CANCER
INFECTIOUS DISEASES
OPHTHALMOLOGY
SURGERY
Research and innovation
Including the race for a safe and effective Covid-19 vaccine, a breath test to detect Covid-19 infection in patients with a false-negative nasal swab test and AI software that can revolutionise patient outcomes with faster results and earlier diagnosis
December 10, 2020
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Race for a safe and effective Covid-19 vaccine gears up
In the past few months, the European Commission has been working to secure supply chains for potential Covid-19 vaccines. The Commission recently approved a fifth contract with the European pharmaceutical company CureVac, which provides for the initial purchase of 225 million doses, plus an option to request up to a further 180 million doses, to be supplied once a vaccine has proven to be safe and effective against Covid-19.
The contract with CureVac enlarges the already broad portfolio of vaccines to be produced in Europe, including the contracts signed with Oxford-AstraZeneca, Sanofi-GSK, Janssen Pharmaceutica NV and BioNtech-Pfizer, and successful exploratory talks with Moderna.
Irish scientist Prof Adrian Hill, director of Oxford University’s Jennings Institute is one of the researchers involved in development of the Oxford-AstraZeneca vaccine. Interim data show the vaccine is 70.4% effective and tests on two dose regimens show that it could be 90%, according to the university.
It is hoped the diversified vaccines portfolio will ensure Europe is well prepared for vaccination, once the vaccines have been proven to be safe and effective. Member states can decide to donate the vaccine to lower- and middle-income countries.
The Commission recently authorised a contract for up to 300 million doses of the vaccine BNT162b2 being developed by German company BioNTech-Pfizer, which is in phase III of clinical trials. The vaccine candidate has been found to be more than 90% effective in preventing Covid-19 in participants without evidence of prior SARS-CoV-2 infection in the first interim efficacy analysis, according to BioNTech-Pfizer.
US biotech firm Moderna has also revealed impressive results from phase III trials of its Covid-19 vaccine mRNA-1273 (95% effective in those over 65). Both vaccines are based on ribonucleic acid (mRNA) technology, an emerging field in medicine.
Commenting on the mRNA vaccines Dr Piotr Kowalski, HRB-funded emerging investigator for health and a lecturer in advanced therapies at UCC’s School of Pharmacy, said: “Therapies utilising the delivery of messenger ribonucleic acid (mRNA) to patients’ cells have many potential applications in vaccine development and gene therapy. The first clinical application of mRNA will clearly be vaccinations.
“Traditional vaccines utilise the inactivated virus or antigen protein itself, manufactured in a cell-based process that takes months to set up and run. With mRNA vaccines, the patient’s own body becomes the antigen factory.
“The speed with which mRNA vaccine candidates can be designed and produced is a key advantage of this new vaccine technology”, he said.
The Janssen Pharmaceutica NV Covid-19 vaccine candidate leverages the AdVac technology platform, which was also used to develop and manufacture Janssen’s recently approved Ebola vaccine and the Zika, RSV and HIV vaccine candidates. This vaccine candidate is also in phase III of clinical trials.
Breath test for Covid-19 detects infection in up to 93.3% of patients who had a false negative nasal swab test
Scientists have used breath samples to detect Covid-19 infection in up to 93.3% of patients who had a false negative nasal swab test. The study, led by researchers from RCSI, is published in the current issue of Thorax.1
The researchers collected breath samples from patients admitted to hospital who tested negative with nasal swab tests but had a clinical diagnosis of Covid-19. The patients were symptomatic for a median of seven days prior to admission.
They found that breath samples were able to detect the virus and that testing multiple genes increases detection. When testing for two genes of the virus, the breath test detected Covid-19 in two-thirds of patients. When the researchers tested for four genes, they detected the disease in 93.3% of patients.
While the study shows breath samples can be used as an effective, non-invasive test that may increase detection of Covid-19 infection, the study has limitations.
Due to decreased admissions as a result of public health measures, the number of patients in the study was too small to establish a statistically significant difference between nasal swabs and breath samples when testing for two genes of the virus. Since the breath samples were collected a median of two days after the nasal swabs, there is a potential for introducing bias favouring the breath test.
“It is essential to detect the disease at an early stage so that the infected person can immediately be isolated from the healthy population,” said Prof Bryan Hennessy, RCSI associate professor of medicine and the study’s co-senior author. “Due to the invasive nature of nasal swabs, some patients are too unwell to provide samples, so it is important to find alternative methods of testing. While more research is needed to confirm our findings, clinicians should consider testing breath samples to aid diagnosis of Covid-19 in patients who they suspect of being infected despite negative results from nasopharyngeal swabs.”
The study was funded by Science Foundation Ireland’s Covid-19 Rapid Response Call and the North East Cancer Research and Education Trust (NECRET).
“Our findings show that breath tests can detect SARS-CoV-2 and that testing multiple genes together increases detection; while our findings need to be repeated in larger studies, breath sampling is easy for the patient and may have further benefits over swabbing where serial testing of individuals is performed,” said Prof Ross Morgan, consultant respiratory physician at Beaumont Hospital and the study’s co-senior author.
Artificial intelligence software can revolutionise patient outcomes with faster results and earlier diagnosis, RETINA conference hears
An algorithm developed by Irish ophthalmologist Dr Pearse Keane can help predict progression of retinal diseases, the recent RETINA conference heard. Dr Keane was the main speaker at this year’s conference, an annual gathering in Ireland to showcase latest advances in treating eye disease and curing sight loss, which took place virtually on Friday November 6, 2021.
Dr Keane, who is based in Moorfields Hospital, London, has been developing artificial intelligence (AI) software to detect eye disease. It operates by interpreting optical coherence tomography (OCT) scans of the back of the eye, which soon will be routine during an eye check.
Automation in analysing scans for diseases such as wet age-related macular degeneration (AMD), the main cause of blindness in Europe, and diabetic retinopathy, is about to revolutionise patient outcomes with faster results affording earlier diagnosis and prompt treatment – and ultimately preventing avoidable sight loss, the conference heard.
Since that initial breakthrough, the Keane team has developed an alert system for a third of people with AMD who later get it in their good eye and, potentially, an early-warning system for onset of neurodegenerative diseases, notably Alzheimer’s.
OCT is similar to ultrasound but uses light rather than sound waves to generate 3D digital images, which provide a detailed map of the eye, but are hard to read and need expert analysis to interpret, Keane explained. If people suddenly develop a problem, such as a bleed at the back of the eye, delays could cost patients their sight but already the AI tool is reducing the incidence of AMD.
The RETINA conference brought together some of the world’s leading scientists working to find treatments and cures for conditions causing vision impairment and blindness.
The event saw the launch of Retina Network Ireland, a new all-island network of researchers, clinicians and allied healthcare professionals working across the spectrum of retinal disease. This initiative is supported by the Health Research Board.
Other topics discussed were:
- Employing adaptive optics to monitor patient populations over time in understanding the rate of progression in inherited retinal diseases for assessing eligibility for clinical trials and for measuring trial outcomes (Dr Jacque Duncan)
- Inherited retinal degenerations and syndromic diseases, and the experiences of patients who have received a gene therapy (Prof Bart Leroy)
- Exploring the power of language and how we can use it to educate, entertain and inspire in science communication (Jonathan McCrea)
- Using the smartphone to screen for glaucoma (Dr Kate Coleman).
For more see www.retina.ie
TCD research discovery leads to clinical trial in childhood cancer
A discovery by researchers at Trinity College Dublin in a form of cancer common in children, has led to the announcement that clinical trials will begin in 2021.
The original discovery in synovial sarcoma – a form of soft tissue cancer that is common in children – was made in 2018. The research, led by Dr Gerard Brien, senior research fellow at the Department of Genetics, TCD, discovered an “Achilles’ heel” in synovial tumours, which provided an opportunity to develop new treatment approaches. Better treatments for these tumours are essential since around 60% of patients diagnosed with synovial sarcoma die from their disease – a figure that hasn’t improved for years.
Dr Brien’s research team focuses on difficult to treat childhood cancers, like synovial sarcoma. Many childhood cancers have been under-studied compared to more common adult diseases. This means that our ability to treat many childhood diseases has not improved at the same rate seen in common adult cancers. As a result, patient survival rates in many of these cancers have not seen significant improvements for years and even decades.
Dr Brien, who trained in childhood cancer research at the Memorial Sloan Kettering Cancer Centre in New York and Harvard Medical School in Boston, explains that recent technological advances are transforming our ability to understand cancer. His lab uses cutting edge genomics technologies to study cancer cells. Dr Brien and his team are making important new discoveries about cancer biology allowing them to understand the “nuts and bolts” of a cancer cell. In turn his team are using these insights to figure out ways to disrupt cancer biology. In other words, develop new treatment approaches to tackle these cancers.
The team discovered that the BRD9 gene is essential for synovial sarcoma tumour growth. Having found this, they wanted to develop new drugs to target BRD9 – a gene that we know very little about other than it is essential for the growth of synovial sarcoma tumours. The team was successful in these efforts, developing drugs that tricked cancer cells into shutting off BRD9 and blocking the growth of synovial sarcoma tumours in pre-clinical testing.
Motivated by these discoveries the Boston-based biopharmaceutical company C4 Therapeutics has pursued BRD9 targeting in synovial sarcoma and recently announced plans to start a clinical trial in 2021.
Dr Gerard Brien said: “ It is incredibly motivating to see our work reaching patients so quickly as it often takes many years for laboratory-based research findings to have any tangible impact on patients. This is an exciting time and we’re all crossing our fingers these trials are successful.”
Dr Brien added: “The new Trinity St James Cancer Institute (TSJCI) is essential to integrate the laboratory and clinical sides of cancer research in Ireland. I certainly hope that building collaborative relationships within TSJCI will provide a basis for establishing future clinical trials here in Ireland.”
UL research reveals extreme levels of uric acid can significantly reduce patient survival
Extreme values of serum uric acid levels in the blood can markedly reduce a patient’s chance of surviving and reduce their lifespans by up to 11 years, according to a new study by researchers at University of Limerick’s School of Medicine.
In one of the largest studies of its kind, researchers found evidence of substantial reductions in patient survival associated with extreme concentrations of serum uric acid (SUA) for both men and women. The study, which was seed-funded by the Health Research Board (HRB), was recently published in the European Journal of Internal Medicine.
“This is the first study to yield detailed survival statistics for SUA concentrations among Irish men and women in the health system,” according to lead author, Dr Leonard Browne, senior research fellow in biostatistics at the UL School of Medicine. “Our key question was to determine whether SUA, a routinely measured blood marker, could help us predict a patient’s lifespan, all else being equal,” Dr Browne added.
To answer this, the research team used data from the National Kidney Disease Surveillance System (NKDSS), based at UL, and created a large cohort of 26,525 patients who entered the health system at University Hospital Limerick between January 1, 2006 and December 31, 2012, following them until December 31, 2013.
Dr Browne said the results were “quite astonishing”. “For men, the message was quite clear. The median survival was reduced by an average of 9.5 years for men with low levels of SUA (< 238µmol/L), and 11.7 years for men with elevated SUA levels (> 535µmol/L) compared to patients with levels of 357-416µmol/L,” he explained.
“Similarly, for women, we found that the median survival was reduced by almost six years for those with SUA levels > 416µmol/L, compared to women with SUA in the normal range.”
The shape of the mortality curves was quite different for men and women, according to Dr Browne. “For men the shape of the association was predominantly U-shaped with optimal survival between 304-454µmol/L, whereas, for women, the pattern of association was J-shaped with elevated risk of mortality only present for women with SUA levels beyond 409µmol/L,” he explained.
Prof Austin Stack, senior author of the study and principal investigator for the NKDSS, said there was good evidence that high levels of SUA are associated with serious chronic medical conditions such as kidney failure, hypertension, heart disease, stroke and diabetes.
“When we looked at the cause of death we found on one hand that men and women with very high SUA levels died from cardiovascular causes of death. On the other hand, and quite surprisingly, we also found that very low levels of SUA were also associated with a higher risk of death primarily in men. This would of course suggest that very low levels of SUA are also detrimental to survival.
“A key consideration is whether we should treat hyperuricaemia and lower SUA levels to a desired target level in order to extend patient survival,” said Prof Stack.
Prospective clinical trials are currently underway using uric acid lowering drugs in order to provide a definitive answer to this question.
Minimally invasive surgical ablation called a convergent procedure can return up to 90% of patients to normal sinus rhythm
A new procedure has been launched at the Beacon Hospital to treat atrial fibrillation.
With atrial fibrillation, the filling and contracting mechanism of the heart is affected so that patients may develop heart failure with symptoms including shortness of breath, palpitation, dizziness, chest pain and tiredness. In some cases, a clot may develop inside the heart chambers, usually in the left atrial appendage, that may dislodge to cause serious complications, most notably stroke.
Patients with this condition may be prescribed medications to help with the heart rate and rhythm, while blood thinners may be administered to reduce the risk of stroke.
In some cases, an electrophysiologist may perform a procedure through the groin referred to as an ablation. This aims to eliminate the abnormal electrical activity inside the heart that cause atrial fibrillation with a success rate of 60% in challenging cases.
The Beacon Hospital’s Heart Rhythm Centre is offering a hybrid staged procedure involving both an electrophysiologist and a thoracic surgeon. The specialist team led by Dr Jonathan Lyne and Prof Karen Redmond offers a minimally invasive surgical ablation called a convergent procedure to return up to 90% of patients to normal sinus rhythm. Simultaneously a clip is applied to occlude the left atrial appendage, the area where a clot may form, to reduce the risk of stroke.
Prof Redmond, consultant thoracic and transplant surgeon, said: “We are delighted to be able to provide this pioneering convergent procedure at the Beacon Hospital. This involves an ablation through a small skin incision treating the back wall of the heart. A clip is also applied to occlude the left atrial appendage at the same time, so that a blood clot cannot form.
“This helps reduce the need for blood thinners or anticoagulants that can be harmful in the long term due to bleeding episodes.”
Dr Lyne, consultant cardiologist and electrophysiologist leading the Beacon Heart Rhythm Centre said: “Traditional ablation techniques may not be enough to return the patient to normal sinus rhythm. Atrial fibrillation can increase the risk of stroke, particularly as patients age and need to be managed.”