What you need to know to prepare for a conversation with your doctor, understand the diagnostic process, and manage your expectations.
Everyone has aches and pains now and then. Most of us know what it’s like to feel extra-tired sometimes, too. These kinds of symptoms are usually due to an injury, or are caused by the flu virus or another temporary illness. But if you’ve had joint pain and extreme fatigue for more than a few weeks, or you’ve noticed unusual hair loss or a face rash—and especially if you have any risk factors for an autoimmune disease—it’s time to stop waiting.
It’s time to take the first step: to have a conversation with your doctor about the changes you’ve been experiencing, how your health is being affected, and whether these signs and symptoms could be due to the autoimmune disease lupus, or some other illness or condition.
In order to deliver you answers about what your symptoms or risk factors may mean, your doctor will likely:
This information will allow the doctor to begin to rule out medical problems that don’t fit your health picture. However, diagnosing lupus isn’t easy. This is because:
So, while the information from your medical history and physical test and lab tests may suggest lupus or another condition or disease, there can still be uncertainty. This is why your doctor will probably not be able to tell you, at your first visit, whether or not you have lupus.
Diagnosing a complex disease such as lupus will often take several months, and two or three doctor appointments, as you continue to track your symptoms, and your doctor continues to monitor your lab test results and your overall health.
If your doctor believes your signs and symptoms point to the possibility of lupus, he/she may recommend a referral to a specialist doctor who has training in the group of autoimmune diseases that includes lupus. This specialist is called a rheumatologist (ROOM-ah-TOHL-ah-JYST).
Learn more: How lupus is diagnosed: An overview
Because lupus is not a simple disease to recognize, it’s a good idea to start by seeing a general medicine doctor—also known as Primary Care Provider, General Practitioner, or Family Physician.
There are several kinds of health care providers who work in the office of a primary care doctor. You may see a medical doctor (MD), a physician assistant (PA), or a nurse practitioner (NP). By asking you questions and listening to your answers, your provider will build a picture of your medical condition and immediate concerns. The clearer the picture, the sooner the provider will be able to deliver you an accurate diagnosis, or refer you to a specialist physician.
No matter which provider you see, it’s helpful to remember that today’s health care system works best when you look at your care as a team effort. You’re also taking on a responsibility, because in any meeting between yourself and a provider, you are the team leader. And as the leader, you can make the job easier for other members of the team.
It can be very hard to take in everything that’s said at a doctor's appointment. Before the doctor leaves the room, ask for a brief summary of his/her assessment of your condition, and the action plan to address it, including follow-up. You can also request a printed summary to be mailed to you, including any instructions.
Your action plan may include some or all of these steps:
It’s not easy to face the unknown. You may need all of your patience and courage while waiting for your doctor to share with you the results of his/her investigations. Stay busy with things you enjoy, get plenty of rest, and try not to worry. By seeking answers that explain sudden or long-term changes in your health you’ve taken a very important step along your journey to improved quality of life. It’s a journey that affects everyone who cares about you and depends upon you!
Most people in the United States have some degree of immune protection against COVID-19, either from vaccination, infection, or a combination of the two. But, just how much protection does any individual person have?
MIT researchers have now developed an easy-to-use test that may be able to answer that question. Their test, which uses the same type of "lateral flow" technology as most rapid antigen tests for COVID-19, measures the level of neutralizing antibodies that target the SARS-CoV-2 virus in a blood sample.
Easy access to this kind of test could help people determine what kind of precautions they should take against COVID infection, such as getting an additional booster shot, the researchers say. They have filed for a patent on the technology and are now hoping to partner with a diagnostic company that could manufacture the devices and seek FDA approval.
"Among the general population, many people probably want to know how well protected they are," says Hojun Li, the Charles W. and Jennifer C. Johnson Clinical Investigator at MIT's Koch Institute for Integrative Cancer Research. "But I think where this test might make the biggest difference is for anybody who is receiving chemotherapy, anybody who's on immunosuppressive drugs for rheumatologic disorders or autoimmune diseases, and for anybody who's elderly or doesn't mount good immune responses in general. These are all people who might need to be boosted sooner or receive more doses to achieve adequate protection."
The test is designed so that different viral spike proteins can be swapped in, allowing it to be modified to detect immunity against any existing or future variant of SARS-CoV-2, the researchers say.
Li, who is also an attending physician at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, is the senior author of the study, which appears online today in Cell Reports Methods. Guinevere Connelly, a former Koch Institute research technician who is now a graduate student at Duke University, and Orville Kirkland, a research support associate at the Koch Institute, are the lead authors of the paper.
A simple test
Li, who joined the Koch Institute in the fall of 2019, studies blood cell development and how blood cells become cancerous. When SARS-CoV-2 emerged, he started thinking about ways to help combat the pandemic. Many other researchers were already working on diagnostic tests for infection, so he turned his attention to developing a test that would reveal how much immune protection someone has against COVID-19.
Currently, the gold standard approach to measuring immunity involves mixing a blood trial with live virus and measuring how many cells in the trial are killed by the virus. That procedure is too hazardous to perform in most labs, so the more commonly used approaches involve noninfectious modified "pseudoviral" particles, or they are based on a test called ELISA (enzyme-linked immunosorbent assay), which can detect antibodies that neutralize a fragment of a viral protein.
However, these approaches still require trained personnel working in a lab with specialized equipment, so they aren't practical for use in a doctor's office to get immediate results. Li wanted to come up with something that could be easily used by a health care provider or even by people at home. He drew inspiration from at-home pregnancy tests, which are based on a type of test called a lateral flow assay.
Lateral flow assays generally consist of paper strips embedded with test lines that bind to a particular target molecule if it is present in a sample. This technology is also the basis of most at-home rapid tests for COVID-19.
Li did not have experience working with this type of test, so he reached out to two MIT faculty members with expertise in devising diagnostics based on lateral flow assays: Hadley Sikes, an associate professor of chemical engineering, and Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science, and a member of the Koch Institute.
With their help, his lab developed a device that can detect the presence of antibodies that block the SARS-CoV-2 receptor binding domain (RBD) from binding to ACE2, the human receptor that the virus uses to infect cells.
The first step in the test is to mix human blood samples with viral RBD protein that has been labeled with tiny gold particles that can be visualized when bound to a paper strip. After allowing time for antibodies in the trial to interact with the viral protein, a few drops of the trial are placed on a test strip embedded with two test lines.
One of these lines attracts free viral RBD proteins, while the other attracts any RBD that has been captured by neutralizing antibodies. A strong signal from the second line indicates a high level of neutralizing antibodies in the sample. There is also a control line that detects free gold particles, confirming that the solution flowed across the entire strip.
To develop the reagents needed for the test, members of Li's lab worked with the labs of Angela Koehler, an associate professor of biological engineering, and Michael Yaffe, a David H. Koch Professor in Science, who are both members of the Koch Institute.
Along with a testing cartridge, which contains the paper test strip, the testing kit also includes a finger prick lancet that can be used to obtain a small blood sample, less than 10 microliters. This trial is then mixed with the reagents needed for the test. After about 10 minutes, the trial is exposed to the test cartridge, and the results are revealed in 10 minutes.
The output can be read two different ways: One, by simply looking at the lines, which indicate whether neutralizing antibodies are present or not. Or, the device can be used to obtain a more precise measurement of antibody levels, using a smartphone app that can measure the intensity of each line and calculate the ratio of neutralized RBD protein to infectious RBD protein. When this ratio is low, it might suggest that another booster shot is needed, or that the individual should take extra precautions to prevent infection.
The researchers tested their device with blood samples collected in December 2020 from about 60 people who had been infected with SARS-CoV-2 and 30 people who had not. They were able to detect neutralizing antibodies in the samples from people previously infected to the virus, with accuracy similar to that of existing laboratory tests. They also tested 30 serial samples from two people before they received an mRNA COVID-19 vaccine and at several time points after vaccination. The level of neutralizing antibodies in the vaccinated individuals peaked around seven weeks after the first dose, then began to slowly decline.
Previous studies of SARS-CoV-2 and other viruses have shown a strong correlation between the amount of neutralizing antibody circulating in an individual's bloodstream and their likelihood of infection.
The test could be easily adapted to different variants of SARS-CoV-2 by swapping in a reagent that is specific to the RBD from the variant of interest, Li says. The researchers now hope to partner with a diagnostics company that could manufacture large quantities of the tests and obtain FDA approval for their use.
This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news about MIT research, innovation and teaching.
Citation: New test may predict COVID immunity (2022, August 9) retrieved 9 August 2022 from https://medicalxpress.com/news/2022-08-covid-immunity.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
Bio-Rad Laboratories (NYSE:BIO) announced that it agreed to acquire all outstanding shares of Curiosity Diagnostics.
Hercules, California-based Bio-Rad bought Curiosity Diagnostics from Scope Fluidics, a Warsaw, Poland-based developer of technologies for the medical diagnostic and healthcare markets, for a total consideration of up to $170 million.
The acquisition consists of approximately $100 million in cash, with up to $70 million in future milestone payments, according to a news release.
“We are excited to have the Curiosity Diagnostics team join Bio-Rad’s Clinical Diagnostics Group and to work closely together to bring a new generation of rapid PCR systems to market,” Dara Wright, Bio-Rad’s EVP and president, clinical diagnostics group, said in the release. “Curiosity’s PCR platform, PCR|ONE, offers a streamlined workflow and rapid turnaround times, and is expected to extend our reach beyond high-complexity labs into near-patient molecular diagnostics labs.”
Curiosity Diagnostics, a late-stage, pre-commercial platform company, is developing the PCR|One platform as a sample-to-answer, rapid diagnostics PCR system for the molecular diagnostics market.
“Our passion at Scope Fluidics is developing innovative technologies addressing the greatest challenges in global health,” Scope Fluidics President and co-founder Piotr Garstecki said. “The dedicated, entrepreneurial team of highly skilled, specialized personnel of Curiosity Diagnostics is looking forward to further developing the PCR|ONE technology under Bio-Rad’s leadership while we at Scope Fluidics continue to pursue new and current projects in disruptive medical diagnostics.”
As the COVID-19 pandemic has run its course, the questions we have been asking ourselves have evolved: from “How do I know if I’m infected?” to “How strong is my immunity?” to “Which strain of the virus do I have?” And, as new variants continue to emerge, it’s likely that we’ll keep asking ourselves those questions, often at the same time.
Now, there’s a way to get answers to all of them in a couple of hours, without needing to send samples to a lab. A new point-of-care diagnostic device created by members of the Wyss Institute for Biologically Inspired Engineering at Harvard University combines the Institute’s eRapid and SHERLOCK technologies into a single, postcard-sized system that can simultaneously detect the presence of both SARS-CoV-2 RNA and antibodies against the virus in a patient’s saliva, and potentially multiple other biomarkers.
“This diagnostic can enable cheaper, multiplexed monitoring of infection and immunity in populations over time, at levels of accuracy that are comparable to expensive lab tests,” said co-first author Devora Najjar, a graduate student at the MIT Media Lab and the Wyss Institute. “Such an approach could dramatically Improve the global response to future pandemics, and also provide insight into which treatment individuals should receive.”
The prototype device is described in a new article published in Nature Biomedical Engineering.
Novel chemistry for a novel virus
The diagnostic was born from a collaboration between the labs of Wyss Core Faculty members Jim Collins, Ph.D., and Don Ingber, M.D., Ph.D., who is also the Institute’s Founding Director. The eRapid team led by Ingber and Wyss Senior Staff Scientist Pawan Jolly, Ph.D., together with the SHERLOCK team led by Collins and Helena de Puig, Ph.D., a Wyss Postdoctoral Fellow, recognized that while SHERLOCK-based diagnostics can detect molecules with exquisite sensitivity, they were inherently limited by their fluorescence-based readout system. If they could figure out a way to translate the molecular detection of a CRISPR-based system like SHERLOCK into an electrochemical signal like that produced by eRapid, they could create a diagnostic with lab-level precision that could be used in a non-lab setting. They started building this hybrid device and chose Lyme disease as their target application. Within a few months, they had gotten it to work.
Then the COVID-19 pandemic hit.
“In the early days, everyone was working on developing diagnostics that could detect either the SARS-CoV-2 virus or antibodies against it, but not both. We knew that we could successfully detect the presence of DNA and RNA molecules electrochemically, thanks to our work on Lyme disease. We decided to figure out how to multiplex that with antibody detection in order to create an all-in-one test to help track infections and fight the pandemic,” said de Puig, a co-first author of the paper.
But creating a platform that could integrate the detection of viral RNA and human proteins was a challenge. The team had to figure out how to perform two separate and very different types of molecular reactions simultaneously, then integrate them into one reporting system so that the results could be read at the same time.
They chose saliva as their trial material, because viral particles and antibodies can both be found there. For the SHERLOCK portion of the diagnostic, which detects the presence of SARS-CoV-2 RNA, the device needed to be able to extract, concentrate, and amplify viral RNA from a saliva sample, then mix it with CRISPR reagents and deliver the resulting solution to the eRapid chip portion for detection.
The team engineered a microfluidic system consisting of multiple reservoirs, channels and heating elements to automatically mix and transfer substances within the prototype device without needing input from a user. In the first chamber, saliva is combined with an enzyme that breaks open any viruses’ outer envelopes to expose their RNA. Then the trial is pumped into a reaction chamber, where it is heated and mixed with loop-mediated isothermal amplification (LAMP) reagents that amplify the viral RNA. After 30 minutes of amplification, a mixture containing SHERLOCK reagents is added to the chamber, and then the trial is pumped onto an eRapid electrode.
In the absence of SARS-CoV-2 genetic material in the mixture, single-stranded (ssDNA) molecules with biotin attached to them bind to a molecule called peptide nucleic acid (PNA) on the electrode’s surface. The biotin then binds to another molecule in the mixture called poly-HRP-streptavidin, which causes a third molecule, tetramethylbenzidine (TMB) to precipitate out of the liquid solution as a solid. When the solid TMB lands on the electrode, it changes its electrical conductivity. This change is detected as a difference in the amount of electrical current flowing through the electrode, indicating that the trial is free of the virus.
If any SARS-CoV-2 genetic material is present in the saliva sample, however, the CRISPR enzyme within the SHERLOCK mixture cuts it as well as the ssDNA. This cutting action separates the biotin molecule from the ssDNA, so that when the ssDNA binds to PNA, it does not trigger the series of reactions that causes the TMB to precipitate onto the electrode. Therefore, the conductivity of the electrode is unchanged, indicating a positive test result.
“The integration of the PNA-based assay with the poly-HRP-streptavidin/TMB reaction chemistry that we created for this device allowed us to detect the presence of SARS-CoV-2 with four times higher sensitivity than our original fluorescence-based SHERLOCK technology, and produced results in about the same amount of time,“ said co-first author Joshua Rainbow, Ph.D., a former Visiting Graduate Student at the Wyss Institute who is now a doctoral student at the University of Bath. “It was also able to detect the presence of viral RNA with 100% accuracy.”
Greater than the sum of its parts
In parallel, the team customized the remaining three eRapid electrodes by studding them with different COVID-related antigens against which patients can develop antibodies: the S1 subunit of the Spike protein (S1), the ribosomal binding domain within that subunit (S1-RBD), and the N protein, which is present in most coronaviruses (N). If a patient’s saliva trial contains one or more of these antibodies, they bind to their partner antigens on the electrodes. A secondary antibody that is attached to biotin will then bind to the target antibody, triggering the same poly-HRP-streptavidin/TMB reaction and causing a change in the electrode’s conductivity.
The researchers tested these antibody-specific sensors using samples of human plasma from patients who had previously tested positive for SARS-CoV-2. The system was able to distinguish between antibodies against S1, S1-RBD, and N with over 95% accuracy.
“Being able to easily distinguish between different types of antibodies is hugely beneficial for determining whether patients’ immunity is due to vaccines versus infection, and tracking the strength of those different immunity levels over time,” said Sanjay Sharma Timilsina, Ph.D., a former Postdoctoral Fellow at the Wyss Institute who is now a Lead Scientist at StataDX. “Integrating that with viral RNA detection in a portable, multiplexed diagnostic platform provides a comprehensive view of a patient’s health both during and after an infection, which is essential for implementing public policy and vaccination strategies.” StataDX is commercializing eRapid for neurological, cardiovascular, and renal applications.
Finally, the team tested the combined viral RNA and antibody electrodes using saliva from SARS-CoV-2 patients. They split the saliva into two portions, adding one portion to the antibody reservoir and the second portion to the RNA reservoir of the device. After two hours, they measured the electrodes’ readouts to see if they had correctly registered the presence of the antibodies and RNA.
The team found that the multiplexed chips correctly identified positive and negative RNA and antibody samples with 100% accuracy, at the same time. It was also ultra-sensitive, able to detect the presence of RNA down to 0.8 copies per microliter.
“Currently, there is a lack of low-cost diagnostic platforms that can enable accurate detection of multiple classes of molecules without requiring a trip to a lab. Our system offers the best of both worlds – high accuracy and low cost in a multiplexed platform – and could provide a lot of value to both patients and clinicians at the point of care. Plus, it’s easily adaptable to a wide range of applications,” said co-first author Jolly.
The prototype device’s low cost and compact design is user-friendly and minimizes the number of steps a patient needs to perform, reducing the possibility of user error. Customized cartridges could be easily manufactured to detect antigens and antibodies from different diseases, and could be fit into a reusable housing and readout device that a user would keep in their home.
“What excites me about this diagnostic device is that it combines a high level of accuracy with a flexible design that could make it a major tool in our arsenal for addressing future pandemics,” said co-senior author Collins, who is also the Termeer Professor of Medical Engineering & Science at MIT. In addition, Collins is a co-founder of Sherlock Biosciences, which is developing the Wyss Institute’s SHERLOCK technology into diagnostics for COVID-19 and other diseases.[BL1]
“I’m very proud of these teams for coming together during a global crisis that ground most activity to a halt, and creating something new and useful that offers great promise for point-of-care diagnosis and management of a broad range diseases around the world,” said co-senior author Ingber, who is also the the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, as well as the Hansjörg Wyss Professor of Bioinspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
Additional authors of the paper include Mohamed Yafia, Nolan Durr, and Hani Sallum from the Wyss Institute; Galit Alter from the Ragon Institute of MGH, MIT, and Harvard; Jonathan Li from Brigham and Women’s Hospital (BWH), Xu Yu from the Ragon Institute and BWH, David Walt from the Wyss Institute, HMS, and BWH; Joseph Paradiso from the MIT Media Lab, and Pedro Estrela from the University of Bath.
This research was supported by the Wyss Institute for Biologically Inspired Engineering at Harvard University, the Paul G. Allen Frontiers Group, the UK Natural Environment Research Council (NERC) GW4 FRESH CDT, the Fonds de recherche du Québec nature et technologie, Ms. Enid Schwartz, the Mark and Lisa Schwartz Foundation, the Massachusetts Consortium for Pathogen Readiness, the Ragon Institute, and the Harvard University Center for AIDS Research.
Nature Biomedical Engineering
Human tissue samples
Lab-on-a-chip multiplexed electrochemical sensor enables simultaneous detection of SARS-CoV-2 RNA and host antibodies
The goal: Improve survival rates for lung cancer patients.
The question researchers want to answer: Are there new ways to determine the best treatment for these patients?
This is what UW Medicine researchers hope to discover through a five-year, $2.7 million grant from the National Cancer Institute.
"Diagnostic tests have known error rates," said Dr. Farhood Farjah, associate professor of surgery, Division of Cardiothoracic Surgery, and associate medical director of the Surgical Outcomes Research Center at UW Medicine.
CT and PET scans both have false positives and negatives, he said. So if physicians rely on imaging alone, the cancer's stage, or determination of whether the disease has spread, might be classified incorrectly. That misclassification can inadvertently result int providing patients with either the wrong or less-than-optimal treatments, he said.
For example, understaging can lead to unnecessary surgery or omission of chemotherapy. Overstaging can lead to unnecessary chemotherapy and omission of surgery. Either can lead to lower survival rates.
Biopsies on lymph nodes in the chest can reduce these errors. But they also can have drawbacks, including false negatives and procedure-related risks such as a collapsed lung, Farjah said.
While there are guidelines that help clinicians determine when to do biopsies, the evidence "is admittedly low," he said.
"As well intentioned as the guidelines are, there are many smart clinicians who will question and deviate from them," Farjah said. Yet some patients who need biopsies aren't getting them when they are necessary, he said.
"The hallmark of clinical and scientific uncertainty is inexplicable variability in care," he added.
When biopsies are needed, they help determine the next steps in treatment, such as surgery, radiation and chemotherapy.
Farjah and other researchers think that the path to a better diagnosis may lie in a micro statistical analysis with maximized safeguards to protect patient confidentiality. This would be conducted on 4,000 lung cancer patient records from Kaiser Permanente Northern California and Marshfield Clinic in Wisconsin.
Other medical systems and universities participating in the research are Medical University of South Carolina, and Kaiser Permanente Bernard J. Tyson School of Medicine.
Within UW Medicine, collaborators on the project include experts in thoracic surgery, pulmonary medicine, radiology, medical and radiation oncology, biostatistics and health economics. The researchers are looking for trends in patient treatments, survivability rates and whether current treatment guidelines were followed.
The study will test a risk prediction model that estimates the probability that a patient actually has cancer that has spread to the lymph nodes. If proven useful, this model might guide decisions on whether to conduct a biopsy. The analytic tool will estimate outcomes under different treatment scenarios. Researchers will test if this tool works just as well as current guidelines for predicting long-term survival while also reducing the number of unneeded biopsies. The study also will determine if the statistical model can accurately predict the best treatment options.
Where we can do better is doing fewer procedures on people who ultimately will not have any nodal disease."
Dr. Farhood Farjah, associate professor of surgery, Division of Cardiothoracic Surgery, and associate medical director of the Surgical Outcomes Research Center at UW Medicine
"Getting the right treatment is the best strategy for best outcomes," he said, including long-term survival and providing a good quality of life.
While advances in screening and treatments often receive national attention, getting the correct staging of cancer "never feels like it gets enough of the spotlight," Farjah said.
"Sometimes the most important things in our lives are right in front of us," he said. "We're just not paying attention."
The grant number for this National Cancer Institute-funded project is R01CA258351-01A1.
Some state statistics on lung cancer: In Washington 26% of patients are alive five years after being diagnosed with lung cancer, according to the American Lung Association, although early detection significantly increases that to 60%. Asian Americans or Pacific Islanders in Washington are least likely to be diagnosed early, according to the 2021 study.
We assessed the opinions of a representative trial of GPs about the 'furosemide test' using an anonymous questionnaire which was handed out during a continuing medical education (CME) course on diabetes in November 2008. We asked the GPs to answer three questions: (i) How often do you apply the furosemide test? (ii) Which symptoms do you monitor and which criteria do you use for a 'positive test'? (iii) Are you convinced of the usefulness of the 'furosemide test' as a diagnostic test in heart failure?
To determine the diagnostic value of the 'furosemide test' we performed a diagnostic accuracy study among a representative, consecutive trial of patients who were suspected of new, slow-onset heart failure by the GP and were referred to the rapid access heart failure outpatient diagnostic facility of the St Antonius Hospital in Nieuwegein, The Netherlands. All patients who consented to participate underwent a standardized diagnostic work-up programme as part of a larger study, the Utrecht Heart Failure Organisation—Initial Assessment (UHFO–IA) study. In short, all participants of the UHFO–IA study were asked about their medical history, signs and symptoms, underwent a 12-lead ECG, blood tests, including B-type natriuretic peptide measurements (NT-proBNP), chest X-ray, spirometry, and echocardiography. The reference ('gold') standard for the diagnosis of heart failure was the decision of an expert panel consisting of a cardiologist, a pulmonologist, and a general physician. They based their decision on the results of all diagnostic tests, including echocardiography, however, without the results of the BNP test or 'furosemide test'. The latter to prevent incorporation bias.[10–12] The criteria for heart failure specified in the European Society of Cardiology guidelines were used for the final decision of the panel, which was made after 6 months of follow-up.
The GP was asked to provide an estimate of the probability of heart failure when the patient was referred to the rapid access facility.
Echocardiographic examinations (M-mode, 2D and Doppler-flow) were obtained in accordance with American Society of Echocardiography guidelines. The left ventricular ejection fraction was assessed semi-quantitatively, where reduced systolic function was defined as ejection fraction <45–50%. Diastolic function was categorized as normal, impaired relaxation, or restrictive filling by a combination of left ventricular wall thickness, transmitral and pulmonary flow patterns, and left atrial volume.
The inclusion criteria for the 'furosemide test' substudy were: (i) referred by the GPs because of suspected heart failure, (ii) physically and mentally able to assess the effects of the 'furosemide test', and (iii) signed informed consent. Patients were excluded if they were already prescribed a loop or thiazide diuretic or if furosemide was deemed contra-indicated.
Before starting the furosemide test treatment the patient's weight was measured and their severity of fatigue, shortness of breath and oedema was assessed. Furthermore, they were given a diary to record their weight and symptoms. Patients were prescribed furosemide 40 or 80 mg once daily for 1 week at the discretion of the physician. Patients were invited to attend the outpatient clinic after this 1 week. Both patients and physician were blinded to the other results of the diagnostic assessment and thus did not know whether the patient had heart failure or not.
The study was approved by the medical Ethics Committee of the St Antonius Hospital, Nieuwegein, The Netherlands.
The effects of the 'furosemide test' were measured from the absolute weight change (kg) in addition to the change in perception of fatigue, shortness of breath, and oedema measured on a 4 point scale, ranging from worse (–1) to distinctly better (+2). A simple summation of the three effects (change in weight, symptomatic complaints, and oedema) was also calculated.
To quantify the association between the effects of the 'furosemide test' and the presence of heart failure, the odds ratio (OR) and P-value as computed by a logistic regression analysis were used. We also computed the area under the receiver operator characteristic curve (c-statistic), a measure that combines the sensitivity and specificity of a diagnostic test, an assessment of discrimination between disease present vs. disease absent.
The OR and c-statistic were also computed for NT-proBNP (on a logarithmic scale) and the probability of heart failure being present as estimated by the referring GP upon referral is also presented.
Toronto, Ontario--(Newsfile Corp. - August 4, 2022) - Therma Bright Inc. (TSXV: THRM) (OTCQB: TBRIF) ("Therma" or the "Company"), developer of its smart-enabled AcuVid™ COVID-19 Rapid Antigen Saliva Test and other progressive diagnostic and medical device technologies, is pleased to provide the following update for Its AcuVid™ COVID-19 Rapid Antigen Saliva Test.
Therma continues to communicate with the FDA regarding its EUA application for its AcuVid™ COVID-19 Rapid Antigen Saliva Test. As well, Therma has sought and utilized advice from Ridge Global and our FDA regulatory consultants to determine how best to accelerate the review of the AcuVid™ EUA application.
In addition to responding to the FDA's initial review and request for additional information, the Company expects to receive further feedback from the FDA once they review the submitted responses.
Health Canada's application for approval under the Interim Order is moving along expeditiously with consistent feedback and answers between Therma and Health Canada's technical and medical reviewers.
"We thank our shareholders for their continued patience and support. The FDA EUA review process is a rigorous and thorough process, as are all regulatory reviews, and therefore patience is required", commented Rob Fia, CEO of Therma Bright.
Therma is also pleased to announce that it has fielded several potential sales inquiries for the AcuVid™ COVID-19 Rapid Antigen Saliva Test. Therma is currently discussing an order utilizing its self-certification CE mark for sales into Eastern Europe and other countries where the self-certification CE mark is accepted.
About Therma Bright Inc.
Therma Bright, developer of the smart-enabled AcuVid™ COVID-19 Rapid Antigen Saliva Test, is a progressive medical diagnostic and device technology company focused on providing consumers and medical professionals with quality, innovative solutions that address some of today's most important medical and healthcare challenges. The Company's initial breakthrough proprietary technology delivers effective, non-invasive and pain-free skincare. Therma Bright received a Class II medical device status from the FDA for its platform technology that is indicated for the relief of the pain, itch, and inflammation of a variety of insect bites or stings. The Company received clearance for the above claims from the U.S. FDA in 1997. Therma Bright Inc. trades on the TSXV (TSXV: THRM) (OTCQB: TBRIF) (FSE: JNX). Visit: www.thermabright.com.
Therma Bright Inc.
Rob Fia, CEO
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FRANKFORT, Ky.—Improving early diagnosis for children with autism is the business strategy of a new virtual clinic called As You Are, which is beginning operations today in Kentucky, Alabama, New Jersey, Ohio andPennsylvania.
Parents can face very long wait times to receive answers. As You Are aims to solve this problem by increasing access to a team of pediatricians who provide evaluations for autism to children 16 months to 10 years old using exclusively telehealth appointments. Families who complete the assessment process can receive a diagnosis in less than one month.
It is managed and operated by Quadrant Biosciences Inc., a life sciences company that aims to Improve the lives of children and families by delivering innovative diagnostic, therapeutic and virtual care solutions. Headquartered in Syracuse, N.Y., and located throughout the SUNY Upstate Medical University campus, Quadrant Biosciences has grown to 180+ employees since 2015.
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According to the company, teams use exclusively virtual appointments to make the experience faster and more accessible and employ an evidence-based approach, making the process as rigorous as possible. By connecting families with physicians, As You Are equips families with the knowledge and resources families need to help children flourish, regardless of their location.
“Over 80% of all counties in the U.S. lack diagnostic resources,” said Kayla Wagner, CEO. “As You Are transcends geographic barriers to provide timely and high-quality care for patients in the comfort of their own home.”
The telehealth access service plans to expand nationwide. To learn more about how to get started, visit AsYouAre.com.
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Background Groin pain in athletes occurs frequently and can be difficult to treat, which may partly be due to the lack of agreement on diagnostic terminology.
Objective To perform a short Delphi survey on terminology agreement for groin pain in athletes by a group of experts.
Methods A selected number of experts were invited to participate in a Delphi questionnaire. The study coordinator sent a questionnaire, which consisted of demographic questions and two ‘real-life’ case reports of athletes with groin pain. The experts were asked to complete the questionnaire and to provide the most likely diagnosis for each case. Questionnaire responses were analysed by an independent researcher. The Cohen's κ statistic was used to evaluate the level of agreement between the diagnostic terms provided by the experts.
Results Twenty-three experts participated (96% of those invited). For case 1, experts provided 9 different terms to describe the most likely diagnosis; for case 2, 11 different terms were provided to describe the most likely diagnosis. With respect to the terms provided for the most likely diagnosis, the Cohen's κ was 0.06 and 0.002 for case 1 and 2, respectively. This heterogeneous taxonomy reflects only a slight agreement between the various diagnostic terms provided by the selected experts.
Conclusions This short Delphi survey of two ‘typical, straightforward’ cases demonstrated major inconsistencies in the diagnostic terminology used by experts for groin pain in athletes. These results underscore the need for consensus on definitions and terminology on groin pain in athletes.
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Groin injuries are prevalent in sports involving rapid directional changes.1 ,2 From an anatomical perspective, the groin region includes several inter-related structures, thus the ability to precisely identify the source of the pain can be difficult.3 Symptoms may arise from gynaecological, urogenital, gastrointestinal, neurological and musculoskeletal structures.4 ,5 This complexity makes the evaluation of groin injuries challenging and likely results in the use of differing terminology by clinicians.
Groin pain terminology can therefore be confusing, leading to difficulties with the interpretation of research results. A systematic review in this issue emphasises the need for uniform terminology, as heterogeneous classification makes interpreting and comparing studies difficult.6 This review on the treatment of groin pain in athletes included 72 studies, of which 33 different diagnostic terms were used.
Improving homogeneity in groin injury terminology could be achieved by a systematic expert opinion approach. The Delphi survey methodology is widely used to ascertain consensus on issues, such as diagnosing medical conditions.7 This predefined decision method uses standardised criteria to evaluate agreement and is therefore more valuable than less formalised consensus approaches.
Our aim was to identify the current heterogeneity of terminology used to diagnose groin pain in athletes. To assess this heterogeneity, we used a short Delphi method in a group of expert clinicians in the field of groin pain in athletes. This procedure served as part of the preparation for the first Doha Agreement Meeting on Definitions and Terminology on Groin Pain in Athletes to which the 23 participating experts (listed in the Acknowledgement section) were invited.8
The study was initiated and managed by researchers (AW and PH) of the ‘Sports Groin Pain Centre’ at Aspetar orthopaedic and sports medicine hospital, Doha, Qatar. Five researchers were involved in the survey design. All invited experts were asked to participate in a Delphi questionnaire.
The invited experts were selected by the study initiators based on at least one of the following criteria: (1) three or more publications in the field of groin pain in athletes; (2) experience in scientific methodology (designing systematic review, Delphi procedure and agreement meeting); or (3) clinical expert and designated member of the conference organising committee. The experts did not represent specific organisations.
One of the initiating researchers acted as coordinator (AW) and prepared a questionnaire, which was sent to all invited experts by email. The first part of this questionnaire consisted of demographic questions. The experts were asked to provide information about: their age, sex and occupation; the number of working years since their qualification; the number of patients with groin pain evaluated per year (and the percentage of athletes in this population); and the number of patients with groin pain evaluated in a research context (for the experts not working as clinicians).
The second part of the questionnaire consisted of two clinical case presentations in which the history, physical examination and selected imaging findings were comprehensively described. These were ‘real-life’ cases from the practice of the coordinating researcher. The experts all completed a standardised questionnaire and provided their diagnoses. There was no limit to the number of diagnoses that the expert could list, but the first diagnosis was regarded as the most likely and the last diagnosis as the least likely. Experts were asked to answer the questions with only the details provided; no extra information was given, so that every expert would base his or her answers on the same information. All the questions were answered in English and non-native speakers were asked to use the closest English translation of their native language diagnosis. The results were returned to the coordinator (AW) with the experts being blinded to each others’ answers. Once all members had completed and returned the questionnaire, a summary of the results was circulated to the members.
Case 1 described a 27-year-old male amateur runner and soccer player with a first episode of unilateral groin pain. The history, examination and X-rays and MRI of the pelvis (both including reports from a musculoskeletal radiologist) were displayed.
Case 2 described a 31-year-old male professional soccer player with recurrent bilateral groin pain and persistent left-sided groin pain. The history, examination, X-rays of the pelvis and hips (including report), and ultrasound report from a musculoskeletal radiologist were displayed. A detailed description of these cases can be found in the online supplementary file.
All replies were collected by the coordinating researcher (AW) and analysed by an independent researcher (R-JdV). This researcher summarised the demographics of the experts and the diagnoses they provided based on the given information of the two case presentations. Data with normal distribution were displayed as mean±SD and skewed data as median±IQR. The Cohen's κ statistic was used to evaluate the level of agreement between the diagnostic terms provided by the experts. Based on the existing literature, a κ<0 reflects ‘poor’, 0–0.20 ‘slight’, 0.21–0.4 ‘fair’, 0.41–0.60 ‘moderate’, 0.61–0.8 ‘substantial’ and above 0.81 ‘almost perfect’ agreement. Negative values indicate agreement less than a value that would be expected by chance, which could be regarded as potential systematic disagreement among the experts.9
Twenty-four experts were contacted to participate in this short Delphi study and 23 (96%) agreed to participate. The expert group represented 11 different countries and three different continents. Their mean (SD) age was 49.7 (10.3) years and 21 (91%) were male. The group consisted of sports physicians (n=6), physiotherapists (n=6), general surgeons (n=5), orthopaedic surgeons (n=4), a radiologist, and a combined orthopaedic and general surgeon. The mean (SD) years of experience postqualification was 22.8 (8.9). The median number of groin patients (IQR) that the experts evaluated in the previous year was 150 (30–400) and a median (IQR) of which 90 (30–90) were athletes.
For case 1, a first diagnosis was provided by all 23 experts, a second diagnosis by 13 and a third diagnosis by 3. The 23 experts provided 9 different terms to describe the first diagnosis, 11 different terms to describe the second diagnosis and 3 different terms to describe the third diagnosis (table 1).
For case 2, a first diagnosis was provided by all 23 experts, a second diagnosis by 10 and a third diagnosis by 4. The 23 experts provided 11 different terms to describe the first diagnosis, 9 different terms to describe the second diagnosis and 4 different terms to describe the third diagnosis (table 2).
For the first, second and third diagnostic terms in case 1, the Cohen's κ was 0.06, −0.03 and −0.13, respectively. Likewise, the Cohen's κ was, respectively, 0.002, −0.01 and 0.000 for the first, second and third diagnostic terms in case 2. This result reflects a disagreement to slight agreement in the choice of diagnostic terms among the experts.
This study aimed to identify the current diagnostic terminology used for athletes with groin pain among 23 experienced researchers and clinicians from around the world. The results of this short Delphi survey confirm the disparity in current terminology. In the first case, 9 different terms were provided for the most likely diagnosis, and in the second case, 11 different terms were provided for the most likely diagnosis. There was only slight agreement in diagnostic terminology among the experts in both cases.
The results of this study illustrate that a lack of agreement on diagnostic terminology is a major problem in the field of groin pain in athletes. While different terms may in some instances refer to the same diagnosis (eg, adductor tendinitis and adductor tendinopathy), the lack of consensus on diagnostic taxonomy makes it almost impossible to compare different study results.5 One systematic review in this BJSM issue revealed that 33 different diagnostic terms were used for groin pain in athletes,6 and this inconsistency meant that the data could not be pooled. The use of uniform terminology and definitions that are based on clinical findings is imperative to interpret and compare studies investigating groin pain in athletes, as well as for the implementation of research findings into clinical decision-making. To reach consensus in this terminology, an agreement meeting was planned with the group of experts following the completion of this Delphi procedure. The results of this agreement meeting are included in the June 2015 issue (#12) of BJSM (Doha Agreement meeting on terminology and definitions in groin pain in athletes). In science, consistency in the use of terminology and definitions together with minimum reporting standards can Improve clinical management and quality of study design and reporting.
To our knowledge, the Delphi method has never been applied before in the field of groin pain terminology. A previous study examined the alternative approaches used by a panel of experts from a variety of specialities and the different diagnostic terms they proposed for the same patients.4 Our study was specifically designed to register the different diagnostic terms used by a broad range of experts. Furthermore, in order to prevent interpretation bias, the questionnaire responses were anonymised and the researchers performing the analysis were blinded as to which questionnaire was completed by each expert. A limitation of this Delphi survey is that a short version has been employed. A standard Delphi survey methodology consists of three subsequent rounds of questionnaire distribution and completion by an expert panel.10 Our short Delphi survey only consisted of one round, because our aim was to assess the current level of agreement in terminology. A future survey among experts and among a group of novice clinicians who have read the new agreement statement on terminology could be performed to examine whether the proposed terminology in the June 2015 issue (#12) of BJSM facilitates improved agreement.
Many different diagnostic terms were provided by a panel of international experts evaluating the same case presentations. The level of agreement between the experts was found to be only slight for the term describing the most likely diagnosis, and slight agreement to disagreement for the terms provided to describe the other possible diagnoses. These results highlight the need for more systematic terminology and definitions when reporting on groin pain in athletes. In clinical practice, the challenge will be to implement new terminology and test whether it helps to achieve the ultimate goal—improving care of athletes.
The authors thank the expert group for their cooperation in this survey. The expert group consisted of the following other members: Brukner P, Ekstrand J, Griffin DR, Khan KM, Lovell G, Meyers WC, Muschaweck U, Orchard JW, Paajanen H, Philippon M, Reboul G, Robinson P, Schilders E, Serner A, Silvers HJ, Thorborg K, Tyler TF, Verrall GM, Vuckovic Z.