Some hospital organizations are pushing back, stating that the new regulations are ‘too rigid’ and interfere with doctors’ treatment of patients
In August, the Biden administration finalized provisions for hospitals to meet specific treatment metrics for all patients with suspected sepsis. Hospitals that fail to meet these requirements risk the potential loss of millions of dollars in Medicare reimbursements annually. This new federal rule did not go over well with some in the hospital industry.
Sepsis kills about 350,000 people every year. One in three people who contract the deadly blood infection in hospitals die, according to the Centers for Disease Control and Prevention (CDC). Thus, the federal government has once again implemented a final rule that requires hospitals, clinical laboratories, and medical providers to take immediate actions to diagnose and treat sepsis patients.
The effort has elicited pushback from several healthcare organizations that say the measure is “too rigid” and “does not allow clinicians flexibility to determine how recommendations should apply to their specific patients,” according to Becker’s Hospital Review.
Perform blood tests within a specific period of time to look for biomarkers in patients that may indicate sepsis, and to
Administer antibiotics within three hours after a possible case is identified.
It also mandates that certain other tests are performed, and intravenous fluids administered, to prevent blood pressure from dipping to dangerously low levels.
“These are core things that everyone should do every time they see a septic patient,” said Steven Simpson, MD, Professor of medicine at the University of Kansas told Fierce Healthcare. Simpson is also the chairman of the Sepsis Alliance, an advocacy group that works to battle sepsis.
Simpson believes there is enough evidence to prove that the SEP-1 guidelines result in improved patient care and outcomes and should be enforced.
“It is quite clear that this works better than what was present before, which was nothing,” he said. “If the current sepsis mortality rate could be cut by even 5%, we could save a lot of lives. Before, even if you were reporting 0% compliance, you didn’t lose your money. Now you actually have to do it,” Simpson noted.
“We are encouraged by the increased attention to sepsis and support CMS’ creation of a sepsis mortality measure that will encourage hospitals to pay more attention to the full breadth of sepsis care,” Chanu Rhee, MD (above), Infectious Disease/Critical Care Physician and Associate Hospital Epidemiologist at Brigham and Women’s Hospital told Healthcare Finance. The new rule, however, requires doctors and medical laboratories to conduct tests and administer antibiotic treatment sooner than many healthcare providers deem wise. (Photo copyright: Brigham and Women’s Hospital.)
Healthcare Organizations Pushback against Final Rule
“By encouraging the use of broad spectrum antibiotics when more targeted ones will suffice, this measure promotes the overuse of the antibiotics that are our last line of defense against drug-resistant bacteria,” the AHA’s letter states.
In its recent coverage of the healthcare organizations’ pushback to CMS’ final rule, Healthcare Finance News explained, “The SEP-1 measure requires clinicians to provide a bundle of care to all patients with possible sepsis within three hours of recognition. … But the SEP-1 measure doesn’t take into account that many serious conditions present in a similar fashion to sepsis … Pushing clinicians to treat all these patients as if they have sepsis … leads to overuse of broad-spectrum antibiotics, which can be harmful to patients who are not infected, those who are infected with viruses rather than bacteria, and those who could safely be treated with narrower-spectrum antibiotics.”
CMS’ latest rule follows the same evolutionary path as previous federal guidelines. In August 2007, CMS announced that Medicare would no longer pay for additional costs associated with preventable errors, including situations known as Never Events. These are “adverse events that are serious, largely preventable, and of concern to both the public and healthcare providers for the purpose of public accountability,” according to the Leapfrog Group.
In 2014, the CDC suggested that all US hospitals have an antibiotic stewardship program (ASP) to measure and improve how antibiotics are prescribed by clinicians and utilized by patients.
Research Does Not Show Federal Sepsis Programs Work
He points to analysis which showed that though use of broad-spectrum antibiotics increased after the original 2015 SEP-1 regulations were introduced, there has been little change to patient outcomes.
“Unfortunately, we do not have good evidence that implementation of the sepsis policy has led to an improvement in sepsis mortality rates,” Rhee told Fierce Healthcare.
Rhee believes that the latest regulations are a step in the right direction, but that more needs to be done for sepsis care. “Retiring past measures and refining future ones will help stimulate new innovations in diagnosis and treatment and ultimately improve outcomes for the many patients affected by sepsis,” he told Healthcare Finance.
Sepsis is very difficult to diagnose quickly and accurately. Delaying treatment could result in serious consequences. But clinical laboratory blood tests for blood infections can take up to three days to produce a result. During that time, a patient could be receiving the wrong antibiotic for the infection, which could lead to worse problems.
The new federal regulation is designed to ensure that patients receive the best care possible when dealing with sepsis and to lower mortality rates in those patients. It remains to be seen if it will have the desired effect.
Best of all, the researchers say the test could provide an inexpensive means of early diagnosis. This assay could also be used to monitor how well patients respond to cancer therapy, according to a news release.
The protein had previously been identified as a promising biomarker and is readily detectable in tumor tissue, they wrote. However, it is found in extremely low concentrations in blood plasma and is “well below detection limits of conventional clinical laboratory methods,” they noted.
To overcome that obstacle, they employed an ultra-sensitive immunoassay known as a Simoa (Single-Molecule Array), an immunoassay platform for measuring fluid biomarkers.
“We were shocked by how well this test worked in detecting the biomarker’s expression across cancer types,” said lead study author gastroenterologist Martin Taylor, MD, PhD, Instructor in Pathology, Massachusetts General Hospital and Harvard Medical School, in the press release. “It’s created more questions for us to explore and sparked interest among collaborators across many institutions.”
“We’ve known since the 1980s that transposable elements were active in some cancers, and nearly 10 years ago we reported that ORF1p was a pervasive cancer biomarker, but, until now, we haven’t had the ability to detect it in blood tests,” said pathologist and study co-author Kathleen Burns, MD, PhD (above), Chair of the Department of Pathology at Dana-Farber Cancer Institute and a Professor of Pathology at Harvard Medical School, in a press release. “Having a technology capable of detecting ORF1p in blood opens so many possibilities for clinical applications.” Clinical laboratories may soon have a new blood test to detect multiple types of cancer. (Photo copyright: Dana-Farber Cancer Institute.)
Simoa’s Advantages
In their press release, the researchers described ORF1p as “a hallmark of many cancers, particularly p53-deficient epithelial cancers,” a category that includes lung, breast, prostate, uterine, pancreatic, and head and neck cancers in addition to the cancers noted above.
“Pervasive expression of ORF1p in carcinomas, and the lack of expression in normal tissues, makes ORF1p unlike other protein biomarkers which have normal expression levels,” Taylor said in the press release. “This unique biology makes it highly specific.”
Simoa was developed at the laboratory of study co-author David R. Walt, PhD, the Hansjörg Wyss Professor of Bioinspired Engineering at Harvard Medical School, and Professor of Pathology at Harvard Medical School and Brigham and Women’s Hospital.
The Simoa technology “enables 100- to 1,000-fold improvements in sensitivity over conventional enzyme-linked immunosorbent assay (ELISA) techniques, thus opening the window to measuring proteins at concentrations that have never been detected before in various biological fluids such as plasma or saliva,” according to the Walt Lab website.
Simoa assays take less than two hours to run and require less than $3 in consumables. They are “simple to perform, scalable, and have clinical-grade coefficients of variation,” the researchers wrote.
Study Results
Using the first generation of the ORF1p Simoa assay, the researchers tested blood samples of patients with a variety of cancers along with 406 individuals, regarded as healthy, who served as controls. The test proved to be most effective among patients with colorectal and ovarian cancer, finding detectable levels of ORF1p in 58% of former and 71% of the latter. Detectable levels were found in patients with advanced-stage as well as early-stage disease, the researchers wrote in Cancer Discovery.
Among the 406 healthy controls, the test found detectable levels of ORF1p in only five. However, the control with the highest detectable levels, regarded as healthy when donating blood, “was six months later found to have prostate cancer and 19 months later found to have lymphoma,” the researchers wrote.
They later reengineered the Simoa assay to increase its sensitivity, resulting in improved detection of the protein in blood samples from patients with colorectal, gastroesophageal, ovarian, uterine, and breast cancers.
The researchers also employed the test on samples from 19 patients with gastroesophageal cancer to gauge its utility for monitoring therapeutic response. Although this was a small sample, they found that among 13 patients who had responded to therapy, “circulating ORF1p dropped to undetectable levels at follow-up sampling.”
“More Work to Be Done”
The Simoa assay has limitations, the researchers acknowledged. It doesn’t identify the location of cancers, and it “isn’t successful in identifying all cancers and their subtypes,” the press release stated, adding that the test will likely be used in conjunction with other early-detection approaches. The researchers also said they want to gauge the test’s accuracy in larger cohorts.
“The test is very specific, but it doesn’t tell us enough information to be used in a vacuum,” Walt said in the news release. “It’s exciting to see the early success of this ultrasensitive assessment tool, but there is more work to be done.”
More studies will be needed to valid these findings. That this promising new multi-cancer immunoassay is based on a clinical laboratory blood sample means its less invasive and less painful for patients. It’s a good example of an assay that takes a proteomic approach looking for protein cancer biomarkers rather than the genetic approach looking for molecular DNA/RNA biomarkers of cancer.
Dogs’ acute sense of smell can even surpass effectiveness of some clinical laboratory testing in detecting certain diseases in humans
When it comes to COVID-19 testing, a recent Italian study demonstrates that trained dogs can detect SARS-CoV-2 with accuracy comparable to rapid molecular tests used in clinical laboratories. The researchers wanted to determine if dogs could be more effective at screening people for COVID-19 at airports, schools, and other high-traffic environments as a way to detect the coronavirus and reduce the spread of this infectious disease.
Scientists at the State University of Milan in Italy conducted a study that shows dogs can be trained to accurately identify the presence of the COVID-19 infection from both biological samples and by simply smelling an individual.
For their validation study, the Italian team trained three dogs named Nala, Otto, and Helix, “to detect the presence of SARS-CoV-2 in sweat samples from infected people. At the end of the training, the dogs achieved an average sensitivity of 93% and a specificity of 99%, showing a level of accuracy highly consistent with that of the RT-PCR [reverse transcription polymerase chain reaction] used in molecular tests and a moderate to strong reproducibility over time,” Nature reported.
RT-PCR tests are the current gold-standard for SARS-CoV-2 detection. This is yet another example of scientists training dogs to smell a disease with “acceptable” accuracy. This time for COVID-19.
“We only recruited dogs that showed themselves predisposed and positively motivated to carry out this type of activity. One of the fundamental aspects was not to cause stress or anxiety in the subjects used,” Federica Pirrone, PhD (above), Associate Professor, Department of Veterinary Medicine and Animal Sciences, University of Milan, and one of the authors of the study told Lifegate. “Training always takes place using positive reinforcement of a food nature: whether it’s a particularly appetizing morsel, a biscuit, or something that associates the dog’s search with a rewarding prize.” In some instances, dogs have been shown to be as good or more effective at detecting certain diseases than clinical laboratory testing. (Photo copyright: Facebook.)
Dogs More Accurate than Rapid Antigen Testing
Nala and four other dogs (Nim, Hope, Iris and Chaos) were later trained by canine technicians from Medical Detection Dogs Italy (MDDI) to identify the existence of the SARS-CoV-2 virus by directly smelling people waiting in line in pharmacies to get a nasal swab to test for the coronavirus.
Working with their handlers, the five dogs accurately signaled the presence or absence of the virus with 89% sensitivity and 95% specificity. That rate is “well above the minimum required by the WHO [World Health Organization] for rapid swabs for SARS-CoV-2,” according to Nature.
“The results of studies published so far on the accuracy of canine smell in detecting the presence of SARS-CoV-2 in biological samples (e.g., saliva, sweat, urine, trachea-bronchial secretions) from infected people suggest that sniffer dogs might reach percentages of sensitivity and specificity comparable to, or perhaps even higher, than those of RT-PCR,” the scientists wrote in Scientific Reports.
“However, although most of these studies are of good quality, none of them provided scientific validation of canine scent detection, despite this being an important requirement in the chemical analysis practice. Therefore, further applied research in this field is absolutely justified to provide definitive validation of this biodetection method,” the researchers concluded.
Other Studies into Using Dogs for Detecting Disease
Scientists from the Division of Biological and Health Sciences, Department of Agriculture and Livestock at the University of Sonora; and the Canine Training Center Obi-K19, both in Hermosillo, Mexico, conducted the study “as part of a Frontiers of Science Project of the National Council of Science and Technology (CONACYT), in which in addition to analyzing sweat compounds, trained dogs are put to sniff the samples and make detections in people who show symptoms or could be positive for coronavirus,” Mexico Daily Post reported.
The researchers trained four dogs with sweat samples and three dogs with saliva samples of COVID-19 positive patients. The samples were obtained from a health center located in Hermosillo, Sonora, in Mexico. The dogs were restricted to spend five minutes per patient and the researchers calculated the performance of the dogs by measuring sensitivity, specificity, and their 95% confidence intervals (CI).
The researchers concluded that all four of the dogs could detect COVID-19 from either sweat or saliva samples “with sensitivity and specificity rates significantly different from random [sampling] in the field.” According to the Frontiers in Medicine study, the researchers found their results promising because, they said, it is reasonable to expect the detection rate would improve with longer exposure to the samples.
The objective of the Mexican researchers is for the dogs to ultimately reach the sensitivity range requested by WHO for the performance of an antigen test, which is at least 80% sensitivity and 97% specificity. If that goal is achieved, dogs could become important partners in the control of the COVID-19 pandemic, the scientists wrote.
Data obtained so far from these studies indicate that biosensing dogs may represent an effective method of screening for COVID-19 as well as other diseases. More studies and clinical trials are needed before the widespread use of dogs might become feasible. Nevertheless, scientists all over the world are finding that Man’s best friend can be a powerful ally in the fight against the spread of deadly diseases.
In the meantime, the gold standard in COVID-19 testing will continue to be the FDA-cleared assays used by clinical laboratories throughout the United States.
Goal is to demonstrate how whole human genome sequencing of newborns can deliver important diagnostic findings associated with 250 genetic conditions
Clinical laboratory testing and genetics are moving closer to the delivery room than ever before. In the largest study of its kind in North America, genomic scientists plan to supplement traditional screening for inherited diseases—traditionally performed on a blood sample taken shortly after birth—with whole genome sequencing (WGS) on 100,000 newborns in New York City during their first five years of life, LifeSciencesIntelligence reported.
Conducted by genetic scientists at NewYork-Presbyterian (NYP) and Columbia University, in collaboration with genetic company GeneDx, a wholly-owned subsidiary of health intelligence company Sema4 (NASDAQ:SMFR), the genetic research study, called GUARDIAN (Genomic Uniform-screening Against Rare Diseases In All Newborns), will screen newborn babies for 250 rare diseases that are generally not tested for.
The GUARDIAN program will “drive earlier diagnosis and treatment to improve the health of the babies who participate, generate evidence to support the expansion of newborn screening through genomic sequencing, and characterize the prevalence and natural history of rare genetic conditions,” according to a Sema4 news release.
“The appetite for this is growing. The awareness of this is growing. We all see it as inevitable,” medical geneticist Robert Green, MD, at Brigham and Women’s Hospital and Harvard Medical School told USA Today. “We are grossly underutilizing the life-saving benefits of genetics and we have to get past that.” Clinical laboratory leaders understand the value of early detection of disease and subsequent early treatment. (Photo copyright: Harvard Medical School.)
Improving Health of Babies Through Early Detection of Disease
GUARDIAN aims to use WGS to identify conditions at birth that can affect long-term health and subsequently enhance treatment options and possibly prevent disability or death.
The 250 different diseases GUARDIAN will be screening for typically strike young children. They are mostly rare conditions that:
have an onset before five years of age,
have a greater than 90% probability of the condition developing based on the genetic result,
have effective approaches and treatments that are already available, and/or
have a well-established natural history of the condition.
“We’re entering the therapeutic era and leaving the diagnostic era,” Paul Kruszka, MD, Chief Medical Officer at GeneDx told USA Today. “This potentially has the opportunity to change the way we practice medicine, especially in rare disease.”
Some Parents Reluctant to Agree to Genetic Testing
Green and his research team first began analyzing the genetic sequences of newborns back in 2013. They believe the costs of performing infant WGS is worthwhile because it can improve lives. However, Green also recognizes that some parents are reluctant to agree to this type of genetic testing due to concerns regarding privacy and the fear of discovering their baby may have an illness.
“You’ve gone through all this pregnancy and you’re sitting there with a healthy baby (and I’m) offering you the opportunity to find out something that’s devastating and terrifying,” he told USA Today. “How fun is that?”
Green continued. “We can respect people who don’t want to know, but also respect people who do want to know. Some families will say ‘I treasure the precious ignorance.’ Others will say ‘If I could have known, I would have poured my heart and soul into clinical trials or spent more time with the child when she was healthy.’”
WGS Screening Identifies Undiagnosed Illnesses in Newborn’s Family
The scientists also found that performing WGS in newborns can detect diseases in the infants as well as unknown illnesses in the families of those babies. According to Kruszka, many parents often seek a diagnosis for a rare disease present in their children for several years. Since many common diseases develop as a result of certain combinations of genes, if illnesses are diagnosed at birth, it could extradite the treatment process, prevent complications, and provide better health outcomes for patients.
“We are relentlessly focused on accelerating the adoption and use of genomic information to impact the lives of as many people as possible, particularly newborns and children,” said Katherine Stueland, President and CEO, Sema4, in the Sema4 news release. “As the first commercial laboratory to launch a rapid whole genome sequencing offering, to address broad unmet needs for early diagnosis, participation in this study is an important step forward for healthcare and in delivering on our goal to sequence once, analyze forever.”
The study is open to all babies in New York City who are born in a health system that participates in the GUARDIAN program, regardless of their race, income, or health insurance coverage.
“The results from this study will help us understand the true impact sequencing at birth can have on newborns and their families in comparison to the current standard of care, particularly as we’ll evaluate clinical outcomes in addition to the psychosocial effect on families,” said Kruszka in the Sema4 news release.
Anything that improves the health of newborn babies is a good thing. Regardless of the cost, if DNA analysis can give newborns and their families a better chance at detecting inherited diseases early while clinical laboratory treatment could make a difference, it is worth pursuing.
Viral reservoir could be behind persistence, says study, which also suggests a blood biomarker could be found for clinical laboratory testing
Microbiologists and virologists working closely with physicians treating long COVID-19 patients will gain new insights in a study that found coronavirus spike protein in COVID-19 patients’ blood up to 12 months after diagnosis. The researchers believe their findings could be used to develop a clinical laboratory biomarker for long COVID-19.
Researchers at Brigham and Women’s Hospital and Massachusetts General Hospital said medical experts are not sure why some people have unwelcome symptoms weeks and months after a positive COVID-19 diagnosis, while others clear the infection without lingering effects.
The scientists believe if this work is validated, clinical laboratories might gain an assay to use in the diagnosis of long COVID-19.
“The half-life of spike protein in the body is pretty short, so its presence indicates that there must be some kind of active viral reservoir,” said David Walt, PhD (above), Professor of Pathology, Brigham and Women’s Hospital, and lead author of the study that found coronavirus spike protein in long COVID patients. The study findings indicate a potential clinical laboratory biomarker for long COVID-19. (Photo copyright: Brigham and Women’s Hospital.)
Viral Reservoir Possibly Behind Long COVID-19
The study suggests that SARS-CoV-2 finds a home in the body, particularly the gastrointestinal tract, “through viral reservoirs, where it continues to release spike protein and trigger inflammation,” Medical News Today reported.
Lead author of the study David Walt, PhD, Professor of Pathology, Brigham and Women’s Hospital and the Hansjörg Wyss Professor Biologically Inspired Engineering at Harvard Medical School, told The Guardian he “was motivated to carry out the study after earlier research by his colleagues detected genetic material from the COVID virus (viral RNA) in stool samples from children with multisystem inflammatory syndrome (a rare but serious condition that often strikes around four weeks after catching COVID) as well as spike protein and a marker of gut leakiness in their blood.”
Long COVID—also known as long-haul COVID, post-COVID-19, or its technical name, post-acute sequelae of COVID-19 or PASC—can involve health problems continuing weeks, months, or even years after a positive diagnosis, according to the federal Centers for Disease Control and Prevention (CDC).
Symptoms of long COVID, according to the researchers, include:
fatigue,
loss of smell,
memory loss,
gastrointestinal distress, and
shortness of breath.
“If someone could somehow get to that viral load and eliminate it, it might lead to resolution of symptoms,” Walt told the Boston Globe, which noted that the researchers may explore a clinical trial involving antiviral drugs for treatment of long COVID-19.
Clues from Earlier Studies on Long COVID-19
Medical conditions that persisted following a COVID-19 infection have been studied for some time. In fact, in an earlier study, Walt and others found children who developed a multisystem inflammation syndrome weeks after being infected by SARS-CoV-2, according to their 2021 paper published in The Journal of Clinical Investigation, titled, “Multisystem Inflammatory Syndrome in Children Is Driven by Zonulin-Dependent Loss of Gut Mucosal Barrier.”
Although these earlier studies provided clues, the cause of PASC remains unclear, the researchers noted. They planned to take a more precise look at PASC biology by using appropriate sampling and patient recruitment.
“Disentangling the complex biology of PASC will rely on the identification of biomarkers that enable classification of patient phenotypes. Here, we analyze plasma samples collected from PASC and COVID-19 patients to determine the levels of SARS-CoV-2 antigens and cytokines and identify a blood biomarker that appears in the majority of PASC patients,” the researchers wrote.
Finding a Marker of a Persistent Infection
The researchers used plasma samples from 63 people with a previous SARS-CoV-2 diagnosis (37 also had PASC), Medical News Today reported. Over a 12-month period, the researchers’ findings included:
Detection in 65% of PASC samples of full-length spike, S1 spike, and nucleocapsid throughout the year of testing.
Spike detected in 60% of PASC patient samples, and not found in the COVID-19 samples.
In an interview with Scientific American, bioengineer Zoe Swank PhD, post-doctoral researcher, Brigham and Women’s Hospital, and co-author of the study, said, “Our main hypothesis is that the spike protein is not causing the symptoms, but it’s just a marker that is released because you still have infection of some cells with SARS-CoV-2.”
In that article, Swank shared the scientists’ intent to do more research involving hundreds of samples over the course of the COVID-19 pandemic from many hospitals and people.
COVID-19 Not the Only Virus That Hangs On
Having a long-haul COVID-19 marker is a “game-changer,” according to an infectious disease expert who was not involved in the study.
“There has not so far been a clear, objective marker that is measurable in the blood of people experiencing long COVID-19,” Michael Peluso, MD, Assistant Professor, Medicine, University of California San Francisco, told Scientific American. “I hope their findings will hold up. It really would make a difference for a lot of people if a marker like this could be validated,” he added.
However, COVID-19 is not the only virus that could persist. Ebola also may linger in areas that skirt the immune system, such as the eye interior and central nervous system, according to a World Health Organization fact sheet.
Thus, medical laboratory leaders may want to follow the Brigham and Women’s Hospital research to see if the scientists validate their finding, discover a biomarker for long-haul COVID-19, and pursue a clinical trial for antiviral drugs. Such discoveries could have implications for how diagnostic professionals work with physicians to care for long COVID patients.
