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Non-urgent pediatric surgeries postponed at Winnipeg children’s hospital amid unprecedented flu season

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Non-urgent pediatric surgeries are being postponed in Winnipeg as the children’s emergency department struggles to keep up with an unprecedented number of critically ill children and infants being admitted with respiratory illnesses, the COO of the Health Sciences Centre said on Wednesday.

Over a 48-hour period on Sunday and Monday, 10 infants and children were admitted to the pediatric ICU (PICU), bringing the overall number of critically ill pediatric patients at HSC to 21, Dr. Shawn Young said at a Wednesday morning virtual news conference.

The pre-pandemic pediatric ICU capacity was nine, he said.

As a result, some non-urgent pediatric surgeries will be postponed as of tomorrow, so that staff can be deployed to support the pediatric ICU.

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“Postponement [will] focus on patients who can safely remain at home until their surgery, and where this will not result in negative medical outcomes,” Young said.

These surgical patients likely would have required a post-procedure stay in the PICU, where resources are limited, he said.

Postponing surgeries will allow the equivalent of 4.7 full-time nurses to be redeployed to the PICU to support veteran care teams, he said.

Young children are more often more vulnerable to severe outcomes from respiratory viruses.

“Having them avoid travel and admission to hospital for non-urgent surgery at our height of respiratory [virus] season will help lessen the risks that they face,” Young said.

Surgeries that should not be delayed due to concern about medical consequences to the patient will not be delayed, and at this time, Young said these changes will not impact adult surgeries.

Majority of critically ill patients under 2 months old: doctor

The children’s hospital is seeing a higher number of daily admissions — the emergency department saw 128 pediatric patients yesterday, and 18 were admitted.

Dr. Elisabete Doyle, the head of pediatric medicine, said the severity of illness is much higher, with over 50 per cent of cases being triaged as moderate to high acuity.

The primary illnesses that are driving the surge are respiratory syncytial virus (RSV) and influenza.

“In November of this year, we saw 196 cases of influenza in [the emergency department], this is about four times the number that we were seeing in pre-pandemic times,” Doyle said.

So far in December, the emergency department has seen 87 influenza cases.

“Currently at this pace, we are set to see 245 cases [this month], which would be higher than any flu season in the past five years,” she said.

All but a handful of patients are infants and toddlers. Most are under two months old.

In the last 48 hours, Young has put out a call for nurses across the province with pediatric critical care experience who may be able to help with the surge in critically ill children.

The number of patients in the neonatal ICU (NICU) is currently 48, nearing the baseline capacity of 50.

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GLP-1 Agonists Protected Kidneys in T2D With Advanced DKD – Medscape

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Researchers published the study covered in this summary on Research Square as a preprint that has not yet been peer reviewed.

Key Takeaways

  • In patients with advanced diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2), treatment with a glucagon-like peptide-1 (GLP-1) agonist had a neutral effect on cardiovascular outcomes but significantly linked with preservation of kidney function and improved survival in a propensity-score matched, retrospective analysis of observational data from more than 2000 people with type 2 diabetes in Taiwan.

Why This Matters

  • Cardiovascular disease is a leading cause of mortality in people with type 2 diabetes and among those with chronic kidney disease.

  • GLP-1 agonists reduce all-cause mortality and cardiovascular death in people with type 2 diabetes, but their role in patients with advanced DKD is controversial.

  • Research on the effect of GLP-1 agonists on cardiovascular outcomes in patients with advanced DKD is limited. Trials that have assessed GLP-1 agonists in people with type 2 diabetes have generally excluded those with advanced DKD and completely excluded those with end-stage kidney disease (eGFR < 30 mL/min/1.73m2).

  • Treatment with GLP-1 agonists has been associated with a significant reduction in composite cardiovascular outcomes in people with type 2 diabetes and relatively fair kidney function (eGFR > 30 mL/min/1.73m2), but among people with type 2 diabetes and lower levels of kidney function, research has shown neutral composite cardiovascular outcomes levels. However, limitations of previous studies include being mainly based on subgroup analysis or including a limited sample of patients.

Study Design

  • Retrospective analysis of observational data from nearly 9000 people in Taiwan with type 2 diabetes and an eGFR < 30 mL/min/1.73m2 who received a first prescription for a GLP-1 agonist or dipeptidyl peptidase 4 (DPP-4) inhibitor in 2012-2021 and had the data necessary for this analysis in their records.

  • The data came from the largest multi-institutional electronic medical record database in Taiwan, which includes two medical centers and five general hospitals and information on more than 11 million patients, from 2001 to 2019.

  • Researchers used propensity scoring to match 602 people treated with a GLP-1 agonist with 1479 people treated with a DPP-4 inhibitor.

Key Results

  • During a mean follow-up of 2.1 years, the rate of the composite cardiovascular outcome (cardiovascular death, myocardial infarction, and ischemic stroke) did not significantly differ between the GLP-1 agonist and DPP-4 inhibitor groups, with incidence rates of 13.0% and 13.8%, respectively, and a nonsignificant hazard ratio of 0.88. Rates of each of the three components of the composite endpoint also did not significantly differ between the two groups.

  • Progression to end-stage kidney disease with dialysis was significantly lower in those treated with a GLP-1 agonist compared with a DPP-4 inhibitor, with incidence rates of 23.4% and 27.5%, respectively, and a significant hazard ratio of 0.72.

  • The incidence of a greater than 50% drop in eGFR from baseline was 32.2% with GLP-1 agonist treatment compared to 35.9% with a DPP-4 inhibitor, with a significant hazard ratio of 0.74.

  • Median time until patients needed new-onset dialysis was 1.9 years with GLP-1 agonist treatment and 1.3 years with DPP-4 inhibitor treatment, which was a significant difference.

  • The rate of all-cause death was 18.4% with GLP-1 agonist treatment compared with 25.1% with DPP-4 inhibitor treatment, a hazard ratio of 0.71 that was significant.  

Limitations

  • Because the study was a retrospective analysis of observational data it cannot prove causality.

  • The study could be subject to residual confounding despite propensity-score matching.

  • The data came from health records that could have included coding errors.

  • Treatment compliance was unknown.

Disclosures

This is a summary of a preprint research study, “The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease,” by researchers in Taiwan on Research Square and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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Research by UBC professor lays groundwork for life-saving breast cancer treatment – UBC Faculty of Medicine

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A drug originally designed to prevent osteoporosis is now expected to save and improve the lives of millions of people with breast cancer, thanks in part to decades of foundational research by Dr. Josef Penninger, a professor in UBC’s Faculty of Medicine and director of the Life Sciences Institute.

The achievement highlights how UBC scientists are developing effective new treatments — and unlocking the full potential of existing drugs – through research into the fundamental biological principles behind disease. By advancing scientific discoveries from the lab to the clinic, UBC researchers are bringing life-changing treatments to patients everywhere.

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The drug, called Denosumab, was recently shown in a long-term Phase 3 clinical trial to improve survival among postmenopausal women with hormone receptor-positive early breast cancer receiving aromatase inhibitor treatment. Moreover, the drug markedly improved patients’ quality of life by reducing broken bones by 50 per cent, a common side effect of breast cancer treatment. The results of the trial were recently reported in The New England Journal of Medicine.

Denosumab is a monoclonal antibody developed by American biopharmaceutical company Amgen to prevent bone loss. In the early 2000s, research by Dr. Penninger and his team revealed the therapeutic potential of Denosumab, as well as the drug’s surprising connections with breast cancer.

“More than two decades ago we started the experimental groundwork that revealed Donosumab’s potential as a treatment for breast cancer patients,” says Dr. Penninger. “These results are incredibly exciting and will help improve the lives of millions of patients. I am very proud of all the people in my lab over the years who did that work and helped pave the way for this achievement.”

Discovering the link between osteoporosis and breast cancer

Denosumab works by binding to and inhibiting the activity of a protein called RANKL, which plays a key role in bone-resorbing cells called osteoclasts. By blocking RANKL, denosumab reduces the activity of osteoclasts and slows down bone resorption, helping to increase bone density and preventing osteoporosis.

Dr. Josef Penninger

Dr. Josef Penninger

Dr. Penninger and his team began to draw the connection between osteoporosis and HR-positive breast cancer when they generated the first RANKL “knock-out” mice in the late 1990s.

A knockout mouse is a laboratory mouse that has been genetically engineered to have certain genes deactivated, or “knocked-out”. Dr. Penninger’s team engineered mice that lacked the genes necessary to produce the RANKL protein in an effort to study the protein’s essential function in bone metabolism.

However, to the researchers’ surprise, they discovered that the RANKL-deficient mice failed to develop a lactating mammary gland in pregnancy – a process that depends on sex hormones.

“This proved an evolutionary link: showing how bone loss is regulated by sex hormones, and how pregnant mammals activate RANKL to form breast tissue for lactation among other functions,” says Dr. Penninger.

Based on this initial finding, Dr. Penninger’s team went on to show that RANKL played a key role in progestin-driven breast cancer, as well as breast cancer driven by BRCA1 mutations.

“Further researcher revealed how RANKL controls the stem cells in the breast that respond to sex hormones and thereby drives growth of the breast tissue at every menstruation cycle and in particular in pregnancy and lactation,” adds Dr. Penninger.

In the case of breast cancer, RANKL spurs mammary epithelial cells to divide, and helps to maintain the stem cells that give rise to breast tumours.

A dual benefit drug

One in eight Canadian women will be diagnosed with breast cancer in their lifetime according to the Canadian Breast Cancer Network. An estimated 70 to 80 per cent of these breast cancers are hormone receptor-positive (HR-positive), making it the most prevalent breast cancer subtype.

The current standard treatment for HR-positive breast cancer involves surgery and radiation, followed by treatment with aromatase inhibitors for 5 to 7 years. While aromatase inhibitors diminish sex hormones that drive new cancer growth, they can have serious adverse effects on bone health, including increased risk of osteoporosis and fractures.

The now-published clinical trial, led by the Austrian Breast and Colorectal Cancer Study Group, was conducted to see if Denosumab could help in two ways: by reducing these negative effects on bone health, while also improving breast cancer survival outcomes.

“These results are incredibly exciting and will help improve the lives of millions of patients.”
Dr. Josef Penninger

The results reveal that 6 mg of Denosumab every six months — the recommended treatment level for osteoporosis — improved disease-free survival, bone metastasis-free survival, and overall survival among participants. It also effectively reduced bone fractures over the long term.

“Blocking RANKL in breast cancer patients reduces broken bones by 50 per cent, massively improving their quality of life, and even at a very low treatment dose,” says Dr. Penninger. “We now know that RANKL drives breast cancer cell growth, is the critical mechanism behind bone loss, and has also an effect on anti-cancer immunity and immunological rewiring in pregnancy. These clinical results in patients show how blocking RANKL could save the lives of 50,000 women among one million women with the diagnosis of breast cancer.”

Based on the data, the researchers behind the trials are recommending that Denosumab be considered for routine clinical use in postmenopausal breast cancer patients receiving aromatase inhibitor therapy.

These trials were largely based on the foundational research published by the Penninger laboratory, including Kong et al. Nature 1999, Fata et al. Cell 2000, Jones Nature 2006, Schramek et al. Nature 2010, Sigl et al. Cell Research 2016, and Paolino et al. Nature 2021.

Dr. Penninger is now part of a large international prevention trial evaluating Denosumab in young women who carry BRCA1 mutations.

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Respiratory illness peaked in December at Chatham Kent Health Alliance: Suni – Chatham-Kent This Week

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Chatham-Kent Health Alliance officials are reporting a drop in patients visiting the emergency departments with respiratory illnesses between December and January, but admissions from the emergency rooms to the hospitals remain high.

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Caen Suni, the hospital group’s vice president of clinical programs and operations, said patients with illnesses like influenza, COVID-19 and respiratory syncytial virus dropped 50 per cent in January compared to December among children and by one-third among adults.

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“The community is I think essentially working its way through seasonal illness at this point,” he said during a media teleconference Monday.

December also showed a 25 per cent increase over December 2021 for pediatric admissions and of those, 77 per cent were for respiratory illnesses, Suni said.

“That’s impactful and I think that’s what we’ve seen across the health sector in our entire region at this point,” he said.

Suni said the number of people seeking treatment at the emergency departments – which includes patients not admitted – is not “historically high,” but admissions to the hospitals increased in December by three per cent over the previous month.

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This translates to an extra two to three extra patients a day who require a bed. The health alliance also experienced almost 2.5 per cent more admissions in December than any month in the previous year.

However, December also had the lowest daily average of visits to the emergency departments of any month during the Health Alliance’s current fiscal year.

This means a higher proportion of patients require admission to the hospital and patients presenting at the emergency departments are more ill, Suni said.

Since December, the trends are now “pointing towards a decrease,” Suni said, “which we’re thankful for, as the community bounces back from seasonal illness.”

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