TORONTO — Children five and under in Ontario should be vaccinated against COVID-19 and influenza before the holiday season amid surging hospital admissions, infectious disease experts are warning.
In a joint statement earlier this week, experts from four of the province’s pediatric hospitals said vaccinations are a critical tool to help mitigate the effects of a viral season that could prove longer and more severe than years past.
“In the current context of increased circulation of respiratory viruses such as SARS-CoV-2, influenza and RSV, optimizing the uptake of both COVID-19 and influenza vaccines in children are of crucial importance, especially before the winter and holiday season,” said the statement from the Hospital for Sick Children, CHEO, the Children’s Hospital at London Health Sciences Centre and McMaster Children’s Hospital.
Data released by Public Health Ontario shows that as of Nov. 6, only seven per cent of Ontario children aged six months to five years had received a first dose of a COVID-19 vaccine and as few as two per cent were fully vaccinated.
The experts said that’s particularly concerning because children aged four and under have a higher risk for hospitalization from COVID-19 than any other group of kids and teens.
The province has not yet released data on uptake for the influenza shot this season.
Several Ontario pediatric hospitals have recently announced they would cut back on surgeries and deploy staff to help backstop overburdened intensive care units and emergency rooms.
Hospital admissions are surging under a triple-threat of respiratory syncytial virus, influenza and COVID-19, at a time when the health-care system was already grappling with record numbers of job vacancies.
This report by The Canadian Press was first published Nov. 30, 2022.
Toronto’s medical officer of health is warning the public that this year’s flu season is projected to peak just as people gather for the holidays in a few weeks’ time and she is urging everyone to get a flu shot as soon as possible.
“I am urging Torontonians – in the strongest possible terms – to receive their flu vaccine soon as possible,” Dr. Eileen de Villa said in a statement released Wednesday. “Vaccination is the strongest defence against getting the flu virus and appointments are available throughout the city of Toronto, including at any one of the six immunization clinics operated by Toronto Public Health.”
A positivity rate above five per cent, the city said, indicates that influenza is circulating in the community and that the influenza season is well underway.
“Historically, influenza activity in a region usually peaks within about five weeks of this positivity rate,” the city said. “This means Toronto will likely enter a peak influenza infection period as people gather for Hanukkah, Christmas, Kwanzaa and New Year celebrations.”
The health-care system has already been overwhelmed with a wave of respiratory illnesses over the past few weeks, mainly from influenza and RSV. Children’s hospitals have been particularly strained amid the rise in infections.
Ontario’s chief medical officer of health recently advised people to mask up in crowded indoor settings and for people to wear masks around young children if they have even mild symptoms of illness.
However the province has stopped short of re-introducing mask mandates.
The city is holding a telephone town hall about this year’s flu season with Associate Medical Officer of Health Dr. Vinita Dubey at 7 p.m. Wednesday. The event is being held so that people can ask questions about this year’s flu season and respiratory illnesses. People can join the town hall by calling 1-833-490-0778 or connecting online.
As Health Sciences Centre’s children’s emergency department continues to grapple with a surge in flu season traffic, health-care providers are urging parents and caregivers to choose the appropriate health-care option for sick kids.
Dr. Elisabete Doyle, section head of pediatric medicine at HSC Children’s Hospital, said this influenza season came earlier than expected, combining the effects of respiratory syncytial virus (RSV), influenza and COVID-19.
According to Doyle, 174 patients visited the children’s ER Monday. Sixteen were ultimately admitted, half of which had respiratory illness.
“Although we’re still seeing some COVID, we are seeing a lot of RSV and influenza, influenza A in particular,” Dr. Doyle said in a news conference Tuesday.
“Our care teams continue to see children who are testing positive for multiple viruses at one time.”
Doyle said so far this month, her team treated 181 cases of influenza A, which is more than four times higher than the same month in 2019.
She said most have an ‘uncomplicated course’, but some develop complications like bacterial pneumonia or otitis media. Doyle notes parents and caregivers should look for worsening symptoms on day four or five as a sign to see a physician.
Additionally, her department saw 140 cases of bronchiolitis this month, a lung infection commonly caused by RSV. That number was three times higher than in November 2019.
To help alleviate the strain on the children’s ER, Shared Health launched a new website to help parents and caregivers determine where to take their sick or injured child, be it to the ER, to their family physician, or another health-care option.
It also gives information on dosing of adult-strength Tylenol or ibuprofen for kids over 11 kilograms. Young infants who weigh less must visit pharmacists.
Doyle believes more education on the appropriate health-care option could help curb traffic in the children’s ER.
“Most of the patients don’t need specific emergency treatment, so they could be seen at a physician’s office,” she said.
“I would suspect based on what we’re seeing, at least a 25 per cent decrease in the number of visits if we could have patients directed to the appropriate place for care.”
CHILDREN’S ER STILL MANAGING AMID CRISIS
While Dr. Doyle described the surge in traffic as a crisis last week, she notes the health-care system is still weathering the storm.
“We’re at a position right now where we’re still able to manage things,” she said.
“I would still say it’s a crisis, in the sense that it’s really challenging our resources. But, has it overcome our resources? No.”
Despite the fast and furious flu season, vaccination numbers in Manitoba remain low, with only six per cent of kids under four and six per cent of kids over four currently vaccinated against influenza.
Still, Doyle urges parents and caregivers to get children vaccinated, even if they already had the flu, as she anticipates this influenza season will last longer and peak at higher numbers.
“What we’re seeing is unprecedented, so we don’t know the direction that it’s going to go.”
People in Guelph who have cold and flu symptoms will be able to be assessed and treated through an assessment centre set up for COVID-19.
The centre, located at 400 Southgate Dr., has been where people have gone to get tested for COVID-19 for two years. Starting Thursday, it will become the Guelph COVID Cold Flu Care Clinic.
The goal is to help people in the city get care while also working to "ease the pressure on the emergency department at Guelph General Hospital," a news release said. The clinic is run by the hospital and the Guelph Family Health Team.
People will be able to make appointments at the clinic seven days a week, although weekend hours will be shorter. They're also encouraged to contact their family doctor before booking an appointment at the Guelph COVID Cold Flu Care Clinic.
"People with mild respiratory symptoms are advised to monitor their symptoms, rest and drink plenty of fluids," the news release said.
It also noted "most people in the community with symptoms are not eligible for COVID-19 testing" because they must meet provincial guidelines, which prioritizes people at increased risk of severe outcomes and people who live and work in high-risk settings.
WATCH | Have a lingering cough? Urgent-care doctor explains when it's normal and when it's not:
Have a lingering cough? Urgent care doctor explanis when it's normal, and when it's not
6 days ago
Duration 4:59
Cold and flu season started early this year, and it's still going strong. Many adults are dealing with ongoing coughs and other symptoms. Calgary urgent care doctor Dr. Raj Bhardwaj spoke with CBC Calgary News at 6 host Rob Brown about why coughs can stick around and when you should seek medical attention.
Feel sick? 'Do not go and join the party'
Marianne Walker is president and chief executive officer of Guelph General Hospital and also the hospital lead for Waterloo Wellington's COVID-19 response.
She said that in Waterloo region, Guelph and Wellington County, hospitals are over capacity with both adult and child patients.
"I think our major issue right now is managing the issues with very sick children, and so we are working with Ontario Health to look at taking a provincial approach to that," Walker said.
To help manage capacity in the health-care system and ensure "not everyone is getting sick at the same time," Walker said people should listen to public health experts, who are recommending getting vaccinated for COVID-19 and getting the flu shot, wearing masks, avoiding large gatherings and staying home if you're not feeling well.
Walker said that advice is particularly important as December is a time when many people might get together with family and friends.
"The big thing too is making sure that if you're sick, do not go and join the party," she said.
LISTEN | Guelph General Hospital's Marianne Walker on what local hospitals are facing right now and how to avoid becoming sick:
The Morning Edition - K-W6:48Not feeling well? Skip the holiday parties until you're better, Guelph hospital's CEO says
Marianne Walker, president and CEO of Guelph General Hospital and the hospital lead for Waterloo-Wellington's COVID-19 response, talks about what local hospitals are facing right now and what people can do to avoid getting sick during a busy time of year.
“The other aspect of this study that really fascinated us was how patients are getting information about cancer genetic testing,” says Sameer Thakker, MD.
In this video, Sameer Thakker, MD, discusses noteworthy findings from the Urology Practice study, “Attitudes, Perceptions, and Use of Cancer-based Genetic Testing Among Healthy U.S. Adults and Those With Prostate and Breast/Ovarian Cancer,” for which he served as a study author. Thakker is a urology resident at New York University Langone Health, New York City.
November 28, 2022 - The Thunder Bay District Health Unit (TBDHU) and Southbridge Care Homes confirm that the COVID-19 outbreak previously declared at Southbridge Roseview has been updated to include Cheshire and Renaissance Units only, Primrose Unit has been resolved.
TBDHU has initiated a thorough assessment of the situation. Further measures will be taken as needed to manage this situation.
Prior to the outbreak, significant measures were already in place to reduce likelihood of transmission of the virus within the facility. For additional information about COVID-19 and the TBDHU area, please see the TBDHU Website.
-30-
For more information - Health Unit Media: news@tbdhu.com.
Children in school uniforms and toddlers with their parents lined up Monday for polio vaccinations in the Sigli town square on the northern tip of the Indonesian island of Sumatra, after four children were found infected with the highly contagious disease that was declared eliminated in the country less than a decade ago.
The virus was first detected in October in a 7-year-old boy suffering from partial paralysis in the province of Aceh near Sigli, and since then three other cases have been detected, prompting the mass immunization and information drive.
Official say that polio immunization rates in the conservative province are well behind the rest of the country, with efforts hampered by widespread disinformation the vaccine is incompatible with religious beliefs, among other things. The government has also been prioritizing COVID-19 vaccinations since they became available.
The campaign that started Monday aims to vaccinate some 1.2 million children in the province, said Maxi Rein Rondonuwu, the Health Ministry's director general for disease control and prevention.
"There is no cure for polio, the only treatment is prevention and the tool for prevention is vaccination," Rondonuwu said, adding that the child is still able to walk, albeit with a limp.
With some 275 million people, Indonesia is the world's fourth most populous, and the largest Muslim-majority nation.
Aceh is particularly Conservative, and is Indonesia's only province allowed to practice Shariah, which was a concession made by the national government in 2006 to end a war with separatists.
False rumours that the polio vaccine contains pork or alcohol, prohibited according to Muslim beliefs, have proliferated, especially in rural areas, complicating vaccination efforts, said the head of the Aceh Health Office, Hanif, who only goes by one name like many Indonesians.
"We cannot work alone, we need support from all parties, including religious leaders, to that people understand the importance of immunization," said Hanif.
Azhar, the father of the 7-year-old who contracted polio, said he had opted not to immunize his son after other villagers where he lived told him the vaccines may cause harmful chemicals or non-halal substances.
"My neighbours said that my son don't need to be immunized and I didn't want my son get sick because of harmful chemicals that are against Islam," the 45-year-old said.
For Dewi Safitri, a mother of three who was getting them vaccinated on Monday, it was simply a matter of not knowing it was necessary.
She said she was convinced after health workers spelled out the risks of paralysis or death if her children were to go unvaccinated.
"I didn't even know about immunization," she said.
The World Health Assembly adopted a resolution for the global eradication of polio in 1988 and since then, wild poliovirus cases have decreased by more than 99%, according to the World Health Organization.
It was eliminated in Indonesia in 2014, and is today only still endemic in two countries – Afghanistan and Pakistan.
Polio primarily affects children under the age of 5, according to the WHO. Unvaccinated people of any ages can contract the disease, however, and sporadic cases continue to crop up.
In September in New York, for example, the state stepped up its polio-fighting efforts after the disease was detected in the wastewater in the New York City area.
Officials began checking for signs of the virus there after the first case of polio in the United States was identified in July in Rockland County, which is north of the city. It was confirmed in a young adult who was unvaccinated.
The statewide polio vaccination rate is 79% but Rockland's rate was lower, and New York health officials urged all unvaccinated residents, including children by 2 months of age, to get vaccinated immediately.
Last week, new poliovirus cases were found in Afghanistan, Algeria, Chad, Democratic Republic of Congo, Ethiopia and Nigeria, according to the WHO's Global Polio Eradication Initiative.
Of the three other children in Indonesia from the same village as the initially confirmed case none had their basic vaccinations, Rondonuwu said.
"It has to be reported as an outbreak, because it had been declared eradicated in Indonesia, but it turns out that there is still wild polio virus," he said.
Rondonuwu said his ministry is keeping a close watch on the cases by doing door-to-door screening to ensure that there are no additional infections that have not been reported.
The polio virus is transmitted person-to-person, generally through the "fecal-oral" route, according to the WHO. In Indonesia, authorities have also pointed to unsanitary conditions as a probable cause of the new infections after finding out that some local residents still defecate directly into a river where children are often found playing.
Across Indonesia, polio vaccination coverage has been slipping since the outbreak of COVID-19. Despite the challenges of reaching people in the archipelago nation of five main islands and thousands of smaller ones, 73.4% of Indonesians are now fully vaccinated for COVID-19 and 87.5% have at least one shot.
For polio, 86.8% of babies were vaccinated in their first year in 2020 countrywide, which fell to 80.7% in 2021 as the country was forced to focus most of its health facilities and workers on addressing the pandemic.
By comparison, only 50.9% of the infants born in Aceh in 2021 received a polio vaccination. It was the second lowest on a national scale after West Papua, where only 43.4% of babies were vaccinated.
The countrywide decline was part of a broader drop in basic immunizations, such as for measles and rubella, according to UNICEF.
Dicky Budiman, an Indonesian epidemiologist from Australia's Griffith University, said the discovery of polio in Aceh must be responded to seriously because "the threat is real for Indonesia," noting that basic immunization coverage is still low, putting the country in a high-risk category.
"This is what the government really has to pursue, because it's dangerous if we don't," Budiman said.
"We must move immediately by strengthening basic immunization or there will be a potential additional health disaster for Indonesia."
A modelling study to explore optimal allocation of vaccine against monkeypox virus (MPXV) provides a road map for public health to maximize the impact of a limited supply of vaccines.
The article, led by Unity Health Toronto researchers and published in CMAJ (Canadian Medical Association Journal), confirms that prioritizing vaccines to larger networks with more initial infections and greater potential for spread is best.
“We hope that these insights can then be applied by policy makers across diverse and dynamic epidemic contexts across Canada and beyond, to maximize infections averted early in an epidemic with limited vaccine supply,” writes Dr. Sharmistha Mishra, MAP Centre for Urban Health Solutions, Unity Health Toronto.
As of November 4, 2022, there were 1,444 cases of MPXV in Canada. Early in the epidemic, a very limited supply of smallpox vaccines was available to vaccinate in populations experiencing disproportionate risks, including gay, bisexual and other men who have sex with men (GBMSM).
Researchers modelled two hypothetical cities as interconnected networks with a combined GBMSM community size of 100,000. The team then varied the characteristics of the two cities across a range of plausible settings, and simulated roll-out of 5,000 vaccine doses shortly after the first detected case of MPXV.
They found that the strongest factors for optimal vaccine allocation between the cities were the relative reproduction number (epidemic potential) in each city, share of initial cases, and city (or network) size. If a larger city had greater epidemic potential and most of the initial cases, it was best to allocate the majority of vaccines to that city. The team varied the reproduction number with a single parameter, but they highlight how many factors could influence local epidemic potential, including the density and characteristics of the sexual network, access to prevention and care, and the underlying social and structural contexts that shape sexual networks and shape access.
Jesse Knight
“Under our modelling assumptions, we found that vaccines could generally avert more infections when prioritized to a larger network, a network with more initial infections, and a network with greater epidemic potential. Our findings further highlight the importance of global vaccine equity in responding to outbreaks, and also in preventing them in the first place” writes Jesse Knight, lead author and PhD candidate at University of Toronto and MAP Centre for Urban Health Solutions, Unity Health Toronto.
The study emphasizes the interconnectedness of regions and that a population-level perspective is necessary.
“Strategic prioritization of a limited vaccine supply by network-level risk factors can maximize infections averted over short time horizons in the context of an emerging epidemic, such as the current global monkeypox outbreak,” conclude the authors.
A 65-year-old woman who was receiving a promising experimental treatment to slow the cognitive decline caused by her early Alzheimer’s disease recently died from a massive brain hemorrhage that some researchers link to the drug. The clinical trial death, described in an unpublished case report Science has obtained, is the second thought to be associated with the antibody called lecanemab. The newly disclosed fatality intensifies questions about its safety and how widely lecanemab should be prescribed if ultimately approved by regulators.
The woman, who received infusions of the antibody as part of the trial, suffered a stroke and a type of swelling and bleeding previously seen with such antibodies, which bind to and remove forms of amyloid-beta, a protein widely theorized to cause Alzheimer’s. After the stroke was diagnosed in an emergency room at Northwestern University Medical Center in Chicago, she was given a common intervention, the powerful blood-clot busting medication tissue plasminogen activator (tPA). Substantial bleeding immediately followed throughout her brain’s outer layer immediately followed, and the woman died a few days later, according to the case report.
Rudolph Castellani, a Northwestern neuropathologist who studies Alzheimer’s and conducted an autopsy at the request of the patient’s husband, called the case “very dramatic.” The report, co-authored by Castellani, concluded that the woman, like the other person whose death was linked to lecanemab, had amyloid deposits surrounding many of her brain’s blood vessels. This pre-existing condition, found in both Alzheimer’s patients and to a lesser degree in the general population, frequently goes undetected other than by autopsy. It likely contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels. The vessels apparently burst when exposed to tPA—known to cause brain bleeds even in some conventional stroke cases.
“It was a one-two punch,” Castellani says. “There’s zero doubt in my mind that this is a treatment-caused illness and death. If the patient hadn’t been on lecanemab she would be alive today.” (Castellani says his comments reflect personal views and were not reviewed or approved by Northwestern. The patient’s husband told Science he authorized Castellani to speak publicly about his wife’s case. Science agreed to withhold both names to protect the family’s privacy.)
Castellani, his co-authors, and other researchers say the newly disclosed death suggests that tPA and perhaps other, less potent blood thinners pose safety considerations for Alzheimer’s patients receiving the antiamyloid antibody drugs, including lecanemab. The 30-page consent form for trial participants, obtained by Science, carries this warning about blood thinners: “You may continue with these medications, but you and the investigator should discuss the risk of bleeding since medications which prevent clots and [lecanemab] are both associated with a slight risk of bleeding in the brain.” It does not address tPA directly.
The woman’s husband says the events surrounding her death were fully disclosed to Great Lakes Clinical Trials, the Chicago-based contract research organization that administered lecanemab to his wife as part of the antibody’s international, multicenter study. He attended a postmortem meeting with Great Lakes principal investigator and psychiatrist Jeffrey Ross, and a Northwestern physician who had participated in his wife’s stroke care. According to the husband, Ross said during the meeting that he had shared details of the case with Eisai Co., the Japanese company that originally developed lecanemab with the Swedish firm BioArctic and sponsored the trial with its U.S. biotech partner Biogen. Ross did not respond to requests for comment.
Eisai declined to comment on the woman’s case, including whether it knew about the death. “All the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause,” the company said in a statement to Science. It also declined to describe any other deaths in the woman’s trial, citing the need to protect the privacy of participants, although it said there was no greater frequency of deaths among lecanemab-treated people in an earlier, smaller trial that had a placebo group. Any safety information is reported to regulators and the trial’s principal investigators, Eisai’s statement noted.
This week, Eisai is scheduled to provide the first detailed account of the phase 3 trial, known as Clarity AD, which enrolled about 1800 people with signs of early Alzheimer’s disease. Outside scientists have been eager to scrutinize the data to assess whether the modest benefits announced in September in a brief press release—people on lecanemab had less amyloid in the brain and 27% less cognitive decline than participants who received a placebo over an 18-month period—hold up and outweigh any safety concerns.
If approved, lecanemab would be the second antiamyloid drug to reach the clinic. Aducanumab, a recently approved drug for Alzheimer’s disease also from Eisai and Biogen, is now on the market as Aduhelm. But many Alzheimer’s researchers question the evidence that aducanumab works and were surprised it received U.S. Food and Drug Administration (FDA) approval.
Now some urge caution about its potential successor. “[Regulators] should take this case report seriously into account, because we're talking about significant side effects,” says Andreas Charidimou, a neuroscientist at Boston University who examined the report on the woman’s death for Science. “When there's so many unknowns it’s better to be more conservative.”
“Her body was on fire”
When speaking to Science last week, the dead woman’s spouse was at times overcome by emotion as he described a shattering and chaotic scene after his wife entered the emergency department with stroke symptoms. He informed the doctors about the lecanemab trial and contacted Great Lakes, which provided a web link to information about the antibody. After the attending physician reviewed the website, the care team proposed infusing tPA, describing its risks as relatively small.
“As soon as they put it in her, it was like her body was on fire. She was screaming, and it took like eight people to hold her down,” the husband says. “It was horrific. Everybody's running in and [asking] ‘What the hell is going on?’” His wife was sedated and moved into intensive care, he adds. A priest came to deliver the “Anointing of the Sick” prayer.
Soon after, the husband says, his wife suffered a series of seizures and was placed on a ventilator. A few days later, the family approved disconnecting the device, and she died. Her doctors told him they had never before seen such massive bleeding under those circumstances, and that they wanted to write up the details of the case for a medical journal.
Lecanemab targets a soluble, “protofibril” version of amyloid-beta, and also binds—albeit more weakly—to the extracellular amyloid deposits known as plaques that are a hallmark of Alzheimer’s disease. Other antibodies, including Aduhelm, bind to those plaques more strongly. Many physicians and Alzheimer’s experts already advise against combining Aduhelm and blood thinners.
STAT recently reported that an 80-year-old man in lecanemab’s phase 3 trial died of a brain hemorrhage linked to possible interaction between the experimental antibody and the blood thinner apixaban, sold under the name Eliquis. Doctors commonly prescribe the drug for atrial fibrillation—an irregular heart beat that can lead to stroke or heart failure. According to STAT, Eisai conceded in adverse event reports for the trial that its drug could have played a part in the fatal brain hemorrhage. (Such reports, submitted to FDA by family members, doctors, or others, are not regarded as proof that a tested therapy caused the event.) But the company later called the death unrelated and STAT said the case remains under investigation.
This micrograph of a blood vessel from the surface of the frontal lobe of a human brain shows how amyloid-beta plaques (blue) have replaced vascular smooth muscle (red). Researchers say vessel membranes (green) can become inflamed and weakened—and subject to bleeding—after treatment with anti-amyloid antibodies.Wilber Romero Fernandes
The woman who died after receiving tPA for her stroke had remained physically active throughout the lecanemab trial. She had retired about a year ago from a professional job that required sophisticated communication and analytic skills, but she had maintained civic involvement.
During the 18-month core trial, the woman might have received either the antibody or the placebo. But there was no question that she was given the antibody during the month preceding her death as part of an open-label trial extension, in which participants who want to take the experimental medication can do so.
Several physicians and researchers not involved in the trial or the woman’s care reviewed the case report at Science’s request and concurred with its findings that lecanemab likely contributed to her death. They said the woman probably received the placebo during the first part of the trial, because the inflammation seen in her blood vessels typically occurs within the first weeks of treatment with antiamyloid antibodies. Her husband agrees, recalling that during the core trial, she did not develop the headaches that she experienced after each infusion of the drug during the trial extension.
In its statement, Eisai said, “It can be difficult to determine what contributed to the death in any given patient, in particular when they are elderly, have multiple medical problems and may have recently received a concomitant treatment or intervention for an acute condition.”
James Nicoll, a neuropathologist at the University of Southampton and a Biogen consultant, was among those asked to review the report. He says although no single case provides proof of a harmful side effect, this death exposed “a very legitimate concern.” Nicoll called the combined use of lecanemab and blood thinners “something you would want to keep a close eye on” should the antibody achieve approval and wide use.
What will FDA decide?
Eisai and Biogen made headlines in September when they announced that lecanemab had more clearly slowed cognitive decline in people with early Alzheimer’s than any previous amyloid-targeted therapy. The conclusion was based on a standardized clinical measure of dementia that draws on observations of memory, judgment, personal care, and other factors by patients, family members, caregivers, and health professionals. But clinicians disagreed about whether the modest slowing would translate into benefits perceptible by patients or their loved ones.
As in other trials of antiamyloid antibodies, many of the people who received lecanemab in the phase 3 trial experienced amyloid-related imaging abnormalities (ARIA)—a term that describes brain swelling and bleeding. ARIA occurred in more than 21% of those who were on the drug; 17% experienced brain bleeds, but none of the ARIA cases was life-threatening, according to the Eisai and Biogen press release.
Still, one reason to think lecanemab contributed to the woman’s death is that her autopsy revealed widespread cerebral amyloid angiopathy (CAA), a condition in which amyloid deposits gradually replace the smooth muscle of blood vessel walls. Castellani, Nicoll, and others who reviewed her case suspect CAA made her blood vessels vulnerable to weakening when lecanemab did what it is expected to do: strip amyloids from the brain. The tPA treatment then likely ruptured those weakened vessels, leading to serious ARIA—and apparently fatal brain bleeding, according to the Northwestern report authors and independent CAA or Alzheimer’s experts.
Nearly half of Alzheimer’s patients also have CAA—including, according to STAT, the man whose death was previously linked to combining lecanemab and blood thinners. Eisai screened potential trial participants with tests often used to detect moderate or serious CAA. For example, applicants had MRI brain scans and anyone whose scan showed more than four “microhemorrhages”—tiny bleeds—or other signs of possibly serious CAA were not allowed to enroll. But the condition can be hard to detect says Charidimou, who studies CAA. The two deaths show that even in the trial population, some patients with serious CAA slipped through.
Many Alzheimer’s patients with CAA also suffer from other ailments, such as atrial fibrillation, that are normally treated with blood thinners, says Matthew Schrag, a Vanderbilt University physician and neuroscientist who specializes in CAA and assessed the report on the woman’s death for Science. That means both risk factors are likely to be present in a significant fraction of the patients who might be prescribed lecanemab if it is approved and marketed widely. Training physicians to interpret tests for CAA will be key to ensure that vulnerable Alzheimer’s patients and their caregivers are properly informed and warned about the possible hazards of lecanemab, Charidimou says.
Assuming a close look at Clarity AD’s data validates the companies’ press release, lecanemab could still help early Alzheimer’s patients who don’t have moderate or severe CAA, says University of Kentucky neuroscientist Donna Wilcock, who also reviewed the report on the death. “Even if that [only] means 6 or 12 more months of knowing who their kids are … it’s meaningful to dementia patients and their families.”
But FDA should require meticulous screening for CAA and a warning against concurrent tPA use, Wilcock adds. “If lots of people [on lecanemab] who go into the hospital with garden-variety strokes end up dying, that sets the field back decades.” FDA has promised to make a decision on whether to approve lecanemab, and impose any conditions on its use, by 6 January 2023.
This story was supported by the Science Fund for Investigative Reporting.
In a recent study published in the Biomedicine & Pharmacotherapy journal, researchers explored the anti-allergic and anti-inflammatory properties of flavonoids.
Chronic inflammation is crucial to the initiation and progression of chronic disorders such as diabetes, cancer, hypertension, asthma, and allergies. Bioactive flavonoids are plentiful in numerous food groups, including vegetables, nuts, fruits, drinks, and cereals. Recent research on flavonoids has revealed their capacity to regulate or prevent inflammation. Due to their antioxidative, anti-inflammatory, and immune-modulatory capabilities, flavonoids are an indispensable ingredient in pharmaceutical, nutraceutical, and medical applications. However, extensive research is required to understand the anti-inflammatory mechanism of these compounds.
Flavonoids function as anti-inflammatory agents by blocking the transcription factors as well as regulatory enzymes responsible for inflammation and its propagation, among other mechanisms. Various kinases, including C-protein kinase, phosphoinositol kinase, tyrosine kinase, cyclin-dependent kinase-4, or phosphatidylinositol kinase, are involved in signal transduction via lipid or protein phosphorylation and play an essential role in cell activation during inflammation. Flavonoids may potentially affect protein kinases by suppressing the nuclear factor kappa-B (Nf-κB). Several studies have demonstrated that flavonoids can modulate IkB and Nf-κB, which directly correlate with cell activation. In addition, they regulate transcription factors like signal transducer and activator of transcription (STAT)-6 and GATA-3 of CD4+T helper 2 (Th2) cytokines.
Flavonoids as an anti-allergic agent
Approximately four different types of allergic immunological responses develop following allergen or medication exposure. Type 1, which is Th-cell-mediated, is the focus of the investigation. It consists of two phases, namely the inductive phase involving the formation of immunoglobulin (Ig)-E against allergen in the presence of Th2 predominance. The second phase is the triggering phase involving the robust secretion of chemical mediators from immune cells, including the mast cells, which then re-interact with the allergen. The flavonoid's interference with Th-cell activation appears to be the primary mechanism for suppressing allergic reactions. By taking this approach, flavonoids can play a pathological role in treating allergy-related conditions.
in vitro and in vivo studies of flavonoids
Luteolin, myricetin, kaempferol, and quercetin were found to be beneficial against allergy-specific cytokines in in vitro and in vivo experiments. All have been reported to inhibit the generation of interleukin (IL)-4 and IL-13 from mast cells and basophils.
Quercetin
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Quercetin is a potential component due to its antioxidant action in radical scavenging and anti-allergic characteristics manifested via immunological activation. It also functions as an antihistamine and anti-inflammatory agent by decreasing the production of histamine from both basophils and mast cells, respectively, and by preventing the secretion of pro-inflammatory cytokines. In vitro and in vivo studies exhibited quercetin's anti-allergic and anti-inflammatory properties. Both galangin and quercetin alleviated atopic dermatitis in macrophages activated with lipopolysaccharide (LPS) by targeting the NF-κB, extracellular signal-regulated kinases (ERKs)-1/2, and c-Jun N-terminal kinase (JNK) pathways. In addition, galangin and quercetin alone or together reduce serum IgE and ameliorate skin lesions in a balb-c mouse model of atopic dermatitis (AD).
Kaemferol
Kaemferol is a plant-based flavonol with anti-allergic, anti-inflammatory, and antioxidant activities demonstrated in animal and human studies. By interfering with NF-κB signaling, it significantly controls allergic airway inflammation among mice. Kaempferol decreased the CD69 expression and the generation of allergen-inducing inflammatory cytokines, such as IL-12. In addition, pulldown experiments demonstrated that kaempferol reduces the activity of multidrug resistance-associated protein 1 (MRP-1) by directly binding to it. Kaempferol inhibited the TAK1-IKK-mediated NF-κB pathway as well as JNK phosphorylation in activated T-cells. Similar to in vitro research, kaempferol improved the appearance of atopic dermatitis among mice.
Myricetin
Myricetin possesses antioxidant, anti-inflammatory, and anti-allergic characteristics. Toluene 2,4-diisocyanate–induced (TDI) allergic mice exhibited decreased sneezing, erythema, rhinorrhea, and edema following oral treatment of Sonneratia caseolaris crude extract. It has also been found that polyphenolic chemicals, in particular vanillic acid, myricetin, and ellagic, reduced allergic symptoms by directly binding to histamine receptors and suppressing the production of Th-cell cytokines that are involved in the allergic illness.
Luteolin
The anti-allergic activity of luteolin was investigated in Balb-c mice with asthma caused by ova-albumin. In a mouse model, Luteolin-treated animals exhibited reduced allergy symptoms, including decreased infiltration of inflammatory cells as well as Th2-mediated inflammatory cytokines. Rats with allergic rhinitis were studied to determine how luteolin helps alleviate allergic inflammation and Th1/Th2 balance by regulating the toll-like receptor 4 (TLR4)/NF-κB pathway. In ova-albumin-induced allergic mice, the Artemisia argyi component luteolin significantly decreased airway hypersensitivity, inflammatory cell count, Th2, and IgE cytokines.
Overall, the study findings showed that flavonoids possess anti-inflammatory, antioxidant, and anti-allergic characteristics. Recent studies of four key anti-inflammatory and anti-allergic flavonoids have confirmed their beneficial effects on allergic diseases by balancing Th1/ Th2 cells and impairing the stimulation of basophils and mast cells.
Preventable diseases like measles could follow trends seen elsewhere in the world and spread quickly in Canada due to a drop in routine vaccinations during the COVID-19 pandemic, say pediatricians who are urging parents to ensure their kids are fully immunized.
Provinces and territories log data on vaccinations provided in the community against infectious diseases like measles, diphtheria, polio and whooping cough, as well as vaccines against other illnesses administered in school immunization clinics.
Although much current data doesn't cover years beyond 2019, provinces with more recent figures are already seeing a dramatic decline in routine vaccinations.
Pediatricians are concerned about possible outbreaks of preventable diseases if too many children were underimmunized or not vaccinated at all while public health clinics focused on COVID-19 vaccines. Widespread school closures and vaccine disinformation that swayed some parents against immunization efforts complicated matters still further.
Recent data from Public Health Ontario shows that for 12-year-olds, vaccination against the liver infection hepatitis B plummeted to about 17 per cent in the 2020 to 2021 school year, compared with 67 per cent in the school year ending in 2019.
For human papillomavirus, or HPV, which can cause cancer, the vaccination numbers were even lower, plunging to 0.8 per cent last year, compared with 58 per cent in 2019. For the meningococcal vaccine, which helps protect against four types of the bacteria that cause a rare disease, vaccinations fell to about 17 per cent from 80 per cent over the same time. Risks of the potentially deadly illness include meningitis, an infection of the lining of the brain and spinal cord.
"The large decline in coverage in 2019-20 and 2020-21 illustrates the impact of the COVID-19 pandemic, as there was limited capacity to deliver school-based immunization programs," Public Health Ontario said in a statement.
It said data for uptake of vaccines aimed at protecting younger kids against measles, for example, is not available beyond 2019, and a report on later numbers is expected to be released next spring.
Dr. Monika Naus, medical director of Immunization Programs and Vaccine Preventable Diseases Service at the BC Centre for Disease Control, said in-school vaccines, starting in Grade 6, were delayed, but work is underway to return to pre-pandemic levels.
Younger children missed appointments at doctors' offices while physicians were seeing patients virtually and public health clinics, which mostly administer routine vaccines for kids outside of the Lower Mainland region of the province, were busy with COVID-19 shots, Naus said.
Dr. Sam Wong, director of medical affairs for the Canadian Paediatric Society, said disinformation and vaccine hesitancy during the pandemic, "combined with the failure of the public health system" to provide routine vaccines, mean certain populations could be left vulnerable to highly contagious diseases like measles, which spreads through coughing and sneezing.
"You could walk into a room an hour after someone's been in there and potentially get infected," he said.
"We're worried, as a group of health-care providers, that if you have lower rates of vaccinations that you're more likely to have localized outbreaks of vaccine-preventable illnesses such as measles or mumps and chickenpox," Wong said.
Wong said it's important for doctors and parents to discuss the importance of routine vaccinations that have been proven effective for decades, adding some people believe young kids' immune systems are not ready so they'd rather wait until they're older.
"But that's why you want to give the vaccine, because their immune system is not able to fight off infections," he said.
"Some parents don't want to even have discussions with me about it. But if there is an opening, I'm happy to talk about it," said Wong, who works in Yellowknife, Edmonton and Victoria.
The Public Health Agency of Canada said Canadian studies have found immunization coverage declined during the pandemic for the measles, mumps and rubella vaccine.
Quebec saw a 39 per cent drop in April 2020 compared with 2019, the agency said, with the greatest impact seen in children aged 18 months.
In Alberta, the agency said vaccination for those diseases declined by 10 per cent in April 2020 compared with the same month a year earlier. Coverage for Ontario children under two decreased by 1.7 per cent, it added.
"The Public Health Agency of Canada continues to work with provinces and territories on an ongoing basis to understand the impact of the pandemic on routine immunization coverage across Canada, and to improve the availability of high-quality data to inform immunization programs," it said in a statement.
It is currently in discussions with all jurisdictions on ways to monitor coverage of vaccines, similar to a surveillance system used for COVID-19 vaccines, the agency said.
Nova Scotia Health said its last report on childhood vaccines was completed three years ago, and numbers have fallen during the pandemic.
"Anecdotally, we know there was a drop in childhood vaccination, but we do not have the specific numbers available at this time," it said in a statement.
However, the school immunization program is aiming to help students catch up on vaccines that were missed early in the pandemic, mostly through doctors' offices, it said, adding that getting an appointment was a challenge for some families.
"We know that a substantial number of Nova Scotians do not have a family doctor. Public Health often works with local primary care clinics to provide vaccines to those who do not have a family doctor and some public health offices will offer clinics to this population."
Last week, the World Health Organization and the United States Centers for Disease Control and Prevention released a statement saying a record high of nearly 40 million children missed first and second doses of the measles vaccine in 2021 due to disruptions in immunization programs since the start of the pandemic.
The two groups said there were an estimated nine million measles cases and 128,000 related deaths worldwide in 2021, and 22 countries experienced large outbreaks.
Dr. Noni MacDonald, a professor of pediatrics and infectious diseases at Dalhousie University in Halifax, said a national registry that could quickly tell doctors which children have not been vaccinated is essential in Canada.
"I feel like I'm banging my head against a brick wall," she said of her efforts to call for that change.
"How can we do proper health-care planning when we don't have the data?"
Canada is an "outlier" that lags behind most European countries on the measles vaccine, she said, adding a coverage rate of 95 per cent is needed to create so-called herd immunity against the highly infectious disease.
Canada recently had 84 per cent uptake of the second dose of the measles vaccine. MacDonald said Australia, in comparison, had 94 per cent based on the most recent data from the WHO. She used the two countries as an example because they had a similar number of births — 368,000 in Canada, and 300,000 in Australia in 2021.
"We are just not in the same league, and we should be embarrassed."
This report by The Canadian Press was first published Nov. 27, 2022.
This story was produced with financial assistance from the Canadian Medical Association.
Many parents are at a loss when it comes to assisting their children with their eyesight, and just as many are overlooking the symptoms of potential vision disorders.
Mosman,Australia – November 27, 2022 —
How To You Tell If Your Child Has Eye or Vision Issues
Parents who are raising children are aware of what to anticipate in terms of toilet training, helping them to crawl, and eventually stand and walk. They encourage them to speak and caution them not to touch certain objects. They expose their children to a variety of tastes and smells, all of which are simple enough to name, discuss, explain, and comprehend. However, according to renowned Australian behavioural optometrist Gary Rodney, fellow of the International Academy of Orthokeratology and Myopia Control (FIAOMC), whose Smart Vision Optometry has a special interest in this area, many parents are at a loss when it comes to assisting their children with their eyesight or vision, and just as many are overlooking the symptoms of potential vision disorders.
Being a step or two behind while starting school
Because some children do not perceive the world or anything in it the same way that their classmates do, Rodney believes that many youngsters arrive to school a few steps behind their peers. Instead, everything has a blurry appearance or is not able to be visually processed properly. Also, it can make children feel uneasy in various situations. This can result in a variety of learning issues.
“When students first start school, they are exposed to a whole new environment, and they sometimes feel inferior to their new classmates when it comes to academic performance. They don’t understand why their reading skills may deteriorate and other learning abilities may lag. So many of them can start to display behavioural issues or refrain from participating in a procedure that looks too challenging. Many people don’t want to start doing sports, and some don’t want to read,” explains Rodney.
The issue of distance
Myopia (nearsightedness) and hyperopia (farsightedness) are two of the most well-known eye conditions, which coupled with other conditions afflict at least 22% of Australians under the age of 14. Both cause children’s vision to become hazy, whether they are trying to see anything at a distance, as is the situation with myopia or up close, as is the case with hyperopia. Both are refraction mistakes brought on by light rays that concentrate in front of or behind the retina rather than on it as they ought to.
However, Rodney has discovered that optical blur only makes up 11% of all other visual issues on school screenings. Both perceptual vision and functional vision abilities can create a lot more problems. Therefore, focusing just on refractive defects will not reveal the great majority of visual obstacles to reading and learning.
How to Recognise the Symptoms
Parents can be alert for certain warning signs that indicate their children may have issues with visual function or the processing of objects at various distances. Some can be seen clearly in their bodily acts.
These include the habit of moving very close to what they are attempting to view, such as while watching television, or bringing books very close to their eyes when attempting to read. Children with eye issues may also become lost in a book when reading, let their eyes follow the text while using a finger as a guide, or begin to avoid tasks that are too challenging for them. According to Rodney, this may apply to literature or even sports since the blur makes it too tough because the required attention is uncomfortable for them.
In order to have the stronger eye perform the work and prevent the weaker eye from becoming “lazy” and further deteriorating, they may also squint or tilt their heads to one side.
“Frequent headaches, light sensitivity, and complaints of “sore eyes” may result from difficulties focusing. Additionally, it may cause children to refuse to do the recommended tasks when they read a book or use a computer or need to have great motivation to attend While this is frequently seen as poor behaviour, it may actually be the very genuine outcome of an eye condition,” says Rodney.
What parents can do
With this information in hand, parents are encouraged to set an appointment with a Smart Vision optometrist like those at Eyes InDesign Mosman to book a Smart Vision Skills Assessment to evaluate their children and get them the help they need.
Smart Vision Optometry Eyes InDesign Mosman, provides professional expertise to best evaluate and treat eye-related queries and visual problems and supports patients to optimise their visual health.
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Organization: Eyes In Design Mosman
Address: 832 Military Rd, Mosman NSW 2088, Australia, Mosman, NSW 2088, Australia
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Website: https://www.smartvisionoptometry.com.au/
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Two years ago, Cobourg resident Stuart Morley became the first-ever patient at Peterborough Regional Health Centre (PRHC) to receive life-changing cancer treatment by interventional radiology-radiofrequency ablation for a tumour on his kidney. (Photo courtesy of PRHC Foundation)
Two years ago, a doctor looked at a CT scan of Stuart Morley’s kidney and saw a tumour. It was small — only 15 millimetres — but the Cobourg resident was over 80 years old, so major surgery wasn’t the best option for him. Instead, he was a candidate for a minimally invasive interventional radiology procedure.
Stuart became the first-ever patient at Peterborough Regional Health Centre (PRHC) to receive life-changing cancer treatment by interventional radiology-radiofrequency ablation.
The amateur photographer and retired radiographer tells how PRHC’s Dr. Kebby King put a metal probe through a small cut in his skin and, using a CT to guide her, found the tumour and dissolved it with radio waves.
Interventional radiologist Dr. Kebby King (right) and registered technologist Saara King prepare for a minimally invasive interventional radiology procedure at Peterborough Regional Health Centre (PRHC). Often described as ‘the future of medicine’, it’s used to diagnose and treat a wide range of emergency and chronic health conditions, such as cancer and other illnesses, without the use of conventional surgery. (Photo courtesy of PRHC Foundation)
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“It was amazing,” Stuart recalls. “I felt no pain and I was able to go home later that afternoon. Now I’m back taking photos and looking forward to travelling the world again. I worked in diagnostic imaging for 12 years. But back in the ’60s, we could never have imagined the kinds of things doctors can do these days.”
Interventional radiology is often described as ‘the future of medicine’. It’s used to diagnose and treat a wide range of emergency and chronic health conditions such as cancer and other illnesses, without the use of conventional surgery and the associated pain, complications, and longer hospital stays.
For patients in the Peterborough region, this means they can go home sooner, with less pain and less risk, all without having to travel far away.
VIDEO: Interventional Radiology is helping to revolutionize cancer care at PRHC
Interventional radiologist Dr. King describes that difference as “night and day.”
It’s remarkable how many life-threatening health conditions can be diagnosed and treated with this innovative specialty. It can be used to biopsy or treat tumours like Stuart’s, put in ports for chemotherapy, or stop bleeding — in as little as an hour.
Dr. King and her colleagues already perform 6,000 interventional radiology procedures each year at PRHC, and the need for this kind of care is only growing in our region. PRHC’s interventional radiology suites are 14 years old, however, and are too small to fit new advanced technology and the staff required to use it.
Interventional radiologist Dr. Kebby King (right) and registered technologist Saara King at Peterborough Regional Health Centre (PRHC). Dr. King and her colleagues perform 6,000 interventional radiology procedures a year for patients like Stuart Morley from across the region. To meet the growing need for this service, PRHC’s facilities must be upgraded with a $6 million investment. (Photo courtesy of PRHC Foundation)
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A $6 million investment in state-of-the-art equipment, upgraded suites, and an expanded recovery room is essential to meeting the need — so more patients with more complex conditions can be diagnosed and treated close to home.
Grateful for the great care he received and determined to help pave the way for new ground-breaking therapies to be offered at PRHC in the near future, Stuart donated to the PRHC Foundation for the first time. He wants to support the interventional radiology renovation and upgrade, and he knows that the government doesn’t fund hospital equipment.
“Our regional hospital needs our help,” Stuart says. “I’m asking everyone to join me in donating to support the interventional radiology facilities. Pictures can save lives. I know this because medical imaging saved mine. Now, our donations will help others. Thank you for helping to give people like me a brighter future.”
Grateful for the great care he received at Peterborough Regional Health Centre (PRHC) two years ago and determined to help pave the way for new ground-breaking therapies to be offered at PRHC in the near future, Cobourg resident Stuart Morley donated to the PRHC Foundation and is encouraging others to do the same. (Photo courtesy of PRHC Foundation)
Not only do donations fund state-of-the-art technology not funded by the government, fuel innovation, and bring new services to our region, they also help PRHC attract and retain the best and brightest healthcare professionals. Doctors, nurses and staff want to do their jobs to the best of their abilities, and advanced equipment and innovative treatments support them in doing that.
This holiday season, donors and grateful patients like Stuart can help ensure PRHC’s frontline workers have the tools they need to provide expert, compassionate care, and receive some good cheer. Tribute donations can include a message of thanks or best wishes to a hospital department or individual physician, nurse or staff member when made online at prhcfoundation.ca or by phone at 705-876-5000.
To donate, find out more about interventional radiology, or share your own PRHC grateful patient story, please visit prhcfoundation.ca or call 705-876-5000.
This branded editorial was published in partnership with the PRHC Foundation. If your organization or business is interested in a branded editorial, contact us.
