Twofer Vaccine in the Making Works Against ‘Twindemic’ of Flu, COVID-19

Kenneth Bender wrote . . . . . . . . .

A one-and-done vaccine that prevents both influenza and COVID-19 might help alleviate vaccine hesitancy for both conditions.

The first clinical trial to assess concomitant administration of any vaccine with either an adenoviral vector or mRNA COVID-19 vaccine found the combination with influenza vaccine is safe, produces immunogenicity associated with separate vaccination, and supports the combination as an efficient intervention against the possible “twindemic.”

Validation of a more efficient means to vaccinate against these viral infections is particularly welcome as flu season has commenced in the US and northern hemisphere countries, and a recent survey from the National Foundation for Infectious Diseases (NFID) shows that 44% of the US population are unsure or do not plan to get vaccinated against influenza.

Rajeka Lazarus, DPhil, Department of Microbiology, University Hospitals Bristol and Weston, NHS Foundation Trust, Bristol, UK, and colleagues of the ComFluCOV Trial Group anticipate that concomitant administration would reduce burden on health care systems, and report, “concomitant vaccination raises no safety concerns and preserves the immune response to both vaccines.”

The investigators recruited 679 participants who had received the first dose of either the adenoviral vector SARS-CoV-2 vaccine ChAd0x1 (AstraZeneca) or the mRNA vaccine BNT162b2 (Pfizer/BioNTech) and randomized 1:1 to receive either placebo or an age-appropriate dosed influenza vaccine (adjuvanted trivalent or cellular or recombinant quadrivalent) with their second COVID-19 vaccine dose. Follow-up monitoring was available for 665 participants.

The study monitored for adverse effects and assessed laboratory indicators of immunogenicity from April 1 through June 26, 2021, outside influenza season. The study was interrupted April 8 when notice was received of thomboembolic events associated with ChAd0x1, and resumed April 9 with exclusion of participants with risk factors for thrombotic events.

The primary outcome was one or more solicited reports of systemic reaction within 7 days after vaccination such as fever, chills, or joint pains. Secondary outcomes involving safety and adverse response included solicited local reactions such as pain or tenderness and unsolicited adverse events, including medically-attended adverse events.

The secondary outcome of immune response was determined from measures including SARS-CoV-2 S-protein immunoglobulin G (anti-S IgG) concentration in serum collected on day of vaccination (D0) and day 21; and hemagglutinin antibody inhibition (HAI) against the 4 strains of influenza contained in the 2020/21 formulations, on D0, day 21 and day 42. Other immunological measures that will be in a subsequent report include neutralizing antibodies against SARS-CoV-2 on D0 and day 21 and mucosal immune responses to COVID-19 vaccines in saliva.

Lazarus and colleagues reported that, overall, 555/665 (83.5%) of participants had at least one solicited local adverse reaction after vaccination on DO; in 85.2% of those receiving concomitant vaccinations and 81.7% with placebo in lieu of influenza. The numbers with local reactions 7 days after injection were similar in both groups, although higher among those receiving the active combination at day 21. Rates of medically assisted adverse events were similar between groups following both D0 and day 21.

The Anti-S IgG geometric mean units (GMU) at day 21 were similar between those who received either SARS-CoV-2 vaccine alone or with concomitant influenza vaccine. Seroconversion rates (SCR) ranged from 89-100% and 79-93% 21 days after either BNT162b2 or CHAd0x1, respectively, whether administered alone or in combination with influenza vaccine. There were no significant differences in the HAI GMR for any influenza strain 21 days after influenza concomitant vaccination with SARS-CoV-2 vaccine compared to previously studied cohorts receiving influenza vaccination alone.

“By performing the trial in relation to the second rather than the first dose of COVID-19 vaccine, we have evaluated safety and immunogenicity in primed individuals,” Lazarus and colleagues point out. “Therefore, the findings are also likely to be more relevant to the question of concomitant administration of booster doses and seasonal influenza vaccines, which over time may become the ‘norm’ in many parts of the world.”

Source: Infection Control Today

Anti-Nausea Drug May Boost Survival for Some Cancer Patients

Patients who undergo surgery for certain types of cancer may have better short-term survival if they receive a particular anti-nausea drug, a preliminary study suggests.

Among more than 74,000 patients who had cancer surgery, researchers found that those who received the drug — called dexamethasone — were less likely to die in the next 90 days.

The vast majority of all patients survived that long. But those given dexamethasone during surgery were about one-third less likely to die, the study found.

Dexamethasone has gained attention during the pandemic because it was shown to help some patients seriously ill with COVID-19. But the medication, an anti-inflammatory corticosteroid, has a long history of use.

When given during surgery, it helps control postoperative nausea and vomiting.

The new findings suggest dexamethasone might improve short-term survival after some cancer surgeries, said senior researcher Dr. Maximilian Schaefer, of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston.

But to prove that, he said, there would need to be a clinical trial where patients with these cancers were randomly assigned to either receive dexamethasone during surgery or not.

“I think these findings lay the groundwork for clinical trials,” Schaefer said.

He reported the findings Saturday at the annual meeting of the American Society of Anesthesiologists (ASA), in San Diego. Studies presented at meetings are generally considered preliminary until they are published in a peer-reviewed journal.

This study is not the first to look at whether giving dexamethasone during cancer surgery is associated with patients’ short-term survival. Several have investigated the question and have come to mixed conclusions depending on the type of cancer — suggesting no effect, a survival benefit, or a higher risk of death.

In theory, dexamethasone could have both positive and negative effects on survival. The drug, Schaefer said, has been shown to inhibit tumor growth in the lab, but it also suppresses the immune system.

In their study, Schaefer’s team found a survival benefit specifically among patients with cancers considered “non-immunogenic.” That means the cancer does not elicit a strong immune response, and the immune system does not play a major role in controlling its growth.

Those cancers include tumors of the breast, uterus, ovaries, esophagus, pancreas, thyroid, bones and joints.

Among patients who had surgery for those cancers, the study found, about 0.8% of those given dexamethasone died within 90 days. That compared with just over 3% of those who did not receive the anti-nausea drug.

Still, it’s not clear that dexamethasone is responsible for the benefit, said Dr. Juan Cata, a member of the ASA’s Committee on Research, and an associate professor of anesthesiology at MD Anderson Cancer Center in Houston.

“This is a very well-done study,” said Cata, who was not involved in the research.

But, he said, the study was observational: It looked at records from 74,058 patients who had cancer surgery between 2005 and 2020. And in any observational study, Cata said, it’s difficult to account for all the differences between patients who receive a treatment and those who do not.

Schaefer and his team weighed the variables they could, such as patients’ age (dexamethasone is often given to younger patients), sex, indicators of their overall health and whether they’d had chemotherapy before surgery. And patients who received dexamethasone were still one-third less likely to die within 90 days of surgery.

There could, though, be other differences at work, too, according to Cata. He noted that dexamethasone patients were, on average, in surgery significantly longer — and the question is why.

There’s also the question of what caused patients’ deaths. Cata said that deaths within 90 days of surgery are often related to postoperative complications rather the cancer itself.

While the findings do not prove cause and effect, Schaefer said they do have implications for medical practice. They can give anesthesiologists “more confidence,” he said, in giving dexamethasone to patients undergoing surgery for non-immunogenic cancers.

Cata said the drug is an effective and low-cost way to help prevent post-surgery nausea and vomiting — and that alone is meaningful to patients.

Source: HealthDay

Study: Two Meds Better Than One for Many With High Blood Pressure

Cara Murez wrote . . . . . . . . .

Nearly half of Americans have high blood pressure and only 24% have it under control, but what’s the best way to treat it — one high-dose pill or two at a lower dose?

A large new study suggests that two medications may be better than one for many older patients. Lowering elevated blood pressure to a sustainable level is important because it reduces a patient’s risk of heart attack, stroke and kidney failure.

“In geriatrics, we typically try to limit the number of medications,” said study author Dr. Lillian Min, associate professor of geriatric and palliative medicine at the University of Michigan. “The traditional method of practicing medicine is to start low, go slow, is the mantra.”

That means that doctors typically prescribe one blood pressure medicine at a low dose and increase its strength as needed, to the maximum beneficial level. If blood pressure remains stubbornly high, they start a second medication.

But guidelines issued in the past decade recommend starting multiple doses of medicines. So patients might take two medications in one combo pill or separately in two pills, Min said. The aim is to lessen the risk of a side effect while offering the benefits of both medications.

“So now the question becomes: If we’re going to go up on the medicine, should we exhaust one before starting another or should we now implement that new advice?” she said.

It depends on the patient, according to a new study of more than 178,000 seniors treated through the U.S. Veterans Health Administration.

Researchers noted that high blood pressure is one of the most common chronic conditions affecting older patients. And the older people get, the more chronic conditions they are likely to have and the more medications they are likely to take.

The new study included patients taking at least one blood pressure medicine but not at its maximum dose. About a quarter had been given an added blood pressure medication, while 75% had received higher doses of existing ones.

Both treatments reduced their blood pressure, the study found, but one reduced it more.

While taking just one medication was more likely to be something patients would continue, smaller doses of more meds led to slightly larger reductions in blood pressure, the study found.

Researchers found that when doctors intensified patients’ treatment on one drug, 65% were still taking it months later compared to 50% of those whose doctors had added medications instead.

“Where this is the most clinically applicable would be to think about clinically complex patients who have a lot of medicines already, and to start considering more of the nuances of their preferences,” Min said. “What makes sense in terms of discussing the blood pressure goals between the physician or provider and the patient based on what’s going on in the big picture? Is it more important to have a more manageable regimen or is it more important to get to the goal just a little bit faster?”

The findings were published in the Annals of Internal Medicine.

Dan Lackland, a professor of epidemiology at the Medical University of South Carolina in Charleston, reviewed the findings.

He said the advantage to receiving low doses of more than one medication is that the side effects tend to be lower with these smaller doses.

On the other hand, some patients don’t want to take more than one pill or have a harder time accepting multiple pills because they feel it indicates their condition might be worse — even if it’s not, he said.

“What the paper was saying is: Take a good look at it. We need to do more studies … to really kind of compare those,” Lackland said. “One pill with a higher dose, two pills with a lower dose. And also looking very strongly at the individual patient. Is the patient going to take two pills? Are they going to be reluctant?”

He said future research could consider what strategies would help patients be more comfortable taking more than one pill, helping them comply with that regimen and explaining the reasons for it.

“This is important and I think it, again, emphasizes the importance of taking your blood pressure medication and getting that blood pressure down,” Lackland said. “And as you get the blood pressure down, you are indeed reducing your risk of cardiovascular disease and stroke, which is where we want to be.”

Source: HealthDay

Statins: Good for the Heart, Maybe Not So Good for Diabetes

Steven Reinberg wrote . . . . . . . . .

Statins are proven to lower cholesterol, but they may also come with a downside for patients with diabetes: A new study finds they may make the blood sugar disease worse.

Researchers found that among those taking statins, 56% saw their diabetes progress, compared with 48% of those not taking statins. And the higher the dose of the statin, the faster the progression of the diabetes.

“This study should be a start to more research examining the balance of benefits and harms of statins in patients with diabetes,” said senior researcher Dr. Ishak Mansi. He is a professor in the Departments of Medicine and Data and Population Science at the University of Texas Southwestern in Dallas.

“We know well about the benefits of statins, but the harms are much less investigated,” Mansi said. “Specifically, what is the population that may benefit less from the use of statins for primary prevention or be harmed? Answering these questions impact hundreds of millions of patients and cannot be postponed.”

He cautioned that based solely on this one finding, no patient should stop taking their statins and that association does not prove causation.

For the study, Mansi and his colleagues collected data on more than 83,000 diabetic patients who used statins and more than 83,000 who didn’t.

Those who were taking statins were more likely to see their diabetes progress and need to start using insulin and other types of drugs to lower high blood sugar levels sooner than those who weren’t taking statins.

“The study may alert clinicians that they may need to pay close attention and expect to adjust anti-diabetes medications when they initiate statins,” Mansi said.

Dr. Joel Zonszein, an emeritus professor of medicine at the Albert Einstein College of Medicine in New York City, said that blood sugar is not the only key to managing type 2 diabetes.

“Management of type 2 diabetes is not centered on lowering blood sugars,” explained Zonszein, who wasn’t part of the study. “In addition to lifestyle changes, medications are often necessary to prevent or attenuate complications. Statins are highly effective in lowering cholesterol and protecting against heart attacks and strokes.”

Statins do not cause diabetes and the modestly increased rate in precipitating new-onset diabetes is well-known, though the exact mechanism remains unknown, he said.

“The benefits of statins in patients with type 2 diabetes are far greater than the potential side effects,” Zonszein added.

Millions of people have been treated with statins, and its widespread application has been a major public health advance, he noted.

Treatment of obesity, hypertension and high cholesterol is as important as improving glycemic control, Zonszein added, and statins are one of the best medications for these in patients with type 2 diabetes.

“When prescribing any medication, a careful balance between benefits and side effects is discussed between the health care provider and the patient,” Zonszein said. “In the case of statins, the benefits, particularly in patients with type 2 diabetes, are by far better than potential side effects.”

The report was published online in the journal JAMA Internal Medicine.

Source: HealthDay

4 in 1 blood Pressure Pill Much More Effective than Monotherapy

The first large-scale, long-term trial of a new strategy using combinations of very low doses in one capsule, has demonstrated significantly improved control of high blood pressure – the leading cause of heart attack and stroke.

High blood pressure is the world’s leading killer but poor rates of blood pressure control remain common. A new strategy where patients are started on a pill containing four medicines, each at a quarter of their usual doses, has been shown to be much more effective in getting blood pressure under control, compared to the common practice of monotherapy, where treatment commences with just one drug.

This first large-scale, randomised controlled clinical trial of starting this novel combination blood pressure medication brought blood pressure under control in 80 percent of participants in 12 weeks, compared to 60 percent in the control group who nonetheless had access to the best patient care.

Traditionally doctors have started with one drug and then follow up to consider adding or changing treatment – but this strategy is often not successful in practice and blood pressure control rates have remained stubbornly low for decades.

The results of the Australian study published today in The Lancet and are being presented at the world-leading European Society of Cardiology conference, ESC Congress 2021.

Professor Clara Chow, lead and corresponding author and Director of the University of Sydney’s Westmead Applied Research Centre, said in a separate Comment in The Lancet this week that control of high blood pressure, known as hypertension, was not ideal anywhere, and in some regions such as Africa fewer than one in 10 had hypertension under control.

“Statistics on the global burden of high blood pressure this week show that there’s been a doubling in the past 30 years of hypertension cases – the leading cause of the world’s top killer: heart attack and stroke,” Professor Chow said.

Dr Emily Atkins from The George Institute for Global Health, UNSW Sydney and the University of Sydney said: “In settings with high levels of specialist care and full access to a range of existing blood pressure medicines – like the centres in this trial – the improved reduction in blood pressure with this strategy would be expected to reduce the risk of heart attacks and strokes by about 20 percent. In settings with little or no existing hypertension treatment, the benefits would be much greater.”

About the trial

The multi-centre, Australian clinical trial of a potential future ‘quadpill’ dose of four medications, termed Quadruple UltrA-low-dose tReatment for hypErTension (QUARTET), has demonstrated that a single pill containing ultra-low quadruple combination is much more effective than the traditional approach of starting with monotherapy (single drug).

The study funded by the National Health and Medical Research Council enrolled 591 participants with high blood pressure either in no treatment or single therapy across 10 centres in Australia. The primary outcome was the significantly reduced blood pressure in the group starting on the quadpill, at 12 weeks. These differences were sustained, with blood pressure control still better with the quadpill approach compared to the standard approach at 12 months, and no differences in side effects.

Senior author Professor Anthony Rodgers of The George Institute, UNSW Sydney and Imperial College London, said: “Our trial has overwhelmingly demonstrated the efficacy, tolerability and safety of this ultra-low-dose combination strategy – a potentially simple and scalable hypertension management strategy to treat hypertension.”

Professor Chow said the study built on their previous study comparing a quadpill approach to placebo. “We aimed to test this new quadpill strategy against usual care in Australia; as is often seen in clinical trials, people in the comparison group got much better treatment than average. Nonetheless our new quadpill strategy was much better,” she said.

“This was the first study to show the benefits are maintained long-term without any reduction over time. Even though much more add-on blood pressure medicines were used in the comparison group throughout follow-up, they never caught up with the quadpill group.”

Changing global practice

Professor Chow said there were still important research questions. “For people who may be having side effects from their current treatments, we would like to know whether a switch to an utra-low-dose combination can improve things.”

“Also, the WHO Hypertension Guidelines released this week, just like other recent hypertension guidelines in Europe, US and elsewhere, recommend most patients start on two blood pressure drugs rather than one. We need to know how that would compare to a quadpill strategy.”

There is also a major research translation challenge ahead: “These kinds of strategies will only make a major impact on global health if they are available and affordable for patients most in need,” said Professor Chow.

“When we find treatments that are this effective, simple and safe we must do our best to get them to those who can benefit most.”

Professor Chow said a simple and effective combination quadpill strategy had potential to impact people’s lives worldwide. “High blood pressure is the leading cause of preventable deaths globally – we hope our world-leading findings will be translated swiftly into a product available for the general public,” she concluded.

Source: The University of Sydney