Category: Lab Tests

Shortage of Blood Test Tubes Prompts Saving Efforts

Blood sample being drawn
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A pandemic-related shortage of a mundane item, ‘blue top’ blood test tubes used toollect blood samples from patients, has caused headaches for health systems worldwide.

But it may also have a silver lining: A lesson in how to reduce unneeded medical tests, whether or not there’s a shortage, according to a new study published in JAMA Internal Medicine.

The shortage gave researchers a chance to see if alerting doctors at the moment they’re placing an order could encourage them to seek a test only when results will immediately affect care.

In the new study, an alert led to a nearly immediate 29% drop in orders for one common test. The reduced level persisted for months.

“This shows that small interventions can make a big difference, and suggests the potential for other types of low-value care to benefit from a similar intervention,” says lead author Madison Breeden, MD, who conducted the study during her year as chief resident of Quality and Patient Safety. She’s already exploring if the approach might reduce unnecessary antibiotic prescriptionse

Breeden and her colleagues describe what happened in spring 2021 when University of Michigan Health supply chain and pathology experts began worrying about a potential shortage of ‘blue top’ tubes. The pandemic had created very high demand for the chemical the tubes contain: sodium citrate, which stabilises blood samples until a laboratory team can analyse three blood clotting-related properties, called PT, INR and PTT.

After emailing all providers, U-M Health added a ‘best practices alert’ to doctors’ test-ordering electronic system. They could still order PT/INR/PTT tests, but were asked for “thoughtful restraint in reflexive ordering.”

The alert began popping up a month before the FDA issued an official shortage notice and the issue got widespread attention. The shortage continues today and has grown to other types of tests.

The researchers looked at what happened for six months after the alert began appearing at U-M Health, and compared it with data from six months before.

“There are very important reasons to order this test in some patients, for instance before an operation or when managing certain conditions and treatments,” Breeden explains. “But it may also be part of a standard order set that’s put in during an emergency department visit and continues to be ordered repeatedly after the patient is admitted to the hospital, even though the results won’t change their care.” For such patients, a one-time test might be indicated, but not repeated testing.

Busy doctors entering orders for tests don’t tend to think about the supplies and people power needed to carry out those tests, Breeden notes. In the face of a shortage, or of strong evidence that a test is often over-ordered, an alert could help prioritize the tests for those who need them most.

Canadian experts have actually flagged PT/INR/PTT tests as a target for reducing unnecessary care, through the Choosing Wisely program. So has the American Society for Clinical Laboratory Science, a medical professional group.

AI Picks up Incidental Pulmonary Embolism on Chest CT

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According to a study published in the American Journal of Roentgenology, an AI tool for detection of incidental pulmonary embolus (iPE) on conventional contrast-enhanced chest CT examinations had high false negative and moderate false positive rates for detection, and was even able to pick up some iPEs missed by radiologists.

“Potential applications of the AI tool include serving as a second reader to help detect additional iPEs or as a worklist triage tool to allow earlier iPE detection and intervention,” wrote lead investigator Kiran Batra from the University of Texas Southwestern Medical Center in Dallas. “Various explanations of misclassifications by the AI tool (both false positives and false negatives) were identified, to provide targets for model improvement.”

Batra and colleagues’ retrospective study included 2,555 patients (1,340 women, 1,215 men; mean age, 53.6 years) who underwent 3,003 conventional contrast-enhanced chest CT examinations between September 2019 and February 2020 at Parkland Health in Dallas, TX. Using an FDA-approved, commercially available AI tool (Aidoc) to detect acute iPE on the images, a vendor-supplied natural language processing algorithm was then applied to the clinical reports to identify examinations interpreted as positive for iPE.

Ultimately, the commercial AI tool had NPV of 99.8% and PPV of 86.7% for detection of iPE on conventional contrast-enhanced chest CT examinations (ie, not using CT pulmonary angiography protocols). Of 40 iPEs present in the team’s study sample, 7 were detected only by the clinical reports, and 4 were detected only by AI.

Noting that both the AI tool and clinical reports detected iPEs missed by the other method, “the diagnostic performance of the AI tool did not show significant variation across study subgroups,” the authors added.

Source: American Roentgen Ray Society

Nuclear Stress Testing Identifies Candidates Most in Need of Angioplasty

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Patients identified by nuclear stress testing as having severe stress-induced myocardial ischaemia may benefit from angioplasty, while those with mild or no ischaemia will not, according to a new study reported in the Journal of the American College of Cardiology.

Following stress testing, coronary revascularisation restores blood flow to blocked arteries. For patients with severe ischaemia, early revascularisation saw a more than 30% reduction in mortality compared to patients with severe ischaemia who were treated with medication, but there was no benefit for the other groups.

Conducted by the Icahn School of Medicine at Mount Sinai, this is the first large-scale study to investigate stress testing in patient management when applied to the full spectrum of patients who have both varying degrees of myocardial ischaemia and heart function. This new study can help guide physicians on how to manage caring for patients with suspected heart disease.

Stress tests are indicated when physicians suspect that a patient’s chest pain or other clinical symptoms are from coronary artery disease (CAD). These help determine if a patient has obstructive CAD which leads to significant ischaemia. If the ischaemia due to obstructive CAD is severe, adequate blood flow can be restored with coronary artery bypass grafting surgery or percutaneous coronary intervention (PCI), where a catheter is used to place stents in the blocked coronary arteries. Nuclear stress testing is the most common stress test used to detect myocardial ischaemia.

“There is keen interest in assessing how measurement of myocardial ischaemia during stress testing can help shape physicians’ decision to refer patients for coronary revascularisation procedures, but this issue has not been well studied among patients who have underlying heart damage,” explains lead author Alan Rozanski, MD. “Our study, which evaluated a large number of patients with pre-existing heart damage who underwent cardiac stress testing, finally addresses this clinical void.”

The researchers analysed records of more than 43 000 patients who underwent nuclear stress testing with suspected CAD between 1998 and 2017 with a median 11-year follow-up for mortality/survival. The investigators grouped patients according to both their level of myocardial ischaemia during stress testing as well as their left ventricular ejection fraction (LVEF). Low LVEF measurements indicate prior heart damage that could be from scarring of the heart due to a prior heart attack.

The study provides two important clinical insights. First, the study showed that the frequency of myocardial ischemia during stress testing varies according to patients’ heart function. Of the 39 883 patients with normal heart function (LVEF > 55%), fewer than 8% of them had ischaemia. However, among the 3560 patients with reduced heart function (LVEF less than 45%, which indicates prior heart damage), more than 40% of them had myocardial ischaemia. The study also showed that the presence of myocardial ischaemia increases the risk of death in patients with normal and reduced heart function. Among both groups of patients, performing bypass or PCI procedures was not associated with improved survival among patients with either no or only mild ischaemia during the cardiac stress test. Among patients with severe ischaemia, coronary procedures were associated with more than 30% higher survival rates compared to those managed with medication only. This was the case for patients with and without heart damage.

“These results confirm the benefits of stress testing for clinical management. What you want from any test when considering coronary revascularisation procedures is that the test will identify a large percentage of patients who are at low clinical risk and do so correctly, while identifying only a small percentage of patients who are at high clinical risk and do so correctly. That is what we found with nuclear stress testing in this study,” explains Dr Rozanski. “Importantly, the presence of severe ischaemia does not necessarily mean that coronary revascularisation should be applied. New data from a large clinical trial suggests that when medical therapy is optimised it may be as effective as coronary revascularisation in such patients. But regardless, the presence of severe ischaemia indicates high clinical risk which then requires aggressive management to reduce clinical risk.”

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Substantial Discrepancies found Between Estimated and Measured GFR

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A cross sectional study published in Annals of Internal Medicine uncovered substantial discrepancies between individual estimated glomerular filtration rate (eGFR) and directly measured GFR (mGFR).The authors suggest that eGFR calculations on lab reports also state this distribution of uncertainty, and also that renaming the eGFR as a population average GFR (or paGFR) merits further discussion.

GFR is the standard metric used to assess and monitor kidney function. Directly measured GFR, or mGFR, requires injecting a filtration marker and measuring plasma or urinary clearance by serial blood and urine sampling under standardized conditions is not possible for every patient. So eGFR calculated from serum creatinine is often used by clinicians to predict an mGFR. Population-level discrepancies between eGFR and mGFR are low, but individual discrepancies are much higher. It is important to understand the magnitude of these individual-level differences for clinical decision making.

Researchers calculated eGFR from serum creatinine alone and cystatin C and creatinine using the Chronic Kidney Disease Epidemiology Collaboration equations for 3223 participants and compared their eGFR to their mGFR to quantify the magnitude and consequences of the individual-level differences between the two. The authors found substantial discrepancies between directly measured GFR and estimated GFR, resulting in only about 50% agreement between CKD stages. Individual-level differences between the mGFR and the eGFR did not improve substantially using cystatin C.

The authors suggested that several factors contribute to these discrepancies: creatinine and cystatin C have non-GFR factors influencing their serum concentration; variability in the mGFR can result from normal physiology and measurement error from mGFR markers and technique; and as GFR estimation models the ratio of mGFR–body surface area as a function of serum markers, it incorporates errors in mGFR and errors in body surface area calculated from height and weight.

The authors say that their findings highlight the need to make direct GFR measurements available to patients who need them. They note that implementation studies are needed in this area, and research is needed to assess how the availability and use of mGFRs change clinical management.

Source: EurekAlert!

PET/CT Scans Fail to Beat MRI for Prostate Cancer Detection

Credit: Darryl Leja / National-Human-Genome Research Institute / National Institutes of Health

Researchers found that MRI scans, the current gold standard, can still detect prostate cancer more accurately than the newer, prostate-specific -PSMA PET/CT scanning technique.

The findings were presented at the European Association of Urology’s annual congress (EAU22).

Prostate-specific membrane antigen (PSMA) PET/CT scans, approved by the US FDA in 2020, use a radioactive dye to highlight areas of PSMA, which is overexpressed on the surface of prostate cancer cells. Presently, these scans are used to manage prostate cancer, as they can accurately measure the progression or recurrence of the disease. The researchers set out to find if they could be used to diagnose prostate cancer as well.

The PEDAL trial recruited 240 patients at risk of prostate cancer, with each patient given both an MRI scan and a PSMA PET/CT scan. If imaging suggested the presence of prostate cancer, a biopsy was performed by the patient’s urologist.

The MRI scans picked up abnormalities in 141 patients, while the PSMA PET/CT scans picked up abnormalities in 198 patients. A total of 181 patients (75%) underwent a prostate biopsy, and subsequently 82 of those patients were found to have clinically significant prostate cancer.

The MRI scans were significantly more accurate at detecting any grade of prostate cancer than the PSMA PET scans.

The research team was led by Associate Professor Lih-Ming Wong, who explained: “Our analysis found that MRI scans were better than PSMA-PET for detecting any grade of prostate cancer. When we looked only at clinically significant prostate cancers, there was no difference in accuracy.  As this study is one of the first to explore using PSMA-PET to diagnose cancer within the prostate, we are still learning and adjusting how to improve using PSMA-PET in this setting.

Although detection thresholds will be  fine-tuned as diagnostic use develops,  Prof Wong believes the trial has important lessons for clinicians. 

He said: “This study confirms that the existing ‘gold standard’ of pre-biopsy detection – the MRI – is indeed a high benchmark. Even with fine-tuning, we suspect PSMA PET/CT won’t replace the MRI as the main method of prostate cancer detection. But it will likely have application in the future as an adjunct to the MRI, or for people for whom an MRI is unsuitable, or as a single combined “diagnostic and staging” scan for appropriately selected patients.”

Source: EurekAlert!

Retinal Scans May be Able to Detect ASD and ADHD

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By measuring the electrical activity of the retina in responses to a light stimulus, researchers found that they may be able to neurodevelopmental disorders such as ASD and ADHD, as reported in new research published in Frontiers in Neuroscience.

In this groundbreaking study, researchers found that recordings from the retina could identify distinct signals for both Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) providing a potential biomarker for each condition.

Using the ‘electroretinogram’ (ERG) – a diagnostic test that measures the electrical activity of the retina in response to a light stimulus – researchers found that children with ADHD showed higher overall ERG energy, whereas children with ASD showed less ERG energy.

Research optometrist at Flinders University, Dr Paul Constable, said the preliminary findings indicate promising results for improved diagnoses and treatments in the future.

“ASD and ADHD are the most common neurodevelopmental disorders diagnosed in childhood. But as they often share similar traits, making diagnoses for both conditions can be lengthy and complicated,” Dr Constable says.

“Our research aims to improve this. By exploring how signals in the retina react to light stimuli, we hope to develop more accurate and earlier diagnoses for different neurodevelopmental conditions.

“Retinal signals have specific nerves that generate them, so if we can identify these differences and localise them to specific pathways that use different chemical signals that are also used in the brain, then we can show distinct differences for children with ADHD and ASD and potentially other neurodevelopmental conditions.”

“This study delivers preliminary evidence for neurophysiological changes that not only differentiate both ADHD and ASD from typically developing children, but also evidence that they can be distinguished from each other based on ERG characteristics.”

According to the World Health Organization, one in 100 children has ASD, with 5–8% of children diagnosed with ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterised by being overly active, struggling to pay attention, and difficulty controlling impulsive behaviours. Autism spectrum disorder (ASD) is also a neurodevelopmental condition where children behave, communicate, interact, and learn in ways that are different from most other people.

Co-researcher and expert in human and artificial cognition at the University of South Australia, Dr Fernando Marmolejo-Ramos, says the research has potential to extend across other neurological conditions.

“Ultimately, we’re looking at how the eyes can help us understand the brain,” Dr Marmolejo-Ramos says.

“While further research is needed to establish abnormalities in retinal signals that are specific to these and other neurodevelopmental disorders, what we’ve observed so far shows that we are on the precipice of something amazing.

“It is truly a case of watching this space; as it happens, the eyes could reveal all.”

Source: Flinders University

Rapid Blood Assay to Test for COVID Immunity

Blood sample being drawn
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Researchers have developed a rapid blood assay that measures the strength and duration of an individual’s immunity to SARS-CoV-2. This test will allow population-scale monitoring immunity and vaccine effectiveness. This will help to design revaccination strategies for vulnerable immunosuppressed individuals, according to a study published by the researchers from Mount Sinai in Nature Biotechnology.

The test, which measures the activation of T cells, is performed in under 24 hours and can be scaled up significantly.

“The assay we have created has the ability to measure the population’s cellular immunity and broadly test the efficacy of novel vaccines,” said one of the study’s senior authors, Ernesto Guccione, PhD, Professor at Mount Sinai. “We know that vulnerable populations don’t always mount an antibody response, so measuring T cell activation is critical to assess the full extent of a person’s immunity. Additionally, the emergence of SARS-CoV-2 variants like Omicron, which evade most of the neutralising ability of antibodies, points to the need for assays that can measure T cells, which are more effective against emerging variants of concern.”

Long-term protection from viral infection is mediated by both antibodies and T cell response. Many recent studies point to the importance of determining T cell function in individuals who have recovered from or been vaccinated against COVID to help design vaccination campaigns. However, before this study, measurement of T cell responses has been rarely performed because of the associated technical challenges.

Researchers optimised qPCR-based assays that had the potential to be globally scalable, sensitive, and accurate tests. They then selected the two assays that offered the most scalability. One, the qTACT assay, was accurate and sensitive but had a relatively longer processing time of 24 hours per 200 blood samples, a moderate price, and a medium level of technical skill. The other, the dqTACT assay, was accurate and had a reduced processing time and cost, and required minimal lab experience, making it easy to implement.

The dqTACT assay has recently received the European CE-IVD (in vitro diagnostics) certification, while U.S. Food and Drug Administration and European Medicines Agency clinical validation is ongoing.

“The assays presented here are based on the ability of SARS-CoV-2 T cells to respond to peptides covering different proteins of the virus,” said another senior author, Jordi Ochando, PhD, Assistant Professor at Mount Sinai. “With the possibility of using different peptide pools, our approach represents a flexible strategy that can be easily implemented to detect the presence of T cells responding to different viral proteins. These T cells have an important role in protection from emerging mutant strains, thus immediately gauging the impact that viral mutations might have on cellular immunity.”

Megan Schwarz, a graduate student at Icahn Mount Sinai and first author of the study, added: “Precise measurement of cellular responses underlying virus protection represents a crucial parameter of our levels of immune defence.”

Source: EurekAlert!

Amid Shortage, Suggested Ways to Conserve Contrast Agent

Technician and patient with MRI machine
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Amid an ongoing worldwide shortage of contrast agent for medical imaging, a new UC San Francisco research letter in JAMA described strategies that can be used to safely reduce contrast agent use in computed tomography (CT) by up to 83%.

The three conservation strategies are weight-based (rather than fixed) dosing, reducing contrast dose while reducing tube voltage on scanners, and replacing contrast-enhanced CT with nonenhanced CT when it will minimally affect diagnostic accuracy.

That third strategy – not using the contrast agent in certain CT scans where there is only a small improvement in accuracy – yielded the most dramatic reduction of contrast agent use: 78%.

“Contrast is essential in any situation where we need to assess the blood vessels – for example, for some trauma patients or those with a suspected acute gastrointestinal bleed – and it is also needed for evaluation of certain cancers, such as in the liver or pancreas,” said senior study author Rebecca Smith-Bindman, MD, professor at UCSF.

“However, most CT scans are done for less specific indications such as abdominal pain in a patient with suspected appendicitis,” Prof Smith-Bindman added. “These can and should be done without contrast during the shortage, because the loss of information in these patients will be acceptable for most patients.”

The global shortage of contrast agent started in April with a COVID-related supply chain disruption of GE Healthcare in Shanghai and is expected to last at least several more weeks. More than 54 million diagnostic imaging exams using contrast agents are done every year in the US, a majority being CT scans, and these conservation methods could continue past the current shortage to reduce the use of contrast agent in general, the authors noted.

Referring clinicians are key to conservation
Researchers modelled the three strategies individually and in combination using a sample of 1.04 million CT exams in the UCSF International CT Dose Registry from January 2015 to March 2021.

On its own, weight-based dosing for abdomen, chest, cardiac, spine and extremity imaging reduced contrast agent use by 10%; reducing the tube voltage in appropriate patients allowed a contrast agent reduction of 25%. These two measures combined with using non-contrast CT when possible led to a total reduction of 83%.

Following all three strategies at once may not be possible for some facilities, but each can help conserve supply, Prof Smith-Bindman said. And it is not just radiologists who need to know about them.

“Given the acute shortage, it’s important that clinicians who order imaging exams coordinate with radiology to cancel scans that aren’t absolutely necessary, postpone exams that can be safely delayed, replace CT with MRI and ultrasound where possible, and order an unenhanced scan where possible. Further, clinicians should communicate with their patients about why this is necessary. It is crucial that contrast be conserved for clinical situations where its use is essential for accurate diagnosis,” said Prof Smith-Bindman.

After the shortage ends, medical facilities should consider continuing some of these practices that conserve contrast agent, she added. For example, reducing the tube voltage not only reduces the contrast agent used but also lowers the radiation dose. Tailoring doses weight allows lower dosing volumes for many patients.

In addition, Prof Smith-Bindman noted that this analysis highlights the large amount of contrast agent that is wasted when single-dose vials are used Hospitals and imaging centres that routinely use single-dose contrast agent vials should consider using larger multi-dose vials, which allows for exact dosing and obviates the need to discard unused portions, she said.

“By carrying some of these practices forward, we can mitigate future supply-chain risk and reduce overall waste,” said Smith-Bindman.

Source: University of California – San Francisco

A Bright Idea for MRI Cancer Detection

MRI or CT machine
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Researchers at the University of Waterloo have developed a new form of magnetic resonance imaging (MRI) that makes cancerous tissue glow in medical images. This innovation could enable more accurate detection and tracking of cancer over time.

“Our studies show this new technology has promising potential to improve cancer screening, prognosis and treatment planning,” said first author Professor Alexander Wong.

Irregular packing of cells leads to differences in the way water molecules move in cancerous tissue compared to healthy tissue. The new technology, called synthetic correlated diffusion imaging, highlights these differences by capturing, synthesising and mixing MRI signals at different gradient pulse strengths and timings.

In the largest study of its kind, the researchers collaborated with medical experts at the Lunenfeld-Tanenbaum Research Institute, several Toronto hospitals and the Ontario Institute for Cancer Research to apply the technology to a cohort of 200 patients with prostate cancer.

The synthetic correlated diffusion imaging was found to be better at delineating significant cancerous tissue than current imaging technique, making it a potentially powerful addition to the toolbox for doctors and radiologists.

“Prostate cancer is the second most common cancer in men worldwide and the most frequently diagnosed cancer among men in more developed countries,” said Prof Wong. “That’s why we targeted it first in our research.

“We also have very promising results for breast cancer screening, detection, and treatment planning. This could be a game-changer for many kinds of cancer imaging and clinical decision support.”

Source: University of Waterloo

Cardiac CT Matches Coronary Angiography with Fewer Complications

Coronary artery showing atherosclerosis. Image source: Wikimidia CC0

A clinical trial found that cardiac computed tomography (CT) offers similar diagnostic accuracy to catheterisation – the current standard diagnostic test for intermediate-risk patients – in people with suspected coronary artery disease, as well as being associated with a lower risk of complications. The trial’s findings were published in the New England Journal of Medicine.

The current standard diagnostic test for coronary artery disease (CAD) is coronary angiography (often along with cardiac catheterisation). This minimally invasive procedure uses dye marker visible on X-ray imaging to detect arterial narrowing. Any narrowing detected in this manner can be treated during the procedure itself using stents, which prop open the newly widened blood vessels. More than 3.5 million of these procedures are carried out in European catheterisation laboratories every year, and more are carried out every year. Approximately two million of these do not involve immediate treatment in the cath lab. In these cases, the procedure is able to rule out narrowed or blocked coronary arteries.

The main question addressed by the DISCHARGE Trial Group was whether the low-risk, non-invasive coronary CT method can provide a safe alternative to catheterization in certain patients with suspected CAD. In order to test the effectiveness of both of these diagnostic imaging techniques in patients with stable chest pain, the project followed more than 3500 patients for a duration of four years. Patients were randomised to either computed tomography or cardiac catheterisation. If their initial evaluation ruled out obstructive coronary artery disease, participants were discharged back to their referring physician for further treatment – a step which gave the trial its name: DISCHARGE. Patients who were diagnosed as having the disease were managed in accordance with European guidelines at the time of the study.

Discussing the long-term results, trial leader Professor Dr Marc Dewey said: “The trial confirmed that a CT-based management is safe in patients with stable (ie, non-acute) chest pain and suspected coronary artery disease.”

Evaluation of safety was based on the incidence of major cardiovascular events over a period of up to four years. He added: “Among the patients referred for cardiac catheterisation and included in this trial, the risk of major adverse cardiovascular events was found to be similar in both the CT and catheterisation groups, occurring in 2.1% and 3.0% of patients, respectively. The incidence of major procedure-related complications was found to be four-times lower in patients managed with an initial CT strategy.”

Other outcome measures were included in the DISCHARGE trial, such as improvements in chest pain and quality of life over the course of the trial. This new strategy could help relieve pressure on health care systems by helping to reduce the volume of catheterisation procedures. Prof Dewey said: “Now that CT has been standardised and quality-tested as part of the DISCHARGE trial, this method could be made more widely available as part of the routine clinical care of people with intermediate CAD risk.”

As a next step, the trial’s method for estimating a person’s clinical risk of having coronary artery disease will need to be further evaluated to determine whether it can improve referral and indication for CT in routine clinical care. Health economics are an important component in making decisions about reimbursement in health care systems. As mentioned in the discussion of the publication, further methodologically very rigorous cost-effectiveness analyses of CT and cardiac catheterisation are necessary and will be conducted by the DISCHARGE Trial Group.

Source: University of Glasgow