NOVAPAK Nasal Packing: Safety Study in Shellfish Allergic Patients
NOVAPAK is a sponge-like material made from materials found in shellfish. It is commonly used after nasal surgery or in nasal bleeding, as it promotes healing, decreases bleeding, and has antibacterial properties. Although NOVOPAK does not contain proteins or compounds known to be responsible for allergic reactions in people with a known allergy to shellfish, out of an abundance of caution, the manufacturer (Medtronic) has recommended avoidance in those with known shellfish allergy. There have been no reported allergic reactions in patients with shellfish allergy who were given chitosan bandages in emergencies (e.g. military applications). The study aims to investigate the safety of its use in patients with known shellfish allergy to improve healthcare quality and patient care support.
Stellate Ganglion Block With Lidocaine for the Treatment of COVID-19-Induced Parosmia: Double-Blinded, Placebo-Controlled Randomized Clinical Trial
Chronic olfactory dysfunction, both hyposmia and parosmia, from the COVID-19 pandemic is a growing public health crisis, affecting up to 1.2 million people in the United States. Olfactory dysfunction significantly impacts one's quality of life by decreasing the enjoyment of foods, creating environmental safety concerns, and affecting one's ability to perform specific jobs. Olfactory loss is also an independent predictor of anxiety, depression, and mortality. Recent research suggests that parosmia, more so than hyposmia, can increase anxiety, depression, and even suicidal ideation. While the pandemic has advanced the scientific community's interest in combating the burgeoning health crisis, few effective treatments currently exist for olfactory dysfunction. Persistent symptoms after an acute COVID-19 infection, or "Long COVID" symptoms, have been hypothesized to result from sympathetic nervous system dysfunction. Stellate ganglion blocks have been proposed to treat this hyper-sympathetic activation by blocking the sympathetic neuronal firing and resetting the balance of the autonomic nervous system. Studies before the COVID-19 pandemic have supported a beneficial effect of stellate ganglion blocks on olfactory dysfunction, and recent news reports and a published case series have described a dramatic benefit in both olfactory function and other long COVID symptoms in patients receiving stellate ganglion blocks. A previous pilot study using stellate ganglion blocks of 20 participants with persistent COVID-19 olfactory dysfunction resulted in modest improvements in subjective olfactory function, smell identification, and olfactory-specific quality of life, but it lacked a control group. Therefore, we propose a double-blinded, placebo-controlled, randomized clinical trial assessing the efficacy of a stellate ganglion block with Lidocaine versus saline injection in up to 50 participants with persistent COVID-19-associated olfactory dysfunction.
Intranasal Ketamine for Procedural Sedation: a Feasibility Cohort Study
The trial (Intranasal ketamine for procedural sedation in children: a randomized controlled non-inferiority multicenter trial or INK; ReDA 5496; CTO 1545) is being scheduled for launch in Spring 2019. Due to the possibility of failure of the experimental intervention (intranasal ketamine 10 mg/kg), the data safety monitoring board (DSMB) and statistical methods team would like to explore the possibility of developing a stopping rule to prevent patients from being enrolled in a futile trial and conserve resources. In order to get accurate data to develop a statistically robust stopping rule, it is necessary to conduct a cohort study of patients that receive the INK trial's experimental intervention and according to it's protocol. This cohort study will help estimate the chance of adequate sedation and inform the final dosing protocol for the INK trial.
Recent studies suggest histamine and d-lactate may negatively impact host health. As excess histamine is deleterious to the host, the identification of bacterial producers has contributed to concerns over the consumption of probiotics or live microorganisms in fermented food items. Some probiotic products have been suspected of inducing d-lactic-acidosis; an illness associated with neurocognitive symptoms such as ataxia. The goals of the present study were to test the in vitro production of histamine and d-lactate by a 24-strain daily synbiotic and to outline methods that others can use to test for their production. Using enzymatic based assays, no significant production of histamine was observed compared to controls (P > 0.05), while d-lactate production was comparable to a commercially available probiotic with no associated health risk. These assays provide a means to add to the safety profile of synbiotic and probiotic products.
Cohort-specific serological recognition of 2 SARS-CoV-2 variant RBD antigens
作者: Fraser, Douglas D. ; Miller, Michael R. ; Martin, Claudio M. ; Slessarev, Marat ; Hahn, Paul ; Higgins, Ian ; Melo, Christopher ; Pest, Michael A. ; Rothery, Nate ; Wang, Xiaoqin ; Zeidler, Johannes ; Cruz-Aguado, Jorge A.
Background: Estimating the response of different cohorts (e.g. vaccinated or critically ill) to new SARS-CoV-2 variants is important to customize measures of control. Thus, our goal was to evaluate binding of antibodies from sera of infected and vaccinated people to different antigens expressed by SARS-CoV-2 variants. Methods: We compared sera from vaccinated donors with sera from four patient/donor cohorts: critically ill patients admitted to an intensive care unit (split in sera collected between 2 and 7 days after admission and more than ten days later), a NIBSC/WHO reference panel of SARS-CoV-2 pos. individuals, and ambulatory or hospitalized (but not critically ill) pos. donors. Samples were tested with an anti-SARS-CoV-2 IgG serol. assay designed with microplates coated with a SARS-CoV-2 RBD recombinant antigen. The same sample sets were also tested with microplates coated with antigens harbouring RBD mutations present in eleven of the most widespread variants. Results: Sera from vaccinated individuals exhibited higher antibody binding (P<0.001) than sera from infected (but not critically ill) individuals when tested against the WT and each of 11 variants' RBD. The optical d. generated by sera from non-critically ill convalescence individuals upon binding to variant's antigens was different (P<0.05) from that of the WT in some variants-noteworthy, Beta, Gamma, Delta, and Delta Plus variants. Conclusions: Understanding differences in binding and neutralizing antibody titers against WT vs variant RBD antigens from different donor cohorts can help design variant-specific immunoassays and complement other diagnostic and clin. data to evaluate the epidemiol. of new variants.
Using a Human Circulation Mathematical Model to Simulate the Effects of Hemodialysis and Therapeutic Hypothermia
作者: Joseph, Jermiah J. ; Hunter, Timothy J. ; Sun, Clara ; Goldman, Daniel ; Kharche, Sanjay R. ; McIntyre, Christopher W.
Featured Application: Human circulation and dialysis 0D model.Abstract: Background: We developed a hemodynamic math. model of human circulation coupled to a virtual hemodialyzer. The model was used to explore mechanisms underlying our clin. observations involving hemodialysis. Methods: The model consists of whole body human circulation, baroreflex feedback control, and a hemodialyzer. Four model populations encompassing baseline, dialysed, therapeutic hypothermia treated, and simultaneous dialysed with hypothermia were generated. In all populations atrial fibrillation and renal failure as co-morbidities, and exercise as a treatment were simulated. Clin. relevant measurables were used to quantify the effects of each in silico experiment Sensitivity anal. was used to uncover the most relevant parameters. Results: Relative to baseline, the modelled dialysis increased the population mean diastolic blood pressure by 5%, large vessel wall shear stress by 6%, and heart rate by 20%. Therapeutic hypothermia increased systolic blood pressure by 3%, reduced large vessel shear stress by 15%, and did not affect heart rate. Therapeutic hypothermia reduced wall shear stress by 15% in the aorta and 6% in the kidneys, suggesting a potential anti-inflammatory benefit. Therapeutic hypothermia reduced cardiac output under atrial fibrillation by 12% and under renal failure by 20%. Therapeutic hypothermia and exercise did not affect dialyser function, but increased water removal by approx. 40%. Conclusions: This study illuminates some mechanisms of the action of therapeutic hypothermia. It also suggests clin. measurables that may be used as surrogates to diagnose underlying diseases such as atrial fibrillation.
Homelessness is a complex and challenging phenomenon, not just in the U.S. but across its neighbor to the north: It has been estimated that anywhere from 100,000 to 300,000 individuals experience homelessness in a given year in Canada, with more than 35,000 individuals experiencing homelessness on any given night in the country.
The increasing economic pressures faced by people across all levels of society – combined with other recent public health disruptions, such as the pandemic – have placed a spotlight on the growing crisis. The causes and solutions to homelessness are multifaceted and often politically charged.
"Prior to the pandemic, I had been working with various colleagues at the Western University Arthur Labatt Family School of Nursing, Lawson Health Research Institute, and ICES – formerly known as the Institute for Clinical Evaluative Sciences – on topics related to the effectiveness of housing interventions and other approaches to assist
people experiencing homelessness
," or PEH, said Richard Booth, RN, an associate professor at Western University Arthur Labatt Family School of Nursing in London, Ontario.
"One evaluation direction we had begun to explore was the use of secondary healthcare administrative data to better understand homelessness," he explained. "In some of our previous studies, using healthcare administrative data was a secondary objective to the primary intervention being studied; for example, housing interventions or shelter deferral interventions."
That all changed in late 2019 when the Public Health Agency of Canada (PHAC) released a sizable expression of interest funding contribution, to which the Labatt Family School of Nursing decided to apply and propose a two-armed study to explore homelessness in Canada using both qualitative and quantitative methods.
"We were successfully funded, and the Homelessness Counts project came to life in late 2020," Booth recalled. "My co-primary investigator, Dr. Cheryl Forchuk, led the qualitative arm of the study and has, to date, traveled across Canada to every province and territory multiple times over the last three years, interviewing PEH and other service providers to better understand contemporary homelessness.
"With more than 400 interviews, I'm fairly certain Dr. Forchuk has conducted what is the single largest collection of voices and experiences of homelessness in Canada during the height of the pandemic," he continued.
From a quantitative perspective, Booth led aspects of a larger analysis to refine and test a case ascertainment algorithm that could be used to identify cases of homelessness within healthcare administrative data.
"Working with ICES Staff Scientist Dr. Salimah Shariff and other colleagues at ICES, we began leveraging a previously developed and validated case-ascertainment algorithm that could be used within secondary healthcare administrative data to
locate cases of people who had experienced a recent episode of homelessness
," Booth said.
"Development of an algorithm like this had not been attempted within Canada's data science research domain, and we felt if we were able to generate an algorithm that had reliable sensitivity, we could use this approach to better understand aspects of the homelessness phenomenon," he continued.
Most Ontarian residents receive medically necessary services under the single-payer, provincially funded Ontario Health Insurance Plan (OHIP), which includes primary and specialty physician services, emergency department visits, hospital stays, laboratory and diagnostic testing, and other community healthcare services.
These data are prospectively collected and available in centralized databases at ICES, which is an independent, nonprofit research institute. Its legal status under Ontario’s health information privacy law allows it to collect and analyze healthcare and demographic data without consent for health system evaluation and improvement.
ICES comprises a set of linked databases, connecting more than 100 different sources of health and health-related data on Ontarians (population more than 15 million), encompassing more than 30,000,000,000 records and several hundred thousand variables, spanning a 30-year period.
"From this point, with our PHAC study Homelessness Counts launching in fall 2020 during the height of the pandemic, we set out to generate multi-dimensional interpretations of homelessness in Canada," Booth said. "From a data science perspective, we quickly realized our case ascertainment algorithm could be used to generate immediate and important policy insights.
"We were able to calculate the testing, infection and complication rates of COVID-19 among
people with a recent history of homelessness
," he continued. "Shortly after, we were also able to use our case ascertainment algorithm to uncover the
vaccination coverage of PEH versus others in Ontario
. Both of these studies demonstrated the utility of this algorithm and how it could be used to assist in generating policy and practice insights, especially related to contemporary issues."
Homelessness is a complex phenomenon with many moving parts, and no simple solutions exist. The Homelessness Counts project is intended to be one small element in a larger movement required to address modern-day homelessness.
"Homelessness is evolving in its complexity and nuance due to pressures experienced during the pandemic and other socio-economic-environmental factors currently affecting society," Booth explained. "Therefore, while our project and use of data analytics to address questions regarding homelessness are far from a panacea for homelessness, we believe our methodological approaches can be leveraged by others to generate more timely and accurate interpretations of homelessness and the health and wellbeing of this vulnerable population.
"In many ways, unless something is quantified, it can be overlooked in policymaking," he continued. "Through our approaches, we can quickly and cost-effectively quantify homelessness along with other variables of interest; for example, healthcare utilization, individual health, comorbidities, living location, etc. This ability allows us to enumerate the situations faced by PEH, providing evidence to confirm the existence of these situations."
For instance, in ongoing and future work related to this project, staff have both identified and enumerated emerging trends of concern within PEH populations, including the significant burden of Alzheimer’s disease and related dementias, and the high rates of opioid-toxicity mortality compared to other subpopulations and the entire Ontarian population.
"We believe our approaches provide us with much better abilities to generate population-level, quantitative evidence and insights into the realities faced by PEH," Booth said. "While far from being a solution to homelessness, having more accurate numerical insights into the issues at hand can assist in generating more targeted and proactive solutions.
"We have generated
a methodological publication explaining
our case ascertainment approach, including its benefits, limitations and other considerations," he added.
MEETING THE CHALLENGE
Western University Arthur Labatt Family School of Nursing was fortunate to collaborate with ICES in Ontario to complete various aspects of the larger Homelessness Counts project, Booth noted.
"Since most Ontarians receive healthcare services under the single-payer, provincially funded Ontario Health Insurance Plan (OHIP), we can use administrative data, including homelessness definitions within this data, to create cohorts of people who have recently experienced homelessness," he explained.
"While other healthcare organizations, such as the United States Veterans Affairs, and insurance companies may have linked databases like this, we are exceptionally fortunate within Ontario to have an organization like ICES that can explore phenomena at the population level," he added. "More information about ICES can be found on
their brief YouTube video
describing their data and organization."
The three organizations working together have been able to enumerate various contemporary phenomena in PEH populations, including increased testing, infection and complications of COVID-19 infection across six waves of the pandemic.
Additionally, they have identified reduced coverage of COVID-19 vaccination in PEH, an increasing trend of opioid-toxicity mortality in PEH over the last several years, and rising trends of dementia in PEH populations.
They have other preliminary findings from various projects related to Homelessness Counts, but these are still being finalized.
"Two weeks after the publication of our paper in
outlining the testing, infection and complication rates of COVID-19 among people with a recent history of homelessness in early 2021, individuals experiencing homelessness were added to the prioritization list for early COVID-19 vaccination in Ontario," Booth reported.
"While a temporal association does not imply causation, we suspect our findings in this work may have been used to inform early vaccination distribution efforts and to help prioritize PEH populations," he said.
ADVICE FOR OTHERS
"If anything, having the ability to ask robust and important questions of data; and, having the insights to know what constitutes an appropriate question to ask of large data sets, is by far more important in this type of work than any specific software or technology," Booth advised. "Researchers and practitioners must confirm the underlying data is of good quality, as otherwise they can run the risk of producing results that follow the 'garbage in/garbage out' process – or worse, create or propagate harms."
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Western University has developed a ground-breaking method for predicting which intensive care unit (ICU) patients will survive a severe brain injury by combining functional magnetic resonance imaging (fMRI) with state-of-the art machine learning techniques.
Two graduate students from Western University have developed a ground-breaking method for predicting which intensive care unit (ICU) patients will survive a severe brain injury.
Matthew Kolisnyk and Karnig Kazazian combined functional magnetic resonance imaging (fMRI) with state-of-the art machine learning techniques to tackle one of the most complex issues in critical care.
Whether it is the result of a stroke, cardiac arrest or traumatic brain injury, lives can forever be changed by a serious brain injury. When patients are admitted to the ICU, families are faced with tremendous uncertainty. Will my loved one recover? Are they aware of what is going on? Will they ever be the same again? Despite these essential questions, health-care professionals are equally uncertain about the potential of a good recovery.
The graduate students are PhD candidates at Schulich School of Medicine & Dentistry in the lab of neuroscientist Adrian Owen.
"For years we've lacked the tools and techniques to know who is going to survive a serious brain injury," said Owen.
An interdisciplinary team of researchers from Western, in collaboration with neurologists at London Health Sciences Centre and Lawson Health Research Institute sought to find a solution to this problem. They were led by Loretta Norton, a psychology professor at King's University College at Western, who was one of the first researchers in the world to measure brain activity in the ICU.
The team measured brain activity in 25 patients at one of London's two ICUs in the first few days after a serious brain injury and tested whether it could predict who would survive and who would not.
"We previously found that information about the potential for recovery in these patients was captured in the way different brain regions communicate with each other," said Norton. "Intact communication between brain regions is an important factor for regaining consciousness."
The breakthrough occurred when the team realized they could combine this imaging technique with an application of AI known as machine learning. They found they could predict patients who would recover with an accuracy of 80 per cent, which is higher than the current standard of care.
"Modern artificial intelligence has shown incredible predictive capabilities. Combining this with our existing imaging techniques was enough to better predict who will recover from their injuries," said Kolisnyk.
While encouraging, the researchers say the prediction was not perfect and needs further research and testing.
"Given that these models learn best when they have lots of data, we hope our findings will lead to further collaborations with ICUs across Canada," said Kazazian.
Researchers have found that fecal microbiota transplants (FMT) from healthy donors are safe and show promise in improving response to immunotherapy in patients with advanced melanoma.
In a world-first clinical trial published in the journal Nature Medicine, a multi-centre study from Lawson Health Research Institute, the Centre hospitalier de l'Université de Montréal (CHUM) and the Jewish General Hospital (JGH) has found fecal microbiota transplants (FMT) from healthy donors are safe and show promise in improving response to immunotherapy in patients with advanced melanoma.
Immunotherapy drugs stimulate a person's immune system to attack and destroy cancer. While they can significantly improve survival outcomes in those with melanoma, they are only effective in 40 to 50 per cent of patients. Preliminary research has suggested that the human microbiome -- the diverse collection of microbes in our body -- may play a role in whether or not a patient responds.
"In this study, we aimed to improve melanoma patients' response to immunotherapy by improving the health of their microbiome through fecal transplants," says Dr. John Lenehan, Medical Oncologist at London Health Sciences Centre's (LHSC) London Regional Cancer Program (LRCP), Associate Scientist at Lawson and Associate Professor in the Department of Oncology at Western University's Schulich School of Medicine & Dentistry.
A fecal transplant involves collecting stool from a healthy donor, screening and preparing it in a lab, and transplanting it to the patient. The goal is to transplant the donor's microbiome so that healthy bacteria will prosper in the patient's gut.
"The connection between the microbiome, the immune system and cancer treatment is a growing field in science," explains Dr. Saman Maleki, Scientist at Lawson and LHSC's LRCP, Assistant Professor in Schulich Medicine's Departments of Oncology, Pathology and Laboratory Medicine, and Medical Biophysics, and senior investigator on the study. "This study aimed to harness microbes to improve outcomes for patients with melanoma."
The phase I trial included 20 melanoma patients recruited from LHSC, CHUM and Jewish General Hospital. Patients were administered approximately 40 fecal transplant capsules orally during a single session, one week before they started immunotherapy treatment.
The study found that combining fecal transplants with immunotherapy is safe for patients -- which is the primary objective of a phase I trial (also called 'safety trials'). The study also found 65 per cent of patients who retained the donors' microbiome had a clinical response to the combination treatment. Five patients experienced adverse events sometimes associated with immunotherapy and had their treatment discontinued.
"We have reached a plateau in treating melanoma with immunotherapy, but the microbiome has the potential to be a paradigm shift," says Dr. Bertrand Routy, Oncologist and Director of CHUM's Microbiome Center. "This study puts Canada at the forefront of microbiome research by showing we can safely improve patients' response to immunotherapy through fecal transplants."
"These exciting results add to a rapidly growing list of publications suggesting that targeting the microbiome may provide a major advance in the use of immunotherapy for our patients with cancer," adds Dr. Wilson H. Miller Jr. of the JGH and Professor in the Departments of Medicine and Oncology at McGill University.
The study is unique due to its administration of fecal transplants (from healthy donors) in capsule form to cancer patients -- a technique pioneered in London by Dr. Michael Silverman, Lawson Scientist, Chair of Infectious Diseases at Schulich Medicine and Medical Director of the Infectious Disease Care Program at St. Joseph's Health Care London.
"Our group has been doing fecal transplants for 20 years, initially finding success treating C. difficile infections. This has enabled us to refine our methods and provide an exceptionally high rate of the donor microbes surviving in the recipient's gut with just a single dose," says Dr. Silverman. "Our data suggests at least some of the success we are seeing in melanoma patients is related to the efficacy of the capsules."
The team has already started a larger phase II trial involving centres in Ontario and Quebec. Lawson researchers are also studying the potential of fecal transplants in the treatment of other cancers, including renal cell carcinoma, pancreatic cancer and lung cancer, as well as HIV and rheumatoid arthritis.
This research is supported in part through donor funding from London Health Sciences Foundation, Western University, the Lotte and John Hecht Memorial Foundation, the JGH Foundation, Canadian Cancer Society's Impact Grant program and The Terry Fox Foundation.