During the 2021-2022 influenza season, vaccination significantly reduced outpatient visits, consistent with prior seasons during which A(H3N2) viruses were predominant, especially among younger patients, recent study data showed.
“CDC estimates influenza vaccine effectiveness annually and has published estimates most seasons since 2004-05,” Jessie R. Chung, MPH, CDC epidemiologist in the Influenza Division, told Healio. “Estimates were not available in the 2020-21 influenza season due to historically low levels of influenza circulation.”
To assess estimates from the most recent completed influenza season running from October 2021 and April 2022, staff at seven sites enrolled patients aged 6 months and older seeking outpatient care for acute respiratory illness with cough and used a test negative design to assess vaccine efficacy (VE) against influenza A(H3N2).
According to the study, among 7,031 participants with acute respiratory infections at the seven sites, 2,657 were excluded due to influenza vaccination less than 2 weeks before illness onset, missing testing or vaccination data or codetection of influenza and COVID-19.
Among influenza-positive participants, 440 (94%) were subtyped as A(H3N2), with 206 A(H3N2) viruses belonging to genetic group 3C.2a1b subclade 2a.2 — which the researchers noted has antigenic differences from the A(H3N2) influenza vaccine component that belongs to clade 3C.2a1b subclade 2a.1.
After excluding patients who tested positive for SARS-CoV-2 who were tested for influenza, 4,312 patients were included in analyses of influenza VE, although only 2,463 (57%) were vaccinated against influenza. For all ages combined, VE against influenza A was 36% (95% CI, 21%-48%) and 36% (95% CI, 20%-49%) for A(H3N2), specifically.
According to the study, VE against A(H3N2) varied by age from 51% (95% CI, 19%-70%) among patients aged 6 months to 8 years and 32% (95% CI, 3%-52%) among adults aged 18 to 49 years. For adults aged 50 years and older, the researchers determined VE was 10% (95% CI, –60% to 49%), noting that they were “unable to detect statistically significant protection.”
“In general, detection of statistically significant VE below 30% with high vaccine coverage requires a larger sample size than we were able to enroll this season,” they explained.
Also of note was a sensitivity analysis that included participants who tested positive for SARS-CoV-2 at enrollment. The analysis showed that VE was slightly lower at 30% (95% CI, 14%-43%) for the full enrollment period.
The researchers added that there was no statistically significant difference between VE among those enrolled on or before Jan. 15, 2022, (VE = 29%; 95% CI, 5% to 53%) compared with those enrolled after Jan. 15, 2022 (VE = 37%; 95% CI, 19%-51%).
Based on these results, Chung concluded that “influenza vaccine is an effective tool against mild to moderate influenza that requires a medical encounter in the outpatient setting.”
GLP-1 Agonists Protected Kidneys in T2D With Advanced DKD
Researchers published the study covered in this summary on Research Square as a preprint that has not yet been peer reviewed.
- 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.
- 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.
- 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.
- 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.
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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Cite this: GLP-1 Agonists Protected Kidneys in Type 2 Diabetes With Advanced DKD – Medscape – Jan 31, 2023.
Research by UBC professor lays groundwork for life-saving breast cancer treatment
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.
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. 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.
Respiratory illness peaked in December at Chatham Kent Health Alliance: Suni – Chatham-Kent This Week
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.
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.
“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.
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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