Omicron subvariant XBB.1.5 possibly more likely to infect the vaccinated

 The department added that getting vaccinated against the virus, including receiving an updated booster shot, remains the best way to protect against hospitalization and death, including from new variants.

According to data from the Centers for Disease Control and Prevention, XBB.1.5 accounts for 43% of cases in the U.S.

In the first week of January, the subvariant accounted for about 30% of cases. 

XBB.1.5, an offshoot of XBB, was first detected in October.

Omicron subvariant XBB.1.5 now accounts for 73% of all sequenced COVID-19 cases in NYC. XBB.1.5 is the most transmissible form of COVID-19 that we know of to date and may be more likely to infect people who have been vaccinated or already had COVID-19. pic.twitter.com/1Ux8LNHwUu

— nychealthy (@nycHealthy) January 13, 2023

The World Health Organization warned earlier this week that it may lead to an increased number of cases based on genetic characteristics and early growth rate estimates.

Scientists have cautioned that the virus will surely keep evolving. 

“Our concern is how transmissible it is,” Maria Van Kerkhove, the WHO’s technical lead on COVID-19, said. 

“The more this virus circulates, the more chances it will have to change,” she noted.

Van Kerkhove said there is no data yet to prove that XBB.1.5 causes more severe disease, but that the agency is working on a new risk assessment of the variant that it expects to release soon.

https://nypost.com/2023/01/14/omicron-subvariant-xbb-1-5-possibly-more-likely-to-infect-the-vaccinated-officials/

Next-gen Covid vaccines: No more quick variant updates and RCTs may be required: Marks

 Gone are the days of Covid-19 vaccine developers promising to quickly shift their mRNA vaccines to target the next variant every three to four months.

Now, CBER Director Peter Marks is calling on the Modernas and BioNTech/Pfizers of the world to really start considering to develop a “distinctly improved generation of SARS-CoV-2 vaccines offering longer protection with greater scope.”

https://endpts.com/next-gen-covid-vaccines-no-more-quick-variant-updates-and-rcts-may-be-required-cber-leader-writes/

Old antipsychotic pimozide may offer new option to treat type 2 diabetes

 Researchers have found that a class of older antipsychotic drugs could be a promising new therapeutic option for people with type 2 diabetes, helping fill a need among patients who aren't able to take other currently available treatments.

"There is a growing need to find new therapies for type 2 diabetes," says John Ussher, professor in the Faculty of Pharmacy & Pharmaceutical Sciences and lead author of the recent study published in the journal Diabetes.

As Ussher explains, the drug metformin is one of the most common therapeutics for type 2 diabetes, but about 15 percent of patients aren't able to take it. Another type of commonly used drug class (insulin secretagogues) to treat diabetes isn't as effective for later-stage patients, who also need a different option.

"For the patients who can't take metformin, patients with late-stage diabetes where their beta cells aren't working as well, when you're trying to find new therapies or new combination therapies as the disease progresses, it becomes more important to find new drug classes that target new mechanisms so then you have more options to try and lower blood sugar in those individuals," Ussher explains.

The mechanism Ussher and his team turned their attention to is succinyl CoA:3-ketoacid CoA transferase (SCOT), an enzyme involved in the body's process of making energy from ketones. They used computer modeling to find drugs that could potentially interact with SCOT and landed on an older generation of antipsychotic drugs, a drug class called diphenylbutylpiperidines, or DPBP for short.

Ussher and his team had previously found that a specific drug within this class called pimozide could be repurposed to help treat diabetes, but they've since expanded their focus to see whether more of the DPBP class could also be useful for treating the disease.

"We've tested three drugs now, and they all interact with this enzyme," says Ussher. "They all improve blood sugar control by preventing the muscle from burning ketones as a fuel source."

"We believe this SCOT inhibition is the reason these antipsychotics might actually have a second life for repurposing as an anti-diabetic agent," he adds.

Fast-tracking drug development

Developing a drug is a complicated, time-consuming and expensive process. It involves clinical trials to test the safety and efficacy of the drug, and can easily cost hundreds of millions of dollars. Not to mention, it can take years to go from development in the laboratory to use in the clinic or hospital. Repurposing an existing drug may help fast-track the process, Ussher notes.

"With something that's an older drug which we used historically in humans that we no longer use, we know what the adverse effects are, we know in general that it's safe," he says.

Though clinical trials are still needed, repurposing a drug allows researchers to focus specifically on the efficacy and safety of the new intended use—offering the potential to provide a new therapeutic more quickly and cost-effectively.

"As you already have safety data, it somewhat accelerates the process," says Ussher. "And from an economic standpoint, often because a lot of these drugs being pursued for repurposing are older, they're off patent and cheaper."

Finding a new target

Repurposing is effective because it capitalizes on a main characteristic of most drugs—they're not restricted to just one target in the body. As Ussher explains, most drugs actually have numerous targets they can influence.

"That's where repurposing comes in," he says. "Can we identify the other targets that a drug may interact with, and by identifying those other targets, can this drug serve a purpose for a different disease?"

This is what Ussher's lab did in recognizing the DPBP drug class could target SCOT activity as well as the dopamine receptors it targets in its original intended use to treat psychosis.

Knowledge of these original targets can also provide valuable context when refining and improving the repurposed drug. Since DPBP drugs were originally antipsychotics, many of their potential side-effects such as drowsiness, dizziness or fatigue arise from their effects on their original target: the dopamine receptors in the brain. Ussher's lab is planning to try creating a modified version of the drug class that doesn't reach the brain and has fewer potential adverse effects.

"For us, the excitement is that it looks like the entire family of these compounds interacts with this protein [SCOT] and can improve blood sugar control in type 2 diabetes."

More information: Seyed Amirhossein Tabatabaei Dakhili et al, The Antipsychotic Dopamine 2 Receptor Antagonist Diphenylbutylpiperidines Improve Glycemia in Experimental Obesity by Inhibiting Succinyl-CoA:3-Ketoacid CoA Transferase, Diabetes (2022). DOI: 10.2337/db22-0221

https://medicalxpress.com/news/2023-01-antipsychotic-drugs-option-diabetes.html

Insurers and Middlemen Drive Up Out-of-Pocket Costs for Patients at the Pharmacy

 A new analysis of commercially insured patients taking brand medicines finds that patients with deductibles and coinsurance are paying significantly higher costs at the pharmacy than patients with copays.

Data analyzed by the sponsored health care data analytics firm IQVIA shows that in 2021, commercially insured patients with deductibles or coinsurance spent six times more out of pocket, on average, for their brand and generic medicines than those with only copays. Patients were also nearly four times more likely to abandon new brand medicines filled in a plan with a deductible compared to those with copays.

The analysis underscores how health plans and pharmacy benefit managers (PBMs) often require patients with deductibles or coinsurance to pay their out-of-pocket costs based on the full price of the medicine instead of the lower, negotiated price the insurer or PBM receives.

“No one should have to pay more for medicines just because insurance companies refuse to pass along the discounts they receive,” said PhRMA president and CEO Stephen J. Ubl. “This is more evidence that insurers are passing costs on to patients and providing less coverage in return. Health plans and PBMs have a responsibility to treat patients fairly, and they should be held accountable for tactics that force patients to leave their medicines at the pharmacy counter.”

Other key findings from the analysis show that many commercially insured patients taking one or more brand medicines in 2021 were exposed to high out-of-pocket costs at the pharmacy counter, including:

• Patients filling a brand prescription in the deductible paid eight times more, on average, for their medicine than a patient filling a brand prescription with a copay.
• Deductibles and coinsurance accounted for 60% of patients’ out-of-pocket spending on brand medicines. 
• Insurers and PBMs subjected two-thirds of patients taking brand medicines to deductibles or coinsurance.
• Patients using cost-sharing assistance from manufacturers to access their brand medicines reduced their annual out-of-pocket costs by nearly 60%, leading to average savings of nearly $500.

“With deductibles expected to go up next year for employees of small businesses, the challenges patients experience at the pharmacy will only get worse,” continued Ubl. “As long as policymakers give insurers and middlemen a free pass, patients will continue to pay more for their medicines than their insurer.” 

https://phrma.org/resource-center/Topics/Insurance-Coverage/Analysis-Shows-How-Insurers-and-Middlemen-Drive-Up-Out-of-Pocket-Costs-for-Patients-at-the-Pharmacy

Can the Fourteenth Amendment Be Used to Protect Human Life Before Birth?

 ...

Conclusion

The Fourteenth Amendment protects the rights of “any person” to due process when a state deprives him or her of life, liberty, or property, and to the “equal protection of the laws.” By overruling Roe v. Wade, the Supreme Court eliminated Roe’s deeply flawed holding that “the word ‘person,’ as used in the Fourteenth Amendment, does not include the unborn.”162

Roe, 410 U.S. at 158.

 Since a sound case can be made that interpreting “person” to include all human beings is consistent with the Fourteenth Amendment’s original public meaning, Congress should do so for purposes of its power to enforce the Fourteenth Amendment.

The Fourteenth Amendment’s Equal Protection Clause is more suitable than the Due Process Clause as a basis for enforcement legislation and Congress may create a cause of action by the Attorney General against states that deny to prenatal persons the equal protection of the laws. This occurs when a state prohibits killing a person after—but not before—birth or prohibits killing prenatal persons in some circumstances but not others.

The success of this strategy will depend on the legal standard the courts will apply. In the absence of contrary Supreme Court precedent, Congress can, for purposes of its Fourteenth Amendment enforcement power, legislatively recognize a fundamental right to life for Fourteenth Amendment persons or recognize prenatal persons as a suspect class. Either approach prompts the courts to apply strict scrutiny, requiring states to show that failing to prohibit abortion is the least restrictive means of achieving a compelling government purpose.

Congress can strengthen this and other pro-life legislative goals, as well as contribute to success in litigation challenging them, by establishing a comprehensive record on key issues including:

• The original public meaning of the Fourteenth Amendment;
• America’s history and tradition of increasing legal protection for prenatal life;
• The medical and scientific consensus that, as Texas argued in its Roe brief, “human life is a continuum, which commences in the womb…. The child is as much a child in those several days before birth as he is in those several days after;”163

  Brief for Appellee, supra note 40, at 53-54.

• The many ways that the law recognizes human beings before birth as legal persons with rights, undermining the rationality of leaving unborn persons without legal protection for their lives; and
• The foundation for, and implications of, recognizing a substantive constitutional right to life.

Justice Lewis Powell offered a principle that is especially poignant here: “The guarantee of equal protection cannot mean one thing when applied to one individual and something else when applied to [another person]. If both are not accorded the same protection, then it is not equal.”164

Regents of Univ. of California v. Bakke, 438 U.S. 265, 289–90 (1978) (opinion of Powell, J.).

Thomas Jipping is Senior Legal Fellow in the Edwin Meese III Center for Legal and Judicial Studies at The Heritage Foundation.

https://www.heritage.org/life/report/can-the-fourteenth-amendment-be-used-protect-human-life-birth

Are Vaccines Fueling New Covid Variants?

 Public-health experts are sounding the alarm about a new Omicron variant dubbed XBB that is rapidly spreading across the Northeast U.S. Some studies suggest it is as different from the original Covid strain from Wuhan as the 2003 SARS virus. Should Americans be worried?

It isn’t clear that XBB is any more lethal than other variants, but its mutations enable it to evade antibodies from prior infection and vaccines as well as existing monoclonal antibody treatments. Growing evidence also suggests that repeated vaccinations may make people more susceptible to XBB and could be fueling the virus’s rapid evolution.

Prior to Omicron’s emergence in November 2021, there were only four variants of concern: Alpha, Beta, Delta and Gamma. Only Alpha and Delta caused surges of infections globally. But Omicron has begotten numerous descendents, many of which have popped up in different regions of the world curiously bearing some of the same mutations.

“Such rapid and simultaneous emergence of multiple variants with enormous growth advantages is unprecedented,” a Dec. 19 study in the journal Nature notes. Under selective evolutionary pressures, the virus appears to have developed mutations that enable it to transmit more easily and escape antibodies elicited by vaccines and prior infection.

The same study posits that immune imprinting may be contributing to the viral evolution. Vaccines do a good job of training the immune system to remember and knock out the original Wuhan variant. But when new and markedly different strains come along, the immune system responds less effectively.

Bivalent vaccines that target the Wuhan and BA.5 variants (or breakthrough infections with the latter) prompt the immune system to produce antibodies that target viral regions the two strains have in common. In Darwinian terms, mutations that allow the virus to evade common antibodies win out—they make it “fitter.”

XBB has evolved to elude antibodies induced by the vaccines and breakthrough infections. Hence, the Nature study suggests, “current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants.”

A New England Journal of Medicine study published last month provides more evidence of the vulnerability caused by immune imprinting. Neutralizing antibodies of people who had received the bivalent were 26 times as high against the original Wuhan variant as they were against XBB and four times as high as they were against Omicron and the BA.5 variant.

Similarly, a study this month in the journal Cell found that antibody levels of people who had received four shots were 145 times as high against the original Wuhan strain as the XBB variant. A bivalent booster only slightly increased antibodies against XBB. Experts nevertheless claim that boosters improve protection against XBB. That’s disinformation, to use their favored term.

A Cleveland Clinic study that tracked its healthcare workers found that bivalent vaccines reduced the risk of getting infected by 30% while the BA.5 variant was spreading. But, as the study explained, the reason might be that workers who were more cautious—i.e., more likely to wear N95 masks and avoid large gatherings—may have also been more likely to get boosted.

Notably, workers who had received more doses were at higher risk of getting sick. Those who received three more doses were 3.4 times as likely to get infected as the unvaccinated, while those who received two were only 2.6 times as likely.

“This is not the only study to find a possible association with more prior vaccine doses and higher risk of COVID-19,” the authors noted. “We still have a lot to learn about protection from COVID-19 vaccination, and in addition to a vaccine’s effectiveness it is important to examine whether multiple vaccine doses given over time may not be having the beneficial effect that is generally assumed.”

Two years ago, vaccines were helpful in reducing severe illness, particularly among the elderly and those with health risks like diabetes and obesity. But experts refuse to concede that boosters have yielded diminishing benefits and may even have made individuals and the population as a whole more vulnerable to new variants like XBB.

It might not be a coincidence that XBB surged this fall in Singapore, which has among the highest vaccination and booster rates in the world. Over the past several weeks a XBB strain has become predominant in New York, New Jersey, Connecticut and Massachusetts, making up about three-quarters of virus samples that have been genetically sequenced. The variant has been slower to take off in other regions, making up only 6% of the Midwest and about 20% in the South. The Northeast is also the most vaccinated and boosted region in the country.

Hospitalizations in the Northeast have risen too, but primarily among those over 70. One reason may be that the T-Cell response—the cavalry riding behind the front-line antibodies—is weaker in older people. The virus can’t evade T-Cells elicited by vaccines and infections as easily as it can antibodies. Because of T-Cells, younger people are still well-protected against new variants.

Another reason may be that monoclonal antibodies are ineffective against XBB, and many older people who catch Covid can’t take the antiviral Paxlovid because they have medical conditions such as severe kidney disease or take drugs that interfere with it.

The Biden administration’s monomaniacal focus on vaccines over new treatments has left the highest-risk Americans more vulnerable to new variants. Why doesn’t that seem to worry the experts?

https://archive.ph/KwuFU#selection-287.0-535.190

Miami Heat home arena gets temporary name after FTX collapse

 The home of the Miami Heat has yet another name: Miami-Dade Arena.

That will be the temporary moniker for the building where the NBA team plays its home games, while the search for a more permanent naming-rights partner commences.

The Heat and Miami-Dade County announced the new name Friday, two days after a bankruptcy court terminated the county’s naming rights deal with collapsed cryptocurrency exchange FTX.

A county official had said earlier in the week that it would be referred to as “the Arena,” though those plans quickly changed.

“Effective immediately, Miami-Dade County and the Miami Heat have agreed that, until such time as there is a new naming rights partner, to refer to the arena as Miami-Dade Arena,” the parties said in a joint statement. “The removal of the facility’s existing signage and the changeover of branding elements will be ongoing in the coming weeks.”

The process of removing FTX branding from all aspects of the arena will take some time.

The company’s logo appears on the court, is on many of the entrances, is embroidered on the shirts many security and in-game personnel wear, is on the arena roof and even was placed on the swipe cards that employees use to access the facility.

The county asked for the naming rights deal to be terminated in November, saying at the time that continuing to refer to the building as FTX Arena will only add to the “enduring hardships” brought on by the collapse of the cryptocurrency exchange.

It will take time for all FTX logos and signs to be removed from the arena.

Getty Images

The county owns the arena and negotiated what was to be a 19-year, $135 million naming rights deal with FTX.

The Heat — who have played in the building since Jan. 2, 2000 — were to receive $2 million annually as part of that deal, which went into effect in June 2021. The county and the Heat say they will work together to find a new naming partner.

Before the FTX deal, the building had been referred to as AmericanAirlines Arena since its opening in 1999.

FTX Arena is featured underneath the center video board at Miami-Dade Arena.

Getty Images

The airline giant, which has a hub in Miami, said in 2019 that it would not renew its deal past the expiration date of Jan. 1, 2020. The airline’s name remained on the building until 2021.

FTX was the third-largest cryptocurrency exchange, though it ended up with billions of dollars’ worth of losses — estimates range from $8 billion to $10 billion — before seeking bankruptcy protection after a spectacular crash that took only a few days.

Its founder, Sam Bankman-Fried, 30, was arrested last month in the Bahamas and extradited to the U.S. to face criminal charges in what U.S. Attorney Damian Williams has called “one of the biggest frauds in American history.”

Bankman-Fried has been released on bail and is scheduled to go on trial in October. He has pleaded not guilty.

https://nypost.com/2023/01/14/miami-heat-home-arena-gets-temporary-name-after-ftx-collapse/