New technique could allow emergency responders to determine severity of LVO stroke while patient is still in the ambulance
Researchers at Brigham and Women’s Hospital in Massachusetts say they have developed a clinical laboratory test that can quickly determine whether a patient is experiencing one of the deadliest types of strokes, known as an ischemiclarge vessel occlusion (LVO) stroke. The development team believes this new assay could be deployed as a point-of-care test to enable faster diagnosis of stroke events.
The test combines measurement of two blood plasma biomarkers with an established clinical score used by clinicians and EMS personnel to assess stroke severity. Compared with current approaches, their technique more accurately differentiates LVO strokes from other types of strokes, making it more likely that patients receive appropriate treatment in a timely manner, the researchers said in a Brigham news release.
Dark Daily has long predicted that advances in technology and computing power would make it possible for pathologists and clinical laboratory scientists to combine multiple established biomarkers (individually not associated with the disease state targeted) with other clinical and patient data to create the ability to make an accurate and earlier diagnosis.
Ultimately, Brigham’s research could “aid in the development of a point‐of‐care diagnostic test capable of guiding prehospital LVO stroke triage,” wrote Joshua Bernstock, MD, PhD, Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital, lead author of the study, and colleagues.
“We have developed a game-changing, accessible tool that could help ensure that more people suffering from stroke are in the right place at the right time to receive critical, life-restoring care,” said Joshua Bernstock, MD, PhD (above), Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital and lead author of the Brigham study that developed the clinical laboratory test that the researchers say can enable emergency caregivers to determine quickly and accurately if a patient is having an ischemic large vessel occlusion (LVO) stroke. (Photo copyright: Brigham and Women’s Hospital.)
Early Identification of LVO Stroke
As explained in the news release, an LVO stroke is a type of ischemic stroke caused by obstruction in a major brain artery. The researchers noted that LVO strokes account for “62% of poststroke disabilities and 96% of poststroke death.”
These strokes are readily treatable using endovascular thrombectomy (EVT), in which the blockages are surgically removed, the news release note. However, the researchers observed that EVT “requires specialized teams and equipment, limiting its availability to comprehensive stroke centers and other EVT‐capable centers.”
This can lead to delays as patients are transferred to those facilities, worsening outcomes and increasing the risk of death, the researchers wrote in Stroke: Vascular and Interventional Neurology. So, early identification of LVO stroke is key to ensuring patients receive timely treatment.
Identifying False Negatives/Positives
One challenge, the news release notes, is that brain bleeds (hemorrhagic stroke) can present similar symptoms, yet require “vastly different” treatment.
“A growing body of work has, therefore, evaluated prehospital stroke assessment scales in an effort to identify LVO strokes in the field,” the researchers wrote. “However, such severity scales lack the sensitivity and specificity required for triaging LVO patients with confidence, resulting in false negatives in patients with LVO as well as false positives in patients with stroke mimics or hemorrhagic stroke.”
As explained by EMS Aware, these assessment scales, such as FAST-ED (field assessment stroke triage for emergency destination) and RACE (rapid arterial occlusion evaluation), attempt to determine the severity of a stroke by assigning scores based on symptoms such as facial palsy, arm weakness, and speech difficulties.
To develop their test, Bernstock and colleagues proposed combining the scales with measurement of two blood proteins:
In their study, they attempted to validate cutoff values for the biomarkers and scales.
To do so, the researchers analyzed data from 323 patients admitted to a Florida hospital with suspected stroke between May 2021 and August 2022. Each was assigned to one of four diagnostic categories based on clinical data from their medical records, which included results of computed tomography (CT scan) or magnetic resonance angiography (MRA). The diagnostic categories included:
The patients were assessed using five stroke severity scales. The researchers used frozen blood samples from the patients to measure the biomarkers. They then used this data to determine the likelihood of LVO stroke and compared the results with the diagnoses as determined by the clinical data.
“Combinations of the blood biomarkers with the scales FAST‐ED or RACE showed the best performance for LVO detection, with a specificity of 94% (for either scale combination) and a sensitivity of 71% for both scales,” the researchers wrote.
Sensitivity was higher in patients who presented within the first six hours from onset of symptoms.
“Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage,” the researchers wrote. However, they also suggested that their algorithm could be adjusted to enable early identification of hemorrhagic stroke.
The researchers noted that they chose biomarker cutoffs to maximize specificity, so “a certain number of LVOs are missed. However, as such patients default into ‘standard‐of‐care’ triaging pathways, such a decision is unlikely to represent much clinical risk.”
Testing in the Field
The Brigham researchers used established biological biomarkers combined with modern computing—in combination with the scores from a field assessment test—to develop their new clinical laboratory test that identifies the type of stroke.
Their next step is to carry out “another prospective trial to measure the test’s performance when used in an ambulance,” the news release states. “They have also designed an interventional trial that leverages the technology to expedite the triage of stroke patients by having them bypass standard imaging and move directly to intervention.”
“In stroke care, time is brain,” Bernstock said. “The sooner a patient is put on the right care pathway, the better they are going to do. Whether that means ruling out bleeds or ruling in something that needs an intervention, being able to do this in a prehospital setting with the technology that we built is going to be truly transformative.”
More research and clinical studies are needed. However, the fact that the Brigham team wants to deploy this approach in ambulances is an indication that there is high clinical value from this approach.
Clinical pathologists and medical laboratory managers will want to watch the ongoing development and deployment of this new assay, whether it is run in near-patient settings or core clinical laboratories in support of patients presenting in emergency departments.
Norwegian researchers reviewed large clinical trials of six common cancer screenings, including clinical laboratory tests, but some experts question the findings
Cancer screenings are a critical tool for diagnosis and treatment. But how much do they actually extend the lives of patients? According to researchers at the University of Oslo in Norway, not by much. They recently conducted a review and meta-analysis of 18 long-term clinical trials, five of the six most commonly used types of cancer screening—including two clinical laboratory tests—and found that with few exceptions, the screenings did not significantly extend lifespans.
The 18 long-term clinical trials included in the study were randomized trials that collectively included a total of 2.1 million participants. Median follow-up periods of 10 to 15 years were used to gauge estimated lifetime gain and mortality.
“The findings of this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy,” the researchers wrote in their published paper.
The researchers noted, however, that their analysis does not suggest all screenings should be abandoned. They also acknowledged that some lives are saved by screenings.
“Without screening, these patients may have died of cancer because it would have been detected at a later, incurable stage,” the scientists wrote, MedPage Today reported. “Thus, these patients experience a gain in lifetime.”
Still, some independent experts questioned the validity of the findings.
Gastroenterologist Michael Bretthauer, MD, PhD (above), a professor at the University of Oslo in Norway led the research into cancer screenings. In their JAMA Internal Medicine paper, he and his team wrote, “The findings of this meta-analysis suggest that colorectal cancer screening with sigmoidoscopy may extend life by approximately three months; lifetime gain for other screening tests appears to be unlikely or uncertain.” How their findings might affect clinical laboratory and anatomic pathology screening for cancer remains to be seen. (Photo copyright: University of Oslo.)
Pros and Cons of Cancer Screening
The clinical trials, according to MedPage Today and Oncology Nursing News covered the following tests:
Mammography screening for breast cancer (two trials).
As reported in these trials, “colorectal cancer screening with sigmoidoscopy prolonged lifetime by 110 days, while fecal testing and mammography screening did not prolong life,” the researchers wrote. “An extension of 37 days was noted for prostate cancer screening with prostate-specific antigen testing and 107 days with lung cancer screening using computed tomography, but estimates are uncertain.”
The American Cancer Society (ACS) recommends certain types of screening tests to detect cancers and pre-cancers before they can spread, thus improving the chances for survival.
The ACS advises screenings for breast cancer, colorectal cancer, and cervical cancer regardless of whether the individual is considered high risk. Lung cancer screenings are advised for people with a history of smoking. Men who are 45 to 50 or older should discuss the pros and cons of prostate cancer screening with their healthcare providers, the ACS states.
A CNN report about the University of Oslo study noted that the benefits and drawbacks of cancer screening have long been well known to doctors.
“Some positive screening results are false positives, which can lead to unnecessary anxiety as well as additional screening that can be expensive,” CNN reported. “Tests can also give a false negative and thus a false sense of security. Sometimes too, treatment can be unnecessary, resulting in a net harm rather than a net benefit, studies show.”
In their JAMA paper, the University of Oslo researchers wrote, “The critical question is whether the benefits for the few are sufficiently large to warrant the associated harms for many. It is entirely possible that multicancer detection blood tests do save lives and warrant the attendant costs and harms. But we will never know unless we ask,” CNN reported.
Hidden Impact on Cancer Mortality
ACS Chief Scientific Officer William Dahut, MD, told CNN that screenings may have an impact on cancer mortality in ways that might not be apparent from randomized trials. He noted that there’s been a decline in deaths from cervical cancer and prostate cancer since doctors began advising routine testing.
“Cancer screening was never really designed to increase longevity,” Dahut said. “Screenings are really designed to decrease premature deaths from cancer.” For example, “if a person’s life expectancy at birth was 80, a cancer screening may prevent their premature death at 65, but it wouldn’t necessarily mean they’d live to be 90 instead of the predicted 80,” CNN reported.
Dahut told CNN that fully assessing the impact of cancer screenings on life expectancy would require a clinical trial larger than those in the new study, and one that followed patients “for a very long time.”
“From its title, one would have expected this paper to be based on analysis of individual lifetime data. However, it is not,” he wrote in a compilation of expert commentary from the UK’s Science Media Center. “The paper’s conclusions are based on arithmetic manipulation of relative rates of all-cause mortality in some of the screening trials. It is therefore difficult to give credence to the claim that screening largely does not extend expected lifetime.”
He also questioned the inclusion of one particular trial in the University of Oslo study—the Canadian National Breast Screening Study—“as there is now public domain evidence of subversion of the randomization in this trial,” he added.
Another expert, Leigh Jackson, PhD, of the University of Exeter in the UK, described the University of Oslo study as “methodologically sound with some limitations which the authors clearly state.”
But he observed that “the focus on 2.1 million individuals is slightly misleading. The study considered many different screening tests and 2.1 million was indeed the total number of included patients, however, no calculation included that many people.”
Jackson also characterized the length of follow-up as a limitation. “This may have limited the amount of data included and also not considering longer follow-up may tend to underestimate the effects of screening,” he said.
This published study—along with the range of credible criticisms offered by other scientists—demonstrates how analysis of huge volumes of data is making it possible to tease out useful new insights. Clinical laboratory managers and pathologists can expect to see other examples of researchers assembling large quantities of data across different areas of medicine. This huge pools of data will be analyzed to determine the effectiveness of many medical procedures that have been performed for years with a belief that they are helpful.
Researchers note medical laboratories uniquely qualified to help doctors optimize lab test utilization, and to educate physicians on testing trends and improvements
Automation and informatics have revolutionized the modern medical laboratory. These same technologies also are powering the next generation of healthcare through precision medicine, genomics, and an increased ability to assess and leverage population health trends. In fact, exciting work is being done to use these technologies to help physicians and clinical laboratory professionals better work together.
When it comes to how physicians order and use medical laboratory tests, changing their long-standing habits can be a lengthy process. By using dedicated systems to define proper lab test usage, track lab orders and patient outcomes, and share data between clinical laboratory and healthcare environments, pathologists, medical laboratory scientists, and physicians could seamlessly access the knowledge needed to improve decision making.
Low-Value versus High-Value Care Ordering
Research published recently in the Journal of the American Medical Association Internal Medicine (JAMA Internal Medicine) investigated the order rates and utilization of low-value medical laboratory services and other diagnostic tests associated with headaches, respiratory tract infections, and back pain.
Their findings indicated that physicians in hospital-based practices ordered more “low-value care” than physicians in community-based practices. According to the research, low-value care includes:
The researchers found similar patterns in specialty referrals when comparing hospital-owned community practices and physician-owned practices.
The study authors noted, “Visits with a generalist other than the patient’s primary care provider were associated with greater provision of low-value care, but mainly within hospital-based settings.”
Medical Laboratories Critical to Increasing Care Value/Reimbursements
According to the study, physicians often develop routines and habits when ordering diagnostic testing and when utilizing clinical laboratory services. By taking a proactive role in educating physicians and managing lab test utilization, laboratories could assist physicians in shifting these habits and reduce the number of low-value or outmoded tests ordered.
Avoiding low-value or unwarranted testing:
Reduces order load on the laboratory;
Improves efficiency for healthcare providers; and
Improves the quality of care for patients.
This is particularly critical as value-based care continues to change the way both laboratories and healthcare facilities get reimbursed for services.
In a press release, Janet B. Kreizman, CEO of the American Association for Clinical Chemistry (AACC) stated, “The changing Medicare payment paradigm creates new opportunities for health systems to advance patient care while more efficiently and effectively utilizing their resources. Laboratory medicine experts are uniquely positioned to ensure this is achieved by working with physicians to devise optimal diagnostic and therapeutic protocols, leading to better health outcomes and reduced costs.”
Graphic above from the Institutes of Medicine (IOM) report, “Best Care at Lower Cost: The Path to Continuously Learning Health Care in America.” (Graphic copyright: National Academy of Sciences, Engineering, and Medicine.)
7% were uncertain about which diagnostic tests to order;
3% were uncertain on how to interpret results; and
Respondents only consulted with pathology or laboratory experts 6% of the time.
Thus, an important opportunity exists for laboratory experts to work with PCPs—both within hospitals and outpatient settings—to further improve understanding of the ever-shifting menu of testing options and how to best utilize available lab services.
Optimizing the Cost and Safety of Care through Cooperation
The program asked nearly 400,000 physicians to name five diagnostic test and procedures related to their specialty that offered questionable value to patients and outcomes. In a Kaiser Health News (KHN) article, Daniel Wolfson, COO at ABIMF, attributed the “Choosing Wisely” campaign to launching a national conversation on unwarranted and low-value care.
The KHN report also noted the impact of “Choosing Wisely” on Cedars-Sinai in Los Angeles, one of the largest hospitals in the nation. Harry Sax, MD, Executive Vice Chairman for Surgery at Cedars-Sinai explained how the hospital avoided $6-million in spending in 2013 alone by implementing program recommendations, and by being more selective regarding tests and procedures utilized at the hospital.
Using Lab Utilization Management Technology to Improve Testing Value
The authors of the AJCP study compared testing costs at the Richard L. Roudebush VA Medical Center in Indianapolis before and after implementing an electronic laboratory utilization management system. They attributed six-figure savings to a reduction in high-volume large-panel testing and redundant tests. Savings were realized without increasing length-of-stay or adversely effecting patient care.
As big data continues to shape the future of healthcare, and clinical laboratories continue to implement lean laboratory routines to maintain growth, these systems could offer increased opportunities to help physicians become better at ordering the right test at the right time for the right patient, while helping the clinical laboratories performing these tests to further trim waste, increase the value of care, increase reimbursement, and improve outcomes for patients.
Pathologists and clinical laboratory managers should be aware of the possibility of ‘inattentional blindness’ as a potential cause for diagnostic and laboratory error
Pathologists and clinical laboratory professionals who regularly analyze images will be interested in the findings of a research study designed to assess how the phenomenon called “inattentional blindness” among radiologists could cause them to possibly miss things hiding in plain sight.
‘Inattentional Blindness’ Occurs Even Among Highly-trained Radiologists
Evolving imaging technology could begin to replace some traditional autopsy methodologies and encourage an increase in the number of autopsies performed
New imaging technology may give pathologists in the United Kingdom a new way to perform non-invasive autopsies. It is another example of how long-standing clinical practices can be transformed by the capabilities of newly developed technologies.
Leading experts within the field of post-mortem cross-sectional imaging in Britain have recommended that England’s National Health Service (NHS) introduce alternative techniques for performing non-invasive autopsies. A review of current procedures in the NHS system showed that alternative autopsy methodologies offer important advantages. In some circumstances, the non-invasive approach could replace traditional autopsy methods. (more…)
