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Medical Articles

SimulConsult supports both old and new HGNC gene symbols

The SimulConsult Genome-Phenome Analyzer supports all HGNC gene symbols in use since 1 January 2010, even if the symbol has been changed. The hyperlinked article details how HGNC is systematically changing all the symbols that Excel turns into dates in a spreadsheet. But even if you use the old symbols such as SEPT12 in a variant table, or search for it in the software, SimulConsult recognizes that as being the HGNC symbol SEPTIN12.

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Efficacy study of the Genome-Phenome Analyzer published in Orphanet Journal of Rare Diseases

In the 81 cases (with 216 individuals) the gene abnormality was recognized in 100%, and it was ranked #1 in 94% of cases. Large CNVs could be analyzed in an integrated analysis, performed in 24 of the cases. The process is rapid enough to allow for periodic reanalysis of unsolved cases.

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UCSD study shows high efficacy for SimulConsult Genome-Phenome Analyzer

“In all families (84 pregnancies) pertinence was > 95% between signs/symptoms and molecular cause”, meaning that not only was the correct diagnosis ranked as #1 but no other diagnoses were close.

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Experience with Integrating Diagnostic Decision Support Software with Electronic Health Records: Benefits versus Risks of Information Sharing

Published in The Journal for Electronic Health Data and Methods on December 6, 2017 by Michael M. Segal, Alanna K. Rahm, Nathan C. Hulse, Grant Wood, Janet L. Williams, Lynn Feldman, Gregory J. Moore, David Gehrum, Michelle Yefko, Steven Mayernick, Roger Gildersleeve, Margie C. Sunderland, Steven B. Bleyl, Peter Haug, Marc S. Williams

The article describes the result of an NIH-sponsored study of integrating SimulConsult’s diagnostic decision support system with Electronic Health Record systems.

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Impact of a Patient-Facing Enhanced Genomic Results Report to Improve Understanding, Engagement, and Communication

Published in the Journal of Genetic Counselors in April 2018 (open access) by Williams JL, Rahm AK, Zallen DT, Stuckey H, Fultz K, Fan AL, Bonhag M, Feldman L, Segal MM, Williams MS.

The article describes the result of a PCORI-sponsored study of providing information about genetic testing to patients, including a display driven by the highly granular onset information in SimulConsult’s diagnostic decision support system.

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Evidence-Based Decision Support for Pediatric Rheumatology Reduces Diagnostic Errors

Published by the Journal of Pediatric Rheumatology Online on December 13, 2016 (open access) by Michael M. Segal, Balu Athreya, Mary Beth F. Son, Irit Tirosh, Jonathan S. Hausmann, Elizabeth Y. N. Ang, David Zurakowski, Lynn K. Feldman, and Robert P. Sundel

The article describes the result of an NIH-sponsored study of adding rheumatology information to the SimulConsult diagnostic decision support system. The 26 clinicians demonstrated a significant reduction in diagnostic errors following introduction of the software, from 28% errors while unaided to 15% using decision support (p < 0.0001). Improvement was greatest for emergency medicine physicians (p = 0.013) and clinicians in practice for less than 10 years (p = 0.012). This error reduction occurred despite the fact that testers employed an “open book” approach to generate their initial lists of potential diagnoses, spending an average of 8.6 min using printed and electronic sources of medical information before using the diagnostic software.

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Enhancing Genomic Laboratory Reports: A Qualitative Analysis of Provider Review

Published in the American Journal of Medical Genetics in May 2016 (open access) by Williams JL, Rahm AK, Stuckey H, Green J, Feldman L, Zallen DT, Bonhag M, Segal MM, Fan AL, Williams MS.

The article describes the responses by clinicians to SimulConsult’s prognosis table, as used in genomic reports. One sample: “I love it—no clicks, detailed, comprehensive enough that I didn’t feel I needed another source—everything a pediatrician would think about.”

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Genome interpretation: Clinical correlation is recommended

Published in Applied Translational Genomics, in July 22, 2015 by Michael M. Segal.

In a brain MRI report, the following words often appear: “clinical correlation is recommended”. These words signify that inadequate clinical information was provided, or that an unexpected finding on the MRI should be assessed clinically. “Clinical correlation is recommended” is less common in a report about a single gene or simple gene panel. This is because the very act of ordering the test conveys much of what is important about the clinical situation, and only rarely is further information needed.

Genetics labs are moving into new territory as they adopt next-generation genomic sequencing. When moving beyond single gene tests and simple panels, more clinical correlation is needed. The complexity of interpretation becomes similar to a brain MRI, only more so.

In an exome, thousands of variants are found. Even after comparing to other family members, and using estimates of variant pathogenicity, many genes must be considered. Sometimes clinical correlation can be as simple as using the key clinical finding, assuming that you know which finding is key. But sometimes the situation is more complicated: variants are found in a gene that hadn’t been considered clinically, or two genes are needed to explain the clinical picture, and more clinical correlation is needed.

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Clinical Pertinence Metric Enables Hypothesis-Independent Genome-Phenome Analysis for Neurologic Diagnosis

Published in the Journal of Child Neurology in June of 2015 by Michael M. Segal, MD, PhD, Mostafa Abdellateef, Ayman W. El-Hattab, MD, Brian S. Hilbush, PhD, Francisco M. De La Vega, PhD, Gerard Tromp, PhD, Marc S. Williams, MD, Rebecca A. Betensky, PhD, and Joseph Gleeson, MD

We describe an “integrated genome-phenome analysis” that combines both genomic sequence data and clinical information for genomic diagnosis. It is novel in that it uses robust diagnostic decision support and combines the clinical differential diagnosis and the genomic variants using a “pertinence” metric. This allows the analysis to be hypothesis-independent, not requiring assumptions about mode of inheritance, number of genes involved, or which clinical findings are most relevant. Using 20 genomic trios with neurologic disease, we find that pertinence scores averaging 99.9% identify the causative variant under conditions in which a genomic trio is analyzed and family-aware variant calling is done. The analysis takes seconds, and pertinence scores can be improved by clinicians adding more findings. The core conclusion is that automated genome-phenome analysis can be accurate, rapid, and efficient. We also conclude that an automated process offers a methodology for quality improvement of many components of genomic analysis.

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Enhancing genomic laboratory reports from the patients’ view: A qualitative analysis

Published by the American Journal of Medical Genetics (open access) on June 18, 2015 by Heather Stuckey, Janet L. Williams, Audrey L. Fan, Alanna Kulchak Rahm, Jamie Green, Lynn Feldman, Michele Bonhag, Doris T. Zallen, Michael M. Segal, Marc S. Williams

The article describes the responses by families to SimulConsult’s Prognosis Table, as used in genomic reports. Some samples:

– Gives idea of what to look for in the future
– Timeframes very helpful
– Would use as baseline for reference
– Everything on it is necessary
– Can use with provider for discussion

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Evidence-Based Decision Support for Neurological Diagnosis Reduces Errors and Unnecessary Workup

Published in the Journal of Child Neurology in April 2014 by Segal MM, Williams MS, Gropman AL, Torres AR, Forsyth R, Connolly AM, El-Hattab AW, Perlman SJ, Samanta D, Parikh S, Pavlakis SG, Feldman LK, Betensky RA, Gospe SM Jr.

Using vignettes of real cases and the SimulConsult diagnostic decision support software, neurologists listed a differential diagnosis and workup before and after using the decision support. Using the software, there was a significant reduction in error, up to 75% for diagnosis and 56% for workup. This error reduction occurred despite the baseline being one in which testers were allowed to use narrative resources and Web searching. A key factor that improved performance was taking enough time (>2 minutes) to enter clinical findings into the software accurately. Under these conditions and for instances in which the diagnoses changed based on using the software, diagnostic accuracy improved in 96% of instances. There was a 6% decrease in the number of workup items accompanied by a 34% increase in relevance. The authors conclude that decision support for a neurological diagnosis can reduce errors and save on unnecessary testing.

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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

Published in Genome Biology on March 25, 2014 by Brownstein CA et al.

The article describes the CLARITY genome interpretation contest, and how SimulConsult had by far the fastest analysis times.

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Genome-Phenome Analysis for Diagnosis and Gene Discovery

Presented on March 22, 2013 by Segal MM, Wiliams MS, Tromp G and Gleeson JG at the American College of Medical Genetics 2013 annual Meeting.

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Decision support for diagnosis: co-evolution of tools and resources

Published in Neurology on May 15, 2012 by Segal MM and Schiffmann R.

The editorial discusses the role for diagnostic decision support in facilitating an evidence-based discussion between clinicians and payers.

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The Impact of Computer Resources on Child Neurology

Published in “Pediatric Neurology: Principles and Practice”, Swaiman KF et al., editors, 5th edition, Saunders, Chapter 108 by Segal M and Lever S

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Attenuated variants of Lesch–Nyhan disease: the case of King James VI/I

Published in Brain on July 12, 2010 by Peter Garrard John Stephenson Vijeya Ganesan Timothy Peters

The authors used SimulConsult to analyze a historical diagnosis.

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A Handbook of Neurological Investigations in Children

Published as a book in September 2009 by King MD and Stephenson BP, Mac Keith Press

In the book the authors discuss SimulConsult, beginning on page 1 with “With the explosion of electronic information such as found on PubMed and the availability of freely accessible diagnostic software such as SimulConsult one might ask what possible use is there for a handbook like this.

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How doctors think, and how software can help avoid cognitive errors in diagnosis

Published in Acta Pediatric in November 12, 2007 by Michael M Segal, MD PhD

Textbooks teach about diagnosis by describing diseases and the collection of findings in each disease. However, patients show up with findings, not diseases, and we must invert our knowledge to take the patient’s collection of findings and figure out the correct diagnosis. It is not so simple to do this, particularly in pediatrics. The Office of Rare Diseases at the National Institutes of Health estimates that 8% of people have one of the 7000 diseases listed as ‘rare’, and most of these diseases have onset in the pediatric years.

This is a lot of information to consider, and as a result diagnosis is wrong an estimated 15% of the time.

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Top Ten Physician Inventors

MD NetGuide article “Top Ten Physician Inventors” (on page 7) cites as #2 Michael Segal MD PhD: “Was responsible for the development of SimulConsult, a decision-support software that combines clinical and laboratory findings to help physicians come to a simultaneous diagnosis on a disease.”

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Blogs, Wikis and Other Cutting Edge Technologies for Neurology

Published in Neurology Today on February 6, 2007 by Orly Avitzur MD.

A sophisticated neurology wiki that helps doctors make clinical decisions is exactly what child neurologist Michael M. Segal, MD, PhD, had in mind when he created SimulConsult. SimulConsult users input data into software that helps them arrive at a differential diagnosis of neurological syndromes.

David J. Michelson, MD, assistant professor of neurology at Loma Linda University School of Medicine, said he has been amazed by SimulConsult’s ability to generate perfect matches to single conditions.

“The software is very user-friendly and intuitive,” he said. “It is designed to highlight metabolic and genetic syndromes which often only differ by certain specific findings.” … a 7-year-old boy with a neurodegenerative disorder with dementia, cerebellar atrophy, and spastic quadriplegia – despite EMG and muscle biopsy results suggesting denervation – was a perfect match for neuroaxonal dystrophy. He quipped, “Steven Ashwal made that diagnosis within five seconds of hearing me describe the child, which just proves that I need the program a lot more than he does.”

The tool has matured and increased in accuracy through a collaborative effort of many neurologists. In contrast to Wikipedia, all submissions to the SimulConsult database are reviewed by doctors following the existing norms for medical journals. Dr. Segal contends that wikis are more descriptive, providing details about findings in diseases, than prescriptive, providing rules tailored for particular clinical situations. The descriptive information available through wikis is a good way to aggregate evidence-based medicine, Dr. Segal added.

“Our software addresses 1,400 inherited and congenital neurological diseases, and uses over 24,000 data points,” said Dr. Segal. “Since there are no clinical rules, adding new material is straightforward and can be done merely by changing individual data points.”

SimulConsult also created a blog format for clinical cases in which medical terms from a case narrative are hyperlinked into the diagnostic software ( Physicians can click into the software with all patient findings already entered. The cases blog format is being developed together with the Child Neurology Society for residents and other doctors in practice who want to keep their skills sharp and up-to-date with the latest advances in diagnostic knowledge.

The ability to click into information tools from narratives about patients has the potential for much wider application. “In essence, a medical chart is a privacy-protected blog,” Dr. Segal pointed out. If data such as labs, tests, history and physical exam findings can be filtered into software, physicians can be easily assisted in medical decision-making.”

“The cases blog illustrates the potential of a neurology wiki,” Dr. Segal continued. “As similar tools become an integral part of practice, opportunities for collecting the wisdom of the neurology community in these ways will increase.”