"We're Coming After You" - How Some On The Left Found Peace Through Hate

 by Jonathan Turley,

In Shakespeare’s Richard III, Queen Elizabeth — whose husband King Edward IV was overthrown and her twins taken to the Tower — asks the older Queen Margaret (widow of the murdered King Henry VI) to “teach me how to curse mine enemies.” The Queen responds that it is easy: “Think that thy babes were sweeter than they were, And he that slew them fouler than he is.”

The lesson: The key to hate is to decouple it entirely from reason and reality. Only then can you hate completely without restraint or regret.

It seems that the left has learned how to hate. Hateful speech is in vogue as Democratic leaders ramp up violent rhetoric and political violence rises. The key is to get voters to hate your opponent so much that they forget how much they dislike you.

The irony is crushing. For years, liberals have sought to criminalize hate speech while expanding the range of viewpoints considered to fall within this category. Democratic leaders, from senators to former presidential candidates, have falsely claimed that hate speech is not protected under the First Amendment.

In “The Indispensable Right: Free Speech in an Age of Rage,” I write about rage and the uncomfortable fact: “What few today want to admit is that they like it. They like the freedom that it affords, the ability to hate and harass without a sense of responsibility.” Rage is addictive, and it is contagious.

What rage-addicts cannot tolerate are those who cling to residual impulses of decency or humanity. In an age of rage, reason is viewed as a reactionary tendency.

This week, Bravo star and liberal podcast host Jennifer Welch praised footage of a “No Kings” protester celebrating the death of Charlie Kirk, holding her up as an example for all liberals.

In the clip, the elderly woman said, “Charlie Kirk is horrible. Yes. I’m glad he’s not here.” When pressed if she was actually happy that the husband and father of two had been murdered, the woman said “Yes…because he was horrible on the campuses. Horrible person.”

After playing the clip, Welch laughed with joy and declared, “So listen up, Democratic establishment. You can either jump on board with this s—, or we’re coming after you in the same way that we come after MAGA. Period.”

Celebrities like Jamie Lee Curtis certainly got that message. The actress was facing a social and professional meltdown after openly mourning Kirk’s death in a podcast interview. “I disagreed with him on almost every point I ever heard him say,” she said. “But I believe he was a man of faith, and I hope in that moment when he died, that he felt connected to his faith, even though his ideas were abhorrent to me.”

It appeared to be a moment of weakness that briefly overrode wokeness. Curtis quickly found herself persona non grata in Hollywood, as an angry liberal mob began to circle her. Curtis quickly saw the light and effectively retracted her fleeting expression of humanity, claiming it had been “mistranslated.” It is said that in the land of the blind, the one-eyed man is king. But that does not apply if you then gouge out your own eye. Now fully and comfortably blinded by her own hand, Curtis is back as a member of good standing in Hollywood.

Internationally, the left has pushed for criminalizing the speech of those with opposing views as hateful and harmful. UNESCO works off a definition of hate speech as including “pejorative or discriminatory language with reference to a person or a group on the basis of who they are, in other words, based on their religion, ethnicity, nationality, race, color, descent, gender or other identity factor.” This includes “scapegoating, stereotyping, stigmatization and the use of derogatory language” based on any “identity factor.”

Countries are also “required to prohibit” speech tied to “conspiracy theories, disinformation and denial and distortion of historical events.”

In the past, some leftists have included political criticism or parodies of their leaders as hate speech. For example, when a rodeo clown, Tuffy Gessling, donned a President Barack Obama mask at the Missouri State Fair as part of a skit years ago, the response was calls for his arrest. The President of the Missouri chapter of the NAACP, Mary Radliff, insisted that it constituted criminal hate speech.

But things have changed. The left has now discovered the thrill of uninhibited hate.

Recently, in Chicago, elementary school teacher Lucy Martinez was shown on video reacting to an image of Kirk by mockingly making a gesture akin to being shot in the neck, mimicking how Kirk had been assassinated.

Another educator, Wilbur Wright College Adult Education Manager Moises Bernal, screamed to a crowd that “ICE agents gotta get shot and wiped out.” Bernal told the crowd, “You gotta grab a gun!” and “We gotta turn around the guns on this fascist system!”

In academia, hateful speech has long been a way to establish one’s bona fides as a faculty member. By attacking and excluding others, you reaffirm your own protected status.

Faculty have thrilled their colleagues and students by talking about “detonating white people,” abolishing white people,  calling for Republicans to suffer,  strangling police officers, celebrating the death of conservatives, calling for the killing of Trump supporters, and supporting the murder of conservative protesters.

Even school board members have referred to taking faculty “to the slaughterhouse” for questioning diversity, equity and inclusion policies.

Last week, Democratic strategist James Carville went on a hate-filled rant, to the delight of his podcast audience. He declared that anyone supporting Trump and the Republicans will be treated like collaborators in World War II who were publicly abused and paraded by mobs.

“You know what we do with collaborators?” he said. “I think these corporations [funding White House renovations] — my fantasy dream is that this nightmare ends in 2029 and I think we ought to have radical things. I think they all ought to have their heads shaven, they should be put in orange pajamas and they should be marched down Pennsylvania Avenue and the public should be invited to spit on them.”

Carville later repeated the call that “The universities, the corporations, the law firms, all of these collaborators should be shaved, pajamaed and spit on.”

For years, Democratic leaders have given their base the license for such blind rage by calling Republicans “Nazis” and claiming that democracy will die unless their opponents are stopped.

The effect has been transformative across the party. In the current race for Virginia Attorney General, Democratic nominee Jay Jones admitted to sending text messages expressing the desire to kill a political opponent, “piss on the grave” of a dead Republican, and kill his children, whom he dismissed as “little fascists,” in their mother’s arms.

There was a time when such a candidate would be denounced by those on the ticket from his party and made a nonentity in politics. Instead, the Virginia Democratic gubernatorial nominee, Abigail Spanberger (who had previously told her supporters to “Let your rage fuel you”), has refused to withdraw her endorsement. Moreover, the race remains close, with most Democratic voters still planning to cast their ballots for him.

It is a lesson many hope will take hold in the midterm elections. Like Queen Elizabeth, these voters have overcome all inhibitions and can now teach others “how to curse.”

https://www.zerohedge.com/political/were-coming-after-you-how-some-left-found-peace-through-hate

The Corrupt Anatomy Of The SNAP Panic

 by Jeffrey Tucker via The Epoch Times,

Americans ought to be deeply embarrassed at the national panic over the future of food stamps. The level of dependency on this program (42 million people and 22 million households) runs contrary to our entire civic culture and history.

It is a betrayal of the founding vision of commerce, independence, and agronomy. It reveals a fundamentally dangerous rot at the core of the functioning of the food system.

We can hope that the widespread meltdown over even the slightest pause in the program provokes a rethinking of the entire scheme.

The term food stamps is of course deprecated in favor of SNAP (Supplemental Nutrition Assistance Program) delivered via an EBT (Electronic Benefits Transfer). This is all technocratic euphemism. They are food stamps. The name was changed to disguise the disgrace and the mode of delivery turned into a card that looks like any other.

It was much better when people had to deliver their stamps in front of other customers. At least that preserved some of the stigma with which it was associated. As for nutrition, not so much. The SNAP program amounts to a huge subsidy for the snack-food industry, which turns out to be the key lobbying force behind the entire thing.

The origin of the program traces to 1933. Its main point was not to save people from starvation but to save industry from a downturn at the onset of the Great Depression. The price of wheat, milk, and meat were falling dramatically. The problem was not a lack of demand but a huge overproduction brought about by market distortions.

To understand the economic issue, you have to go back to the Great War when wartime disruptions in Europe provoked reliance on U.S. production. U.S. exports of food expanded dramatically and so did the amount of farmed acreage. The industry kept growing throughout the 1920s, based in part on leverage and inflated expectations of urbanization.

The stock market crashed and this was followed by an immediate trade war that harmed U.S. exports. The bubble broke and prices began to drop dramatically. In other words, the market corrected exactly as it should have given the circumstances.

The market is a beautiful thing: it provided cheap food exactly when it was needed most. But in 1933, a new president took power who was not a fan of the market. He hired a slew of new appointees who imagined themselves to be social and economic planners. So instead of allowing the correction, Washington got in the business of propping up industry.

The Agricultural Adjustment Act of 1933 had the government buying up surplus food from farmers and distributors and giving it away to people. This was plainly and purely a program of price support. That was the entire point. That’s why the program was administered by the Department of Agriculture, not some other welfare agency.

Meanwhile, the true American system of helping people did the heavy lifting. It was the soup kitchens and church pantries that truly got to work on solving the hunger problem. All the new food stamps did was keep food prices higher than they otherwise would be, and kept the agricultural industry from adjusting according to prevailing conditions.

From then to now, that has been the essence of the program. It’s an industry subsidy. The grocery chains depend on it. So do Big Ag producers. It also works as a vote-buying program by promoting dependency among the citizenry.

The program is completely unregulated in the way a church soup kitchen would be. Privately run food pantries do more than dish up food; they assist people toward fixing up their lives. When they see the program being abused, they cut people off. The Good Samaritan did not just give money but rather life assistance. So too for private charity today.

Government doesn’t do this. It subsidizes large industrial players while promoting dependency. Imagine tiny birds in a nest with their mouths open waiting for the mother bird to arrive with worms. Or think of dogs waiting beneath the table for scraps from plates. That’s how the architects of this program see the American people.

Think of the whole institution of Thanksgiving. It is our number one holiday even though it is not technically part of any religious calendar. You could say it is a high holy day of our civic religion.

And what does it celebrate? It honors the blessings of God in the form of food that nourishes our bodies. When we thank God for the food, what we mean is to thank God for our lives and hands and capacities to work to get that food. It celebrates the capacity of a free and godly people to manage themselves in independence. It celebrates how a society learned to feed itself.

Food stamps from government turn the whole message of Thanksgiving on its head. Instead of work and merit, it institutionalizes dependency on the Crown to feed, which is exactly the practice against which the Founders rebelled. They rejected the Crown’s tea and emoluments in favor of national independence and productivity.

How pathetic that we’ve spent weeks in wailing and gnashing of teeth over possible cuts in free food via electronic transfer! Industry and welfare recipients are screaming: “Oh no no, please don’t take away our free stuff!”

Friends, this is inconsistent with the habits and values of a free and dignified people! I get that these are very hard times. And people are in need.

On the other hand, this is the most obese and sick country in the world, poisoned by an overabundance of genetically modified calorie-rich junk food and burdened with corporate cartels that are equally dependent on government handouts.

"Freedom From Want," between 1941–1945, by Norman Rockwell. U.S. National Archives and Records Administration, Public Domain

It’s a national disgrace that an entire nation would be yelling and demanding more free food. It’s utter humiliation. This program runs contrary to everything we ever aspired to be as a nation. I hope this pause in benefits serves as a wakeup call to find our way back to our core values before it is too late.

It is not part of our national DNA to have people and industries that are dependent on government handouts in any form. Get some dignity, folks, and man up. Look at the Norman Rockwell painting of Thanksgiving and the pride on the breadwinner’s face as he serves his huge family. That’s who we are. That’s who we can be again.

https://www.zerohedge.com/political/corrupt-anatomy-snap-panic

'Caution Urged for Virtual Care Partnerships in Canada'

 Provincial governments that partnered with for-profit virtual healthcare companies, and those considering doing so, must be cautious to protect public trust, experts warned in a new analysis.

Lauren Lapointe-Shaw, MD

“To address the primary care access crisis, some provincial governments have partnered with virtual care corporations to provide formalized pathways to phone-, video-, and text messaging-based medical care,” wrote Lauren Lapointe-Shaw, MD, associate professor of medicine at the University of Toronto, Canada, and colleagues.

“However, there are risks associated with direct-to-consumer virtual ‘walk-in’ care, related to access, quality of care, and data privacy,” they wrote. “These risks require careful consideration, particularly as formal partnerships could further entrench corporate virtual care within Canadian healthcare systems.”

Lapointe-Shaw noted that corporate partnerships “arose out of provincial governments facing primary care access challenges for their populations. Partnerships offered a way to quickly expand some form of primary care access.

“However, where healthcare budgets are fixed, increasing access to one form of primary care can come at the cost of further investment in other forms of care, such as high-continuity primary care, which has demonstrated benefits across a range of outcomes,” she told Medscape News Canada. “As well, the relatively frictionless nature of corporate virtual care means that there is a greater risk of supply-induced demand, where patients seek more care for minor and self-resolving conditions, such as viral upper respiratory tract infections.” The analysis was published November 3 in CMAJ.

Partnership Models Varied

Researchers identified current partnerships between corporate care platforms and provincial or territorial governments after doing a structured Web search in November 2024. They defined a corporate virtual care partnership with a provincial government as cases that met the following criteria: Virtual healthcare services were provided by a shareholder-owned corporation, such as Telus or Teladoc Health Canada, not a physician medical professional corporation; they had a formal contract; and they provided services endorsed on the government’s official health services website.

Ongoing corporate virtual care partnerships were identified in the following four Canadian provinces: New Brunswick, Newfoundland and Labrador, Nova Scotia, and Prince Edward Island. Even though the stated reason for establishing corporate virtual care partnerships was to support primary care access, the partnership models varied and had benefits and risks.

For example, although virtual care services were provided free of charge to patients who were not registered on a primary care clinician’s roster (ie, unattached patients), New Brunswick offered two corporate-provided virtual care programs, one of which offered services to both unattached and attached patients. Another program offered virtual and in-person appointments to patients on the primary care wait list. By contrast, in Nova Scotia, the corporate provider had two tiers of care, one of which was available to unattached patients for on-demand virtual visits. 

Information on other services and pricing was sparse for all the programs.

‘Implied Endorsement’ 

The potential benefits of these partnerships, according to the authors, may include increased convenience and access for patients who cannot travel to their nearest primary care clinic or hospital, such as those with mobility issues, those who can’t take time off work, and those who need to arrange childcare.

The authors identified several potential risks, however. One relates to access to and equity of care, since video- and text-based visits benefit those who are confident working digitally, have high internet bandwidth, and have a device that can connect to the internet. Virtual-only walk-in care also can create demand that might not otherwise have existed, which has implications for healthcare system use and costs.

These partnerships also entail risks related to the safety and quality of care, particularly when access to medical records is limited and there is no physical examination or relationship between the patient and physician. Privacy and transparency risks also arise, since virtual care corporations are private, investor-owned third-party companies with an incentive to generate profits. Finally, the partnerships entail higher risks for patients with limited fluency in the clinician’s language, those with disabilities, and those with complex pre-existing conditions.

Governments must be aware that when they partner with corporate care providers, “endorsement of the quality of services they provide is implied,” the authors wrote. 

“Corporate virtual partnerships may also further entrench private companies within the broader healthcare system, becoming a permanent fixture even if provinces later improve access to full-service longitudinal primary care,” they continued. “Ongoing checks and balances are necessary to ensure standards are met and rules are not breached.”

Furthermore, Lapointe-Shaw said, “ We do not know how well on-demand virtual care works in comparison to other forms of last-resort care, such as walk-in clinics and going to the emergency department.

“Walk-in clinics and emergency departments have higher operating costs but allow for a physical exam to be completed, which is essential in the assessment of many conditions,” she continued. “Information on the effectiveness and efficiency of last-resort care across these settings for those without a regular source of primary care could inform the development of better care pathways.” 

For now, she said, “Most important is improving overall transparency [of these partnerships], including being transparent about the terms of virtual care contracts as well as ensuring independent evaluation of corporate virtual care processes and health outcomes achieved.”

‘Substantial Investment’ Required

Onil Bhattacharyya, MD, PhD, director of the Women's College Hospital Institute for Health Systems Solutions and Virtual Care and associate professor at the University of Toronto, Canada, commented on the article for Medscape Medical News.

Onil Bhattacharyya, MD, PhD

“While there are legitimate risks in partnering with the private sector, particularly regarding data privacy and security, the ability to respond quickly may be advantageous, given staffing constraints and rising demand in many regions,” he said. Bhattacharyya did not participate in drafting the article. 

“If the overarching goal in Canada is to increase patient attachment and strengthen capacity for comprehensive primary care, it is essential to ‘right-size’ episodic virtual care programs, corporate or not, so they do not take away human resources from comprehensive primary care delivery,” he said. “For this to happen, these programs need to be flexible and responsive to changing demand, which may make corporate partnerships attractive at certain points in time.”

That said, he added, many of the issues highlighted in the article (ie, limited access, lack of system integration, usability challenges, costs, and concerns around safety and quality) also apply to noncorporate, government-funded virtual care programs. “The main difference is that these programs are not driven by profit or data monetization, though they also tend to move more slowly, which can limit their ability to scale.”

Corporate healthcare partnerships are not limited to virtual care, he noted, pointing to Medavie Health Services New Brunswick, which provides land and ambulance services, home health services, community paramedic programs, 911 services, and telehealth services. 

“These models thrive in part because current primary care models are underdesigned and often subscale, because of the ad hoc structure of most clinics,” he said. “Incorporating a range of communication channels such as voice, video, and text, as well as in-person care, with new workflows could increase access, comprehensiveness, and continuity, but it will require substantial investment and ongoing iteration on how care is organized and delivered.”

Lapointe-Shaw reported receiving research funding from the PSI Foundation and a grant from INSPIRE-PHC. She also reported salary support from the PSI Foundation Graham Farquharson Knowledge Translation Fellowship and the Myrna Daniels Seniors’ Emergency Medicine Centre at the University Health Network. Bhattacharyya reported no relevant financial relationships. 

https://www.medscape.com/viewarticle/caution-urged-virtual-care-partnerships-canada-2025a1000uja

De-escalating GLP-1s to Every-2-Weeks Maintenance Option

 De-escalating GLP-1 therapy from weekly to every-other-week dosing following weight normalization may be an effective strategy for maintaining both weight and metabolic improvements, new findings suggested.

“In my clinical experience, people who first reach a normal weight and improve their metabolic health following standard weekly dosing of GLP-1 drugs usually maintain it if they switch to every other week,” Mitch Biermann, MD, PhD, staff physician and investigator at Scripps Health, San Diego, told Medscape Medical News.

Biermann presented the findings on November 4, 2025, here at the Obesity Society’s Obesity Week 2025 meeting, where he noted that this study addresses a common patient concern about how long they’ll need to take the drug. GLP-1 drug cost and suboptimal insurance coverage lend urgency to the issue, he noted.

The idea for de-escalation by spreading out the frequency of drug dosing came from patients. “Patients were telling me they switched to taking it every other week…I started recommending it to people who wanted to de-escalate their therapy. There’s no current standard of care on how to de-escalate,” he noted, although Lilly’s SURMOUNT-MAINTAIN trial is examining de-escalation via dose reduction.

The study involved 30 patients with normalized weight and/or resolution of weight-related comorbidities who agreed to transition from weekly to every-other-week dosing of a GLP-1 medication. Of those, four regained weight and returned to weekly dosing. The other 26 continued on reduced frequency regimens, including 16 every 2 weeks, 5 every 10-14 days, and 5 greater than every 2 weeks. “They basically did what they wanted,” he commented.

Most were on nonmaximal doses throughout, with averages of 7.5 mg for tirzepatide and 1.7 mg for semaglutide, for a duration of 38 weeks prior to their weight plateau and/or metabolic normalization. They had lost an average of about 30 lb on weekly treatment, with a small but significant trend toward greater weight loss at 38 weeks after transitioning to every 2 weeks, of about 2-3 lb.

By percentage, they had lost an average of about 15%, followed by another 1% after moving to every-other-week dosing. Their average BMI at the start was 29.5, which dropped to 25 during weekly treatment and then to 24.5 after de-escalation.

Similar patterns were seen in body composition. The men lost an average of about 27% body fat and the women about 38%, decreasing to 21% and 32%, respectively, with weekly treatment, followed by a small, nonsignificant further loss in body fat after de-escalation.

Improvements achieved in A1c, triglycerides, and systolic blood pressure were also maintained or slightly improved following de-escalation, although not significantly.

“At least among patients who achieve normal weight and metabolic syndrome parameters taking these medications every week, they will likely remain successful even if you reduce the frequency. The dose doesn’t have to be the maximum, and the frequency doesn’t even have to be every other week,” he concluded.

Asked to comment, session moderator Kimberly A. Gudzune, MD, chief medical officer of the American Board of Obesity Medicine, told Medscape Medical News, “It’s a small study, and we definitely need more data to understand what’s the right approach for different patients long term, so this is an initial look at this approach.”

Pointing to the four who had regained weight with de-escalation, Gudzune cautioned, “If you’re going to try this, there really needs to be very close follow-up because you don’t want folks to lose all the health benefits that they gained.”

She also pointed out that this was a special study population. “They were all people who had quite dramatic results as far as their weight loss and their metabolic improvements…So that’s another caveat we need to be mindful of.”

Biermann reported having research relationships with Eli Lilly and Company and Novo Nordisk. Gudzune reported having no current disclosures.

https://www.medscape.com/viewarticle/de-escalating-glp-1s-every-2-weeks-maintenance-option-2025a1000ug4

'Under Prasad, employees of key FDA center fear speaking out, look for exits'

 A slow-boiling feud between Vinay Prasad and his staff at the Food and Drug Administration is threatening the future of the center that regulates the nation’s vaccines, biological products, and blood supply. 

Dozens of scientists are considering leaving the Center for Biologics Evaluation and Research, where Prasad serves as director, to escape a work environment that eight agency officials described to STAT as rife with mistrust and paranoia. These officials said staffers are terrified of pushing back on Prasad, lest they face retaliation. 

https://www.statnews.com/2025/10/31/vinay-prasad-fda-cber-management-issues-insiders-say/

One of the people Prasad ousted was Richard Forshee, PhD, who was in charge of the office that oversees vaccine safety and surveillance. Prasad took over this role himself, and has overrode CBER staff to uplift his own views on multiple occasions.

CBER employees told STAT that Prasad is not a transparent or communicative manager and his main leadership goal seems to be adding more scrutiny to vaccines. Several employees have filed human resources complaints about Prasad's management. Prasad also has a tendency to ignore chains of command and reach out to people directly; this deviates form the norm so much that some of Prasad's emails have been reported as phishing.

Prasad's tenure as CBER director has been tumultuous. He was fired after 3 months on the job and rehired just 2 weeks later when HHS Secretary Robert F. Kennedy Jr. and FDA commissioner Marty Makary, MD, MPH stuck their necks out for him.

https://www.medpagetoday.com/special-reports/features/118320

'Pfizer COVID Vaccine Sales Tumble After Government Guidance on the Shots Narrows'

 The fall COVID-19 vaccine season is starting slowly for Pfizer, with U.S. sales of its Comirnaty shots sinking 25% after federal regulators narrowed recommendations on who should get them.

Approval of updated shots also came several weeks later than usual, and Pfizer said Tuesday that hurt sales as well.

Many Americans get vaccinations in the fall, to protect against any disease surges in the coming winter. Experts say interest in COVID-19 shots has been declining, and that trend could pick up this fall due to anti-vaccine sentiment and confusion about whether the shots are necessary.

The CDC last month stopped recommending COVID-19 shots for anyone, instead leaving the choice up to patients. The government agency said it was adopting recommendations made by advisers picked by U.S. Health Secretary Robert F. Kennedy Jr.

Before this year, U.S. health officials -- following the advice of infectious disease experts -- recommended annual COVID-19 boosters for all Americans ages 6 months and older. The idea was to update protection as the coronavirus evolves.

But that sentiment started to shift earlier this year when Kennedy, who has questioned the safety of COVID-19 vaccines, said they were no longer recommended for healthy children and pregnant women.

Amesh Adalja, MD, said vaccine rates have been "suboptimal" in recent years even for people considered a high risk for catching a bad case of COVID-19.

"That's only going to fall off more this season," the senior scholar at the Johns Hopkins Center for Health Security said recently.

The shifting guidance caused some confusion in September, once updated shots began arriving at drugstores, the main place Americans go to get vaccinated. Some locations required prescriptions or started asking customers if they had a condition that made them susceptible to a bad case of COVID-19.

The change in government guidance also created questions about whether insurance coverage would continue. A major industry group, America's Health Insurance Plans, has since clarified that its members will cover the shots.

CVS Health announced earlier this month that it will not require prescriptions at its stores and clinics.

Pharmacy owner Theresa Tolle says this fall has probably been one of the more confusing seasons for her customers. Tolle runs the independent Bay Street Pharmacy in Sebastian, Florida.

She said her COVID-19 vaccine business has been busy because she has an older patient population. Many still want the shots. But she's also had more customers tell her this year that they don't want them.

"There's just so many messages out there, they don't know who to believe," she said. "I've had people tell me they are afraid of it when they've had it many times."

Pfizer saw U.S. Comirnaty sales drop to $870 million in the recently completed third quarter from $1.16 billion in the same time frame last year. That came after vaccine sales rose the first two quarters of the year.

Pfizer also said Tuesday that sales of its COVID-19 treatment, nirmatrelvir/ritonavir (Paxlovid), dropped more than 50% in the quarter both in the U.S. and internationally due to lower infection rates.

Wall Street analysts also expect sales of the COVID-19 vaccine Spikevax from Moderna to tumble about 50% in the third quarter, according to the data firm FactSet.

Moderna will report its third-quarter results on Thursday.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/118322

'Digestive Tract Decontamination Fails to Cut Deaths in Intubated ICU Patients'

 

• Selective decontamination of the digestive tract (SDD) did not lower in-hospital deaths among patients undergoing mechanical ventilation.
• At 90 days, 27.9% of patients who underwent SDD died before they were discharged from the hospital, compared with 29.5% of patients who had standard care.
• Secondary analyses showed lower rates of new bloodstream infections with the SDD approach.

Using antibiotics to decontaminate the digestive tracts of mechanically ventilated patients in the intensive care unit (ICU) wasn't significantly better than standard care at preventing in-hospital deaths, according to an international trial of more than 9,000 patients.

At 90 days, 27.9% of patients who underwent selective decontamination of the digestive tract (SDD) died before they were discharged from the hospital, compared with 29.5% of patients who had standard care only (OR 0.94, 95% CI 0.84-1.05, P=0.27), reported John Myburgh, MBBCh, PhD, of the George Institute for Global Health in Sydney, and colleagues in the New England Journal of Medicine.

Despite the mortality outcomes, "there is strong evidence that SDD, particularly when used as a combination of intravenous and topical antibiotics, is associated with improved patient-centered outcomes in mechanically ventilated patients in the ICU," Myburgh told MedPage Today.

"While the overall result for the primary patient-centered outcome -- death in hospital -- did not reach statistical significance, the direction and magnitude of the point estimate includes a clinically important difference that represents a number needed to treat of 50 patients to prevent one death," Myburgh suggested.

The findings were also presented at the annual congress of the European Society of Intensive Care Medicine in Munich.

SDD uses oral and intravenous antibiotics during mechanical ventilation to prevent hospital-acquired lower respiratory tract infections from upper gastrointestinal tract bacteria and yeasts. Although it has shown a consistent benefit in reducing mortality in numerous studies, concerns about potential development of SDD-associated antibiotic resistance has kept adoption low.

There were some trends toward better outcomes with SDD compared with standard care among the study's secondary clinical outcomes, but with the study's statistical design none of those differences were significant. Deaths in the ICU occurred in 22% of the 4,223-patient SDD group compared with 24.2% of the 5,066-patient standard-care group. Median days alive and free of ICU admission were 59.3 in the SDD group and 56.9 in those receiving standard care.

In a concurrent observational study assessing patients' microbial ecology, 4.9% of SDD patients developed new bloodstream infections compared with 6.8% of standard-care patients (adjusted mean difference -1.30 percentage points, 95% CI -2.55 to -0.05).

New antibiotic-resistant organisms were cultured in 16.8% of SDD patients and 26.8% of standard-care patients (adjusted mean difference -9.60 percentage points, 95% CI -12.40 to -6.80). An ecological assessment was unable to confirm noninferiority with SDD for new antibiotic-resistant organisms, but SDD was noninferior with regard to new bloodstream and Clostridioides difficile infections.

The two groups saw virtually no difference in median defined daily dose of antibiotics over 28 days, at 12 days in the SDD group and 11.8 days in the standard-care group.

Those microbial results counter a substantial concern among clinicians about SDD, Myburgh said.

"The SuDDICU trial confirms that the use of SDD is not associated with the development of new hospital-acquired infections and antibiotic resistance," he noted. "This is an important result because of the long-held and largely unsubstantiated concerns that the use of SDD would increase these outcomes."

The Selective Decontamination of the Digestive Tract in Intensive Care Unit (SuDDICU) trial used a crossover, cluster-randomized design in which 19 ICUs in Australia and seven ICUs in Canada were randomly assigned to use either SDD or standard care during two alternating 12-month periods. Patients crossed over to the other treatment group after a 3-month gap between the periods. The study also included an observational study from baseline to the trial's end to assess changes to patients' microbial ecology.

Eligible patients were receiving mechanical ventilation via an endotracheal tube on ICU admission or received mechanical ventilation during ICU admission. The study's Australian trial enrolled patients from 2017 through 2022, while the Canadian trial was conducted from 2019 through 2023.

There were 9,289 patients enrolled in the trial. Mean age was about 58 years, and 36% were female; median APACHE II score was 20.0 and the median MODS score was 5.0.

SDD patients received topical oral antibiotic paste applied to the oropharynx and buccal mucosa, as well as an antibiotic suspension delivered to the upper gastrointestinal tract by tube. The group also received a 4-day course of intravenous antibiotics.

The study's primary outcome was all-cause in-hospital death within 90 days after enrollment during the initial hospital admission. In a post hoc subgroup analysis, investigators observed lower mortality in the SDD group among patients with acute brain injuries (OR 0.80, 95% CI 0.68-0.94).

SDD has shown a consistent benefit signal in mechanically ventilated patients with acute brain injuries, such as traumatic brain injury, stroke syndromes, and encephalopathy, Myburgh told MedPage Today. Based on the SuDDICU results, a large pragmatic, randomized clinical trial is underway in Australia to assess the effect of preventive antibiotics in such patients.

Study limitations included the use of a nonblinded intervention. The ecological assessment's relative lack of power and short observation period allowed the researchers limited ability to confirm or refute SDD's noninferiority. The overall low incidence of antibiotic-resistant infections may make the study's results not generalizable to areas with greater antibiotic resistance rates.

Disclosures

The National Health and Medical Research Council of Australia and the Canadian Institutes of Health Research supported the study.

Myburgh had no relevant conflicts. Colleagues disclosed relationships with AM Pharma, AstraZeneca, Baxter, Matisse Pharmaceuticals, Health Research Council of New Zealand, Unity Health Toronto, University of Toronto, and Partner Therapeutics.

Primary Source

New England Journal of Medicine

Source Reference: Cuthbertson BH, et al "Selective decontamination of the digestive tract during ventilation in the ICU" N Engl J Med 2025; DOI: 10.1056/NEJMoa2506398.

https://www.medpagetoday.com/criticalcare/generalcriticalcare/118323