (0% in 2000, 15.4% in 2014) or no conflicts (5.6% in 2000, 50.0% in 2014) increased. Articles published in journals in the clinical medicine category versus other fields were almost twice as likely to not include any information on funding and to have private funding. This study provides baseline data to compare future progress in improving these indicators in the scientific literature.

What is translational genomics? An expanded research agenda for improving individual and population health.

Clinical utility of genetic and genomic services: context matters.

Genomics in Public Health: Perspective from the Office of Public Health Genomics at the Centers for Disease Control and Prevention (CDC).

The national effort to use genomic knowledge to save lives is gaining momentum, as illustrated by the inclusion of genomics in key public health initiatives, including Healthy People 2020, and the recent launch of the precision medicine initiative. The Office of Public Health Genomics (OPHG) at the Centers for Disease Control and Prevention (CDC) partners with state public health departments and others to advance the translation of genome-based discoveries into disease prevention and population health. To do this, OPHG has adopted an "identify, inform, and integrate" model: identify evidence-based genomic applications ready for implementation, inform stakeholders about these applications, and integrate these applications into public health at the local, state, and national level. This paper addresses current and future work at OPHG for integrating genomics into public health programs.

Planning for the Future of Epidemiology in the Era of Big Data and Precision Medicine.

We live in the era of genomics and big data. Evaluating the impact on health of large-scale biological, social, and environmental data is an emerging challenge in the field of epidemiology. In the past 3 years, major discussions and plans for the future of epidemiology, including with several recommendations for actions to transform the field, have been launched by 2 institutes within the National Institutes of Health. In the present commentary, I briefly explore the themes of these recommendations and their effects on leadership, resources, cohort infrastructure, and training. Ongoing engagement within the epidemiology community is needed to determine how to shape the evolution of the field and what truly matters for changing population health. We also need to assess how to leverage existing epidemiology resources and develop new studies to improve human health. Readers are invited to examine these recommendations, consider others that might be important, and join in the conversation about the future of epidemiology.

Precision Public Health for the Era of Precision Medicine.

Targeted Cancer Screening in Average-Risk Individuals.

Targeted cancer screening refers to use of disease risk information to identify those most likely to benefit from screening. Researchers have begun to explore the possibility of refining screening regimens for average-risk individuals using genetic and non-genetic risk factors and previous screening experience. Average-risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without comorbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. In this paper, we describe the goals of targeted cancer screening in average-risk individuals, present factors on which cancer screening has been targeted, discuss inclusion of targeting in screening guidelines issued by major U.S. professional organizations, and present evidence to support or question such inclusion. Screening guidelines for average-risk individuals currently target age; smoking (lung cancer only); and, in some instances, race; family history of cancer; and previous negative screening history (cervical cancer only). No guidelines include common genomic polymorphisms. RCTs suggest that targeting certain ages and smoking histories reduces disease-specific cancer mortality, although some guidelines extend ages and smoking histories based on statistical modeling. Guidelines that are based on modestly elevated disease risk typically have either no or little evidence of an ability to affect a mortality benefit. In time, targeted cancer screening is likely to include genetic factors and past screening experience as well as non-genetic factors other than age, smoking, and race, but it is of utmost importance that clinical implementation be evidence-based.

A public health perspective on a national precision medicine cohort: balancing long-term knowledge generation with early health benefit.