COVID-19 has made telehealth an important tool. New technologies may help clinical laboratories collect blood samples ordered by physicians treating patients remotely
Even before COVID-19, telehealth services were gaining in popularity. But the SARS-CoV-2 pandemic fully opened the door to widespread use of mobile healthcare (mHealth) technologies. This has had an on-going impact on clinical laboratories.
Pre-pandemic, if a patient visited a healthcare provider and that provider ordered medical laboratory tests, the patient could simply walk down the hall to the lab’s patient service center and provide a blood sample. But when patients and providers meet through telehealth services, it is not so easy for lab personnel to collect samples for testing.
Several questions face healthcare providers and clinical laboratories as the pandemic subsides:
Will telehealth remain popular?
Does it benefit patient care?
Can physicians fit it into their workflows?
Will it continue to be reimbursed fairly?
COVID-19 Gives Telehealth Adoption a Big Boost
Telemedicine became important very quickly as SARS-CoV-2 coronavirus infections spread in early 2020. And not just in the United States. Clinicians worldwide began to embrace mHealth technology as a method of delivering care in a way that reduced the transmission of the virus.
The number of telemedicine consultations has declined since April 2020 but continues to be significantly higher than before the pandemic. It is also interesting to note that 90% of telemedicine visits were by phone in Australia and Canada, according to an article published in JAMA Network, titled, “Paying for Telemedicine After the Pandemic.”
Telehealth Popular with Community Health Centers but Disparities Remain
One of the big issues with telehealth, according to the NACHC, is that not all patients have access to the technology necessary for telehealth to be a viable alternative to traditional office visits. And that patients who use NACHC clinics tend to be “low income, minority, and uninsured or publicly insured.”
Thus, the NACHC lists “inadequate broadband” as one of the biggest issues regarding the continued use of telehealth. “Patients without reliable internet or the necessary technology still face difficulties accessing services, which has resulted in forgone or delayed care,” the NACHC noted.
Although in-person visits declined by 50%, the AJPM study’s authors noted that telehealth did not completely bridge the gap, particularly in areas where there were higher levels of poverty.
Physician Practices Are Businesses Too
The pandemic hurt businesses of all types, including independent physician’s offices. Approximately 8% of practices closed due to the pandemic, and 4% expect they will shut down within the next year. Along with the financial burden of shutdowns, physicians are burning out, Fast Company reported.
Organizations now have the technology in place and some patients have learned to utilize the service. However, the situation does raise important questions:
Will telehealth remain a critical component of healthcare in the future?
As physician’s offices close, will telehealth fill the gap?
Telehealth and Payment
Becker’s Hospital Review asked nine hospital CIOs if telehealth would “have staying power.” Every executive mentioned either reimbursement or payers in their response. Therefore, whether telehealth remains a viable method of care delivery may depend more on who will pay for it and less on popularity or patient access.
During the COVID-19 pandemic, CMS revised the rules surrounding telehealth. This allowed practitioners to charge the same for telehealth visits as they would for in-person visits. Many private payers followed suit as well. However, those rules were temporary and it is not certain that they will be extended.
“Payers must continue to reimburse for telehealth visits,” Mark Amey, CIO, Alameda Health System, told Becker’s Hospital Review. “This has been approved with emergency orders, but there are questions on whether this will become permanent. The sooner this is addressed and resolved, the sooner organizations can make sure they are investing in permanent—not temporary—solutions.”
Tests that use nasal swabs and saliva have seen an enormous boom thanks to demand for COVID-19 testing that can be done at home, and COVID-19 antibody tests also are in high demand. Additionally, direct-to-consumer (DTC) tests that use blood samples also are seeing advancements. However, none of those factors—not even reimbursement—help medical laboratory managers who are trying to identify new methods of collecting specimens for testing that support telehealth doctors.
“Innovations in blood sample collection are proving their utility and validity just in time for the home-based medicine push,” noted the AACC. The article goes on to describe Mitra microsampling devices, produced by Neoteryx. These devices collect 20 uL of blood via a finger prick and are already used by organ transplant recipients.
Another method involves the use of dried blood spots.
Though COVID-19 is a factor, it is not the only one driving development of new healthcare technologies that may expand options for medical laboratories looking for ways to collect samples remotely.
As the COVID-19 pandemic progresses, we will continue to bring you news about healthcare technology that can enhance clinical laboratories’ ability to collect patient samples, include advancements in remote sampling techniques and technologies.
By mining results of unrelated blood tests, the CIRRUS algorithm can inform doctors and patients earlier than usual of liver disease
For years Dark Daily and its sister publication The Dark Report have predicted that the same type of analytical software used on Wall Street to analyze bundles of debt, such as car loans, mortgages, and installment loans, would eventually find application in healthcare and clinical laboratory medicine. Now, researchers at the University of Southampton in England have developed just such an analytical tool.
The UK researchers call their algorithm CIRRUS, which stands for CIRRhosis Using Standard tests. It can, they say, accurately predict if a patient has cirrhosis of the liver at a much earlier stage than usual and produce information that is clinically actionable, using results from several common, routinely-ordered medical laboratory tests.
The University of Southampton scientists published their findings in BMJ Open.
Currently, the leading edge for this in clinical laboratory medicine is analysis of digital pathology images using image analysis tools and artificial intelligence (AI). However, CIRRUS is an example that analytical software is advancing in its ability to mine data from a number of clinically-unrelated lab tests on a patient and identify a health condition that might otherwise remain unknown.
The UK researchers designed the CIRRUS algorithm using routine clinical laboratory blood tests often requested in general practice to identify individuals at risk of advanced liver disease. These tests include:
“More than 80% of liver cirrhosis deaths are linked to alcohol or obesity and are potentially preventable,” noted Nick Sheron, MD, FRCP, Head of Population Hepatology at University of Southampton, and lead author of the study, in a press release. “However, the process of developing liver cirrhosis is silent and often completely unsuspected by GPs [general practitioners]. In 90% of these patients, the liver blood test that is performed is normal, and so liver disease is often excluded.
“This new CIRRUS algorithm can find a fingerprint for cirrhosis in the common blood tests done routinely by GPs,” he continued. “In most cases the data needed to find these patients already exists and we could give patients the information they need to change their lifestyle. Even at this late stage, if people address the cause by stopping drinking alcohol or reducing their weight, the liver can still recover.”
Mining Clinical Laboratory Blood Test Results
To perform the study, the research team analyzed data on blood test results for nearly 600,000 patients. Unlike most diagnostic liver algorithms, the CIRRUS model was created using a dataset comprised of patients from both primary and secondary care without the main intent of preselecting for liver disease. This renders it better suited for detecting liver disease outside a secondary care hepatology environment.
“Whilst we are all preoccupied with the coronavirus pandemic we must not lose sight of other potentially preventable causes of death and serious illness,” said Michael Moore, BM, BS, MRCP, FRCGP, Professor of Primary Health Care Research and Head of Academic Unit Primary Care and Population Sciences at University of Southampton, in the press release. Professor Moore co-authored the CIRRUS study.
“This test using routine blood test data available, gives us the opportunity to pick up serious liver disease earlier, which might prevent future emergency admission to hospital and serious ill health,” he said.
According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), cirrhosis is most common in adults ages 45 to 54 and about 1 in 400 adults in the US live with the disease. However, the actual number may be much higher as many people are not aware they have cirrhosis, because they do not experience symptoms until the liver is badly damaged.
The NIDDK reports complications from cirrhosis include:
Portal Hypertension, a condition where scar tissue partially blocks the normal flow of blood through the liver,
“Liver cirrhosis is a silent killer. The tests used most by GPs are not picking up the right people and too many people are dying preventable deaths. We looked at half a million anonymous records and the data we needed to run CIRRUS was already there in 96% of the people who went on to have a first liver admission,” stated Sheron in the press release. “With just a small change in the way we handle this data it should be possible to intervene in time to prevent many of these unnecessary deaths.”
“Alcohol-related liver diseases are far and away the most significant cause of alcohol-specific deaths, yet currently the vast majority of people find out that their liver is diseased way too late,” said Richard Piper, PhD, Chief Executive of Alcohol Change UK, a British charity and campaign group dedicated to reducing harm caused by alcohol abuse. “What is needed is a reliable means of alerting doctors and their patients to potential liver disease as early as possible. The CIRRUS process shows real promise, and we want to see it further developed, tested and implemented, to help save hundreds of thousands, if not millions, of lives.”
CIRRUS is a true milestone in the development of computer-assisted healthcare diagnostics. It will need more research, but the University of Southampton study shows that analytical software tools can mine clinical laboratory test results that were ordered for unrelated diagnostics and identify existing health conditions that might otherwise remain hidden to the patient’s physicians.
Since the early 1980s, UBC’s CMPT program, led by medical microbiologist Michael Noble, MD, has provided external quality assessment (EQA) for clinical microbiology and water testing laboratories. This includes providing biological samples related to:
“Typical of every jurisdiction in North America and probably around the world, BCCDC got swamped beyond swamped,” said Noble, the Clinical Microbiology Proficiency Testing (CMPT) program’s first and current Chair, in an exclusive interview with Dark Daily. “The increase was 10-fold, and they were unable to provide all the services they wanted to do. And since I was already running a proficiency testing program across the province, they asked if I would provide that service for COVID-19 for laboratories that were doing the testing.”
CMPT’s Proficiency Testing Serves Labs Worldwide
UBC’s CMPT external quality assessment (EQA) program serves all medical laboratories in British Columbia, as well as other labs in Canada, Europe, South America, and the Caribbean. Just over 200 laboratories currently participate in the program. More labs participated in past years, before lab consolidation affected CMPT and other programs as well, Noble said.
CMPT’s proficiency testing ensures that participant laboratories that have been provided with simulated samples can perform tests at the “level of quality and competence required,” notes UBC’s CMPT website.
COVID-19 Brings Non-Traditional ‘Laboratories’ to CMPT’s Proficiency Testing Program
UBC’s proficiency testing for SARS-CoV-2, the coronavirus that causes the COVID-19 infection, differs from other CMPT programs. That’s due to new participants that entered the laboratory testing program during the COVID-19 pandemic that are performing COVID-19 testing in non-traditional locations, Noble stated.
“In our proficiency programs, we had mainly been dealing with traditional clinical laboratories,” Noble explained. “But now, we find people doing COVID-19 testing—even though defined as medical laboratories—who are working in airports, or in tourism, or the movie industry, or forestry. They may never have worked in an actual clinical laboratory. So, it’s a very different style of proficiency testing. There has been a lot of handholding, teleconferences, discussions, and one-on-ones with that group,” Noble said.
In his career, Noble transitioned from medical microbiology to qualitology, which he describes as “the study of quality in the medical laboratory.”
In stressing the importance of laboratory quality testing, Noble describes the possibility of laboratory testing going awry and leading to a microbiological public health emergency.
“What happens if there’s a stool sample, and someone misses the presence of Campylobacteriosis in the stool? What happens if that’s part of a foodborne disease and there’s an outbreak in the city and samples are being missed? How many people will be impacted as a result of that error?” he asked.
University of British Columbia Endows a Chair for Laboratory Quality Management
Noble says UBC’s Program Office for Laboratory Quality Management (POLQM) has involved organizations worldwide and certified more than 500 people.
“The impact they have over their laboratories has been huge. Maybe that would have happened without us. But we were a part of that. And our impact is not one laboratory or one city or one province but widespread, and that’s a real and enriching experience to have,” he said.
But now it is time for him to move on. Noble secured (through UBC), a benefactor to establish the endowed Chair for Laboratory Quality Management. The family of the late Donald B. Rix, MD, a Canadian pathologist and philanthropist, gave $1.5 million (matched by the university) to create the Associate Professor (Grant Tenure) Donald B. Rix Professorship in Laboratory Quality at UBC, Department of Pathology and Laboratory Medicine.
Long-serving pathologists and medical laboratory professionals may remember that Rix was the founder and chair of MDS Metro Laboratory Services (now known as LifeLabs Medical Laboratory Services). It grew into the largest private medical laboratory in Western Canada.
Referring to this endowed new Chair for Laboratory Quality Management, Noble said, “I think this is the first named position of laboratory quality in North America.” UBC has commenced reviewing applications for the position, which is expected to be effective in January 2022. Pathologists and clinical laboratory scientists with appropriate qualifications and interest in this position should contact Dr. Noble’s office at the University of British Columbia Faculty of Medicine.
The technique allows the researchers to measure polymorphisms—variations in gene lengths—that are associated with many cancers and neurological diseases. The VCU scientists say the new technique costs less than $1 to scan each dPCR reaction.
“We chose to focus on FLT3 mutations because they are difficult to [diagnose], and the standard assay is limited in capability,” said physicist Jason Reed, PhD, Assistant Professor in the Virginia Commonwealth University Department of Physics, in a VCU press release.
Reed is an expert in nanotechnology as it relates to biology and medicine. He led a team that included other researchers in VCU’s physics department as well as physicians from VCU Massey Cancer Center and the Department of Internal Medicine at VCU School of Medicine.
The researchers said their technique matched the results of the LeukoStrat test in diagnosing the mutations. But unlike that test, the new technique also can measure variant allele frequency (VAL). This “can show whether the mutation is inherited and allows the detection of mutations that could potentially be missed by the current test,” states the VCU press release.
“We plan to continue developing and testing this technology in other diseases involving DNA structural mutations,” Reed said. “We hope it can be a powerful and cost-effective tool for doctors around the world treating cancer and other devastating diseases driven by DNA mutations.”
“In our approach we first used digital PCR, in which a mixed sample is diluted to less than one target molecule per aliquot and the aliquots are amplified to yield homogeneous populations of amplicons,” he said. “Then, we deposited each population onto an atomically-flat partitioned surface.”
The VCU researchers “scanned each partition with high-speed atomic force microscopy, in which an extremely sharp tip is rastered across the surface, returning a 3D map of the surface with nanoscale resolution,” he said. “We wrote code that traced the length of each imaged DNA molecule, and the distribution of lengths was used to determine whether the aliquot was a wild type [unmutated] or variant.”
In Diagnostics World, Reed said the method “doesn’t really have any more complexity than a PCR assay itself. It can easily be done by most lab technicians.”
A VCU press release from 2017 noted that Reed’s research team had developed technology that uses optical lasers (similar to those in a DVD player) to accelerate the scanning. The researchers previously published a study about the technique in Nature Communications, and a patent is currently pending.
“DNA sequencing is a powerful tool, but it is still quite expensive and has several technological and functional limitations that make it difficult to map large areas of the genome efficiently and accurately,” Reed said in the 2017 VCU press release. “Our approach bridges the gap between DNA sequencing and other physical mapping techniques that lack resolution. It can be used as a stand-alone method or it can complement DNA sequencing by reducing complexity and error when piecing together the small bits of genome analyzed during the sequencing process.”
Using CRISPR technology, the team also developed what they described as a “chemical barcoding solution,” placing markers on DNA molecules to identify genetic mutations.
New DNA Clinical Laboratory Testing?
Cancer diagnostics are constantly evolving and improving. It is not clear how long it will be before VCU’s new technique will reach clinical laboratories that perform DNA testing, if at all. But VCU’s new technique is intriguing, and should it prove viable for clinical diagnostic use it could revolutionize cancer diagnosis. It is a development worth watching.
The technology uses an easy-to-administer low-cost patch that can be applied to the skin like an adhesive bandage. The patch is virtually painless because the microneedles are too small to reach nerve receptors. Another unique aspect to this innovative approach to collecting a specimen for diagnostic testing is that the Washington University in St. Louis (WashU) research team designed the microneedle patch to include plasmonic-fluor. These are ultrabright gold nanolabels that light up target protein biomarkers and can make the biomarkers up to 1,400 times brighter at low concentrations, compared to traditional fluorescent labels.
The patch, states a WashU news release, “… can be applied to the skin, capture a biomarker of interest and, thanks to its unprecedented sensitivity, allow clinicians to detect its presence.”
The technology is low cost, easy for clinicians or patients themselves to use, and could eliminate the need for a trip to patient service center where a phlebotomist would draw blood for clinical laboratory testing, the news release states.
“We used the microneedle patch in mice for minimally invasive evaluation of the efficiency of a cocaine vaccine, for longitudinal monitoring of the levels of inflammatory biomarkers, and for efficient sampling of the calvarial periosteum [a skull membrane]—a challenging site for biomarker detection—and the quantification of its levels of the matricellular protein periostin, which cannot be accurately inferred from blood or other systemic biofluids,” the researchers wrote. “Microneedle patches for the minimally invasive collection and analysis of biomarkers in interstitial fluid might facilitate point-of-care diagnostics and longitudinal monitoring.”
Mark Prausnitz, PhD, Regents’ Professor, J. Erskine Love Jr. Chair in Chemical and Biomolecular Engineering, and Director of the Center for Drug Design, Development, and Delivery at Georgia Tech, told WIRED, “Blood is a tiny fraction of the fluid in our body. Other fluids should have something useful—it’s just hard to get those fluids.”
“Previously, concentrations of a biomarker had to be on the order of a few micrograms per milliliter of fluid,” said Zheyu (Ryan) Wang, a PhD candidate in Srikanth Singamaneni’s lab at McKelvey School of Engineering and a lead author of the paper, in the WashU news release. By using plasmonic-fluor, researchers were able to detect biomarkers on the order of picograms per milliliter—one millionth of the concentration.
“That’s orders of magnitude more sensitive,” Wang said.
Can Microneedles Be Used as a Diagnostic Tool?
As reported in WIRED, the polystyrene patch developed by Srikanth Singamaneni’s lab at McKelvey School of Engineering removes interstitial fluid from the skin and turns the needles into “biomarker traps” by coating them with antibodies known to bind to specific proteins, such as Interleukin 6 (IL-6). Once the microneedles are mixed with plasmonic-fluor, the patch will glow if the IL-6 biomarkers are present.
The development of such a highly sensitive biomarker-detection method means skin becomes a potential pathway for using microneedles to diagnose conditions, such as myocardial infarction or to measure COVID-19 antibodies in vaccinated persons.
Because the WashU study is a proof-of-concept in mice, it may be many years before this technology finds its way to clinical application. Many skin biomarkers will need to be verified for direct links to disease before microneedle patches will be of practical use to clinicians for diagnostics. However, microneedle patch technology has already proven viable for the collection of blood.
In 2017, Massachusetts-based Seventh Sense Biosystems (7SBio) received 510(k) clearance for a new microneedle blood collection device. Called TAP, the device is placed on the upper arm and blood collection starts with a press of a button. The process takes two to three minutes.
Initially, the FDA clearance permitted only healthcare workers to use the device “to collect capillary blood for hemoglobin A1c (HbA1c) testing, which is routinely used to monitor blood sugar levels in diabetic or pre-diabetic patients,” a Flagship Pioneering news release noted.
Then, in 2019, the FDA extended its authorization “to include blood collection by laypersons. Regulators are also allowing the device to be used ‘at-home’ for wellness testing,” a 7SBio news release stated. This opened the door for a microneedle device to be used for home care blood collection.
“No one likes getting blood drawn, but blood is the single-most important source of medical information in healthcare today, with about 90% of all diagnostic information coming from blood and its components,” Howard Weisman, former CEO of 7SBio and current CEO of PaxMedica, a clinical-stage biopharmaceutical company, said in the Flagship Pioneering news release. “TAP has the potential to transform blood collection from an inconvenient, stressful, and painful experience to one people can do themselves anywhere, making health monitoring much easier for both healthcare professionals and patients.”
As microneedle technology continues to evolve, clinical laboratories should expect patches to be used in a growing number of drug delivery systems and diagnostic tests. But further research will be needed to determine whether interstitial fluid can provide an alternate pathway for diagnosing disease.
The palm-sized device could one day be engineered to track down explosives and gas leaks or could even be used by medical laboratories to detect disease
Here’s a technology breakthrough with many implications for diagnostics and clinical laboratory testing. Researchers at the at the University of Washington (UW) are pushing the envelope on what can be achieved by combining technology with biology. They developed “Smellicopter,” a flying drone that uses a living moth antenna to hunt for odors.
According to their published study, the UW scientists believe an odor-guided drone could “reduce human hazard and drastically improve performance on tasks such as locating disaster survivors, hazardous gas leaks, incipient fires or explosives.”
“Nature really blows our human-made odor sensors out of the water,” lead author Melanie Anderson, a UW doctoral student in mechanical engineering, told UW News. “By using an actual moth antenna with Smellicopter, we’re able to get the best of both worlds: the sensitivity of a biological organism on a robotic platform where we can control its motion.”
The researchers believe their Smellicopter is the first odor-sensing flying biohybrid robot system to incorporate a live moth antenna that capitalizes on the insect’s excellent odor-detecting and odor-locating abilities.
In their paper, titled, “A Bio-Hybrid Odor-Guided Autonomous Palm-Sized Air Vehicle,” published in the IOPscience journal Bioinspiration and Biomimetics, the researchers wrote, “Biohybrid systems integrate living materials with synthetic devices, exploiting their respective advantages to solve challenging engineering problems. … Our robot is the first flying biohybrid system to successfully perform odor localization in a confined space, and it is able to do so while detecting and avoiding obstacles in its flight path. We show that insect antennae respond more quickly than metal oxide gas sensors, enabling odor localization at an improved speed over previous flying robots. By using the insect antennae, we anticipate a feasible path toward improved chemical specificity and sensitivity by leveraging recent advances in gene editing.”
How Does it Work?
In nature, a moth uses its antennae to sense chemicals in its environment and navigate toward sources of food or a potential mate.
“Cells in a moth antenna amplify chemical signals,” said study co-author Thomas Daniel, PhD, UW Professor of Biology, in UW News. “The moths do it really efficiently—one scent molecule can trigger lots of cellular responses, and that’s the trick. This process is super-efficient, specific, and fast.”
Because the moth antenna is hollow, researchers are able to add wires into the ends of the antenna. By connecting the antenna to an electrical circuit, they can measure the average signal from all of the cells in the antenna. When compared to a metal oxide gas sensor, the antenna-powered sensor responded more quickly to a floral scent. It also took less time to recover between tracking puffs of scent.
Anderson compared the antenna-drone circuitry to a human heart monitor.
“A lot like a heart monitor, which measures the electrical voltage that is produced by the heart when it beats, we measure the electrical signal produced by the antenna when it smells odor,” Anderson told WIRED. “And very similarly, the antenna will produce these spike-shaped pulses in response to patches of odor.”
Making a Drone Hunt Like a Moth
Anderson told WIRED her team programmed the drone to hunt for odors using the same technique moths employ to stay targeted on an odor, called crosswind casting.
“If the wind shifts, or you fly a little bit off-course, then you’ll lose the odor,” Anderson said. “And so, you cast crosswind to try and pick back up that trail. And in that way, the Smellicopter gets closer and closer to the odor source.”
However, the researchers had to figure out how to keep the commercially available $195 Crazyflie drone facing upwind. The fix, co-author and co-advisor Sawyer Fuller, PhD, UW Assistant Professor of Mechanical Engineering told UW News, was to add two plastic fins to create drag and keep the vehicle on course.
“From a robotics perspective, this is genius,” Fuller said. “The classic approach in robotics is to add more sensors, and maybe build a fancy algorithm or use machine learning to estimate wind direction. It turns out, all you need is to add a fin.”
Other Applications for Odor Detecting Robots
While any practical clinical application of this breakthrough is years away, the scientific team’s next step is to use gene editing to engineer moths with antennae sensitive to a specific desired chemical, such as those found in explosives.
“I think it is a powerful concept,” roboticist Antonio Loquercio, a PhD candidate in machine learning at the University of Zurich who researches drone navigation, told WIRED. “Nature provides us plenty of examples of living organisms whose life depends on this capacity. This could have as well a strong impact on autonomous machines—not only drones—that could use odors to find, for example, survivors in the aftermath of an earthquake or could identify gas leaks in a man-made environment.”
Could a palm-sized autonomous device one day be used to not only track down explosives and gas leaks but also to detect disease?
As clinical pathologists and medical laboratory scientists know, dogs have demonstrated keen ability to detect disease using their heightened sense of smell.