Though not biomarkers per se, these scores for certain genetic traits may someday be used by clinical laboratories to identify individuals’ risk for specific diseases
Can polygenic risk scores (a number that denotes a person’s genetic predisposition for certain traits) do a better job at predicting the likelihood of developing specific diseases, perhaps even before the onset of symptoms? Researchers at the Broad Institute of MIT and Harvard (Broad Institute) believe so, and their study could have implications for clinical laboratories nationwide.
In cooperation with medical centers across the US, the scientists “optimized 10 polygenic scores for use in clinical research as part of a study on how to implement genetic risk prediction for patients,” according to a Broad Institute news release.
The research team “selected, optimized, and validated the tests for 10 common diseases [selected from a total of 23 conditions], including heart disease, breast cancer, and type 2 diabetes. They also calibrated the tests for use in people with non-European ancestries,” the news release notes.
As these markers for genetic risk become better understood they may work their way into clinical practice. This could mean clinical laboratories will have a role in sequencing patients’ DNA to provide physicians with information about the probability of a patient’s elevated genetic risk for certain conditions.
However, the effectiveness of polygenic risk scores has faced challenges among diverse populations, according to the news release, which also noted a need to appropriately guide clinicians in use of the scores.
“With this work, we’ve taken the first steps toward showing the potential strength and power of these scores across a diverse population,” said Niall Lennon, PhD (above), Chief Scientific Officer of Broad Clinical Labs. “We hope in the future this kind of information can be used in preventive medicine to help people take actions that lower their risk of disease.” Clinical laboratories may eventually be tasked with performing DNA sequencing to determine potential genetic risk for certain diseases. (Photo copyright: Broad Institute.)
Polygenic Scores Need to Reflect Diversity
“There have been a lot of ongoing conversations and debates about polygenic risk scores and their utility and applicability in the clinical setting,” said Niall Lennon, PhD, Chair and Chief Scientific Officer of Broad Clinical Labs and first author of the study, in the news release. However, he added, “It was important that we weren’t giving people results that they couldn’t do anything about.”
In the paper, Lennon and colleagues explained polygenic risk scores “aggregate the effects of many genetic risk variants” to identify a person’s genetic predisposition for a certain disease or phenotype.
“But their development and application to clinical care, particularly among ancestrally diverse individuals, present substantial challenges,” they noted. “Clinical use of polygenic risk scores may ultimately prevent disease or enable its detection at earlier, more treatable stages.”
The scientists set a research goal to “optimize polygenic risk scores for a diversity of people.”
While performing the polygenic risk score testing on participants, Broad Clinical Labs focused on 10 conditions—including cardiometabolic diseases and cancer—selected by the research team based on “polygenic risk score performance, medical actionability, and clinical utility,” the Nature Medicine paper explained.
For each condition, the researchers:
Identified “exact spots in the genome that they would analyze to calculate the risk score.”
Used information from the NIH’s All of Us Research Program to “create a model to calibrate a person’s polygenic risk score according to that individual’s genetic ancestry.”
The All of Us program, which aims to collect health information from one million US residents, has three times more people of non-European ancestry than other data sources developing genetic risk scores, HealthDay News reported.
20% of Study Participants Showed High Risk for Disease
To complete their studies, Broad Institute researchers processed a diverse group of eMERGE participants to determine their clinical polygenic risk scores for each of the 10 diseases between July 2022 and August 2023.
Listed below are all conditions studied, as well as the number of participants involved in each study and the number of people with scores indicating high risk of the disease, according to their published paper:
Over 500 people (about 20%) of the 2,500 participants, had high risk for at least one of the 10 targeted diseases, the study found.
Participants in the study self-reported their race/ancestry as follows, according to the paper:
White: 32.8%
Black: 32.8%
Hispanic: 25.4%
Asian: 5%
American Indian: 1.5%
Middle Eastern: 0.9%
No selection: 0.8%
“We can’t fix all biases in the risk scores, but we can make sure that if a person is in a high-risk group for a disease, they’ll get identified as high risk regardless of what their genetic ancestry is,” Lennon said.
Further Studies, Scoring Implications
With 10 tests in hand, Broad Clinical Labs plans to calculate risk scores for all 25,000 people in the eMERGE network. The researchers also aim to conduct follow-up studies to discover what role polygenic risk scores may play in patients’ overall healthcare.
“Ultimately, the network wants to know what it means for a person to receive information that says they’re at high risk for one of these diseases,” Lennon said.
The researchers’ findings about disease risk are likely also relevant to healthcare systems, which want care teams to make earlier, pre-symptomatic diagnosis to keep patients healthy.
Clinical laboratory leaders may want to follow Broad Clinical Labs’ studies as they perform the 10 genetic tests and capture information about what participants may be willing to do—based on risk scores—to lower their risk for deadly diseases.
New federal funds likely to spark additional growth in hospital-at-home programs across the US while creating need for clinical laboratories to serve these homebound patients
In one of the latest examples of health systems’ providing acute care to patients outside of traditional hospital settings, Orlando Health announced its launch of the Orlando Health Hospital Care at Home program serving central Florida.
According to an Orlando Health press release, “The Orlando Health program is the first in Central Florida to be approved for Medicare and Medicaid patients, with future plans to expand the service for patients with private insurance and at other Orlando Health locations. It is an extension of a federal initiative created during the height of the COVID-19 pandemic to increase hospital capacity and maximize resources.”
Orlando Health is a not-for-profit healthcare system with 3,200 beds at 23 hospitals and emergency departments. It is the fourth largest employer in Central Florida with 4,500 physicians and 23,000 employees. Its Hospital Care at Home program serves patients who meet clinical criteria with 24/7 telehealth remote monitoring and virtual care from the Orlando Health Patient Care Hub. In-person nursing visits are also offered daily, according to Orlando Health.
“Orlando Health wanted to be able to provide a different level of care for its patients and give them a different opportunity to be cared for other than the brick-and-mortar of the hospital,” Linda Fitzpatrick (above), Assistant Vice President for Advanced Care at Orlando Health told Health News Florida. “We’ll have decreased infectious rates in their homes, decreased exposures. It is a healthier and happier place to be in order to heal.” Clinical laboratories in the Orlando area will have the opportunity to serve healthcare providers diagnosing patients in non-traditional healthcare settings. (Photo copyright: Orlando Sentinel.)
Lowering Costs and Avoiding In-hospital Infections, Medical Errors
Treating patients at home, even after inpatient visits, can save them money. At the same time, patients are more comfortable in their own homes and that contributes to faster recoveries.
“[We’ll be able to measure] heart rate, respiration, temperature, and blood pressure. We’ll also do video conferencing from that location with the patient. We’ll have nurses going to the patient’s home at least twice a day,” interventional cardiologist Rajesh Arvind Shah, MD, Senior Medical Director of Hospital Care at Home, Orlando Health, told Health News Florida.
Orlando Health patients can be safely treated in their homes for many conditions including:
According to the American Hospital Association (AHA), “many are seeing the hospital-at-home model as a promising approach to improve value. … This care delivery model has been shown to reduce costs, improve outcomes, and enhance the patient experience. In November 2020, the Centers for Medicare and Medicaid Services launched the Acute Hospital Care at Home program to provide hospitals expanded flexibility to care for patients in their homes.”
Hospital-in-the-Home (HITH) is considered by many experts to be safer for patients, as they are not exposed to nosocomial (hospital-acquired) infections, falls, and medical errors. In its landmark “To Err is Human” report of 1999, the Institute of Medicine (IOM) estimated that medical errors killed as many as 98,000 patients in hospitals annually.
And in “Australia’s Hospital-in-the-Home Care Model Demonstrates Major Cost Savings and Comparable Patient Outcomes,” we predicted that wider adoption of that country’s HITH model of patient care would directly affect pathologists and clinical laboratory managers who worked in Australia’s hospital laboratories. Having more HITH patients would increase the need to collect specimens in patient’s homes and transport them to a local clinical laboratory for testing, and, because they are central to the communities they serve, hospital-based medical laboratories would be well-positioned to provide this diagnostic testing.
New Federal Funds for HITH Programs
One recent impetus to create new HITH programs was the passing of the Consolidated Appropriations Act, 2023 (HR 2617). The federal bill includes two-year extensions of the telehealth waivers and Acute Hospital Care at Home (AHCaH) individual waiver that got started during the COVID-19 pandemic.
As of March 20, the federal Centers for Medicare and Medicaid Services (CMS) listed 123 healthcare systems and 277 hospitals in 37 states that had been approved to use the AHCaH wavier.
Now that federal funding for AHCaH waivers has been extended, more healthcare providers will likely start or expand existing HITH programs.
“I think [the renewed funding] is going to allow for additional programs to come online,” Stephen Parodi, MD, Executive Vice President External Affairs, Communications, and Brand, Permanente Federation; and Associate Executive Director, Permanente Medical Group, told Home Health Care News.
“For the next two years, there’s going to be a regulatory framework and approval for being able to move forward. It allows for the collection of more data, more information on quality, safety, and efficiency of these existing programs,” he added. Parodi also oversees Kaiser Permanente’s Care at Home program.
Labs without Walls
Clinical laboratories can play a major role in supporting HITH patients who require timely medical test results to manage health conditions and hospital recovery. Lab leaders may want to reach out to colleagues who are planning or expanding HITH programs now that federal funding has been renewed.
It may not be a boom trend, but more non-invasive diagnostic tests are coming to market as clinical laboratory tests that use breath as the specimen
Here’s a development that reinforces two important trends in diagnostics: non-invasive clinical laboratory assays and patient-self testing. Recently, the FDA expanded the clearance of one diagnostic test to allow patients to collect their own breath specimen at home under the supervision of the test manufacturer’s telehealth team.
Recently, however, the FDA announced it has “expanded the approval of the company’s 13C-Spirulina Gastric Emptying Breath Test (GEBT) to now include ‘at home’ administration under virtual supervision of Cairn Diagnostics.”
Self-administration of at-home tests by patients guided virtually by healthcare professionals is a major advancement in telehealth. But will this virtual-healthcare method be popular with both patients and their physicians?
Clinical Laboratory Diagnostics and Telehealth
Spurring a far greater acceptance of telehealth among patients and healthcare providers is one of the many ways the COVID-19 pandemic has impacted healthcare.
“Telehealth, particularly during the COVID-19 pandemic, has emerged as a preferred option for healthcare providers,” noted Kerry Bush, President and COO of Cairn Diagnostics, in a 2021 news release.
Cairn’s GEBT detects gastroparesis, a disease which, according to the NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), affects 50 people in every 100,000. According to the CDC, it is also sometimes a complication of diabetes. Symptoms include nausea, heartburn, bloating, a feeling of fullness long after eating a meal, vomiting, belching, and pain in the upper abdomen, the NIDDK notes.
In people with gastroparesis—sometimes called “delayed gastric emptying”—muscles that normally move food from the stomach to the small intestine do not work as they should, and the food remains in the stomach for too long. The traditional diagnostic tool used to diagnose gastroparesis is scintigraphy. The patient consumes a meal that has radioactive material mixed in and the digestion process is observed using a nuclear medicine camera as the material is eliminated through the bowels.
Cairn Diagnostics’ C-Spirulina Gastric Emptying Breath Test (above) recently received an expansion to its initial 2015 FDA approval that enables patients to self-administer the test at-home while being virtually guided by the company’s telehealth team. GEBTs are interpreted by CLIA-certified clinical laboratories and the results sent to patients’ doctors within 24-48 hours after testing. (Photo copyright: Cairn Diagnostics.)
Virtual Telehealth GEBT versus Scintigraphy
The telehealth process for Cairn Diagnostic’s Gastric Emptying Breath Test (GEBT) differs significantly from traditional scintigraphy testing. Once a physician prescribes the test, Cairn’s telehealth team contacts the patient to describe the virtual process. The team then ships the at-home test kit to the patient. To complete the testing, Cairn provides the patient with a web-based link to a secure audio/video platform.
During administration of the GEBT, a Cairn technician coaches the patient and supervises via video. Once the test is complete, the patient returns the breath samples to the CLIA-certified clinical laboratory by overnight courier. The test results are sent to the prescribing physician within 24-48 hours after the lab receives the samples.
Discovering New Uses for Breath as a Specimen for Clinical Laboratory Testing
For obvious reasons, patients prefer diagnostics that use specimens obtained noninvasively. GEBT is the latest in a growing list of diagnostic tests that use breath as a specimen.
For example, at Johns Hopkins clinicians employ breath testing to diagnose several conditions, including:
Each of these tests involves the patient consuming a particular substance, technicians capturing breath samples at certain intervals, and clinical laboratory personnel analyzing the samples to look for indicators of disease or intolerance.
New Types of Breath Tests
Breath samples are commonly used to diagnose gastrointestinal issues, but researchers also are seeking methods of using them to diagnose and monitor respiratory conditions as well.
In a recent study published in Nature Nanotechnology, scientists explored how breath can be used to monitor respiratory disease, noting that although breath contains numerous volatile metabolites, it is rarely used clinically because biomarkers have not been identified.
“Here we engineered breath biomarkers for respiratory disease by local delivery of protease-sensing nanoparticles to the lungs. The nanosensors shed volatile reporters upon cleavage by neutrophil elastase, an inflammation-associated protease with elevated activity in lung diseases such as bacterial infection and alpha-1 antitrypsin deficiency,” the researchers wrote.
Indeed, the search for new ways to use breath as a biological sample is being pursued by numerous groups and organizations. Owlstone Medical in the UK, for example, is developing breathalyzer tests for the detection of cancer as well as inflammatory and infectious disease.
“Whilst we are still in this discovery stage it is time to refine our study designs so that we can make progress towards tailored clinical application,” they wrote. “Breathomics is perhaps at the ‘end of the beginning’ for asthma at least; it has a ‘sexy’ name, some promising and consistent findings, and the key questions are at least being recognized.”
Better for Patients, Clinicians, and Clinical Laboratories
Virtual telehealth tests, ordered by physicians, administered at home, and interpreted in CLIA-certified clinical laboratories, is a trend pathologists may want to watch carefully, along with the development of other tests that use human breath as the specimen.
Less invasive, more personalized diagnostic tools that can be administered at home are better for patients. When those tools also provide detailed information, clinicians can make better decisions regarding care. Clinical laboratories that approach the use of at-home tests creatively, and which can accurately and quickly process these new types of tests, may have a market advantage and an opportunity to expand and grow.
The study ‘shows that measurement using a urine test provides improved accuracy relative to other measurement methods, for example certain kinds of blood tests,’ a KI news release states
Researchers at the Karolinska Institute (KI) in Sweden have developed a non-invasive urine-based test that can identify what type of asthma a patient has and its severity. If developed into a clinical laboratory diagnostic, such a test also could give clinicians a better idea of what treatment is more likely to be effective—a core goal of precision medicine.
Another benefit of this methodology is that it is a non-invasive test. Should further studies conclude that this urine-based test produces accurate results acceptable for clinical settings, medical laboratories would certainly be interested in offering this assay, particularly for use in pediatric patients who are uncomfortable with the venipunctures needed to collect blood specimens. Also, given the incidence of asthma in the United States, there is the potential for a urine-based asthma test to generate a substantial number of test requests.
The objective of the study, according to the Karolinska Institute researchers, was “To test if urinary eicosanoid metabolites can direct asthma phenotyping.” The team used mass spectrometry to measured certain lipid biomarkers (prostaglandins and leukotrienes), which are known to play a key role in the inflammation that occurs during asthma attacks.
According to a KI news release, “The study is based on data from the U-BIOPRED study (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes), which was designed to investigate severe asthma. The study included 400 participants with severe asthma, which often requires treatment with corticosteroid tablets, nearly 100 individuals with milder forms of asthma, and 100 healthy control participants.”
“We discovered particularly high levels of the metabolites of the mast cell mediator prostaglandin D2 and the eosinophil product leukotriene C4 in asthma patients with what is referred to as Type 2 inflammation. Using our methodology, we were able to measure these metabolites with high accuracy and link their levels to the severity and type of asthma,” said Johan Kolmert, PhD (above), a post-doctoral researcher at the Institute of Environmental Medicine, Karolina Institute, and first author of the study, in the KI news release. If perfected, such accuracy could lead to effective precision medicine clinical laboratory tests. (Photo copyright: Karolinska Institute.)
More Accurate Testing Could Lead to Biomarker-guided Precision Medicine
In the US alone, 25,131,132 people currently suffer from asthma, about five million of which are children under the age of 18, according to 2019 CDC statistics. The World Health Organization (WHO) reports that worldwide, “Asthma affected an estimated 262 million people in 2019 and caused 461,000 deaths.”
People with mild asthma may have good success using steroid inhalers. However, for those with moderate to severe asthma where inhalers are not effective, oral corticosteroids may also be necessary. But corticosteroids have been associated with high blood pressure and diabetes, among other negative side effects.
“To replace corticosteroid tablets, in recent times several biological medicines have been introduced to treat patients with Type 2 inflammation characterized by increased activation of mast cells and eosinophils,” said Sven-Erik Dahlén, Professor at the Institute of Environmental Medicine, Karolinska Institute, in the news release.
Currently, there are no simple tests that show what type of asthma a patient has. Instead, clinicians rely on lung function tests, patient interviews, allergy tests, and blood tests.
Earlier this year, researchers at Brigham and Women’s Hospital and Exosome Diagnostics in Massachusetts investigated a non-invasive, urine-based test for transplant rejection. According to a news release, “Patients can spend up to six years waiting for a kidney transplant. Even when they do receive a transplant, up to 20% of patients will experience rejection.”
“If rejection is not treated, it can lead to scarring and complete kidney failure. Because of these problems, recipients can face life-long challenges,” said Jamil Azzi, MD, Director of the Kidney Transplantation Fellowship Program at Brigham and Women’s Hospital, and Associate Professor of Medicine at Harvard School of Medicine. “Our goal is to develop better tools to monitor patients without performing unnecessary biopsies. We try to detect rejection early, so we can treat it before scarring develops,” he said.
Detecting Bladder Cancer with Urine Testing
Another condition where urine tests are being investigated is bladder cancer. An article in Trends in Urology and Men’s Health states, “Several point-of-care urine tests have been developed to help identify patients who may be at higher risk of bladder cancer.” Those tests could have the potential for use in primary care, which could mean fewer people would need invasive, painful, and risk-carrying cystoscopies.
“New tests to help identify hematuria patients who are at a higher risk of cancer would help to improve the diagnostic pathway, reduce the number diagnosed by emergency presentation, lessen the burden on urology services, and spare those who do not have cancer an invasive and costly examination, such as cystoscopy,” the article’s authors wrote.
These urine-based tests are still under investigation by various research teams and more research is needed before clinical trials can be conducted and the tests can be submitted for regulatory approval. Though still in the early stages of development, urine-based diagnostic testing represents far less invasive, and therefore safer, ways to identify and treat various diseases.
Studies into how the elements in urine might be used as biomarkers for clinical laboratory tests may lead to improved non-invasive precision medicine diagnostics that could save many lives.
Clinical laboratory leaders will want to pay close attention to a significant development in Maryland. The state’s All-Payer Medicare program—the nation’s only all-payer hospital rate regulation system—is broadening in scope to include outpatient services starting Jan. 1. The expanded program could impact independent medical laboratories, according to the Maryland Hospital Association (MHA), which told Dark Daily that those labs may see hospitals reaching out to them.
The Centers for Medicare and Medicaid Services (CMS) and the state of Maryland expect to save $1 billion by 2023 in expanding Maryland’s existing All-Payer Model—which focused only on inpatient services since 2014—to also include primary care physicians, skilled nursing facilities, independent clinical laboratories, and more non-hospital settings, according to a CMS statement.
Healthcare Finance notes that it represents “the first time, CMS is holding a state fully at risk for the total cost of care for Medicare beneficiaries.”
Value of Precision Medicine and Coordination of Care to Clinical Labs
“If a patient receives care at a [medical] laboratory outside of a hospital, Maryland hospitals would be looking at ways to coordinate the sharing of that freestanding laboratory information, so that the hospital can coordinate the care of that patient both within and outside the hospital setting,” Erin Cunningham, Communications Manager at MHA, told Dark Daily. Such a coordinating of efforts and sharing of clinical laboratory patient data should help promote precision medicine goals for patients engaged with physicians throughout Maryland’s healthcare networks.
The test of the new program—called the Total Cost of Care (TCOC) Model—also could be an indication that Medicare officials are intent on moving both inpatient and outpatient healthcare providers away from reimbursements based on fees-for-services.
CMS and the state of Maryland said TCOC gives diverse providers incentives to coordinate, center on patients, and save Medicare per capita costs of care each year.
“What they are really doing is tracking how effective we are at managing the quality and the costs of those particular patients that are managed by the physicians and the hospitals together,” Kevin Kelbly, VP and Chief Financial Officer at Carroll Hospital in Westminster, told the Carroll County Times. “They will have set up certain parameters. If we hit those parameters, there could be a shared savings opportunity between the hospitals and the providers,” he added. (Photo copyright: LifeBridge Health.)
The TCOC runs from 2019 through 2023, when it may be extended by officials for an additional five years.
How Does it Work?
The TCOC Model, like the earlier All-Payer Model, will limit Medicare’s costs in Maryland through a per capita, population-based payment, Healthcare Finance explained.
It includes three programs, including the:
Maryland Primary Care Program (MDPCP), designed to incentivize physician practices by giving additional per beneficiary, per month CMS payments, and incentives for physicians to reduce the number of patients hospitalize;
Care Redesign Program (CRP), which is a way for hospitals to make incentive payments to their partners in care. In essence, rewards may be given to providers that work efficiently with the hospital to improve quality of services; and,
Hospital Payment Program, a population-based payment model that reimburses Maryland hospitals annually for hospital services. CMS provides financial incentives to hospitals that succeed in value-based care and reducing unnecessary hospitalizations and readmissions.
CMS and Maryland officials also identified these six high-priority areas for population health improvement:
Substance-use disorder;
Diabetes;
Hypertension;
Obesity;
Smoking; and
Asthma.
“We are going to save about a billion dollars over the next five years, but we are also providing better quality healthcare. So it’s going to affect real people in Maryland, and it helps us keep the whole healthcare system from collapsing, quite frankly,” Maryland Gov. Larry Hogan, told the Carroll County Times.
OneCare in Vermont, Different Approach to One Payer
Maryland is not the only state to try an all-payer model. Vermont’s OneCare is a statewide accountable care organization (ACO) model involving the state’s largest payers: Medicare, Medicaid, and Blue Cross and Blue Shield of Vermont, Healthcare Dive pointed out. The program aims to increase the number of patients under risk-based contracting and, simultaneously, encourage providers to meet population health goals, a Commonwealth Fund report noted.
Both Maryland’s and Vermont’s efforts indicate that payment plans which include value-based incentives are no longer just theory. In some markets, fees-for-service payment models may be gone for good.
Clinical laboratory leaders may want to touch base with their colleagues in Maryland and Vermont to learn how labs in those states are engaging providers and performing under payment programs that, if successful, could replace existing Medicare payment models in other states.
