How To Ensure A Big, Ugly War With Iran

 by Victor Davis Hanson via American Greatness,

Iranian-backed militias have attacked American installations and forces in Syria, Iraq, and Jordan some 170 times

Ostensibly, these terrorist groups claim they are hitting US forces to coerce America into dropping its support of Israel and demanding a cease-fire in the Gaza war.

In reality, these satellite terrorists are being directed in a larger effort by Iran to pry the US. out of the Middle East, in the manner of the 1983 Marine barracks bombing.

That way, Iran will be free to fulfill its old dream of becoming a nuclear shield for a new Shiite/Persian terrorist axis from Tehran to Damascus to Beirut to the West Bank and Gaza—surrounding Israel and intimidating the Gulf regimes and more moderate states like Jordan and Egypt into concessions.

These Iranian appendages have made a number of unfortunately correct assumptions about America in general and the Biden administration in particular.

One, after the recent serial humiliations of the flight from Afghanistan, the passivity of watching a Chinese spy balloon traverse with impunity the continental United States, the mixed American signals on the eve of the Ukraine war, the troubled Pentagon’s recruitment and leadership lapses, and the destruction of the US southern border, both Iran and its surrogates feel that the United States either cannot or will do much of anything in response to their aggression.

They see the U.S. military short thousands of recruits, its leadership politicized, its munition stocks depleted by arms shipments to Ukraine and Israel, and the massive abandonment of weapons in Kabul.

Two, they view Joe Biden’s serial appeasement as a force multiplier of these perceptions of American weakness. After entering office, the Biden administration begged for a renewed Iran deal from a preening theocracy. It sought to ensure calm by delisting the Houthis from global terrorist designations and sending hundreds of millions of dollars to Hamas and radical Palestinians to buy good behavior.

Biden may have agreed that Iran was the spider in the center of the Middle East Islamic terrorist web, but only thereby to win over it with bribes such as lifting embargoes and sanctions to ensure an Iranian windfall of $90 or more billion in oil sales revenue.

Biden greenlighted a bribery payment of $6 billion to Iran to return American hostages, thereby ensuring more will be taken. It loudly distanced itself from the Netanyahu government. The gulf encouraged radicals to believe they could coerce Israel into accepting radical Islamic states on the West Bank and Gaza.

Three, after hitting American stations and bases 170 times and seeing little sustained, much less disproportionate, responses, Iran and its satellites now feel they are winning proxy wars with the US.

They have all but shut down the Red Sea as an international shipping route—damaging Europe, Egypt, and Israel, which all depend on Red Sea commerce for vital imports and exports.

Iran has forced Biden to publicly alienate the Netanyahu government and push a ceasefire down Israel’s throat. And it has helped to spark international pro-Hamas protests throughout Europe and the US that timid and compliant left-wing governments fear could lose them close elections.

But most damaging are administration spokesmen who mouth the same empty script after each serial attack:

1) The US will respond at the time and place of its own choosing.

2) The US finds no direct evidence of Iranian involvement, although it clearly has supplied the attackers;

3) The US does not wish a wider war and has no plans to attack Iran itself.

Translated to our enemies, it means an 80-year-old non-compos-mentis president is in no position to prevent, much less win, a theater-wide Middle East war that his own serial appeasement has now nearly birthed.

Biden and the Democratic Party know, as National Security Advisor Jake Sullivan pointed out just prior to the October 7 attacks on Israel, that the administration inherited a deterred and quiet Middle East. And then it blew up on their appeasing watch.

Now they are terrified of a theater-wide conflict breaking out during an election year—a fact known to all of America’s Middle East enemies.

Biden and company have forgotten the ancient wisdom that preparing loudly only for peace guarantees war. To prevent war, it should return to oil sanctions on Iran, embargo its banking transactions, slap a travel ban on Iran and its allies, cut off all aid to Hamas and the West Bank, and restore a true terrorist designation for the Houthis.

US officials must stop aimlessly babbling. If the administration must speak, Washington should do so by conveying disproportionality and unpredictability. And if, and when, America were to strike, it should do so in silent and devastating fashion.

When serially attacked, loudly responding that we will only proportionally strike back and wish no wider war will only ensure a big, ugly one.

https://www.zerohedge.com/geopolitical/how-ensure-big-ugly-war-iran-vdh

Rep Massie Hints At Impeachment If Biden Starts A War With Iran

  by Dave DeCamp via AntiWar.com,

Rep. Thomas Massie (R-KY) on Wednesday appeared to threaten to pursue the impeachment of President Biden if he started a war with Iran. Massie posted a video from 2007 on X of then-Senator Biden threatening President George W. Bush with impeachment if he went to war with Iran without congressional approval.

"I made it clear to the president that if he takes this nation to war in Iran without congressional approval, I will make it my business to impeach him," Biden said in the video.

In his post, Massie wrote: "In 2007, Sen. Biden put the President on notice that he would impeach him for going to war with Iran without Congressional approval. Consider this your notice [President Biden]."

Massie’s post came amid reports that President Biden is planning to launch a weeks-long bombing campaign that could target Iranian assets outside of Iran in response to the drone attack in Jordan that killed three US troops.

The Pentagon has admitted it has no evidence Iran was involved in the drone attack beyond its arming of the Shia militias the US believes was responsible.

Another comment Biden made during the Trump administration related to Iran has surfaced amid the tensions.

"Let’s be clear: Donald Trump does not have the authority to take us into war with Iran without Congressional approval. A president should never take this nation to war without the informed consent of the American people," he tweeted on January 6, 2020, a few days after Trump killed Iranian Gen. Qasem Soleimani by drone strike in Baghdad.

Biden has come under criticism from some members of Congress for launching strikes against the Houthis in Yemen without congressional approval, but he has continued to bomb the country.

https://www.zerohedge.com/geopolitical/rep-massie-hints-impeachment-if-biden-starts-war-iran

'Well-Funded Cabal' Influenced The 2020 Election—What Lies Ahead In 2024?

 by Kevin Stocklin via The Epoch Times (emphasis ours),

While former President Donald Trump appears to be cruising toward the GOP nomination, and with a polling lead over incumbent President Joe Biden in key swing states, Republicans will likely face a much steeper climb in the general election than they realize.

Fundamental changes in state election laws, coupled with an alliance of left-wing federal, corporate, financial, and nonprofit entities, have handed the Democratic Party advantages that the GOP may be unable to overcome.

In the decades before 2020, the Republican National Committee (RNC) and Democratic National Committee (DNC) machines each had their own unique strengths: The RNC had the money and the DNC had the troops.

As noted in the book “The Victory Lab,” an analysis by political journalist Sasha Issenberg, Republicans excelled at fundraising and spent heavily on messaging through paid television, radio, and online ads. The DNC, with its voters often concentrated in urban centers, called on its foot soldiers, most notably students and union leaders, to go door-to-door and stir up support.

In 2020, the landscape shifted in the wake of two events: The COVID-19 pandemic and the death of George Floyd in police custody. A narrative emerged that existing state voting laws were hazardous to public health and racist and that they had to change.

The 2020 ‘Shadow Campaign’

In a laudatory 2021 article in Time titled “The Secret History of the Shadow Campaign That Saved the 2020 Election,” author Molly Ball detailed a “well-funded cabal of powerful people, ranging across industries and ideologies, working together behind the scenes to influence perceptions, change rules and laws, steer media coverage, and control the flow of information.”

While praising the effort, Ms. Ball said that the actors “were not rigging the election; they were fortifying it.”

The “conspiracy,” as Ms. Ball described it, included DNC operatives, union leaders, tech and social-media companies, Wall Street bankers, and a network of nonprofit donor funds that pooled hundreds of millions of dollars to finance “armies of poll workers and got millions of people to vote by mail for the first time.”

While the coalition’s purpose, ostensibly, was “saving democracy,” the overriding goal was to keep President Trump from winning a second term.

And the “well-funded cabal” appears to be gearing up for a repeat performance in 2024, with a few new twists.

An editor looks at the official Twitter account of President Donald Trump in Los Angeles on May 26, 2020, with two tweets by the president under which Twitter posted a link reading “Get the facts about mail-in ballots.” (-/AFP via Getty Images)

The DNC and groups allied with them rely on a five-part strategy to ensure that President Trump didn’t then and will not now get a second term.

That strategy includes intense legal pressure on state election officials to loosen voter integrity laws, a data nerve center that contains personal profiles of voters to predict how they will vote, an alliance of left-wing foot soldiers to bring out Democratic votes in key swing states, a collection of groups capable of bringing violence and mass unrest to cities and towns if called upon, and a network of financing vehicles to fund it all.

The first order of business, once the “well-funded cabal” was assembled, was to change state election laws.

Rewriting Election Rules

Following the mantra to “never let a crisis go to waste,” a nationwide campaign of DNC-sponsored lawsuits forced many states, even some with Republican governors, to drop what had once been standard voter integrity practices.

“That effort involved voiding basic security protocols on election procedures, including absentee ballots, and pushing for the equivalent of all-mail elections, which would give their activists a free hand in pressuring, coercing, and influencing voters in their homes in ways they are unable to do in polling places,” political analysts John Fund and Hans von Spakovsky wrote in their 2021 book titled “Our Broken Elections.”

“To force these changes, they ended up filing more election-related lawsuits than had ever been filed in an election year in U.S. history,” the authors said.

Perhaps the most enticing of all the electoral opportunities presented by the pandemic and civil unrest was the advent of universal, unsolicited mail-in ballots, which are still in use in some states.

According to the U.S. Census Bureau, 43 percent of American voters cast their ballot by mail in 2020, compared to 21 percent who did so in 2016.

In their book, Mr. Fund and Mr. von Spakovsky wrote that “the flood of millions of mail-in ballots opened the system to unprecedented confusion and largely untraceable fraud.”

“There’s a reason that a bipartisan commission co-chaired by former President Jimmy Carter in 2005 called mail-in absentee ballots the ‘largest source of potential voter fraud’ and that most countries in the European Union have banned ‘postal voting’ over the same concerns,” they wrote.

Poll workers receive Vote-by-Mail ballots in a drive thru system setup at the Election Headquarters polling station on October 19, 2020 in Doral, Florida. (Photo by Joe Raedle/Getty Images)

The topic of election fraud has become sharply politicized, with conservatives insisting that it’s a significant enough problem to sway the outcome of elections, and left-wing groups insisting it isn’t. 

The Heritage Foundation, a conservative think-tank, keeps an ongoing database of cases of voter fraud, documenting 1,500 cases to date and 1,276 criminal convictions. The group stated that illegal voting has resulted in election results being overturned in at least a dozen races.

However, the left-leaning Brookings Institution stated that what’s recorded in the Heritage database “may sound like big numbers, however ... the findings encompass more than a decade of data during which, nationally, hundreds of millions of votes have been cast.” 

In December 2023, Rasmussen Reports and The Heartland Institute conducted a survey of more than 1,000 voters regarding how they cast ballots in 2020; responses were evenly split between Republican and Democratic voters, and 30 percent of respondents said they voted by mail. 

Of the respondents who voted by mail, 21 percent said they had done so in a way that, whether they were aware of it or not, violated election laws. This includes filling out ballots for friends and relatives and forging other people’s signatures on ballots.

“We asked if they voted by mail in a state in which they are no longer a permanent resident, which is voter fraud,” Justin Haskins, a director at the Heartland Institute, told The Epoch Times. “About one in five respondents who voted by mail in the 2020 election said yes.”

The survey also found that 8 percent of respondents said a friend, family member, or organization offered to pay or reward them for voting in the 2020 election.

The Privatization of State Voting Systems

The “voter suppression” narrative, which gained acceptance throughout many parts of America, played to the strengths of the Democratic Party.

“Because the tax code allowed nonprofit organizations to run registration and turnout drives as long as they did not push a particular candidate,” Mr. Issenberg wrote, “organizing ‘historically disenfranchised’ communities became a backdoor approach to ginning up Democratic votes outside the campaign finance laws.”

One example of what Mr. Fund and Mr. von Spakovsky call the “privatization” of state election systems by wealthy donors, is the Chicago-based Center for Tech and Civic Life (CTCL), a group that is nominally nonpartisan but led by Democrat activists.

CTCL received $350 million from Facebook founder Mark Zuckerberg’s Chan Zuckerberg Initiative, ostensibly to protect the health of voters and election officials during the pandemic.

These “Zuckerbucks,” as they have come to be known, were channeled through CTCL into 2,500 mostly liberal jurisdictions to pay for new polling locations, ballot drop boxes, “voter education” centers, and campaigns to reach non-English-speaking voters, according to the authors.

In one instance, CTCL gave $10 million to the city of Philadelphia, whose entire election administration budget was $15 million before the grant. However, CTCL stipulated that the funds be used for “private printing and postage for mail-in ballots and to scatter ballot drop boxes,” the authors wrote.

https://www.zerohedge.com/political/well-funded-cabal-influenced-2020-election-what-lies-ahead-2024

Arvinas started at Buy by Goldman

 Target $70

https://finviz.com/quote.ashx?t=ARVN&p=d

Camp Lejeune Water Contamination Tied to a Range of Cancers, CDC Study Says

 Military personnel stationed at Camp Lejeune from 1975 to 1985 had at least a 20% higher risk for a number of cancers than those stationed elsewhere, federal health officials said Wednesday

opens in a new tab or window in a long-awaited study about the North Carolina base's contaminated drinking water.

Federal health officials called the research one the largest ever done in the U.S. to assess cancer risk by comparing a group who live and worked in a polluted environment to a similar group that did not.

The study found military personnel stationed at U.S. Marine Corps Base Camp Lejeune were at higher risk for some types of leukemia and lymphoma and cancers of the lung, breast, throat, esophagus, and thyroid. Civilians who worked at the base also were at a higher risk for a shorter list of cancers.

The study is "quite impressive," but cannot count as final proof that the tainted drinking water caused the cancers, said David Savitz, PhD, an epidemiologist at Brown University in Providence, Rhode Island, who is consulting for plaintiffs' attorneys in Camp Lejeune-related litigation.

"This is not something we're going to be able to resolve definitively," he said. "We are talking about exposures that happened (decades ago) that were not well documented."

But he said the new research will add weight to arguments made on behalf of people who got sick after living and working at the base.

Camp Lejeune was built in a sandy pine forest along the North Carolina coast in the early 1940s. Its drinking water was contaminated with industrial solvents from the early 1950s to 1985. The contamination -- detected in the early 1980s -- was blamed on a poorly maintained fuel depot and indiscriminate dumping on the base, as well as from an off-base dry cleaner.

Before wells were shut down, contaminated water was piped to barracks, offices, housing for enlisted families, schools, and the base's hospital. Military personnel and families drank it, cooked with it, and bathed in it.

The contamination has spawned a wave of litigation by law firms who have aggressively sought out clients with TV ads.

People who got sick after being at Camp Lejeune have accused the Marine Corps of failing to protect the health of its personnel and criticized the federal government for being slow to investigate. Marine Corps officials have repeatedly said that federal environmental regulations for these cancer-causing chemicals were not finalized until 1989, after the wells were shut down.

The Agency for Toxic Substances and Disease Registry (ATSDR), an Atlanta-based sister agency to the CDC, has done about a half-dozen studies focused on health problems in people at Camp Lejeune. Those studies were smaller than the new one, and had varied focuses, including male breast cancer rates and birth defects in children born to base personnel.

The earlier studies pointed out health risks, but the new work "more fully establishes the scope," said Richard Clapp, DSc, emeritus public health professor at Boston University, who has been involved in past Camp Lejeune research.

Aaron Bernstein, MD, MPH, the head of the ATSDR and CDC's environmental health programs, called the new study "remarkable" for being bigger and more rigorous than past research.

In the new paperopens in a new tab or window, the ATSDR investigated cancer in about 211,000 people who were stationed at or worked at Camp Lejeune between 1975 and 1985 and compared them to about 224,000 people at California's Camp Pendleton -- which was not known to have polluted groundwater -- during the same time period.

Frank Bove, ScD, a senior epidemiologist, has led the agency's Camp Lejeune research for many years and was in charge of the latest study. He relied on staff at Battelle Memorial Institute and others to comb through cancer registries across the country to look for cases tied to either base.

They found a similar number of malignant cancers in each group, about 12,000. But the numbers -- and the relative risks calculated from those numbers -- were higher in the Camp Lejeune population for a number of specific types of cancer. That list included some that weren't clearly identified in some earlier studies, most notably thyroid cancer, Clapp said.

A federal law signed by President Biden in August 2022 included language to address concerns of people who developed certain health problems they believe were linked to Camp Lejeune water contamination. It gave them a 2-year window to file claims.

The new study may lead to inclusion of thyroid cancer to be added to the list of diseases for which Camp Lejeune personnel and their families might one day be compensated, Clapp said.

The paper, which underwent external peer review, is being submitted for publication, agency officials said.

https://www.medpagetoday.com/publichealthpolicy/environmentalhealth/108521

Why Aren't More Doctors Prescribing Paxlovid to High-Risk Patients?

 Recent evidence is piling up that many people at high risk for severe COVID-19 don't receive nirmatrelvir/ritonavir (Paxlovid) -- or any outpatient antiviral treatment -- when diagnosed with a SARS-CoV-2 infection. MedPage Today looked at new studies and talked to experts to find out why.

In a new observational study, people on Medicare who were at highest risk for severe COVID-19 were actually less likely to receive outpatient antiviral treatments, such as nirmatrelvir/ritonavir, than Medicare beneficiaries at lower risk. For example, individuals 90 years and older were 36% less likely to receive the drugs compared with those ages 65 to 69 years (adjusted odds ratio [aOR] 0.64, 95% CI 0.62-0.65).

Moreover, when researchers performed a simulation analysis of data, they found that reallocation of nirmatrelvir/ritonavir according to patient risk could have prevented about 10,300 hospitalizations and 16,500 deaths in 2022 alone, Michael Barnett, MD, from the Harvard T.H. Chan School of Public Health in Boston, and colleagues reported in JAMA Health Forumopens in a new tab or window.

Especially concerning was the finding that people in nursing homes were less likely to receive any COVID-19 treatment compared to people living in the community (aOR 0.78, 95% CI 0.75-0.81), despite the fact that nursing home residents were more likely to be tested for COVID-19 or have a COVID-19 related healthcare visit, the authors wrote.

Differences could not be explained by contraindications to nirmatrelvir/ritonavir, drug-drug interactions, access to ambulatory visits, variation in COVID-19 testing, or geographic variation. Given that nirmatrelvir/ritonavir treatment was available at no cost in 2022 when the study was conducted, cost barriers did not explain the findings, Barnett told MedPage Today.

In a separate study, appearing in Morbidity and Mortality Weekly Reportopens in a new tab or window, 80% of immunosuppressed patients with mild-to-moderate COVID-19 were not offered any antiviral medication, even though those patients were at high risk for severe disease.

For almost 50% of those patients, the main reason given was that the patient had "mild symptoms," Paul Monach, MD, PhD, of the VA Boston Healthcare System, and colleagues reported. About one in five of these patients were not offered antiviral treatment because more than 5 days had elapsed since symptom onset. Just 5.7% were not prescribed an antiviral medication because of potential contraindications. Notably, 20% of patients were offered antiviral medication, but refused treatment.

So, What Is Going on With Paxlovid?

It's, well, complicated.

'The mechanisms underlying low and disparate use of COVID-19 therapies are unclear," Barnett and colleagues wrote in their study. "Possible factors include differential access to clinicians willing to prescribe antivirals or administer antibodies, concerns about drug interactions, patient preferences, the timing of when patients sought care, ... or numerous nonclinical barriers, such as poverty and structural racism."

Social media and forum sites are replete with anecdotal tales of people being unable to get a prescription for nirmatrelvir/ritonavir when they test positive.

MedPage Today contacted several physicians to find out why they are hesitant to prescribe nirmatrelvir/ritonavir. None responded to a request for an interview.

The new icing on the cake is that Pfizer recently raised the priceopens in a new tab or window for a single course of the drug from the roughly $530 the U.S. government paid during the public health emergency to to nearly $1,400. Pfizer did set up the patient assistance program PAXCESS to help patients obtain nirmatrelvir/ritonavir, and Medicare or Medicaid recipients and the uninsuredopens in a new tab or window will be able to access nirmatrelvir/ritonavir at no cost through the end of 2024. Nevertheless, out-of-pocket costs for some privately insured patients are likely to be prohibitive.

Politics and Misinformation

"I worry that a lot of the difference in Paxlovid [uptake] is that there's a large education and awareness gap where a lot of people don't know what Paxlovid is or are skeptical of it," Barnett told MedPage Today. In his experience, most patients who ask for nirmatrelvir/ritonavir are well-educated and white, he said.

Medical misinformation, politicization of COVID-19, and distrust in the medical establishment and pharmaceutical industry have likely contributed to poor uptake of antiviral medications for COVID-19 among patients and healthcare providers alike, Suraj Saggar, DO, chief of infectious diseases at Holy Name Medical Center in Teaneck, New Jersey, told MedPage Today.

But not every patient who requests nirmatrelvir/ritonavir is at high risk for severe COVID-19. "I spend a significant amount of time telling people why they don't need it as well as telling people why they do," Saggar said. "It's become harder as this pandemic has evolved, where it's not a one-size-fits-all." He said he considers the patient's age and comorbidities, but also whether they live with people who are at high risk for severe COVID-19.

Even Doctors Struggle to Get Treatment

It's notable that even physicians report difficulties getting nirmatrelvir/ritonavir for themselves or high-risk family members. Christina Mangurian, MD, vice dean of Faculty and Academic Affairs at University of California San Francisco (UCSF) School of Medicine, wrote in JAMA about her ordealopens in a new tab or window obtaining nirmatrelvir/ritonavir for her aging parents after they contracted COVID-19. The replies to her article -- many of them from physicians -- were telling:

"We had a similar experience with my husband, who takes an anticoagulant and a statin, is 87, and is in great shape," wrote one physician in the comments section of Mangurian's article. "Six calls to the supposed COVID team for his medical group. Finally, a refusal to prescribe."

"I was recently shocked when 3 of my cousins, both in their 80s and one on immunosuppressants ... were recommended not to take Paxlovid," another physician commented. "One was told by an internist that it was too dangerous a medicine and not worth the risk because of drug interactions."

"The article struck a nerve," Mangurian told MedPage Today. "I think why it got so much attention is because so many people had encountered similar problems." In fact, in response to her article, leaders at UCSF sent out information to all patients confirming that nirmatrelvir/ritonavir was available and how to access it, she said.

"I don't think the issue is so much that there are bad doctors. I think that doctors aren't given the tools they need" to confidently prescribe it, Mangurian, an implementation scientist, explained. One step would be to make sure clinical decision support tools or flow sheets are updated to include nirmatrelvir/ritonavir prescribing alerts and ways to manage drug-drug interactions, she suggested.

In fact, drug-drug interactions do remain a key stumbling block opens in a new tab or windowfor physicians when considering nirmatrelvir/ritonavir. Often, patients at high risk for severe COVID-19 are on the very medications that have known interactions with nirmatrelvir/ritonavir. "As a clinician, I don't think that's a good excuse because there's a very tiny number of medications that interact with Paxlovid that are harmful to stop for a week," Barnett told MedPage Today. "It's a much better risk-benefit ratio for someone to stop their statin and take Paxlovid while they're sick."

Telehealth: Good for Healthcare Providers, Not So Good for Older Adults

Another key problem is that face-to-face primary care appointments are hard to come by within the 5-day timeframe required from symptom onset to treatment initiation with nirmatrelvir/ritonavir. Although telehealth programs are convenient for healthcare providers, they aren't always the best solution for older or disabled individuals, since they often encounter obstacles in navigating online platforms. "Older patients a lot of times can't figure out how to use an iPhone, can't use a smartphone or a tablet, can't get on Doximity or other third-party apps," Saggar said. "Lower income patients maybe don't have wifi."

Current Recommendations Still Stand

Virologists and infectious disease specialists continue to recommend nirmatrelvir/ritonavir for high-risk patients, such as people over 65, and those with obesity, hypertension, diabetes, and chronic lung or heart disease. "I think it would be reasonable for people over 75, even without comorbidities, to take Paxlovid, primarily because age is associated with a lessening of the immune response," Paul Offit, MD, a virology expert at the Children's Hospital of Philadelphia, told MedPage Today.

"There is no evidence that Paxlovid is not active against the new variants," said Robert Schooley, MD, an infectious disease specialist at University of California San Diego. Because new strains of SARS-CoV-2 may be less pathogenic and more people are vaccinated or have had COVID-19, "fewer people are hospitalized these days so the difference Paxlovid would make in terms of hospitalization would be less apparent," he added.

Disclosures

The JAMA Health Forum study was funded by a grant from the National Institute on Aging (NIA). Barnett reported grants from NIA during the conduct of the study and personal fees from California Department of Health Services. Co-authors reported relationships with Moderna, GRAIL, and the Analysis Group, as well as a number of government and nonprofit entities.

Monach reported institutional support from Gilead Sciences and consulting fees from HI-Bio. One co-author reported institutional support from Gilead Sciences.

Saggar is on the speaker's board of Abbvie and has consulted for Gilead Sciences.

Schooley has consulted for Abbvie.

Mangurian and Offit reported no conflicts of interest.

Primary Source

JAMA Health Forum

Source Reference: opens in a new tab or windowWilcock AD, et al "Clinical risk and outpatient therapy utilization for COVID-19 in the Medicare population" JAMA Health Forum 2024; DOI: 10.1001/jamahealthforum.2023.5044.

Secondary Source

Morbidity and Mortality Weekly Report

Source Reference: opens in a new tab or windowMonach PA, et al "Underuse of antiviral drugs to prevent progression to severe COVID-19 -- Veterans Health Administration, March-September 2022" MMWR Morb Mortal Wkly Rep 2024; DOI: 10.15585/mmwr.mm7303a2.

https://www.medpagetoday.com/infectiousdisease/covid19/108480

Lupus, Other Autoimmune Diseases Strike Far More Women Than Men

 Women are far more likely than men to get autoimmune diseases, when an out-of-whack immune system attacks their own bodies -- and new research may finally explain why.

It's all about how the body handles females' extra X chromosome, Stanford University researchers reported Thursday -- a finding that could lead to better ways to detect a long list of diseases that are hard to diagnose and treat.

"This transforms the way we think about this whole process of autoimmunity, especially the male-female bias," said University of Pennsylvania immunologist E. John Wherry, PhD, who wasn't involved in the study.

More than 24 million Americans, by some estimates up to 50 million, have an autoimmune disorder -- diseases such as lupus, rheumatoid arthritis, multiple sclerosis and dozens more. About four of every five patients are women, a mystery that has baffled scientists for decades.

One theory is that the X chromosome might be a culprit. After all, females have two X chromosomes while males have one X and one Y.

The new research, published in the journal Cellopens in a new tab or window, shows that extra X is involved -- but in an unexpected way.

Our DNA is carried inside each cell in 23 pairs of chromosomes, including that final pair that determines biological sex. The X chromosome is packed with hundreds of genes, far more than males' much smaller Y chromosome. Every female cell must switch off one of its X chromosome copies to avoid getting a toxic double dose of all those genes.

Performing that so-called X-chromosome inactivation is a special type of RNA called Xist, pronounced like "exist." This long stretch of RNA parks itself in spots along a cell's extra X chromosome, attracts proteins that bind to it in weird clumps, and silences the chromosome.

Stanford dermatologist Howard Chang, MD, PhD, was exploring how Xist does its job when his lab identified nearly 100 of those stuck-on proteins. Chang recognized many as related to skin-related autoimmune disorders -- patients can have "autoantibodies" that mistakenly attack those normal proteins.

"That got us thinking: These are the known ones. What about the other proteins in Xist?" Chang said. Maybe this molecule, found only in women, "could somehow organize proteins in such a way as to activate the immune system."

If true, Xist by itself couldn't cause autoimmune disease or all women would be affected. Scientists have long thought it takes a combination of genetic susceptibility and an environmental trigger, such as an infection or injury, for the immune system to run amok. For example, the Epstein-Barr virus is linked to multiple sclerosisopens in a new tab or window.

Chang's team decided to engineer male lab mice to artificially make Xist -- without silencing their only X chromosome -- and see what happened.

Researchers also specially bred mice susceptible to a lupus-like condition that can be triggered by a chemical irritant.

The mice that produced Xist formed its hallmark protein clumps and, when triggered, developed lupus-like autoimmunity at levels similar to females, the team concluded.

"We think that's really important, for Xist RNA to leak out of the cell to where the immune system gets to see it. You still needed this environmental trigger to cause the whole thing to kick off," explained Chang, who is paid by the Howard Hughes Medical Institute, which also supports the AP's Health and Science Department.

Beyond mice, researchers also examined blood samples from 100 patients -- and uncovered autoantibodies targeting Xist-associated proteins that scientists hadn't previously linked to autoimmune disorders. A potential reason, Chang suggests: standard tests for autoimmunity were made using male cells.

Lots more research is necessary but the findings "might give us a shorter path to diagnosing patients that look clinically and immunologically quite different," said Penn's Wherry.

"You may have autoantibodies to Protein A and another patient may have autoantibodies to Proteins C and D," but knowing they're all part of the larger Xist complex allows doctors to better hunt disease patterns, he added. "Now we have at least one big part of the puzzle of biological context."

Stanford's Chang wonders if it may even be possible to one day interrupt the process. "How does that go from RNA to abnormal cells, this will be a next step of the investigation."

https://www.medpagetoday.com/rheumatology/lupus/108531