GLP-1s May Increase Post-Endoscopy Aspiration Pneumonia Risk

 The use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may lead to an increased risk for aspiration pneumonia after endoscopic procedures, according to a new large population-based study.

In June 2023, the American Society of Anesthesiologists (ASA) recommended holding GLP-1 RAs before an endoscopic or surgical procedure to reduce the risk for complications associated with anesthesia and delayed stomach emptying.

In response, the American Gastroenterological Association (AGA) published a rapid clinical practice update in November 2023 that found insufficient evidence to support patients stopping the medications before endoscopic procedures.

Ali Rezaie, MD

"It is known that GLP-1 RAs significantly reduce the motility of the stomach and small bowel. As more and more patients are being started on GLP-1 RAs at higher doses and longer half-life, the question became whether the current recommended fasting durations are enough to reasonably assume the stomach is empty prior to procedures that require sedation," said senior author Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai Medical Center in Los Angeles, California.

"We wanted to see if these medications in fact increased the chance of aspiration before the ASA suggestion went into effect," he said. "However, this is not an easy task, as aspiration is a rare event and a large sample size is needed to confidently answer that question. That is why we evaluated nearly 1 million cases."

The study was published online in Gastroenterology.

Analyzing GLP-1 RA Use

Rezaie and colleagues conducted a population-based, retrospective cohort study of the TriNetX dataset, which includes 114 million deidentified individual health records from 80 healthcare organizations. The research team analyzed nearly 1 million records for adult patients between ages 21 and 70 who underwent upper and lower endoscopies between January 2018 and December 2020.

The researchers defined GLP-1 RA users as those who had the medication for more than 6 months and two or more refills within 6 months before the procedure. They adjusted for 59 factors that could affect gut motility or aspiration risks, such as obesity, numerous chronic diseases, and dozens of medications. The primary outcome was aspiration pneumonia within a month after the procedure.

Among 963,184 patients who underwent endoscopy, 46,935 (4.9%) were considered GLP-1 RA users. Among those, 20,099 GLP-1 RA users met the inclusion criteria and had their results compared with non-GLP-1 RA users.

After propensity score matching for the 59 potential confounders, GLP-1 RA use had a higher incidence rate of aspiration pneumonia (0.83% vs 0.63%) and was associated with a significantly higher risk for aspiration pneumonia, with a hazard ratio (HR) of 1.33.

An even higher risk was seen among patients with propofol-assisted endoscopies (HR, 1.49) but not among those without propofol (HR, 1.31).

In a subgroup analysis based on endoscopy type, an elevated risk was observed among patients who underwent upper endoscopy (HR, 1.82) and combined upper and lower endoscopy (HR, 2.26) but not lower endoscopy (HR, 0.56).

"The results were not necessarily surprising given the mechanism of action of GLP-1 RAs. However, for the first time, this was shown with a clinically relevant outcome, such as aspiration pneumonia," Rezaie said. "Aspiration during sedation can have devastating consequences, and the 0.2% difference in risk of aspiration can have a significant effect on healthcare as well."

More than 20 million endoscopies are performed across the United States annually. Based on the assumption that about 3% of those patients are taking GLP-1 RAs, about 1200 aspiration cases per year can be prevented by raising awareness, he said.

Considering Next Steps

The varying risk profiles observed with separate sedation and endoscopy types point to a need for more tailored guidance in managing GLP-1 RA use before a procedure, the study authors wrote.

Although holding the medications before endoscopy may disrupt diabetes management, the potential increased risk for aspiration could justify a change in practice, particularly for upper endoscopy and propofol-associated procedures, they added.

At the same time, additional studies are needed to understand the optimal drug withholding windows before endoscopies and other procedures, they concluded.

"We will need more data on what is the optimal duration of holding GLP-1 RAs," Rezaie said. "But given our data and current ASA guidance, stopping these medications prior to elective procedures is the safe thing to do."

For now, AGA guidance remains the same as offered in the November 2023 update, suggesting an individual approach for each patient on a GLP-1 RA rather than a "blanket statement" on how to manage all patients taking these medications.

Andrew Wang, MD

"Overall, I believe that this study is important, but we require more high-level data to inform clinical decision-making regarding patients using GLP-1 receptor agonists prior to gastrointestinal endoscopy," said Andrew Wang, MD, chief of gastroenterology and hepatology and director of interventional endoscopy at the University of Virginia in Charlottesville, Virginia.

Wang, who wasn't involved with this study, co-authored the AGA rapid clinical practice update. He and colleagues advised continuing with a procedure as planned for patients on GLP-1 RAs who followed standard pre-procedure fasting instructions and didn't have nausea, vomiting, dyspepsia, or abdominal distention.

Among patients with symptoms that suggest retained gastric contents, rapid sequence intubation may be considered, though it may not be possible in ambulatory or office-based endoscopy settings, Wang and colleagues wrote. As another option in lieu of stopping GLP-1 RAs, patients can be placed on a liquid diet for 1 day before the procedure.

"While this study found a signal suggesting that patients using GLP-1 RAs had an increased risk of aspiration pneumonia within 1 month following upper endoscopy or combined upper and lower endoscopy, it does not inform us if having patients stop GLP-1 RAs before endoscopic procedures — especially for a single dose — will mitigate this potential risk," Wang said.

"It was also interesting that these investigators found that patients taking GLP-1 RAs who underwent lower endoscopy alone were not at increased risk for aspiration pneumonia," Wang noted.

The authors didn't report a funding source and disclosed no potential conflicts. Wang reported no relevant disclosures.

https://www.medscape.com/viewarticle/glp-1s-may-increase-post-endoscopy-aspiration-pneumonia-risk-2024a10007hv

Antipsychotics in Dementia Tied to Wider Range of 'Serious Harms'

 Use of antipsychotics in dementia patients was associated with an increased risk for a wider range of adverse outcomes than previously acknowledged, a population-based matched cohort study from England showed.

In the analysis of more than 170,000 adults with dementia, those prescribed antipsychotics were more than twice as likely to be diagnosed with pneumonia within 90 days as non-users (HR 2.19, 95% CI 2.10-2.28), and increases in risk were seen for nearly all outcomes evaluated:

• Acute kidney injury: HR 1.72 (95% CI 1.61-1.84)
• Venous thromboembolism (VTE): HR 1.62 (95% CI 1.46-1.80)
• Stroke: HR 1.61 (95% CI 1.52-1.71)
• Fracture: HR 1.43 (95% CI 1.35-1.52)
• Myocardial infarction: HR 1.28 (95% CI 1.15-1.42)
• Heart failure: HR 1.27 (95% CI 1.18-1.37)

Relative hazards were highest in the first 7 days of use for nearly all the outcomes. Notably, the risk of pneumonia was nearly 10 times higher in that initial period (HR 9.99, 95% CI 8.78-11.40), researchers led by Pearl Mok, PhD, of Manchester Academic Health Science Center in England, reported in The BMJopens in a new tab or window.

Indeed, the number needed to harm (NNH) through 90 days for pneumonia was nine, whereas the next-lowest NNH was stroke, at 29, followed by acute kidney injury at 35. Cumulative incidence of pneumonia at that point reached 4.48% among antipsychotic users versus 1.49% in the matched controls.

"The range of adverse outcomes was wider than previously highlighted in regulatory alerts, which were based on the risks of stroke and death," Mok told MedPage Today. "Risks for these wide-ranging adverse outcomes need to be considered before prescribing antipsychotic drug treatment to people with dementia."

Antipsychotics are still commonly prescribed to patients with dementia to manage behavioral and psychological symptoms, despite longstanding concerns about their safetyopens in a new tab or window, Mok said. On top of that, the efficacy of antipsychotics for the treatment of those symptoms is limited, she said.

In the U.S., all atypical antipsychotics have carried black box warningsopens in a new tab or window since 2005 over an increased risk of death when used to treat dementia-related psychosis, this was extended to all typical antipsychotics in 2008.

In the study, the risks for all the outcomes noted above were higher with typical versus atypical antipsychotics in the 90 days after a prescription except for VTE and myocardial infarction, where no significant differences were observed.

"Our study shows that it is even more important to take account of risk of harm when considering prescribing these medicines, and to use alternative non-drug approaches wherever possible," Mok said.

In an accompanying editorialopens in a new tab or window, Raya Elfadel Kheirbek, MD, and Cristina LaFon, BS, both of the University of Maryland School of Medicine in Baltimore, said the findings indeed expand the scope of known risks associated with prescribing antipsychotics in dementia.

"The findings of this study will equip healthcare professionals with more nuanced data to help guide personalized treatment decisions," they wrote, adding that the study highlighted "the need for careful justification of antipsychotic use in dementia care, including a comprehensive assessment of the benefits weighed against a broader range of serious harms than previously acknowledged."

To conduct the study, the authors collected data from anonymized electronic health records on patients diagnosed with dementia from January 1998 through May 2018 from the Clinical Practice Research Datalink in England. Most patients were women (63%) and had a mean age of 82 years.

In total, 35,339 of the 173,910 included patients were prescribed an antipsychotic drug during the study period. Risperidone (29.8% of all prescriptions) and quetiapine (28.7%) were the most prescribed antipsychotics, followed by haloperidol (10.5%) and olanzapine (8.8%).

Beyond pneumonia, Mok and colleagues found that the risk of adverse outcomes was highest in the first week after initiating any antipsychotic, including for stroke (HR 3.75, 95% CI 3.00-4.69), acute kidney injury (HR 3.79, 95% CI 2.96-4.87), and heart failure (HR 2.85, 95% CI 2.15-3.78).

Through 90 days, the cumulative incidences of other outcomes for those on antipsychotics versus controls were as follows: stroke (1.74% vs 1.04%), acute kidney injury (1.46% vs 0.74%), VTE (0.39% vs 0.26%), myocardial infarction (0.46% vs 0.33%), heart failure (1.15% vs 0.74%), fracture (1.88% vs 1.42%). Significant differences remained for all except heart failure at 1 year as well.

Risks of many adverse outcomes were higher for haloperidol than for quetiapine, including pneumonia (HR 2.53, 95% CI 2.21-2.89) and VTE (HR 1.99, 95% CI 1.33-2.97), the researchers reported.

The study was limited by its observational approach, and by the potential for residual confounders, which they attempted to address by adjusting for a wide range of patient characteristics.

Kheirbek and LaFon noted that the lack of effective nonpharmacological treatment alternatives for behavioral and psychological symptoms of dementia poses a challenge to reducing the use of antipsychotics.

Mok told MedPage Today that since the "number of people living with dementia [is] forecast to increase greatly in the coming years, further research into safer drug and more efficacious non-drug treatments for behavioral and psychological symptoms of dementia are needed."

Disclosures

This study was funded by the National Institute for Health and Care Research (NIHR).

Authors reported relationships with the NIHR, the National Health Service England, AbbVie, Almirall, Celgene, Eli Lilly, Janssen, Novartis, UCB, and the Leo Foundation.

The editorial authors reported no conflicts of interest.

Primary Source

The BMJ

Source Reference: opens in a new tab or windowMok PLH, et al "Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study" BMJ 2024; DOI: 10.1136/bmj‑2023‑076268.

Secondary Source

The BMJ

Source Reference: opens in a new tab or windowKheirbek RE, LaFon C "Use of antipsychotics in adults with dementia" BMJ 2024; DOI: 10.1136/bmj.q819.

https://www.medpagetoday.com/psychiatry/generalpsychiatry/109722

Trader Joe's Sold Contaminated Product, CDC Warns

 The CDC and FDA are warning about a multistate outbreak of Salmonella typhimurium

opens in a new tab or window infections linked to fresh basil sold at Trader Joe's stores in over two dozen states.

Twelve cases have been reported across seven states as of April 17, including one hospitalization. Exposure to fresh organic basil from Trader Joe's prior to illness was confirmed in seven of eight individuals with additional case information.

Miami-based Infinite Herbs, which makes the basil, has agreed to a voluntary recall, and the herbs have been pulled from store shelves.

"If you already bought organic basil from Trader Joe's and removed it from the packaging or froze it and cannot tell if it was Infinite Herbs-brand, do not eat or use it and throw it away," the FDA said in its statementopens in a new tab or window.

The product was sold in a 2.5-oz clamshell-style container at Trader Joe's stores in Washington, D.C., and 29 statesopens in a new tab or window, with most east of the Mississippi River. Cases have been reported in Florida, Georgia, Minnesota, Missouri, New Jersey, Rhode Island, and Wisconsin.

An investigation is ongoing to determine whether additional products are linked to the illnesses, the FDA noted.

Twelve cases have been reported across seven states.

Salmonellosis, the illness caused by Salmonella, usually occurs within 12 to 72 hoursopens in a new tab or window of consuming a contaminated food. Symptoms may include diarrhea, fever, and abdominal cramps that last 4 to 7 days.

In most, the illness resolves on its own, but "some people -- especially children younger than 5 years, adults 65 years and older, and people with weakened immune systems -- may experience more severe illnesses that require medical treatment or hospitalization," the CDC stated.

Each year in the U.S., about 420 people dieopens in a new tab or window from acute cases of salmonellosis.

The CDC recommends that people with severe Salmonella symptoms contact a healthcare provider. These can include diarrhea with a fever above 102°F; diarrhea that does not improve after more than 3 days; bloody diarrhea; vomiting so much liquids cannot be kept down; or signs of dehydration, such as not peeing much, a dry mouth/throat, and feeling dizzy when standing.

https://www.medpagetoday.com/publichealthpolicy/productalert/109731

Nepali Plaintiffs Double Down on 'Severe Harm' Caused by Invalidated USMLE Scores

 The Nepali medical graduates who filed a class action lawsuit against the National Board of Medical Examiners (NBME) have amended and refiled their complaint

opens in a new tab or window.

In their latest suit, the plaintiffs alleged that having their U.S. Medical Licensing Examination (USMLE) scores invalidated caused "severe harm" and was the result of discrimination based on national origin, citing the Civil Rights Act. They demanded $80 million in damages, which would equal just over $96,000 per person with invalidated scores.

Back in February, the USMLE invalidated test scoresopens in a new tab or window for 832 examinees after an ongoing investigation identified "a pattern of anomalous exam performance" primarily associated with Nepal, with many Nepali test-takers scoring much higher and answering questions faster than average.

Shortly after this, Latika Giri, MBBS, a Nepali medical graduate, launched a class action lawsuit. However, a judge quickly denied an emergency motionopens in a new tab or window to restore score validity.

Now, Swechha Shrestha, MD, has joined the lawsuit as another class representative.

Giri and Shrestha have a few notable differences. Both hold Nepali citizenship, but Giri lives in Kathmandu, while Shrestha lives in Nevada. All three of Giri's scores were invalidated, while Shrestha only had Step 3 invalidated.

Educational Commission for Foreign Medical Graduates (ECFMG) certification, which evaluates international medical graduates (IMGs), is required for IMGs to enter Accreditation Council for Graduate Medical Education (ACGME) residencies. One requirement for ECFMG certification is passing Steps 1 and 2 of the USMLE.

Bryan Carmody, MD, who runs the popular medical education blog, "The Sheriff of Sodium," and has been following the scandal closely, told MedPage Today that many IMGs take Step 3 earlier than required to boost their chances of matching into residency.

On Xopens in a new tab or window, Carmody noted that the judge had previously said that someone who had already matched into residency before their scores were invalidated, and therefore were at risk of being removed from the program and losing their visa, would be a more compelling plaintiff. While Shrestha is in residency, she is not required to leave the country since her ECFMG certification is intact, though she will have to retake Step 3 while "maintaining a demanding schedule."

"I don't know that many people would find that to be that severe -- all she has to do is pass the retake and she'll be okay," Carmody noted. He also pointed out that U.S. medical graduates take Step 3 during residency and because the test costs nearly $1,000, it's not uncommon for people to take it later in residency.

However, Giri, who was applying to residency this year, became ineligible for the Match when her scores were invalidated. The complaint said that those like Giri "will effectively be barred from the practice of medicine in the U.S. for many years and their careers will be derailed permanently."

The lawsuit also included the USMLE policy on score validationopens in a new tab or window, which details that people who had their scores invalidated will be able to retake the tests for free. The retake for Step 1 will be in August, Step 2 in September, and Step 3 in December, with more retake dates in 2025. If an examinee fails their retake, they will be suspended from the USMLE for 3 years. Invalidated outcomes will remain on USMLE transcripts "in perpetuity" and marked with "Score Not Available."

Carmody doesn't think having that mark on their transcript will have major consequences unless licensing bodies change policies to prohibit licensing people who have had a score invalidated.

In terms of "severe harm" to plaintiffs, the refiled complaint also noted that "perhaps worst of all, NBME, by loudly and publicly invalidating Nepali doctors' scores, has cast a discriminatory stigma over their whole community."

A spokesperson for the Federation of State Medical Boards, which co-runs the USMLE alongside the NBME, declined to answer MedPage Today's questions about whether they are looking into cheating in other countries or if scores from other countries have been invalidated. The spokesperson said they cannot comment on pending litigation.

https://www.medpagetoday.com/special-reports/features/109720

'White House Aims to Keep Gasoline Prices in Check'

 In a bid to stabilize gas prices amid the upcoming summer driving season and Presidential election, the Biden administration wants to ensure that the United States remains on a steady economic course. White House economic adviser Lael Brainard emphasized the administration's commitment to maintaining gas prices within current ranges during a statement on Thursday, according to Reuters, without elaborating on how that would be achieved.

In the past, steps to keep gasoline prices in check included attempts to strong-arm OPEC/OPEC+ to boost crude oil production and selling off hundreds of millions of barrels of crude oil from the nation's Strategic Petroleum Reserve.

With summer fast approaching, gas prices traditionally tend to rise due to increased demand for travel and transportation. However, concerns about potential spikes in prices ahead of this year's presidential election have prompted the administration to address the issue preemptively. Brainard's remarks underscore the administration's recognition of the importance of affordable fuel for American consumers and businesses—particularly in an election year.

The administration's focus on stabilizing gas prices aligns with broader efforts to support economic recovery and mitigate inflationary pressures. Maintaining affordable gas prices is crucial for sustaining consumer purchasing power and bolstering business operations.

Brainard's statement comes amid ongoing global uncertainties surrounding energy markets, including geopolitical tensions between Russia and Ukraine, and Israel and Iran and Hamas.

However, while the administration aims to keep gas prices within current ranges, it must also cater to calls for an energy strategy that would satisfy the climate crowd and promote sustainability and resilience. The Biden Administration's vision for the energy sector includes massive Investments in renewable energy sources and infrastructure upgrades in hopes of reducing dependence on fossil fuels and fulfilling the nation's climate change pledges.

https://oilprice.com/Latest-Energy-News/World-News/White-House-Aims-to-Keep-Gasoline-Prices-in-Check.html

23andMe Jumps as CEO Floats Taking DNA Tester Private

 DNA testing firm 23andMe Holding Co.’s shares soared after Chief Executive Officer Anne Wojcicki said she’s considering taking the struggling company private, less than three years after it began selling shares.

Wojcicki told board members she is proposing to acquire the company in a potential go-private transaction, according to a filing with the Securities and Exchange Commission. The stock, which has traded below $1 a share since late last year, rose as much as 33% on Thursday, the biggest jump since August 2022, before paring some of the gain.

23andMe agreed to go public in 2021 via a merger with a special purpose acquisition company founded by billionaire Virgin Group founder Richard Branson. At the time, it was valued at $3.5 billion. In just a few years, the stock has lost more than 90% of its value as the personalized DNA revolution the company heralded has been slow to catch on.

In the filing, Wojcicki indicated that she plans to maintain control of the company and “will not be willing to support any alternative transaction.” The filing said she was working with advisers and intended to begin speaking to potential partners and financing sources. The Wednesday filing noted that she had informed members of a special committee of the board of the plan on April 13.

Company representatives declined to comment.

In February, Wojcicki told Bloomberg she was considering a number of strategies to revive the company’s sagging stock price, among them splitting the company’s drug-development business from its consumer spit kit business.

As sales of its DNA testing kits have slowed in recent years, 23andMe has pivoted to offering subscription products in hopes of creating repeat customers for its consumer business. Its latest product, Total Health, is a $1,188 program that includes blood tests and regular check-ins with company health-care providers in addition to DNA testing. Wojcicki hopes to move the company further into the business of health-care delivery, and making it a necessity for people interested in preventive care.

https://finance.yahoo.com/news/23andme-jumps-ceo-floats-plan-123820071.html

Struyven, Head of Oil research at Goldman Sachs, talks about a ceiling for Brent

Daan Struyven, head of oil research at Goldman Sachs, says that if no new geopolitical tensions emerge, the price of Brent crude oil should fall. In his view, the higher-than-expected oil stocks data are unreliable enough on their own to justify lower prices. Other factors, such as the reduction in the geopolitical risk premium, currently between $5 and $10 per barrel, and the fall in demand from Asian refiners, are amplified by algorithmic selling.

Struyven suggests that, without geopolitical disruptions affecting supply, $90 could be the ceiling for Brent prices this year. However, he acknowledges that US sanctions on Venezuela and Iran could affect supply and prices. He notes that production in these two countries is increasing despite the sanctions, and that Chinese demand for oil remains a key factor in the growth of world demand.

He also mentions the possibility of OPEC+ extending its production cuts, as well as potential geopolitical shocks that could affect supply. The options market illustrates a demand for hedging against oil price rises.

Finally, Struyven suggests that the summer season could boost demand. He advises caution when prices reach the upper end of the range and recommends buying when prices are at the lower end, stressing the importance of gold and oil as hedges against geopolitical risks.

https://www.marketscreener.com/quote/stock/THE-GOLDMAN-SACHS-GROUP-I-12831/news/Daan-Struyven-Head-of-Oil-research-at-Goldman-Sachs-talks-about-a-ceiling-for-Brent-crude-oil-46460976/