Should their research result in new ways to identify and diagnose disease, doctors and clinical laboratories would do confirmatory testing and then initiate a precision medicine plan.
Dan Roden, MD, Senior Vice President for Personalized Medicine at VUMC and Senior Author of the Circulation study, said in a VUMC news release that the findings support the growing use of genetic information in clinical care.
“The questions we asked were: How many people who had no previous indication for cardiac genetic testing had pathogenic or likely pathogenic variants, and how many of those people actually had a phenotype in the electronic health records?” he explained.
Arrhythmia More Common than Previously Thought
The VUMC researchers drew data for their reports from the eMERGE Phase III study, which investigated the feasibility of population genomic screening by sequencing 109 genes across the spectrum of Mendelian diseases—genetic diseases that are caused by a mutation in a single gene—in more than 20,000 individuals. The scientists returned variant results to the participants and used EHR and follow-up clinical data to ascertain patient phenotypes, according to a Northwestern University Feinberg School of Medicine news release.
The research team looked specifically at the 120 consortium participants that had disease-associated pathogenic or likely pathogenic (P/LP) variants in the arrhythmia-associated genes. An analysis of the EHR data showed that 0.6% of the studied population had a variant that increases risk for potentially life-threatening arrhythmia, and that there was overrepresentation of arrhythmia phenotypes among patients, the VUMC news release noted.
The research team returned results to 54 participants and, with clinical follow-up, made 19 diagnoses (primarily long-QT syndrome) of inherited arrhythmia syndromes. Twelve of those 19 diagnoses were made only after variant results were returned, the study’s authors wrote.
Carlos G. Vanoye, PhD, Research Associate Professor of Pharmacology at Northwestern University (NU), said the study suggests arrhythmia genes may be more common than previously thought.
“A person can carry a disease-causing gene variant but exhibit no obvious signs or symptoms of the disease,” he said in the NU news release. “Because the genes we studied are associated with sudden death, which may have no warning signs, discovery of a potentially life-threatening arrhythmia gene variant can prompt additional clinical work-up to determine risks and guide preventive therapies.”
“The take-home message is that 3% of people will carry a pathogenic or likely pathogenic variant in a disease-causing gene and many others will carry variants of uncertain significance,” said Dan Roden, MD (above), Senior Vice President for Personalized Medicine at VUMC and Senior Author of the Circulation study in the VUMC news release. “We can use genetic testing, electronic health record phenotypes, and in vitro technologies to evaluate and find people who have unrecognized genetic disease and save lives by making earlier diagnoses.” Clinical laboratories will play a key role in making those early diagnoses and in managing personalized medical treatment plans. (Photo copyright: Vanderbilt University.)
Variants of Uncertain Significance
According to the NU news release, the scientists determined the functional consequences of the variants of uncertain significance they found and used that data to refine the assessment of pathogenicity. In the end, they reclassified 11 of the variants: three that were likely benign and eight that were likely pathogenic.
In the JAMA Oncology study, the VUMC scientists and other researchers conducted a phenome-wide association study to find EHR phenotypes associated with variants in 23 hereditary cancer genes. According to the VUMC news release, they identified 19 new associations:
The VUMC study findings could improve disease diagnosis and management for cancer patients and help identify high-risk individuals, the researchers noted in their published report.
In an editorial published in Circulation, titled, “First Steps of Population Genomic Medicine in the Arrhythmia World: Pros and Cons,” the professors noted that using genomic information in the case of potentially lethal inherited arrhythmia syndromes could be “lifesaving,” but questioned the benefits of reporting such secondary findings when patients are undergoing genome sequencing for other indications such as cancer.
“The likelihood that these ‘genetic diagnoses’ are translated into clinical diagnoses have not been completely evaluated,” they wrote. “In addition to the challenge of accurately identifying disease-causing genetic variants, defining the penetrance of such variants is critical to this process, i.e., what proportion of individuals in the general population with apparently pathogenic variants will develop the associated phenotype? If penetrance is low for particular gene/phenotype combinations, the costs associated with clinical screening and the psychological effects on individuals informed that they have potentially life-threatening variants may outweigh the benefits of the few new clinical diagnoses.”
These latest studies provide further evidence of the value of big data in healthcare and offer another lesson to clinical laboratories and pathologist about the future role data streaming from clinical laboratories and pathology assays may have in the growth of personalized medicine.
Clinical laboratories and microbiologists will want to be on the alert for this deadly infectious agent that has killed patients through blood infections
Healthcare continues to struggle with the issue of how much to disclose to the public when new and deadly infectious agents are identified in a limited number of patients. Timely disclosure of new pathogens is a matter of great concern to clinical laboratory scientists, microbiologists, and clinical pathologists because their laboratories get specimens from infected patients and they must correctly identify rare or emerging pathogens to help minimize the spread of disease.
This is why many medical laboratory professionals were surprised to see national news headlines recently about a particularly deadly new form of a pathogen. The Centers for Disease Control and Prevention (CDC) has been dealing with one particularly nasty example of Candida auris, or C. auris. This “superbug” fungus has been appearing in hospitals and healthcare clinics across the globe and it has killed people.
The news coverage of C. auris focused on two
elements:
First, how the pathogen was recognized by such
healthcare agencies as the CDC.
Second, why CDC and others did not issue a
public alert to hospitals, physicians, and other caregivers once it was known
that C. auris was responsible for the death of several patients.
Once C. auris takes hold, it can enter a patient’s bloodstream or wounds and cause life- threatening complications like sepsis. When hospitals rooms are not properly decontaminated, life-threatening hospital-acquired infections (HAIs), also known as nosocomial infections, can occur.
Incidences of HAIs have been on the rise in the past few
years. Dark Dailyhas reported
on this disturbing trend many times.
The New York Times (NYT) reported on one such HAI that had tragic consequences. A patient admitted to Mount Sinai Hospital in New York for abdominal surgery was later discovered to have contracted C. auris. He was immediately isolated and spent 90 days in the hospital before passing away. Tests showed that Candida auris was everywhere in his room.
“Everything was positive—the walls, the bed, the doors, the curtains, the phones, the sink, the whiteboard, the poles, the pump,” Scott Lorin, MD, President and Chief Operating Officer at Mount Sinai Brooklyn Hospital, told the NYT. “The mattress, the bed rails, the canister holes, the window shades, the ceiling, everything in the room was positive,” he said.
The hospital had to use special cleaning equipment to
sterilize the room and even found it necessary to tear out some ceiling and
floor tiles to annihilate the fungus, the NYT reported.
Media News Coverage of ‘Culture of Secrecy’
When this deadly fungus first emerged in America, it was not
disclosed to the public for a lengthy period of time. Then, when details of
deaths in hospitals due to the superbug went public, the national news media
reacted but then went silent. Why?
In that article, the NYT states that “under its
agreement with states, the CDC is barred from publicly identifying hospitals
that are battling to contain the spread of dangerous pathogens.” So, the CDC is
prevented from revealing to the public the names and locations of facilities
that are dealing with C. auris. And state governments typically do not
share that information either.
The NYT article also states, “The CDC declined to
comment, but in the past officials have said their approach to confidentiality
is necessary to encourage the cooperation of hospitals and nursing homes, which
might otherwise seek to conceal infectious outbreaks.”
And that, “Those pushing for increased transparency say they
are up against powerful medical institutions eager to protect their
reputations, as well as state health officials who also shield hospitals from
public scrutiny.”
Common Yeast Infection or Killer Superbug? Both!
C. auris grows as a common yeast infection. However,
it can be life threatening if it enters the bloodstream.
“The average person calls Candida infections yeast infections,” William Schaffner, MD, Professor and Chair, Department of Preventative Medicine at Vanderbilt University Medical Center, told Prevention. “However, Candida auris infections are much more serious than your standard yeast infection. They’re a variety of so-called superbugs [that] can complicate the therapy of very sick people.”
The CDC reports that, as of May 31, 2019, there have been a total of 685 cases of C. auris reported in the US. The majority of those cases occurred in Illinois (180), New Jersey (124), and New York (336). Twenty more cases were reported in Florida, and eight other states—California, Connecticut, Indiana, Maryland, Massachusetts, Oklahoma, Texas, and Virginia—each had less than 10 confirmed cases of C. auris.
The CDC states the infection seems to be most prominent among populations that have had extended stays in hospitals or nursing facilities. Patients who have had lines or tubes such as breathing tubes, feeding tubes, or central venous catheters entering their body, and those who have recently been given antibiotics or antifungal medications, seem to be the most vulnerable to contracting C. auris.
The fungus typically attacks people who are already sick or have weakened immune systems, which can make it challenging to diagnose, the CDC notes. C. auris infections are typically diagnosed with special clinical laboratory testing of blood specimens or other body fluids. Infections have been found in patients of all ages, from infants to the elderly.
Data from the CDC indicates that C. auris can cause
bloodstream infections, wound infections, and ear infections. Common symptoms
that indicate a person has Candida auris include fever, chills,
weakness, low blood pressure, and general malaise that do not improve with
antibiotics.
“A patient’s temperature may go up, their blood pressure can
go down, and they have complications of a pre-existing illness because of Candida
auris,” Schaffner told Prevention.
The CDC reports that more than one in three patients with
invasive C. auris dies. Even though the mortality rates for Candida
auris are high, it is unclear whether patients are dying from the infection
or from their underlying illnesses. “Whatever the cause, having Candida
auris doesn’t help a patient in any way,” Schaffner noted.
The CDC states that it and its public health partners are
working hard to discover more about this fungus, and to devise ways to protect
people from contracting it. Average healthy people probably don’t need to worry
about becoming infected with Candida auris. However, individuals who are
at high risk, and healthcare professionals, microbiologists, and pathologists,
should be on the alert for this new superbug strain of fungus.
Genetic testing, gene sequencing done by clinical laboratories and anatomic pathology groups underpin how first-mover hospitals, health networks are improving patient outcomes
In just a few weeks, an unprecedented gathering will bring together the nation’s most prominent first-mover health networks, hospitals, and companies operating programs that deliver precision medicine daily to patients in clinical care settings.
On Sept. 12-13, 2018, “Breakthroughs with Genetic and Precision Medicine: What All Health Network CEOs Need to Know,” will take place at the Hutton Hotel in Nashville, Tenn. “What differentiates these sessions is the emphasis on each organization’s strategy, how it launched its precision medicine programs, what is improving in patient outcomes, and how payers are reimbursing for these services,” stated Robert L. Michel, Executive Director of the Precision Medicine Institute in Austin, Texas. “This is not about the science of precision medicine. Rather, it is about the practical elements required for any hospital, health system, or physician group to actually set up and deliver a precision medicine service to patients on a daily basis.”
Precision Medicine’s First-Mover Hospitals and Providers to Speak
Health systems and hospitals headlining this special conference are:
Exhibitors include the above, plus: Thermo Fisher, Philips, Sunquest, and MyGenetx.
“This meeting will give you the insider’s understanding about delivering precision medicine in real patient care settings that cannot be accessed at other venues,” noted Michel. “The goal is to have first-mover providers share their experiences, thus providing a road map that other hospitals, physician practices, and other providers at this conference can take back and follow with confidence.”
Michel said that sessions will be dedicated to precision medicine strategies, how it is being used in oncology, primary care, the role of pharmacogenomics, and use of healthcare big data. Speakers will describe the clever ways innovative health networks and hospitals are using healthcare big data to inform physicians in ways that improve outcomes, lower the cost of care and, in two real-world case studies, are generating seven-figure reimbursement from shared savings programs with certain health plans.
This year’s keynote address is by Jeffrey R. Balser, MD, PhD (above), President and CEO, Vanderbilt University Medical Center and Dean of the Vanderbilt University School of Medicine, one of the most progressive and innovative health systems in the country. (Photo copyright: Vanderbilt University.)
Using Healthcare Big Data to Achieve Precision Medicine Success, Shared Savings
“Shared savings successes will be one of the breakthrough achievements reported at the Nashville event,” he explained. “We’ve invited two prominent provider organizations to share how they are using healthcare big data to support physicians in achieving improved patient outcomes while at the same time impressively reducing the overall cost of care. To my knowledge, this is the first time these precision medicine case studies have been presented at a national meeting.”
One such presentation will be delivered by Philip Chen, MD, PhD, Chief Healthcare Informatics Officer at Sonic Healthcare USA Austin, Texas. Their precision medicine goal was to use healthcare big data to help physicians better manage diabetes and other chronic conditions in their practices. This program involved a large primary care practice and a major health insurer. Now in its fourth year, Sonic Healthcare USA is earning six- and seven-figure payments as part of a shared savings arrangement with the insurer.
“Shared savings is definitely a Holy Grail for all large health networks and physician groups as payers drop fee-for-service and switch providers to value-based payments,” said Michel. “The experience of Sonic Healthcare in this innovative three-way collaboration with an insurer and a very large physician group demonstrates that a strong data analytics capability and engagement with physicians can simultaneously bend the cost-of-care-curve downward while improving patient outcomes, as measured year-by-year. This is a presentation every C-Suite executive should attend.
Strategic, Business, Operational, and Financial Aspects of Precision Medicine
“This conference—centered upon the strategic, business, operational, and financial aspects of a precision medicine program—came to be because it is the unmet need of every health network CEO and C-Suite administrator,” observed Michel. “Every healthcare leader tasked with developing an effective clinical and financial strategy for his or her institution knows that the real challenge in launching a precision medicine program for patient care is not the science.
“Rather, the true challenges come from how to support clinical needs with the availability of capital, recruiting experienced clinicians, and putting the right informatics capabilities in place,” he stated. “Most hospital and health network administrators recognize the risk of launching a precision medicine program too early. They know such programs can suck up huge amounts of resources without producing significant improvements in patient care. What adds to the risk is that payers may be slow to reimburse for precision medicine.”
Register by September 1 and save $300 on tuition! Plus, take advantage of our special Team Discount Program, so you and your key team members can get the most out of the conference by attending together.
“Breakthroughs with Genetic and Precision Medicine: What All Health Network CEOs Need to Know” is the gold-standard summit for everyone active or interested in succeeding with precision medicine programs. Don’t miss out—register today!
SHERLOCK makes accurate, fast diagnoses for about 61-cents per test with no refrigeration needed; could give medical laboratories a new diagnostic tool
The tool is called SHERLOCK, which stands for (Specific High-sensitivity Enzymatic Reporter unLOCKing). And it is causing excitement in the scientific community for several reasons:
It can detect pathogens in extremely small amounts of genetic matter;
Tests can be performed using urine and/or saliva rather than blood;
The tests are extremely sensitive; and they
Cost far less than the diagnostic tests currently in use.
How SHERLOCK and CRISPR Differ and Why That’s Important
Scientists have long suspected that CRISPR could be used to detect viruses. However, far more attention has been given to the its genome editing capabilities. And, there are significant differences between how CRISPR and SHERLOCK work. According to the Science article, when CRISPR is used to edit genes, a small strip of RNA directs an enzyme capable of cutting DNA to a precise location within a genome. The enzyme that CRISPR uses is called Cas9 (CRISPR associated protein 9). It works like scissors, snipping the strand of DNA, so that it is either damaged or replaced by a healthy, new sequence.
SHERLOCK, however, uses a different enzyme—Cas13a (originally dubbed C2c2 by the researchers who discovered it). Cas13a goes to RNA, rather than DNA, and once it starts cutting, it doesn’t stop. It chops through any RNA it encounters. The researchers who developed SHERLOCK describe these cuts as “collateral cleavage.” According to an article published by STAT, “All that chopping generates a fluorescent signal that can be detected with a $200 device or, sometimes, with the naked eye.”
The screenshot above is from a video in which Feng Zhang, PhD (center), a Core Member of the Broad Institute at MIT and one of the lead researchers working on SHERLOCK, and his research team, explain the difference and value SHERLOCK will make in the detection of diseases like Zika. Click on the image above to watch the video. (Video copyright: Broad Institute/MIT.)
Early Stage Detection in Clinical Laboratories
A research paper published in Science states that SHERLOCK can provide “rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity.” Attomolar equates to about one part per quintillion—a billion-billion. According to the article on the topic also published in Science, “The detection sensitivity of the new CRISPR-Cas13a system for specific genetic material is one million times better than the most commonly used diagnostic technique.” Such sensitivity suggests that clinical laboratories could detect pathogens at earlier stages using SHERLOCK.
The Stat article notes that, along with sensitivity, SHERLOCK has specificity. It can detect a difference of a single nucleotide, such as the difference between the African and Asian strains of Zika (for example, the African strain has been shown to cause microcephaly, whereas the Asian strain does not). Thus, the combination of sensitivity and specificity could mean that SHERLOCK would be more accurate and faster than other diagnostic tests.
Clinicians in Remote Locations Could Diagnose and Treat Illness More Quickly
Perhaps one of the most important aspects of SHERLOCK is the portability and durability of the test. It can be performed on glass fiber paper and works even after the components have been freeze dried. “We showed that this system is very stable, so you can really put it on a piece of paper and it will survive. You don’t have to refrigerate it all the times,” stated Feng Zhang, PhD, in an interview with the Washington Post. Zhang is a Core Member of the Broad Institute at MIT and was one of the scientists who developed CRISPR.
The researchers note that SHERLOCK could cost as little as 61-cents per test to perform. For clinicians working in remote locations with little or no power, such a test could improve their ability to diagnose and treatment illness in the field and possibly save lives.
“If you had something that could be used as a screening test, very inexpensively and rapidly, that would be a huge advance, particularly if it could detect an array of agents,” stated William Schaffner, MD, Professor and Chair of the Department of Preventive Medicine at Vanderbilt University Medical Center, in the Post article. Schaffner describes the Broad Institute’s research as being “very, very provocative.”
The test could radically change the delivery of care in more modern settings, as well. “It looks like one significant step on the pathway [that] is the Holy Grail, which is developing point-of-care, or bedside detection, [that] doesn’t require expensive equipment or even reliable power,” noted Scott Weaver, PhD, in an article on Big Think. Weaver is a Professor and Director at the Institute for Human Infections and Immunity University of Texas Medical Branch in Galveston, Texas.
Just the Beginning
Anatomic pathologists and clinical laboratories will want to follow SHERLOCK’s development. It could be on the path to fundamentally transforming the way disease gets diagnosed in their laboratories and in the field.
According to the Post article, “The scientists have filed several US patent applications on SHERLOCK, including for uses in detecting viruses, bacteria, and cancer-causing mutations.” In addition to taking steps to secure patents on the technology, the researchers are exploring ways to commercialize their work, as well as discussing the possibility of launching a startup. However, before this technology can be used in medical laboratory testing, SHERLOCK will have to undergo the regulatory processes with various agencies, including applying for FDA approval.
Panel of webinar speakers included several physicians, a pathologist, and a director from the Food and Drug Administration (FDA)
Patient safety continues to be a major factor in the ongoing transformation of healthcare in the United States. As it does, more scrutiny is being given to how medical laboratories and anatomic pathology groups can contribute to improving patient safety.
Issues of patient safety associated with medical laboratories was a major topic during this webinar, including discussion about concerns associated with the clinical use of laboratory-developed tests. (more…)